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Sample records for comprehensive molecular interaction

  1. Comprehensive characterization of molecular interactions based on nanomechanics.

    Directory of Open Access Journals (Sweden)

    Murali Krishna Ghatkesar

    Full Text Available Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6 Da adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions.

  2. Discerning molecular interactions: A comprehensive review on biomolecular interaction databases and network analysis tools.

    Science.gov (United States)

    Miryala, Sravan Kumar; Anbarasu, Anand; Ramaiah, Sudha

    2018-02-05

    Computational analysis of biomolecular interaction networks is now gaining a lot of importance to understand the functions of novel genes/proteins. Gene interaction (GI) network analysis and protein-protein interaction (PPI) network analysis play a major role in predicting the functionality of interacting genes or proteins and gives an insight into the functional relationships and evolutionary conservation of interactions among the genes. An interaction network is a graphical representation of gene/protein interactome, where each gene/protein is a node, and interaction between gene/protein is an edge. In this review, we discuss the popular open source databases that serve as data repositories to search and collect protein/gene interaction data, and also tools available for the generation of interaction network, visualization and network analysis. Also, various network analysis approaches like topological approach and clustering approach to study the network properties and functional enrichment server which illustrates the functions and pathway of the genes and proteins has been discussed. Hence the distinctive attribute mentioned in this review is not only to provide an overview of tools and web servers for gene and protein-protein interaction (PPI) network analysis but also to extract useful and meaningful information from the interaction networks. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Elucidating the interaction of clofazimine with bovine liver catalase; a comprehensive spectroscopic and molecular docking approach.

    Science.gov (United States)

    Zaman, Masihuz; Nusrat, Saima; Zakariya, Syed Mohammad; Khan, Mohsin Vahid; Ajmal, Mohammad Rehan; Khan, Rizwan Hasan

    2017-08-01

    Nowadays, understanding of interface between protein and drugs has become an active research area of interest. These types of interactions provide structural guidelines in drug design with greater clinical efficacy. Thus, structural changes in catalase induced by clofazimine were monitored by various biophysical techniques including UV-visible spectrometer, fluorescence spectroscopy, circular dichroism, and dynamic light scattering techniques. Increase in absorption spectra (UV-visible spectrum) confers the complex formation between drug and protein. Fluorescence quenching with a binding constants of 2.47 × 10 4  M -1 revealed that clofazimine binds with protein. Using fluorescence resonance energy transfer, the distance (r) between the protein (donor) and drug (acceptor) was found to be 2.89 nm. Negative Gibbs free energy change (ΔG°) revealed that binding process is spontaneous. In addition, an increase in α-helicity was observed by far-UV circular dichroism spectra by adding clofazimine to protein. Dynamic light scattering results indicate that topology of bovine liver catalase was slightly altered in the presence of clofazimine. Hydrophobic interactions are the main forces between clofazimine and catalase interaction as depicted by molecular docking studies. Apart from hydrophobic interactions, some hydrogen bonding was also observed during docking method. The results obtained from the present study may establish abundant in optimizing the properties of ligand-protein mixtures relevant for numerous formulations. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Interaction mechanisms between organic UV filters and bovine serum albumin as determined by comprehensive spectroscopy exploration and molecular docking.

    Science.gov (United States)

    Ao, Junjie; Gao, Li; Yuan, Tao; Jiang, Gaofeng

    2015-01-01

    Organic UV filters are a group of emerging PPCP (pharmaceuticals and personal care products) contaminants. Current information is insufficient to understand the in vivo processes and health risks of organic UV filters in humans. The interaction mechanism of UV filters with serum albumin provides critical information for the health risk assessment of these active ingredients in sunscreen products. This study investigates the interaction mechanisms of five commonly used UV filters (2-hydroxy-4-methoxybenzophenone, BP-3; 2-ethylhexyl 4-methoxycinnamate, EHMC; 4-methylbenzylidene camphor, 4-MBC; methoxydibenzoylmethane, BDM; homosalate, HMS) with bovine serum albumin (BSA) by spectroscopic measurements of fluorescence, circular dichroism (CD), competitive binding experiments and molecular docking. Our results indicated that the fluorescence of BSA was quenched by these UV filters through a static quenching mechanism. The values of the binding constant (Ka) ranged from (0.78±0.02)×10(3) to (1.29±0.01)×10(5) L mol(-1). Further exploration by synchronous fluorescence and CD showed that the conformation of BSA was demonstrably changed in the presence of these organic UV filters. It was confirmed that the UV filters can disrupt the α-helical stability of BSA. Moreover, the results of molecular docking revealed that the UV filter molecule is located in site II (sub-domain IIIA) of BSA, which was further confirmed by the results of competitive binding experiments. In addition, binding occurred mainly through hydrogen bonding and hydrophobic interaction. This study raises critical concerns regarding the transportation, distribution and toxicity effects of organic UV filters in human body. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Atomic and Molecular Interactions

    International Nuclear Information System (INIS)

    2002-01-01

    The Gordon Research Conference (GRC) on Atomic and Molecular Interactions was held at Roger Williams University, Bristol, RI. Emphasis was placed on current unpublished research and discussion of the future target areas in this field

  6. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

    NARCIS (Netherlands)

    Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn; Danilova, Ludmila; Robertson, A. Gordon; Johnson, Amy R.; Lichtenberg, Tara M.; Murray, Bradley A.; Ghayee, Hans K.; Else, Tobias; Ling, Shiyun; Jefferys, Stuart R.; de Cubas, Aguirre A.; Wenz, Brandon; Korpershoek, Esther; Amelio, Antonio L.; Makowski, Liza; Rathmell, W. Kimryn; Gimenez-Roqueplo, Anne Paule; Giordano, Thomas J.; Asa, Sylvia L.; Tischler, Arthur S.; Akbani, Rehan; Ally, Adrian; Amar, Laurence; Amelio, Antonio L.; Arachchi, Harindra; Asa, Sylvia L.; Auchus, Richard J.; Auman, J. Todd; Baertsch, Robert; Balasundaram, Miruna; Balu, Saianand; Bartsch, Detlef K.; Baudin, Eric; Bauer, Thomas; Beaver, Allison; Benz, Christopher; Beroukhim, Rameen; Beuschlein, Felix; Bodenheimer, Tom; Boice, Lori; Bowen, Jay; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Carter, Suzie; Cassol, Clarissa A.; Cherniack, Andrew D.; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cope, Leslie; Crain, Daniel; Curley, Erin; Danilova, Ludmila; de Cubas, Aguirre A.; de Krijger, Ronald R.; Demchok, John A.; Deutschbein, Timo; Dhalla, Noreen; Dimmock, David; Dinjens, Winand N M; Else, Tobias; Eng, Charis; Eschbacher, Jennifer; Fassnacht, Martin; Felau, Ina; Feldman, Michael; Ferguson, Martin L.; Fiddes, Ian; Fishbein, Lauren; Frazer, Scott; Gabriel, Stacey B.; Gardner, Johanna; Gastier-Foster, Julie M.; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Geurts, Jennifer; Ghayee, Hans K.; Gimenez-Roqueplo, Anne Paule; Giordano, Thomas J.; Goldman, Mary; Graim, Kiley; Gupta, Manaswi; Haan, David; Hahner, Stefanie; Hantel, Constanze; Haussler, David; Hayes, D. Neil; Heiman, David I.; Hoadley, Katherine A.; Holt, Robert A.; Hoyle, Alan P.; Huang, Mei; Hunt, Bryan; Hutter, Carolyn M.; Jefferys, Stuart R.; Johnson, Amy R.; Jones, Steven J M; Jones, Corbin D.; Kasaian, Katayoon; Kebebew, Electron; Kim, Jaegil; Kimes, Patrick; Knijnenburg, Theo; Korpershoek, Esther; Lander, Eric; Lawrence, Michael S.; Lechan, Ronald; Lee, Darlene; Leraas, Kristen M.; Lerario, Antonio; Leshchiner, Ignaty; Lichtenberg, Tara M.; Lin, Pei; Ling, Shiyun; Liu, Jia; LiVolsi, Virginia A.; Lolla, Laxmi; Lotan, Yair; Lu, Yiling; Ma, Yussanne; Maison, Nicole; Makowski, Liza; Mallery, David; Mannelli, Massimo; Marquard, Jessica; Marra, Marco A.; Matthew, Thomas; Mayo, Michael; Méatchi, Tchao; Meng, Shaowu; Merino, Maria J.; Mete, Ozgur; Meyerson, Matthew; Mieczkowski, Piotr A.; Mills, Gordon B.; Moore, Richard A.; Morozova, Olena; Morris, Scott; Mose, Lisle E.; Mungall, Andrew J.; Murray, Bradley A.; Naresh, Rashi; Nathanson, Katherine L.; Newton, Yulia; Ng, Sam; Ni, Ying; Noble, Michael S.; Nwariaku, Fiemu; Pacak, Karel; Parker, Joel S.; Paul, Evan; Penny, Robert; Perou, Charles M.; Perou, Amy H.; Pihl, Todd; Powers, James; Rabaglia, Jennifer; Radenbaugh, Amie; Ramirez, Nilsa C.; Rao, Arjun; Rathmell, W. Kimryn; Riester, Anna; Roach, Jeffrey; Robertson, A. Gordon; Sadeghi, Sara; Saksena, Gordon; Salama, Sofie; Saller, Charles; Sandusky, George; Sbiera, Silviu; Schein, Jacqueline E.; Schumacher, Steven E.; Shelton, Candace; Shelton, Troy; Sheth, Margi; Shi, Yan; Shih, Juliann; Shmulevich, Ilya; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Sofia, Heidi J.; Sokolov, Artem; Soloway, Matthew G.; Sougnez, Carrie; Stuart, Josh; Sun, Charlie; Swatloski, Teresa; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Tarvin, Katherine; Thiessen, Nina; Thorne, Leigh B.; Timmers, Henri J.; Tischler, Arthur S.; Tse, Kane; Uzunangelov, Vlado; van Berkel, Anouk; Veluvolu, Umadevi; Vicha, Ales; Voet, Doug; Waldmann, Jens; Walter, Vonn; Wan, Yunhu; Wang, Zhining; Wang, Tracy S.; Weaver, Joellen; Weinstein, John N.; Weismann, Dirk; Wenz, Brandon; Wilkerson, Matthew D.; Wise, Lisa; Wong, Tina; Wong, Christopher; Wu, Ye; Yang, Liming; Zelinka, Tomas; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Zhang, Wei; Zhu, Jingchun; Zinzindohoué, Franck; Zmuda, Erik; Pacak, Karel; Nathanson, Katherine L.; Wilkerson, Matthew D.

    2017-01-01

    We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight

  7. Interaction of new kinase inhibitors cabozantinib and tofacitinib with human serum alpha-1 acid glycoprotein. A comprehensive spectroscopic and molecular Docking approach

    Science.gov (United States)

    Ajmal, Mohammad Rehan; Abdelhameed, Ali Saber; Alam, Parvez; Khan, Rizwan Hasan

    2016-04-01

    In the current study we have investigated the interaction of newly approved kinase inhibitors namely Cabozantinib (CBZ) and Tofacitinib (TFB) with human Alpha-1 acid glycoprotein (AAG) under simulated physiological conditions using fluorescence quenching measurements, circular dichroism, dynamic light scattering and molecular docking methods. CBZ and TFB binds to AAG with significant affinity and the calculated binding constant for the drugs lie in the order of 104. With the increase in temperature the binding constant values decreased for both CBZ and TFB. The fluorescence resonance energy transfer (FRET) from AAG to CBZ and TFB suggested the fluorescence intensity of AAG was quenched by the two studied drugs via the formation of a non-fluorescent complex in the static manner. The molecular distance r value calculated from FRET is around 2 nm for both drugs, fluorescence spectroscopy data was employed for the study of thermodynamic parameters, standard Gibbs free energy change at 300K was calculated as - 5.234 kcal mol- 1 for CBZ-AAG interaction and - 6.237 kcal mol- 1 for TFB-AAG interaction, standard enthalpy change and standard entropy change for CBZ-AAG interaction are - 9.553 kcal mol- 1 and - 14.618 cal mol- 1K- 1 respectively while for AAG-TFB interaction, standard enthalpy and standard entropy change was calculated as 4.019 kcal mol- 1 and 7.206 cal mol- 1K- 1 respectively. Protein binding of the two drugs caused the tertiary structure alterations. Dynamic light scattering measurements demonstrated the reduction in the hydrodynamic radii of the protein. Furthermore molecular docking results suggested the Hydrophobic interaction and hydrogen bonding were the interactive forces in the binding process of CBZ to AAG while in case of TFB only hydrophobic interactions were found to be involved, overlap of the binding site for two studied drugs on the AAG molecule was revealed by docking results.

  8. Molecular Interactions at Membranes

    DEFF Research Database (Denmark)

    Jagalski, Vivien

    . Today, we know more than ever before about the properties of biological membranes. Advanced biophysical techniques and sophisticated membrane models allow us to answer specific questions about the structure of the components within membranes and their interactions. However, many detailed structural...... the surface-immobilization of LeuT by exchanging the detergent with natural phosphatidylcholine (PC) lipids. Various surface sensitive techniques, including neutron reflectometry (NR), are employed and finally enabled us to confirm the gross structure of LeuT in a lipid environment as predicted by molecular...... dynamic simulations. In a second study, the co-localization of three toxic plant-derived diterpene resin acids (RAs) within DPPC membranes was investigated. These compounds are reported to disrupt the membrane and increase its fluidity. The RAs used in this study vary in their toxicity while...

  9. Comprehensive molecular characterization of gastric adenocarcinoma

    Science.gov (United States)

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  10. Investigating Molecular Interactions

    DEFF Research Database (Denmark)

    Clausen, Henrik Fanø

    2010-01-01

    ···π interactions are accommodated by electrostatic complementarity. The crystal structure of both the α- and the β-polymorph of hydroquinone is presented in Chapter 6 with focus on close intermolecular contacts between the molecules via Hirshfeld surface analysis. The charge density distribution of the empty β....... The last chapter of this dissertation presents the analysis of intermolecular interaction using both the Hirshfeld surface and charge density distribution of the acetonitrile β-hydroquinone clathrate. The local packing and related close contacts are examined by breakdown of the fingerprint plots revealing......, are also introduced, as a goal of the analysis of charge density distributions is to obtain further understanding of these macroscopic properties. Neutron diffraction will be used as a complementary tool to the X-ray diffraction experiment, as positional and thermal parameters of hydrogen atoms can...

  11. Topology of molecular interaction networks

    NARCIS (Netherlands)

    Winterbach, W.; Van Mieghem, P.; Reinders, M.; Wang, H.; De Ridder, D.

    2013-01-01

    Molecular interactions are often represented as network models which have become the common language of many areas of biology. Graphs serve as convenient mathematical representations of network models and have themselves become objects of study. Their topology has been intensively researched over

  12. Molecular interactions in nanocellulose assembly

    Science.gov (United States)

    Nishiyama, Yoshiharu

    2017-12-01

    The contribution of hydrogen bonds and the London dispersion force in the cohesion of cellulose is discussed in the light of the structure, spectroscopic data, empirical molecular-modelling parameters and thermodynamics data of analogue molecules. The hydrogen bond of cellulose is mainly electrostatic, and the stabilization energy in cellulose for each hydrogen bond is estimated to be between 17 and 30 kJ mol-1. On average, hydroxyl groups of cellulose form hydrogen bonds comparable to those of other simple alcohols. The London dispersion interaction may be estimated from empirical attraction terms in molecular modelling by simple integration over all components. Although this interaction extends to relatively large distances in colloidal systems, the short-range interaction is dominant for the cohesion of cellulose and is equivalent to a compression of 3 GPa. Trends of heat of vaporization of alkyl alcohols and alkanes suggests a stabilization by such hydroxyl group hydrogen bonding to be of the order of 24 kJ mol-1, whereas the London dispersion force contributes about 0.41 kJ mol-1 Da-1. The simple arithmetic sum of the energy is consistent with the experimental enthalpy of sublimation of small sugars, where the main part of the cohesive energy comes from hydrogen bonds. For cellulose, because of the reduced number of hydroxyl groups, the London dispersion force provides the main contribution to intermolecular cohesion. This article is part of a discussion meeting issue `New horizons for cellulose nanotechnology'.

  13. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  14. Theoretical studies of molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Lester, W.A. Jr. [Univ. of California, Berkeley (United States)

    1993-12-01

    This research program is directed at extending fundamental knowledge of atoms and molecules including their electronic structure, mutual interaction, collision dynamics, and interaction with radiation. The approach combines the use of ab initio methods--Hartree-Fock (HF) multiconfiguration HF, configuration interaction, and the recently developed quantum Monte Carlo (MC)--to describe electronic structure, intermolecular interactions, and other properties, with various methods of characterizing inelastic and reaction collision processes, and photodissociation dynamics. Present activity is focused on the development and application of the QMC method, surface catalyzed reactions, and reorientation cross sections.

  15. The Implications of Interactive eBooks on Comprehension

    Science.gov (United States)

    Frye, Sheila K.

    2014-01-01

    This study examined how the interactive features of eBooks affect comprehension, the behaviors that participants engage in during the Read-to-Me and Read-and-Play reading modes, and the affordances and constraints of these reading modes. A repeated measures design was used to analyze the reading behaviors of 30 second grade, lower-level readers…

  16. Interaction between molecular complexes in dispersive media

    International Nuclear Information System (INIS)

    Banagas, E.A.; Manykin, E.A.

    1987-01-01

    The interaction between molecular complexes in different dispersive media with local and nonlocal screening is investigated theoretically. On the basis of results of numerical analysis on a computer, the dependence of the coupled-system spectrum and the interaction energy of the polarized modes on the characteristic parameters of the dispersive media is considered

  17. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Speech comprehension aided by multiple modalities: behavioural and neural interactions

    Science.gov (United States)

    McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K.

    2014-01-01

    Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources – e.g. voice, face, gesture, linguistic context – to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with

  19. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    Science.gov (United States)

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  20. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  1. Determination of morphological features and molecular interactions ...

    African Journals Online (AJOL)

    This research focused on identifying the morphological features and molecular interactions of the Nigerian Bentonitic clays using Scanning Electron Microscope (SEM) characterisation technique. The SEM microstructure images indicated that the bentonite samples are generally moderately dispersive to dispersive with ...

  2. Atomic and Molecular Manipulation of Chemical Interactions

    National Research Council Canada - National Science Library

    Ho, Wilson

    2007-01-01

    .... In effect, the goal is to carry out chemical changes by manipulating individual atoms and molecules to induce different bonding geometry and to create new interactions with their environment. These studies provide the scientific basis for the advancement of technology in catalysis, molecular electronics, optics, chemical and biological sensing, and magnetic storage.

  3. Microbial interactions: ecology in a molecular perspective.

    Science.gov (United States)

    Braga, Raíssa Mesquita; Dourado, Manuella Nóbrega; Araújo, Welington Luiz

    2016-12-01

    The microorganism-microorganism or microorganism-host interactions are the key strategy to colonize and establish in a variety of different environments. These interactions involve all ecological aspects, including physiochemical changes, metabolite exchange, metabolite conversion, signaling, chemotaxis and genetic exchange resulting in genotype selection. In addition, the establishment in the environment depends on the species diversity, since high functional redundancy in the microbial community increases the competitive ability of the community, decreasing the possibility of an invader to establish in this environment. Therefore, these associations are the result of a co-evolution process that leads to the adaptation and specialization, allowing the occupation of different niches, by reducing biotic and abiotic stress or exchanging growth factors and signaling. Microbial interactions occur by the transference of molecular and genetic information, and many mechanisms can be involved in this exchange, such as secondary metabolites, siderophores, quorum sensing system, biofilm formation, and cellular transduction signaling, among others. The ultimate unit of interaction is the gene expression of each organism in response to an environmental (biotic or abiotic) stimulus, which is responsible for the production of molecules involved in these interactions. Therefore, in the present review, we focused on some molecular mechanisms involved in the microbial interaction, not only in microbial-host interaction, which has been exploited by other reviews, but also in the molecular strategy used by different microorganisms in the environment that can modulate the establishment and structuration of the microbial community. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. 2010 Atomic & Molecular Interactions Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Todd Martinez

    2010-07-23

    The Atomic and Molecular Interactions Gordon Conferences is justifiably recognized for its broad scope, touching on areas ranging from fundamental gas phase and gas-condensed matter collision dynamics, to laser-molecule interactions, photophysics, and unimolecular decay processes. The meeting has traditionally involved scientists engaged in fundamental research in gas and condensed phases and those who apply these concepts to systems of practical chemical and physical interest. A key tradition in this meeting is the strong mixing of theory and experiment throughout. The program for 2010 conference continues these traditions. At the 2010 AMI GRC, there will be talks in 5 broadly defined and partially overlapping areas of intermolecular interactions and chemical dynamics: (1) Photoionization and Photoelectron Dynamics; (2) Quantum Control and Molecules in Strong Fields; (3) Photochemical Dynamics; (4) Complex Molecules and Condensed Phases; and (5) Clusters and Reaction Dynamics. These areas encompass many of the most productive and exciting areas of chemical physics, including both reactive and nonreactive processes, intermolecular and intramolecular energy transfer, and photodissociation and unimolecular processes. Gas phase dynamics, van der Waals and cluster studies, laser-matter interactions and multiple potential energy surface phenomena will all be discussed.

  5. Echinococcus-Host Interactions at Cellular and Molecular Levels.

    Science.gov (United States)

    Brehm, K; Koziol, U

    2017-01-01

    The potentially lethal zoonotic diseases alveolar and cystic echinococcosis are caused by the metacestode larval stages of the tapeworms Echinococcus multilocularis and Echinococcus granulosus, respectively. In both cases, metacestode growth and proliferation occurs within the inner organs of mammalian hosts, which is associated with complex molecular host-parasite interactions that regulate nutrient uptake by the parasite as well as metacestode persistence and development. Using in vitro cultivation systems for parasite larvae, and informed by recently released, comprehensive genome and transcriptome data for both parasites, these molecular host-parasite interactions have been subject to significant research during recent years. In this review, we discuss progress in this field, with emphasis on parasite development and proliferation. We review host-parasite interaction mechanisms that occur early during an infection, when the invading oncosphere stage undergoes a metamorphosis towards the metacestode, and outline the decisive role of parasite stem cells during this process. We also discuss special features of metacestode morphology, and how this parasite stage takes up nutrients from the host, utilizing newly evolved or expanded gene families. We comprehensively review mechanisms of host-parasite cross-communication via evolutionarily conserved signalling systems and how the parasite signalling systems might be exploited for the development of novel chemotherapeutics. Finally, we point to an urgent need for the development of functional genomic techniques in this parasite, which will be imperative for hypothesis-driven analyses into Echinococcus stem cell biology, developmental mechanisms and immunomodulatory activities, which are all highly relevant for the development of anti-infective measures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Using Dictogloss As An Interactive Method Of Teaching Listening Comprehension

    Directory of Open Access Journals (Sweden)

    Ramlatu Jibir-Daura

    2013-07-01

    Full Text Available Listening is one of the important language skills. Traditionally, listening skills have been taught in isolation or it is sometimes combined with speaking tasks. Dictogloss is an interactive method which promotes cooperative learning and can assist in the development of both the teacher and students’ listening skills. Unlike in the traditional method of dictation, in dictogloss only the gist of the text is expected to be produced by the students. To find the usefulness of the method in a second language learning context, twenty BA ED (Hausa one hundred level students from the Language Arts section of the Ahmadu Bello University were used. Two texts, one from ‘Oliver Twist’ and the other was ‘The Seven Voyages of Simbad’. These were dictated to the students, one for each day. The result of the second task was recorded. The first exercise served as practice for the students to become familiar with the procedure. Although it is a new procedure, the results showed an improvement from the results of the first task. The students enjoyed the excercise and were willing to continue the next day even though the first results were not very good. Recommendations were given on how second language teachers could use dictogloss to their advantage for cooperative learning in listening comprehension classes.

  7. Comprehensive study of tartrazine/cationic surfactant interaction.

    Science.gov (United States)

    Shahir, Afshin Asadzadeh; Javadian, Soheila; Razavizadeh, Bi Bi Marzieh; Gharibi, Hussein

    2011-12-15

    Interaction of a food dye, tartrazine, with some cationic conventional and gemini surfactants, tetradecyltrimethylammonium bromide (TTAB), N,N'-ditetradecyl-N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (14,4,14), and N,N'-didodecyl-N,N,N',N'-tetramethyl-N,N'-butanediyl-diammonium dibromide (12,4,12), were first investigated comprehensively employing conductometry, tensiometry, and UV-visible spectroscopy. Tartrazine was found to behave in the same manner as aromatic counterions. The formation of ion pairs reflected as a considerable increase of the surfactant efficiency in tensiometry plots and their stoichiometry were determined by Job's method of continuous variations. For the tartrazine/TTAB system, nonionic DS(3), ionic DS(2-), and/or DS(2)(-) ion pairs, their small premicelles, and tartrazine-rich micelles were constituted as well as dye-containing TTAB-rich micelles. Insoluble J-aggregates of DS(-) ion pairs and cylindrical surfactant-rich micelles were also formed in tartrazine/gemini surfactant systems and recognized by transmission electron microscopy. The zeta potential and the size of the aggregates were determined using dynamic light scattering and confirmed the suggested models for the processes happening in each system. Cyclic voltammetry was applied successfully to track all of these species using tartrazine's own reduction peak current for the first time.

  8. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat; Bellmunt, Joaquim; Guo, Guangwu; Cherniack, Andrew D; Hinoue, Toshinori; Laird, Peter W; Hoadley, Katherine A; Akbani, Rehan; Castro, Mauro A A; Gibb, Ewan A; Kanchi, Rupa S; Gordenin, Dmitry A; Shukla, Sachet A; Sanchez-Vega, Francisco; Hansel, Donna E; Czerniak, Bogdan A; Reuter, Victor E; Su, Xiaoping; de Sa Carvalho, Benilton; Chagas, Vinicius S; Mungall, Karen L; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Lu, Yiling; Klimczak, Leszek J; Zhang, Jiexin; Choo, Caleb; Ojesina, Akinyemi I; Bullman, Susan; Leraas, Kristen M; Lichtenberg, Tara M; Wu, Catherine J; Schultz, Nicholaus; Getz, Gad; Meyerson, Matthew; Mills, Gordon B; McConkey, David J; Weinstein, John N; Kwiatkowski, David J; Lerner, Seth P

    2017-10-19

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Molecular interactions with ice: Molecular embedding, adsorption, detection, and release

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, K. D.; Langlois, Grant G.; Li, Wenxin; Sibener, S. J., E-mail: s-sibener@uchicago.edu [The James Franck Institute and Department of Chemistry, The University of Chicago, 929 E. 57th Street, Chicago, Illinois 60637 (United States); Killelea, Daniel R. [Department of Chemistry and Biochemistry, Loyola University Chicago, 1068 W. Sheridan Ave., Chicago, Illinois 60660 (United States)

    2014-11-14

    The interaction of atomic and molecular species with water and ice is of fundamental importance for chemistry. In a previous series of publications, we demonstrated that translational energy activates the embedding of Xe and Kr atoms in the near surface region of ice surfaces. In this paper, we show that inert molecular species may be absorbed in a similar fashion. We also revisit Xe embedding, and further probe the nature of the absorption into the selvedge. CF{sub 4} molecules with high translational energies (≥3 eV) were observed to embed in amorphous solid water. Just as with Xe, the initial adsorption rate is strongly activated by translational energy, but the CF{sub 4} embedding probability is much less than for Xe. In addition, a larger molecule, SF{sub 6}, did not embed at the same translational energies that both CF{sub 4} and Xe embedded. The embedding rate for a given energy thus goes in the order Xe > CF{sub 4} > SF{sub 6}. We do not have as much data for Kr, but it appears to have a rate that is between that of Xe and CF{sub 4}. Tentatively, this order suggests that for Xe and CF{sub 4}, which have similar van der Waals radii, the momentum is the key factor in determining whether the incident atom or molecule can penetrate deeply enough below the surface to embed. The more massive SF{sub 6} molecule also has a larger van der Waals radius, which appears to prevent it from stably embedding in the selvedge. We also determined that the maximum depth of embedding is less than the equivalent of four layers of hexagonal ice, while some of the atoms just below the ice surface can escape before ice desorption begins. These results show that energetic ballistic embedding in ice is a general phenomenon, and represents a significant new channel by which incident species can be trapped under conditions where they would otherwise not be bound stably as surface adsorbates. These findings have implications for many fields including environmental science, trace gas

  10. Effects of Strength of Accent on an L2 Interactive Lecture Listening Comprehension Test

    Science.gov (United States)

    Ockey, Gary J.; Papageorgiou, Spiros; French, Robert

    2016-01-01

    This article reports on a study which aimed to determine the effect of strength of accent on listening comprehension of interactive lectures. Test takers (N = 21,726) listened to an interactive lecture given by one of nine speakers and responded to six comprehension items. The test taker responses were analyzed with the Rasch computer program…

  11. Comprehensive Molecular Screening in Chinese Usher Syndrome Patients.

    Science.gov (United States)

    Sun, Tengyang; Xu, Ke; Ren, Yanfan; Xie, Yue; Zhang, Xiaohui; Tian, Lu; Li, Yang

    2018-03-01

    Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

  12. Molecular effects: interactions with chemicals and viruses

    International Nuclear Information System (INIS)

    Hanawalt, P.C.

    1980-01-01

    Research focused upon an understanding of the cellular responses to the molecular effects of ionizing radiation should be an essential program component in the Federal Strategy for Research into the Biological Effects of Ionizing Radiation. Although we know that DNA is a principal target molecule for some highly significant biological effects of ionizing radiation, we need to learn which other target substances such as membrane components may also be important. Most of the emphasis should continue to be on DNA effects and highest priority should be assigned to the identification of the complete spectrum of products produced in DNA. Once the lesions are known we can proceed to determine how these behave as blocks to replication and transcription or as modulators on the fidelity of these crucial processes. Considerable work should be done on the repair of these lesions. High priority should be given to the search for mutants in mammalian cell systems with evident defects in the processing of specific lesions. Viruses should provide important tools for the research in this area, as probes for host cell repair responses and also for the isolation of mutants. Furthermore, it is important to consider the interaction of viruses and ionizing radiation with regard to possible modulating effects on repair processes and tumorigenesis. Finally we must consider the important problem of the modification of repair responses by environmental factors

  13. Reconstruction and validation of RefRec: a global model for the yeast molecular interaction network.

    Directory of Open Access Journals (Sweden)

    Tommi Aho

    2010-05-01

    Full Text Available Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is approximately 67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in approximately 590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our

  14. The malaria parasite RhopH protein complex interacts with erythrocyte calmyrin identified from a comprehensive erythrocyte protein library.

    Science.gov (United States)

    Miura, Toyokazu; Takeo, Satoru; Ntege, Edward H; Otsuki, Hitoshi; Sawasaki, Tatsuya; Ishino, Tomoko; Takashima, Eizo; Tsuboi, Takafumi

    2018-06-02

    Malaria merozoite apical organelles; microneme and rhoptry secreted proteins play functional roles during and following invasion of host erythrocytes. Among numerous proteins, the rhoptries discharge high molecular weight proteins known as RhopH complex. Recent reports suggest that the RhopH complex is essential for growth and survival of the malaria parasite within erythrocytes. However, an in-depth understanding of the host-parasite molecular interactions is indispensable. Here we utilized a comprehensive mouse erythrocyte protein library consisting of 443 proteins produced by a wheat germ cell-free system, combined with AlphaScreen technology to identify mouse erythrocyte calmyrin as an interacting molecule of the rodent malaria parasite Plasmodium yoelii RhopH complex (PyRhopH). The PyRhopH interaction was dependent on the calmyrin N-terminus and divalent cation capacity. The finding unveils a recommendable and invaluable usefulness of our comprehensive mouse erythrocyte protein library together with the AlphaScreen technology in investigating a wide-range of host-parasite molecular interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Developing a molecular roadmap of drug-food interactions.

    Directory of Open Access Journals (Sweden)

    Kasper Jensen

    2015-02-01

    Full Text Available Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.

  16. The independent molecular interaction sites model. Pt. 1

    International Nuclear Information System (INIS)

    Naumann, K.H.; Lippert, E.

    1981-01-01

    A new reference system for the treatment of molecular fluids within the framework of thermodynamic perturbation theory is presented. The basic ingredient of our approach is a potential transformation which allows us to view molecular liquids and gases as mixtures of formally independent molecular interaction sites (IMIS model). Some relations between out method and the RAM theory are discussed. (orig.)

  17. Molecular interactions with reference to manifestation of solvation ...

    African Journals Online (AJOL)

    The density and viscosity data were analyzed by some semi-empirical viscosity models, and the results have been discussed in terms of molecular interactions and structural effects. The excess properties were found to be either negative or positive depending on the molecular interactions and the nature of liquid mixtures.

  18. Conformation, orientation and interaction in molecular monolayers

    International Nuclear Information System (INIS)

    Superfine, R.; Huang, J.Y.; Shen, Y.R.

    1989-01-01

    Knowledge of the conformation and ordering of molecular monolayers is essential for a detailed understanding of a wide variety of surface and interfacial phenomena. Over the past several years, surface second harmonic generation (SHG) has proven to be a valuable and versatile probe of monolayer systems. Our group has recently extended the technique to infrared-visible sum frequency generation (SFG) which has unique capabilities for surface vibrational spectroscopy. Like second harmonic generation, SFG is highly surface specific with submonolayer sensitivity at all interfaces accessible by light. The orientation of individual groups within an adsorbate molecule can be deduced by a polarization analysis of the SFG signal from the vibrational modes of the groups. The authors have used SHG and SFG to study orientations and conformations of surfactant and liquid crystal (LC) monolayers and their interaction on a substrate. The interfacial properties of LC are of great interest to many researchers for both basic science understanding and practical application to LC devices. It is well known that the bulk alignment of a liquid crystal in a cell is strongly affected by the surface treatment of the cell walls. The reason behind it is not yet clear. The theoretical background and experimental arrangement of SHG and SFG have been described elsewhere. In the setup, a 30 psec. Nd:YAG mode-locked laser system together with nonlinear accessories generates a visible beam at .532μm and an infrared beam tunable about 3.4μm. Both beams are focused to a common spot of 300μm dia. The typical signal off the surface from a compact ordered alkyl chain monolayer is ∼500 photons per pulse, easily detected with a photomultiplier tube

  19. RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

    Science.gov (United States)

    2018-01-01

    With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA–ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field. PMID:29297679

  20. Hybrid E-Textbooks as Comprehensive Interactive Learning Environments

    Science.gov (United States)

    Ghaem Sigarchian, Hajar; Logghe, Sara; Verborgh, Ruben; de Neve, Wesley; Salliau, Frank; Mannens, Erik; Van de Walle, Rik; Schuurman, Dimitri

    2018-01-01

    An e-TextBook can serve as an interactive learning environment (ILE), facilitating more effective teaching and learning processes. In this paper, we propose the novel concept of an EPUB 3-based Hybrid e-TextBook, which allows for interaction between the digital and the physical world. In that regard, we first investigated the gap between the…

  1. A comprehensive study into the molecular methodology and molecular biology of methanogenic Archaea

    DEFF Research Database (Denmark)

    Lange, M.; Ahring, Birgitte Kiær

    2001-01-01

    Methanogens belong to the kingdom of Euryarchaeota in the domain of Archaea. The Archaea differ from Bacteria in many aspects important to molecular work. Among these are cell wall composition, their sensitivity to antibiotics, their translation and transcription machinery, and their very strict ...... procedures. Efficient genetic manipulation systems, including shuttle and integration vector systems, have appeared for mesophilic, but not for thermophilic species within the last few years and will have a major impact on future investigations of methanogenic molecular biology....

  2. Biodiversity of Antarctic echinoids: a comprehensive and interactive database

    Directory of Open Access Journals (Sweden)

    Bruno David

    2005-12-01

    Full Text Available Eighty-one echinoid species are present south of the Antarctic Convergence, and they represent an important component of the benthic fauna. “Antarctic echinoids” is an interactive database synthesising the results of more than 100 years of Antarctic expeditions, and comprising information about all echinoid species. It includes illustrated keys for determination of the species, and information about their morphology and ecology (text, illustrations and glossary and their distribution (maps and histograms of bathymetrical distribution; the sources of the information (bibliography, collections and expeditions are also provided. All these data (taxonomic, morphologic, geographic, bathymetric… can be interactively queried in two main ways: (1 display of listings that can be browsed, sorted according to various criteria, or printed; and (2 interactive requests crossing the different kinds of data. Many other possibilities are offered, and an on-line help file is also available.

  3. Modeling of ultrafast THz interactions in molecular crystals

    DEFF Research Database (Denmark)

    Pedersen, Pernille Klarskov; Clark, Stewart J.; Jepsen, Peter Uhd

    2014-01-01

    In this paper we present a numerical study of terahertz pulses interacting with crystals of cesium iodide. We model the molecular dynamics of the cesium iodide crystals with the Density Functional Theory software CASTEP, where ultrafast terahertz pulses are implemented to the CASTEP software...... to interact with molecular crystals. We investigate the molecular dynamics of cesium iodide crystals when interacting with realistic terahertz pulses of field strengths from 0 to 50 MV/cm. We find nonlinearities in the response of the CsI crystals at field strengths higher than 10 MV/cm....

  4. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    Science.gov (United States)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  5. Molecular and biological interactions in colorectal cancer

    NARCIS (Netherlands)

    Heer, Pieter de

    2007-01-01

    The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3

  6. Probing gas-surface interactions with a molecular beam

    International Nuclear Information System (INIS)

    Spruit, M.E.M.

    1988-01-01

    The dynamics of direct scattering, trapping and sticking in molecular beam scattering is probed. The O 2 /Ag interaction was chosen, using the close-packed (111) plane of Ag as target surface. 170 refs.; 22 figs.; 3 tabs

  7. Maximum power operation of interacting molecular motors

    DEFF Research Database (Denmark)

    Golubeva, Natalia; Imparato, Alberto

    2013-01-01

    , as compared to the non-interacting system, in a wide range of biologically compatible scenarios. We furthermore consider the case where the motor-motor interaction directly affects the internal chemical cycle and investigate the effect on the system dynamics and thermodynamics.......We study the mechanical and thermodynamic properties of different traffic models for kinesin which are relevant in biological and experimental contexts. We find that motor-motor interactions play a fundamental role by enhancing the thermodynamic efficiency at maximum power of the motors...

  8. Tick-Pathogen Ensembles: Do Molecular Interactions Lead Ecological Innovation?

    Czech Academy of Sciences Publication Activity Database

    Cabezas Cruz, Alejandro; Estrada-Peňa, A.; Rego, Ryan O. M.; de la Fuente, J.

    2017-01-01

    Roč. 7, 13 March (2017), č. článku 74. ISSN 2235-2988 Institutional support: RVO:60077344 Keywords : tick-pathogen interactions * transcriptional reprogramming * epigenetics * ecological adaptation * Anaplasma phagocytophilum Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.300, year: 2016

  9. On the strong influence of molecular interactions over large distances

    Science.gov (United States)

    Pfennig, Andreas

    2018-03-01

    Molecular-dynamics simulations of liquid water show deterministic chaos, i.e. an intentionally introduced molecular position shift of an individual molecule increases exponentially by a factor of 10 in 0.23 ps. This is a Lyaponov instability. As soon as it reaches molecular scale, the direction of the resulting shift in molecular motions is unpredictable. The influence of any individual distant particle on an observed molecule will be minute, but the effect will quickly increase to molecular scale and beyond due to this exponential growth. Consequently, any individual particle in the universe will affect the behavior of any molecule within at most 33 ps after the interaction reaches it. A larger distance of the faraway particle does not decrease the influence on an observed molecule, but the effect reaches molecular scale only some ps later. Thus in evaluating the interactions, nearby and faraway molecules have to be equally accounted for. The consequences of this quickly reacting network of interactions on universal scale are fundamental. Even in a strictly deterministic view, molecular behavior is principally unpredictable, and thus has to be regarded random. Corresponding statements apply for any particles interacting. This result leads to a fundamental rethinking of the structure of interactions of molecules and particles as well as the behavior of reality.

  10. Molecular Characterization of Macrophage-Biomaterial Interactions.

    Science.gov (United States)

    Moore, Laura Beth; Kyriakides, Themis R

    2015-01-01

    Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulation. In this review, we discuss the molecular events that contribute to macrophage activation and fusion with a focus on the role of the inflammasome, signaling pathways such as JAK/STAT and NF-κB, and the putative involvement of micro RNAs in the regulation of these processes.

  11. Molecular Characterization of Macrophage-Biomaterial Interactions

    OpenAIRE

    Moore, Laura Beth; Kyriakides, Themis R.

    2015-01-01

    Implantation of biomaterials in vascularized tissues elicits the sequential engagement of molecular and cellular elements that constitute the foreign body response. Initial events include the non-specific adsorption of proteins to the biomaterial surface that render it adhesive for cells such as neutrophils and macrophages. The latter undergo unique activation and in some cases undergo cell-cell fusion to form foreign body giant cells that contribute to implant damage and fibrotic encapsulati...

  12. DockingShop: A Tool for Interactive Molecular Docking

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ting-Cheng; Max, Nelson L.; Ding, Jinhui; Bethel, E. Wes; Crivelli, Silvia N.

    2005-04-24

    Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. Docking Shop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output--the structure of aprotein-ligand or protein-protein complex--may serve as an input for aprotein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

  13. Molecular basis and regulation of OTULIN-LUBAC interaction

    DEFF Research Database (Denmark)

    Elliott, Paul R.; Al-Saoudi, Sofie Vincents; Marco-Casanova, Paola

    2014-01-01

    Ub. Now, we show that OTULIN binds via a conserved PUB-interacting motif (PIM) to the PUB domain of the LUBAC component HOIP. Crystal structures and nuclear magnetic resonance experiments reveal the molecular basis for the high-affinity interaction and explain why OTULIN binds the HOIP PUB domain...

  14. Cellular and molecular interaction in HIV infection: A review | Timbo ...

    African Journals Online (AJOL)

    Objective: To review the cellular and molecular interactions between HIV and the host immune system that lead to full-blown AIDS. Data Sources: Published reports on HIV/host interaction during a fifteen year period beginning from 1987. Study selection: Only those studies involving humans and non-human primates were ...

  15. Strategy and pattern recognition in expert\\ud comprehension of 2 × 2 interaction graphs

    OpenAIRE

    Peebles, David

    2013-01-01

    I present a model of expert comprehension performance for 2 × 2 "interaction" graphs typically used to present data from two-way factorial research designs. Developed using the ACT-R cognitive architecture, the model simulates the cognitive and perceptual operations involved in interpreting interaction graphs and provides a detailed characterisation of the information\\ud extracted from the diagram, the prior knowledge required to interpret interaction graphs, and the knowledge generated durin...

  16. Soft matter interactions at the molecular scale: interaction forces and energies between single hydrophobic model peptides.

    Science.gov (United States)

    Stock, Philipp; Utzig, Thomas; Valtiner, Markus

    2017-02-08

    In all realms of soft matter research a fundamental understanding of the structure/property relationships based on molecular interactions is crucial for developing a framework for the targeted design of soft materials. However, a molecular picture is often difficult to ascertain and yet essential for understanding the many different competing interactions at play, including entropies and cooperativities, hydration effects, and the enormous design space of soft matter. Here, we characterized for the first time the interaction between single hydrophobic molecules quantitatively using atomic force microscopy, and demonstrated that single molecular hydrophobic interaction free energies are dominated by the area of the smallest interacting hydrophobe. The interaction free energy amounts to 3-4 kT per hydrophobic unit. Also, we find that the transition state of the hydrophobic interactions is located at 3 Å with respect to the ground state, based on Bell-Evans theory. Our results provide a new path for understanding the nature of hydrophobic interactions at the single molecular scale. Our approach enables us to systematically vary hydrophobic and any other interaction type by utilizing peptide chemistry providing a strategic advancement to unravel molecular surface and soft matter interactions at the single molecular scale.

  17. Prediction and Dissection of Protein-RNA Interactions by Molecular Descriptors.

    Science.gov (United States)

    Liu, Zhi-Ping; Chen, Luonan

    2016-01-01

    Protein-RNA interactions play crucial roles in numerous biological processes. However, detecting the interactions and binding sites between protein and RNA by traditional experiments is still time consuming and labor costing. Thus, it is of importance to develop bioinformatics methods for predicting protein-RNA interactions and binding sites. Accurate prediction of protein-RNA interactions and recognitions will highly benefit to decipher the interaction mechanisms between protein and RNA, as well as to improve the RNA-related protein engineering and drug design. In this work, we summarize the current bioinformatics strategies of predicting protein-RNA interactions and dissecting protein-RNA interaction mechanisms from local structure binding motifs. In particular, we focus on the feature-based machine learning methods, in which the molecular descriptors of protein and RNA are extracted and integrated as feature vectors of representing the interaction events and recognition residues. In addition, the available methods are classified and compared comprehensively. The molecular descriptors are expected to elucidate the binding mechanisms of protein-RNA interaction and reveal the functional implications from structural complementary perspective.

  18. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

    Science.gov (United States)

    Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

    2013-10-07

    Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

  19. Shaping distinct magnetic interactions in molecular compounds

    International Nuclear Information System (INIS)

    Filoti, George; Bartolome, Juan; Palade, Petru; Prisecaru, Ion; Valsangiacom, Cristina; Kuncser, Victor; Mindru, Ioana; Patron, Luminita

    2011-01-01

    Oxalates containing various 3d transitional elements and positive NH 4 or negative OH groups were newly synthesized. Each above-mentioned component has directly influenced the structure, the electronic or interaction properties, while some unexpected behaviors were revealed by various magnetic and Moessbauer measurements. The main magnetic parameters, the long-range anti-ferromagnetic couplings observed at very low temperature and, particularly the uncompensated moment are discussed in detail. The induced lower spin states for bivalent ions and especially the anti-parallel arrangement of the spins belonging to trivalent and bivalent iron inside the molecule are also emphasized. - Research highlights: → Nine new oxalates, with 3d elements, showing interesting characteristics were synthesized. →The oxalate units and the positive or negative groups have induced various magnetic properties. → The Moessbauer data revealed two different positions for each valence state of iron in molecule. → There is a competition of anti-ferromagnetic couplings inside the magnetic units and between them. → An overall ferri-magnetic long range ordering was demonstrated unambiguously.

  20. Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

    Science.gov (United States)

    Subbiah, Vivek; Wagner, Michael J; McGuire, Mary F; Sarwari, Nawid M; Devarajan, Eswaran; Lewis, Valerae O; Westin, Shanon; Kato, Shumei; Brown, Robert E; Anderson, Pete

    2015-12-01

    Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are

  1. Interactive Molecular Graphics for Augmented Reality Using HoloLens.

    Science.gov (United States)

    Müller, Christoph; Krone, Michael; Huber, Markus; Biener, Verena; Herr, Dominik; Koch, Steffen; Reina, Guido; Weiskopf, Daniel; Ertl, Thomas

    2018-06-13

    Immersive technologies like stereo rendering, virtual reality, or augmented reality (AR) are often used in the field of molecular visualisation. Modern, comparably lightweight and affordable AR headsets like Microsoft's HoloLens open up new possibilities for immersive analytics in molecular visualisation. A crucial factor for a comprehensive analysis of molecular data in AR is the rendering speed. HoloLens, however, has limited hardware capabilities due to requirements like battery life, fanless cooling and weight. Consequently, insights from best practises for powerful desktop hardware may not be transferable. Therefore, we evaluate the capabilities of the HoloLens hardware for modern, GPU-enabled, high-quality rendering methods for the space-filling model commonly used in molecular visualisation. We also assess the scalability for large molecular data sets. Based on the results, we discuss ideas and possibilities for immersive molecular analytics. Besides more obvious benefits like the stereoscopic rendering offered by the device, this specifically includes natural user interfaces that use physical navigation instead of the traditional virtual one. Furthermore, we consider different scenarios for such an immersive system, ranging from educational use to collaborative scenarios.

  2. Plant-aphid interactions: molecular and ecological perspectives.

    Science.gov (United States)

    Goggin, Fiona L

    2007-08-01

    Many aphids are major agricultural pests because of their unparalleled reproductive capacity and their ability to manipulate host plant physiology. Aphid population growth and its impact on plant fitness are strongly influenced by interactions with other organisms, including plant pathogens, endophytes, aphid endosymbionts, predators, parasitoids, ants, and other herbivores. Numerous molecular and genomic resources have recently been developed to identify sources of aphid resistance in plants, as well as potentially novel targets for control in aphids. Moreover, the same model systems that are used to explore direct molecular interactions between plants and aphids can be utilized to study the ecological context in which they occur.

  3. Multimedia Listening Comprehension: Metacognitive Instruction or Metacognitive Instruction through Dialogic Interaction

    Science.gov (United States)

    Bozorgian, Hossein; Alamdari, Ebrahim Fakhri

    2018-01-01

    This study is an attempt to investigate the effect of metacognitive instruction through dialogic interaction in a joint activity on advanced Iranian English as a foreign language (EFL) learners' multimedia listening and their metacognitive awareness in listening comprehension. The data were collected through (N = 180) male and female Iranian…

  4. Emergent Readers' Social Interaction Styles and Their Comprehension Processes during Buddy Reading

    Science.gov (United States)

    Christ, Tanya; Wang, X. Christine; Chiu, Ming Ming

    2015-01-01

    To examine the relations between emergent readers' social interaction styles and their comprehension processes, we adapted sociocultural and transactional views of learning and reading, and conducted statistical discourse analysis of 1,359 conversation turns transcribed from 14 preschoolers' 40 buddy reading events. Results show that interaction…

  5. 2004 Atomic and Molecular Interactions Gordon Research Conference

    International Nuclear Information System (INIS)

    Dr. Paul J. Dagdigian

    2004-01-01

    The 2004 Gordon Research Conference on Atomic and Molecular Interactions was held July 11-16 at Colby-Sawyer College, New London, New Hampshire. This latest edition in a long-standing conference series featured invited talks and contributed poster papers on dynamics and intermolecular interactions in a variety of environments, ranging from the gas phase through surfaces and condensed media. A total of 90 conferees participated in the conference

  6. 2004 Atomic and Molecular Interactions Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Paul J. Dagdigian

    2004-10-25

    The 2004 Gordon Research Conference on Atomic and Molecular Interactions was held July 11-16 at Colby-Sawyer College, New London, New Hampshire. This latest edition in a long-standing conference series featured invited talks and contributed poster papers on dynamics and intermolecular interactions in a variety of environments, ranging from the gas phase through surfaces and condensed media. A total of 90 conferees participated in the conference.

  7. Design of a Comprehensive Biochemistry and Molecular Biology Experiment: Phase Variation Caused by Recombinational Regulation of Bacterial Gene Expression

    Science.gov (United States)

    Sheng, Xiumei; Xu, Shungao; Lu, Renyun; Isaac, Dadzie; Zhang, Xueyi; Zhang, Haifang; Wang, Huifang; Qiao, Zheng; Huang, Xinxiang

    2014-01-01

    Scientific experiments are indispensable parts of Biochemistry and Molecular Biology. In this study, a comprehensive Biochemistry and Molecular Biology experiment about "Salmonella enterica" serovar Typhi Flagellar phase variation has been designed. It consisted of three parts, namely, inducement of bacterial Flagellar phase variation,…

  8. A comprehensive study of extended tetrathiafulvalene cruciform molecules for molecular electronics: synthesis and electrical transport measurements.

    Science.gov (United States)

    Parker, Christian R; Leary, Edmund; Frisenda, Riccardo; Wei, Zhongming; Jennum, Karsten S; Glibstrup, Emil; Abrahamsen, Peter Bæch; Santella, Marco; Christensen, Mikkel A; Della Pia, Eduardo Antonio; Li, Tao; Gonzalez, Maria Teresa; Jiang, Xingbin; Morsing, Thorbjørn J; Rubio-Bollinger, Gabino; Laursen, Bo W; Nørgaard, Kasper; van der Zant, Herre; Agrait, Nicolas; Nielsen, Mogens Brøndsted

    2014-11-26

    Cruciform-like molecules with two orthogonally placed π-conjugated systems have in recent years attracted significant interest for their potential use as molecular wires in molecular electronics. Here we present synthetic protocols for a large selection of cruciform molecules based on oligo(phenyleneethynylene) (OPE) and tetrathiafulvalene (TTF) scaffolds, end-capped with acetyl-protected thiolates as electrode anchoring groups. The molecules were subjected to a comprehensive study of their conducting properties as well as their photophysical and electrochemical properties in solution. The complex nature of the molecules and their possible binding in different configurations in junctions called for different techniques of conductance measurements: (1) conducting-probe atomic force microscopy (CP-AFM) measurements on self-assembled monolayers (SAMs), (2) mechanically controlled break-junction (MCBJ) measurements, and (3) scanning tunneling microscopy break-junction (STM-BJ) measurements. The CP-AFM measurements showed structure-property relationships from SAMs of series of OPE3 and OPE5 cruciform molecules; the conductance of the SAM increased with the number of dithiafulvene (DTF) units (0, 1, 2) along the wire, and it increased when substituting two arylethynyl end groups of the OPE3 backbone with two DTF units. The MCBJ and STM-BJ studies on single molecules both showed that DTFs decreased the junction formation probability, but, in contrast, no significant influence on the single-molecule conductance was observed. We suggest that the origins of the difference between SAM and single-molecule measurements lie in the nature of the molecule-electrode interface as well as in effects arising from molecular packing in the SAMs. This comprehensive study shows that for complex molecules care should be taken when directly comparing single-molecule measurements and measurements of SAMs and solid-state devices thereof.

  9. READING COMPREHENSION EXERCISES ONLINE: THE EFFECTS OF FEEDBACK, PROFICIENCY AND INTERACTION

    Directory of Open Access Journals (Sweden)

    Philip Murphy

    2007-02-01

    Full Text Available This paper describes an ongoing project to create an online version of a reading programme, a custom-designed English language proficiency course at a university in Japan. Following an interactionist view of second language acquisition, it was hypothesised that comprehension of a reading passage could be enhanced by online materials promoting interaction between students as they completed a multiple-choice reading comprehension exercise. Interaction was promoted: (a through pair work at a single computer and (b by providing Elaborative feedback in the form of hints about incorrect answers as a means of stimulating discussion about corrections. Students were randomly selected from upper and lower levels of English proficiency, as determined by the Kanda English Proficiency Test (Bonk & Ockey, 2003, to receive either Elaborative feedback or Knowledge of Correct Response feedback (which supplies the correct answers. Within these groups, some students worked in pairs and some alone. Quantitative results show that the interaction between Type of feedback and Manner of study (individual or pair work was statistically significant; students performed best on a follow-up comprehension exercise when in pairs and having been provided with Elaborative feedback. Furthermore, qualitative analysis of transcribed interactions also shows that Elaborative feedback was conducive to quality interaction.

  10. JAMI: a Java library for molecular interactions and data interoperability.

    Science.gov (United States)

    Sivade Dumousseau, M; Koch, M; Shrivastava, A; Alonso-López, D; De Las Rivas, J; Del-Toro, N; Combe, C W; Meldal, B H M; Heimbach, J; Rappsilber, J; Sullivan, J; Yehudi, Y; Orchard, S

    2018-04-11

    A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types. A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats. Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.

  11. Molecular dynamics study of the silica-water-SDA interactions

    NARCIS (Netherlands)

    Szyja, B.M.; Jansen, A.P.J.; Verstraelen, T.; Santen, van R.A.

    2009-01-01

    In this paper we have applied the molecular dynamics simulations in order to analyse the role of the structure directing tetrapropylammonium ions in the aggregation process that leads to silicalite formation. We address the specific question of how the interactions between silica precursor species

  12. Modeling molecular boiling points using computed interaction energies.

    Science.gov (United States)

    Peterangelo, Stephen C; Seybold, Paul G

    2017-12-20

    The noncovalent van der Waals interactions between molecules in liquids are typically described in textbooks as occurring between the total molecular dipoles (permanent, induced, or transient) of the molecules. This notion was tested by examining the boiling points of 67 halogenated hydrocarbon liquids using quantum chemically calculated molecular dipole moments, ionization potentials, and polarizabilities obtained from semi-empirical (AM1 and PM3) and ab initio Hartree-Fock [HF 6-31G(d), HF 6-311G(d,p)], and density functional theory [B3LYP/6-311G(d,p)] methods. The calculated interaction energies and an empirical measure of hydrogen bonding were employed to model the boiling points of the halocarbons. It was found that only terms related to London dispersion energies and hydrogen bonding proved significant in the regression analyses, and the performances of the models generally improved at higher levels of quantum chemical computation. An empirical estimate for the molecular polarizabilities was also tested, and the best models for the boiling points were obtained using either this empirical polarizability itself or the polarizabilities calculated at the B3LYP/6-311G(d,p) level, along with the hydrogen-bonding parameter. The results suggest that the cohesive forces are more appropriately described as resulting from highly localized interactions rather than interactions between the global molecular dipoles.

  13. Gesture Interaction Browser-Based 3D Molecular Viewer.

    Science.gov (United States)

    Virag, Ioan; Stoicu-Tivadar, Lăcrămioara; Crişan-Vida, Mihaela

    2016-01-01

    The paper presents an open source system that allows the user to interact with a 3D molecular viewer using associated hand gestures for rotating, scaling and panning the rendered model. The novelty of this approach is that the entire application is browser-based and doesn't require installation of third party plug-ins or additional software components in order to visualize the supported chemical file formats. This kind of solution is suitable for instruction of users in less IT oriented environments, like medicine or chemistry. For rendering various molecular geometries our team used GLmol (a molecular viewer written in JavaScript). The interaction with the 3D models is made with Leap Motion controller that allows real-time tracking of the user's hand gestures. The first results confirmed that the resulting application leads to a better way of understanding various types of translational bioinformatics related problems in both biomedical research and education.

  14. NGLview-interactive molecular graphics for Jupyter notebooks.

    Science.gov (United States)

    Nguyen, Hai; Case, David A; Rose, Alexander S

    2018-04-01

    NGLview is a Jupyter/IPython widget to interactively view molecular structures as well as trajectories from molecular dynamics simulations. Fast and scalable molecular graphics are provided through the NGL Viewer. The widget supports showing data from the file-system, online data bases and from objects of many popular analysis libraries including mdanalysis, mdtraj, pytraj, rdkit and more. The source code is freely available under the MIT license at https://github.com/arose/nglview. Python packages are available from PyPI and bioconda. NGLview uses Python on the server-side and JavaScript on the client. The integration with Jupyter is done through the ipywidgets package. The NGL Viewer is embedded client-side to provide WebGL accelerated molecular graphics. asr.moin@gmail.com.

  15. Formalization and Interaction: Toward a Comprehensive History of Technology-Related Knowledge in Early Modern Europe.

    Science.gov (United States)

    Popplow, Marcus

    2015-12-01

    Recent critical approaches to what has conventionally been described as "scientific" and "technical" knowledge in early modern Europe have provided a wealth of new insights. So far, the various analytical concepts suggested by these studies have not yet been comprehensively discussed. The present essay argues that such comprehensive approaches might prove of special value for long-term and cross-cultural reflections on technology-related knowledge. As heuristic tools, the notions of "formalization" and "interaction" are proposed as part of alternative narratives to those highlighting the emergence of "science" as the most relevant development for technology-related knowledge in early modern Europe.

  16. Molecular and Thermodynamic Properties of Zwitterions versus Ionic Liquids: A Comprehensive Computational Analysis to Develop Advanced Separation Processes.

    Science.gov (United States)

    Moreno, Daniel; Gonzalez-Miquel, Maria; Ferro, Victor R; Palomar, Jose

    2018-04-05

    Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid-liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Modeling of nanotoxicity molecular interactions of nanomaterials with bionanomachines

    CERN Document Server

    Zhou, Ruhong

    2015-01-01

    This book provides a comprehensive overview of the fundamentals of nanotoxicity modeling and its implications for the development of novel nanomedicines. It lays out the fundamentals of nanotoxicity modeling for an array of nanomaterial systems, ranging from carbon-based nanoparticles to noble metals, metal oxides, and quantum dots. The author illustrates how molecular (classical mechanics) and atomic (quantum mechanics) modeling approaches can be applied to bolster our understanding of many important aspects of this critical nanotoxicity issue. Each chapter is organized by types of nanomaterials for practicality, making this an ideal book for senior undergraduate students, graduate students, and researchers in nanotechnology, chemistry, physics, molecular biology, and computer science. It is also of interest to academic and industry professionals who work on nanodrug delivery and related biomedical applications, and aids readers in their biocompatibility assessment efforts in the coming age of nanotechnology...

  18. Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae

    Science.gov (United States)

    Reguly, Teresa; Breitkreutz, Ashton; Boucher, Lorrie; Breitkreutz, Bobby-Joe; Hon, Gary C; Myers, Chad L; Parsons, Ainslie; Friesen, Helena; Oughtred, Rose; Tong, Amy; Stark, Chris; Ho, Yuen; Botstein, David; Andrews, Brenda; Boone, Charles; Troyanskya, Olga G; Ideker, Trey; Dolinski, Kara; Batada, Nizar N; Tyers, Mike

    2006-01-01

    Background The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference. Results We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID () and SGD () databases. Conclusion Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks. PMID:16762047

  19. Hadronic molecular states from the K anti K* interaction

    Energy Technology Data Exchange (ETDEWEB)

    Lue, Pei-Liang; He, Jun [Chinese Academy of Sciences, Theoretical Physics Division, Institute of Modern Physics, Lanzhou (China); Institute of Modern Physics of CAS and Lanzhou University, Research Center for Hadron and CSR Physics, Lanzhou (China)

    2016-12-15

    In this work, the K anti K* interaction is studied in a quasipotential Bethe-Salpeter equation approach combined with the one-boson-exchange model. With the help of the hidden-gauge Lagrangian, the exchanges of pseudoscalar mesons (π and η) and vector mesons (ρ, ω and φ) are considered to describe the K anti K* interaction. Besides the direct vector-meson exchange which can be related to the Weinberg-Tomozawa term, pseudoscalar-meson exchanges also play important roles in the mechanism of the K anti K* interaction. The poles of scattering amplitude are searched to find the molecular states produced from the K anti K* interaction. In the case of quantum number I{sup G}(J{sup PC}) = 0{sup +}(1{sup ++}), a pole is found with a reasonable cutoff, which can be related to the f{sub 1}(1285) in experiment. Another bound state with 0{sup -}(1{sup +-}) is also produced from the K anti K* interaction, which can be related to the h{sub 1}(1380). In the isovector sector, the interaction is much weaker and a bound state with 1{sup +}(1{sup +}) relevant to the b{sub 1}(1235) is produced but at a larger cutoff. Our results suggest that in the hadronic molecular state picture the f{sub 1}(1285) and b{sub 1}(1235) are the strange partners of the X(3872) and Z{sub c}(3900), respectively. (orig.)

  20. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

    2010-01-01

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

  1. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    Directory of Open Access Journals (Sweden)

    Vaithilingam Aparna

    2010-05-01

    Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

  2. RAID: a comprehensive resource for human RNA-associated (RNA–RNA/RNA–protein) interaction

    Science.gov (United States)

    Zhang, Xiaomeng; Wu, Deng; Chen, Liqun; Li, Xiang; Yang, Jinxurong; Fan, Dandan; Dong, Tingting; Liu, Mingyue; Tan, Puwen; Xu, Jintian; Yi, Ying; Wang, Yuting; Zou, Hua; Hu, Yongfei; Fan, Kaili; Kang, Juanjuan; Huang, Yan; Miao, Zhengqiang; Bi, Miaoman; Jin, Nana; Li, Kongning; Li, Xia; Xu, Jianzhen; Wang, Dong

    2014-01-01

    Transcriptomic analyses have revealed an unexpected complexity in the eukaryote transcriptome, which includes not only protein-coding transcripts but also an expanding catalog of noncoding RNAs (ncRNAs). Diverse coding and noncoding RNAs (ncRNAs) perform functions through interaction with each other in various cellular processes. In this project, we have developed RAID (http://www.rna-society.org/raid), an RNA-associated (RNA–RNA/RNA–protein) interaction database. RAID intends to provide the scientific community with all-in-one resources for efficient browsing and extraction of the RNA-associated interactions in human. This version of RAID contains more than 6100 RNA-associated interactions obtained by manually reviewing more than 2100 published papers, including 4493 RNA–RNA interactions and 1619 RNA–protein interactions. Each entry contains detailed information on an RNA-associated interaction, including RAID ID, RNA/protein symbol, RNA/protein categories, validated method, expressing tissue, literature references (Pubmed IDs), and detailed functional description. Users can query, browse, analyze, and manipulate RNA-associated (RNA–RNA/RNA–protein) interaction. RAID provides a comprehensive resource of human RNA-associated (RNA–RNA/RNA–protein) interaction network. Furthermore, this resource will help in uncovering the generic organizing principles of cellular function network. PMID:24803509

  3. Controlling single-molecule junction conductance by molecular interactions

    Science.gov (United States)

    Kitaguchi, Y.; Habuka, S.; Okuyama, H.; Hatta, S.; Aruga, T.; Frederiksen, T.; Paulsson, M.; Ueba, H.

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment. PMID:26135251

  4. Nanoscale swimmers: hydrodynamic interactions and propulsion of molecular machines

    Science.gov (United States)

    Sakaue, T.; Kapral, R.; Mikhailov, A. S.

    2010-06-01

    Molecular machines execute nearly regular cyclic conformational changes as a result of ligand binding and product release. This cyclic conformational dynamics is generally non-reciprocal so that under time reversal a different sequence of machine conformations is visited. Since such changes occur in a solvent, coupling to solvent hydrodynamic modes will generally result in self-propulsion of the molecular machine. These effects are investigated for a class of coarse grained models of protein machines consisting of a set of beads interacting through pair-wise additive potentials. Hydrodynamic effects are incorporated through a configuration-dependent mobility tensor, and expressions for the propulsion linear and angular velocities, as well as the stall force, are obtained. In the limit where conformational changes are small so that linear response theory is applicable, it is shown that propulsion is exponentially small; thus, propulsion is nonlinear phenomenon. The results are illustrated by computations on a simple model molecular machine.

  5. Atom-scale molecular interactions in lipid raft mixtures

    DEFF Research Database (Denmark)

    Niemelä, Perttu S; Hyvönen, Marja T; Vattulainen, Ilpo

    2009-01-01

    We review the relationship between molecular interactions and the properties of lipid environments. A specific focus is given on bilayers which contain sphingomyelin (SM) and sterols due to their essential role for the formation of lipid rafts. The discussion is based on recent atom-scale molecular...... dynamics simulations, complemented by extensive comparison to experimental data. The discussion is divided into four sections. The first part investigates the properties of one-component SM bilayers and compares them to bilayers with phosphatidylcholine (PC), the focus being on a detailed analysis...... examples of this issue. The third part concentrates on the specificity of intermolecular interactions in three-component mixtures of SM, PC and cholesterol (CHOL) under conditions where the concentrations of SM and CHOL are dilute with respect to that of PC. The results show how SM and CHOL favor one...

  6. Immobilized enzymes: understanding enzyme - surface interactions at the molecular level.

    Science.gov (United States)

    Hoarau, Marie; Badieyan, Somayesadat; Marsh, E Neil G

    2017-11-22

    Enzymes immobilized on solid supports have important and industrial and medical applications. However, their uses are limited by the significant reductions in activity and stability that often accompany the immobilization process. Here we review recent advances in our understanding of the molecular level interactions between proteins and supporting surfaces that contribute to changes in stability and activity. This understanding has been facilitated by the application of various surface-sensitive spectroscopic techniques that allow the structure and orientation of enzymes at the solid/liquid interface to be probed, often with monolayer sensitivity. An appreciation of the molecular interactions between enzyme and surface support has allowed the surface chemistry and method of enzyme attachement to be fine-tuned such that activity and stability can be greatly enhanced. These advances suggest that a much wider variety of enzymes may eventually be amenable to immobilization as green catalysts.

  7. Weak Molecular Interactions in Clathrin-Mediated Endocytosis

    Directory of Open Access Journals (Sweden)

    Sarah M. Smith

    2017-11-01

    Full Text Available Clathrin-mediated endocytosis is a process by which specific molecules are internalized from the cell periphery for delivery to early endosomes. The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. This review discusses the structural and functional data that have improved our knowledge and understanding of the main weak molecular interactions implicated in clathrin-mediated endocytosis, with a particular focus on the two key proteins: AP2 and clathrin.

  8. Fanconi Anemia Proteins and Their Interacting Partners: A Molecular Puzzle

    Science.gov (United States)

    Kaddar, Tagrid; Carreau, Madeleine

    2012-01-01

    In recent years, Fanconi anemia (FA) has been the subject of intense investigations, primarily in the DNA repair research field. Many discoveries have led to the notion of a canonical pathway, termed the FA pathway, where all FA proteins function sequentially in different protein complexes to repair DNA cross-link damages. Although a detailed architecture of this DNA cross-link repair pathway is emerging, the question of how a defective DNA cross-link repair process translates into the disease phenotype is unresolved. Other areas of research including oxidative metabolism, cell cycle progression, apoptosis, and transcriptional regulation have been studied in the context of FA, and some of these areas were investigated before the fervent enthusiasm in the DNA repair field. These other molecular mechanisms may also play an important role in the pathogenesis of this disease. In addition, several FA-interacting proteins have been identified with roles in these “other” nonrepair molecular functions. Thus, the goal of this paper is to revisit old ideas and to discuss protein-protein interactions related to other FA-related molecular functions to try to give the reader a wider perspective of the FA molecular puzzle. PMID:22737580

  9. Molecular Analysis of AFP and HSA Interactions with PTEN Protein

    Directory of Open Access Journals (Sweden)

    Mingyue Zhu

    2015-01-01

    Full Text Available Human cytoplasmic alpha-fetoprotein (AFP has been classified as a member of the albuminoid gene family. The protein sequence of AFP has significant homology to that of human serum albumin (HSA, but its biological characteristics are vastly different from HSA. The AFP functions as a regulator in the phosphatidylinositol 3-kinase (PI3K/protein kinase B (AKT pathway, but HSA plays a key role as a transport protein. To probe their molecular mechanisms, we have applied colocalization, coimmunoprecipitation (co-IP, and molecular docking approaches to analyze the differences between AFP and HSA. The data from colocalization and co-IP displayed a strong interaction between AFP and PTEN (phosphatase and tensin homolog, demonstrating that AFP did bind to PTEN, but HSA did not. The molecular docking study further showed that the AFP domains I and III could contact with PTEN. In silicon substitutions of AFP binding site residues at position 490M/K and 105L/R corresponding to residues K490 and R105 in HSA resulted in steric clashes with PTEN residues R150 and K46, respectively. These steric clashes may explain the reason why HSA cannot bind to PTEN. Ultimately, the experimental results and the molecular modeling data from the interactions of AFP and HSA with PTEN will help us to identify targets for designing drugs and vaccines against human hepatocellular carcinoma.

  10. Probing Molecular Insights into Zika Virus–Host Interactions

    Directory of Open Access Journals (Sweden)

    Ina Lee

    2018-05-01

    Full Text Available The recent Zika virus (ZIKV outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1 what virologic factors are involved in the ZIKV-associated human diseases; (2 which ZIKV protein(s contributes to the enhanced viral pathogenicity; and (3 how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions.

  11. Probing Molecular Insights into Zika Virus–Host Interactions

    Science.gov (United States)

    Lee, Ina; Li, Ge; Wang, Shusheng; Desprès, Philippe; Zhao, Richard Y.

    2018-01-01

    The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain–Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV–host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV–host Interactions. PMID:29724036

  12. Predicting and understanding comprehensive drug-drug interactions via semi-nonnegative matrix factorization.

    Science.gov (United States)

    Yu, Hui; Mao, Kui-Tao; Shi, Jian-Yu; Huang, Hua; Chen, Zhi; Dong, Kai; Yiu, Siu-Ming

    2018-04-11

    Drug-drug interactions (DDIs) always cause unexpected and even adverse drug reactions. It is important to identify DDIs before drugs are used in the market. However, preclinical identification of DDIs requires much money and time. Computational approaches have exhibited their abilities to predict potential DDIs on a large scale by utilizing pre-market drug properties (e.g. chemical structure). Nevertheless, none of them can predict two comprehensive types of DDIs, including enhancive and degressive DDIs, which increases and decreases the behaviors of the interacting drugs respectively. There is a lack of systematic analysis on the structural relationship among known DDIs. Revealing such a relationship is very important, because it is able to help understand how DDIs occur. Both the prediction of comprehensive DDIs and the discovery of structural relationship among them play an important guidance when making a co-prescription. In this work, treating a set of comprehensive DDIs as a signed network, we design a novel model (DDINMF) for the prediction of enhancive and degressive DDIs based on semi-nonnegative matrix factorization. Inspiringly, DDINMF achieves the conventional DDI prediction (AUROC = 0.872 and AUPR = 0.605) and the comprehensive DDI prediction (AUROC = 0.796 and AUPR = 0.579). Compared with two state-of-the-art approaches, DDINMF shows it superiority. Finally, representing DDIs as a binary network and a signed network respectively, an analysis based on NMF reveals crucial knowledge hidden among DDIs. Our approach is able to predict not only conventional binary DDIs but also comprehensive DDIs. More importantly, it reveals several key points about the DDI network: (1) both binary and signed networks show fairly clear clusters, in which both drug degree and the difference between positive degree and negative degree show significant distribution; (2) the drugs having large degrees tend to have a larger difference between positive degree

  13. A COMPREHENSIVE STUDY OF HYDROGEN ADSORBING TO AMORPHOUS WATER ICE: DEFINING ADSORPTION IN CLASSICAL MOLECULAR DYNAMICS

    Energy Technology Data Exchange (ETDEWEB)

    Dupuy, John L.; Lewis, Steven P.; Stancil, P. C. [Department of Physics and Astronomy and the Center for Simulational Physics, University of Georgia, Athens, GA 30602 (United States)

    2016-11-01

    Gas–grain and gas–phase reactions dominate the formation of molecules in the interstellar medium (ISM). Gas–grain reactions require a substrate (e.g., a dust or ice grain) on which the reaction is able to occur. The formation of molecular hydrogen (H{sub 2}) in the ISM is the prototypical example of a gas–grain reaction. In these reactions, an atom of hydrogen will strike a surface, stick to it, and diffuse across it. When it encounters another adsorbed hydrogen atom, the two can react to form molecular hydrogen and then be ejected from the surface by the energy released in the reaction. We perform in-depth classical molecular dynamics simulations of hydrogen atoms interacting with an amorphous water-ice surface. This study focuses on the first step in the formation process; the sticking of the hydrogen atom to the substrate. We find that careful attention must be paid in dealing with the ambiguities in defining a sticking event. The technical definition of a sticking event will affect the computed sticking probabilities and coefficients. Here, using our new definition of a sticking event, we report sticking probabilities and sticking coefficients for nine different incident kinetic energies of hydrogen atoms [5–400 K] across seven different temperatures of dust grains [10–70 K]. We find that probabilities and coefficients vary both as a function of grain temperature and incident kinetic energy over the range of 0.99–0.22.

  14. Comparison of biomolecules on the basis of Molecular Interaction Potentials

    Directory of Open Access Journals (Sweden)

    Rodrigo Jordi

    2002-01-01

    Full Text Available Molecular Interaction Potentials (MIP are frequently used for the comparison of series of compounds displaying related biological behaviors. These potentials are interaction energies between the considered compounds and relevant probes. The interaction energies are computed in the nodes of grids defined around the compounds. There is a need of detailed and objective comparative analyses of MIP distributions in the framework of structure-activity studies. On the other hand, MIP-based studies do not have to be restricted to series of small ligands, since such studies present also interesting possibilities for the analysis and comparison of biological macromolecules. Such analyses can benefit from the application of new methods and computational approaches. The new software MIPSim (Molecular Interaction Potentials Similarity analysis has recently been introduced with the purpose of analyzing and comparing MIP distributions of series of biomolecules. This program is transparently integrated with other programs, like GAMESS or GRID, which can be used for the computation of the potentials to be analyzed or compared. MIPSim incorporates several definitions of similarity coefficients, and is capable of combining several similarity measures into a single one. On the other hand, MIPSim can perform automatic explorations of the maximum similarity alignments between pairs of molecules.

  15. Molecular electrostatics for probing lone pair-π interactions.

    Science.gov (United States)

    Mohan, Neetha; Suresh, Cherumuttathu H; Kumar, Anmol; Gadre, Shridhar R

    2013-11-14

    An electrostatics-based approach has been proposed for probing the weak interactions between lone pair containing molecules and π deficient molecular systems. For electron-rich molecules, the negative minima in molecular electrostatic potential (MESP) topography give the location of electron localization and the MESP value at the minimum (Vmin) quantifies the electron-rich character of that region. Interactive behavior of a lone pair bearing molecule with electron deficient π-systems, such as hexafluorobenzene, 1,3,5-trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene explored within DFT brings out good correlation of the lone pair-π interaction energy (E(int)) with the Vmin value of the electron-rich system. Such interaction is found to be portrayed well with the Electrostatic Potential for Intermolecular Complexation (EPIC) model. On the basis of the precise location of MESP minimum, a prediction for the orientation of a lone pair bearing molecule with an electron deficient π-system is possible in the majority of the cases studied.

  16. Proteomics at the center of nutrigenomics: comprehensive molecular understanding of dietary health effects.

    Science.gov (United States)

    Kussmann, Martin; Affolter, Michael

    2009-01-01

    Apart from the air we breathe, food is the only physical matter we take into our body during our life. Nutrition exhibits therefore the most important life-long environmental impact on human health. Food components interact with our body at system, organ, cellular, and molecular levels. These dietary components come in complex mixtures, in which not only the presence and concentrations of a single compound but also interactions of multiple compounds determine ingredient bioavailability and bioefficacy. Modern nutritional and health research focuses on promoting health, preventing or delaying the onset of disease, and optimizing performance. Deciphering the molecular interplay between food and health requires therefore holistic approaches because nutritional improvement of certain health aspects must not be compromised by deterioration of others. In other words, in nutrition, we have to get everything right. Proteomics is a central platform in nutrigenomics that describes how our genome expresses itself as a response to diet. Nutrigenetics deals with our genetic predisposition and susceptibility toward diet and helps stratify subject cohorts and discern responders from non-responders. Epigenetics represent DNA sequence-unrelated biochemical modifications of DNA itself and DNA-binding proteins and appears to provide a format for life-long or even transgeneration imprinting of metabolism. Proteomics in nutrition can identify and quantify bioactive proteins and peptides and addresses questions of nutritional bioefficacy. In this review, we focus on these latter aspects, update the reader on technologic developments, and review major applications.

  17. Developing a Molecular Roadmap of Drug-Food Interactions

    DEFF Research Database (Denmark)

    Jensen, Kasper; Ni, Yueqiong; Panagiotou, Gianni

    2015-01-01

    therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present...... view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in Drug-Bank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing......Recent research has demonstrated that consumption of food -especially fruits and vegetables-can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful...

  18. Comprehension through explanation as the interaction of the brain’s coherence and cognitive control networks

    Directory of Open Access Journals (Sweden)

    Jarrod eMoss

    2015-10-01

    Full Text Available Discourse comprehension processes attempt to produce an elaborate and well-connected representation in the reader’s mind. A common network of regions including the angular gyrus, posterior cingulate, and dorsal frontal cortex appears to be involved in constructing coherent representations in a variety of tasks including social cognition tasks, narrative comprehension, and expository text comprehension. Reading strategies that require the construction of explicit inferences are used in the present research to examine how this coherence network interacts with other brain regions. A psychophysiological interaction analysis was used to examine regions showing changed functional connectivity with this coherence network when participants were engaged in either a non-inferencing reading strategy, paraphrasing, or a strategy requiring coherence-building inferences, self-explanation. Results of the analysis show that the coherence network increases in functional connectivity with a cognitive control network that may be specialized for the manipulation of semantic representations and the construction of new relations among these representations.

  19. Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

    2013-03-15

    Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

  20. AFD: an application for bi-molecular interaction using axial frequency distribution.

    Science.gov (United States)

    Raza, Saad; Azam, Syed Sikander

    2018-03-06

    Conformational flexibility and generalized structural features are responsible for specific phenomena existing in biological pathways. With advancements in computational chemistry, novel approaches and new methods are required to compare the dynamic nature of biomolecules, which are crucial not only to address dynamic functional relationships but also to gain detailed insights into the disturbance and positional fluctuation responsible for functional shifts. Keeping this in mind, axial frequency distribution (AFD) has been developed, designed, and implemented. AFD can profoundly represent distribution and density of ligand atom around a particular atom or set of atoms. It enabled us to obtain an explanation of local movements and rotations, which are not significantly highlighted by any other structural and dynamical parameters. AFD can be implemented on biological models representing ligand and protein interactions. It shows a comprehensive view of the binding pattern of ligand by exploring the distribution of atoms relative to the x-y plane of the system. By taking a relative centroid on protein or ligand, molecular interactions like hydrogen bonds, van der Waals, polar or ionic interaction can be analyzed to cater the ligand movement, stabilization or flexibility with respect to the protein. The AFD graph resulted in the residual depiction of bi-molecular interaction in gradient form which can yield specific information depending upon the system of interest.

  1. Probing molecular interactions in bone biomaterials: Through molecular dynamics and Fourier transform infrared spectroscopy

    International Nuclear Information System (INIS)

    Bhowmik, Rahul; Katti, Kalpana S.; Verma, Devendra; Katti, Dinesh R.

    2007-01-01

    Polymer-hydroxyapatite (HAP) composites are widely investigated for their potential use as bone replacement materials. The molecular interactions at mineral polymer interface are known to have significant role of mechanical response of the composite system. Modeling interactions between such dissimilar molecules using molecular dynamics (MD) is an area of current interest. Molecular dynamics studies require potential function or force field parameters. Some force fields are described in literature that represents the structure of hydroxyapatite reasonably well. Yet, the applicability of these force fields for studying the interaction between dissimilar materials (such as mineral and polymer) is limited, as there is no accurate representation of polymer in these force fields. We have obtained the parameters of consistent valence force field (CVFF) for monoclinic hydroxyapatite. Validation of parameters was done by comparing the computationally obtained unit cell parameters, vibrational spectra and atomic distances with XRD and FTIR experiments. Using the obtained parameters of HAP, and available parameters of polymer (polyacrylic acid), interaction study was performed with MD simulations. The MD simulations showed that several hydrogen bonds may form between HAP and polyacrylic acid depending upon the exposed surface of HAP. Also there are some favourable planes of HAP where polyacrylic acid is most likely to attach. We have also simulated the mineralization of HAP using a 'synthetic biomineralization'. These modeling studies are supported by photoacoustic spectroscopy experiments on both porous and non porous composite samples for potential joint replacement and bone tissue engineering applications

  2. Comprehensive molecular sampling yields a robust phylogeny for geometrid moths (Lepidoptera: Geometridae.

    Directory of Open Access Journals (Sweden)

    Pasi Sihvonen

    Full Text Available BACKGROUND: The moth family Geometridae (inchworms or loopers, with approximately 23,000 described species, is the second most diverse family of the Lepidoptera. Apart from a few recent attempts based on morphology and molecular studies, the phylogeny of these moths has remained largely uninvestigated. METHODOLOGY/PRINCIPAL FINDINGS: We performed a rigorous and extensive molecular analysis of eight genes to examine the geometrid affinities in a global context, including a search for its potential sister-taxa. Our maximum likelihood analyses included 164 taxa distributed worldwide, of which 150 belong to the Geometridae. The selected taxa represent all previously recognized subfamilies and nearly 90% of recognized tribes, and originate from all over world. We found the Geometridae to be monophyletic with the Sematuridae+Epicopeiidae clade potentially being its sister-taxon. We found all previously recognized subfamilies to be monophyletic, with a few taxa misplaced, except the Oenochrominae+Desmobathrinae complex that is a polyphyletic assemblage of taxa and the Orthostixinae, which was positioned within the Ennominae. The Sterrhinae and Larentiinae were found to be sister to the remaining taxa, followed by Archiearinae, the polyphyletic assemblage of Oenochrominae+Desmobathrinae moths, Geometrinae and Ennominae. CONCLUSIONS/SIGNIFICANCE: Our study provides the first comprehensive phylogeny of the Geometridae in a global context. Our results generally agree with the other, more restricted studies, suggesting that the general phylogenetic patterns of the Geometridae are now well-established. Generally the subfamilies, many tribes, and assemblages of tribes were well supported but their interrelationships were often weakly supported by our data. The Eumeleini were particularly difficult to place in the current system, and several tribes were found to be para- or polyphyletic.

  3. Specificity of molecular interactions in transient protein-protein interaction interfaces.

    Science.gov (United States)

    Cho, Kyu-il; Lee, KiYoung; Lee, Kwang H; Kim, Dongsup; Lee, Doheon

    2006-11-15

    In this study, we investigate what types of interactions are specific to their biological function, and what types of interactions are persistent regardless of their functional category in transient protein-protein heterocomplexes. This is the first approach to analyze protein-protein interfaces systematically at the molecular interaction level in the context of protein functions. We perform systematic analysis at the molecular interaction level using classification and feature subset selection technique prevalent in the field of pattern recognition. To represent the physicochemical properties of protein-protein interfaces, we design 18 molecular interaction types using canonical and noncanonical interactions. Then, we construct input vector using the frequency of each interaction type in protein-protein interface. We analyze the 131 interfaces of transient protein-protein heterocomplexes in PDB: 33 protease-inhibitors, 52 antibody-antigens, 46 signaling proteins including 4 cyclin dependent kinase and 26 G-protein. Using kNN classification and feature subset selection technique, we show that there are specific interaction types based on their functional category, and such interaction types are conserved through the common binding mechanism, rather than through the sequence or structure conservation. The extracted interaction types are C(alpha)-- H...O==C interaction, cation...anion interaction, amine...amine interaction, and amine...cation interaction. With these four interaction types, we achieve the classification success rate up to 83.2% with leave-one-out cross-validation at k = 15. Of these four interaction types, C(alpha)--H...O==C shows binding specificity for protease-inhibitor complexes, while cation-anion interaction is predominant in signaling complexes. The amine ... amine and amine...cation interaction give a minor contribution to the classification accuracy. When combined with these two interactions, they increase the accuracy by 3.8%. In the case of

  4. Ultrasonic Studies of Molecular Interactions in Organic Binary Liquid Mixtures

    Directory of Open Access Journals (Sweden)

    S. Thirumaran

    2010-01-01

    Full Text Available The ultrasonic velocity, density and viscosity have been measured for the mixtures of 1-alkanols such as 1-propanol and 1-butanol with N-N dimethylformamide (DMF at 303 K. The experimental data have been used to calculate the acoustical parameters namely adiabatic compressibility (β, free length (Lf, free volume (Vf and internal pressure (πi. The excess values of the above parameters are also evaluated and discussed in the light of molecular interaction existing in the mixtures. It is obvious that there is a formation of hydrogen bonding between DMF and 1-alkanols. Further, the addition of DMF causes dissociation of hydrogen bonded structure of 1-alkanols. The evaluated excess values confirm that the molecular association is more pronounced in system-II comparing to the system-I.

  5. Molecular phenology in plants: in natura systems biology for the comprehensive understanding of seasonal responses under natural environments.

    Science.gov (United States)

    Kudoh, Hiroshi

    2016-04-01

    Phenology refers to the study of seasonal schedules of organisms. Molecular phenology is defined here as the study of the seasonal patterns of organisms captured by molecular biology techniques. The history of molecular phenology is reviewed briefly in relation to advances in the quantification technology of gene expression. High-resolution molecular phenology (HMP) data have enabled us to study phenology with an approach of in natura systems biology. I review recent analyses of FLOWERING LOCUS C (FLC), a temperature-responsive repressor of flowering, along the six steps in the typical flow of in natura systems biology. The extensive studies of the regulation of FLC have made this example a successful case in which a comprehensive understanding of gene functions has been progressing. The FLC-mediated long-term memory of past temperatures creates time lags with other seasonal signals, such as photoperiod and short-term temperature. Major signals that control flowering time have a phase lag between them under natural conditions, and hypothetical phase lag calendars are proposed as mechanisms of season detection in plants. Transcriptomic HMP brings a novel strategy to the study of molecular phenology, because it provides a comprehensive representation of plant functions. I discuss future perspectives of molecular phenology from the standpoints of molecular biology, evolutionary biology and ecology. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

  6. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins.

    Science.gov (United States)

    Couvineau, Alain; Laburthe, Marc

    2012-05-01

    The vasoactive intestinal peptide (VIP) is a neuropeptide with wide distribution in both central and peripheral nervous systems, where it plays important regulatory role in many physiological processes. VIP displays a large biological functions including regulation of exocrine secretions, hormone release, fetal development, immune responses, etc. VIP appears to exert beneficial effect in neuro-degenerative and inflammatory diseases. The mechanism of action of VIP implicates two subtypes of receptors (VPAC1 and VPAC2), which are members of class B receptors belonging to the super-family of GPCR. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC receptors. The structure-function relationship of VPAC1 receptor has been extensively studied, allowing to understand the molecular basis for receptor affinity, specificity, desensitization and coupling to adenylyl cyclase. Those studies have clearly demonstrated the crucial role of the N-terminal ectodomain (N-ted) of VPAC1 receptor in VIP recognition. By using different approaches including directed mutagenesis, photoaffinity labelling, NMR, molecular modelling and molecular dynamic simulation, it has been shown that the VIP molecule interacts with the N-ted of VPAC1 receptor, which is itself structured as a 'Sushi' domain. VPAC1 receptor also interacts with a few accessory proteins that play a role in cell signalling of receptors. Recent advances in the structural characterization of VPAC receptor and more generally of class B GPCRs will lead to the design of new molecules, which could have considerable interest for the treatment of inflammatory and neuro-degenerative diseases. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  7. Coulomb interactions via local dynamics: a molecular-dynamics algorithm

    International Nuclear Information System (INIS)

    Pasichnyk, Igor; Duenweg, Burkhard

    2004-01-01

    We derive and describe in detail a recently proposed method for obtaining Coulomb interactions as the potential of mean force between charges which are dynamically coupled to a local electromagnetic field. We focus on the molecular dynamics version of the method and show that it is intimately related to the Car-Parrinello approach, while being equivalent to solving Maxwell's equations with a freely adjustable speed of light. Unphysical self-energies arise as a result of the lattice interpolation of charges, and are corrected by a subtraction scheme based on the exact lattice Green function. The method can be straightforwardly parallelized using standard domain decomposition. Some preliminary benchmark results are presented

  8. Molecular interaction of pinic acid with sulfuric acid

    DEFF Research Database (Denmark)

    Elm, Jonas; Kurtén, Theo; Bilde, Merete

    2014-01-01

    We investigate the molecular interactions between the semivolatile α-pinene oxidation product pinic acid and sulfuric acid using computational methods. The stepwise Gibbs free energies of formation have been calculated utilizing the M06-2X functional, and the stability of the clusters is evaluated...... cluster. The involvement of more than one pinic acid molecule in a single cluster is observed to lead to the formation of favorable (pinic acid)2(H2SO4) and (pinic acid)2(H2SO4)2 clusters. The identified most favorable growth paths starting from a single pinic acid molecule lead to closed structures...

  9. Using interactive graphical and technological strategies for EFL reading comprehension: A case study involving engineering students

    Directory of Open Access Journals (Sweden)

    Julia Valeska Barraza

    2014-09-01

    Full Text Available This qualitative study engaged a group of engineering students in the use of interactive graphical and technological strategies called IGOs (interactive, graphic organisers software in order to improve their level of EFL reading comprehension. The learners were asked to use three different types of IGOs, causes and effects, a sequence of events and pros and cons. Data was gathered through an opinion’s survey with the intention of collecting and evaluating the students’ perceptions on the use of the IGOs software. Findings revealed that most of the learners answered positively. Students also expressed they wanted more opportunities to use this software; because they not only could improve their scores but also, they enjoyed the experience they had using the new strategies software.

  10. Comprehensive molecular diagnosis of Epstein-Barr virus-associated lymphoproliferative diseases using next-generation sequencing.

    Science.gov (United States)

    Ono, Shintaro; Nakayama, Manabu; Kanegane, Hirokazu; Hoshino, Akihiro; Shimodera, Saeko; Shibata, Hirofumi; Fujino, Hisanori; Fujino, Takahiro; Yunomae, Yuta; Okano, Tsubasa; Yamashita, Motoi; Yasumi, Takahiro; Izawa, Kazushi; Takagi, Masatoshi; Imai, Kohsuke; Zhang, Kejian; Marsh, Rebecca; Picard, Capucine; Latour, Sylvain; Ohara, Osamu; Morio, Tomohiro

    2018-05-18

    Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.

  11. Comprehensive physical models and simulation package for plasma/material interactions during plasma instabilities

    International Nuclear Information System (INIS)

    Hassanein, A.; Konkashbaev, I.

    1999-01-01

    Damage to plasma-facing components (PFCs) from plasma instabilities remains a major obstacle to a successful tokamak concept. The extent of the damage depends on the detailed physics of the disrupting plasma, as well as on the physics of plasma-material interactions. A comprehensive computer package called high energy interaction with general heterogeneous target systems (HEIGHTS) has been developed and consists of several integrated computer models that follow the beginning of a plasma disruption at the scrape-off layer (SOL) through the transport of the eroded debris and splashed target materials to nearby locations as a result of the deposited energy. The package can study, for the first time, plasma-turbulent behavior in the SOL and predict the plasma parameters and conditions at the divertor plate. Full two-dimensional (2-D) comprehensive radiation magnetohydrodynamic (MHD) models are coupled with target thermodynamics and liquid hydrodynamics to evaluate the integrated response of plasma-facing materials. Factors that influence the lifetime of plasma-facing and nearby components, such as loss of vapor cloud confinement and vapor removal due to MHD effects, damage to nearby components due to intense vapor radiation, melt splashing, and brittle destruction of target materials, are also modeled and discussed. (orig.)

  12. Comprehensive physical models and simulation package for plasma/material interactions during plasma instabilities

    International Nuclear Information System (INIS)

    Hassanein, A.

    1998-01-01

    Damage to plasma-facing components (PFCS) from plasma instabilities remains a major obstacle to a successful tokamak concept. The extent of the damage depends on the detailed physics of the disrupting plasma, as well as on the physics of plasma-material interactions. A comprehensive computer package called High Energy Interaction with General Heterogeneous Target Systems (HEIGHTS) has been developed and consists of several integrated computer models that follow the beginning of a plasma disruption at the scrape-off layer (SOL) through the transport of the eroded debris and splashed target materials to nearby locations as a result of the deposited energy. The package can study, for the first time, plasma-turbulent behavior in the SOL and predict the plasma parameters and conditions at the divertor plate. Full two-dimensional (2-D) comprehensive radiation magnetohydrodynamic (MHD) models are coupled with target thermodynamics and liquid hydrodynamics to evaluate the integrated response of plasma-facing materials. Factors that influence the lifetime of plasma-facing and nearby components, such as loss of vapor-cloud confinement and vapor removal due to MHD effects, damage to nearby components due to intense vapor radiation, melt splashing, and brittle destruction of target materials, are also modeled and discussed

  13. Molecular interactions in particular Van der Waals nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Jungclas, Hartmut; Schmidt, Lothar [Marburg Univ. (Germany). Chemistry Dept.; Komarov, Viacheslav V.; Popova, Anna M. [Marburg Univ. (Germany). Chemistry Dept.; Lomonosov Moscow State Univ. (Russian Federation). Skobeltzin Inst. of Nuclear Physics

    2017-04-01

    A method is presented to analyse the interaction energies in a nanocluster, which is consisting of three neutral molecules bound by non-covalent long range Van der Waals forces. One of the molecules (M{sub 0}) in the nanocluster has a permanent dipole moment, whereas the two other molecules (M{sub 1} and M{sub 2}) are non-polar. Analytical expressions are obtained for the numerical calculation of the dispersion and induction energies of the molecules in the considered nanocluster. The repulsive forces at short intermolecular distances are taken into account by introduction of damping functions. Dispersion and induction energies are calculated for a nanocluster with a definite geometry, in which the polar molecule M{sub 0} is a linear hydrocarbon molecule C{sub 5}H{sub 10} and M{sub 1} and M{sub 2} are pyrene molecules. The calculations are done for fixed distances between the two pyrene molecules. The results show that the induction energies in the considered three-molecular nanocluster are comparable with the dispersion energies. Furthermore, the sum of induction energies in the substructure (M{sub 0}, M{sub 1}) of the considered nanocluster is much higher than the sum of induction energies in a two-molecular nanocluster with similar molecules (M{sub 0}, M{sub 1}) because of the absence of an electrostatic field in the latter case. This effect can be explained by the essential intermolecular induction in the three-molecular nanocluster.

  14. Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review

    Science.gov (United States)

    Csermely, Peter; Korcsmáros, Tamás; Kiss, Huba J.M.; London, Gábor; Nussinov, Ruth

    2013-01-01

    Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach. PMID:23384594

  15. Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China

    Directory of Open Access Journals (Sweden)

    Kang Dongyang

    2009-09-01

    Full Text Available Abstract Background Every year, 30,000 babies are born with congenital hearing impairment in China. The molecular etiology of hearing impairment in the Chinese population has not been investigated thoroughly. To provide appropriate genetic testing and counseling to families, we performed a comprehensive investigation of the molecular etiology of nonsyndromic deafness in two typical areas from northern and southern China. Methods A total of 284 unrelated school children with hearing loss who attended special education schools in China were enrolled in this study, 134 from Chifeng City in Inner Mongolia and the remaining 150 from Nangtong City in JiangSu Province. Screening was performed for GJB2, GJB3, GJB6, SLC26A4, 12S rRNA, and tRNAser(UCN genes in this population. All patients with SLC26A4 mutations or variants were subjected to high-resolution temporal bone CT scan to verify the enlarged vestibular aqueduct. Results Mutations in the GJB2 gene accounted for 18.31% of the patients with nonsyndromic hearing loss, 1555A>G mutation in mitochondrial DNA accounted for 1.76%, and SLC26A4 mutations accounted for 13.73%. Almost 50% of the patients with nonsyndromic hearing loss in these typical Chinese areas carried GJB2 or SLC26A4 mutations. No significant differences in mutation spectrum or prevalence of GJB2 and SLC26A4 were found between the two areas. Conclusion In this Chinese population, 54.93% of cases with hearing loss were related to genetic factors. The GJB2 gene accounted for the etiology in about 18.31% of the patients with hearing loss, SLC26A4 accounted for about 13.73%, and mtDNA 1555A>G mutation accounted for 1.76%. Mutations in GJB3, GJB6, and mtDNA tRNAser(UCN were not common in this Chinese cohort. Conventionally, screening is performed for GJB2, SLC26A4, and mitochondrial 12S rRNA in the Chinese deaf population.

  16. Molecular basis of Bcl-X(L-p53 interaction: insights from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Nagakumar Bharatham

    Full Text Available Bcl-X(L, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-X(L: BH3 peptide and Bcl-X(L: SN15 peptide (a peptide derived from residues S15-N29 of p53 complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-X(L and other Bcl-2 family proteins have 4 hydrophobic pockets (p1-p4, which are occupied by four systematically spaced hydrophobic residues (h1-h4 of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26 of p53 (SN15 peptide anchor into three hydrophobic pockets (p2-p4 of Bcl-X(L in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-X(L with p53.

  17. Calsyntenin-3 molecular architecture and interaction with neurexin 1α.

    Science.gov (United States)

    Lu, Zhuoyang; Wang, Yun; Chen, Fang; Tong, Huimin; Reddy, M V V V Sekhar; Luo, Lin; Seshadrinathan, Suchithra; Zhang, Lei; Holthauzen, Luis Marcelo F; Craig, Ann Marie; Ren, Gang; Rudenko, Gabby

    2014-12-12

    Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1α (n1α), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1α to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1α directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1α biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca(2+), and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1α interact directly and that both Cstn3 monomers and tetramers bind n1α with nanomolar affinity. The interaction is promoted by Ca(2+) and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1α compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1α. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1α to recruit and spatially organize proteins into networks essential for synaptic function. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Molecular interactions in gelatin/chitosan composite films.

    Science.gov (United States)

    Qiao, Congde; Ma, Xianguang; Zhang, Jianlong; Yao, Jinshui

    2017-11-15

    Gelatin and chitosan were mixed at different mass ratios in solution forms, and the rheological properties of these film-forming solutions, upon cooling, were studied. The results indicate that the significant interactions between gelatin and chitosan promote the formation of multiple complexes, reflected by an increase in the storage modulus of gelatin solution. Furthermore, these molecular interactions hinder the formation of gelatin networks, consequently decreasing the storage modulus of polymer gels. Both hydrogen bonds and electrostatic interactions are formed between gelatin and chitosan, as evidenced by the shift of the amide-II bands of polymers. X-ray patterns of composite films indicate that the contents of triple helices decrease with increasing chitosan content. Only one glass transition temperature (T g ) was observed in composite films with different composition ratios, and it decreases gradually with an increase in chitosan proportion, indicating that gelatin and chitosan have good miscibility and form a wide range of blends. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Generation and Comprehensive Analysis of an Influenza Virus Polymerase Cellular Interaction Network▿†§

    Science.gov (United States)

    Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E.; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

    2011-01-01

    The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response. PMID:21994455

  20. Generation and comprehensive analysis of an influenza virus polymerase cellular interaction network.

    Science.gov (United States)

    Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

    2011-12-01

    The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response.

  1. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

    Directory of Open Access Journals (Sweden)

    Rong Shen

    2015-10-01

    Full Text Available The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels, each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good

  2. Interactive display of molecular models using a microcomputer system

    Science.gov (United States)

    Egan, J. T.; Macelroy, R. D.

    1980-01-01

    A simple, microcomputer-based, interactive graphics display system has been developed for the presentation of perspective views of wire frame molecular models. The display system is based on a TERAK 8510a graphics computer system with a display unit consisting of microprocessor, television display and keyboard subsystems. The operating system includes a screen editor, file manager, PASCAL and BASIC compilers and command options for linking and executing programs. The graphics program, written in USCD PASCAL, involves the centering of the coordinate system, the transformation of centered model coordinates into homogeneous coordinates, the construction of a viewing transformation matrix to operate on the coordinates, clipping invisible points, perspective transformation and scaling to screen coordinates; commands available include ZOOM, ROTATE, RESET, and CHANGEVIEW. Data file structure was chosen to minimize the amount of disk storage space. Despite the inherent slowness of the system, its low cost and flexibility suggests general applicability.

  3. Phase equilibria and molecular interaction studies on (naphthols + vanillin) systems

    International Nuclear Information System (INIS)

    Gupta, Preeti; Agrawal, Tanvi; Das, Shiva Saran; Singh, Nakshatra Bahadur

    2012-01-01

    Highlights: ► Phase equilibria of (naphthol + vanillin) systems have been studied for the first time. ► Eutectic type phase diagrams are obtained. ► Eutectic mixtures show nonideal behaviour. ► There is a weak molecular interaction between the components in the eutectic mixtures. ► α-Naphthol–vanillin eutectic is more stable as compared to β-naphthol–vanillin. - Abstract: Phase equilibria between (α-naphthol + vanillin) and (β-naphthol + vanillin) systems have been studied by thaw-melt method and the results show the formation of simple eutectic mixtures. Crystallization velocities of components and eutectic mixtures were determined at different stages under cooling. With the help of differential scanning calorimeter (DSC), the enthalpy of fusion of components and eutectic mixtures was determined and from the values excess thermodynamic functions viz., excess Gibbs free energy (G E ), excess entropy (S E ), excess enthalpy (H E ) of hypo-, hyper- and eutectic mixtures were calculated. Flexural strength measurements were made in order to understand the non-ideal nature of eutectics. FT-IR spectral studies indicate the formation of hydrogen bond in the eutectic mixture. Anisotropic and isotropic microstructural studies of components, hypo-, hyper- and eutectic mixtures were made. Jackson’s roughness parameter was calculated and found to be greater than 2 suggesting the faceted morphology with irregular structures. The overall results have shown that there is a weak molecular interaction between the components in the eutectic mixtures and the (α-naphthol + vanillin) eutectic is more stable as compared to the (β-naphthol + vanillin) eutectic system.

  4. How and when predictability interacts with accentuation in temporally selective attention during speech comprehension.

    Science.gov (United States)

    Li, Xiaoqing; Lu, Yong; Zhao, Haiyan

    2014-11-01

    The present study used EEG to investigate how and when top-down prediction interacts with bottom-up acoustic signals in temporally selective attention during speech comprehension. Mandarin Chinese spoken sentences were used as stimuli. We systematically manipulated the predictability and de/accentuation of the critical words in the sentence context. Meanwhile, a linguistic attention probe 'ba' was presented concurrently with the critical words or not. The results showed that, first, words with a linguistic attention probe elicited a larger N1 than those without a probe. The latency of this N1 effect was shortened for accented or lowly predictable words, indicating more attentional resources allocated to these words. Importantly, prediction and accentuation showed a complementary interplay on the latency of this N1 effect, demonstrating that when the words had already attracted attention due to low predictability or due to the presence of pitch accent, the other factor did not modulate attention allocation anymore. Second, relative to the lowly predictable words, the highly predictable words elicited a reduced N400 and enhanced gamma-band power increases, especially under the accented conditions; moreover, under the accented conditions, shorter N1 peak-latency was found to correlate with larger gamma-band power enhancement, which indicates that a close relationship might exist between early selective attention and later semantic integration. Finally, the interaction between top-down selective attention (driven by prediction) and bottom-up selective attention (driven by accentuation) occurred before lexical-semantic processing, namely before the N400 effect evoked by predictability, which was discussed with regard to the language comprehension models. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  6. Diagnosis for the interaction of supersonic molecular beam with plasma

    International Nuclear Information System (INIS)

    Yao Lianghua; Feng Beibing; Feng Zhen; Luo Junlin; Dong Jiafu; Yan Longwen; Hong Wenyu

    2001-01-01

    Supersonic Molecular Beam Injection (SMBI) is a new fuelling method for Tokamaks and has recently been improved to enhance the flux of the beam and to make a survey of the cluster effect within the beam. There are a series of new phenomena, which implicate the interaction of the beam (including clusters) with the toroidal plasma of HL-1M Tokamak. The H α signals from the edge show a regular variation around the torus. Around the injection port, the edge H α signals are positive rectangular wave, which is consistent with that of the injection beam pulses. The edge electron temperature, measured with movable Langmuir probes, decreases by an order of magnitude and the density increases by an order of magnitude. H α emission at the beam injection port, measured with CCD camera at an angle of 13.4 degrees to the SMBI line, shows many separate peaks within the contour plot. These peaks may show the strong emission produced by the interaction of the hydrogen clusters with the plasma. Hydrogen clusters may be produced in the beam according to the empirical scaling (Hagena) law of clustering onset, Γ* = kd 0.85 P 0 /T 0 2.29 , here d is the nozzle diameter in μm, P 0 the stagnation pressure in mbar, T 0 the source temperature in K, and k is a constant related to the gas species. If Γ* > 100, clusters will be formed. In present experiment Γ* is about 127

  7. Molecular interactions between (--epigallocatechin gallate analogs and pancreatic lipase.

    Directory of Open Access Journals (Sweden)

    Shihui Wang

    Full Text Available The molecular interactions between pancreatic lipase (PL and four tea polyphenols (EGCG analogs, like (--epigallocatechin gallate (EGCG, (--gallocatechin gallate (GCG, (--epicatechin gallate (ECG, and (--epigallocatechin (EC, were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent.

  8. Comprehensive studies on the interactions between chitosan nanoparticles and some live cells

    International Nuclear Information System (INIS)

    Zheng Aiping; Liu Huixue; Yuan Lan; Meng Meng; Wang Jiancheng; Zhang Xuan; Zhang Qiang

    2011-01-01

    As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer and its nanoparticles, especially the effects on the biomembrane. Several techniques, including surface plasmon resonance (SPR), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, fluorescence polarization spectroscopy (FP), flow cytometry (FCM) with quantitative analysis, and confocal images with antibody staining were employed toward this end. The cytotoxicity in vitro was also evaluated. Chitosan (CS), a polycationic polymer, was used to prepare the nanoparticles. We demonstrate that chitosan nanoparticles (CS-NP) induce strong alterations in the distribution of membrane proteins, fluidity of membrane lipids, and general membrane structure. Furthermore, the uptake of CS-NP into Caco-2 cells was found to have a similar mechanism to that of CS molecules, but the differences in degree were noted. These results indicate that positive charge and nanoscale size were the factors that most significantly affected the interactions between the nanoparticles of polycationic polymers and live cells. However, no difference in cytotoxicity toward the Caco-2 cells was found between CS and CS-NP. This supports the idea that CS-NP is an effective and safe carrier for oral drug delivery.

  9. Interactions from diffraction data: historical and comprehensive overview of simulation assisted methods

    International Nuclear Information System (INIS)

    Toth, Gergely

    2007-01-01

    A large part of statistical mechanics is concerned with the determination of condensed matter structure on the basis of known microscopic interactions. An increasing emphasis has been put on the opposite situation in the last decades as well, where structural data, e.g. pair-distance statistics, are known from diffraction experiments, and one looks for the corresponding interaction functions. The solution of this inverse problem was searched for within the integral equation theories of condensed matter in the early investigations, but before long computer simulation assisted methods were suggested. The interest in this field showed an increasing trend after some attempts appeared in the late 1980s. Several methods were published in the 1990s, and one-two methods appear annually nowadays. In this paper a comprehensive and historical overview is given on the solution of the inverse problem with simulation assisted methods. Emphasis is put on the theoretical grounds of the methods, on the choice of possible input structural functions, on the numerically local or global schemes of the potential modifications, on some advantages and limits of the different methods and on the scientific impact of the methods

  10. A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

    Science.gov (United States)

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-07-08

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):299-304, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  11. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

    NARCIS (Netherlands)

    Berger, Ashton C.; Korkut, Anil; Kanchi, Rupa S.; Hegde, Apurva M.; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H.; Yau, Christina; Bowlby, Reanne; Robertson, A. Gordon; Tiezzi, Daniel G.; Wang, Chen; Cherniack, Andrew D.; Godwin, Andrew K.; Kuderer, Nicole M.; Rader, Janet S.; Zuna, Rosemary E.; Sood, Anil K.; Lazar, Alexander J.; Ojesina, Akinyemi I.; Adebamowo, Clement; Adebamowo, Sally N.; Baggerly, Keith A.; Chen, Ting Wen; Chiu, Hua Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P.; Wentzensen, Nicolas; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Angulo Gonzalez, Ana Maria; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, Jonathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Mora Pinero, Edna M.; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz; Weinstein, John N.; Mills, Gordon B.; Levine, Douglas A.; Akbani, Rehan

    2018-01-01

    We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations

  12. Stable Molecular Diodes Based on π-π Interactions of the Molecular Frontier Orbitals with Graphene Electrodes.

    Science.gov (United States)

    Song, Peng; Guerin, Sarah; Tan, Sherman Jun Rong; Annadata, Harshini Venkata; Yu, Xiaojiang; Scully, Micheál; Han, Ying Mei; Roemer, Max; Loh, Kian Ping; Thompson, Damien; Nijhuis, Christian A

    2018-03-01

    In molecular electronics, it is important to control the strength of the molecule-electrode interaction to balance the trade-off between electronic coupling strength and broadening of the molecular frontier orbitals: too strong coupling results in severe broadening of the molecular orbitals while the molecular orbitals cannot follow the changes in the Fermi levels under applied bias when the coupling is too weak. Here, a platform based on graphene bottom electrodes to which molecules can bind via π-π interactions is reported. These interactions are strong enough to induce electronic function (rectification) while minimizing broadening of the molecular frontier orbitals. Molecular tunnel junctions are fabricated based on self-assembled monolayers (SAMs) of Fc(CH 2 ) 11 X (Fc = ferrocenyl, X = NH 2 , Br, or H) on graphene bottom electrodes contacted to eutectic alloy of gallium and indium top electrodes. The Fc units interact more strongly with graphene than the X units resulting in SAMs with the Fc at the bottom of the SAM. The molecular diodes perform well with rectification ratios of 30-40, and they are stable against bias stressing under ambient conditions. Thus, tunnel junctions based on graphene with π-π molecule-electrode coupling are promising platforms to fabricate stable and well-performing molecular diodes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Molecular Ecological Insights into Neotropical Bird-Tick Interactions.

    Science.gov (United States)

    Miller, Matthew J; Esser, Helen J; Loaiza, Jose R; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds' role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually-sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna). Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical-Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically-identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly-discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology and the dynamics of

  14. Molecular Ecological Insights into Neotropical Bird-Tick Interactions.

    Directory of Open Access Journals (Sweden)

    Matthew J Miller

    Full Text Available In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In contrast, immature Neotropical ticks are often found on wild birds, yet difficulties in identifying immatures hinder studies of birds' role in tropical tick ecology and tick-borne disease transmission. In Panama, we found immature ticks on 227 out of 3,498 individually-sampled birds representing 93 host species (24% of the bird species sampled, and 13% of the Panamanian land bird fauna. Tick parasitism rates did not vary with rainfall or temperature, but did vary significantly with several host ecological traits. Likewise, Neotropical-Nearctic migratory birds were significantly less likely to be infested than resident species. Using a molecular library developed from morphologically-identified adult ticks specifically for this study, we identified eleven tick species parasitizing birds, indicating that a substantial portion of the Panamanian avian species pool is parasitized by a diversity of tick species. Tick species that most commonly parasitized birds had the widest diversity of avian hosts, suggesting that immature tick species are opportunistic bird parasites. Although certain avian ecological traits are positively associated with parasitism, we found no evidence that individual tick species show specificity to particular avian host ecological traits. Finally, our data suggest that the four principal vectors of Rocky Mountain Spotted Fever in the Neotropics rarely, if ever, parasitize Panamanian birds. However, other tick species that harbor newly-discovered rickettsial parasites of unknown pathogenicity are frequently found on these birds. Given our discovery of broad interaction between Panamanian tick and avian biodiversity, future work on tick ecology

  15. Molecular modeling of human neutral sphingomyelinase provides insight into its molecular interactions.

    Science.gov (United States)

    Dinesh; Goswami, Angshumala; Suresh, Panneer Selvam; Thirunavukkarasu, Chinnasamy; Weiergräber, Oliver H; Kumar, Muthuvel Suresh

    2011-01-01

    The neutral sphingomyelinase (N-SMase) is considered a major candidate for mediating the stress-induced production of ceramide, and it plays an important role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress responses. Recent studies have identified a small region at the very N-terminus of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced activation of N-SMase. There is no direct association between TNF-R55 NSD and N-SMase; instead, a protein named factor associated with N-SMase activation (FAN) has been reported to couple the TNF-R55 NSD to N-SMase. Since the three-dimensional fold of N-SMase is still unknown, we have modeled the structure using the protein fold recognition and threading method. Moreover, we propose models for the TNF-R55 NSD as well as the FAN protein in order to study the structural basis of N-SMase activation and regulation. Protein-protein interaction studies suggest that FAN is crucially involved in mediating TNF-induced activation of the N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses. Inhibition of N-SMase may lead to reduction of ceramide levels and hence may provide a novel therapeutic strategy for inflammation and autoimmune diseases. Molecular dynamics (MD) simulations were performed to check the stability of the predicted model and protein-protein complex; indeed, stable RMS deviations were obtained throughout the simulation. Furthermore, in silico docking of low molecular mass ligands into the active site of N-SMase suggests that His135, Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based on our results, these ligands are proposed to be potent and selective N-SMase inhibitors, which may ultimately prove useful as lead compounds for drug development.

  16. Molecular dynamics simulations of lipid bilayers : major artifacts due to truncating electrostatic interactions

    NARCIS (Netherlands)

    Patra, M.; Karttunen, M.E.J.; Hyvönen, M.T.; Falck, E.; Lindqvist, P.; Vattulainen, I.

    2003-01-01

    We study the influence of truncating the electrostatic interactions in a fully hydrated pure dipalmitoylphosphatidylcholine (DPPC) bilayer through 20 ns molecular dynamics simulations. The computations in which the electrostatic interactions were truncated are compared to similar simulations using

  17. Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

    Science.gov (United States)

    2017-10-01

    including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations...2% Movember-Prostate Cancer Foundation $250,000/yr Challenge Award Interrogating DNA Repair Defects to Improve Management...Improve Treatment for Advanced Prostate Cancer Goal(s): Comprehensively interrogate DNA repair alterations in both AR-positive and AR-negative CRPC

  18. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. | Office of Cancer Genomics

    Science.gov (United States)

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival.

  19. Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.

    Directory of Open Access Journals (Sweden)

    Subhash C Verma

    Full Text Available Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human malignancies including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. KSHV like other herpesviruses establishes life-long latency in the infected host by persisting as chromatin and tethering to host chromatin through the virally encoded protein Latency Associated Nuclear Antigen (LANA. LANA, a multifunctional protein, is capable of binding to a large number of cellular proteins responsible for transcriptional regulation of various cellular and viral pathways involved in blocking cell death and promoting cell proliferation. This leads to enhanced cell division and replication of the viral genome, which segregates faithfully in the dividing tumor cells. The mechanism of genome segregation is well known and the binding of LANA to nucleosomal proteins, throughout the cell cycle, suggests that these interactions play an important role in efficient segregation. Various biochemical methods have identified a large number of LANA binding proteins, including histone H2A/H2B, histone H1, MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may have various functions in tethering of the viral genome during specific phases of the viral life cycle. Therefore, we performed a comprehensive analysis of their interaction with LANA using a number of different assays. We show that LANA binds to core nucleosomal histones and also associates with other host chromatin proteins including histone H1 and high mobility group proteins (HMGs. We used various biochemical assays including co-immunoprecipitation and in-vivo localization by split GFP and fluorescence resonance energy transfer (FRET to demonstrate their association.

  20. The two sides of sensory-cognitive interactions: effects of age, hearing acuity, and working memory span on sentence comprehension

    Directory of Open Access Journals (Sweden)

    Renee eDeCaro

    2016-02-01

    Full Text Available Reduced hearing acuity is among the most prevalent of chronic medical conditions among older adults. An experiment is reported in which comprehension of spoken sentences was tested for older adults with good hearing acuity or with a mild-to-moderate hearing loss, and young adults with age-normal hearing. Comprehension was measured by participants’ ability to determine of the agent of an action in sentences that expressed this relation with a syntactically less complex subject-relative construction or a syntactically more complex object-relative construction. Agency determination was further challenged by inserting a prepositional phrase into sentences between the person performing an action and the action being performed. As a control, prepositional phrases of equivalent length were also inserted into sentences in a non-disruptive position. Effects on sentence comprehension of age, hearing acuity, prepositional phrase placement and sound level of stimulus presentations appeared only for comprehension of sentences with the more syntactically complex object-relative structures. Working memory as tested by reading span scores accounted for a significant amount of the variance in comprehension accuracy. Once working memory capacity and hearing acuity were taken into account, chronological age among the older adults contributed no further variance to comprehension accuracy. Results are discussed in terms of the positive and negative effects of sensory-cognitive interactions in comprehension of spoken sentences and lend support to a framework in which domain-general executive resources, notably verbal working memory, play a role in both linguistic and perceptual processing.

  1. Application of the RISM theory to Lennard-Jones interaction site molecular fluids

    International Nuclear Information System (INIS)

    Johnson, E.; Hazoume, R.P.

    1979-01-01

    It seems that reference interaction site model (RISM) theory atom--atom distribution functions have been obtained directly from the RISM equations only for fused hard sphere molecular fluids. RISM distribution functions for Lennard-Jones interaction site fluids are presented. Results presented suggest that these distribution functions are as accurate as RISM distribution functions for fused hard sphere molecular fluids

  2. Nanoparticle decoration with surfactants: Molecular interactions, assembly, and applications

    Science.gov (United States)

    Heinz, Hendrik; Pramanik, Chandrani; Heinz, Ozge; Ding, Yifu; Mishra, Ratan K.; Marchon, Delphine; Flatt, Robert J.; Estrela-Lopis, Irina; Llop, Jordi; Moya, Sergio; Ziolo, Ronald F.

    2017-02-01

    Nanostructures of diverse chemical nature are used as biomarkers, therapeutics, catalysts, and structural reinforcements. The decoration with surfactants has a long history and is essential to introduce specific functions. The definition of surfactants in this review is very broad, following its lexical meaning ;surface active agents;, and therefore includes traditional alkyl modifiers, biological ligands, polymers, and other surface active molecules. The review systematically covers covalent and non-covalent interactions of such surfactants with various types of nanomaterials, including metals, oxides, layered materials, and polymers as well as their applications. The major themes are (i) molecular recognition and noncovalent assembly mechanisms of surfactants on the nanoparticle and nanocrystal surfaces, (ii) covalent grafting techniques and multi-step surface modification, (iii) dispersion properties and surface reactions, (iv) the use of surfactants to influence crystal growth, as well as (v) the incorporation of biorecognition and other material-targeting functionality. For the diverse materials classes, similarities and differences in surfactant assembly, function, as well as materials performance in specific applications are described in a comparative way. Major factors that lead to differentiation are the surface energy, surface chemistry and pH sensitivity, as well as the degree of surface regularity and defects in the nanoparticle cores and in the surfactant shell. The review covers a broad range of surface modifications and applications in biological recognition and therapeutics, sensors, nanomaterials for catalysis, energy conversion and storage, the dispersion properties of nanoparticles in structural composites and cement, as well as purification systems and classical detergents. Design principles for surfactants to optimize the performance of specific nanostructures are discussed. The review concludes with challenges and opportunities.

  3. Understanding Molecular Interactions within Chemically Selective Layered Polymer Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Gary J. Blanchard

    2009-06-30

    This work focuses on two broad issues. These are (1) the molecular origin of the chemical selectivity achieved with ultrathin polymer multilayers, and (2) how the viscoelastic properties of the polymer layers are affected by exposure to solvent and analytes. These issues are inter-related, and to understand them we need to design experiments that probe both the energetic and kinetic aspects of interfacial adsorption processes. This project focuses on controling the chemical structure, thickness, morphology and sequential ordering of polymer layers bound to interfaces using maleimide-vinyl ether and closely related alternating copolymerization chemistry and efficient covalent cross-linking reactions that allow for layer-by-layer polymer deposition. This chemistry has been developed during the funding cycle of this Grant. We have measure the equilibrium constants for interactions between specific layers within the polymer interfaces and size-controlled, surface-functionalized gold nanoparticles. The ability to control both size and functionality of gold nanoparticle model analytes allows us to evaluate the average “pore size” that characterizes our polymer films. We have measured the “bulk” viscosity and shear modulus of the ultrathin polymer films as a function of solvent overlayer identity using quartz crystal microbalance complex impedance measurements. We have measured microscopic viscosity at specific locations within the layered polymer interfaces with time-resolved fluorescence lifetime and depolarization techniques. We combine polymer, cross-linking and nanoparticle synthetic expertise with a host of characterization techniques, including QCM gravimetry and complex impedance analysis, steady state and time-resolved spectroscopies.

  4. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    OpenAIRE

    Christopher J. Ricketts; Aguirre A. De Cubas; Huihui Fan; Christof C. Smith; Martin Lang; Ed Reznik; Reanne Bowlby; Ewan A. Gibb; Rehan Akbani; Rameen Beroukhim; Donald P. Bottaro; Toni K. Choueiri; Richard A. Gibbs; Andrew K. Godwin; Scott Haake

    2018-01-01

    Summary: Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of sub...

  5. Contributions to advances in blend pellet products (BPP) research on molecular structure and molecular nutrition interaction by advanced synchrotron and globar molecular (Micro)spectroscopy.

    Science.gov (United States)

    Guevara-Oquendo, Víctor H; Zhang, Huihua; Yu, Peiqiang

    2018-04-13

    To date, advanced synchrotron-based and globar-sourced techniques are almost unknown to food and feed scientists. There has been little application of these advanced techniques to study blend pellet products at a molecular level. This article aims to provide recent research on advanced synchrotron and globar vibrational molecular spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction. How processing induced molecular structure changes in relation to nutrient availability and utilization of the blend pellet products. The study reviews Utilization of co-product components for blend pellet product in North America; Utilization and benefits of inclusion of pulse screenings; Utilization of additives in blend pellet products; Application of pellet processing in blend pellet products; Conventional evaluation techniques and methods for blend pellet products. The study focus on recent applications of cutting-edge vibrational molecular spectroscopy for molecular structure and molecular structure association with nutrient utilization in blend pellet products. The information described in this article gives better insight on how advanced molecular (micro)spectroscopy contributions to advances in blend pellet products research on molecular structure and molecular nutrition interaction.

  6. Molecular infection biology : interactions between microorganisms and cells

    National Research Council Canada - National Science Library

    Hacker, Jörg (Jörg Hinrich); Heesemann, Jurgen

    2002-01-01

    ... and epidemiology of infectious diseases. Investigators, specialists, clinicians, and graduate students in biology, pharmacy, and medicine will find Molecular Infection Biology an invaluable addition to their professional libraries...

  7. A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.

    Science.gov (United States)

    Liu, Wenlong; Dan, Xiuli; Wang, Ting; Lu, William W; Pan, Haobo

    2016-11-01

    The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin + cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin + lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue

  8. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

    NARCIS (Netherlands)

    Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

    Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and

  9. A comprehensive benchmark of kernel methods to extract protein-protein interactions from literature.

    Directory of Open Access Journals (Sweden)

    Domonkos Tikk

    Full Text Available The most important way of conveying new findings in biomedical research is scientific publication. Extraction of protein-protein interactions (PPIs reported in scientific publications is one of the core topics of text mining in the life sciences. Recently, a new class of such methods has been proposed - convolution kernels that identify PPIs using deep parses of sentences. However, comparing published results of different PPI extraction methods is impossible due to the use of different evaluation corpora, different evaluation metrics, different tuning procedures, etc. In this paper, we study whether the reported performance metrics are robust across different corpora and learning settings and whether the use of deep parsing actually leads to an increase in extraction quality. Our ultimate goal is to identify the one method that performs best in real-life scenarios, where information extraction is performed on unseen text and not on specifically prepared evaluation data. We performed a comprehensive benchmarking of nine different methods for PPI extraction that use convolution kernels on rich linguistic information. Methods were evaluated on five different public corpora using cross-validation, cross-learning, and cross-corpus evaluation. Our study confirms that kernels using dependency trees generally outperform kernels based on syntax trees. However, our study also shows that only the best kernel methods can compete with a simple rule-based approach when the evaluation prevents information leakage between training and test corpora. Our results further reveal that the F-score of many approaches drops significantly if no corpus-specific parameter optimization is applied and that methods reaching a good AUC score often perform much worse in terms of F-score. We conclude that for most kernels no sensible estimation of PPI extraction performance on new text is possible, given the current heterogeneity in evaluation data. Nevertheless, our study

  10. The architecture of visual narrative comprehension: the interaction of narrative structure and page layout in understanding comics.

    Science.gov (United States)

    Cohn, Neil

    2014-01-01

    How do people make sense of the sequential images in visual narratives like comics? A growing literature of recent research has suggested that this comprehension involves the interaction of multiple systems: The creation of meaning across sequential images relies on a "narrative grammar" that packages conceptual information into categorical roles organized in hierarchic constituents. These images are encapsulated into panels arranged in the layout of a physical page. Finally, how panels frame information can impact both the narrative structure and page layout. Altogether, these systems operate in parallel to construct the Gestalt whole of comprehension of this visual language found in comics.

  11. Atomistic interactions of clusters on surfaces using molecular dynamics and hyper molecular dynamics

    International Nuclear Information System (INIS)

    Sanz-Navarro, Carlos F.

    2002-01-01

    The work presented in this thesis describes the results of Molecular Dynamics (MD) simulations applied to the interaction of silver clusters with graphite surfaces and some numerical and theoretical methods concerning the extension of MD simulations to longer time scales (hyper-MD). The first part of this thesis studies the implantation of clusters at normal incidence onto a graphite surface in order to determine the scaling of the penetration depth (PD) against the impact energy. A comparison with experimental results is made with good agreement. The main physical observations of the impact process are described and analysed. It is shown that there is a threshold impact velocity above which the linear dependence on PD on impact energy changes to a linear dependence on velocity. Implantation of silver clusters at oblique incidence is also considered. The second part of this work analyses the validity and feasibility of the three minimisation methods for the hyper-MD simulation method whereby time scales of an MD simulation can be extended. A correct mathematical basis for the iterative method is derived. It is found that one of the iterative methods, upon which hyper-lD is based, is very likely to fail in high-dimensional situations because it requires a too expensive convergence. Two new approximations to the hyper-MD approach are proposed, which reduce the computational effort considerably. Both approaches, although not exact, can help to search for some of the most likely transitions in the system. Some examples are given to illustrate this. (author)

  12. Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.

    Science.gov (United States)

    Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J; Ahmed, Mansoor M; Coleman, C Norman

    2016-11-01

    New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd.

  13. Molecular Interactions and Reaction Dynamics in Supercritical Water Oxidation

    National Research Council Canada - National Science Library

    Johnston, K

    1998-01-01

    .... From UV-vis spectroscopic measurements and molecular dynamics simulation of chemical equilibria, we have shown that density effects on broad classes of reactions may be explained in terms of changes...

  14. Probing Interactions in Complex Molecular Systems through Ordered Assembly

    International Nuclear Information System (INIS)

    De Yoreo, J.J.; Bartelt, M.C.; Orme, C.A.; Villacampa, A.; Weeks, B.L.; Miller, A.E.

    2002-01-01

    Emerging from the machinery of epitaxial science and chemical synthesis, is a growing emphasis on development of self-organized systems of complex molecular species. The nature of self-organization in these systems spans the continuum from simple crystallization of large molecules such as dendrimers and proteins, to assembly into large organized networks of nanometer-scale structures such as quantum dots or nanoparticles. In truth, self-organization in complex molecular systems has always been a central feature of many scientific disciplines including fields as diverse as structural biology, polymer science and geochemistry. But over the past decade, changes in those fields have often been marked by the degree to which researchers are using molecular-scale approaches to understand the hierarchy of structures and processes driven by this ordered assembly. At the same time, physical scientists have begun to use their knowledge of simple atomic and molecular systems to fabricate synthetic self-organized systems. This increasing activity in the field of self-organization is testament to the success of the physical and chemical sciences in building a detailed understanding of crystallization and epitaxy in simple atomic and molecular systems, one that is soundly rooted in thermodynamics and chemical kinetics. One of the fundamental challenges of chemistry and materials science in the coming decades is to develop a similarly well-founded physical understanding of assembly processes in complex molecular systems. Over the past five years, we have successfully used in situ atomic force microscopy (AFM) to investigate the physical controls on single crystal epitaxy from solutions for a wide range of molecular species. More recently, we have combined this method with grazing incidence X-ray diffraction and kinetic Monte Carlo modeling in order to relate morphology to surface atomic structure and processes. The purpose of this proposal was to extend this approach to assemblies

  15. Energy transformation in molecular electronic systems: Comprehensive progress report, 1986--1989

    International Nuclear Information System (INIS)

    Kasha, M.

    1989-01-01

    Our research focuses on discovering the fundamental issues in proton-transfer and charge-transfer excitations in model systems, with an eye on which molecular systems will serve as the best guide to biological systems. This report addresses an intramolecular proton transfer classification system, proton-transfer potentials, proton-transfer spectroscopy of benzanilides, proton-transfer in aminosalicylates, proton-transfer in lumichrome, development of proton-transfer lasers, and triplet excitation enhancement via proton-transfer tunneling. 6 refs., 2 figs

  16. Erdheim-Chester Disease: Comprehensive Review of Molecular Profiling and Therapeutic Advances.

    Science.gov (United States)

    Haroun, Faysal; Millado, Kristen; Tabbara, Imad

    2017-06-01

    The revised 2016 World Health Organization classification introduced Erdheim-Chester disease (ECD) as a provisional entity within the histiocytic and dendritic cell neoplasms separate from the juvenile xanthogranuloma family based on distinct molecular features. However, evolving knowledge regarding the molecular and genetic aberrations in addition to common clinical features of ECD support the classification of ECD together with Langerhans cell histiocytosis (LCH). Accordingly, ECD can be thought of as an inflammatory myeloid clonal disorder based on the detection of various activating mutations along the mitogen activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) pathway with most notable variant being a valine to a glutamic acid substitution at amino acid 600 in the B-rapidly accelerated fibrosarcoma protein (BRAFV600E). In this group, targeted therapy with a B-Raf inhibitor alone or combined with a MAPK-ERK (MEK) inhibitor has shown promising results based on several case reports. Currently, two phase II trials with BRAF inhibitors are underway and could potentially change the standard of care. MEK inhibitors may also be efficacious in ECD harboring mutations in MAP2K1; other potential targetable aberrations include programed cell death receptor 1 and mutations in phosphoinositide 3-kinase. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Comprehensive Analysis of Low-Molecular-Weight Human Plasma Proteome Using Top-Down Mass Spectrometry.

    Science.gov (United States)

    Cheon, Dong Huey; Nam, Eun Ji; Park, Kyu Hyung; Woo, Se Joon; Lee, Hye Jin; Kim, Hee Cheol; Yang, Eun Gyeong; Lee, Cheolju; Lee, Ji Eun

    2016-01-04

    While human plasma serves as a great source for disease diagnosis, low-molecular-weight (LMW) proteome (mass spectrometry to analyze the LMW proteoforms present in four types of human plasma samples pooled from three healthy controls (HCs) without immunoaffinity depletion and with depletion of the top two, six, and seven high-abundance proteins. The LMW proteoforms were first fractionated based on molecular weight using gel-eluted liquid fraction entrapment electrophoresis (GELFrEE). Then, the GELFrEE fractions containing up to 30 kDa were subjected to nanocapillary-LC-MS/MS, and the high-resolution MS and MS/MS data were processed using ProSightPC 3.0. As a result, a total of 442 LMW proteins and cleaved products, including those with post-translational modifications and single amino acid variations, were identified. From additional comparative analysis of plasma samples without immunoaffinity depletion between HCs and colorectal cancer (CRC) patients via top-down approach, tens of LMW proteoforms, including platelet factor 4, were found to show >1.5-fold changes between the plasma samples of HCs and CRC patients, and six of the LMW proteins were verified by Western blot analysis.

  18. Biodiversity and dynamics of meat fermentations: the contribution of molecular methods for a better comprehension of a complex ecosystem.

    Science.gov (United States)

    Cocolin, Luca; Dolci, Paola; Rantsiou, Kalliopi

    2011-11-01

    The ecology of fermented sausages is complex and includes different species and strains of bacteria, yeasts and molds. The developments in the field of molecular biology, allowed for new methods to become available, which could be applied to better understand dynamics and diversity of the microorganisms involved in the production of sausages. Methods, such as denaturing gradient gel electrophoresis (DGGE), employed as a culture-independent approach, allow to define the microbial dynamics during the fermentation and ripening. Such approach has highlighted that two main species of lactic acid bacteria, namely Lactobacillus sakei and Lb. curvatus, are involved in the transformation process and that they are accompanied by Staphylococcus xylosus, as representative of the coagulase-negative cocci. These findings were repeatedly confirmed in different regions of the world, mainly in the Mediterranean countries where dry fermented sausages have a long tradition and history. The application of molecular methods for the identification and characterization of isolated strains from fermentations highlighted a high degree of diversity within the species mentioned above, underlining the need to better follow strain dynamics during the transformation process. While there is an important number of papers dealing with bacterial ecology by using molecular methods, studies on mycobiota of fermented sausages are just a few. This review reports on how the application of molecular methods made possible a better comprehension of the sausage fermentations, opening up new fields of research that in the near future will allow to unravel the connection between sensory properties and co-presence of multiple strains of the same species. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing.

    Science.gov (United States)

    Oishi, Maho; Oishi, Akio; Gotoh, Norimoto; Ogino, Ken; Higasa, Koichiro; Iida, Kei; Makiyama, Yukiko; Morooka, Satoshi; Matsuda, Fumihiko; Yoshimura, Nagahisa

    2014-10-16

    Retinitis pigmentosa (RP), a major cause of blindness in developed countries, has multiple causative genes; its prevalence differs by ethnicity. Usher syndrome is the most common form of syndromic RP and is accompanied by hearing impairment. Although molecular diagnosis is challenging, recent technological advances such as targeted high-throughput resequencing are efficient screening tools. We performed comprehensive molecular testing in 329 Japanese RP and Usher syndrome patients by using a custom capture panel that covered the coding exons and exon/intron boundaries of all 193 known inherited eye disease genes combined with Illumina HiSequation 2500. Candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed according to the frequency of the variants in normal populations, in silico prediction tools, and compatibility with known phenotypes or inheritance patterns. Molecular diagnoses were made in 115/317 RP patients (36.3%) and 6/12 Usher syndrome patients (50%). We identified 104 distinct mutations, including 66 novel mutations. EYS, USH2A, and RHO were common causative genes. In particular, mutations in EYS accounted for 15.0% of the autosomal recessive/simplex RP patients or 10.7% of the entire RP cohort. Among the 189 previously reported mutations detected in the current study, 55 (29.1%) were found commonly in Japanese or other public databases and were excluded from molecular diagnoses. By screening a large cohort of patients, this study catalogued the genetic variations involved in RP and Usher syndrome in a Japanese population and highlighted the different distribution of causative genes among populations. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  20. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    2007-07-01

    Full Text Available Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease.In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the specific genes identified within each class

  1. Insight into molecular interactions between two PB1 domains

    NARCIS (Netherlands)

    van Drogen-Petit, A.; Zwahlen, C.; Peter, M.; Bonvin, A.M.J.J.

    2004-01-01

    Specific protein–protein interactions play crucial roles in the regulation of any biological process. Recently, a new protein–protein interaction domain termed PB1 (Phox and Bem1) was identified, which is conserved throughout evolution and present in diverse proteins functioning in signal

  2. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

    International Nuclear Information System (INIS)

    Alam, Parvez; Chaturvedi, Sumit Kumar; Anwar, Tamanna; Siddiqi, Mohammad Khursheed; Ajmal, Mohd Rehan; Badr, Gamal; Mahmoud, Mohamed H.; Hasan Khan, Rizwan

    2015-01-01

    Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×10 3 M −1 . The average binding distance between drug and Trp 214 of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV–visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH=−26.01 kJ mol −1 and TΔS=6.5 kJ mol −1 ) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations. - Highlights: • Comprehensive insight into the interaction of CBDA with HSA. • The interaction process is spontaneous and exothermic. • The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding. • CBDA binds at subdomain IB on HSA

  3. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Parvez; Chaturvedi, Sumit Kumar [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Anwar, Tamanna [Center of Bioinformatics Research and Technology, Aligarh 202002 (India); Siddiqi, Mohammad Khursheed; Ajmal, Mohd Rehan [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Badr, Gamal [Laboratory of Immunology & Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, 71516 Assiut (Egypt); Mahmoud, Mohamed H. [Food Science and Nutrition Department, National Research Center, Dokki, Cairo (Egypt); Deanship of Scientific Research, King Saud University, Riyadh (Saudi Arabia); Hasan Khan, Rizwan, E-mail: rizwanhkhan@hotmail.com [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India)

    2015-08-15

    Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×10{sup 3} M{sup −1}. The average binding distance between drug and Trp{sup 214} of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV–visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH=−26.01 kJ mol{sup −1} and TΔS=6.5 kJ mol{sup −1}) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations. - Highlights: • Comprehensive insight into the interaction of CBDA with HSA. • The interaction process is spontaneous and exothermic. • The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding. • CBDA binds at subdomain IB on HSA.

  4. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christopher J. Ricketts

    2018-04-01

    Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

  5. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    International Nuclear Information System (INIS)

    Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

    2015-01-01

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA

  6. Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Y., E-mail: kurita@cs.tut.ac.jp; Murakawa, T., E-mail: kurita@cs.tut.ac.jp; Shimamura, K., E-mail: kurita@cs.tut.ac.jp; Oishi, M., E-mail: kurita@cs.tut.ac.jp; Ohyama, T., E-mail: kurita@cs.tut.ac.jp; Kurita, N., E-mail: kurita@cs.tut.ac.jp [Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580 (Japan)

    2015-02-27

    The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

  7. Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

    Science.gov (United States)

    Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

    2013-11-01

    Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

  8. Fragment molecular orbital method for studying lanthanide interactions with proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tsushima, Satoru [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Komeiji, Y. [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Mochizuki, Y. [Rikkyo Univ., Tokyo (Japan)

    2017-06-01

    The binding affinity of the calcium-binding protein calmodulin towards Eu{sup 3+} was studied as a model for lanthanide protein interactions in the large family of ''EF-hand'' calcium-binding proteins.

  9. Current molecular profile of juvenile nasopharyngeal angiofibroma: First comprehensive study from India.

    Science.gov (United States)

    Pandey, Praveen; Mishra, Anupam; Tripathi, Ashoak Mani; Verma, Veerendra; Trivedi, Ritu; Singh, Hitendra Prakash; Kumar, Sunil; Patel, Brijesh; Singh, Vinay; Pandey, Shivani; Pandey, Amita; Mishra, Subhash Chandra

    2017-03-01

    An attempt is made to analyze the molecular behavior of juvenile nasopharyngeal angiofibroma (JNA). Case Series METHODS: Quantification of mRNAs expression was undertaken through real-time polymerase chain reaction in JNA (9-24) samples for VEGF-A, basic fibroblast growth factor (b-FGF), platelet-derived growth factor PDGF-A, KIT proto-oncogene receptor tyrosine kinase (c-Kit), Avian myelomatosis viral oncogene homolog (c-Myc), Harvey rat sarcoma viral oncogene homolog (H-Ras), tumor suppressor gene TP53, and androgen receptor and interleukin 6 (IL-6). The β-catenin expression was evaluated by western blot in 16 samples. Nasal polyp was taken as control. A significantly increased (P < 0.01) expression of c-myc, VEGFA, bFGF, PDGFA, c-kit, and TP53 was seen, along with enhanced expression of β-catenin. A massive enhancement of H-Ras expression was seen for the first time. Androgen receptor expression was no different, whereas IL-6 despite showing upregulation trend was not significant. The enhanced expressions of various markers suggest their potential role in JNA. Although the biological significance of c-kit, c-myc, and one of the novel markers H-Ras has yet to be defined, their significant expression may have a therapeutic importance. NA. Laryngoscope, 127:E100-E106, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Comprehensive representation of the Lennard-Jones equation of state based on molecular dynamics simulation data

    Science.gov (United States)

    Pieprzyk, S.; Brańka, A. C.; Maćkowiak, Sz.; Heyes, D. M.

    2018-03-01

    The equation of state (EoS) of the Lennard-Jones fluid is calculated using a new set of molecular dynamics data which extends to higher temperature than in previous studies. The modified Benedict-Webb-Rubin (MBWR) equation, which goes up to ca. T ˜ 6, is reparametrized with new simulation data. A new analytic form for the EoS, which breaks the fluid range into two regions with different analytic forms and goes up to ca. T ≃ 35, is also proposed. The accuracy of the new formulas is at least as good as the MBWR fit and goes to much higher temperature allowing it to now encompass the Amagat line. The fitted formula extends into the high temperature range where the system can be well represented by inverse power potential scaling, which means that our specification of the equation of state covers the entire (ρ, T) plane. Accurate analytic fit formulas for the Boyle, Amagat, and inversion curves are presented. Parametrizations of the extrema loci of the isochoric, CV, and isobaric, CP, heat capacities are given. As found by others, a line maxima of CP terminates in the critical point region, and a line of minima of CP terminates on the freezing line. The line of maxima of CV terminates close to or at the critical point, and a line of minima of CV terminates to the right of the critical point. No evidence for a divergence in CV in the critical region is found.

  11. Current immunological and molecular biological perspectives on seafood allergy: a comprehensive review.

    Science.gov (United States)

    Leung, Nicki Y H; Wai, Christine Y Y; Shu, ShangAn; Wang, Jinjun; Kenny, Thomas P; Chu, Ka Hou; Leung, Patrick S C

    2014-06-01

    Seafood is an important component in human diet and nutrition worldwide. However, seafood also constitutes one of the most important groups of foods in the induction of immediate (type I) food hypersensitivity, which significantly impacts the quality of life and healthcare cost. Extensive efforts within the past two decades have revealed the molecular identities and immunological properties of the major fish and shellfish allergens. The major allergen involved in allergy and cross-reactivity among different fish species was identified as parvalbumin while that responsible for shellfish (crustaceans and mollusks) allergy was identified as tropomyosin. The cloning and expression of the recombinant forms of these seafood allergens facilitate the investigation on the detailed mechanisms leading to seafood allergies, mapping of IgE-binding epitopes, and assessment of their allergenicity and stability. Future research focusing on the immunological cross-reactivity and discovery of novel allergens will greatly facilitate the management of seafood allergies and the design of effective and life-long allergen-specific immunotherapies.

  12. Simulation of aerosol flow interaction with a solid body on molecular level

    Science.gov (United States)

    Amelyushkin, Ivan A.; Stasenko, Albert L.

    2018-05-01

    Physico-mathematical models and numerical algorithm of two-phase flow interaction with a solid body are developed. Results of droplet motion and its impingement upon a rough surface in real gas boundary layer simulation on the molecular level obtained via molecular dynamics technique are presented.

  13. Interactive scalable condensation of reverse engineered UML class diagrams for software comprehension

    NARCIS (Netherlands)

    Osman, Mohd Hafeez Bin

    2015-01-01

    Software design documentation is a valuable aid in software comprehension. However, keeping the software design up-to-date with evolving source code is challenging and time-consuming. Reverse engineering is one of the options for recovering software architecture from the implementation code.

  14. Comprehensive DFT study on molecular structures of Lewisites in support of the Chemical Weapons Convention

    Science.gov (United States)

    Saeidian, Hamid; Sahandi, Morteza

    2015-11-01

    The structure of all of Lewisite's stereoisomers has been examined by B3LYP/6-311++G(3df,3pd) calculations. The geometry analysis for trans Lewisite L1-1 shows that the calculated bond angles, bond distances and dipole moment have a satisfactory relation compared with experimental values. HOMO-LUMO analysis of Lewisites reveals that L1-2 and L3-7 have the maximum and minimum electrophilicity index, respectively. The calculated chemical shifts were compared with experimental data, showing a very good agreement both for 1H and 13C. The vibrational and Raman frequencies of Lewisites have been precisely assigned and theoretical data were compared with the experimental vibrations. The bonding trends and Mulliken and atomic polar tensor charge distribution in Lewisites can be explained by the Bent's rule and the donor-acceptor interaction, respectively.

  15. Intra-membrane molecular interactions of K+ channel proteins :

    Energy Technology Data Exchange (ETDEWEB)

    Moczydlowski, Edward G.

    2013-07-01

    Ion channel proteins regulate complex patterns of cellular electrical activity and ionic signaling. Certain K+ channels play an important role in immunological biodefense mechanisms of adaptive and innate immunity. Most ion channel proteins are oligomeric complexes with the conductive pore located at the central subunit interface. The long-term activity of many K+ channel proteins is dependent on the concentration of extracellular K+; however, the mechanism is unclear. Thus, this project focused on mechanisms underlying structural stability of tetrameric K+ channels. Using KcsA of Streptomyces lividans as a model K+ channel of known structure, the molecular basis of tetramer stability was investigated by: 1. Bioinformatic analysis of the tetramer interface. 2. Effect of two local anesthetics (lidocaine, tetracaine) on tetramer stability. 3. Molecular simulation of drug docking to the ion conduction pore. The results provide new insights regarding the structural stability of K+ channels and its possible role in cell physiology.

  16. Conserved molecular interactions in centriole-to-centrosome conversion.

    Science.gov (United States)

    Fu, Jingyan; Lipinszki, Zoltan; Rangone, Hélène; Min, Mingwei; Mykura, Charlotte; Chao-Chu, Jennifer; Schneider, Sandra; Dzhindzhev, Nikola S; Gottardo, Marco; Riparbelli, Maria Giovanna; Callaini, Giuliano; Glover, David M

    2016-01-01

    Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.

  17. Pulsed flow modulation two-dimensional comprehensive gas chromatography-tandem mass spectrometry with supersonic molecular beams.

    Science.gov (United States)

    Poliak, Marina; Fialkov, Alexander B; Amirav, Aviv

    2008-11-07

    Pulsed flow modulation (PFM) two-dimensional comprehensive gas chromatography (GC x GC) was combined with quadrupole-based mass spectrometry (MS) via a supersonic molecular beam (SMB) interface using a triple-quadrupole system as the base platform, which enabled tandem mass spectrometry (MS-MS). PFM is a simple GC x GC modulator that does not consume cryogenic gases while providing tunable second GC x GC column injection time for enabling the use of quadrupole-based mass spectrometry regardless its limited scanning speed. The 20-ml/min second column flow rate involved with PFM is handled, splitless, by the SMB interface without affecting the sensitivity. The combinations of PFM GC x GC-MS with SMB and PFM GC x GC-MS-MS with SMB were explored with the analysis of diazinon and permethrin in coriander. PFM GC x GC-MS with SMB is characterized by enhanced molecular ion and tailing-free fast ion source response time. It enables universal pesticide analysis with full scan and data analysis with reconstructed single ion monitoring on the enhanced molecular ion and another prominent high mass fragment ion. The elimination of the third fragment ion used in standard three ions method results in significantly reduced matrix interference. GC x GC-MS with SMB improves the GC separation, and thereby our ability for sample identification using libraries. GC-MS-MS with SMB provides better reduction (elimination) of matrix interference than GC x GC-MS. However, it is a target method, which is not always applicable. GC x GC-MS-MS does not seem to further reduce matrix interferences over GC-MS-MS and unlike GC x GC-MS, it is incompatible with library identification, but it is beneficial to have both GC x GC and MS-MS capabilities in the same system.

  18. Vitamin E-drug interactions: molecular basis and clinical relevance.

    Science.gov (United States)

    Podszun, Maren; Frank, Jan

    2014-12-01

    Vitamin E (α-, β-, γ- and δ-tocopherol and -tocotrienol) is an essential factor in the human diet and regularly taken as a dietary supplement by many people, who act under the assumption that it may be good for their health and can do no harm. With the publication of meta-analyses reporting increased mortality in persons taking vitamin E supplements, the safety of the micronutrient was questioned and interactions with prescription drugs were suggested as one potentially underlying mechanism. Here, we review the evidence in the scientific literature for adverse vitamin E-drug interactions and discuss the potential of each of the eight vitamin E congeners to alter the activity of drugs. In summary, there is no evidence from animal models or randomised controlled human trials to suggest that the intake of tocopherols and tocotrienols at nutritionally relevant doses may cause adverse nutrient-drug interactions. Consumption of high-dose vitamin E supplements ( ≥  300 mg/d), however, may lead to interactions with the drugs aspirin, warfarin, tamoxifen and cyclosporine A that may alter their activities. For the majority of drugs, however, interactions with vitamin E, even at high doses, have not been observed and are thus unlikely.

  19. MIiSR: Molecular Interactions in Super-Resolution Imaging Enables the Analysis of Protein Interactions, Dynamics and Formation of Multi-protein Structures.

    Directory of Open Access Journals (Sweden)

    Fabiana A Caetano

    2015-12-01

    Full Text Available Our current understanding of the molecular mechanisms which regulate cellular processes such as vesicular trafficking has been enabled by conventional biochemical and microscopy techniques. However, these methods often obscure the heterogeneity of the cellular environment, thus precluding a quantitative assessment of the molecular interactions regulating these processes. Herein, we present Molecular Interactions in Super Resolution (MIiSR software which provides quantitative analysis tools for use with super-resolution images. MIiSR combines multiple tools for analyzing intermolecular interactions, molecular clustering and image segmentation. These tools enable quantification, in the native environment of the cell, of molecular interactions and the formation of higher-order molecular complexes. The capabilities and limitations of these analytical tools are demonstrated using both modeled data and examples derived from the vesicular trafficking system, thereby providing an established and validated experimental workflow capable of quantitatively assessing molecular interactions and molecular complex formation within the heterogeneous environment of the cell.

  20. A Comprehensive Study of Molecular Evolution at the Self-Incompatibility Locus of Rosaceae.

    Science.gov (United States)

    Ashkani, Jahanshah; Rees, D J G

    2016-03-01

    The family Rosaceae includes a range of important fruit trees, most of which have the S-RNase-based self-incompatibility (SI). Several models have been developed to explain how pollen (SLF) and pistil (S-RNase) components of the S-locus interact. It was discovered in 2010 that additional SLF proteins are involved in pollen specificity, and a Collaborative Non-Self Recognition model has been proposed for SI in Solanaceae; however, the validity of such model remains to be elucidated for other species. The results of this study support the divergent evolution of the S-locus genes from two Rosaceae subfamilies, Prunoideae/Amygdaloideae and Maloideae, The difference identified in the selective pressures between the two lineages provides evidence for positive selection at specific sites in both the S-RNase and the SLF proteins. The evolutionary findings of this study support the role of multiple SLF proteins leading to a Collaborative Non-Self Recognition model for SI in the Maloideae. Furthermore, the identification of the sites responsible for SI specificity determination and the mapping of these sites onto the modelled tertiary structure of ancestor proteins provide useful information for rational functional redesign and protein engineering for the future engineering of new functional alleles providing increased diversity in the SI system in the Maloideae.

  1. Ultrasonic study of molecular interaction in binary liquid mixtures at ...

    Indian Academy of Sciences (India)

    The variation of these parameters with composition of the mixture helps us in understanding the nature and extent of interaction between unlike molecules in the mixtures. Further, theoretical values of ultrasonic speed were evaluated using theories and empirical relations. The relative merits of these theories and relations ...

  2. Interacting with molecular structures : user performance versus system complexity

    NARCIS (Netherlands)

    Liere, van R.; Martens, J.B.; Kok, A.J.F.; van Tienen, M.H.A.; Blach, R.; Kjems, E.

    2005-01-01

    Effective interaction in a virtual environment requires that the user can adequately judge the spatial relationships between the objects in a 3D scene. In order to accomplish adequate depth perception, existing virtual environments create useful perceptual cues through stereoscopy, motion parallax

  3. Studies on Molecular Interaction in Ternary Liquid Mixtures

    Directory of Open Access Journals (Sweden)

    R. Uvarani

    2010-01-01

    Full Text Available Ultrasonic velocity, density and viscosity for the ternary liquid mixtures of cyclohexanone with 1-propanol and 1-butanol in carbon tetrachloride were measured at 303 K. The acoustical parameters and their excess values were calculated. The trends in the variation of these excess parameters were used to discuss the nature and strength of the interactions present between the component molecules.

  4. Long-range interactions and parallel scalability in molecular simulations

    NARCIS (Netherlands)

    Patra, M.; Hyvönen, M.T.; Falck, E.; Sabouri-Ghomi, M.; Vattulainen, I.; Karttunen, M.E.J.

    2007-01-01

    Typical biomolecular systems such as cellular membranes, DNA, and protein complexes are highly charged. Thus, efficient and accurate treatment of electrostatic interactions is of great importance in computational modeling of such systems. We have employed the GROMACS simulation package to perform

  5. Molecular ecological insights into neotropical bird-tick interactions

    NARCIS (Netherlands)

    Miller, Matthew J.; Esser, Helen J.; Loaiza, Jose R.; Herre, Edward Allen; Aguilar, Celestino; Quintero, Diomedes; Alvarez, Eric; Bermingham, Eldredge

    2016-01-01

    In the tropics, ticks parasitize many classes of vertebrate hosts. However, because many tropical tick species are only identifiable in the adult stage, and these adults usually parasitize mammals, most attention on the ecology of tick-host interactions has focused on mammalian hosts. In

  6. Molecular simulations of lipid-mediated protein-protein interactions

    NARCIS (Netherlands)

    de Meyer, F.J.M.; Venturoli, M.; Smit, B.

    2008-01-01

    Recent experimental results revealed that lipid-mediated interactions due to hydrophobic forces may be important in determining the protein topology after insertion in the membrane, in regulating the protein activity, in protein aggregation and in signal transduction. To gain insight into the

  7. A MOLECULAR DYNAMICS STUDY ON SLOW ION INTERACTIONS WITH THE POLYCYCLIC AROMATIC HYDROCARBON MOLECULE ANTHRACENE

    NARCIS (Netherlands)

    Postma, J.; Hoekstra, Ronnie; Tielens, A. G. G. M.; Schlathölter, Thomas

    2014-01-01

    Atomic collisions with polycyclic aromatic hydrocarbon (PAH) molecules are astrophysically particularly relevant for collision energies of less than 1 keV. In this regime, the interaction dynamics are dominated by elastic interactions. We have employed a molecular dynamics simulation based on

  8. Channel-facilitated molecular transport: The role of strength and spatial distribution of interactions

    Energy Technology Data Exchange (ETDEWEB)

    Uppulury, Karthik, E-mail: karthik.uppulury@gmail.com [Department of Chemistry, Texas Tech University, Lubbock, TX 79409 (United States); Kolomeisky, Anatoly B. [Department of Chemistry, Department of Chemical and Biomolecular Engineering, Center for Theoretical Biological Physics, Rice University, Houston, TX 77005 (United States)

    2016-12-20

    Highlights: • Molecular flux strongly depends on the strength of the molecule-pore interactions. • There exists an optimal molecule-pore interaction potential for maximal flux. • Volume of interactions depends inversely on the strength for maximal flux. • Stronger interactions need more number of attractive sites for maximal flux. • Channels with few special sites need more attractive sites for higher flux. - Abstract: Molecular transport across channels and pores is critically important for multiple natural and industrial processes. Recent advances in single-molecule techniques have allowed researchers to probe translocation through nanopores with unprecedented spatial and temporal resolution. However, our understanding of the mechanisms of channel-facilitated molecular transport is still not complete. We present a theoretical approach that investigates the role of molecular interactions in the transport through channels. It is based on the discrete-state stochastic analysis that provides a fully analytical description of this complex process. It is found that a spatial distribution of the interactions strongly influences the translocation dynamics. We predict that there is the optimal distribution that leads to the maximal flux through the channel. It is also argued that the channel transport depends on the strength of the molecule-pore interactions, on the shape of interaction potentials and on the relative contributions of entrance and diffusion processes in the system. These observations are discussed using simple physical-chemical arguments.

  9. Molecular interactions in the betaine monohydrate-polyol deep eutectic solvents: Experimental and computational studies

    Science.gov (United States)

    Zahrina, Ida; Mulia, Kamarza; Yanuar, Arry; Nasikin, Mohammad

    2018-04-01

    DES (deep eutectic solvents) are a new class of ionic liquids that have excellent properties. The strength of interaction between molecules in the DES affects their properties and applications. In this work, the strength of molecular interactions between components in the betaine monohydrate salt and polyol (glycerol or/and propylene glycol) eutectic mixtures was studied by experimental and computational studies. The melting point and fusion enthalpy of the mixtures were measured using STA (Simultaneous Thermal Analyzer). The nature and strength of intermolecular interactions were observed by FT-IR and NMR spectroscopy. The molecular dynamics simulation was used to determine the number of H-bonds, percent occupancy, and radial distribution functions in the eutectic mixtures. The interaction between betaine monohydrate and polyol is following order: betaine monohydrate-glycerol-propylene glycol > betaine monohydrate-glycerol > betaine monohydrate-propylene glycol, where the latter is the eutectic mixture with the lowest stability, strength and extent of the hydrogen bonding interactions between component molecules. The presence of intra-molecular hydrogen bonding interactions, the inter-molecular hydrogen bonding interactions between betaine molecule and polyol, and also interactions between polyol and H2O of betaine monohydrate in the eutectic mixtures.

  10. Channel-facilitated molecular transport: The role of strength and spatial distribution of interactions

    International Nuclear Information System (INIS)

    Uppulury, Karthik; Kolomeisky, Anatoly B.

    2016-01-01

    Highlights: • Molecular flux strongly depends on the strength of the molecule-pore interactions. • There exists an optimal molecule-pore interaction potential for maximal flux. • Volume of interactions depends inversely on the strength for maximal flux. • Stronger interactions need more number of attractive sites for maximal flux. • Channels with few special sites need more attractive sites for higher flux. - Abstract: Molecular transport across channels and pores is critically important for multiple natural and industrial processes. Recent advances in single-molecule techniques have allowed researchers to probe translocation through nanopores with unprecedented spatial and temporal resolution. However, our understanding of the mechanisms of channel-facilitated molecular transport is still not complete. We present a theoretical approach that investigates the role of molecular interactions in the transport through channels. It is based on the discrete-state stochastic analysis that provides a fully analytical description of this complex process. It is found that a spatial distribution of the interactions strongly influences the translocation dynamics. We predict that there is the optimal distribution that leads to the maximal flux through the channel. It is also argued that the channel transport depends on the strength of the molecule-pore interactions, on the shape of interaction potentials and on the relative contributions of entrance and diffusion processes in the system. These observations are discussed using simple physical-chemical arguments.

  11. A comprehensive modeling and vibration analysis of AFM microcantilevers subjected to nonlinear tip-sample interaction forces

    International Nuclear Information System (INIS)

    Eslami, Sohrab; Jalili, Nader

    2012-01-01

    Precise and accurate representation of an Atomic Force Microscopy (AFM) system is essential in studying the effects of boundary interaction forces present between the probe's tip and the sample. In this paper, a comprehensive analytical model for the AFM system utilizing a distributed-parameters based approach is proposed. More specifically, we consider two important attributes of these systems; namely the rotary inertia and shear deformation when compared with the Euler–Bernoulli beam theory. Moreover, a comprehensive nonlinear interaction force is assumed between probe's and sample in order to reveal the response of the system more realistically. This nanoscale interaction force is based on a general form consisting of both attractive and repulsive components as well as a function of the tip-sample distance and the microcantilever's base and sample oscillations. Mechanical properties of the sample could interact with the nanomechanical coupling field between the probe' tip and sample and be implemented in studying the composition information of the sample and the ultra-small features inside it. Therefore, by modulating the dynamics of the AFM system such as the driving amplitude of the microcantilever the procedure for the subsurface imaging is described. The presented approach here could be implemented for designing the AFM probes by examining the tip-sample interaction forces dominant by the van der Waals forces. Several numerical case studies are presented and the force–distance diagram reveals that the proposed nonlinear nanomechanical force along with the distributed-parameters model for the microcantilever is able to fulfill the mechanics of the Lennard–Jones potential. -- Highlights: ► We present a comprehensive distributed-parameters model for AFM microcantilever. ► Assuming a nonlinear and implicit interaction force between tip and sample. ► Timoshenko beam is compared with the Euler–Bernoulli having the same force model. ► Frequency

  12. Post-foil interaction in foil-induced molecular dissociation

    International Nuclear Information System (INIS)

    Faibis, A.; Kanter, E.P.; Koenig, W.; Plesser, I.; Vager, Z.

    1985-01-01

    The authors have investigated the foil-induced dissociation of 175- 250- keV/amu CH + , NH + , and OH + , FH + and NeH + ions by coincident detection of the fragment atoms. The dissociation energies corresponding to in-foil and post-foil interactions were deduced from the measured relative flight times of the fragment pairs to a set of detectors downstream from the target. The authors considered final states consisting of a) a proton and a heavy-ion and, b) a hydrogen atom and a heavy-ion. Surprisingly, in both cases the energy released in the post-target interaction shows a similar linear increase with the charge state of the heavy partner

  13. Molecular Interaction of Bone Marrow Adipose Tissue with Energy Metabolism.

    Science.gov (United States)

    Suchacki, Karla J; Cawthorn, William P

    2018-01-01

    The last decade has seen a resurgence in the study of bone marrow adipose tissue (BMAT) across diverse fields such as metabolism, haematopoiesis, skeletal biology and cancer. Herein, we review the most recent developments of BMAT research in both humans and rodents, including the distinct nature of BMAT; the autocrine, paracrine and endocrine interactions between BMAT and various tissues, both in physiological and pathological scenarios; how these interactions might impact energy metabolism; and the most recent technological advances to quantify BMAT. Though still dwarfed by research into white and brown adipose tissues, BMAT is now recognised as endocrine organ and is attracting increasing attention from biomedical researchers around the globe. We are beginning to learn the importance of BMAT both within and beyond the bone, allowing us to better appreciate the role of BMAT in normal physiology and disease.

  14. Interaction of Caffeine Molecular Associates with Water: Theory and Experiment

    OpenAIRE

    Shestopalova, Anna V.

    1990-01-01

    Results of a Monte Carlo simulation of the association process of caffeine (1,3,7-trimethyl-2,6-dioxipurine) in water are presented. Simulation was performed in a cluster approximation ; the system contained 200 water molecules. The nature of the stabilization of caffeine stacking associates in water was considered. Hydrophobic behaviour of methyl group s during association of caffeine molecules in water is shown. The peculiarity of interaction of caffeine associates with wa...

  15. DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions.

    Directory of Open Access Journals (Sweden)

    Prashanthi Karyala

    2016-09-01

    Full Text Available Dengue virus (DENV is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue-human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue-human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/.

  16. DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions.

    Science.gov (United States)

    Karyala, Prashanthi; Metri, Rahul; Bathula, Christopher; Yelamanchi, Syam K; Sahoo, Lipika; Arjunan, Selvam; Sastri, Narayan P; Chandra, Nagasuma

    2016-09-01

    Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue-human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue-human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/).

  17. Density functional study of molecular interactions in secondary structures of proteins.

    Science.gov (United States)

    Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

    2016-01-01

    Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

  18. Molecular simulation of polar molecules interaction with MOFs family materials

    International Nuclear Information System (INIS)

    De Toni, M.

    2012-01-01

    The topic of this thesis is the adsorption of simple molecular fluids in nano-porous materials. Many industrial processes are based on this phenomenon, including ionic exchange, selective separation and heterogeneous catalysis. I used molecular simulation to study the adsorption properties of polar molecules of industrial interest (CO 2 and H 2 O) in a new class of crystalline microporous hybrid organic-inorganic materials called Metal-Organic Frameworks (MOFs). They have exceptional adsorption properties due to their topological variety and their versatility, allowed by the large range of possibilities offered by organic and coordination chemistry and functionalizations. I first studied the adsorption of CO 2 in a family of materials called IRMOFs, which share the same topology but have different porous volume, in order to characterize the effect of confinement on their adsorption performance. In particular, a general behavior has been highlighted: the critical temperature decreases when the confinement increases. Then, I looked at a recently synthesized cationic MOF called Zn2(CBTACN). After having localized the extra-framework halogen anions in the unit cell of the material, something which was not possible experimentally, I characterized CO 2 adsorption in this system first as a pure gas and then as a component of different mixtures. Finally, I was interested in the hydrothermal stability of MOFs, a crucial issue for their use in industrial applications. I observed the hydration mechanism of system that is analogous to the MOF-5 (IRMOF-0h) and shed light on some collaborative effects of the attack of water that were unknown to in the literature. (author)

  19. Molecular-scale hydrophobic interactions between hard-sphere reference solutes are attractive and endothermic.

    Science.gov (United States)

    Chaudhari, Mangesh I; Holleran, Sinead A; Ashbaugh, Henry S; Pratt, Lawrence R

    2013-12-17

    The osmotic second virial coefficients, B2, for atomic-sized hard spheres in water are attractive (B2 attractive with increasing temperature (ΔB2/ΔT attractive and endothermic at moderate temperatures. Hydrophobic interactions between atomic-sized hard spheres in water are more attractive than predicted by the available statistical mechanical theory. These results constitute an initial step toward detailed molecular theory of additional intermolecular interaction features, specifically, attractive interactions associated with hydrophobic solutes.

  20. Correlations and symmetry of interactions influence collective dynamics of molecular motors

    International Nuclear Information System (INIS)

    Celis-Garza, Daniel; Teimouri, Hamid; Kolomeisky, Anatoly B

    2015-01-01

    Enzymatic molecules that actively support many cellular processes, including transport, cell division and cell motility, are known as motor proteins or molecular motors. Experimental studies indicate that they interact with each other and they frequently work together in large groups. To understand the mechanisms of collective behavior of motor proteins we study the effect of interactions in the transport of molecular motors along linear filaments. It is done by analyzing a recently introduced class of totally asymmetric exclusion processes that takes into account the intermolecular interactions via thermodynamically consistent approach. We develop a new theoretical method that allows us to compute analytically all dynamic properties of the system. Our analysis shows that correlations play important role in dynamics of interacting molecular motors. Surprisingly, we find that the correlations for repulsive interactions are weaker and more short-range than the correlations for the attractive interactions. In addition, it is shown that symmetry of interactions affect dynamic properties of molecular motors. The implications of these findings for motor proteins transport are discussed. Our theoretical predictions are tested by extensive Monte Carlo computer simulations. (paper)

  1. Effect of molecular interactions on retention and selectivity in reversed-phase liquid chromatography.

    Science.gov (United States)

    Szepesy, László

    2002-06-25

    The linear solvation energy relationships (LSERs) have been applied in the last years for description and prediction of retention and selectivity in reversed-phase liquid chromatography with good results. Widely different stationary phases have been compared and characterized by LSERs. In recent publications the influence of the type of the organic moderator and the composition of the mobile phase have also been described. However, the influence of the molecular properties of the solutes to be separated has never been discussed. According to the LSER model variation in retention factors (log k) with solute structure can be related to their potential for various intermolecular interactions. The retention factor is given as the sum of the terms of the LSER equation representing various types of molecular interactions. For this reason the influence of the structure and molecular properties of the solutes to be separated can also be investigated using the LSER equation. In this study we shall demonstrate how the specific molecular interactions influence chromatographic retention and selectivity. We intend to show that retention and selectivity depend on all participants of the system. In addition to the structure and properties of the stationary phase and the type and composition of the mobile phase the molecular properties of the solutes, characterized by the solvation parameters, will also influence the type and extent of the various molecular interactions governing retention and selectivity.

  2. Measuring pair-wise molecular interactions in a complex mixture

    Science.gov (United States)

    Chakraborty, Krishnendu; Varma, Manoj M.; Venkatapathi, Murugesan

    2016-03-01

    Complex biological samples such as serum contain thousands of proteins and other molecules spanning up to 13 orders of magnitude in concentration. Present measurement techniques do not permit the analysis of all pair-wise interactions between the components of such a complex mixture to a given target molecule. In this work we explore the use of nanoparticle tags which encode the identity of the molecule to obtain the statistical distribution of pair-wise interactions using their Localized Surface Plasmon Resonance (LSPR) signals. The nanoparticle tags are chosen such that the binding between two molecules conjugated to the respective nanoparticle tags can be recognized by the coupling of their LSPR signals. This numerical simulation is done by DDA to investigate this approach using a reduced system consisting of three nanoparticles (a gold ellipsoid with aspect ratio 2.5 and short axis 16 nm, and two silver ellipsoids with aspect ratios 3 and 2 and short axes 8 nm and 10 nm respectively) and the set of all possible dimers formed between them. Incident light was circularly polarized and all possible particle and dimer orientations were considered. We observed that minimum peak separation between two spectra is 5 nm while maximum is 184nm.

  3. Effects of molecular interactions and the existence of different molecular forms of sodium fluoresceinate in solutions

    International Nuclear Information System (INIS)

    Golubeva, N.G.

    1989-01-01

    The results of measurement of fluorescence and absorption spectra of sodium fluoresceinate (FLNa) in different solutions and blood plasma are presented. The influence of solvent nature, its polarity, medium concentration and acidity on frequency, intensity and shape of fluorescence and absorption lines was analyzed. A general medium effect on fluorescence line spectral absorption was calculated from Lippert's equation. The influence of specific interactions has been analyzed on the example of acid-base interactions and hydrogen bonds in two- and multicomponent solutions. Computer processing of the spectra obtained allows to separate some forms of existing fluorophor molecules and to get data on the dynamics of their changes in different solutions. A special attention was given to the analysis of absorption and fluorescence bands of FLNa at its interaction with different proteins and lipids in solutions. From the analysis of data obtained a number of conclusions was drawn on the state of fluophor at its interactions with biological media. (author)

  4. Insect-plant interactions: new pathways to a better comprehension of ecological communities in Neotropical savannas.

    Science.gov (United States)

    Del-Claro, Kleber; Torezan-Silingardi, Helena M

    2009-01-01

    The causal mechanisms shaping and structuring ecological communities are among the most important themes in ecology. The study of insect-plant interactions in trophic nets is pointed out as basic to improve our knowledge on this issue. The cerrado tropical savanna, although extremely diverse, distributed in more than 20% of the Brazilian territory and filled up with rich examples of multitrophic interactions, is underexplored in terms of biodiversity interaction. Here, this ecosystem is suggested as valuable to the study of insect-plant interactions whose understanding can throw a new light at the ecological communities' theory. Three distinct systems: extrafloral nectary plants or trophobiont herbivores and the associated ant fauna; floral herbivores-predators-pollinators; and plants-forest engineers and associated fauna, will serve as examples to illustrate promising new pathways in cerrado. The aim of this brief text is to instigate young researchers, mainly entomologists, to initiate more elaborated field work, including experimental manipulations in multitrophic systems, to explore in an interactive way the structure that maintain preserved viable communities in the Neotropical savanna.

  5. Comprehensive spectroscopic studies on the interaction of biomolecules with surfactant detached multi-walled carbon nanotubes.

    Science.gov (United States)

    Sekar, Gajalakshmi; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2015-04-01

    This paper investigates the interaction of ten diverse biomolecules with surfactant detached Multi-Walled Carbon Nanotubes (MWCNTs) using multiple spectroscopic methods. Declining fluorescence intensity of biomolecules in combination with the hyperchromic effect in UV-Visible spectra confirmed the existence of the ground state complex formation. Quenching mechanism remains static and non-fluorescent. 3D spectral data of biomolecules suggested the possibilities of disturbances to the aromatic microenvironment of tryptophan and tyrosine residues arising out of CNTs interaction. Amide band Shifts corresponding to the secondary structure of biomolecules were observed in the of FTIR and FT-Raman spectra. In addition, there exists an increased Raman intensity of tryptophan residues of biomolecules upon interaction with CNTs. Hence, the binding of the aromatic structures of CNTs with the aromatic amino acid residues, in a particular, tryptophan was evidenced. Far UV Circular spectra have showed the loss of alpha-helical contents in biomolecules upon interaction with CNTs. Near UV CD spectra confirmed the alterations in the tryptophan positions of the peptide backbone. Hence, our results have demonstrated that the interaction of biomolecules with OH-MWCNTs would involve binding cum structural changes and alteration to their aromatic micro-environment. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Molecular analysis of the interaction between the hematopoietic master transcription factors GATA-1 and PU.1

    DEFF Research Database (Denmark)

    Liew, Chu Wai; Rand, Kasper Dyrberg; Simpson, Raina J Y

    2006-01-01

    GATA-1 and PU.1 are transcription factors that control erythroid and myeloid development, respectively. The two proteins have been shown to function in an antagonistic fashion, with GATA-1 repressing PU.1 activity during erythropoiesis and PU.1 repressing GATA-1 function during myelopoiesis. It has...... also become clear that this functional antagonism involves direct interactions between the two proteins. However, the molecular basis for these interactions is not known, and a number of inconsistencies exist in the literature. We have used a range of biophysical methods to define the molecular details...... of the GATA-1-PU.1 interaction. A combination of NMR titration data and extensive mutagenesis revealed that the PU.1-Ets domain and the GATA-1 C-terminal zinc finger (CF) form a low affinity interaction in which specific regions of each protein are implicated. Surprisingly, the interaction cannot be disrupted...

  7. Molecular interactions of alcohols with zeolite BEA and MOR frameworks.

    Science.gov (United States)

    Stückenschneider, Kai; Merz, Juliane; Schembecker, Gerhard

    2013-12-01

    Zeolites can adsorb small organic molecules such as alcohols from a fermentation broth. Also in the zeolite-catalyzed conversion of alcohols to biofuels, biochemicals, or gasoline, adsorption is the first step. Several studies have investigated the adsorption of alcohols in different zeolites experimentally, but computational investigations in this field have mostly been restricted to zeolite MFI. In this study, the adsorption of C1-C4 alcohols in BEA and MOR was investigated using density functional theory (DFT). Calculated adsorption geometries and the corresponding energies of the designed cluster models were comparable to periodic calculations, and the adsorption energies were in the same range as the corresponding computational and experimental values reported in the literature for zeolite MFI. Thus, BEA and MOR may be good adsorption materials for alcohols in the field of downstream processing and catalysis. Aside from the DFT calculations, adsorption isotherms were determined experimentally in this study from aqueous solutions. For BEA, the adsorption of significant amounts of alcohol from aqueous solution was observed experimentally. In contrast, MOR was loaded with only a very small amount of alcohol. Although differences were found between the affinities obtained from gas-phase DFT calculations and those observed experimentally in aqueous solution, the computational data presented here represent molecular level information on the geometries and energies of C1-C4 alcohols adsorbed in zeolites BEA and MOR. This knowledge should prove very useful in the design of zeolite materials intended for use in adsorption and catalytic processes, as it allows adsorption behavior to be predicted via judiciously designed computational models.

  8. Storage costs and heuristics interact to produce patterns of aphasic sentence comprehension performance.

    Science.gov (United States)

    Clark, David Glenn

    2012-01-01

    Despite general agreement that aphasic individuals exhibit difficulty understanding complex sentences, the nature of sentence complexity itself is unresolved. In addition, aphasic individuals appear to make use of heuristic strategies for understanding sentences. This research is a comparison of predictions derived from two approaches to the quantification of sentence complexity, one based on the hierarchical structure of sentences, and the other based on dependency locality theory (DLT). Complexity metrics derived from these theories are evaluated under various assumptions of heuristic use. A set of complexity metrics was derived from each general theory of sentence complexity and paired with assumptions of heuristic use. Probability spaces were generated that summarized the possible patterns of performance across 16 different sentence structures. The maximum likelihood of comprehension scores of 42 aphasic individuals was then computed for each probability space and the expected scores from the best-fitting points in the space were recorded for comparison to the actual scores. Predictions were then compared using measures of fit quality derived from linear mixed effects models. All three of the metrics that provide the most consistently accurate predictions of patient scores rely on storage costs based on the DLT. Patients appear to employ an Agent-Theme heuristic, but vary in their tendency to accept heuristically generated interpretations. Furthermore, the ability to apply the heuristic may be degraded in proportion to aphasia severity. DLT-derived storage costs provide the best prediction of sentence comprehension patterns in aphasia. Because these costs are estimated by counting incomplete syntactic dependencies at each point in a sentence, this finding suggests that aphasia is associated with reduced availability of cognitive resources for maintaining these dependencies.

  9. Development of a Comprehensive and Interactive Tool to Inform State Violence and Injury Prevention Plans.

    Science.gov (United States)

    Wilson, Lauren; Deokar, Angela J; Zaesim, Araya; Thomas, Karen; Kresnow-Sedacca, Marcie-Jo

    The Center of Disease Control and Prevention's Core State Violence and Injury Prevention Program (Core SVIPP) provides an opportunity for states to engage with their partners to implement, evaluate, and disseminate strategies that lead to the reduction and prevention of injury and violence. Core SVIPP requires awardees to develop or update their state injury and violence plans. Currently, literature informing state planning efforts is limited, especially regarding materials related to injury and violence. Presumably, plans that are higher quality result in having a greater impact on preventing injury and violence, and literature to improve quality would benefit prevention programming. (1) To create a comprehensive injury-specific index to aid in the development and revision of state injury and violence prevention plans, and (2) to assess the reliability and utility of this index. Through an iterative development process, a workgroup of subject matter experts created the Violence and Injury Prevention: Comprehensive Index Tool (VIP:CIT). The tool was pilot tested on 3 state injury and violence prevention plans and assessed for initial usability. Following revisions to the tool (ie, a rubric was developed to further delineate consistent criteria for rating; items were added and clarified), the same state plans were reassessed to test interrater reliability and tool utility. For the second assessment, reliability of the VIP:CIT improved, indicating that the rubric was a useful addition. Qualitative feedback from states suggested that the tool significantly helped guide plan development and communicate about planning processes. The final VIP:CIT is a tool that can help increase plan quality, decrease the research-to-practice gap, and increase connectivity to emerging public health paradigms. The tool provides an example of tailoring guidance materials to reflect academic literature, and it can be easily adapted to other topic areas to promote quality of strategic plans

  10. Nanopore wall-liquid interaction under scope of molecular dynamics study: Review

    Science.gov (United States)

    Tsukanov, A. A.; Psakhie, S. G.

    2017-12-01

    The present review is devoted to the analysis of recent molecular dynamics based on the numerical studies of molecular aspects of solid-fluid interaction in nanoscale channels. Nanopore wall-liquid interaction plays the crucial role in such processes as gas separation, water desalination, liquids decontamination, hydrocarbons and water transport in nano-fractured geological formations. Molecular dynamics simulation is one of the most suitable tools to study molecular level effects occurred in such multicomponent systems. The nanopores are classified by their geometry to four groups: nanopore in nanosheet, nanotube-like pore, slit-shaped nanopore and soft-matter nanopore. The review is focused on the functionalized nanopores in boron nitride nanosheets as novel selective membranes and on the slit-shaped nanopores formed by minerals.

  11. Nonfiction Reading Comprehension in Middle School: Exploring in Interactive Software Approach

    Science.gov (United States)

    Wolff, Evelyn S.; Isecke, Harriet; Rhoads, Christopher; Madura, John P.

    2013-01-01

    The struggles of students in the United States to comprehend non-fiction science text are well documented. Middle school students, in particular, have minimal instruction in comprehending nonfiction and flounder on assessments. This article describes the development process of the Readorium software, an interactive web-based program being…

  12. Video-Based Interaction, Negotiation for Comprehensibility, and Second Language Speech Learning: A Longitudinal Study

    Science.gov (United States)

    Saito, Kazuya; Akiyama, Yuka

    2017-01-01

    This study examined the impact of video-based conversational interaction on the longitudinal development (one academic semester) of second language production by college-level Japanese English-as-a-foreign-language learners. Students in the experimental group engaged in weekly dyadic conversation exchanges with native speakers in the United States…

  13. Molecular Model of a Quantum Dot Beyond the Constant Interaction Approximation

    Science.gov (United States)

    Temirov, Ruslan; Green, Matthew F. B.; Friedrich, Niklas; Leinen, Philipp; Esat, Taner; Chmielniak, Pawel; Sarwar, Sidra; Rawson, Jeff; Kögerler, Paul; Wagner, Christian; Rohlfing, Michael; Tautz, F. Stefan

    2018-05-01

    We present a physically intuitive model of molecular quantum dots beyond the constant interaction approximation. It accurately describes their charging behavior and allows the extraction of important molecular properties that are otherwise experimentally inaccessible. The model is applied to data recorded with a noncontact atomic force microscope on three different molecules that act as a quantum dot when attached to the microscope tip. The results are in excellent agreement with first-principles simulations.

  14. Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions.

    Science.gov (United States)

    Huang, Juyang

    2002-08-01

    Experimental evidences have indicated that cholesterol may adapt highly regular lateral distributions (i.e., superlattices) in a phospholipid bilayer. We investigated the formations of superlattices at cholesterol mole fraction of 0.154, 0.25, 0.40, and 0.5 using Monte Carlo simulation. We found that in general, conventional pairwise-additive interactions cannot produce superlattices. Instead, a multibody (nonpairwise) interaction is required. Cholesterol superlattice formation reveals that although the overall interaction between cholesterol and phospholipids is favorable, it contains two large opposing components: an interaction favoring cholesterol-phospholipid mixing and an unfavorable acyl chain multibody interaction that increases nonlinearly with the number of cholesterol contacts. The magnitudes of interactions are in the order of kT. The physical origins of these interactions can be explained by our umbrella model. They most likely come from the requirement for polar phospholipid headgroups to cover the nonpolar cholesterol to avoid the exposure of cholesterol to water and from the sharp decreasing of acyl chain conformation entropy due to cholesterol contact. This study together with our previous work demonstrate that the driving force of cholesterol-phospholipid mixing is a hydrophobic interaction, and multibody interactions dominate others over a wide range of cholesterol concentration.

  15. An autosampling differential scanning calorimeter instrument for studying molecular interactions.

    Science.gov (United States)

    Plotnikov, Valerian; Rochalski, Andrew; Brandts, Michael; Brandts, John F; Williston, Samuel; Frasca, Verna; Lin, Lung-Nan

    2002-11-01

    A new ultrasensitive differential scanning calorimeter (DSC) instrument is described, which utilizes autosampling for continuous operation. High scanning rates to 250 deg/h with rapid cooling and equilibration between scans facilitates higher sample throughput up to 50 samples during each 24 h of unattended operation. The instrument is suited for those pharmaceutical applications where higher throughput is important, such as screening drug candidates for binding constant or screening solution conditions for stability of liquid protein formulations. Results are presented on the binding of five different anionic inhibitors to ribonuclease A, which included cytidine 2'-monophosphate (2'CMP), 3'CMP, uridine 3'-monophosphate, pyrophosphate, and phosphate. Binding constants K(B) (or dissociation constants K(d)) are obtained from the shift in the transition temperature T(M) for ribonuclease thermal unfolding in the presence of ligand relative to the transition temperature in the absence of ligand. Measured binding constants ranged from 155 M(-1) (K(d) = 6.45 mM) for the weak-binding phosphate anion to 13100 M(-1) (K(d) = 76.3 microM) for the strongest binding ligand, 2'CMP. The DSC method for measuring binding constants can also be extended to ultratight interactions involving either ligand-protein or protein-protein binding.

  16. π-Cation Interactions in Molecular Recognition: Perspectives on Pharmaceuticals and Pesticides.

    Science.gov (United States)

    Liang, Zhibin; Li, Qing X

    2018-04-04

    The π-cation interaction that differs from the cation-π interaction is a valuable concept in molecular design of pharmaceuticals and pesticides. In this Perspective we present an up-to-date review (from 1995 to 2017) on bioactive molecules involving π-cation interactions with the recognition site, and categorize into systems of inhibitor-enzyme, ligand-receptor, ligand-transporter, and hapten-antibody. The concept of π-cation interactions offers use of π systems in a small molecule to enhance the binding affinity, specificity, selectivity, lipophilicity, bioavailability, and metabolic stability, which are physiochemical features desired for drugs and pesticides.

  17. Molecular recognition of malachite green by hemoglobin and their specific interactions: insights from in silico docking and molecular spectroscopy.

    Science.gov (United States)

    Peng, Wei; Ding, Fei; Peng, Yu-Kui; Sun, Ying

    2014-01-01

    Malachite green is an organic compound that can be widely used as a dyestuff for various materials; it has also emerged as a controversial agent in aquaculture. Since malachite green is proven to be carcinogenic and mutagenic, it may become a hazard to public health. For this reason, it is urgently required to analyze this controversial dye in more detail. In our current research, the interaction between malachite green and hemoglobin under physiological conditions was investigated by the methods of molecular modeling, fluorescence spectroscopy, circular dichroism (CD) as well as hydrophobic ANS displacement experiments. From the molecular docking, the central cavity of hemoglobin was assigned to possess high-affinity for malachite green, this result was corroborated by time-resolved fluorescence and hydrophobic ANS probe results. The recognition mechanism was found to be of static type, or rather the hemoglobin-malachite green complex formation occurred via noncovalent interactions such as π-π interactions, hydrogen bonds and hydrophobic interactions with an association constant of 10(4) M(-1). Moreover, the results also show that the spatial structure of the biopolymer was changed in the presence of malachite green with a decrease of the α-helix and increase of the β-sheet, turn and random coil suggesting protein damage, as derived from far-UV CD and three-dimensional fluorescence. Results of this work will help to further comprehend the molecular recognition of malachite green by the receptor protein and the possible toxicological profiles of other compounds, which are the metabolites and ramifications of malachite green.

  18. Comprehensive analysis of pharmaceutical products using simultaneous mixed-mode (ion-exchange/reversed-phase) and hydrophilic interaction liquid chromatography.

    Science.gov (United States)

    Kazarian, Artaches A; Nesterenko, Pavel N; Soisungnoen, Phimpha; Burakham, Rodjana; Srijaranai, Supalax; Paull, Brett

    2014-08-01

    Liquid chromatographic assays were developed using a mixed-mode column coupled in sequence with a hydrophilic interaction liquid chromatography column to allow the simultaneous comprehensive analysis of inorganic/organic anions and cations, active pharmaceutical ingredients, and excipients (carbohydrates). The approach utilized dual sample injection and valve-mediated column switching and was based upon a single high-performance liquid chromatography gradient pump. The separation consisted of three distinct sequential separation mechanisms, namely, (i) ion-exchange, (ii) mixed-mode interactions under an applied dual gradient (reversed-phase/ion-exchange), and (iii) hydrophilic interaction chromatography. Upon first injection, the Scherzo SS C18 column (Imtakt) provided resolution of inorganic anions and cations under isocratic conditions, followed by a dual organic/salt gradient to elute active pharmaceutical ingredients and their respective organic counterions and potential degradants. At the top of the mixed-mode gradient (high acetonitrile content), the mobile phase flow was switched to a preconditioned hydrophilic interaction liquid chromatography column, and the standard/sample was reinjected for the separation of hydrophilic carbohydrates, some of which are commonly known excipients in drug formulations. The approach afforded reproducible separation and resolution of up to 23 chemically diverse solutes in a single run. The method was applied to investigate the composition of commercial cough syrups (Robitussin®), allowing resolution and determination of inorganic ions, active pharmaceutical ingredients, excipients, and numerous well-resolved unknown peaks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. A comprehensive treatment of electromagnetic interactions and the three-body spectator equations

    Energy Technology Data Exchange (ETDEWEB)

    Jiri Adam; Jay Van Orden

    2004-10-01

    We present a general derivation the three-body spectator (Gross) equations and the corresponding electromagnetic currents. As in previous paper on two-body systems, the wave equations and currents are derived from those for Bethe-Salpeter equation with the help of algebraic method using a concise matrix notation. The three-body interactions and currents introduced by the transition to the spectator approach are isolated and the matrix elements of the e.m. current are presented in detail for system of three indistinguishable particles, namely for elastic scattering and for two and three body break-up. The general expressions are reduced to the one-boson-exchange approximation to make contact with previous work. The method is general in that it does not rely on introduction of the electromagnetic interaction with the help of the minimal replacement. It would therefore work also for other external fields.

  20. Interaction of pathology and molecular characterization of thyroid cancers

    International Nuclear Information System (INIS)

    Williams, E.D.; Cherstvoy, E.; Egloff, B.; Hoefler, H.; Vecchio, G.; Bogdanova, T.; Bragarnik, M.; Tronko, N.D.

    1996-01-01

    This paper presents the results of joint studies of thyroid cancer in children under 15 years of age between departments in Cambridge, Brussels, Naples and Munich in the European Union, and departments in Minsk, Kiev and Obninsk in the newly independent states of Eastern Europe. The pathology of 264 cases of childhood thyroid cancer out of 430 that have occurred since 1990 in the 3 countries in which high levels of fallout from the Chernobyl accident occurred has been restudied by NIS and EU pathologists. The overall level of agreement reached was about 97%. The diagnosis was supported by immunocytochemistry and ISH for the differentiation markers, thyroglobulin and calcitonin, and the tumors were classified according to the WHO, with papillary carcinomas being further subclassified. 99% of the 134 Belarussian cases were papillary carcinomas, as were 94% of the 114 Ukrainian tumors. All 9 of the Russian cases available for study were papillary in type. 76 of 154 cases of childhood thyroid cancer reviewed over a 30 year period in England and Wales and were also studied, 68% of these were papillary carcinoma. Histological study showed that a subtype of papillary carcinoma, rarely found in adults, with a solid/follicular architecture occurred in children. It was found in 72% of the Belarussian papillary carcinomas, 76% of the Ukrainian cases, but only 40% of the England and Wales cases. Molecular biological studies showed that the proportion of cases of papillary carcinoma expressing the ret gene was not significantly different in the exposed and the unexposed tumors, studies of the type of translocation leading to ret gene expression are not yet conclusive. Ras gene mutations were found as expected in follicular carcinoma, but were absent from any papillary carcinoma, whether from exposed or unexposed cases. TSH receptor mutations, normally found in follicular tumors were not found in any papillary carcinomas, nor were any p53 mutations identified. All these results

  1. Free-solution, label-free molecular interactions studied by back-scattering interferometry

    DEFF Research Database (Denmark)

    Bornhop, D.J.; Latham, J.C.; Kussrow, A.

    2007-01-01

    Free-solution, label-free molecular interactions were investigated with back-scattering interferometry in a simple optical train composed of a helium-neon laser, a microfluidic channel, and a position sensor. Molecular binding interactions between proteins, ions and protein, and small molecules...... and protein, were determined with high dynamic range dissociation constants (K-d spanning six decades) and unmatched sensitivity (picomolar K-d's and detection limits of 10,000s of molecules). With this technique, equilibrium dissociation constants were quantified for protein A and immunoglobulin G...

  2. Lipid bilayers driven to a wrong lane in molecular dynamics simulations by subtle changes in long-range electrostatic interactions

    NARCIS (Netherlands)

    Patra, M.; Karttunen, M.E.J.; Hyvönen, M.T.; Falck, E.; Vattulainen, I.

    2004-01-01

    We provide compelling evidence that different treatments of electrostatic interactions in molecular dynamics simulations may dramatically affect dynamic properties of lipid bilayers. To this end, we consider a fully hydrated pure dipalmitoylphosphatidylcholine bilayer through 50-ns molecular

  3. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Sonali S. Bharate

    2010-09-01

    Full Text Available Studies of active drug/excipient compatibility represent an important phase in the preformulation stage of the development of all dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. The present review covers the literature reports of interaction and incompatibilities of commonly used pharmaceutical excipients with different active pharmaceutical ingredients in solid dosage forms. Examples of active drug/excipient interactions, such as transacylation, the Maillard browning reaction, acid base reactions and physical changes are discussed for different active pharmaceutical ingredients belonging to different therapeutic categories viz antiviral, anti-inflammatory, antidiabetic, antihypertensive, anti-convulsant, antibiotic, bronchodialator, antimalarial, antiemetic, antiamoebic, antipsychotic, antidepressant, anticancer, anticoagulant and sedative/hypnotic drugs and vitamins. Once the solid-state reactions of a pharmaceutical system are understood, the necessary steps can be taken to avoid reactivity and improve the stability of drug substances and products.

  4. Optical spectroscopy and system–bath interactions in molecular aggregates with full configuration interaction Frenkel exciton model

    Energy Technology Data Exchange (ETDEWEB)

    Seibt, Joachim; Sláma, Vladislav; Mančal, Tomáš, E-mail: mancal@karlov.mff.cuni.cz

    2016-12-20

    Highlights: • Standard Frenkel exciton model is extended to include inter-band coupling. • It is formally linked with configuration interaction method of quantum chemistry. • Spectral shifts due to inter-band coupling are found in molecular aggregates. • Effects of peak amplitude redistribution in two-dimensional spectra are found. - Abstract: Standard application of the Frenkel exciton model neglects resonance coupling between collective molecular aggregate states with different number of excitations. These inter-band coupling terms are, however, of the same magnitude as the intra-band coupling between singly excited states. We systematically derive the Frenkel exciton model from quantum chemical considerations, and identify it as a variant of the configuration interaction method. We discuss all non-negligible couplings between collective aggregate states, and provide compact formulae for their calculation. We calculate absorption spectra of molecular aggregate of carotenoids and identify significant band shifts as a result of inter-band coupling. The presence of inter-band coupling terms requires renormalization of the system–bath coupling with respect to standard formulation, but renormalization effects are found to be weak. We present detailed discussion of molecular dimer and calculate its time-resolved two-dimensional Fourier transformed spectra to find weak but noticeable effects of peak amplitude redistribution due to inter-band coupling.

  5. Ab initio calculation of molecular energies including parity violating interactions

    International Nuclear Information System (INIS)

    Bakasov, A.; Ha Taekyu; Quack, M.

    1995-01-01

    A new approach, RHF-CIS, based on the perturbation of the ground state RHF wave function by the CIS excitations, has been implemented for evaluation of energy of parity violating interaction in molecules, E pv . The earlier approach, RHF-SDE, was based on the perturbation of the RHF ground states by the single-determinant ''excitations'' (SDE). The results obtained show the dramatic difference between E pv values in the RHF-CIS framework and those in the RHF-SDE framework: the E pv values of the RHF-CIS formalism are more than one order of magnitude greater compared to the RHF-SDE formalism as well as the corresponding tensor components. The maximal total value obtained for hydrogen peroxide in the RHF-CIS framework is 3.661 X 10 -19 E H (DZ ** basis set) while the maximal E pv value for the RHF-SDE formalism is just 3.635 X 10 -20 E H (TZ basis set). It is remarkable that both in the RFH-CIS and in the RHF-SDE approaches the diagonal tensor components of E pv strictly follow the geometry of a molecule and are always different from zero at chiral conformations. The zeros of the total E pv at chiral geometries are now found to be the results of the interplay between the diagonal tensor components values. We have carried out exhaustive analysis of the RHF-SDE formalism and found that it is not sufficiently accurate for studies of E pv . To this end, we have completely reproduced the previous work, which has been done in the RHF-SDE frame-work, and developed it further, studying how the RHF-SDE results vary when changing size and quality of basis sets. This last resource does not save the RHF-SDE formalism for evaluations of E pv from the general failure. Packages of FORTRAN routines called ENWEAK/RHFSDE-93 and ENWEAK/RHFCIS-94 have been developed which run on top of an ab initio MO package. We used 6-31G and 6-31G**, DZ and DZ**, TZ and TZ**, and (10s, 6p,**) basis sets. We will discuss the importance of the present results for possible measurement of the parity

  6. Large Scale Molecular Simulation of Nanoparticle-Biomolecule Interactions and their Implications in Nanomedicine

    Science.gov (United States)

    Zhou, Ruhong

    Nanoscale particles have become promising materials in various biomedical applications, however, in order to stimulate and facilitate these applications, there is an urgent need for a better understanding of their biological effects and related molecular mechanism/physics as well. In this talk, I will discuss some of our recent works, mostly molecular modelling, on nanotoxicity and their implications in de novo design of nanomedicine. We show that carbon-based nanoparticles (carbon nanotubes, graphene nanosheets, and fullerenes) can interact and disrupt the structures and functions of many important proteins. The hydrophobic interactions between the carbon nanotubes and hydrophobic residues, particularly aromatic residues through the so-called π- π stacking interactions, are found to play key roles. Meanwhile, metallofullerenol Gd@C82(OH)22 is found to inhibit tumour growth and metastases with both experimental and theoretical approaches. Graphene and graphene oxide (GO) nanosheets show strong destructive interactions to E. coli cell membranes (antibacterial activity) and A β amyloid fibrils (anti-AD, Alzheimer's disease, capability) with unique molecular mechanisms, while on the other hand, they also show a strong supportive role in enzyme immobilisation such as lipases through lid opening. In particular, the lid opening is assisted by lipase's sophisticated interaction with GO, which allows the adsorbed lipase to enhance its enzyme activity. The lipase enzymatic activity can be further optimized through fine tuning of the GO surface hydrophobicity. These findings might provide a better understanding of ``nanotoxicity'' at the molecular level with implications in de novo nanomedicine design.

  7. Comprehensive process model of clinical information interaction in primary care: results of a "best-fit" framework synthesis.

    Science.gov (United States)

    Veinot, Tiffany C; Senteio, Charles R; Hanauer, David; Lowery, Julie C

    2018-06-01

    To describe a new, comprehensive process model of clinical information interaction in primary care (Clinical Information Interaction Model, or CIIM) based on a systematic synthesis of published research. We used the "best fit" framework synthesis approach. Searches were performed in PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Library and Information Science Abstracts, Library, Information Science and Technology Abstracts, and Engineering Village. Two authors reviewed articles according to inclusion and exclusion criteria. Data abstraction and content analysis of 443 published papers were used to create a model in which every element was supported by empirical research. The CIIM documents how primary care clinicians interact with information as they make point-of-care clinical decisions. The model highlights 3 major process components: (1) context, (2) activity (usual and contingent), and (3) influence. Usual activities include information processing, source-user interaction, information evaluation, selection of information, information use, clinical reasoning, and clinical decisions. Clinician characteristics, patient behaviors, and other professionals influence the process. The CIIM depicts the complete process of information interaction, enabling a grasp of relationships previously difficult to discern. The CIIM suggests potentially helpful functionality for clinical decision support systems (CDSSs) to support primary care, including a greater focus on information processing and use. The CIIM also documents the role of influence in clinical information interaction; influencers may affect the success of CDSS implementations. The CIIM offers a new framework for achieving CDSS workflow integration and new directions for CDSS design that can support the work of diverse primary care clinicians.

  8. Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

    Science.gov (United States)

    Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

    2015-09-04

    comprehensive genetic characterization of a large collection of Chinese USH patients. Up to 90 % of USH patients have disease caused by mutations in known USH disease genes. By combining NGS-based molecular diagnosis and patient clinical information, a more accurate diagnosis, prognosis and personalized treatment of USH patients can be achieved.

  9. DyNet: visualization and analysis of dynamic molecular interaction networks.

    Science.gov (United States)

    Goenawan, Ivan H; Bryan, Kenneth; Lynn, David J

    2016-09-01

    : The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most 'rewired' nodes across many network states. DyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet). david.lynn@sahmri.com Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  10. Rigidity, Chaos and Integration: Hemispheric Interaction and Individual Differences in Metaphor Comprehension

    Directory of Open Access Journals (Sweden)

    Miriam eFaust

    2014-07-01

    Full Text Available Neurotypical individuals cope flexibly with the full range of semantic relations expressed in human language, including metaphoric relations. This impressive semantic ability may be associated with distinct and flexible patterns of hemispheric interaction, including higher right hemisphere (RH involvement for processing novel metaphors. However, this ability may be impaired in specific clinical conditions, such as Asperger syndrome and schizophrenia. The impaired semantic processing is accompanied by different patterns of hemispheric interaction during semantic processing, showing either reduced (in Asperger or excessive (in schizophrenia RH involvement. This paper interprets these individual differences using the terms Rigidity, Chaos and Integration, which describe patterns of semantic memory network states that either lead to semantic well-being or are disruptive of it. We argue that these semantic network states lie on a rigidity-chaos semantic continuum. We define these terms via network science terminology and provide network, cognitive and neural evidence to support our claim. This continuum includes LH hyper-rigid semantic memory state on one end (e.g., in persons with Asperger syndrome, and RH chaotic and over-flexible semantic memory state on the other end (e.g., in persons with schizophrenia. In between these two extremes lie different states of semantic memory structure which are related to individual differences in semantic creativity. We suggest that efficient semantic processing is achieved by semantic integration, a balance between semantic rigidity and semantic chaos. Such integration is achieved via intra-hemispheric communication. However, impairments to this well-balanced and integrated pattern of hemispheric interaction, e.g., when one hemisphere dominates the other, may lead to either semantic rigidity or semantic chaos, moving away from semantic integration and thus impairing the processing of metaphoric language.

  11. Characterization of Hydrophobic Interactions of Polymers with Water and Phospholipid Membranes Using Molecular Dynamics Simulations

    Science.gov (United States)

    Drenscko, Mihaela

    Polymers and lipid membranes are both essential soft materials. The structure and hydrophobicity/hydrophilicity of polymers, as well as the solvent they are embedded in, ultimately determines their size and shape. Understating the variation of shape of the polymer as well as its interactions with model biological membranes can assist in understanding the biocompatibility of the polymer itself. Computer simulations, in particular molecular dynamics, can aid in characterization of the interaction of polymers with solvent, as well as polymers with model membranes. In this thesis, molecular dynamics serve to describe polymer interactions with a solvent (water) and with a lipid membrane. To begin with, we characterize the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained molecular simulation. We next explore the scaling behavior of the collapsed globular shape at the minimum energy configuration, characterized by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behavior of the Solvent Accessible Surface Area (SASA) as a function of chain length, finding a similar exponent for both all-atomistic and coarse-grained simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths. Next, in order to investigate the molecular interactions between single hydrophobic polymer chains and lipids in biological membranes and at lipid membrane/solvent interface, we perform a series of molecular dynamics simulations of

  12. Photodissociation comprehensive study of OH- on alkali halides and their interaction with colour centers

    International Nuclear Information System (INIS)

    Gomes, L.

    1985-01-01

    This work shows that the OH - defect induces changes in the electronics processes of the alkali halides such as in radiation damage and optical cycles of colour centers. Two cases were considered: with the presence of an OH - ion in the (1) excited state and (2) in the ground state; 1) the comprehensive study of resonant OH - photodissociation in several hosts showed that deep traps (for electrons) can be produced from the OH - dissociation. These traps can be effective for the capture of electrons produced in the radiation damage of the lattice as well as for trapping electrons from ionized color centers. It was observed a second channel (new) for the de-excitation of the (OH - )* molecule in KI and RbI. This effect can be effective only when the lattice around the molecule holds a large enough interstitial space. This new mechanism is responsible for the strong production at LNT of F centers and OH 0 molecules at the expenses of OH - defects. Considering the complete investigation of the full cycle it was proposed a phenomenological model that would explain the observed behaviour when one covers a wide variation of lattice parameters (KCl -> RbI); 2) It was verified that the OH - ion present in the lattice induces strong changes in the de-excitation processes of electronic defects with a spread out wave function (like F centers). A change in the reorientation behaviour of excited F 2 and F + 2 centers was also verified. Two main effects should be mentioned: A) The induced de-excitation is very fast and non-radiative on F centers. B) Another type of system investigated (F 2 and F + 2 ) has shown an intense increase of the speed of reorientation of the F 2 and F + 2 excited centers. (autor) [pt

  13. Investigation of the molecular level interactions between mucins and food proteins: Spectroscopic, tribological and rheological studies

    OpenAIRE

    Celebioglu, Hilal Yilmaz; Chronakis, Ioannis S.; Lee, Seunghwan; Guðjónsdóttir, María

    2017-01-01

    The thesis investigated the structure and molecular-level interaction of β-lactoglobulin (BLG) and mucins, representing major components of the dairy products and saliva/digestion systems, respectively. Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer covers epithelial surfaces throughout the body. A literature review of the interactions of different mucin types and saliva mucins with several food proteins and food protein emulsions, as well as their f...

  14. A molecular dynamics study on the interaction between epoxy and functionalized graphene sheets

    DEFF Research Database (Denmark)

    Melro, Liliana Sofia S. F. P.; Pyrz, Ryszard; Jensen, Lars Rosgaard

    2016-01-01

    The interaction between graphene and epoxy resin was studied using molecular dynamics simulations. The interfacial shear strength and pull out force were calculated for functionalised graphene layers (carboxyl, carbonyl, and hydroxyl) and epoxy composites interfaces. The influence of functional...... groups, as well as their distribution and coverage density on the graphene sheets were also analysed through the determination of the Young's modulus. Functionalisation proved to be detrimental to the mechanical properties, nonetheless according to interfacial studies the interaction between graphene...

  15. A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling.

    Science.gov (United States)

    Wieczorek, Dagmar; Bögershausen, Nina; Beleggia, Filippo; Steiner-Haldenstätt, Sabine; Pohl, Esther; Li, Yun; Milz, Esther; Martin, Marcel; Thiele, Holger; Altmüller, Janine; Alanay, Yasemin; Kayserili, Hülya; Klein-Hitpass, Ludger; Böhringer, Stefan; Wollstein, Andreas; Albrecht, Beate; Boduroglu, Koray; Caliebe, Almuth; Chrzanowska, Krystyna; Cogulu, Ozgur; Cristofoli, Francesca; Czeschik, Johanna Christina; Devriendt, Koenraad; Dotti, Maria Teresa; Elcioglu, Nursel; Gener, Blanca; Goecke, Timm O; Krajewska-Walasek, Malgorzata; Guillén-Navarro, Encarnación; Hayek, Joussef; Houge, Gunnar; Kilic, Esra; Simsek-Kiper, Pelin Özlem; López-González, Vanesa; Kuechler, Alma; Lyonnet, Stanislas; Mari, Francesca; Marozza, Annabella; Mathieu Dramard, Michèle; Mikat, Barbara; Morin, Gilles; Morice-Picard, Fanny; Ozkinay, Ferda; Rauch, Anita; Renieri, Alessandra; Tinschert, Sigrid; Utine, G Eda; Vilain, Catheline; Vivarelli, Rossella; Zweier, Christiane; Nürnberg, Peter; Rahmann, Sven; Vermeesch, Joris; Lüdecke, Hermann-Josef; Zeschnigk, Michael; Wollnik, Bernd

    2013-12-20

    Chromatin remodeling complexes are known to modify chemical marks on histones or to induce conformational changes in the chromatin in order to regulate transcription. De novo dominant mutations in different members of the SWI/SNF chromatin remodeling complex have recently been described in individuals with Coffin-Siris (CSS) and Nicolaides-Baraitser (NCBRS) syndromes. Using a combination of whole-exome sequencing, NGS-based sequencing of 23 SWI/SNF complex genes, and molecular karyotyping in 46 previously undescribed individuals with CSS and NCBRS, we identified a de novo 1-bp deletion (c.677delG, p.Gly226Glufs*53) and a de novo missense mutation (c.914G>T, p.Cys305Phe) in PHF6 in two individuals diagnosed with CSS. PHF6 interacts with the nucleosome remodeling and deacetylation (NuRD) complex implicating dysfunction of a second chromatin remodeling complex in the pathogenesis of CSS-like phenotypes. Altogether, we identified mutations in 60% of the studied individuals (28/46), located in the genes ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA2, and PHF6. We show that mutations in ARID1B are the main cause of CSS, accounting for 76% of identified mutations. ARID1B and SMARCB1 mutations were also found in individuals with the initial diagnosis of NCBRS. These individuals apparently belong to a small subset who display an intermediate CSS/NCBRS phenotype. Our proposed genotype-phenotype correlations are important for molecular screening strategies.

  16. TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Lepoivre Cyrille

    2012-01-01

    Full Text Available Abstract Background Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. Results We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices, (ii potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii regulatory interactions curated from the literature, (iv predicted post-transcriptional regulation by micro-RNA, (v protein kinase-substrate interactions and (vi physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration

  17. TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.

    Science.gov (United States)

    Lepoivre, Cyrille; Bergon, Aurélie; Lopez, Fabrice; Perumal, Narayanan B; Nguyen, Catherine; Imbert, Jean; Puthier, Denis

    2012-01-31

    Deciphering gene regulatory networks by in silico approaches is a crucial step in the study of the molecular perturbations that occur in diseases. The development of regulatory maps is a tedious process requiring the comprehensive integration of various evidences scattered over biological databases. Thus, the research community would greatly benefit from having a unified database storing known and predicted molecular interactions. Furthermore, given the intrinsic complexity of the data, the development of new tools offering integrated and meaningful visualizations of molecular interactions is necessary to help users drawing new hypotheses without being overwhelmed by the density of the subsequent graph. We extend the previously developed TranscriptomeBrowser database with a set of tables containing 1,594,978 human and mouse molecular interactions. The database includes: (i) predicted regulatory interactions (computed by scanning vertebrate alignments with a set of 1,213 position weight matrices), (ii) potential regulatory interactions inferred from systematic analysis of ChIP-seq experiments, (iii) regulatory interactions curated from the literature, (iv) predicted post-transcriptional regulation by micro-RNA, (v) protein kinase-substrate interactions and (vi) physical protein-protein interactions. In order to easily retrieve and efficiently analyze these interactions, we developed In-teractomeBrowser, a graph-based knowledge browser that comes as a plug-in for Transcriptome-Browser. The first objective of InteractomeBrowser is to provide a user-friendly tool to get new insight into any gene list by providing a context-specific display of putative regulatory and physical interactions. To achieve this, InteractomeBrowser relies on a "cell compartments-based layout" that makes use of a subset of the Gene Ontology to map gene products onto relevant cell compartments. This layout is particularly powerful for visual integration of heterogeneous biological information

  18. Depletion interactions in two-dimensional colloid-polymer mixtures: molecular dynamics simulations

    International Nuclear Information System (INIS)

    Kim, Soon-Chul; Seong, Baek-Seok; Suh, Soong-Hyuck

    2009-01-01

    The depletion interactions acting between two hard colloids immersed in a bath of polymers, in which the interaction potentials include the soft repulsion/attraction, are extensively studied by using the molecular dynamics simulations. The collision frequencies and collision angle distributions for both incidental and reflection conditions are computed to study the dynamic properties of the colloidal mixtures. The depletion effect induced by the polymer-polymer and colloid-polymer interactions are investigated as well as the size ratio of the colloid and polymer. The simulated results show that the strong depletion interaction between two hard colloids appears for the highly asymmetric hard-disc mixtures. The attractive depletion force at contact becomes deeper and the repulsive barrier becomes wider as the asymmetry in size ratio increases. The strong polymer-polymer attraction leads to the purely attractive depletion interaction between two hard colloids, whereas the purely repulsive depletion interaction is induced by the strong colloid-polymer attraction.

  19. Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages.

    Science.gov (United States)

    He, XiaoCong; Qu, ZhiGuo; Xu, Feng; Lin, Min; Wang, JiuLing; Shi, XingHua; Lu, TianJian

    2014-01-07

    Studying dendrimer-biomembrane interactions is important for understanding drug and gene delivery. In this study, coarse-grained molecular dynamics simulations were performed to investigate the behaviors of polyamidoamine (PAMAM) dendrimers (G4 and G5) as they interacted with asymmetric membranes from different sides of the bilayer, thus mimicking different dendrimer transport stages. The G4 dendrimer could insert into the membrane during an equilibrated state, and the G5 dendrimer could induce pore formation in the membrane when the dendrimers interacted with the outer side (outer interactions) of an asymmetric membrane [with 10% dipalmitoyl phosphatidylserine (DPPS) in the inner leaflet of the membrane]. During the interaction with the inner side of the asymmetric membrane (inner interactions), the G4 and G5 dendrimers only adsorbed onto the membrane. As the membrane asymmetry increased (e.g., increased DPPS percentage in the inner leaflet of the membrane), the G4 and G5 dendrimers penetrated deeper into the membrane during the outer interactions and the G4 and G5 dendrimers were adsorbed more tightly onto the membrane for the inner interactions. When the DPPS content reached 50%, the G4 dendrimer could completely penetrate through the membrane from the outer side to the inner side. Our study provides molecular understanding and reference information about different dendrimer transport stages during drug and gene delivery.

  20. GALAXY INFALL BY INTERACTING WITH ITS ENVIRONMENT: A COMPREHENSIVE STUDY OF 340 GALAXY CLUSTERS

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Liyi [SRON Netherlands Institute for Space Research, Sorbonnelaan 2, 3584 CA Utrecht (Netherlands); Wen, Zhonglue [National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Road, Chaoyang District, Beijing 100012 (China); Gandhi, Poshak [School of Physics and Astronomy, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom); Inada, Naohisa [Department of Physics, Nara National College of Technology, Yamatokohriyama, Nara 639-1080 (Japan); Kawaharada, Madoka [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 229-8510 (Japan); Kodama, Tadayuki [National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan); Konami, Saori [Department of Physics, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397 (Japan); Nakazawa, Kazuhiro; Makishima, Kazuo [Department of Physics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Xu, Haiguang [Department of Physics and Astronomy, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang, Shanghai 200240 (China)

    2016-07-20

    To study systematically the evolution of the angular extents of the galaxy, intracluster medium (ICM), and dark matter components in galaxy clusters, we compiled the optical and X-ray properties of a sample of 340 clusters with redshifts <0.5, based on all the available data from the Sloan Digital Sky Survey and Chandra / XMM-Newton . For each cluster, the member galaxies were determined primarily with photometric redshift measurements. The radial ICM mass distribution, as well as the total gravitational mass distribution, was derived from a spatially resolved spectral analysis of the X-ray data. When normalizing the radial profile of galaxy number to that of the ICM mass, the relative curve was found to depend significantly on the cluster redshift; it drops more steeply toward the outside in lower-redshift subsamples. The same evolution is found in the galaxy-to-total mass profile, while the ICM-to-total mass profile varies in an opposite way. The behavior of the galaxy-to-ICM distribution does not depend on the cluster mass, suggesting that the detected redshift dependence is not due to mass-related effects, such as sample selection bias. Also, it cannot be ascribed to various redshift-dependent systematic errors. We interpret that the galaxies, the ICM, and the dark matter components had similar angular distributions when a cluster was formed, while the galaxies traveling in the interior of the cluster have continuously fallen toward the center relative to the other components, and the ICM has slightly expanded relative to the dark matter although it suffers strong radiative loss. This cosmological galaxy infall, accompanied by an ICM expansion, can be explained by considering that the galaxies interact strongly with the ICM while they are moving through it. The interaction is considered to create a large energy flow of 10{sup 4445} erg s{sup 1} per cluster from the member galaxies to their environment, which is expected to continue over cosmological timescales.

  1. Molecular interactions of Leucoagaricus naucinus with uranium(VI) and europium(III)

    Energy Technology Data Exchange (ETDEWEB)

    Wollenberg, Anne; Raff, Johannes [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biogeochemistry; Guenther, A. [Helmholtz Institute Freiberg for Resource Technology, Freiberg (Germany)

    2017-06-01

    With regard to a molecular understanding of the interaction of fungal mycelium with radionuclides and its possible application for precautionary radiation protection and bio-remediation, the binding mechanism of the radionuclide uranium and the metal europium, as surrogate for trivalent actinides, where investigated with different starting conditions by the living fungal cells of Leucoagaricus naucinus.

  2. Getting the ion-protein interactions right in molecular dynamics simulations

    Czech Academy of Sciences Publication Activity Database

    Duboué-Dijon, Elise; Mason, Philip E.; Jungwirth, Pavel

    2017-01-01

    Roč. 46, Suppl 1 (2017), S66 ISSN 0175-7571. [IUPAB congress /19./ and EBSA congress /11./. 16.07.2017-20.07.2017, Edinburgh] Institutional support: RVO:61388963 Keywords : ion-protein interaction * molecular dynamics simulations * neutron scattering * insulin Subject RIV: BO - Biophysics

  3. DP 71 AND BETA DYSTROGLYCAN INTERACTION: A MOLECULAR MODELING APPROACH TO UNDERSTAND DUCHENNE MUSCULAR DYSTROPHY

    Directory of Open Access Journals (Sweden)

    Simanti Bhattacharya,

    2013-12-01

    Full Text Available Dp 71 is the most prevalent and widely expressed non muscle isoform of dystrophin (Dp and its mutations are associated with Duchenne muscular dystrophy, a severe form of muscular disorder. Dp 71 deviates from the canonical Dp by means of its truncated N terminal which also has abolished certain amino acids that comprise WW domain in the canonical form. This WW domain is very crucial for Dp’s interaction with partner proteins to establish a bridge between extra cellular matrices and cellular cytoskeleton. In our current study we have employed molecular modeling technique to understand the structural architecture of the N terminal region of Dp 71 and its deviation from the canonical form. We have further extended our studies to analyze the interaction probabilities between Dp 71 and β-DG applying molecular docking. Our studies for the first time have revealed that in spite of the underlying differences in terms of amino acids and structural organization, Dp 71 can interact with β-DG with its N terminal region which shares the similar molecular surface with the canonical form of Dp. These findings have opened up a platform to investigate the molecular interactions, spatio temporal orientations of the amino acids of Dp 71 and β-DG to understand the onset of DMD in much more greater detail

  4. Comparison of molecular dynamics and kinetic modeling of gas-surface interactions

    NARCIS (Netherlands)

    Frezzotti, A.; Gaastra - Nedea, S.V.; Markvoort, A.J.; Spijker, P.; Gibelli, L.

    2008-01-01

    The interaction of a dilute monatomic gas with a solid surface is studied byMolecular Dynamics (MD) simulations and by numerical solutions of a recently proposed kinetic model. Following previous investigations, the heat transport between parallel walls and Couette flow have been adopted as test

  5. Dzyaloshinskii-Moriya interactions and adiabatic magnetization dynamics in molecular magnets

    NARCIS (Netherlands)

    De Raedt, H; Miyashita, S; Michielsen, K; Machida, M

    A microscopic model of the molecular magnet V-15 is used to study mechanisms for the adiabatic change of the magnetization in time-dependent magnetic fields. The effects of the Dzyaloshinskii-Moriya interaction, the most plausible source for the energy-level repulsions that lead to adiabatic changes

  6. Molecular interactions of Leucoagaricus naucinus with uranium(VI) and europium(III)

    International Nuclear Information System (INIS)

    Wollenberg, Anne; Raff, Johannes

    2017-01-01

    With regard to a molecular understanding of the interaction of fungal mycelium with radionuclides and its possible application for precautionary radiation protection and bio-remediation, the binding mechanism of the radionuclide uranium and the metal europium, as surrogate for trivalent actinides, where investigated with different starting conditions by the living fungal cells of Leucoagaricus naucinus.

  7. Immobilization of molecular cobalt electrocatalyst by hydrophobic interaction with hematite photoanode for highly stable oxygen evolution

    KAUST Repository

    Joya, Khurram

    2015-07-15

    A unique modification of a hematite photoanode with perfluorinated Co-phthalocyanine (CoFPc) by strong binding associated with hydrophobic interaction is demonstrated. The resultant molecular electrocatalyst – hematite photoanode hybrid material showed significant onset shift and high stability for photoelectrochemical oxidation evolution reaction (OER).

  8. PREDICTION OF THE MIXING ENTHALPIES OF BINARY LIQUID ALLOYS BY MOLECULAR INTERACTION VOLUME MODEL

    Institute of Scientific and Technical Information of China (English)

    H.W.Yang; D.P.Tao; Z.H.Zhou

    2008-01-01

    The mixing enthalpies of 23 binary liquid alloys are calculated by molecular interaction volume model (MIVM), which is a two-parameter model with the partial molar infinite dilute mixing enthalpies. The predicted values are in agreement with the experimental data and then indicate that the model is reliable and convenient.

  9. Lysozyme-magnesium aluminum silicate microparticles: Molecular interaction, bioactivity and release studies

    DEFF Research Database (Denmark)

    Kanjanakawinkul, Watchara; Medlicott, Natalie J.; Rades, Thomas

    2015-01-01

    The objectives of this study were to investigate the adsorption behavior of lysozyme (LSZ) onto magnesium aluminum silicate (MAS) at various pHs and to characterize the LSZ–MAS microparticles obtained from the molecular interaction between LSZ and MAS. The results showed that LSZ could be bound...

  10. Immobilization of molecular cobalt electrocatalyst by hydrophobic interaction with hematite photoanode for highly stable oxygen evolution

    KAUST Repository

    Joya, Khurram; Morlanes, Natalia; Maloney, Edward; Rodionov, Valentin; Takanabe, Kazuhiro

    2015-01-01

    A unique modification of a hematite photoanode with perfluorinated Co-phthalocyanine (CoFPc) by strong binding associated with hydrophobic interaction is demonstrated. The resultant molecular electrocatalyst – hematite photoanode hybrid material showed significant onset shift and high stability for photoelectrochemical oxidation evolution reaction (OER).

  11. Crowding of Interacting Fluid Particles in Porous Media through Molecular Dynamics: Breakdown of Universality for Soft Interactions

    Science.gov (United States)

    Schnyder, Simon K.; Horbach, Jürgen

    2018-02-01

    Molecular dynamics simulations of interacting soft disks confined in a heterogeneous quenched matrix of soft obstacles show dynamics which is fundamentally different from that of hard disks. The interactions between the disks can enhance transport when their density is increased, as disks cooperatively help each other over the finite energy barriers in the matrix. The system exhibits a transition from a diffusive to a localized state, but the transition is strongly rounded. Effective exponents in the mean-squared displacement can be observed over three decades in time but depend on the density of the disks and do not correspond to asymptotic behavior in the vicinity of a critical point, thus, showing that it is incorrect to relate them to the critical exponents in the Lorentz model scenario. The soft interactions are, therefore, responsible for a breakdown of the universality of the dynamics.

  12. Cyrus Levinthal, the Kluge and the origins of interactive molecular graphics.

    Science.gov (United States)

    Francoeur, Eric

    2002-12-01

    In the mid-1960s, a group of scientists at Massachusetts Institute of Technology, led by Cyrus Levinthal, took hold of one of the early interactive graphics terminals and used it to visualize, study and model the structure of proteins and nucleic acids. From this encounter between cutting-edge computer technology and molecular biology emerged the crucial elements for the development of a research-technology field known today as interactive molecular graphics. The following account is not only about how computer graphics technology has literally changed the way scientists view the molecular realm, but also a look at how an epistemic and institutional space was created to integrate this technology into scientific research.

  13. Molecular dynamics simulations of interfacial interactions between small nanoparticles during diffusion-limited aggregation

    International Nuclear Information System (INIS)

    Lu, Jing; Liu, Dongmei; Yang, Xiaonan; Zhao, Ying; Liu, Haixing; Tang, Huan; Cui, Fuyi

    2015-01-01

    Graphical abstract: - Highlights: • Diffusion-limited aggregation is analyzed using molecular dynamic simulations. • The aggregation processand aggregate structure vary with particle size. • Particle-particle interaction and surface diffusion result in direct bonding. • Water-mediated interaction is responsible for the separation betweennanoparticles. - Abstract: Due to the limitations of experimental methods at the atomic level, research on the aggregation of small nanoparticles (D < 5 nm) in aqueous solutions is quite rare. The aggregation of small nanoparticles in aqueous solutions is very different than that of normal sized nanoparticles. The interfacial interactions play a dominant role in the aggregation of small nanoparticles. In this paper, molecular dynamics simulations, which can explore the microscopic behavior of nanoparticles during the diffusion-limited aggregation at an atomic level, were employed to reveal the aggregation mechanism of small nanoparticles in aqueous solutions. First, the aggregation processes and aggregate structure were depicted. Second, the particle–particle interaction and surface diffusion of nanoparticles during aggregation were investigated. Third, the water-mediated interactions during aggregation were ascertained. The results indicate that the aggregation of nanoparticle in aqueous solutions is affected by particle size. The strong particle–particle interaction and high surface diffusion result in the formation of particle–particle bonds of 2 nm TiO 2 nanoparticles, and the water-mediated interaction plays an important role in the aggregation process of 3 and 4 nm TiO 2 nanoparticles.

  14. Dynamics of relaxation to a stationary state for interacting molecular motors

    Science.gov (United States)

    Gomes, Luiza V. F.; Kolomeisky, Anatoly B.

    2018-01-01

    Motor proteins are active enzymatic molecules that drive a variety of biological processes, including transfer of genetic information, cellular transport, cell motility and muscle contraction. It is known that these biological molecular motors usually perform their cellular tasks by acting collectively, and there are interactions between individual motors that specify the overall collective behavior. One of the fundamental issues related to the collective dynamics of motor proteins is the question if they function at stationary-state conditions. To investigate this problem, we analyze a relaxation to the stationary state for the system of interacting molecular motors. Our approach utilizes a recently developed theoretical framework, which views the collective dynamics of motor proteins as a totally asymmetric simple exclusion process of interacting particles, where interactions are taken into account via a thermodynamically consistent approach. The dynamics of relaxation to the stationary state is analyzed using a domain-wall method that relies on a mean-field description, which takes into account some correlations. It is found that the system quickly relaxes for repulsive interactions, while attractive interactions always slow down reaching the stationary state. It is also predicted that for some range of parameters the fastest relaxation might be achieved for a weak repulsive interaction. Our theoretical predictions are tested with Monte Carlo computer simulations. The implications of our findings for biological systems are briefly discussed.

  15. A Comprehensive Experiment for Molecular Biology: Determination of Single Nucleotide Polymorphism in Human REV3 Gene Using PCR-RFLP

    Science.gov (United States)

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-01-01

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of…

  16. Molecular dynamics simulations of matrix assisted laser desorption ionization: Matrix-analyte interactions

    International Nuclear Information System (INIS)

    Nangia, Shivangi; Garrison, Barbara J.

    2011-01-01

    There is synergy between matrix assisted laser desorption ionization (MALDI) experiments and molecular dynamics (MD) simulations. To understand analyte ejection from the matrix, MD simulations have been employed. Prior calculations show that the ejected analyte molecules remain solvated by the matrix molecules in the ablated plume. In contrast, the experimental data show free analyte ions. The main idea of this work is that analyte molecule ejection may depend on the microscopic details of analyte interaction with the matrix. Intermolecular matrix-analyte interactions have been studied by focusing on 2,5-dihydroxybenzoic acid (DHB; matrix) and amino acids (AA; analyte) using Chemistry at HARvard Molecular Mechanics (CHARMM) force field. A series of AA molecules have been studied to analyze the DHB-AA interaction. A relative scale of AA molecule affinity towards DHB has been developed.

  17. Characterization of the Interaction between Eupatorin and Bovine Serum Albumin by Spectroscopic and Molecular Modeling Methods

    Science.gov (United States)

    Xu, Hongliang; Yao, Nannan; Xu, Haoran; Wang, Tianshi; Li, Guiying; Li, Zhengqiang

    2013-01-01

    This study investigated the interaction between eupatorin and bovine serum albumin (BSA) using ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, circular dichroism (CD) spectroscopies, and molecular modeling at pH 7.4. Results of UV-vis and fluorescence spectroscopies illustrated that BSA fluorescence was quenched by eupatorin via a static quenching mechanism. Thermodynamic parameters revealed that hydrophobic and electrostatic interactions played major roles in the interaction. Moreover, the efficiency of energy transfer, and the distance between BSA and acceptor eupatorin, were calculated. The effects of eupatorin on the BSA conformation were analyzed using UV-vis, CD, and synchronous fluorescence. Finally, the binding of eupatorin to BSA was modeled using the molecular docking method. PMID:23839090

  18. Molecular interactions in biomineralized hydroxyapatite amino acid modified nanoclay: In silico design of bone biomaterials

    International Nuclear Information System (INIS)

    Katti, Dinesh R.; Sharma, Anurag; Ambre, Avinash H.; Katti, Kalpana S.

    2015-01-01

    A simulations driven approach to design of a novel biomaterial nanocomposite system is described in this study. Nanoclays modified with amino acids (OMMT) were used to mineralize hydroxyapatite (HAP), mimicking biomineralization. Representative models of organically modified montmorillonite clay (OMMT) and OMMT-hydroxyapatite (OMMT-HAP) were constructed using molecular dynamics and validated using X-ray Diffraction (XRD), Fourier Transforms Infrared (FTIR) spectroscopy and Transmission Electron Microscopy (TEM). Attractive interactions exist between Ca atoms of HAP and C=O group of aminovaleric acid, indicating chelate formation in OMMT-HAP. Interaction energy maps describe molecular interactions among different constituents and their quantitative contributions in the OMMT and OMMT-HAP systems at both parallel and perpendicular orientations. High attractive and high repulsive interactions were found between PO 4 3− and MMT clay as well as aminovaleric molecules in OMMT-HAP perpendicular and parallel models. Large non-bonded interactions in OMMT-HAP indicate influence of neighboring environment on PO 4 3− in in situ HAPclay. Extensive hydrogen bonds were observed between functional hydrogen atoms of modifier and MMT clay in OMMT-HAP as compared to OMMT. Thus, HAP interacts with clay through the aminovaleric acid. This computational study provides a framework for materials design and selection for biomaterials used in tissue engineering and other areas of regenerative medicine. - Highlights: • Representative models of a hybrid nanoclay-hydroxyapatite biomaterial are built. • Interaction energy maps are constructed using a molecular dynamics. • Quantitative interactions between the three components of the biomaterial are found. • The modeling and experimental approach provides insight into the complex nanomaterial

  19. Quantifying the molecular origins of opposite solvent effects on protein-protein interactions.

    Directory of Open Access Journals (Sweden)

    Vincent Vagenende

    Full Text Available Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

  20. Comprehensive Characterization of HIV-1 Molecular Epidemiology and Demographic History in the Brazilian Region Most Heavily Affected by AIDS.

    Science.gov (United States)

    Gräf, Tiago; Machado Fritsch, Hegger; de Medeiros, Rúbia Marília; Maletich Junqueira, Dennis; Esteves de Matos Almeida, Sabrina; Pinto, Aguinaldo Roberto

    2016-09-15

    The high incidence of AIDS cases and the dominance of HIV-1 subtype C infections are two features that distinguish the HIV-1 epidemic in the two southernmost Brazilian states (Rio Grande do Sul [RS] and Santa Catarina [SC]) from the epidemic in other parts of the country. Nevertheless, previous studies on HIV molecular epidemiology were conducted mainly in capital cities, and a more comprehensive understanding of factors driving this unique epidemic in Brazil is necessary. Blood samples were collected from individuals in 13 municipalities in the Brazilian southern region. HIV-1 env and pol genes were submitted to phylogenetic analyses for assignment of subtype, and viral population phylodynamics were reconstructed by applying Skygrid and logistic coalescent models in a Bayesian analysis. A high prevalence of subtype C was observed in all sampled locations; however, an increased frequency of recombinant strains was found in RS, with evidence for new circulating forms (CRFs). In the SC state, subtype B and C epidemics were associated with distinct exposure groups. Although logistic models estimated similar growth rates for HIV-1 subtype C (HIV-1C) and HIV-1B, a Skygrid plot reveals that the former epidemic has been expanding for a longer time. Our results highlight a consistent expansion of HIV-1C in south Brazil, and we also discuss how heterosexual and men who have sex with men (MSM) transmission chains might have impacted the current prevalence of HIV-1 subtypes in this region. The AIDS epidemic in south Brazil is expanding rapidly, but the circumstances driving this condition are not well known. A high prevalence of HIV-1 subtype C was reported in the capital cities of this region, in contrast to the subtype B dominance in the rest of the country. This study sought to comparatively investigate the HIV-1 subtype B and C epidemics by sampling individuals from several cities in the two states with the highest AIDS incidences in Brazil. Our analyses showed distinct

  1. Molecular equilibrium structures from experimental rotational constants and calculated vibration-rotation interaction constants

    DEFF Research Database (Denmark)

    Pawlowski, F; Jorgensen, P; Olsen, Jeppe

    2002-01-01

    A detailed study is carried out of the accuracy of molecular equilibrium geometries obtained from least-squares fits involving experimental rotational constants B(0) and sums of ab initio vibration-rotation interaction constants alpha(r)(B). The vibration-rotation interaction constants have been...... calculated for 18 single-configuration dominated molecules containing hydrogen and first-row atoms at various standard levels of ab initio theory. Comparisons with the experimental data and tests for the internal consistency of the calculations show that the equilibrium structures generated using Hartree......-Fock vibration-rotation interaction constants have an accuracy similar to that obtained by a direct minimization of the CCSD(T) energy. The most accurate vibration-rotation interaction constants are those calculated at the CCSD(T)/cc-pVQZ level. The equilibrium bond distances determined from these interaction...

  2. Molecular Understanding of Fullerene - Electron Donor Interactions in Organic Solar Cells

    KAUST Repository

    Ryno, Sean

    2016-09-13

    Organic solar cells hold promise of providing low-cost, renewable power generation, with current devices providing up to 13% power conversion efficiency. The rational design of more performant systems requires an in-depth understanding of the interactions between the electron donating and electron accepting materials within the active layers of these devices. Here, we explore works that give insight into the intermolecular interactions between electron donors and electron acceptors, and the impact of molecular orientations and environment on these interactions. We highlight, from a theoretical standpoint, the effects of intermolecular interactions on the stability of charge carriers at the donor/acceptor interface and in the bulk and how these interactions influence the nature of the charge transfer states as wells as the charge separation and charge transport processes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations

    International Nuclear Information System (INIS)

    Hardy, David J.; Schulten, Klaus; Wolff, Matthew A.; Skeel, Robert D.; Xia, Jianlin

    2016-01-01

    The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle–mesh Ewald method falls short.

  4. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

    Science.gov (United States)

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  5. Arabidopsis mRNA polyadenylation machinery: comprehensive analysis of protein-protein interactions and gene expression profiling

    Directory of Open Access Journals (Sweden)

    Mo Min

    2008-05-01

    Full Text Available Abstract Background The polyadenylation of mRNA is one of the critical processing steps during expression of almost all eukaryotic genes. It is tightly integrated with transcription, particularly its termination, as well as other RNA processing events, i.e. capping and splicing. The poly(A tail protects the mRNA from unregulated degradation, and it is required for nuclear export and translation initiation. In recent years, it has been demonstrated that the polyadenylation process is also involved in the regulation of gene expression. The polyadenylation process requires two components, the cis-elements on the mRNA and a group of protein factors that recognize the cis-elements and produce the poly(A tail. Here we report a comprehensive pairwise protein-protein interaction mapping and gene expression profiling of the mRNA polyadenylation protein machinery in Arabidopsis. Results By protein sequence homology search using human and yeast polyadenylation factors, we identified 28 proteins that may be components of Arabidopsis polyadenylation machinery. To elucidate the protein network and their functions, we first tested their protein-protein interaction profiles. Out of 320 pair-wise protein-protein interaction assays done using the yeast two-hybrid system, 56 (~17% showed positive interactions. 15 of these interactions were further tested, and all were confirmed by co-immunoprecipitation and/or in vitro co-purification. These interactions organize into three distinct hubs involving the Arabidopsis polyadenylation factors. These hubs are centered around AtCPSF100, AtCLPS, and AtFIPS. The first two are similar to complexes seen in mammals, while the third one stands out as unique to plants. When comparing the gene expression profiles extracted from publicly available microarray datasets, some of the polyadenylation related genes showed tissue-specific expression, suggestive of potential different polyadenylation complex configurations. Conclusion An

  6. Spatiotemporal dynamics and epistatic interaction sites in dengue virus type 1: a comprehensive sequence-based analysis.

    Directory of Open Access Journals (Sweden)

    Pei-Yu Chu

    Full Text Available The continuing threat of dengue fever necessitates a comprehensive characterisation of its epidemiological trends. Phylogenetic and recombination events were reconstructed based on 100 worldwide dengue virus (DENV type 1 genome sequences with an outgroup (prototypes of DENV2-4. The phylodynamic characteristics and site-specific variation were then analysed using data without the outgroup. Five genotypes (GI-GV and a ladder-like structure with short terminal branch topology were observed in this study. Apparently, the transmission of DENV1 was geographically random before gradual localising with human activity as GI-GIII in South Asia, GIV in the South Pacific, and GV in the Americas. Genotypes IV and V have recently shown higher population densities compared to older genotypes. All codon regions and all tree branches were skewed toward a negative selection, which indicated that their variation was restricted by protein function. Notably, multi-epistatic interaction sites were found in both PrM 221 and NS3 1730. Recombination events accumulated in regions E, NS3-NS4A, and particularly in region NS5. The estimated coevolution pattern also highlights the need for further study of the biological role of protein PrM 221 and NS3 1730. The recent transmission of emergent GV sublineages into Central America and Europe mandates closely monitoring of genotype interaction and succession.

  7. Compensation effects in molecular interactions and the quantum chemical le Chatelier principle.

    Science.gov (United States)

    Mezey, Paul G

    2015-05-28

    Components of molecular interactions and various changes in the components of total energy changes during molecular processes typically exhibit some degrees of compensation. This may be as prominent as the over 90% compensation of the electronic energy and nuclear repulsion energy components of the total energy in some conformational changes. Some of these compensations are enhanced by solvent effects. For various arrangements of ions in a solvent, however, not only compensation but also a formal, mutual enhancement between the electronic energy and nuclear repulsion energy components of the total energy may also occur, when the tools of nuclear charge variation are applied to establish quantum chemically rigorous energy inequalities.

  8. Interaction sorting method for molecular dynamics on multi-core SIMD CPU architecture.

    Science.gov (United States)

    Matvienko, Sergey; Alemasov, Nikolay; Fomin, Eduard

    2015-02-01

    Molecular dynamics (MD) is widely used in computational biology for studying binding mechanisms of molecules, molecular transport, conformational transitions, protein folding, etc. The method is computationally expensive; thus, the demand for the development of novel, much more efficient algorithms is still high. Therefore, the new algorithm designed in 2007 and called interaction sorting (IS) clearly attracted interest, as it outperformed the most efficient MD algorithms. In this work, a new IS modification is proposed which allows the algorithm to utilize SIMD processor instructions. This paper shows that the improvement provides an additional gain in performance, 9% to 45% in comparison to the original IS method.

  9. Study of Molecular Interactions in Binary Liquid Mixtures by Acoustical Method at 303K

    Directory of Open Access Journals (Sweden)

    P. Paul Divakar

    2012-01-01

    Full Text Available Ultrasonic velocity and density measurements were made in two binary liquid mixtures Isopropyl acetate (IPA and Isobutyl acetate (IBA with cyclohexanone (CY as a common component at 303K, at fixed frequency of 2MHz using single crystal variable path interferometer and specific gravity bottle respectively. The experimental data have been used to calculate the acoustic impedance, adiabatic compressibility, inter molecular free length and molar volume. The excess thermodynamic parameters have been evaluated and discussed in the light of molecular interactions.

  10. Multiscale Molecular Dynamics Simulations of Beta-Amyloid Interactions with Neurons

    Science.gov (United States)

    Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

    2012-10-01

    Early events of human beta-amyloid protein interactions with cholesterol-containing membranes are critical to understanding the pathogenesis of Alzheimer's disease (AD) and to exploring new therapeutic interventions of AD. Atomistic molecular dynamics (AMD) simulations have been extensively used to study the protein-lipid interaction at high atomic resolutions. However, traditional MD simulations are not efficient in sampling the phase space of complex lipid/protein systems with rugged free energy landscapes. Meanwhile, coarse-grained MD (CGD) simulations are efficient in the phase space sampling but suffered from low spatial resolutions and from the fact that the energy landscapes are not identical to those of the AMD. Here, a multiscale approach was employed to simulate the protein-lipid interactions of beta-amyloid upon its release from proteolysis residing in the neuronal membranes. We utilized a forward (AMD to CGD) and reverse (CGD-AMD) strategy to explore new transmembrane and surface protein configuration and evaluate the stabilization mechanisms by measuring the residue-specific protein-lipid or protein conformations. The detailed molecular interactions revealed in this multiscale MD approach will provide new insights into understanding the early molecular events leading to the pathogenesis of AD.

  11. Determination and Quantification of Molecular Interactions in Protein Films: A Review

    Directory of Open Access Journals (Sweden)

    Felicia Hammann

    2014-12-01

    Full Text Available Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography and analysis of solid films (spectroscopy techniques, X-ray scattering methods. To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

  12. Determination and Quantification of Molecular Interactions in Protein Films: A Review.

    Science.gov (United States)

    Hammann, Felicia; Schmid, Markus

    2014-12-10

    Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

  13. Interaction between the SNR Sagittarius A East and the 50-km s-1 Molecular Cloud

    International Nuclear Information System (INIS)

    Tsuboi, Masato; Okumura, Sachiko K; Miyazaki, Atsushi

    2006-01-01

    We performed high-resolution observations of the Galactic Center 50-km s -1 molecular cloud in the CS J = 1 - 0 line using the Nobeyama Millimeter Array. The 50-km s -1 molecular cloud corresponds to a break in the Sagittarius (Sgr) A east shell. A very broad and negative velocity wing feature is detected at an apparent contact spot between the molecular cloud and the Sgr A east shell. The velocity width of the wing feature is over 50-km s -1 . The width is three times wider than those of typical Galactic Center clouds. This strongly suggests that the shell is interacting physically with the molecular cloud. The asymmetric velocity profile of the wing feature indicates that the Sgr A east shell expands and crashes into the far side of the molecular cloud. About 50 clumps are identified in the cloud using CLUMPFIND. The velocity width-size relation and the mass spectrum of clumps in the cloud are similar to those in Central Molecular Zone (CMZ)

  14. Technology acceptance for an Intelligent Comprehensive Interactive Care (ICIC system for care of the elderly: a survey-questionnaire study.

    Directory of Open Access Journals (Sweden)

    Alice M K Wong

    Full Text Available The key components of caring for the elderly are diet, living, transportation, education, and safety issues, and telemedical systems can offer great assistance. Through the integration of personal to community information technology platforms, we have developed a new Intelligent Comprehensive Interactive Care (ICIC system to provide comprehensive services for elderly care. The ICIC system consists of six items, including medical care (physiological measuring system, Medication Reminder, and Dr. Ubiquitous, diet, living, transportation, education (Intelligent Watch, entertainment (Sharetouch, and safety (Fall Detection. In this study, we specifically evaluated the users' intention of using the Medication Reminder, Dr. Ubiquitous, Sharetouch, and Intelligent Watch using a modified technological acceptance model (TAM. A total of 121 elderly subjects (48 males and 73 females were recruited. The modified TAM questionnaires were collected after they had used these products. For most of the ICIC units, the elderly subjects revealed great willingness and/or satisfaction in using this system. The elderly users of the Intelligent Watch showed the greatest willingness and satisfaction, while the elderly users of Dr. Ubiquitous revealed fair willingness in the dimension of perceived ease of use. The old-old age group revealed greater satisfaction in the dimension of result demonstrability for the users of the Medication Reminder as compared to the young-old and oldest-old age groups. The women revealed greater satisfaction in the dimension of perceived ease of use for the users of Dr. Ubiquitous as compared to the men. There were no statistically significant differences in terms of gender, age, and education level in the other dimensions. The modified TAM showed its effectiveness in evaluating the acceptance and characteristics of technologic products for the elderly user. The ICIC system offers a user-friendly solution in telemedical care and improves the

  15. Technology acceptance for an Intelligent Comprehensive Interactive Care (ICIC) system for care of the elderly: a survey-questionnaire study.

    Science.gov (United States)

    Wong, Alice M K; Chang, Wei-Han; Ke, Pei-Chih; Huang, Chun-Kai; Tsai, Tsai-Hsuan; Chang, Hsien-Tsung; Shieh, Wann-Yun; Chan, Hsiao-Lung; Chen, Chih-Kuang; Pei, Yu-Cheng

    2012-01-01

    The key components of caring for the elderly are diet, living, transportation, education, and safety issues, and telemedical systems can offer great assistance. Through the integration of personal to community information technology platforms, we have developed a new Intelligent Comprehensive Interactive Care (ICIC) system to provide comprehensive services for elderly care. The ICIC system consists of six items, including medical care (physiological measuring system, Medication Reminder, and Dr. Ubiquitous), diet, living, transportation, education (Intelligent Watch), entertainment (Sharetouch), and safety (Fall Detection). In this study, we specifically evaluated the users' intention of using the Medication Reminder, Dr. Ubiquitous, Sharetouch, and Intelligent Watch using a modified technological acceptance model (TAM). A total of 121 elderly subjects (48 males and 73 females) were recruited. The modified TAM questionnaires were collected after they had used these products. For most of the ICIC units, the elderly subjects revealed great willingness and/or satisfaction in using this system. The elderly users of the Intelligent Watch showed the greatest willingness and satisfaction, while the elderly users of Dr. Ubiquitous revealed fair willingness in the dimension of perceived ease of use. The old-old age group revealed greater satisfaction in the dimension of result demonstrability for the users of the Medication Reminder as compared to the young-old and oldest-old age groups. The women revealed greater satisfaction in the dimension of perceived ease of use for the users of Dr. Ubiquitous as compared to the men. There were no statistically significant differences in terms of gender, age, and education level in the other dimensions. The modified TAM showed its effectiveness in evaluating the acceptance and characteristics of technologic products for the elderly user. The ICIC system offers a user-friendly solution in telemedical care and improves the quality of

  16. Molecular structure and interactions of nucleic acid components in nanoparticles: ab initio calculations

    International Nuclear Information System (INIS)

    Rubin, Yu.V.; Belous, L.F.

    2012-01-01

    Self-associates of nucleic acid components (stacking trimers and tetramers of the base pairs of nucleic acids) and short fragments of nucleic acids are nanoparticles (linear sizes of these particles are more than 10 A). Modern quantum-mechanical methods and softwares allow one to perform ab initio calculations of the systems consisting of 150-200 atoms with enough large basis sets (for example, 6-31G * ). The aim of this work is to reveal the peculiarities of molecular and electronic structures, as well as the energy features of nanoparticles of nucleic acid components. We had carried out ab initio calculations of the molecular structure and interactions in the stacking dimer, trimer, and tetramer of nucleic base pairs and in the stacking (TpG)(ApC) dimer and (TpGpC) (ApCpG) trimer of nucleotides, which are small DNA fragments. The performed calculations of molecular structures of dimers and trimers of nucleotide pairs showed that the interplanar distance in the structures studied is equal to 3.2 A on average, and the helical angle in a trimer is approximately equal to 30 o : The distance between phosphor atoms in neighboring chains is 13.1 A. For dimers and trimers under study, we calculated the horizontal interaction energies. The analysis of interplanar distances and angles between nucleic bases and their pairs in the calculated short oligomers of nucleic acid base pairs (stacking dimer, trimer, and tetramer) has been carried out. Studies of interactions in the calculated short oligomers showed a considerable role of the cross interaction in the stabilization of the structures. The contribution of cross interactions to the horizontal interactions grows with the length of an oligomer. Nanoparticle components get electric charges in nanoparticles. Longwave low-intensity bands can appear in the electron spectra of nanoparticles.

  17. REVIEW - Advances on molecular studies of the interaction soybean - Asian rust

    Directory of Open Access Journals (Sweden)

    Aguida Maria Alves Pereira Morales

    2012-01-01

    Full Text Available Effective management practices are essential for controlling rust outbreaks. The main control methodused is the application of fungicides, which increases substantially the cost of production and is harmful to theenvironment. Prevention is still the best way to avoid more significant losses in soybean yields. Alternatives,such as planting resistant varieties to the fungus, are also important. The use of resistant or tolerant varietiesis the most promising method for controlling Asian soybean rust. Recently, five dominant genes resistant to soybean rust were described: Rpp1, Rpp2, Rpp3, Rpp4 and Rpp5. However, little is known about the molecular interaction among soybean plant and soybean rust and on the molecular pathway triggered by pathogen recognition. Understanding the molecular mechanisms involved in defense responses is of primary importance for planning strategies to control stress and, consequently, to increase plant adaptation to limiting conditions

  18. Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

    Science.gov (United States)

    Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

    2014-12-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Interaction of Chelerythrine with Keyhole Limpet Hemocyanin: a Fluorescence Spectroscopy and Molecular Docking Study

    Science.gov (United States)

    Zhong, M.; Long, R. Q.; Wang, Y. H.; Chen, C. L.

    2018-05-01

    The quenching mechanism between chelerythrine (CHE) and keyhole limpet hemocyanin (KLH) was investigated using fluorescence spectroscopy and molecular docking. The experiments were conducted at three different temperatures (293, 298, and 303 K). The results revealed that the intrinsic fluorescence of KLH was strongly quenched by CHE through a static quenching mechanism. The thermodynamic parameters (ΔG, ΔH, and ΔS) of the interaction were calculated, indicating that the interaction between CHE and KLH was spontaneous and that van der Waals forces and hydrogen bond formation played major roles in the binding process. The intrinsic fluorescence of the tyrosine and tryptophan residues in KLH was studied by synchronous fluorescence, which suggested that CHE changed the conformation of KLH. Finally, molecular docking was used to obtain detailed information on the binding sites and binding affinities between CHE and KLH.

  20. Interaction of lysozyme with a tear film lipid layer model: A molecular dynamics simulation study.

    Science.gov (United States)

    Wizert, Alicja; Iskander, D Robert; Cwiklik, Lukasz

    2017-12-01

    The tear film is a thin multilayered structure covering the cornea. Its outermost layer is a lipid film underneath of which resides on an aqueous layer. This tear film lipid layer (TFLL) is itself a complex structure, formed by both polar and nonpolar lipids. It was recently suggested that due to tear film dynamics, TFLL contains inhomogeneities in the form of polar lipid aggregates. The aqueous phase of tear film contains lachrymal-origin proteins, whereby lysozyme is the most abundant. These proteins can alter TFLL properties, mainly by reducing its surface tension. However, a detailed nature of protein-lipid interactions in tear film is not known. We investigate the interactions of lysozyme with TFLL in molecular details by employing coarse-grained molecular dynamics simulations. We demonstrate that lysozyme, due to lateral restructuring of TFLL, is able to penetrate the tear lipid film embedded in inverse micellar aggregates. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Interaction of sucralose with whey protein: Experimental and molecular modeling studies

    Science.gov (United States)

    Zhang, Hongmei; Sun, Shixin; Wang, Yanqing; Cao, Jian

    2017-12-01

    The objective of this research was to study the interactions of sucralose with whey protein isolate (WPI) by using the three-dimensional fluorescence spectroscopy, circular dichroism spectroscopy and molecular modeling. The results showed that the peptide strands structure of WPI had been changed by sucralose. Sucralose binding induced the secondary structural changes and increased content of aperiodic structure of WPI. Sucralose decreased the thermal stability of WPI and acted as a structure destabilizer during the thermal unfolding process of protein. In addition, the existence of sucralose decreased the reversibility of the unfolding of WPI. Nonetheless, sucralose-WPI complex was less stable than protein alone. The molecular modeling result showed that van der Waals and hydrogen bonding interactions contribute to the complexation free binding energy. There are more than one possible binding sites of WPI with sucralose by surface binding mode.

  2. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks

    DEFF Research Database (Denmark)

    Soberano de Oliveira, Ana Paula; Patil, Kiran Raosaheb; Nielsen, Jens

    2008-01-01

    is to use the topology of bio-molecular interaction networks in order to constrain the solution space. Such approaches systematically integrate the existing biological knowledge with the 'omics' data. Results: Here we introduce a hypothesis-driven method that integrates bio-molecular network topology......Background: Uncovering the operating principles underlying cellular processes by using 'omics' data is often a difficult task due to the high-dimensionality of the solution space that spans all interactions among the bio-molecules under consideration. A rational way to overcome this problem...... with transcriptome data, thereby allowing the identification of key biological features (Reporter Features) around which transcriptional changes are significantly concentrated. We have combined transcriptome data with different biological networks in order to identify Reporter Gene Ontologies, Reporter Transcription...

  3. Interactive Multimodal Molecular Set – Designing Ludic Engaging Science Learning Content

    DEFF Research Database (Denmark)

    Thorsen, Tine Pinholt; Christiansen, Kasper Holm Bonde; Jakobsen Sillesen, Kristian

    2014-01-01

    This paper reports on an exploratory study investigating 10 primary school students’ interaction with an interactive multimodal molecular set fostering ludic engaging science learning content in primary schools (8th and 9th grade). The concept of the prototype design was to bridge the physical...... and virtual worlds with electronic tags and, through this, blend the familiarity of the computer and toys, to create a tool that provided a ludic approach to learning about atoms and molecules. The study was inspired by the participatory design and informant design methodologies and included design...

  4. Collapse and coexistence for a molecular braid with an attractive interaction component subject to mechanical forces.

    Science.gov (United States)

    Lee, Dominic J O'

    2015-04-15

    Dual mechanical braiding experiments provide a useful tool with which to investigate the nature of interactions between rod-like molecules, for instance actin and DNA. In conditions close to molecular condensation, one would expect an appearance of a local minimum in the interaction potential between the two molecules. We investigate this situation, introducing an attractive component into the interaction potential, using a model developed for describing such experiments. We consider both attractive interactions that do not depend on molecular structure and those which depend on a DNA-like helix structure. In braiding experiments, an attractive term may lead to certain effects. A local minimum may cause molecules to collapse from a loosely braided configuration into a tight one, occurring at a critical value of the moment applied about the axis of the braid. For a fixed number of braid pitches, this may lead to coexistence between the two braiding states, tight and loose. Coexistence implies certain proportions of the braid are in each state, their relative size depending on the number of braid pitches. This manifests itself as a linear dependence in numerically calculated quantities as functions of the number of braid pitches. Also, in the collapsed state, the braid radius stays roughly constant. Furthermore, if the attractive interaction is helix dependent, the left-right handed braid symmetry is broken. For a DNA like charge distribution, using the Kornyshev-Leikin interaction model, our results suggest that significant braid collapse and coexistence only occurs for left handed braids. Regardless of the interaction model, the study highlights the possible qualitative physics of braid collapse and coexistence; and the role helix specific forces might play, if important. The model could be used to connect other microscopic theories of interaction with braiding experiments.

  5. Collapse and coexistence for a molecular braid with an attractive interaction component subject to mechanical forces

    International Nuclear Information System (INIS)

    Lee, Dominic J

    2015-01-01

    Dual mechanical braiding experiments provide a useful tool with which to investigate the nature of interactions between rod-like molecules, for instance actin and DNA. In conditions close to molecular condensation, one would expect an appearance of a local minimum in the interaction potential between the two molecules. We investigate this situation, introducing an attractive component into the interaction potential, using a model developed for describing such experiments. We consider both attractive interactions that do not depend on molecular structure and those which depend on a DNA-like helix structure. In braiding experiments, an attractive term may lead to certain effects. A local minimum may cause molecules to collapse from a loosely braided configuration into a tight one, occurring at a critical value of the moment applied about the axis of the braid. For a fixed number of braid pitches, this may lead to coexistence between the two braiding states, tight and loose. Coexistence implies certain proportions of the braid are in each state, their relative size depending on the number of braid pitches. This manifests itself as a linear dependence in numerically calculated quantities as functions of the number of braid pitches. Also, in the collapsed state, the braid radius stays roughly constant. Furthermore, if the attractive interaction is helix dependent, the left-right handed braid symmetry is broken. For a DNA like charge distribution, using the Kornyshev–Leikin interaction model, our results suggest that significant braid collapse and coexistence only occurs for left handed braids. Regardless of the interaction model, the study highlights the possible qualitative physics of braid collapse and coexistence; and the role helix specific forces might play, if important. The model could be used to connect other microscopic theories of interaction with braiding experiments. (paper)

  6. Molecular modeling studies of interactions between sodium polyacrylate polymer and calcite surface

    Energy Technology Data Exchange (ETDEWEB)

    Ylikantola, A. [University of Jyväskylä, Department of Chemistry, P.O. Box 35, University of Jyväskylä, FI-40014 (Finland); Linnanto, J., E-mail: juha.m.linnanto@gmail.com [University of Jyväskylä, Department of Chemistry, P.O. Box 35, University of Jyväskylä, FI-40014 (Finland); University of Tartu, Institute of Physics, Riia 142, EE-51014 Tartu (Estonia); Knuutinen, J.; Oravilahti, A. [University of Jyväskylä, Department of Chemistry, P.O. Box 35, University of Jyväskylä, FI-40014 (Finland); Toivakka, M. [Åbo Akademi University, Laboratory of Paper Coating and Converting and Center for Functional Materials, FI-20500 Turku/Åbo (Finland)

    2013-07-01

    The interactions between calcite pigment and sodium polyacrylate dispersing agent, widely used in papermaking as paper coating components, were investigated using classical force field and quantum chemical approaches. The objective was to understand interactions between the calcite surface and sodium polyacrylate polymer at 300 K using molecular dynamics simulations. A quantum mechanical ab initio Hartree–Fock method was also used to obtain detailed information about the sodium polyacrylate polymer structure. The effect of water molecules (moisture) on the interactions was also examined. Calculations showed that molecular weight, branching and the orientation of sodium polyacrylate polymers influence the interactions between the calcite surface and the polymer. The force field applied, and also water molecules, were found to have an impact on all systems studied. Ab initio Hartree–Fock calculations indicated that there are two types of coordination between sodium atoms and carboxylate groups of the sodium polyacrylate polymer, inter- and intra-carboxylate group coordination. In addition, ab initio Hartree–Fock calculations of the structure of the sodium polyacrylate polymer produced important information regarding interactions between the polymers and carboxylated styrene-butadiene latex particles.

  7. Interaction of Tenebrio Molitor Antifreeze Protein with Ice Crystal: Insights from Molecular Dynamics Simulations.

    Science.gov (United States)

    Ramya, L; Ramakrishnan, Vigneshwar

    2016-07-01

    Antifreeze proteins (AFP) observed in cold-adapting organisms bind to ice crystals and prevent further ice growth. However, the molecular mechanism of AFP-ice binding and AFP-inhibited ice growth remains unclear. Here we report the interaction of the insect antifreeze protein (Tenebrio molitor, TmAFP) with ice crystal by molecular dynamics simulation studies. Two sets of simulations were carried out at 263 K by placing the protein near the primary prism plane (PP) and basal plane (BL) of the ice crystal. To delineate the effect of temperatures, both the PP and BL simulations were carried out at 253 K as well. The analyses revealed that the protein interacts strongly with the ice crystal in BL simulation than in PP simulation both at 263 K and 253 K. Further, it was observed that the interactions are primarily mediated through the interface waters. We also observed that as the temperature decreases, the interaction between the protein and the ice increases which can be attributed to the decreased flexibility and the increased structuring of the protein at low temperature. In essence, our study has shed light on the interaction mechanism between the TmAFP antifreeze protein and the ice crystal. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

    Science.gov (United States)

    Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

    2018-06-01

    Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation

  9. A probe to study the toxic interaction of tartrazine with bovine hemoglobin at the molecular level.

    Science.gov (United States)

    Li, Yating; Wei, Haoran; Liu, Rutao

    2014-03-01

    Tartrazine is an artificial azo dye commonly used in food products, but tartrazine in the environment is potentially harmful. The toxic interaction between tartrazine and bovine hemoglobin (BHb) was investigated using fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD) and molecular modeling techniques under simulated physiological conditions. The fluorescence data showed that tartrazine can bind with BHb to form a complex. The binding process was a spontaneous molecular interaction, in which van der Waals' forces and hydrogen bonds played major roles. Molecular docking results showed that the hydrogen bonds exist between the oxygen atoms at position 31 of tartrazine and the nitrogen atom NZ7 on Lys99, and also between the oxygen atoms at position 15 of tartrazine and the nitrogen atom NZ7 on Lys104, Lys105. The results of UV-vis and CD spectra revealed that tartrazine led to conformational changes in BHb, including loosening of the skeleton structure and decreasing α helix in the secondary structure. The synchronous fluorescence experiment revealed that tartrazine binds into the hemoglobin central cavity, and this was verified using a molecular modeling study. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Mixtures of nonionic and anionic surfactants: interactions with low-molecular-mass homopeptides

    Czech Academy of Sciences Publication Activity Database

    Forgács, E.; Cserháti, T.; Deyl, Zdeněk; Mikšík, Ivan; Eckhardt, Adam

    2001-01-01

    Roč. 917, 1-2 (2001), s. 287-295 ISSN 0021-9673 R&D Projects: GA ČR GV203/96/K128; GA ČR GA203/99/0191; GA ČR GA203/00/D032 Institutional research plan: CEZ:AV0Z5011922 Keywords : molecular interactions * regression analysis * surfactants Subject RIV: BH - Optics, Masers, Lasers Impact factor: 2.793, year: 2001

  11. Interactions of cephalexin with bovine serum albumin: displacement reaction and molecular docking

    Directory of Open Access Journals (Sweden)

    Hamed Hamishehkar

    2016-09-01

    Conclusion: The outcomes of spectroscopic methods revealed that the conformation of BSA changed during drug-BSA interaction. The results of FRET propose that CPL quenches the fluorescence of BSA by static quenching and FRET. The displacement study showed that phenylbutazon and ketoprofen displaced CPL, indicating that its binding site on albumin is site I and Gentamicin cannot be displaced from the binding site of CPL. All results of molecular docking method agreed with the results of experimental data.

  12. SChiSM2: creating interactive web page annotations of molecular structure models using Jmol.

    Science.gov (United States)

    Cammer, Stephen

    2007-02-01

    SChiSM2 is a web server-based program for creating web pages that include interactive molecular graphics using the freely-available applet, Jmol, for illustration. The program works with Internet Explorer and Firefox on Windows, Safari and Firefox on Mac OSX and Firefox on Linux. The program can be accessed at the following address: http://ci.vbi.vt.edu/cammer/schism2.html.

  13. Quantum molecular modeling of the interaction between guanine and alkylating agents--2--nitrogen mustard.

    Science.gov (United States)

    Hamza, A; Broch, H; Vasilescu, D

    1996-06-01

    The alkylation mechanism of guanine by nitrogen mustard (HN2) was studied by using a supermolecular modeling at the ab initio 6-31G level. Our computations show that interaction of guanine with the aziridinium form of HN2 necessitates a transition state for the N7 alkylation route. The pathway of N7-guanine alkylation by nitrogen and sulfur mustards is discussed on the basis of the Molecular Electrostatic Potential and HOMO-LUMO properties of these molecules.

  14. Mechanism and kinetics of Fe, Cr, Mo and Mn atom interaction with molecular oxygen

    International Nuclear Information System (INIS)

    Akhmadov, U.S.; Zaslonko, I.S.; Smirnov, V.N.

    1988-01-01

    Rate constants of atomic interaction of some transition metals (Fe, Cr, Mo, Mn) with molecular oxygen are measured in shock waves using the resonance atomic-absorption method. A new method for determination of the parameter γ in the modified Lambert-Beer law D=ε(lN)γ is suggested and applied. Bond strength in CrO and MoO molecules is estimated

  15. Molecular dynamics simulations of the DNA interaction with metallic nanoparticles and TiO2 surfaces

    International Nuclear Information System (INIS)

    Kholmurodov, Kh.T.; Krasavin, E.A.; Dushanov, E.B.; Hassan, H.K.; Galal, A.; ElHabashy, H.A.; Sweilam, N.H.; Yasuoka, K.

    2013-01-01

    The understanding of the mechanism of DNA interactions and binding with metallic nanoparticles (NPs) and surfaces represents a great interest in today's medicine applications due to diagnostic and treatment of oncology diseases. Recent experimental and simulation studies involve the DNA interaction with highly localized proton beams or metallic NPs (such as Ag, Au, etc.), aimed at targeted cancer therapy through the injection of metal micro- or nanoparticles into the tumor tissue with consequent local microwave or laser heating. The effects of mutational structure changes in DNA and protein structures could result in destroying of native chemical (hydrogen) bonds or, on the contrary, creating of new bonds that do not normally exist there. The cause of such changes might be the alteration of one or several nucleotides (in DNA) or the substitution of specific amino acid residues (in proteins) that can lead to the essential structural destabilization or unfolding. At the atomic or molecular level, the replacement of one nucleotide by another (in DNA double helices) or replacement of one amino acid residue by another (in proteins) cause essential modifications of the molecular force fields of the environment that break locally important hydrogen bonds underlying the structural stability of the biological molecules. In this work, the molecular dynamics(MD) simulations were performed for four DNA models and the flexibilities of the purine and pyrimidine nucleotides during the interaction process with the metallic NPs and TiO 2 surface were clarified

  16. Molecular interactions and residues involved in force generation in the T4 viral DNA packaging motor.

    Science.gov (United States)

    Migliori, Amy D; Smith, Douglas E; Arya, Gaurav

    2014-12-12

    Many viruses utilize molecular motors to package their genomes into preformed capsids. A striking feature of these motors is their ability to generate large forces to drive DNA translocation against entropic, electrostatic, and bending forces resisting DNA confinement. A model based on recently resolved structures of the bacteriophage T4 motor protein gp17 suggests that this motor generates large forces by undergoing a conformational change from an extended to a compact state. This transition is proposed to be driven by electrostatic interactions between complementarily charged residues across the interface between the N- and C-terminal domains of gp17. Here we use atomistic molecular dynamics simulations to investigate in detail the molecular interactions and residues involved in such a compaction transition of gp17. We find that although electrostatic interactions between charged residues contribute significantly to the overall free energy change of compaction, interactions mediated by the uncharged residues are equally if not more important. We identify five charged residues and six uncharged residues at the interface that play a dominant role in the compaction transition and also reveal salt bridging, van der Waals, and solvent hydrogen-bonding interactions mediated by these residues in stabilizing the compact form of gp17. The formation of a salt bridge between Glu309 and Arg494 is found to be particularly crucial, consistent with experiments showing complete abrogation in packaging upon Glu309Lys mutation. The computed contributions of several other residues are also found to correlate well with single-molecule measurements of impairments in DNA translocation activity caused by site-directed mutations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

    Directory of Open Access Journals (Sweden)

    Angela Simeone

    2014-09-01

    Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

  18. Population reversal driven by unrestrained interactions in molecular dynamics simulations: A dialanine model

    Directory of Open Access Journals (Sweden)

    Filippo Pullara

    2015-10-01

    Full Text Available Standard Molecular Dynamics simulations (MD are usually performed under periodic boundary conditions using the well-established “Ewald summation”. This implies that the distance among each element in a given lattice cell and its corresponding element in another cell, as well as their relative orientations, are constant. Consequently, protein-protein interactions between proteins in different cells—important in many biological activities, such as protein cooperativity and physiological/pathological aggregation—are severely restricted, and features driven by protein-protein interactions are lost. The consequences of these restrictions, although conceptually understood and mentioned in the literature, have not been quantitatively studied before. The effect of protein-protein interactions on the free energy landscape of a model system, dialanine, is presented. This simple system features a free energy diagram with well-separated minima. It is found that, in the case of absence of peptide-peptide (p-p interactions, the ψ = 150° dihedral angle determines the most energetically favored conformation (global free-energy minimum. When strong p-p interactions are induced, the global minimum switches to the ψ = 0° conformation. This shows that the free-energy landscape of an individual molecule is dramatically affected by the presence of other freely interacting molecules of its same type. Results of the study suggest how taking into account p-p interactions in MD allows having a more realistic picture of system activity and functional conformations.

  19. Towards a molecular level understanding of the sulfanilamide-soil organic matter-interaction

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Ashour A., E-mail: ashour.ahmed@uni-rostock.de [University of Rostock, Institute of Physics, Albert-Einstein-Str. 23-24, D-18059 Rostock (Germany); Steinbeis GmbH & Co. KG für Technologietransfer, 70174 Stuttgart (Germany); University of Cairo, Faculty of Science, Department of Chemistry, 12613 Giza (Egypt); Thiele-Bruhn, Sören, E-mail: thiele@uni-trier.de [University of Trier, Soil Science, D-54286 Trier (Germany); Leinweber, Peter, E-mail: peter.leinweber@uni-rostock.de [Steinbeis GmbH & Co. KG für Technologietransfer, 70174 Stuttgart (Germany); University of Rostock, Soil Science, D-18051 Rostock (Germany); Kühn, Oliver, E-mail: oliver.kuehn@uni-rostock.de [University of Rostock, Institute of Physics, Albert-Einstein-Str. 23-24, D-18059 Rostock (Germany)

    2016-07-15

    Sorption experiments of sulfanilamide (SAA) on well-characterized samples of soil size-fractions were combined with the modeling of SAA-soil-interaction via quantum chemical calculations. Freundlich unit capacities were determined in batch experiments and it was found that they increase with the soil organic matter (SOM) content according to the order fine silt > medium silt > clay > whole soil > coarse silt > sand. The calculated binding energies for mass-spectrometrically quantified sorption sites followed the order ionic species > peptides > carbohydrates > phenols and lignin monomers > lignin dimers > heterocyclic compounds > fatty acids > sterols > aromatic compounds > lipids, alkanes, and alkenes. SAA forms H-bonds through its polar centers with the polar SOM sorption sites. In contrast dispersion and π-π-interactions predominate the interaction of the SAA aromatic ring with the non-polar moieties of SOM. Moreover, the dipole moment, partial atomic charges, and molecular volume of the SOM sorption sites are the main physical properties controlling the SAA-SOM-interaction. Further, reasonable estimates of the Freundlich unit capacities from the calculated binding energies have been established. Consequently, we suggest using this approach in forthcoming studies to disclose the interactions of a wide range of organic pollutants with SOM. - Highlights: • Experiment and theory showed that SAA obeys a site-specific sorption on soil surfaces. • SAA-SOM-interaction increases by increasing polarity of SOM sorption site. • H-bonds, dispersion, and π-π-interactions were observed for SAA-SOM-interaction. • Dipole moment and atomic charges of SOM sorption sites control SAA-SOM-interaction. • The Freundlich unit capacities were estimated from the calculated binding energies. • The current SOM model is flexible to describe interactions of SOM with other pollutants.

  20. Molecular interactions between tomato and the leaf mold pathogen Cladosporium fulvum.

    Science.gov (United States)

    Rivas, Susana; Thomas, Colwyn M

    2005-01-01

    The interaction between tomato and the leaf mold pathogen Cladosporium fulvum is controlled in a gene-for-gene manner. This interaction has provided useful insights to the molecular basis of recognition specificity in plant disease resistance (R) proteins, disease resistance (R) gene evolution, R-protein mediated signaling, and cellular responses to pathogen attack. Tomato Cf genes encode type I membrane-associated receptor-like proteins (RLPs) comprised predominantly of extracellular leucine-rich repeats (eLRRs) and which are anchored in the plasma membrane. Cf proteins recognize fungal avirulence (Avr) peptides secreted into the leaf apoplast during infection. A direct interaction of Cf proteins with their cognate Avr proteins has not been demonstrated and the molecular mechanism of Avr protein perception is not known. Following ligand perception Cf proteins trigger a hypersensitive response (HR) and the arrest of pathogen development. Cf proteins lack an obvious signaling domain, suggesting that defense response activation is mediated through interactions with other partners. Avr protein perception results in the rapid accumulation of active oxygen species (AOS), changes in cellular ion fluxes, activation of protein kinase cascades, changes in gene expression and, possibly, targeted protein degradation. Here we review our current understanding of Cf-mediated responses in resistance to C. fulvum.

  1. Separation and characterization of resins and asphaltenes coming from Castilla crude Evaluation of their molecular interaction

    International Nuclear Information System (INIS)

    Navarro, Lina; Alvarez, Mario; Grosso, Jorge Luis; Navarro, Uriel

    2004-01-01

    The study of resins and asphaltenes, the heaviest fractions of oil, has become an area of interest due to the abundance of heavy crude oils in Colombia and Latin America. We studied the chemical composition of the heavy fractions of Castilla crude oil, evaluated some of its molecular parameters and found evidence of the interaction between the resins extracted from the crude with the asphaltenes of the original crude. With this objective, we carried out at the pilot plant level precipitation of the resin-asphaltene (R-A) aggregate by adding and mixing under controlled conditions, a paraffin solvent, from the Apiay refinery, called Apiasol. By extracting Soxhlet with the same solvent, resin 1 of aggregate R-A was separated. Resin ll defined as the soluble fraction that is part of the maltenes, was separated from the deasphalted crude by open column chromatography, using alumina as support, according to the SAR method (Saturated, Aromatics, Resins). The fractions of resins and the asphaltenes obtained, were characterized by: Nuclear Magnetic Resonance (NMR), FT-lR, DRX, elementary analysis (C, H, N, S), metal content (Ni and V), distribution of molecular weight by GPC, and average molecular weight by VPO. The results obtained show evidence that resin l which is part of the aggregate has less average molecular weight than resin ll which is present in the fraction of maltenes. In addition, some changes were found in the elementary analysis of among the resins. On the one hand, and taking into account the existing theories of molecular interactions among these fractions, it was found that the resins l separated from the R-A aggregate, when added to the crude, they stabilize their asphaltenes. This evaluation was carried out by analyzing the flocculation point of the crude and its mixtures with 1,9% and 3,8% of resin l, when they are titrated with a precipitating agent in an NIR cell that works with high pressure and temperature

  2. Broadening the horizon – level 2.5 of the HUPO-PSI format for molecular interactions

    Directory of Open Access Journals (Sweden)

    Cusick Michael E

    2007-10-01

    Full Text Available Abstract Background Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. Results The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. Conclusion The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel.

  3. Molecular Interaction Study of some ortho and para Substituted Anilines with 1-Octanol

    Directory of Open Access Journals (Sweden)

    M. S. Manjunatha

    2010-01-01

    Full Text Available Interactions between ortho and para substituents of anilines such as chloroaniline, methylaniline and methoxyaniline with 1-octanol have been studied in carbon tetrachloride. The most likely association of complex between 1-octanol and substituents of anilines is 1:1 stoichiometric complex, through hydroxyl group of 1-octanol and amine group of ortho and para substituents of anilines. Interactions are studied on the bases of formation constant and free energy changes. Formation constant of the complex has been calculated using Nash method. The result shows that molecular interaction of 1-octanol as proton donor with methyl and chloride substitution of anilines in ortho position is smaller than the para position substitution of anilines. The results shows, the ability of acceptors is in the order p-methoxyaniline < o-chloroaniline

  4. Investigation of the molecular level interactions between mucins and food proteins: Spectroscopic, tribological and rheological studies

    DEFF Research Database (Denmark)

    Celebioglu, Hilal Yilmaz

    The thesis investigated the structure and molecular-level interaction of β-lactoglobulin (BLG) and mucins, representing major components of the dairy products and saliva/digestion systems, respectively. Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer covers...... epithelial surfaces throughout the body. A literature review of the interactions of different mucin types and saliva mucins with several food proteins and food protein emulsions, as well as their functional properties related to the food oral processing is presented at the first chapter of the thesis (Paper...... V). Most of the studies suggest an electrostatic attraction between positively charged food proteins with negatively charged moieties of mucins (mainly on glycosylated region of mucins). The structural changes occurring during the interaction between BLG, the major whey protein, and bovine...

  5. Thermodynamical analyses of molecular simulations of dislocation-defect interactions: simulations at 0 K

    International Nuclear Information System (INIS)

    Monnet, G.

    2008-01-01

    Full text of publication follows. Static molecular (SM) simulations of dislocation-defect interaction are analysed through a framework of different interaction regimes, in which the applied work has different roles. In most regimes, the applied work is transformed into elastic energy, a dissipative energy resulting from the lattice friction and a large quantity of energy needed to enable the dislocation to bow out when it is pinned by the defect. While the dissipative work is entirely evacuated in SM simulations, the elastic and curvature energies contribute to a large increase of the internal energy of the system. A method is presented in this work to evaluate the curvature energy and the result is compared to prediction of the line tension model. These analyses allow the determination of the dislocation-defect interaction energy. (author)

  6. Monitoring peptide-surface interaction by means of molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Nonella, Marco, E-mail: mnonella@pci.uzh.ch [Physikalisch-Chemisches Institut, Universitaet Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich (Switzerland); Seeger, Stefan, E-mail: sseeger@pci.uzh.ch [Physikalisch-Chemisches Institut, Universitaet Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich (Switzerland)

    2010-12-09

    Graphical abstract: Protein-surface interactions play a crucial role in a wide field of research areas like biology, biotechnology, or pharmacology. Only recently, it has been shown that not only peptide adsorption represents an important process but also spreading and clustering of adsorbed proteins. By means of classical molecular dynamics, peptide adsorption as well as the dynamics of adsorbed peptides have been investigated in order to gain deeper insight into such processes. The picture shows a snapshot of an adsorbed peptide on a silica surface showing strong direct hydrogen bonding. Research highlights: {yields} Simulation of peptide surface interaction. {yields} Dynamics of hydrogen bond formation and destruction. {yields} Internal flexibility of adsorbed peptides. - Abstract: Protein adsorption and protein surface interactions have become an important research topic in recent years. Very recently, for example, it has been shown that protein clusters can undergo a surface-induced spreading after adsorption. Such phenomena emphasize the need of a more detailed insight into protein-silica interaction at an atomic level. Therefore, we have studied a model system consisting of a short peptide, a silica slab, and water molecules by means of classical molecular dynamics simulations. The study reveals that, besides of electrostatic interactions caused by the chosen charge distribution, the peptide interacts with the silica surface through formation of direct peptide-surface hydrogen bonds as well as indirect peptide-water-surface hydrogen bonds. The number of created hydrogen bonds varies considerably among the simulated structures. The strength of hydrogen bonding determines the mobility of the peptide on the surface and the internal flexibility of the adsorbed peptide.

  7. Investigation of Interactions between Thrombin and Ten Phenolic Compounds by Affinity Capillary Electrophoresis and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Qiao-Qiao Li

    2018-01-01

    Full Text Available Thrombin plays a vital role in blood coagulation, which is a key process involved in thrombosis by promoting platelet aggregation and converting fibrinogen to form the fibrin clot. In the receptor concept, drugs produce their therapeutic effects via interactions with the targets. Therefore, investigation of interaction between thrombin and small molecules is important to find out the potential thrombin inhibitor. In this study, affinity capillary electrophoresis (ACE and in silico molecular docking methods were developed to study the interaction between thrombin and ten phenolic compounds (p-hydroxybenzoic acid, protocatechuic acid, vanillic acid, gallic acid, catechin, epicatechin, dihydroquercetin, naringenin, apigenin, and baicalein. The ACE results showed that gallic acids and six flavonoid compounds had relative strong interactions with thrombin. In addition, the docking results indicated that all of optimal conformations of the six flavonoid compounds were positioned into the thrombin activity centre and had interaction with the HIS57 or SER195 which was the key residue to bind thrombin inhibitors such as argatroban. Herein, these six flavonoid compounds might have the potential of thrombin inhibition activity. In addition, the developed method in this study can be further applied to study the interactions of other molecules with thrombin.

  8. The Molecular Basis of Polyunsaturated Fatty Acid Interactions with the Shaker Voltage-Gated Potassium Channel.

    Directory of Open Access Journals (Sweden)

    Samira Yazdi

    2016-01-01

    Full Text Available Voltage-gated potassium (KV channels are membrane proteins that respond to changes in membrane potential by enabling K+ ion flux across the membrane. Polyunsaturated fatty acids (PUFAs induce channel opening by modulating the voltage-sensitivity, which can provide effective treatment against refractory epilepsy by means of a ketogenic diet. While PUFAs have been reported to influence the gating mechanism by electrostatic interactions to the voltage-sensor domain (VSD, the exact PUFA-protein interactions are still elusive. In this study, we report on the interactions between the Shaker KV channel in open and closed states and a PUFA-enriched lipid bilayer using microsecond molecular dynamics simulations. We determined a putative PUFA binding site in the open state of the channel located at the protein-lipid interface in the vicinity of the extracellular halves of the S3 and S4 helices of the VSD. In particular, the lipophilic PUFA tail covered a wide range of non-specific hydrophobic interactions in the hydrophobic central core of the protein-lipid interface, while the carboxylic head group displayed more specific interactions to polar/charged residues at the extracellular regions of the S3 and S4 helices, encompassing the S3-S4 linker. Moreover, by studying the interactions between saturated fatty acids (SFA and the Shaker KV channel, our study confirmed an increased conformational flexibility in the polyunsaturated carbon tails compared to saturated carbon chains, which may explain the specificity of PUFA action on channel proteins.

  9. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.

    Science.gov (United States)

    Stenson, Peter D; Mort, Matthew; Ball, Edward V; Shaw, Katy; Phillips, Andrew; Cooper, David N

    2014-01-01

    The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally established in 1996 for the scientific study of mutational mechanisms in human genes. However, it has since acquired a much broader utility as a central unified disease-oriented mutation repository utilized by human molecular geneticists, genome scientists, molecular biologists, clinicians and genetic counsellors as well as by those specializing in biopharmaceuticals, bioinformatics and personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions/non-profit organizations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via BIOBASE GmbH.

  10. MOLECULAR DYNAMICS STUDY OF INTERACTIONS OF POLYMYXIN B3 AND ITS ALA-MUTANTS WITH LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2015-12-01

    Full Text Available Introduction. Emergence of nosocomial bacterial pathogens (especially Gram-negative bacteria with multiple resistance against almost all available antibiotics is a growing medical problem. No novel drugs targeting multidrug-resistant Gram-negative bacteria have been developed in recent years. In this context, there has been greatly renewed interest to cyclic lipodecapeptides polymyxins. Polymyxins exhibit rapid bactericidal activity, they are specific and highly potent against Gramnegative bacteria, but have potential nephrotoxic side effects. So polymyxins are attractive lead compounds to develop analogues with improved microbiological, pharmacological and toxicological properties. A detailed knowledge of the molecular mechanisms of polymyxin interactions with its cell targets is a prerequisite for the purposeful improvement of its therapeutic properties. The primary cell target of a polymyxin is a lipopolysaccharide (LPS in the outer membrane of Gram-negative bacteria. The binding site of polymyxin on LPS has been supposed to be Kdo2-lipid A fragment. Methods. For all molecular modeling and molecular dynamics simulation experiments the YASARA suite of programs was used. Complex of antimicrobial peptide polymyxin В3 (PmB3 with Kdo2-lipid A portion of E. coli lipopolysaccharide was constructed by rigid docking with flexible side chains of the peptide. By alanine scanning of polymyxin В3 bound to LPS followed by simulated annealing minimization of the complexes in explicit water environment, the molecular aspects of PmB3-LPS binding have been studied by 20 ns molecular dynamics simulations at 298 K and pH 7.0. The AMBER03 force field was used with a 1.05 nm force cutoff. To treat long range electrostatic interactions the Particle Mesh Ewald algorithm was used. Results. Ala-mutations of polymyxin’s residues Dab1, Dab3, Dab5, Dab8 and Dab9 in the PmB3-LPS complex caused sustained structural changes resulting in the notable loss in stability of

  11. Exploring molecular and spin interactions of Tellurium adatom in reduced graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Alegaonkar, Ashwini [Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, 411 007, MS (India); Alegaonkar, Prashant [Department of Applied Physics, Defence Institute of Advance Technology, Girinagar, Pune, 411 025, MS (India); Pardeshi, Satish, E-mail: skpar@chem.unipune.ac.in [Department of Chemistry, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, 411 007, MS (India)

    2017-07-01

    The transport of spin information fundamentally requires favourable molecular architecture and tunable spin moments to make the medium pertinent for spintronic. We report on achieving coherent molecular-spin parameters for rGO due to Tellurium (Te) adatom. Initially, GO prepared using graphite, was modified into rGO by in situ incorporation of 1 (w/w)% of Te. Both the systems were subjected to ESCA, FTIR, Raman dispersion, ESR spectroscopy, and electron microscopy. Analysis revealed that, Te substantially reacted with epoxides, carbonyl, and carboxylate groups that improved C-to-O ratio by twice. However, the spin splitting character, between Te and C, seems to be quenched. Moreover, Te altered the dynamical force constant between C-C and C=C that generated the mechanical stress within rGO network. The layer conjugation, nature of folding, symmetry, and electronic states of the edges were also affected by precipitation and entrapment of Te. The calculated dynamic molecular Raman and ESR spin parameters indicated that, Te acted as a bridging element for long range spin transport. This is particularly due to, the p-orbital moments of Te contributing, vectorially, to spin relaxation process operative at broken inversion symmetry sites. Our study suggests that, facile addition of Te in rGO is useful to achieve favourable spintronic properties. - Highlights: • Spin interactions and molecular dynamics modification due to Tellurium adatom in rGO. • Molecular level manipulation of Tellurium adatom for favourable spintronic properties. • Bychocov-Rashaba coupling are the operative channels in rGO. • Extrinsic coupling component get added vectorially by Tellurium. • Te-rGO is a viable medium for molecular spintronics.

  12. Molecular modeling of polymer composite-analyte interactions in electronic nose sensors

    Science.gov (United States)

    Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K. S.

    2003-01-01

    We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites. c2003 Elsevier Science B.V. All rights reserved.

  13. Molecular models of alginic acid: Interactions with calcium ions and calcite surfaces

    Science.gov (United States)

    Perry, Thomas D.; Cygan, Randall T.; Mitchell, Ralph

    2006-07-01

    Cation binding by polysaccharides is observed in many environments and is important for predictive environmental modeling, and numerous industrial and food technology applications. The complexities of these cation-organic interactions are well suited for predictive molecular modeling and the analysis of conformation and configuration of polysaccharides and their influence on cation binding. In this study, alginic acid was chosen as a model polymer system and representative disaccharide and polysaccharide subunits were developed. Molecular dynamics simulation of the torsion angles of the ether linkage between various monomeric subunits identified local and global energy minima for selected disaccharides. The simulations indicate stable disaccharide configurations and a common global energy minimum for all disaccharide models at Φ = 274 ± 7°, Ψ = 227 ± 5°, where Φ and Ψ are the torsion angles about the ether linkage. The ability of disaccharide subunits to bind calcium ions and to associate with the (101¯4) surface of calcite was also investigated. Molecular models of disaccharide interactions with calcite provide binding energy differences for conformations that are related to the proximity and residence densities of the electron-donating moieties with calcium ions on the calcite surface, which are controlled, in part, by the torsion of the ether linkage between monosaccharide units. Dynamically optimized configurations for polymer alginate models with calcium ions were also derived.

  14. Interactions of Borneol with DPPC Phospholipid Membranes: A Molecular Dynamics Simulation Study

    Directory of Open Access Journals (Sweden)

    Qianqian Yin

    2014-11-01

    Full Text Available Borneol, known as a “guide” drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol’s penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol’s presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol’s penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol.

  15. Modeling the intermolecular interactions: molecular structure of N-3-hydroxyphenyl-4-methoxybenzamide.

    Science.gov (United States)

    Karabulut, Sedat; Namli, Hilmi; Kurtaran, Raif; Yildirim, Leyla Tatar; Leszczynski, Jerzy

    2014-03-01

    The title compound, N-3-hydroxyphenyl-4-methoxybenzamide (3) was prepared by the acylation reaction of 3-aminophenol (1) and 4-metoxybenzoylchloride (2) in THF and characterized by ¹H NMR, ¹³C NMR and elemental analysis. Molecular structure of the crystal was determined by single crystal X-ray diffraction and DFT calculations. 3 crystallizes in monoclinic P2₁/c space group. The influence of intermolecular interactions (dimerization and crystal packing) on molecular geometry has been evaluated by calculations performed for three different models; monomer (3), dimer (4) and dimer with added unit cell contacts (5). Molecular structure of 3, 4 and 5 was optimized by applying B3LYP method with 6-31G+(d,p) basis set in gas phase and compared with X-ray crystallographic data including bond lengths, bond angles and selected dihedral angles. It has been concluded that although the crystal packing and dimerization have a minor effect on bond lengths and angles, however, these interactions are important for the dihedral angles and the rotational conformation of aromatic rings. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Pressure Enhancement in Confined Fluids: Effect of Molecular Shape and Fluid-Wall Interactions.

    Science.gov (United States)

    Srivastava, Deepti; Santiso, Erik E; Gubbins, Keith E

    2017-10-24

    Recently, several experimental and simulation studies have found that phenomena that normally occur at extremely high pressures in a bulk phase can occur in nanophases confined within porous materials at much lower bulk phase pressures, thus providing an alternative route to study high-pressure phenomena. In this work, we examine the effect on the tangential pressure of varying the molecular shape, strength of the fluid-wall interactions, and pore width, for carbon slit-shaped pores. We find that, for multisite molecules, the presence of additional rotational degrees of freedom leads to unique changes in the shape of the tangential pressure profile, especially in larger pores. We show that, due to the direct relationship between the molecular density and the fluid-wall interactions, the latter have a large impact on the pressure tensor. The molecular shape and pore size have a notable impact on the layering of molecules in the pore, greatly influencing both the shape and scale of the tangential pressure profile.

  17. Can we better predict the biologic behavior of incidental IPMN? A comprehensive analysis of molecular diagnostics and biomarkers in intraductal papillary mucinous neoplasms of the pancreas.

    Science.gov (United States)

    Tulla, Kiara A; Maker, Ajay V

    2018-03-01

    Predicting the biologic behavior of intraductal papillary mucinous neoplasm (IPMN) remains challenging. Current guidelines utilize patient symptoms and imaging characteristics to determine appropriate surgical candidates. However, the majority of resected cysts remain low-risk lesions, many of which may be feasible to have under surveillance. We herein characterize the most promising and up-to-date molecular diagnostics in order to identify optimal components of a molecular signature to distinguish levels of IPMN dysplasia. A comprehensive systematic review of pertinent literature, including our own experience, was conducted based on the PRISMA guidelines. Molecular diagnostics in IPMN patient tissue, duodenal secretions, cyst fluid, saliva, and serum were evaluated and organized into the following categories: oncogenes, tumor suppressor genes, glycoproteins, markers of the immune response, proteomics, DNA/RNA mutations, and next-generation sequencing/microRNA. Specific targets in each of these categories, and in aggregate, were identified by their ability to both characterize a cyst as an IPMN and determine the level of cyst dysplasia. Combining molecular signatures with clinical and imaging features in this era of next-generation sequencing and advanced computational analysis will enable enhanced sensitivity and specificity of current models to predict the biologic behavior of IPMN.

  18. Comprehensive study of interaction between biocompatible PEG-InP/ZnS QDs and bovine serum albumin.

    Science.gov (United States)

    Sannaikar, M S; Inamdar, Laxmi S; Pujar, G H; Wari, M N; Balasinor, Nafisa H; Inamdar, S R

    2018-05-01

    Polyethylene glycol (PEG) surface modified biocompatible InP/ZnS quantum dots (QDs) act as a potential alternative for conventional carcinogenic cadmium-based quantum dots for in vivo and in vitro studies. Comprehensively, we studied the interaction between a model protein bovine serum albumin (BSA) and PEGylated toxic free InP/ZnS QDs using various spectroscopic tools such as absorption, fluorescence quenching, time resolved and synchronous fluorescence spectroscopic measurements. These studies principally show that tryptophan (Trp) residues of BSA have preferable binding affinity towards PEG-InP/ZnS QDs surface and a blue shift in Trp fluorescence emission is a signature of conformational changes in its hydrophobic microenvironment. Photoluminescence (PL) intensity of Trp is quenched by ground state complex formation (static quenching) at room temperature. However, InP/ZnS@BSA conjugates become unstable with increasing temperature and PL intensity of Trp is quenched via dynamic quenching by PEG-InP/ZnS QDs. Experimentally determined thermodynamic parameters for these conjugates have shown spontaneity, entropy driven and exothermic nature of bio-conjugation. The calculated binding affinity (n ≅ 1, Hill coefficient) suggest that the affinity of InP/ZnS QDs for a BSA protein is not dependent on whether or not other BSA proteins are already bound to the QD surface. Energy transfer efficiency (E), Trp residue to InP/ZnS QDs distances and energy transfer rate (k T ) were all obtained from FÖrster resonance energy. Copyright © 2017 John Wiley & Sons, Ltd.

  19. The selective interaction between silica nanoparticles and enzymes from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    Full Text Available Nanoscale particles have become promising materials in many fields, such as cancer therapeutics, diagnosis, imaging, drug delivery, catalysis, as well as biosensors. In order to stimulate and facilitate these applications, there is an urgent need for the understanding of the interaction mode between the nano-particles and proteins. In this study, we investigate the orientation and adsorption between several enzymes (cytochrome c, RNase A, lysozyme and 4 nm/11 nm silica nanoparticles (SNPs by using molecular dynamics (MD simulation. Our results show that three enzymes are adsorbed onto the surfaces of both 4 nm and 11 nm SNPs during our MD simulations and the small SNPs induce greater structural stabilization. The active site of cytochrome c is far away from the surface of 4 nm SNPs, while it is adsorbed onto the surface of 11 nm SNPs. We also explore the influences of different groups (-OH, -COOH, -NH2 and CH3 coated onto silica nanoparticles, which show significantly different impacts. Our molecular dynamics results indicate the selective interaction between silicon nanoparticles and enzymes, which is consistent with experimental results. Our study provides useful guides for designing/modifying nanomaterials to interact with proteins for their bio-applications.

  20. Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy

    Directory of Open Access Journals (Sweden)

    Minzhong Zhan

    2015-07-01

    Full Text Available The binding interaction between gallic acid (GA and lysozyme (LYS was investigated and compared by molecular dynamics (MD simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA.

  1. Study on the interaction of catalase with pesticides by flow injection chemiluminescence and molecular docking.

    Science.gov (United States)

    Tan, Xijuan; Wang, Zhuming; Chen, Donghua; Luo, Kai; Xiong, Xunyu; Song, Zhenghua

    2014-08-01

    The interaction mechanisms of catalase (CAT) with pesticides (including organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos, dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding processes of pesticides to CAT were spontaneous with the apparent binding constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0. The binding abilities of pesticides to CAT followed the order: fenvalerate>deltamethrin>disulfoton>isofenphos-methyl>carbaryl>malathion>isocarbophos>dimethoate>dipterex>acephate>methomyl>methamidophos, which was generally similar to the order of determination sensitivity of pesticides. The thermodynamic parameters revealed that CAT bound with hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic pesticides by hydrogen bond and van der Waals force. The pesticides to CAT molecular docking study showed that pesticides could enter into the cavity locating among the four subdomains of CAT, giving the specific amino acid residues and hydrogen bonds involved in CAT-pesticides interaction. It was also found that the lgK values of pesticides to CAT increased regularly with increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric property of pesticide played essential roles in its binding to CAT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Power transformations improve interpolation of grids for molecular mechanics interaction energies.

    Science.gov (United States)

    Minh, David D L

    2018-02-18

    A common strategy for speeding up molecular docking calculations is to precompute nonbonded interaction energies between a receptor molecule and a set of three-dimensional grids. The grids are then interpolated to compute energies for ligand atoms in many different binding poses. Here, I evaluate a smoothing strategy of taking a power transformation of grid point energies and inverse transformation of the result from trilinear interpolation. For molecular docking poses from 85 protein-ligand complexes, this smoothing procedure leads to significant accuracy improvements, including an approximately twofold reduction in the root mean square error at a grid spacing of 0.4 Å and retaining the ability to rank docking poses even at a grid spacing of 0.7 Å. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  3. The interaction between 4-aminoantipyrine and bovine serum albumin: Multiple spectroscopic and molecular docking investigations

    International Nuclear Information System (INIS)

    Teng Yue; Liu Rutao; Li Chao; Xia Qing; Zhang Pengjun

    2011-01-01

    4-Aminoantipyrine (AAP) is widely used in the pharmaceutical industry, in biochemical experiments and in environmental monitoring. AAP as an aromatic pollutant in the environment poses a great threat to human health. To evaluate the toxicity of AAP at the protein level, the effects of AAP on bovine serum albumin (BSA) were investigated by multiple spectroscopic techniques and molecular modeling. After the inner filter effect was eliminated, the experimental results showed that AAP effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and binding subdomain were measured, and indicated that AAP could spontaneously bind with BSA on subdomain IIIA through electrostatic forces. Molecular docking results revealed that AAP interacted with the Glu 488 and Glu 502 residues of BSA. Furthermore, the conformation of BSA was demonstrably changed in the presence of AAP. The skeletal structure of BSA loosened, exposing internal hydrophobic aromatic ring amino acids and peptide strands to the solution.

  4. Interaction of molecular oxygen with single wall nanotubes: Role of surfactant contamination

    International Nuclear Information System (INIS)

    Larciprete, R.; Goldoni, A.; Lizzit, S.

    2003-01-01

    The interaction of molecular oxygen with single wall nanotubes in the form of a commercial bucky paper was investigated by high resolution photoemission spectroscopy. Sodium contamination was found in the sample, which was completely removed only after prolonged heating at 1250 K. The C 1s core level spectrum measured on the sample annealed to 1020 K dramatically changed upon exposure to molecular oxygen. On the contrary, when exposing the Na-free SWNTs to several KL of O 2 , the sample remained oxygen free and no modification in the C 1s core level was observed. Therefore the observed sensitivity of the sample to O 2 was due to a Na mediated oxidation, determining a charge transfer from the C tubes to the Na-O complex

  5. Noncovalent Intermolecular Interactions in Organic Electronic Materials: Implications for the Molecular Packing vs Electronic Properties of Acenes

    KAUST Repository

    Sutton, Christopher; Risko, Chad; Bredas, Jean-Luc

    2015-01-01

    Noncovalent intermolecular interactions, which can be tuned through the toolbox of synthetic chemistry, determine not only the molecular packing but also the resulting electronic, optical, and mechanical properties of materials derived from π

  6. Molecular determinants of the interaction between Doa1 and Hse1 involved in endosomal sorting.

    Science.gov (United States)

    Han, Seungsu; Shin, Donghyuk; Choi, Hoon; Lee, Sangho

    2014-03-28

    Yeast Doa1/Ufd3 is an adaptor protein for Cdc48 (p97 in mammal), an AAA type ATPase associated with endoplasmic reticulum-associated protein degradation pathway and endosomal sorting into multivesicular bodies. Doa1 functions in the endosomal sorting by its association with Hse1, a component of endosomal sorting complex required for transport (ESCRT) system. The association of Doa1 with Hse1 was previously reported to be mediated between PFU domain of Doa1 and SH3 of Hse1. However, it remains unclear which residues are specifically involved in the interaction. Here we report that Doa1/PFU interacts with Hse1/SH3 with a moderate affinity of 5 μM. Asn-438 of Doa1/PFU and Trp-254 of Hse1/SH3 are found to be critical in the interaction while Phe-434, implicated in ubiquitin binding via a hydrophobic interaction, is not. Small-angle X-ray scattering measurements combined with molecular docking and biochemical analysis yield the solution structure of the Doa1/PFU:Hse1/SH3 complex. Taken together, our results suggest that hydrogen bonding is a major determinant in the interaction of Doa1/PFU with Hse1/SH3. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Source-sink interaction: a century old concept under the light of modern molecular systems biology.

    Science.gov (United States)

    Chang, Tian-Gen; Zhu, Xin-Guang; Raines, Christine

    2017-07-20

    Many approaches to engineer source strength have been proposed to enhance crop yield potential. However, a well-co-ordinated source-sink relationship is required finally to realize the promised increase in crop yield potential in the farmer's field. Source-sink interaction has been intensively studied for decades, and a vast amount of knowledge about the interaction in different crops and under different environments has been accumulated. In this review, we first introduce the basic concepts of source, sink and their interactions, then summarize current understanding of how source and sink can be manipulated through both environmental control and genetic manipulations. We show that the source-sink interaction underlies the diverse responses of crops to the same perturbations and argue that development of a molecular systems model of source-sink interaction is required towards a rational manipulation of the source-sink relationship for increased yield. We finally discuss both bottom-up and top-down routes to develop such a model and emphasize that a community effort is needed for development of this model. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Molecular fundamentals of drug interactions in the therapy of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2014-03-01

    Full Text Available Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs’ pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  9. [Molecular fundamentals of drug interactions in the therapy of colorectal cancer].

    Science.gov (United States)

    Regulska, Katarzyna; Stanisz, Beata; Regulski, Miłosz; Gieremek, Paulina

    2014-03-04

    Rapid advances in the field of chemotherapy have resulted in the introduction of numerous antineoplastic drugs into clinical practice, which increased the efficiency of patient management. Also the prevalent use of combination treatment based on drug action synergy contributed to the improved clinical effect associated with cytotoxic drug administration. It seems, however, obvious that the multidirectional pharmacotherapy in oncology requires a thorough knowledge of drugs' pharmaceutical behavior in order to maximize their collective action and prevent the occurrence of unintended drug interactions that could potentially impair treatment effectiveness. In fact, drug interactions constitute a serious problem for current oncology primarily resulting from a narrow therapeutic index specific for the majority of anticancer drugs. This, in turn, indicates that even slight deviations of their pharmacokinetics could cause significant clinical consequences, manifested by alteration of the toxicological profile or reduction of therapeutic efficiency. Hence, the investigation of molecular aspects underlying the mechanisms of various drug interactions seems to be essential for proper and safe patient management. The present article is devoted to the extensive subject of drug interactions occurring in the therapy of colorectal cancer. It presents the available literature data on both positive and negative effects of interactions and it discusses their mechanisms complying with their classification into pharmacokinetic and pharmacodynamic ones.

  10. Protein-binding RNA aptamers affect molecular interactions distantly from their binding sites.

    Directory of Open Access Journals (Sweden)

    Daniel M Dupont

    Full Text Available Nucleic acid aptamer selection is a powerful strategy for the development of regulatory agents for molecular intervention. Accordingly, aptamers have proven their diligence in the intervention with serine protease activities, which play important roles in physiology and pathophysiology. Nonetheless, there are only a few studies on the molecular basis underlying aptamer-protease interactions and the associated mechanisms of inhibition. In the present study, we use site-directed mutagenesis to delineate the binding sites of two 2´-fluoropyrimidine RNA aptamers (upanap-12 and upanap-126 with therapeutic potential, both binding to the serine protease urokinase-type plasminogen activator (uPA. We determine the subsequent impact of aptamer binding on the well-established molecular interactions (plasmin, PAI-1, uPAR, and LRP-1A controlling uPA activities. One of the aptamers (upanap-126 binds to the area around the C-terminal α-helix in pro-uPA, while the other aptamer (upanap-12 binds to both the β-hairpin of the growth factor domain and the kringle domain of uPA. Based on the mapping studies, combined with data from small-angle X-ray scattering analysis, we construct a model for the upanap-12:pro-uPA complex. The results suggest and highlight that the size and shape of an aptamer as well as the domain organization of a multi-domain protein such as uPA, may provide the basis for extensive sterical interference with protein ligand interactions considered distant from the aptamer binding site.

  11. Molecular interactions and thermal transport in ionic liquids with carbon nanomaterials.

    Science.gov (United States)

    França, João M P; Nieto de Castro, Carlos A; Pádua, Agílio A H

    2017-07-05

    We used molecular dynamics simulation to study the effect of suspended carbon nanomaterials, nanotubes and graphene sheets, on the thermal conductivity of ionic liquids, an issue related to understanding the properties of nanofluids. One important aspect that we developed is an atomistic model of the interactions between the organic ions and carbon nanomaterials, so we did not rely on existing force fields for small organic molecules or assume simple combining rules to describe the interactions at the liquid/material interface. Instead, we used quantum calculations with a density functional suitable for non-covalent interactions to parameterize an interaction model, including van der Waals terms and also atomic partial charges on the materials. We fitted a n-m interaction potential function with n values of 9 or 10 and m values between 5 and 8, so a 12-6 Lennard-Jones function would not fit the quantum calculations. For the atoms of ionic liquids and carbon nanomaterials interacting among themselves, we adopted existing models from the literature. We studied the imidazolium ionic liquids [C 4 C 1 im][SCN], [C 4 C 1 im][N(CN) 2 ], [C 4 C 1 im][C(CN) 3 ] and [C 4 C 1 im][(CF 3 SO 2 ) 2 N]. Attraction is stronger for cations (than for anions) above and below the π-system of the nanomaterials, whereas anions show stronger attraction for the hydrogenated edges. The ordering of ions around and inside (7,7) and (10,10) single-walled nanotubes, and near a stack of graphene sheets, was analysed in terms of density distribution functions. We verified that anions are found, as well as cations, in the first interfacial layer interacting with the materials, which is surprising given the interaction potential surfaces. The thermal conductivity of the ionic liquids and of composite systems containing one nanotube or one graphene stack in suspension was calculated using non-equilibrium molecular dynamics. Thermal conductivity was calculated along the axis of the nanotube and

  12. FTIR and dielectric studies of molecular interaction between alkyl methacrylates and primary alcohols

    International Nuclear Information System (INIS)

    Dharmalingam, K.; Ramachandran, K.; Sivagurunathan, P.

    2007-01-01

    The molecular interaction between alkyl methacrylates (methyl methacrylate, ethyl methacrylate and butyl methacrylate) and primary alcohols (1-propanol, 1-butanol, 1-pentanol, 1-heptanol, 1-octanol and 1-decanol) has been studied in carbon tetrachloride by FTIR spectroscopic and dielectric methods. The results show that the most likely association between alcohol and ester is 1:1 complex through the free hydroxyl group of the alcohol and the carbonyl group of ester, and the alkyl chain length of both the alcohols and esters plays an important role in the determination of the strength of hydrogen bond (O-H:O=C) formed

  13. Quantum molecular modeling of the interaction between guanine and alkylating agents--1--sulfur mustard.

    Science.gov (United States)

    Broch, H; Hamza, A; Vasilescu, D

    1996-06-01

    Interaction between Guanine and the episulfonium form of Sulfur mustard (HD) was studied using the ab initio LCAO-MO method at the HF/6-31G level. The alkylation mechanism on guanine-N7 was analyzed by using a supermolecular modeling. Our stereostructural results associated with the molecular electrostatic potentials and HOMO-LUMO properties, show that in vacuum the alkylation of the N7 of guanine by HD in the aggressive episulfonium form is a direct process without transition state and of which the pathway is determined.

  14. Electron, ion and atomic beams interaction with solid high-molecular dielectrics

    Energy Technology Data Exchange (ETDEWEB)

    Milyavskij, V V; Skvortsov, V A [Russian Academy of Sciences, Moscow (Russian Federation). High Energy Density Research Center

    1997-12-31

    A mathematical model was constructed and numerical investigation performed of the interaction between intense electron, ion and atomic beams and solid high-molecular dielectrics under various boundary conditions. The model is based on equations of the mechanics of continuum, electrodynamics and kinetics, describing the accumulation and relaxation of space charge and shock-wave processes, as well as the evolution of electric field in the sample. A semi-empirical procedure is proposed for the calculation of energy deposition by electron beam in a target in the presence of a non-uniform electric field. (author). 4 figs., 2 refs.

  15. Molecular dynamics approaches to the design and synthesis of PCB targeting molecularly imprinted polymers: interference to monomer-template interactions in imprinting of 1,2,3-trichlorobenzene.

    Science.gov (United States)

    Cleland, Dougal; Olsson, Gustaf D; Karlsson, Björn C G; Nicholls, Ian A; McCluskey, Adam

    2014-02-07

    The interactions between each component of the pre-polymerisation mixtures used in the synthesis of molecularly imprinted polymers (MIP) specific for 1,2,3,4,5-pentachlorobenzene (1) and 1,2,3-trichlorobenzene (2) were examined in four molecular dynamics simulations. These simulations revealed that the relative frequency of functional monomer-template (FM-T) interactions was consistent with results obtained by the synthesis and evaluation of the actual MIPs. The higher frequency of 1 interaction with trimethylstyrene (TMS; 54.7%) than 1 interaction with pentafluorostyrene (PFS; 44.7%) correlated with a higher imprinting factor (IF) of 2.1 vs. 1.7 for each functional monomer respectively. The higher frequency of PFS interactions with 2 (29.6%) than TMS interactions with 2 (1.9%) also correlated well with the observed differences in IF (3.7) of 2 MIPs imprinted using PFS as the FM than the IF (2.8) of 2 MIPs imprinted using TMS as the FM. The TMS-1 interaction dominated the molecular simulation due to high interaction energies, but the weaker TMS-2 resulted in low interaction maintenance, and thus lower IF values. Examination of the other pre-polymerisation mixture components revealed that the low levels of TMS-2 interaction was, in part, due to interference caused by the cross linker (CL) ethyleneglycol dimethylacrylate (EGDMA) interactions with TMS. The main reason was, however, attributed to MeOH interactions with TMS in both a hydrogen bond and perpendicular configuration. This positioned a MeOH directly above the π-orbital of all TMS for an average of 63.8% of MD2 creating significant interference to π-π stacking interactions between 2 and TMS. These findings are consistent with the deviation from the 'normal' molecularly imprinted polymer synthesis ratio of 1 : 4 : 20 (T : FM : CL) of 20 : 1 : 29 and 15 : 6 : 29 observed with 2 and TMS and PFS respectively. Our molecular dynamics simulations correctly predicted the high level

  16. Molecular Theory and the Effects of Solute Attractive Forces on Hydrophobic Interactions.

    Science.gov (United States)

    Chaudhari, Mangesh I; Rempe, Susan B; Asthagiri, D; Tan, L; Pratt, L R

    2016-03-03

    The role of solute attractive forces on hydrophobic interactions is studied by coordinated development of theory and simulation results for Ar atoms in water. We present a concise derivation of the local molecular field (LMF) theory for the effects of solute attractive forces on hydrophobic interactions, a derivation that clarifies the close relation of LMF theory to the EXP approximation applied to this problem long ago. The simulation results show that change from purely repulsive atomic solute interactions to include realistic attractive interactions diminishes the strength of hydrophobic bonds. For the Ar-Ar rdfs considered pointwise, the numerical results for the effects of solute attractive forces on hydrophobic interactions are opposite in sign and larger in magnitude than predicted by LMF theory. That comparison is discussed from the point of view of quasichemical theory, and it is suggested that the first reason for this difference is the incomplete evaluation within LMF theory of the hydration energy of the Ar pair. With a recent suggestion for the system-size extrapolation of the required correlation function integrals, the Ar-Ar rdfs permit evaluation of osmotic second virial coefficients B2. Those B2's also show that incorporation of attractive interactions leads to more positive (repulsive) values. With attractive interactions in play, B2 can change from positive to negative values with increasing temperatures. This is consistent with the puzzling suggestions of decades ago that B2 ≈ 0 for intermediate cases of temperature or solute size. In all cases here, B2 becomes more attractive with increasing temperature.

  17. Isolate extended state in the DNA molecular transistor with surface interaction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Le, E-mail: wang_le917@gs.zzu.edu.cn; Qin, Zhi-Jie

    2016-02-01

    The field effect characteristic of a DNA molecular device is investigated in a tight binding model with binary disorder and side site correlation. Using the transfer-matrix method and Landauer–Büttiker theory, we find that the system has isolated extended state that is irrespective of the DNA sequence and can be modulated by the gate voltage. When the gate voltage reaches some proper value, the isolated extended state appears at the Fermi level of the system and the long range charge transport is greatly enhanced. We attribute this phenomenon to the combination of the external field, the surface interaction, and the intrinsic disorder of DNA. The result is a generic feature of the nanowire with binary disorder and surface interaction.

  18. Interaction of diuron to human serum albumin: Insights from spectroscopic and molecular docking studies.

    Science.gov (United States)

    Chen, Huilun; Rao, Honghao; Yang, Jian; Qiao, Yongxiang; Wang, Fei; Yao, Jun

    2016-01-01

    This investigation was undertaken to determine the interaction of diuron with human serum albumin (HSA) was studied by monitoring the spectral behavior of diuron-HSA system. The fluorescence of HSA at 340 nm excited at 230 nm was obviously quenched by diuron due to dynamic collision and the quenching constant was of the order of 10(4) L mol(-1) at 310 K. However, no fluorescence quenching was observed when excited at 280 nm. Thermodynamic investigations revealed that the combination between diuron and HSA was entropy driven by predominantly hydrophobic interactions. The binding of diuron induced the drastic reduction in α-helix conformation and the significant enhancement in β-turn conformation of HSA. In addition, both sites marker competition study and molecular modeling simulation evidenced the binding of diuron to HSA primarily took place in subdomain IIIA (Sudlow's site II).

  19. Prediction of drug-packaging interactions via molecular dynamics (MD) simulations.

    Science.gov (United States)

    Feenstra, Peter; Brunsteiner, Michael; Khinast, Johannes

    2012-07-15

    The interaction between packaging materials and drug products is an important issue for the pharmaceutical industry, since during manufacturing, processing and storage a drug product is continuously exposed to various packaging materials. The experimental investigation of a great variety of different packaging material-drug product combinations in terms of efficacy and safety can be a costly and time-consuming task. In our work we used molecular dynamics (MD) simulations in order to evaluate the applicability of such methods to pre-screening of the packaging material-solute compatibility. The solvation free energy and the free energy of adsorption of diverse solute/solvent/solid systems were estimated. The results of our simulations agree with experimental values previously published in the literature, which indicates that the methods in question can be used to semi-quantitatively reproduce the solid-liquid interactions of the investigated systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Translational-rotational interaction in dynamics and thermodynamics of 2D atomic crystal with molecular impurity

    International Nuclear Information System (INIS)

    Antsygina, T.N.; Poltavskaya, M.I.; Chishko, K.A.

    2003-01-01

    The interaction between the rotational degrees of freedom of a diatomic molecular impurity and the phonon excitations of a two-dimensional atomic matrix commensurate with a substrate is investigated theoretically. It is shown, that the translational-rotational interaction changes the form of the rotational kinetic energy operator as compared to the corresponding expression for a free rotator, and also renormalized the parameters of the crystal field without change in its initial form. The contribution of the impurity rotational degrees of freedom to the low-temperature heat capacity for a dilute solution of diatomic molecules in an atomic two-dimensional matrix is calculated. The possibility of experimental observation of the effects obtained is discussed

  1. Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance.

    Science.gov (United States)

    Rimac, Hrvoje; Debeljak, Željko; Bojić, Mirza; Miller, Larisa

    2017-01-01

    Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site. It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug's free, active concentration in blood. In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Molecular modeling of interactions in electronic nose sensors for environmental monitoring

    Science.gov (United States)

    Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Yen, S. -P. S.; Zhou, H.; Manatt, K.

    2002-01-01

    We report a study aimed at understanding analyte interactions with sensors made from polymer-carbon black composite films. The sensors are used in an Electronic Nose (ENose) which is used for monitoring the breathing air quality in human habitats. The model mimics the experimental conditions of the composite film deposition and formation and was developed using molecular modeling and simulation tools. The Dreiding 2.21 Force Field was used for the polymer and analyte molecules while graphite parameters were assigned to the carbon black atoms. The polymer considered for this work is methyl vinyl ether / maleic acid copolymer. The target analytes include both inorganic (NH3) and organic (methanol) types of compound. Results indicate different composite-analyte interaction behavior.

  3. Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).

    Science.gov (United States)

    Pandey, Bharati; Grover, Abhinav; Sharma, Pradeep

    2018-02-12

    The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period. In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I. The results of our study revealed complete dynamic and structural information

  4. Thermodynamic Molecular Switch in Sequence-Specific Hydrophobic Interaction: Two Computational Models Compared

    Directory of Open Access Journals (Sweden)

    Paul Chun

    2003-01-01

    Full Text Available We have shown in our published work the existence of a thermodynamic switch in biological systems wherein a change of sign in ΔCp°(Treaction leads to a true negative minimum in the Gibbs free energy change of reaction, and hence, a maximum in the related Keq. We have examined 35 pair-wise, sequence-specific hydrophobic interactions over the temperature range of 273–333 K, based on data reported by Nemethy and Scheraga in 1962. A closer look at a single example, the pair-wise hydrophobic interaction of leucine-isoleucine, will demonstrate the significant differences when the data are analyzed using the Nemethy-Scheraga model or treated by the Planck-Benzinger methodology which we have developed. The change in inherent chemical bond energy at 0 K, ΔH°(T0 is 7.53 kcal mol-1 compared with 2.4 kcal mol-1, while ‹ts› is 365 K as compared with 355 K, for the Nemethy-Scheraga and Planck-Benzinger model, respectively. At ‹tm›, the thermal agitation energy is about five times greater than ΔH°(T0 in the Planck-Benzinger model, that is 465 K compared to 497 K in the Nemethy-Scheraga model. The results imply that the negative Gibbs free energy minimum at a well-defined ‹ts›, where TΔS° = 0 at about 355 K, has its origin in the sequence-specific hydrophobic interactions, which are highly dependent on details of molecular structure. The Nemethy-Scheraga model shows no evidence of the thermodynamic molecular switch that we have found to be a universal feature of biological interactions. The Planck-Benzinger method is the best known for evaluating the innate temperature-invariant enthalpy, ΔH°(T0, and provides for better understanding of the heat of reaction for biological molecules.

  5. Characterization of wise protein and its molecular mechanism to interact with both Wnt and BMP signals.

    Science.gov (United States)

    Lintern, Katherine B; Guidato, Sonia; Rowe, Alison; Saldanha, José W; Itasaki, Nobue

    2009-08-21

    Cross-talk of BMP and Wnt signaling pathways has been implicated in many aspects of biological events during embryogenesis and in adulthood. A secreted protein Wise and its orthologs (Sostdc1, USAG-1, and Ectodin) have been shown to modulate Wnt signaling and also inhibit BMP signals. Modulation of Wnt signaling activity by Wise is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands. Here we have investigated the mode of action of Wise on Wnt and BMP signals. It was found that Wise binds LRP6 through one of three loops formed by the cystine knot. The Wise deletion construct lacking the LRP6-interacting loop domain nevertheless binds BMP4 and inhibits BMP signals. Moreover, BMP4 does not interfere with Wise-LRP6 binding, suggesting separate domains for the physical interaction. Functional assays also show that the ability of Wise to block Wnt1 activity through LRP6 is not impeded by BMP4. In contrast, the ability of Wise to inhibit BMP4 is prevented by additional LRP6, implying a preference of Wise in binding LRP6 over BMP4. In addition to the interaction of Wise with BMP4 and LRP6, the molecular characteristics of Wise, such as glycosylation and association with heparan sulfate proteoglycans on the cell surface, are suggested. This study helps to understand the multiple functions of Wise at the molecular level and suggests a possible role for Wise in balancing Wnt and BMP signals.

  6. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    Directory of Open Access Journals (Sweden)

    Kaichun Li

    2016-01-01

    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  7. Molecular tweezers modulate 14-3-3 protein-protein interactions

    Science.gov (United States)

    Bier, David; Rose, Rolf; Bravo-Rodriguez, Kenny; Bartel, Maria; Ramirez-Anguita, Juan Manuel; Dutt, Som; Wilch, Constanze; Klärner, Frank-Gerrit; Sanchez-Garcia, Elsa; Schrader, Thomas; Ottmann, Christian

    2013-03-01

    Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

  8. Advanced Characterization of Molecular Interactions in TALSPEAK-like Separations Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nash, Kenneth [Washington State Univ., Pullman, WA (United States); Guelis, Artem [Argonne National Lab. (ANL), Argonne, IL (United States); Lumetta, Gregg J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sinkov, Sergey [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2015-10-21

    Combining unit operations in advanced aqueous reprocessing schemes brings obvious process compactness advantages, but at the same time greater complexity in process design and operation. Unraveling these interactions requires increasingly sophisticated analytical tools and unique approaches for adequate analysis and characterization that probe molecular scale interactions. Conventional slope analysis methods of solvent extraction are too indirect to provide much insight into such interactions. This project proposed the development and verification of several analytical tools based on studies of TALSPEAK-like aqueous processes. As such, the chemistry of trivalent fission product lanthanides, americium, curium, plutonium, neptunium and uranium figure prominently in these studies. As the project was executed, the primary focus fell upon the chemistry or trivalent lanthanides and actinides. The intent of the investigation was to compare and contrast the results from these various complementary techniques/studies to provide a stronger basis for predicting the performance of extractant/diluent mixtures as media for metal ion separations. As many/most of these techniques require the presence of metal ions at elevated concentrations, it was expected that these studies would take this investigation into the realm of patterns of supramolecular organization of metal complexes and extractants in concentrated aqueous/organic media. We expected to advance knowledge of the processes that enable and limit solvent extraction reactions as a result of the application of fundamental chemical principles to explaining interactions in complex media.

  9. New aspects of π–d interactions in magnetic molecular conductors

    Science.gov (United States)

    Sugimoto, Toyonari; Fujiwara, Hideki; Noguchi, Satoru; Murata, Keizo

    2009-01-01

    The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio-diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio-diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS), ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with FeX4− (X = Cl, Br) ions are prepared by electrocrystallization. The crystal structures of these salts are composed of alternately stacked donor molecule and magnetic anion layers. The band structures of the donor molecule layers are calculated using the overlap integrals between neighboring donor molecules and are compared with the observed electronic transport properties. The magnetic ordering of the Fe(III) d spins of FeX4− ions is determined from magnetization and heat capacity measurements. The magnetic ordering temperatures are estimated by considering a combination of a direct d–d interaction between the d spins and an indirect π–d interaction between the conduction π electron and the d spins, whose magnitudes are separately calculated from the crystal structures with an extended Hückel molecular orbital method. The occurrence of a π–d interaction is proved by the negative magnetoresistance, and the magnitude of magnetoresistance reflects the strength of the π–d interaction. The effect of pressure on the magnetoresistance is studied, and the result indicates that the magnitude of magnetoresistance increases, namely, the π–d interaction is enhanced with increasing pressure. From these experimental results it is shown that (EDT-TTFVO)2•FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2•FeX4 (X = Cl, Br) and (EDT-DSDTFVSDS)2•FeBr4 are metals exhibiting antiferromagnetic ordering of the d spins, and (EDO-TTFVO)2•FeCl4 and (EDO-TTFVODS)2•FeBr4•(DCE)0.5 (DCE =-dichloroethane) are

  10. TOPICAL REVIEW: New aspects of π-d interactions in magnetic molecular conductors

    Science.gov (United States)

    Sugimoto, Toyonari; Fujiwara, Hideki; Noguchi, Satoru; Murata, Keizo

    2009-04-01

    The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio-diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio-diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS), ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with FeX4- (X = Cl, Br) ions are prepared by electrocrystallization. The crystal structures of these salts are composed of alternately stacked donor molecule and magnetic anion layers. The band structures of the donor molecule layers are calculated using the overlap integrals between neighboring donor molecules and are compared with the observed electronic transport properties. The magnetic ordering of the Fe(III) d spins of FeX4- ions is determined from magnetization and heat capacity measurements. The magnetic ordering temperatures are estimated by considering a combination of a direct d-d interaction between the d spins and an indirect π-d interaction between the conduction π electron and the d spins, whose magnitudes are separately calculated from the crystal structures with an extended Hückel molecular orbital method. The occurrence of a π-d interaction is proved by the negative magnetoresistance, and the magnitude of magnetoresistance reflects the strength of the π-d interaction. The effect of pressure on the magnetoresistance is studied, and the result indicates that the magnitude of magnetoresistance increases, namely, the π-d interaction is enhanced with increasing pressure. From these experimental results it is shown that (EDT-TTFVO)2•FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2•FeX4 (X = Cl, Br) and (EDT-DSDTFVSDS)2•FeBr4 are metals exhibiting antiferromagnetic ordering of the d spins, and (EDO-TTFVO)2•FeCl4 and (EDO-TTFVODS)2•FeBr4•(DCE)0.5 (DCE =-dichloroethane) are genuine

  11. Study of DNA interactions with bifenthrin by spectroscopic techniques and molecular modeling

    Science.gov (United States)

    Zhu, Pan; Zhang, Guowen; Ma, Yadi; Zhang, Yepeng; Miao, Hong; Wu, Yongning

    2013-08-01

    The interaction between bifenthrin (BF) and calf thymus DNA (ctDNA) in physiological buffer (pH 7.4) was investigated by UV-vis absorption, fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy, coupled with viscosity measurements and molecular docking techniques. It was found that BF molecular could intercalate into the base pairs of ctDNA as evidenced by significant increases in absorption intensity, fluorescence polarization and relative viscosity of ctDNA, decrease in iodide quenching effect, and induced CD spectral changes. The association constant of BF with ctDNA was evaluated to be in the order of 104 L mol-1. Thermodynamic analysis of the binding data obtained at different temperatures suggested that the binding process was primarily driven by hydrogen bonds and van der Waals forces, as the values of the enthalpy change (ΔH) and the entropy change (ΔS) were calculated to be -31.13 ± 1.89 kJ mol-1 and -22.79 ± 1.21 J mol-1 K-1, respectively. The results of FT-IR spectra and molecular docking showed that a specific binding mainly existed between BF and adenine and guanine bases.

  12. Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly.

    Directory of Open Access Journals (Sweden)

    Joy G Ghosh

    2007-06-01

    Full Text Available Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113FISREFHR(120 exposed on the surface of alphaB crystallin decreased microtubule assembly by approximately 45%. In contrast, the interactive sequences, (131LTITSSLSSDGV(142 and (156ERTIPITRE(164, corresponding to the beta8 strand and the C-terminal extension respectively, which are involved in complex formation, increased microtubule assembly by approximately 34-45%. The alphaB crystallin peptides, (113FISREFHR(120 and (156ERTIPITRE(164, inhibited microtubule disassembly by approximately 26-36%, and the peptides (113FISREFHR(120 and (131LTITSSLSSDGV(142 decreased the thermal aggregation of tubulin by approximately 42-44%. The (131LTITSSLSSDGV(142 and (156ERTIPITRE(164 peptides were more effective than the widely used anti-cancer drug, Paclitaxel, in modulating tubulinmicrotubule dynamics. Mutagenesis of these interactive sequences in wt human alphaB crystallin confirmed the effects of the alphaB crystallin peptides on microtubule assembly/disassembly and tubulin aggregation. The regulation of microtubule assembly by alphaB crystallin varied over a narrow range of concentrations. The assembly of microtubules was maximal at alphaB crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1 inhibited microtubule assembly.Interactive sequences on the surface of human alphaB crystallin collectively modulate microtubule assembly through a dynamic subunit exchange mechanism that depends on the concentration and ratio of alphaB crystallin to tubulin. These are the first

  13. Beyond Ribosomal Binding: The Increased Polarity and Aberrant Molecular Interactions of 3-epi-deoxynivalenol

    Directory of Open Access Journals (Sweden)

    Yousef I. Hassan

    2016-09-01

    Full Text Available Deoxynivalenol (DON is a secondary fungal metabolite and contaminant mycotoxin that is widely detected in wheat and corn products cultivated around the world. Bio-remediation methods have been extensively studied in the past two decades and promising ways to reduce DON-associated toxicities have been reported. Bacterial epimerization of DON at the C3 carbon was recently reported to induce a significant loss in the bio-toxicity of the resulting stereoisomer (3-epi-DON in comparison to the parental compound, DON. In an earlier study, we confirmed the diminished bio-potency of 3-epi-DON using different mammalian cell lines and mouse models and mechanistically attributed it to the reduced binding of 3-epi-DON within the ribosomal peptidyl transferase center (PTC. In the current study and by inspecting the chromatographic behavior of 3-epi-DON and its molecular interactions with a well-characterized enzyme, Fusarium graminearum Tri101 acetyltransferase, we provide the evidence that the C3 carbon epimerization of DON influences its molecular interactions beyond the abrogated PTC binding.

  14. Intracellular antibody capture: A molecular biology approach to inhibitors of protein-protein interactions.

    Science.gov (United States)

    Zhang, Jing; Rabbitts, Terence H

    2014-11-01

    Many proteins of interest in basic biology, translational research studies and for clinical targeting in diseases reside inside the cell and function by interacting with other macromolecules. Protein complexes control basic processes such as development and cell division but also abnormal cell growth when mutations occur such as found in cancer. Interfering with protein-protein interactions is an important aspiration in both basic and disease biology but small molecule inhibitors have been difficult and expensive to isolate. Recently, we have adapted molecular biology techniques to develop a simple set of protocols for isolation of high affinity antibody fragments (in the form of single VH domains) that function within the reducing environment of higher organism cells and can bind to their target molecules. The method called Intracellular Antibody Capture (IAC) has been used to develop inhibitory anti-RAS and anti-LMO2 single domains that have been used for target validation of these antigens in pre-clinical cancer models and illustrate the efficacy of the IAC approach to generation of drug surrogates. Future use of inhibitory VH antibody fragments as drugs in their own right (we term these macrodrugs to distinguish them from small molecule drugs) requires their delivery to target cells in vivo but they can also be templates for small molecule drug development that emulate the binding sites of the antibody fragments. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Interaction of Lysozyme with Rhodamine B: A combined analysis of spectroscopic & molecular docking.

    Science.gov (United States)

    Millan, Sabera; Satish, Lakkoji; Kesh, Sandeep; Chaudhary, Yatendra S; Sahoo, Harekrushna

    2016-09-01

    The interaction of Rhodamine B (RB) with Lysozyme (Lys) was investigated by different optical spectroscopic techniques such as absorption, fluorescence, and circular-dichroism (CD), along with molecular docking studies. The fluorescence results (including steady-state and time-resolved mode) revealed that the addition of RB effectively causes strong quenching of intrinsic fluorescence in Lysozyme and mostly, by the static quenching mechanism. Different binding and thermodynamic parameters were calculated at different temperatures and the binding constant value was found to be 2963.54Lmol(-1) at 25°C. The average distance (r0) was found to be 3.31nm according to Förster's theory of non-radiative energy transfer between Lysozyme and RB. The conformational change in Lysozyme during interaction with RB was confirmed from absorbance, synchronous fluorescence, and circular dichroism measurements. Finally, molecular docking studies were done to confirm that the dye binds with Lysozyme. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Caffeine and sulfadiazine interact differently with human serum albumin: A combined fluorescence and molecular docking study

    Science.gov (United States)

    Islam, Mullah Muhaiminul; Sonu, Vikash K.; Gashnga, Pynsakhiat Miki; Moyon, N. Shaemningwar; Mitra, Sivaprasad

    2016-01-01

    The interaction and binding behavior of the well-known drug sulfadiazine (SDZ) and psychoactive stimulant caffeine (CAF) with human serum albumin (HSA) was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of CAF is due to the formation of protein-drug complex in the ground state; whereas in case of SDZ, the experimental results were explained on the basis of sphere of action model. Although both these compounds bind preferentially in Sudlow's site 1 of the protein, the association constant is approximately two fold higher in case of SDZ (∼4.0 × 104 M-1) in comparison with CAF (∼9.3 × 102 M-1) and correlates well with physico-chemical properties like pKa and lipophilicity of the drugs. Temperature dependent fluorescence study reveals that both SDZ and CAF bind spontaneously with HSA. However, the binding of SDZ with the protein is mainly governed by the hydrophobic forces in contrast with that of CAF; where, the interaction is best explained in terms of electrostatic mechanism. Molecular docking calculation predicts the binding of these drugs in different location of sub-domain IIA in the protein structure.

  17. Molecular Dynamics Simulation to Investigate the Interaction of Asphaltene and Oxide in Aggregate

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-01-01

    Full Text Available The asphalt-aggregate interface interaction (AAI plays a significant role in the overall performances of asphalt mixture, which is caused due to the complicated physicochemical processes and is influenced by various factors, including the acid-base property of aggregates. In order to analyze the effects of the chemical constitution of aggregate on the AAI, the average structure C65H74N2S2 is selected to represent the asphaltene in asphalt and magnesium oxide (MgO, calcium oxide (CaO, aluminium sesquioxide (Al2O3, and silicon dioxide (SiO2 are selected to represent the major oxides in aggregate. The molecular models are established for asphaltene and the four oxides, respectively, and the molecular dynamics (MD simulation was conducted for the four kinds of asphaltene-oxide system at different temperatures. The interfacial energy in MD simulation is calculated to evaluate the AAI, and higher value means better interaction. The results show that interfacial energy between asphaltene and oxide reaches the maximum value at 25°C and 80°C and the minimum value at 40°C. In addition, the interfacial energy between asphaltene and MgO was found to be the greatest, followed by CaO, Al2O3, and SiO2, which demonstrates that the AAI between asphalt and alkaline aggregates is better than acidic aggregates.

  18. IAEA activities on atomic, molecular and plasma-material interaction data for fusion

    Science.gov (United States)

    Braams, Bastiaan J.; Chung, Hyun-Kyung

    2013-09-01

    The IAEA Atomic and Molecular Data Unit (http://www-amdis.iaea.org/) aims to provide internationally evaluated and recommended data for atomic, molecular and plasma-material interaction (A+M+PMI) processes in fusion research. The Unit organizes technical meetings and coordinates an A+M Data Centre Network (DCN) and a Code Centre Network (CCN). In addition the Unit organizes Coordinated Research Projects (CRPs), for which the objectives are mixed between development of new data and evaluation and recommendation of existing data. In the area of A+M data we are placing new emphasis in our meeting schedule on data evaluation and especially on uncertainties in calculated cross section data and the propagation of uncertainties through structure data and fundamental cross sections to effective rate coefficients. Following a recent meeting of the CCN it is intended to use electron scattering on Be, Ne and N2 as exemplars for study of uncertainties and uncertainty propagation in calculated data; this will be discussed further at the presentation. Please see http://www-amdis.iaea.org/CRP/ for more on our active and planned CRPs, which are concerned with atomic processes in core and edge plasma and with plasma interaction with beryllium-based surfaces and with irradiated tungsten.

  19. Molecular players involved in the interaction between beneficial bacteria and the immune system

    Directory of Open Access Journals (Sweden)

    Arancha eHevia

    2015-11-01

    Full Text Available The human gastrointestinal tract is a very complex ecosystem, in which there is a continuous interaction between nutrients, host cells, and microorganisms. The gut microbiota comprises trillions of microbes that have been selected during evolution on the basis of their functionality and capacity to survive in, and adapt to, the intestinal environment. Host bacteria and our immune system constantly sense and react to one another. In this regard, commensal microbes contribute to gut homeostasis, whereas the necessary responses are triggered against enteropathogens. Some representatives of our gut microbiota have beneficial effects on human health. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins, or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. This process is mainly performed via the pattern recognition receptors of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognize the molecular effectors that are produced by intestinal microbes. These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria, or increase the number of immune cells or their pattern recognition receptors. This review intends to summarize the molecular players produced by probiotic bacteria, notably Lactobacillus and Bifidobacterium strains, but also other very promising potential probiotics, which affect the human immune system.

  20. Interactions of oxytetracycline with a smectite clay: a spectroscopic study with molecular simulations.

    Science.gov (United States)

    Aristilde, Ludmilla; Marichal, Claire; Miéhé-Brendlé, Jocelyne; Lanson, Bruno; Charlet, Laurent

    2010-10-15

    Binding of antibiotics to clay minerals can decrease both their physical and biological availability in soils. To elucidate the binding mechanisms of tetracycline antibiotics on smectite clays as a function of pH, we probed the interactions of oxytetracycline (OTC) with Na-montmorillonite (MONT) using X-ray diffraction (XRD), infrared (IR), and solid-state nuclear magnetic resonance (NMR) spectroscopies, and Monte Carlo molecular simulations. The XRD patterns demonstrate the presence of OTC in the MONT interlayer space at acidic pH whereas complexation of OTC by external basal and edge sites seems to prevail at pH 8. At both pH, the (1)H-(13)C NMR profile indicates restricted mobility of the adsorbed OTC species; and, -CH(3) deformation and C-N stretching IR vibration bands confirm a binding mechanism involving the protonated dimethylamino group of OTC. Changes in the (23)Na NMR environments are consistent with cation-exchange and cation complexation reactions at the different sites of adsorption. Molecular simulations indicate that MONT interlayer spacing and structural charge localization dictate favorable binding conformations of the intercalated OTC, facilitating multiple interactions in agreement with the spectroscopic data. Our results present complementary insights into the mechanisms of adsorption of TETs on smectites important for their retention in natural and engineered soil environments.

  1. Interaction of VUV-photons with molecules. Spectroscopy and dynamics of molecular superexcited states

    International Nuclear Information System (INIS)

    Hatano, Y.

    2002-01-01

    Complete text of publication follows. A survey is given of recent progress in experimental studies of the interaction of VUV-photons with molecules, i.e., those of photoabsorption, photoionization, and photodissociation of molecules in the excitation photon energy range of 10-50 eV, with a particular emphasis placed on current understanding of the spectroscopy and dynamics of formed molecular superexcited states. These studies are of great importance in understanding the interaction of ionizing radiation with matter. Molecules studied are ranged from simple diatomic and triatomic molecules to polyatomic molecules such as hydrocarbons. Most of the observed molecular superexcited states are assigned to high Rydber states which are vibrationally, doubly, or inner-core excited and converge to each of ion states. Non-Rydberg superexcited states are also observed. Dissociation into neutral fragments in comparison with ionization is of unexpectedly great importance in the observed decay of each of these state-assigned superexcited molecules. Dissociation dynamics as well as its products of superexcited states are remarkably different from those of lower excited states below about ionization thresholds. Some remarks are also presented of molecules in the condensed phase

  2. Effect of electron-vibration interactions on the thermoelectric efficiency of molecular junctions.

    Science.gov (United States)

    Hsu, Bailey C; Chiang, Chi-Wei; Chen, Yu-Chang

    2012-07-11

    From first-principles approaches, we investigate the thermoelectric efficiency of a molecular junction where a benzene molecule is connected directly to the platinum electrodes. We calculate the thermoelectric figure of merit ZT in the presence of electron-vibration interactions with and without local heating under two scenarios: linear response and finite bias regimes. In the linear response regime, ZT saturates around the electrode temperature T(e) = 25 K in the elastic case, while in the inelastic case we observe a non-saturated and a much larger ZT beyond T(e) = 25 K attributed to the tail of the Fermi-Dirac distribution. In the finite bias regime, the inelastic effects reveal the signatures of the molecular vibrations in the low-temperature regime. The normal modes exhibiting structures in the inelastic profile are characterized by large components of atomic vibrations along the current density direction on top of each individual atom. In all cases, the inclusion of local heating leads to a higher wire temperature T(w) and thus magnifies further the influence of the electron-vibration interactions due to the increased number of local phonons.

  3. When biomolecules meet graphene: from molecular level interactions to material design and applications.

    Science.gov (United States)

    Li, Dapeng; Zhang, Wensi; Yu, Xiaoqing; Wang, Zhenping; Su, Zhiqiang; Wei, Gang

    2016-12-01

    Graphene-based materials have attracted increasing attention due to their atomically-thick two-dimensional structures, high conductivity, excellent mechanical properties, and large specific surface areas. The combination of biomolecules with graphene-based materials offers a promising method to fabricate novel graphene-biomolecule hybrid nanomaterials with unique functions in biology, medicine, nanotechnology, and materials science. In this review, we focus on a summarization of the recent studies in functionalizing graphene-based materials using different biomolecules, such as DNA, peptides, proteins, enzymes, carbohydrates, and viruses. The different interactions between graphene and biomolecules at the molecular level are demonstrated and discussed in detail. In addition, the potential applications of the created graphene-biomolecule nanohybrids in drug delivery, cancer treatment, tissue engineering, biosensors, bioimaging, energy materials, and other nanotechnological applications are presented. This review will be helpful to know the modification of graphene with biomolecules, understand the interactions between graphene and biomolecules at the molecular level, and design functional graphene-based nanomaterials with unique properties for various applications.

  4. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc, and copper. Comprehensive progress report, October 1, 1975--December 31, 1978

    International Nuclear Information System (INIS)

    Wasserman, R.H.

    1978-10-01

    Investigations were undertaken to elucidate the mode of transepithelial transport of potentially toxic metal ions across the gastrointestinal tract, with primary attention given to cadmium, zinc, and arsenic. In addition, the toxic effects of cadmium on the metabolism of vitamin D and calcium have been investigated in some detail. Several approaches have been taken, including studies on the localization of heavy metals in the intestinal mucosa, the effects of cadmium on various parameters of calcium metabolism, the modes of intestinal absorption of cadmium, arsenate, and zinc, and the interactions of heavy metals with each other and with calcium, phosphorus, and vitamin D. Details of these experiments are attached in the Comprehensive Progress Report

  5. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc, and copper. Comprehensive progress report, October 1, 1975--December 31, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Wasserman, R. H.

    1978-10-01

    Investigations were undertaken to elucidate the mode of transepithelial transport of potentially toxic metal ions across the gastrointestinal tract, with primary attention given to cadmium, zinc, and arsenic. In addition, the toxic effects of cadmium on the metabolism of vitamin D and calcium have been investigated in some detail. Several approaches have been taken, including studies on the localization of heavy metals in the intestinal mucosa, the effects of cadmium on various parameters of calcium metabolism, the modes of intestinal absorption of cadmium, arsenate, and zinc, and the interactions of heavy metals with each other and with calcium, phosphorus, and vitamin D. Details of these experiments are attached in the Comprehensive Progress Report.

  6. Molecular interactions between the olive and the fruit fly Bactrocera oleae

    Directory of Open Access Journals (Sweden)

    Corrado Giandomenico

    2012-06-01

    Full Text Available Abstract Background The fruit fly Bactrocera oleae is the primary biotic stressor of cultivated olives, causing direct and indirect damages that significantly reduce both the yield and the quality of olive oil. To study the olive-B. oleae interaction, we conducted transcriptomic and proteomic investigations of the molecular response of the drupe. The identifications of genes and proteins involved in the fruit response were performed using a Suppression Subtractive Hybridisation technique and a combined bi-dimensional electrophoresis/nanoLC-ESI-LIT-MS/MS approach, respectively. Results We identified 196 ESTs and 26 protein spots as differentially expressed in olives with larval feeding tunnels. A bioinformatic analysis of the identified non-redundant EST and protein collection indicated that different molecular processes were affected, such as stress response, phytohormone signalling, transcriptional control and primary metabolism, and that a considerable proportion of the ESTs could not be classified. The altered expression of 20 transcripts was also analysed by real-time PCR, and the most striking differences were further confirmed in the fruit of a different olive variety. We also cloned the full-length coding sequences of two genes, Oe-chitinase I and Oe-PR27, and showed that these are wound-inducible genes and activated by B. oleae punctures. Conclusions This study represents the first report that reveals the molecular players and signalling pathways involved in the interaction between the olive fruit and its most damaging biotic stressor. Drupe response is complex, involving genes and proteins involved in photosynthesis as well as in the production of ROS, the activation of different stress response pathways and the production of compounds involved in direct defence against phytophagous larvae. Among the latter, trypsin inhibitors should play a major role in drupe resistance reaction.

  7. Crop epigenetics and the molecular hardware of genotype x environment interactions

    Directory of Open Access Journals (Sweden)

    Graham John King

    2015-11-01

    Full Text Available Crop plants encounter thermal environments which fluctuate on a diurnal and seasonal basis. Future climate resilient cultivars will need to respond to thermal profiles reflecting more variable conditions, and harness plasticity that involves regulation of epigenetic processes and complex genomic regulatory networks. Compartmentalisation within plant cells insulates the genomic central processing unit within the interphase nucleus. This review addresses the properties of the chromatin hardware in which the genome is embedded, focusing on the biophysical and thermodynamic properties of DNA, histones and nucleosomes. It explores the consequences of thermal and ionic variation on the biophysical behaviour of epigenetic marks such as DNA cytosine methylation (5mC, and histone variants such as H2A.Z, and how these contribute to maintenance of chromatin integrity in the nucleus, while enabling specific subsets of genes to be regulated. Information is drawn from theoretical molecular in vitro studies as well as model and crop plants and incorporates recent insights into the role epigenetic processes play in mediating between environmental signals and genomic regulation. A preliminary speculative framework is outlined, based on the evidence of what appears a cohesive set of interactions at molecular, biophysical and electrostatic level between the various components contributing to chromatin conformation and dynamics. It proposes that within plant nuclei, general and localised ionic homeostasis plays an important role in maintaining chromatin conformation, whilst maintaining complex genomic regulation that involve specific patterns of epigenetic marks. More generally, reversible changes in DNA methylation appear to be consistent with the ability of nuclear chromatin to manage variation in external ionic and temperature environment. Whilst tentative, this framework provides scope to develop experimental approaches to understand in greater detail the

  8. Spectroscopic and molecular docking techniques study of the interaction between oxymetholone and human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Madrakian, Tayyebeh, E-mail: madrakian@basu.ac.ir; Bagheri, Habibollah; Afkhami, Abbas; Soleimani, Mohammad

    2014-11-15

    In this study, the binding of oxymetholone (OXM), a doping drug, to human serum albumin (HSA) was explored at pH 7.40 by spectroscopic methods including spectrofluorimetry, three dimensional excitation–emission matrix (3D EEM), UV–vis absorption, resonance rayleigh scattering (RRS) and molecular docking. The fluorescence results showed that there was a considerable quenching of the intrinsic fluorescence of HSA upon binding to OXM by static quenching mechanism. The Stern–Volmer quenching constants (K{sub SV}) between OXM and HSA at three different temperatures 295, 303, 308 K, were obtained as 4.63×10{sup 4}, 3.05×10{sup 4} and 1.49×10{sup 4} L mol{sup −1}, respectively. Furthermore this interaction was confirmed by UV–vis spectrophotometric and RRS techniques. The binding site number, n, apparent binding constant, K{sub b}, and corresponding thermodynamic parameters (ΔS, ΔH and ΔG) were measured at different temperatures. The Van der Waals and hydrogen-bond forces were found to stabilize OXM–HSA complex. The distance (r) between the donor and acceptor was obtained from Förster's theory of fluorescence resonance energy transfer (FRET) and found to be 1.67 nm. The 3D EEM showed that OXM slightly changes the secondary structure of HSA. Furthermore, the molecular docking was employed for identification of drug binding sites and interaction of OXM with amino acid residues. - Highlights: • The binding of OXM as a doping drug with HSA was studied by different techniques. • The binding constant of HSA–OXM was calculated. • The binding site of OXM on HSA was characterized with molecular docking. • The thermodynamic parameters were calculated according to fluorescence technique.

  9. Molecular mechanics and quantum mechanical modeling of hexane soot structure and interactions with pyrene

    Directory of Open Access Journals (Sweden)

    Kubicki JD

    2000-09-01

    Full Text Available Molecular simulations (energy minimizations and molecular dynamics of an n-hexane soot model developed by Smith and co-workers (M. S. Akhter, A. R. Chughtai and D. M. Smith, Appl. Spectrosc., 1985, 39, 143; ref. 1 were performed. The MM+ (N. L. Allinger, J. Am. Chem. Soc., 1977, 395, 157; ref. 2 and COMPASS (H. Sun, J. Phys. Chem., 1998, 102, 7338; ref. 3 force fields were tested for their ability to produce realistic soot nanoparticle structure. The interaction of pyrene with the model soot was simulated. Quantum mechanical calculations on smaller soot fragments were carried out. Starting from an initial 2D structure, energy minimizations are not able to produce the observed layering within soot with either force field. Results of molecular dynamics simulations indicate that the COMPASS force field does a reasonably accurate job of reproducing observations of soot structure. Increasing the system size from a 683 to a 2732 atom soot model does not have a significant effect on predicted structures. Neither does the addition of water molecules surrounding the soot model. Pyrene fits within the soot structure without disrupting the interlayer spacing. Polycyclic aromatic hydrocarbons (PAH, such as pyrene, may strongly partition into soot and have slow desorption kinetics because the PAH-soot bonding is similar to soot–soot interactions. Diffusion of PAH into soot micropores may allow the PAH to be irreversibly adsorbed and sequestered so that they partition slowly back into an aqueous phase causing dis-equilibrium between soil organic matter and porewater.

  10. Theoretical and experimental approach on the molecular interactions of the DL-Alanine with an electrolytic environment

    Science.gov (United States)

    Cantero-López, Plinio; Yañez-Osses, Osvaldo; Páez-Meza, Manuel Silvestre; López, Johana E.; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro

    2017-11-01

    The molecular interactions that promote the stability of proteins and amino acids in saline solutions is a central topic of molecular biophysics. However, a well-supported molecular picture of the phenomena has not been established yet. In this paper, we studied as model system the mix between DL-Alanine in aqueous solutions of STP (Na2S2O3·5H2O) at different temperatures, from volumetric and viscometric properties. The thermophysical properties obtained indicate the presence of a strong preferential solvation, structure-making action and a possible salt in effect. Quantum chemical calculations and molecular dynamic (MD) simulations provide a new insight to support these arguments.

  11. Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

    Science.gov (United States)

    Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

    2008-02-19

    Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

  12. Molecular interactions in a surfactant-water-polyacrylamide system, according to densimetry, viscometry, conductometry, and spectroscopy data

    Science.gov (United States)

    Harutyunyan, R. S.

    2013-08-01

    Molecular interactions in a surfactant-polyacrylamide-water system are investigated. It is established that the interactions affect such physicochemical parameters of the system as viscosity, density, surface tension, conductivity, and critical micelle concentration. It is shown that in a polyacrylamide-water system, raising the polyacrylamide concentration to 0.02% causes conformational changes in its macromolecule.

  13. Facilitating Students' Interaction with Real Gas Properties Using a Discovery-Based Approach and Molecular Dynamics Simulations

    Science.gov (United States)

    Sweet, Chelsea; Akinfenwa, Oyewumi; Foley, Jonathan J., IV

    2018-01-01

    We present an interactive discovery-based approach to studying the properties of real gases using simple, yet realistic, molecular dynamics software. Use of this approach opens up a variety of opportunities for students to interact with the behaviors and underlying theories of real gases. Students can visualize gas behavior under a variety of…

  14. The relationships within the Chaitophorinae and Drepanosiphinae (Hemiptera, Aphididae) inferred from molecular-based phylogeny and comprehensive morphological data

    Science.gov (United States)

    Wieczorek, Karina; Lachowska-Cierlik, Dorota; Kajtoch, Łukasz; Kanturski, Mariusz

    2017-01-01

    The Chaitophorinae is a bionomically diverse Holarctic subfamily of Aphididae. The current classification includes two tribes: the Chaitophorini associated with deciduous trees and shrubs, and Siphini that feed on monocotyledonous plants. We present the first phylogenetic hypothesis for the subfamily, based on molecular and morphological datasets. Molecular analyses were based on the mitochondrial gene cytochrome oxidase subunit I (COI) and the nuclear gene elongation factor-1α (EF-1α). Phylogenetic inferences were obtained individually on each of genes and joined alignments using Bayesian inference (BI) and Maximum likelihood (ML). In phylogenetic trees reconstructed on the basis of nuclear and mitochondrial genes as well as a morphological dataset, the monophyly of Siphini and the genus Chaitophorus was supported. Periphyllus forms independent lineages from Chaitophorus and Siphini. Within this genus two clades comprising European and Asiatic species, respectively, were indicated. Concerning relationships within the subfamily, EF-1α and joined COI and EF-1α genes analysis strongly supports the hypothesis that Chaitophorini do not form a monophyletic clade. Periphyllus is a sister group to a clade containing Chaitophorus and Siphini. The Asiatic unit of Periphyllus also includes Trichaitophorus koyaensis. The analysis of morphological dataset under equally weighted parsimony also supports the view that Chaitophorini is an artificial taxon, as Lambersaphis pruinosae and Pseudopterocomma hughi, both traditionally included in the Chaitophorini, formed independent lineages. COI analyses support consistent groups within the subfamily, but relationships between groups are poorly resolved. These analyses were extended to include the species of closely related and phylogenetically unstudied subfamily Drepanosiphinae, which produced congruent results. Genera Drepanosiphum and Depanaphis are monophyletic and sister. The position of Yamatocallis tokyoensis differs in the

  15. Creating and Using Interactive, 3D-Printed Models to Improve Student Comprehension of the Bohr Model of the Atom, Bond Polarity, and Hybridization

    Science.gov (United States)

    Smiar, Karen; Mendez, J. D.

    2016-01-01

    Molecular model kits have been used in chemistry classrooms for decades but have seen very little recent innovation. Using 3D printing, three sets of physical models were created for a first semester, introductory chemistry course. Students manipulated these interactive models during class activities as a supplement to existing teaching tools for…

  16. Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells

    Directory of Open Access Journals (Sweden)

    Jonathan Laiño

    2016-08-01

    Full Text Available Researchers have demonstrated that lactic acid bacteria (LAB with immunomodulatory capabilities (immunobiotics exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS, that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals.

  17. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Directory of Open Access Journals (Sweden)

    Yonghua Wang

    Full Text Available MicroRNAs (miRNAs are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1 three important (PAZ, Mid and PIWI domains exist in Argonaute which define the global dynamics of the protein; 2 the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3 it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+ plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA. Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  18. Mechanism of microRNA-target interaction: molecular dynamics simulations and thermodynamics analysis.

    Science.gov (United States)

    Wang, Yonghua; Li, Yan; Ma, Zhi; Yang, Wei; Ai, Chunzhi

    2010-07-29

    MicroRNAs (miRNAs) are endogenously produced approximately 21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5'-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg(2+)) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago.

  19. Massively parallel sequencing, aCGH, and RNA-Seq technologies provide a comprehensive molecular diagnosis of Fanconi anemia.

    Science.gov (United States)

    Chandrasekharappa, Settara C; Lach, Francis P; Kimble, Danielle C; Kamat, Aparna; Teer, Jamie K; Donovan, Frank X; Flynn, Elizabeth; Sen, Shurjo K; Thongthip, Supawat; Sanborn, Erica; Smogorzewska, Agata; Auerbach, Arleen D; Ostrander, Elaine A

    2013-05-30

    Current methods for detecting mutations in Fanconi anemia (FA)-suspected patients are inefficient and often miss mutations. We have applied recent advances in DNA sequencing and genomic capture to the diagnosis of FA. Specifically, we used custom molecular inversion probes or TruSeq-enrichment oligos to capture and sequence FA and related genes, including introns, from 27 samples from the International Fanconi Anemia Registry at The Rockefeller University. DNA sequencing was complemented with custom array comparative genomic hybridization (aCGH) and RNA sequencing (RNA-seq) analysis. aCGH identified deletions/duplications in 4 different FA genes. RNA-seq analysis revealed lack of allele specific expression associated with a deletion and splicing defects caused by missense, synonymous, and deep-in-intron variants. The combination of TruSeq-targeted capture, aCGH, and RNA-seq enabled us to identify the complementation group and biallelic germline mutations in all 27 families: FANCA (7), FANCB (3), FANCC (3), FANCD1 (1), FANCD2 (3), FANCF (2), FANCG (2), FANCI (1), FANCJ (2), and FANCL (3). FANCC mutations are often the cause of FA in patients of Ashkenazi Jewish (AJ) ancestry, and we identified 2 novel FANCC mutations in 2 patients of AJ ancestry. We describe here a strategy for efficient molecular diagnosis of FA.

  20. Comprehensive Transcriptome Study to Develop Molecular Resources of the Copepod Calanus sinicus for Their Potential Ecological Applications

    Science.gov (United States)

    Yang, Qing; Sun, Fanyue; Yang, Zhi; Li, Hongjun

    2014-01-01

    Calanus sinicus Brodsky (Copepoda, Crustacea) is a dominant zooplanktonic species widely distributed in the margin seas of the Northwest Pacific Ocean. In this study, we utilized an RNA-Seq-based approach to develop molecular resources for C. sinicus. Adult samples were sequenced using the Illumina HiSeq 2000 platform. The sequencing data generated 69,751 contigs from 58.9 million filtered reads. The assembled contigs had an average length of 928.8 bp. Gene annotation allowed the identification of 43,417 unigene hits against the NCBI database. Gene ontology (GO) and KEGG pathway mapping analysis revealed various functional genes related to diverse biological functions and processes. Transcripts potentially involved in stress response and lipid metabolism were identified among these genes. Furthermore, 4,871 microsatellites and 110,137 single nucleotide polymorphisms (SNPs) were identified in the C. sinicus transcriptome sequences. SNP validation by the melting temperature (T m)-shift method suggested that 16 primer pairs amplified target products and showed biallelic polymorphism among 30 individuals. The present work demonstrates the power of Illumina-based RNA-Seq for the rapid development of molecular resources in nonmodel species. The validated SNP set from our study is currently being utilized in an ongoing ecological analysis to support a future study of C. sinicus population genetics. PMID:24982883

  1. Comprehensive Care

    Science.gov (United States)

    ... Comprehensive Care Share this page Facebook Twitter Email Comprehensive Care Understand the importance of comprehensive MS care ... In this article A complex disease requires a comprehensive approach Today multiple sclerosis (MS) is not a ...

  2. Challenges for automatically extracting molecular interactions from full-text articles.

    Science.gov (United States)

    McIntosh, Tara; Curran, James R

    2009-09-24

    The increasing availability of full-text biomedical articles will allow more biomedical knowledge to be extracted automatically with greater reliability. However, most Information Retrieval (IR) and Extraction (IE) tools currently process only abstracts. The lack of corpora has limited the development of tools that are capable of exploiting the knowledge in full-text articles. As a result, there has been little investigation into the advantages of full-text document structure, and the challenges developers will face in processing full-text articles. We manually annotated passages from full-text articles that describe interactions summarised in a Molecular Interaction Map (MIM). Our corpus tracks the process of identifying facts to form the MIM summaries and captures any factual dependencies that must be resolved to extract the fact completely. For example, a fact in the results section may require a synonym defined in the introduction. The passages are also annotated with negated and coreference expressions that must be resolved.We describe the guidelines for identifying relevant passages and possible dependencies. The corpus includes 2162 sentences from 78 full-text articles. Our corpus analysis demonstrates the necessity of full-text processing; identifies the article sections where interactions are most commonly stated; and quantifies the proportion of interaction statements requiring coherent dependencies. Further, it allows us to report on the relative importance of identifying synonyms and resolving negated expressions. We also experiment with an oracle sentence retrieval system using the corpus as a gold-standard evaluation set. We introduce the MIM corpus, a unique resource that maps interaction facts in a MIM to annotated passages within full-text articles. It is an invaluable case study providing guidance to developers of biomedical IR and IE systems, and can be used as a gold-standard evaluation set for full-text IR tasks.

  3. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high, -low, and -negative colorectal cancers based on protein marker expression and molecular features.

    Science.gov (United States)

    Zlobec, Inti; Bihl, Michel; Foerster, Anja; Rufle, Alex; Lugli, Alessandro

    2011-11-01

    CpG island methylator phenotype (CIMP) is being investigated for its role in the molecular and prognostic classification of colorectal cancer patients but is also emerging as a factor with the potential to influence clinical decision-making. We report a comprehensive analysis of clinico-pathological and molecular features (KRAS, BRAF and microsatellite instability, MSI) as well as of selected tumour- and host-related protein markers characterizing CIMP-high (CIMP-H), -low, and -negative colorectal cancers. Immunohistochemical analysis for 48 protein markers and molecular analysis of CIMP (CIMP-H: ≥ 4/5 methylated genes), MSI (MSI-H: ≥ 2 instable genes), KRAS, and BRAF were performed on 337 colorectal cancers. Simple and multiple regression analysis and receiver operating characteristic (ROC) curve analysis were performed. CIMP-H was found in 24 cases (7.1%) and linked (p CIMP-low or -negative cases. Of the 48 protein markers, decreased levels of RKIP (p = 0.0056), EphB2 (p = 0.0045), CK20 (p = 0.002), and Cdx2 (p CIMP-H, independently of MSI status. In addition to the expected clinico-pathological and molecular associations, CIMP-H colorectal cancers are characterized by a loss of protein markers associated with differentiation, and metastasis suppression, and have increased CD8+ T-lymphocytes regardless of MSI status. In particular, Cdx2 loss seems to strongly predict CIMP-H in both microsatellite-stable (MSS) and MSI-H colorectal cancers. Cdx2 is proposed as a surrogate marker for CIMP-H. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. [Binding interaction of harpagoside and bovine serum albumin: spectroscopic methodologies and molecular docking].

    Science.gov (United States)

    Cao, Tuan-Wu; Huang, Wen-Bing; Shi, Jian-Wei; He, Wei

    2018-03-01

    Scrophularia ningpoensis has exhibited a variety of biological activities and been used as a pharmaceutical product for the treatment of inflammatory ailment, rheumatoid arthritis, osteoarthritis and so on. Harpagoside (HAR) is considerer as a main bioactive compound in this plant. Serum albumin has important physiological roles in transportation, distribution and metabolism of many endogenous and exogenous substances in body. It is of great significance to study the interaction mechanism between HAR and bovine serum albumin (BSA). The mechanism of interaction between HAR and BSA was investigated using 2D and 3D fluorescence, synchronous florescence, ultraviolet spectroscopy and molecular docking. According to the analysis of fluorescence spectra, HAR could strongly quench the fluorescence of BSA, and the static quenching process indicated that the decrease in the quenching constant was observed with the increase in temperature. The magnitude of binding constants (KA) was more than 1×10⁵ L·mol⁻¹, and the number of binding sites(n) was approximate to 1. The thermodynamic parameters were calculated through analysis of fluorescence data with Stern-Volmer and Van't Hoff equation. The calculated enthalpy change (ΔH) and entropy change (ΔS) implied that the main interaction forces of HAR with BSA were the bonding interaction between van der Waals forces and hydrogen. The negative values of energy (ΔG) demonstrated that the binding of HAR with BSA was a spontaneous and exothermic process. The binding distance(r) between HAR and BSA was calculated to be about 2.80 nm based on the theory of Frster's non-radiation energy transfer, which indicated that energy is likely to be transfer from BSA to HAR. Both synchronous and 3D florescence spectroscopy clearly revealed that the microenvironment and conformation of BSA changed during the binding interaction between HAR and BSA. The molecular docking analysis revealed HAR is more inclined to BSA and human serum albumin

  5. Imaging molecular interaction of NO on Cu(110) with a scanning tunneling microscope.

    Science.gov (United States)

    Okuyama, Hiroshi

    2014-10-01

    Molecular interaction on metal surfaces is one of the central issues of surface science for the microscopic understanding of heterogeneous catalysis. In this Personal Account, I review the recent studies on NO/Cu(110) employing a scanning tunneling microscope (STM) to probe and control the molecule-molecule interaction on the surface. An individual NO molecule was observed as a characteristic dumbbell-shaped protrusion, visualizing the 2π* orbital. By manipulating the intermolecular distance with the STM, the overlap of the 2π* orbital between two NO molecules was controlled. The interaction causes the formation of the bonding and antibonding orbitals below and above the Fermi level, respectively, as a function of the intermolecular distance. The 2π* orbital also plays a role in the reaction of NO with water molecules. A water molecule donates a H-bond to NO, giving rise to the down-shift of the 2π* level below the Fermi level. This causes electron transfer from the substrate to NO, weakening, and eventually rupturing, the N-O bond. The facile bond cleavage by water molecules has implications for the catalytic reduction of NO under ambient conditions. Copyright © 2014 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Direct molecular interactions between Beclin 1 and the canonical NFκB activation pathway.

    Science.gov (United States)

    Niso-Santano, Mireia; Criollo, Alfredo; Malik, Shoaib Ahmad; Michaud, Michael; Morselli, Eugenia; Mariño, Guillermo; Lachkar, Sylvie; Galluzzi, Lorenzo; Maiuri, Maria Chaira; Kroemer, Guido

    2012-02-01

    General (macro)autophagy and the activation of NFκB constitute prominent responses to a large array of intracellular and extracellular stress conditions. The depletion of any of the three subunits of the inhibitor of NFκB (IκB) kinase (IKKα, IKKβ, IKKγ/NEMO), each of which is essential for the canonical NFκB activation pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK subunits suffice to stimulate autophagy. The activation of IKK usually relies on TGFβ-activated kinase 1 (TAK1), which is also necessary for the optimal induction of autophagy in multiple settings. TAK1 interacts with two structurally similar co-activators, TAK1-binding proteins 2 and 3 (TAB2 and TAB3). Importantly, in resting conditions both TAB2 and TAB3 bind the essential autophagic factor Beclin 1, but not TAK1. In response to pro-autophagic stimuli, TAB2 and TAB3 dissociate from Beclin 1 and engage in stimulatory interactions with TAK1. The inhibitory interaction between TABs and Beclin 1 is mediated by their coiled-coil domains (CCDs). Accordingly, the overexpression of either TAB2 or TAB3 CCD stimulates Beclin 1- and TAK1-dependent autophagy. These results point to the existence of a direct molecular crosstalk between the canonical NFκB activation pathway and the autophagic core machinery that guarantees the coordinated induction of these processes in response to stress.

  7. Molecular Dynamics Simulation of Barnase: Contribution of Noncovalent Intramolecular Interaction to Thermostability

    Directory of Open Access Journals (Sweden)

    Zhiguo Chen

    2013-01-01

    Full Text Available Bacillus amyloliquefaciens ribonuclease Barnase (RNase Ba is a 12 kD (kilodalton small extracellular ribonuclease. It has broad application prospects in agriculture, clinical medicine, pharmaceutical, and so forth. In this work, the thermal stability of Barnase has been studied using molecular dynamics simulation at different temperatures. The present study focuses on the contribution of noncovalent intramolecular interaction to protein stability and how they affect the thermal stability of the enzyme. Profiles of root mean square deviation and root mean square fluctuation identify thermostable and thermosensitive regions of Barnase. Analyses of trajectories in terms of secondary structure content, intramolecular hydrogen bonds and salt bridge interactions indicate distinct differences in different temperature simulations. In the simulations, Four three-member salt bridge networks (Asp8-Arg110-Asp12, Arg83-Asp75-Arg87, Lys66-Asp93-Arg69, and Asp54-Lys27-Glu73 have been identified as critical salt bridges for thermostability which are maintained stably at higher temperature enhancing stability of three hydrophobic cores. The study may help enlighten our knowledge of protein structural properties, noncovalent interactions which can stabilize secondary peptide structures or promote folding, and also help understand their actions better. Such an understanding is required for designing efficient enzymes with characteristics for particular applications at desired working temperatures.

  8. Binding interaction of atorvastatin with bovine serum albumin: Spectroscopic methods and molecular docking

    Science.gov (United States)

    Wang, Qi; Huang, Chuan-ren; Jiang, Min; Zhu, Ying-yao; Wang, Jing; Chen, Jun; Shi, Jie-hua

    2016-03-01

    The interaction of atorvastatin with bovine serum albumin (BSA) was investigated using multi-spectroscopic methods and molecular docking technique for providing important insight into further elucidating the store and transport process of atorvastatin in the body and the mechanism of action and pharmacokinetics. The experimental results revealed that the fluorescence quenching mechanism of BSA induced atorvastatin was a combined dynamic and static quenching. The binding constant and number of binding site of atorvastatin with BSA under simulated physiological conditions (pH = 7.4) were 1.41 × 105 M- 1 and about 1 at 310 K, respectively. The values of the enthalpic change (ΔH0), entropic change (ΔS0) and Gibbs free energy (ΔG0) in the binding process of atorvastatin with BSA at 310 K were negative, suggesting that the binding process of atorvastatin and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen bonding interaction. Moreover, atorvastatin was bound into the subdomain IIA (site I) of BSA, resulting in a slight change of the conformation of BSA.

  9. Chitosan nanoparticles-trypsin interactions: Bio-physicochemical and molecular dynamics simulation studies.

    Science.gov (United States)

    Salar, Safoura; Mehrnejad, Faramarz; Sajedi, Reza H; Arough, Javad Mohammadnejad

    2017-10-01

    Herein, we investigated the effect of the chitosan nanoparticles (CsNP) on the structure, dynamics, and activity of trypsin. The enzyme activity in complex with the nanoparticles slightly increased, which represents the interactions between the nanoparticles and the enzyme. The kinetic parameters of the enzyme, K m and k cat , increased after adding the nanoparticles, resulting in a slight increase in the catalytic efficiency (k cat /K m ). However, the effect of the nanoparticles on the kinetic stability of trypsin has not exhibited significant variations. Fluorescence spectroscopy did not show remarkable changes in the trypsin conformation in the presence of the nanoparticles. The circular dichroism (CD) spectroscopy results also revealed the secondary structure of trypsin attached to the nanoparticles slightly changed. Furthermore, we used molecular dynamics (MD) simulation to find more information about the interaction mechanisms between the nanoparticles and trypsin. The root mean square deviation (RMSD) of Cα atoms results have shown that in the presence of the nanoparticles, trypsin was stable. The simulation and the calculation of the binding free energy demonstrate that the nonpolar interactions are the most important forces for the formation of stable nanoparticle-trypsin complex. This study has explicitly elucidated that the nanoparticles have not considerable effect on the trypsin. Copyright © 2017. Published by Elsevier B.V.

  10. Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, Leslie A.; Aggarwal, Shilpa; Bussey, Kendra A.; Desmet, Emily A.; Kim, Baek; Takimoto, Toru, E-mail: toru_takimoto@urmc.rochester.edu

    2012-04-25

    The influenza polymerase complex composed of PA, PB1 and PB2, plays a key role in viral replication and pathogenicity. Newly synthesized components must be translocated to the nucleus, where replication and transcription of viral genomes take place. Previous studies suggest that while PB2 is translocated to the nucleus independently, PA and PB1 subunits could not localize to the nucleus unless in a PA-PB1 complex. To further determine the molecular interactions between the components, we created a panel of 16 hybridoma cell lines, which produce monoclonal antibodies (mAbs) against each polymerase component. We showed that, although PB1 interacts with both PA and PB2 individually, nuclear localization of PB1 is enhanced only when co-expressed with PA. Interestingly, one of the anti-PA mAbs reacted much more strongly with PA when co-expressed with PB1. These results suggest that PA-PB1 interactions induce a conformational change in PA, which could be required for its nuclear translocation.

  11. Interaction of Aldehyde dehydrogenase with acetaminophen as examined by spectroscopies and molecular docking

    Directory of Open Access Journals (Sweden)

    Ayodele O. Kolawole

    2017-07-01

    Full Text Available The interaction of acetaminophen, a non-substrate anionic ligand, with Aldehyde Dehydrogenase was studied by fluorescence, UV–Vis absorption, and circular dichroism spectroscopies under simulated physiological conditions. The fluorescence spectra and data generated showed that acetaminophen binding to ALDH is purely dynamic quenching mechanism. The acetaminophen-ALDH is kinetically rapid reversible interaction with a binding constant, Ka, of 4.91×103 L mol−1. There was an existence of second binding site of ALDH for acetaminophen at saturating acetaminophen concentration. The binding sites were non-cooperative. The thermodynamic parameters obtained suggest that Van der Waal force and hydrogen bonding played a major role in the binding of acetaminophen to ALDH. The interaction caused perturbation of the ALDH structures with an obvious reduction in the α-helix. The binding distance of 4.43 nm was obtained between Acetaminophen and ALDH. Using Ficoll 400 as macro-viscosogen and glycerol as micro-viscosogen, Stoke-Einstein empirical plot demonstrated that acetaminophen-ALDH binding was diffusion controlled. Molecular docking showed the participation of some amino acids in the complex formation with −5.3 kcal binding energy. With these, ALDH might not an excipient detoxifier of acetaminophen but could be involved in its pegylation/encapsulation.

  12. HitPredict version 4: comprehensive reliability scoring of physical protein?protein interactions from more than 100 species

    OpenAIRE

    L?pez, Yosvany; Nakai, Kenta; Patil, Ashwini

    2015-01-01

    HitPredict is a consolidated resource of experimentally identified, physical protein?protein interactions with confidence scores to indicate their reliability. The study of genes and their inter-relationships using methods such as network and pathway analysis requires high quality protein?protein interaction information. Extracting reliable interactions from most of the existing databases is challenging because they either contain only a subset of the available interactions, or a mixture of p...

  13. Physics of ionic and molecular interactions - 2006-2010 scientific report, 2012-2015 project

    International Nuclear Information System (INIS)

    Knoop, Martina; Champenois, Caroline; Hagel, Gaetan; Houssin, Marie; Morizot, Olivier; Pedregosa, Jofre; Vedel, Fernande; Vedel, Michel; Marciante, Mathieu; Calisti, A.; Calisti, Annette; Escarguel, Alexandre; Ferri, Sandrine; Godbert-Mouret, Laurence; Koubiti, Mohammed; Marandet, Yannick; Mosse, Caroline; Rosato, Joel; Stamm, Roland; Talin, Bernard; Boland, Denis; Mekkaoui, Abdessamad; Lefevre, Tony; Agullo, Olivier; Benkadda, S.; Beyer, P.; Dubuit, N.; Fuhr, G.; Futatani, S.; Guimarraes, Z.; Muraglia, M.; Pamela, Stanislas; Poye, Alexandre; Solminhac, F. de; Sugita, S.; Voslion, T.; Angot, Thierry; Bisson, Regis; Cartry, Gilles; Layet, Jean-Marc; Salomon, Eric; Areou, Etienne; Ahmad, Ahmad; Singh Katharria, Yashpal; Kumar, Pravin; Engeln, Richard; Abahazem, Alyen; Allouche, Alain; Bisson, R.; Borget, Fabien; Chiavassa, Thierry; Coussan, Stephane; Couturier-Tamburelli, Isabelle; Danger, Gregoire; Duvernay, Fabrice; Ferro, Yves; Marinelli, Francis; Martin, Celine; Morisset, Sabine; Pietri, Nathalie; Pardanaud, Cedric; Roubin, Pascale; Theule, Patrice; Bossa, Jean-Baptiste; Mispelaer, Florent; Ruffe, Remi; Arnas, Cecile; Cherigier-Kovacic, Laurence; Couedel, Lenaic; Claire, Nicolas; Doveil, Fabrice; Elskens, Yves; Escande, Dominique; Escarguel, Alexandre; Bernardi, Pierre; Lejeune, Aurelien

    2010-07-01

    The laboratory 'Physics of ionic and molecular interactions' (PIIM) is a mixed research unit (UMR6633) between the CNRS and the Provence University in Marseille. PIIM is in the Provence region the leading laboratory for the study of dilute matter, and brings together physicists and physico-chemists for studying gases and plasmas, and their interactions with matter and radiation. Our research activities are principally fundamental, and most often mobilize our interdisciplinary talent. They mainly belong to three research axis: atomic physics and radiation, plasma physics, and surface reactivity. The first axis corresponds to fundamental atomic physics experiments performed in ion traps, and to many studies using the atom and ion radiation for diagnosing the gases and plasmas. Experimental and theoretical researches of the dynamic and radiative properties of plasmas constitute the second research axis. The third axis concerns the analysis of reactivity on surfaces in a neutral or ionized environment. PIIM has a permanent staff of 14 CNRS researcher, 36 professors, and 19 engineers or technicians. Our flux of graduate students, postdoctoral fellows is of about twenty. The laboratory provides a management staff, and workshops for mechanics, electronics, instrumentation and computers. We are structured in six research teams developing 12 experiments. Ion confinement and laser manipulations (CIML): The research developed by this team consists in the confinement of ions in an electromagnetic trap. Experiments at the forefront of atomic physics master the confinement of a single ion. A metrology project aims to the achievement of a frequency standard in the optical range. Gas and plasma diagnosis (DGP): The modeling of radiative properties of different types of plasma is the main activity for this team. Numerous national and international collaborations result in the diagnostic of laboratory, astrophysical and thermonuclear fusion plasmas, and in the development of

  14. Molecular screening of compounds to the predicted Protein-Protein Interaction site of Rb1-E7 with p53- E6 in HPV

    Science.gov (United States)

    Shaikh, Faraz; Sanehi, Parvish; Rawal, Rakesh

    2012-01-01

    Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. Human Papillomaviruses (HPVs) which are heterogeneous groups of small double stranded DNA viruses are considered as the primary cause of cervical cancer, involved in 90% of all Cervical Cancers. Two early HPV genes, E6 and E7, are known to play crucial role in tumor formation. E6 binds with p53 and prevents its translocation and thereby inhibit the ability of p53 to activate or repress target genes. E7 binds to hypophosphorylated Rb and thereby induces cells to enter into premature S-phase by disrupting Rb-E2F complexes. The strategy of the research work was to target the site of interaction of Rb1 -E7 & p53-E6. A total of 88 compounds were selected for molecular screening, based on comprehensive literature survey for natural compounds with anti-cancer activity. Molecular docking analysis was carried out with Molegro Virtual Docker, to screen the 88 chosen compounds and rank them according to their binding affinity towards the site of interaction of the viral oncoproteins and human tumor suppressor proteins. The docking result revealed that Nicandrenone a member of Withanolides family of chemical compounds as the most likely molecule that can be used as a candidate drug against HPV induced cervical cancer. Abbreviations HPV - Human Papiloma Virus, HTSP - Human Tumor Suppressor Proteins, VOP - Viral oncoproteins. PMID:22829740

  15. Molecular Interaction Control in Diblock Copolymer Blends and Multiblock Copolymers with Opposite Phase Behaviors

    Science.gov (United States)

    Cho, Junhan

    2014-03-01

    Here we show how to control molecular interactions via mixing AB and AC diblock copolymers, where one copolymer exhibits upper order-disorder transition and the other does lower disorder-order transition. Linear ABC triblock copolymers possessing both barotropic and baroplastic pairs are also taken into account. A recently developed random-phase approximation (RPA) theory and the self-consistent field theory (SCFT) for general compressible mixtures are used to analyze stability criteria and morphologies for the given systems. It is demonstrated that the copolymer systems can yield a variety of phase behaviors in their temperature and pressure dependence upon proper mixing conditions and compositions, which is caused by the delicate force fields generated in the systems. We acknowledge the financial support from National Research Foundation of Korea and Center for Photofunctional Energy Materials.

  16. Surface functionalization of SPR chip for specific molecular interaction analysis under flow condition

    Directory of Open Access Journals (Sweden)

    Tao Ma

    2017-03-01

    Full Text Available Surface functionalization of sensor chip for probe immobilization is crucial for the biosensing applications of surface plasmon resonance (SPR sensors. In this paper, we report a method circulating the dopamine aqueous solution to coat polydopamine film on sensing surface for surface functionalization of SPR chip. The polydopamine film with available thickness can be easily prepared by controlling the circulation time and the biorecognition elements can be immobilized on the polydopamine film for specific molecular interaction analysis. These operations are all performed under flow condition in the fluidic system, and have the advantages of easy implementation, less time consuming, and low cost, because the reagents and devices used in the operations are routinely applied in most laboratories. In this study, the specific absorption between the protein A probe immobilized on the sensing surface and human immunoglobulin G in the buffer is monitored based on this surface functionalization strategy to demonstrated its feasibility for SPR biosensing applications.

  17. Affinity flow fractionation of cells via transient interactions with asymmetric molecular patterns

    Science.gov (United States)

    Bose, Suman; Singh, Rishi; Hanewich-Hollatz, Mikhail; Shen, Chong; Lee, Chia-Hua; Dorfman, David M.; Karp, Jeffrey M.; Karnik, Rohit

    2013-07-01

    Flow fractionation of cells using physical fields to achieve lateral displacement finds wide applications, but its extension to surface molecule-specific separation requires labeling. Here we demonstrate affinity flow fractionation (AFF) where weak, short-range interactions with asymmetric molecular patterns laterally displace cells in a continuous, label-free process. We show that AFF can directly draw neutrophils out of a continuously flowing stream of blood with an unprecedented 400,000-fold depletion of red blood cells, with the sorted cells being highly viable, unactivated, and functionally intact. The lack of background erythrocytes enabled the use of AFF for direct enumeration of neutrophils by a downstream detector, which could distinguish the activation state of neutrophils in blood. The compatibility of AFF with capillary microfluidics and its ability to directly separate cells with high purity and minimal sample preparation will facilitate the design of simple and portable devices for point-of-care diagnostics and quick, cost-effective laboratory analysis.

  18. Kinetics and Thermodynamics of Flexographic-plate Polymer Interaction With Low-molecular Liquids

    Directory of Open Access Journals (Sweden)

    Akaky Dzhvarsheyshvili

    2007-11-01

    Full Text Available Flexographic printing plates contact solvents in the process of their production and operation: washing solvents and printing paint components. As a results of such contact plates swell. Swelling changes polymers’ elastic properties of which the plate is made, changes the scan point sizes that, in the final analysis, affects the printing product quality. The kinetics of swelling flexographic plate polymer interaction with low-molecular liquids used in the process of plate production and operation was studied. Constants of speed, parameters Flory - Huggins, diffusion coefficient D for each solvent was determined. The changes of the basic thermodynamic functions ΔG, ΔS, ΔH of swelling, are calculated. The received data allow to choose the optimum solvents for processes of polygraphic technology.

  19. Polyphilic Interactions as Structural Driving Force Investigated by Molecular Dynamics Simulation (Project 7

    Directory of Open Access Journals (Sweden)

    Christopher Peschel

    2017-09-01

    Full Text Available We investigated the effect of fluorinated molecules on dipalmitoylphosphatidylcholine (DPPC bilayers by force-field molecular dynamics simulations. In the first step, we developed all-atom force-field parameters for additive molecules in membranes to enable an accurate description of those systems. On the basis of this force field, we performed extensive simulations of various bilayer systems containing different additives. The additive molecules were chosen to be of different size and shape, and they included small molecules such as perfluorinated alcohols, but also more complex molecules. From these simulations, we investigated the structural and dynamic effects of the additives on the membrane properties, as well as the behavior of the additive molecules themselves. Our results are in good agreement with other theoretical and experimental studies, and they contribute to a microscopic understanding of interactions, which might be used to specifically tune membrane properties by additives in the future.

  20. Molecular interaction of acetylcholinesterase with carnosic acid derivatives: a neuroinformatics study.

    Science.gov (United States)

    Merad, M; Soufi, W; Ghalem, S; Boukli, F; Baig, M H; Ahmad, K; Kamal, Mohammad A

    2014-04-01

    Alzheimer's disease is a progressive degenerative disease of the brain marked by gradual and irreversible declines in cognitive functions. Acetylcholinesterase (AChE) plays a biological role in the termination of nerve impulse transmissions at cholinergic synapses by rapid hydrolysis of its substrate, "acetylcholine". The deficit level of acetylcholine leads to deprived nerve impulse transmission. Thus the cholinesterase inhibitors would reverse the deficit in acetylcholine level and consequently may reverse the memory impairments, which is characteristic of the Alzheimer's disease. The molecular interactions between AChE and Carnosic acid, a well known antioxidant substance found in the leaves of the rosemary plant has always been an area of interest. Here in this study we have performed in silico approach to identify carnosic acid derivatives having the potential of being a possible drug candidate against AChE. The best candidates were selected on the basis of the results of different scoring functions.

  1. On the origin of the hydration interaction of LIPID bilayers from molecular dynamics simulations

    International Nuclear Information System (INIS)

    Essmann, U.; Perera, L.; Berkowitz, M.L.

    1996-01-01

    To understand the nature of the hydration forces acting between biomembranes we performed computer simulations on DLPE/water and DPPC/water systems in liquid crystalline and gel phases. The simulations show that the influence of the membrane surface on water properties is detectable only over a short range and that the membrane surfaces are rough on the molecular scale. We find that the hydration force is due to (a) the removal of only one or two layers of solvating water from the membrane surface and (b) steric interactions. The detailed structure of the solvating water is responsible for the difference in the hydration force acting between DLPE membranes compared to DPPC membranes

  2. Thermo-acoustical molecular interaction study in binary mixtures of glycerol and ethylene glycol

    Science.gov (United States)

    Kaur, Kirandeep; Juglan, K. C.; Kumar, Harsh

    2017-07-01

    Ultrasonic velocity, density and viscosity are measured over the entire composition range for binary liquid mixtures of glycerol (CH2OH-CHOH-CH2OH) and ethylene glycol (HOCH2CH2OH) at different temperatures and constant frequency of 2MHz using ultrasonic interferometer, specific gravity bottle and viscometer respectively. Measured experimental values are used to obtained various acoustical parameters such as adiabatic compressibility, acoustic impedance, intermolecular free length, relaxation time, ultrasonic attenuation, effective molar weight, free volume, available volume, molar volume, Wada's constant, Rao's constant, Vander Waal's constant, internal pressure, Gibb's free energy and enthalpy. The variation in acoustical parameters are interpreted in terms of molecular interactions between the components of molecules of binary liquid mixtures.

  3. Nuclear magnetic resonance studies of conformations and molecular interactions in lyotropic mesophases - Applications to solubilization problems

    International Nuclear Information System (INIS)

    Caniparoli, Jean-Philippe

    1988-01-01

    After having determined the structural properties of smectic liquid crystals made from double chain surfactants/water binary systems, residual anisotropic interactions and relaxation times measurements were used to investigate the molecular ordering. Phosphorus, deuterium and nitrogen NMR of the surfactant molecules evidenced their high degree of order and the strong anisotropy of their motions. Quantitative results depended on the surfactant polar head -phosphate or ammonium-, while they displayed little variations with the hydrocarbon tail size. The marked dependence of the order and dynamics of small solutes in a lamellar phase on their hydrophilic or hydrophobic behaviour was shown using the same methods. By means of para-magnetically induced relaxation, it was proved that the non-polar solute benzene is located in the organic domain of the liquid crystalline matrix. (author) [fr

  4. Improved Discovery of Molecular Interactions in Genome-Scale Data with Adaptive Model-Based Normalization

    Science.gov (United States)

    Brown, Patrick O.

    2013-01-01

    Background High throughput molecular-interaction studies using immunoprecipitations (IP) or affinity purifications are powerful and widely used in biology research. One of many important applications of this method is to identify the set of RNAs that interact with a particular RNA-binding protein (RBP). Here, the unique statistical challenge presented is to delineate a specific set of RNAs that are enriched in one sample relative to another, typically a specific IP compared to a non-specific control to model background. The choice of normalization procedure critically impacts the number of RNAs that will be identified as interacting with an RBP at a given significance threshold – yet existing normalization methods make assumptions that are often fundamentally inaccurate when applied to IP enrichment data. Methods In this paper, we present a new normalization methodology that is specifically designed for identifying enriched RNA or DNA sequences in an IP. The normalization (called adaptive or AD normalization) uses a basic model of the IP experiment and is not a variant of mean, quantile, or other methodology previously proposed. The approach is evaluated statistically and tested with simulated and empirical data. Results and Conclusions The adaptive (AD) normalization method results in a greatly increased range in the number of enriched RNAs identified, fewer false positives, and overall better concordance with independent biological evidence, for the RBPs we analyzed, compared to median normalization. The approach is also applicable to the study of pairwise RNA, DNA and protein interactions such as the analysis of transcription factors via chromatin immunoprecipitation (ChIP) or any other experiments where samples from two conditions, one of which contains an enriched subset of the other, are studied. PMID:23349766

  5. Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.

    Science.gov (United States)

    Han, Chang Woo; Jeong, Mi Suk; Jang, Se Bok

    2017-09-16

    Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines. However, the specific molecular mechanism by which H-REV107 inhibits Ras is still unknown. In the present study, we suggest that H-REV107 forms a strong complex with activating oncogenic mutation Q61H K-Ras from various biochemical binding assays and modeled structures. In addition, the interaction sites between K-Ras and H-REV107 were predicted based on homology modeling. Here, we found that some structure-based mutants of the K-Ras disrupted the complex formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Molecular interaction and energy transfer between human serum albumin and bioactive component Aloe dihydrocoumarin

    Science.gov (United States)

    Zhang, Xiu-Feng; Xie, Ling; Liu, Yang; Xiang, Jun-Feng; Li, Lin; Tang, Ya-Lin

    2008-10-01

    Aloe dihydrocoumarin is an antioxidant and a candidate of immunomodulatory drug on the immune system and can balance physiological reactive oxygen species (ROS) levels which may be useful to maintain homeostasis. In order to explore the mechanism of drug action at a molecular level, the binding of Aloe dihydrocoumarin with human serum albumin (HSA) has been investigated by fluorescence, ultraviolet (UV), circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy, fluorescence dynamics, and molecular dynamic docking for the first time. We observed a quenching of fluorescence of HSA in the presence of Aloe dihydrocoumarin and also analyzed the quenching results using the Stern-Volmer equation and obtained high affinity binding to HSA. A Förster type fluorescence resonance energy transfer mechanism is involved in this quenching of Trp fluorescence by Aloe dihydrocoumarin. From the CD and FT-IR results, it is apparent that the interaction of Aloe dihydrocoumarin with HSA causes a conformational change of the protein, with the loss of α-helix stability and the gain of β-sheet and β-turn content. Data obtained by fluorescence spectroscopy, fluorescence dynamics, CD, and FT-IR experiments along with the docking studies suggest that Aloe dihydrocoumarin binds to residues located in subdomain IIA of HSA.

  7. Circadian Rhythms in Fear Conditioning: An Overview of Behavioral, Brain System, and Molecular Interactions

    Directory of Open Access Journals (Sweden)

    Anne Albrecht

    2017-01-01

    Full Text Available The formation of fear memories is a powerful and highly evolutionary conserved mechanism that serves the behavioral adaptation to environmental threats. Accordingly, classical fear conditioning paradigms have been employed to investigate fundamental molecular processes of memory formation. Evidence suggests that a circadian regulation mechanism allows for a timestamping of such fear memories and controlling memory salience during both their acquisition and their modification after retrieval. These mechanisms include an expression of molecular clocks in neurons of the amygdala, hippocampus, and medial prefrontal cortex and their tight interaction with the intracellular signaling pathways that mediate neural plasticity and information storage. The cellular activities are coordinated across different brain regions and neural circuits through the release of glucocorticoids and neuromodulators such as acetylcholine, which integrate circadian and memory-related activation. Disturbance of this interplay by circadian phase shifts or traumatic experience appears to be an important factor in the development of stress-related psychopathology, considering these circadian components are of critical importance for optimizing therapeutic approaches to these disorders.

  8. Dissecting the molecular interactions between wheat and the fungal pathogen Zymoseptoria tritici

    Directory of Open Access Journals (Sweden)

    Graeme James Kettles

    2016-04-01

    Full Text Available The Dothideomycete fungus Zymoseptoria tritici (previously known as Mycosphaerella graminicola and Septoria tritici is the causative agent of Septoria tritici leaf blotch (STB disease of wheat (Triticum aestivum L.. In Europe, STB is the most economically damaging disease of wheat, with an estimated ~€1 billion per year in fungicide expenditure directed towards its control. Here, an overview of our current understanding of the molecular events that occur during Z. tritici infection of wheat leaves is presented. On the host side, this includes the contribution of (1 the pathogen-associated molecular pattern-triggered immunity (PTI layer of the plant defence, and (2 major Stb resistance loci to Z. tritici resistance. On the pathogen side of the interaction, we consolidate evidence from recent bioinformatic, transcriptomic and proteomic studies that begin to explain the contribution of Z. tritici effector proteins to the biphasic lifestyle of the fungus. This includes the discovery of chitin-binding proteins in the Z. tritici secretome, which contribute to evasion of immune surveillance by this pathogen, and the possible existence of ‘necrotrophic’ effectors from Z. tritici, which may actively stimulate host recognition in a manner similar to related necrotrophic fungal pathogens. We finish by speculating on how some of these recent fundamental discoveries might be harnessed to help improve resistance to STB in the world’s second largest food crop.

  9. Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mehranfar, Fahimeh [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Bordbar, Abdol-Khalegh, E-mail: bordbar@chem.ui.ac.ir [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Keyhanfar, Mehrnaz; Behbahani, Mandana [Faculty of Advanced Sciences and Technologies, Department of Biotechnology, University of Isfahan, Isfahan, 81746-73441 (Iran, Islamic Republic of)

    2013-11-15

    The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC. -- Highlights: • BDMC binds to the hydrophobic core of β-casein. • The effective encapsulation of BDMC in β-casein micelle nanoparticles was shown. • Enhanced cytotoxicity was observed for encapsulated BDMC in β-casein nanoparticles.

  10. Clavibacter michiganensis ssp. michiganensis: bacterial canker of tomato, molecular interactions and disease management.

    Science.gov (United States)

    Nandi, Munmun; Macdonald, Jacqueline; Liu, Peng; Weselowski, Brian; Yuan, Ze-Chun

    2018-03-12

    Bacterial canker disease is considered to be one of the most destructive diseases of tomato (Solanum lycopersicum), and is caused by the seed-borne Gram-positive bacterium Clavibacter michiganensis ssp. michiganensis (Cmm). This vascular pathogen generally invades and proliferates in the xylem through natural openings or wounds, causing wilt and canker symptoms. The incidence of symptomless latent infections and the invasion of tomato seeds by Cmm are widespread. Pathogenicity is mediated by virulence factors and transcriptional regulators encoded by the chromosome and two natural plasmids. The virulence factors include serine proteases, cell wall-degrading enzymes (cellulases, xylanases, pectinases) and others. Mutational analyses of these genes and gene expression profiling (via quantitative reverse transcription-polymerase chain reaction, transcriptomics and proteomics) have begun to shed light on their roles in colonization and virulence, whereas the expression of tomato genes in response to Cmm infection suggests plant factors involved in the defence response. These findings may aid in the generation of target-specific bactericides or new resistant varieties of tomato. Meanwhile, various chemical and biological controls have been researched to control Cmm. This review presents a detailed investigation regarding the pathogen Cmm, bacterial canker infection, molecular interactions between Cmm and tomato, and current perspectives on improved disease management. © 2018 AGRICULTURE AND AGRI-FOOD CANADA. MOLECULAR PLANT PATHOLOGY © 2018 JOHN WILEY & SONS LTD.

  11. Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

    International Nuclear Information System (INIS)

    Mehranfar, Fahimeh; Bordbar, Abdol-Khalegh; Keyhanfar, Mehrnaz; Behbahani, Mandana

    2013-01-01

    The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC. -- Highlights: • BDMC binds to the hydrophobic core of β-casein. • The effective encapsulation of BDMC in β-casein micelle nanoparticles was shown. • Enhanced cytotoxicity was observed for encapsulated BDMC in β-casein nanoparticles

  12. Interactions between Nanoparticles and Polymer Brushes: Molecular Dynamics Simulations and Self-consistent Field Theory Calculations

    Science.gov (United States)

    Cheng, Shengfeng; Wen, Chengyuan; Egorov, Sergei

    2015-03-01

    Molecular dynamics simulations and self-consistent field theory calculations are employed to study the interactions between a nanoparticle and a polymer brush at various densities of chains grafted to a plane. Simulations with both implicit and explicit solvent are performed. In either case the nanoparticle is loaded to the brush at a constant velocity. Then a series of simulations are performed to compute the force exerted on the nanoparticle that is fixed at various distances from the grafting plane. The potential of mean force is calculated and compared to the prediction based on a self-consistent field theory. Our simulations show that the explicit solvent leads to effects that are not captured in simulations with implicit solvent, indicating the importance of including explicit solvent in molecular simulations of such systems. Our results also demonstrate an interesting correlation between the force on the nanoparticle and the density profile of the brush. We gratefully acknowledge the support of NVIDIA Corporation with the donation of the Tesla K40 GPU used for this research.

  13. Thermal characterization of static and dynamical properties of the confined molecular systems interacting through dispersion force.

    Science.gov (United States)

    Ramos, Sergio Luis L M; Ogino, Michihiko; Oguni, Masaharu

    2015-01-28

    We investigated the thermal properties of liquid methylcyclohexane and racemic sec-butylcyclohexane, as representatives of a molecular system with only dispersion-force intermolecular interactions, confined in the pores (thickness/diameter d = 12, 6, 1.1 nm) of silica gels by adiabatic calorimetry. The results imply a heterogeneous picture for molecular aggregate under confinement consisting of an interfacial region and an inner pore one. In the vicinity of a glass-transition temperature T(g,bulk) of bulk liquid, two distinguishable relaxation phenomena were observed for the confined systems and their origins were attributed to the devitrification, namely glass transition, processes of (1) a layer of interfacial molecules adjacent to the pore walls and (2) the molecules located in the middle of the pore. A third glass-transition phenomenon was observed at lower temperatures and ascribed to a secondary relaxation process. The glass transition of the interfacial-layer molecules was found to proceed at temperatures rather above T(g,bulk), whereas that of the molecules located in the inner pore region occurred at temperatures below T(g,bulk). We discuss the reason why the molecules located in different places in the pores reveal the respectively different dynamical properties.

  14. Noncovalent Intermolecular Interactions in Organic Electronic Materials: Implications for the Molecular Packing vs Electronic Properties of Acenes

    KAUST Repository

    Sutton, Christopher

    2015-10-30

    Noncovalent intermolecular interactions, which can be tuned through the toolbox of synthetic chemistry, determine not only the molecular packing but also the resulting electronic, optical, and mechanical properties of materials derived from π-conjugated molecules, oligomers, and polymers. Here, we provide an overview of the theoretical underpinnings of noncovalent intermolecular interactions and briefly discuss the computational chemistry approaches used to understand the magnitude of these interactions. These methodologies are then exploited to illustrate how noncovalent intermolecular interactions impact important electronic properties-such as the electronic coupling between adjacent molecules, a key parameter for charge-carrier transport-through a comparison between the prototype organic semiconductor pentacene with a series of N-substituted heteropentacenes. Incorporating an understanding of these interactions into the design of organic semiconductors can assist in developing novel materials systems from this fascinating molecular class. © 2015 American Chemical Society.

  15. A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors.

    Science.gov (United States)

    Wang, Luqiao; Nanayakkara, Gayani; Yang, Qian; Tan, Hongmei; Drummer, Charles; Sun, Yu; Shao, Ying; Fu, Hangfei; Cueto, Ramon; Shan, Huimin; Bottiglieri, Teodoro; Li, Ya-Feng; Johnson, Candice; Yang, William Y; Yang, Fan; Xu, Yanjie; Xi, Hang; Liu, Weiqing; Yu, Jun; Choi, Eric T; Cheng, Xiaoshu; Wang, Hong; Yang, Xiaofeng

    2017-10-24

    Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood. To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions. We made the following significant findings: (1) NRs are differentially expressed in tissues, which may be under regulation by oxygen sensors, angiogenesis pathway, stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation indexes; (2) NR sequence mutations are associated with increased risks for development of cancers and metabolic, cardiovascular, and autoimmune diseases; (3) NRs have less tendency to be upregulated than downregulated in cancers, and autoimmune and metabolic diseases, which may be regulated by inflammation pathways and mitochondrial energy enzymes; and (4) the innate immune sensor inflammasome/caspase-1 pathway regulates the expression of most NRs. Based on our findings, we propose a new paradigm that most nuclear receptors are anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs). Our results have provided a novel insight on NRs as therapeutic targets in metabolic diseases, inflammations, and malignancies.

  16. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

    2015-01-01

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

  17. The Molecular Basis of Toxins’ Interactions with Intracellular Signaling via Discrete Portals

    Directory of Open Access Journals (Sweden)

    Adi Lahiani

    2017-03-01

    Full Text Available An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking. In this review, specific examples of different toxins are emphasized to illustrate the fundamental mechanisms of toxicity at different biochemical, molecular and cellular- levels with particular consideration for the nervous system. The target of primary action has been highlighted and operationally classified into 13 sub-categories. Selected examples of toxins were assigned to each target category, denominated as portal, and the modulation of the different portal’s signaling was featured. The first portal encompasses the plasma membrane lipid domains, which give rise to pores when challenged for example with pardaxin, a fish toxin, or is subject to degradation when enzymes of lipid metabolism such as phospholipases A2 (PLA2 or phospholipase C (PLC act upon it. Several major portals consist of ion channels, pumps, transporters and ligand gated ionotropic receptors which many toxins act on, disturbing the intracellular ion homeostasis. Another group of portals consists of G-protein-coupled and tyrosine kinase receptors that, upon interaction with discrete toxins, alter second messengers towards pathological levels. Lastly, subcellular organelles such as mitochondria, nucleus, protein- and RNA-synthesis machineries, cytoskeletal networks and exocytic vesicles are also portals targeted and deregulated by other diverse group of toxins. A fundamental concept can be drawn from these seemingly different

  18. TCM grammar systems: an approach to aid the interpretation of the molecular interactions in Chinese herbal medicine.

    Science.gov (United States)

    Yan, Jing; Wang, Yun; Luo, Si-Jun; Qiao, Yan-Jiang

    2011-09-01

    Interpreting the molecular interactions in Chinese herbal medicine will help to understand the molecular mechanisms of Traditional Chinese medicines (TCM) and predict the new pharmacological effects of TCM. Yet, we still lack a method which could integrate the concerned pieces of parsed knowledge about TCM. To solve the problem, a new method named TCM grammar systems was proposed in the present article. The possibility to study the interactions of TCM at the molecular level using TCM grammar systems was explored using Herba Ephedrae Decoction (HED) as an example. A platform was established based on the formalism of TCM grammar systems. The related molecular network of Herba Ephedrae Decoction (HED) can be extracted automatically. The molecular network indicates that Beta2 adrenergic receptor, Glucocorticoid receptor and Interleukin12 are the relatively important targets for the anti-anaphylaxis asthma function of HED. Moreover, the anti-anaphylaxis asthma function of HED is also related with suppressing inflammation process. The results show the feasibility using TCM grammar systems to interpret the molecular mechanism of TCM. Although the results obtained depend on the database absolutely, recombination of existing knowledge in this method provides new insight for interpreting the molecular mechanism of TCM. TCM grammar systems could aid the interpretation of the molecular interactions in TCM to some extent. Moreover, it might be useful to predict the new pharmacological effects of TCM. The method is an in silico technology. In association with the experimental techniques, this method will play an important role in the understanding of the molecular mechanisms of TCM. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. HitPredict version 4: comprehensive reliability scoring of physical protein-protein interactions from more than 100 species.

    Science.gov (United States)

    López, Yosvany; Nakai, Kenta; Patil, Ashwini

    2015-01-01

    HitPredict is a consolidated resource of experimentally identified, physical protein-protein interactions with confidence scores to indicate their reliability. The study of genes and their inter-relationships using methods such as network and pathway analysis requires high quality protein-protein interaction information. Extracting reliable interactions from most of the existing databases is challenging because they either contain only a subset of the available interactions, or a mixture of physical, genetic and predicted interactions. Automated integration of interactions is further complicated by varying levels of accuracy of database content and lack of adherence to standard formats. To address these issues, the latest version of HitPredict provides a manually curated dataset of 398 696 physical associations between 70 808 proteins from 105 species. Manual confirmation was used to resolve all issues encountered during data integration. For improved reliability assessment, this version combines a new score derived from the experimental information of the interactions with the original score based on the features of the interacting proteins. The combined interaction score performs better than either of the individual scores in HitPredict as well as the reliability score of another similar database. HitPredict provides a web interface to search proteins and visualize their interactions, and the data can be downloaded for offline analysis. Data usability has been enhanced by mapping protein identifiers across multiple reference databases. Thus, the latest version of HitPredict provides a significantly larger, more reliable and usable dataset of protein-protein interactions from several species for the study of gene groups. Database URL: http://hintdb.hgc.jp/htp. © The Author(s) 2015. Published by Oxford University Press.

  20. Reactivities of some thiol collectors and their interactions with Ag (+1) ion by molecular modeling

    International Nuclear Information System (INIS)

    Yekeler, Hulya; Yekeler, Meftuni

    2004-01-01

    The most commonly used collectors for sulfide minerals in the mining industry are the thiol collectors for the recovery of these minerals from their associated gangues by froth flotation. For this reason, a great deal of attention has been paid to understand the attachment mechanism of thiol collectors to metal sulfide surfaces. The density functional theory (DFT) calculations at the B3LYP/3-21G* and B3LYP/6-31++G** levels were employed to propose the flotation responses of these thiol collectors, namely, diethyl dithiocarbamate, ethyl dithiocarbamate, ethyl dithiocarbonate, ethyl trithiocarbonate and ethyl dithiophosphate ions, and to study the interaction energies of these collectors with Ag (+1) ion in connection to acanthite (Ag 2 S) mineral. The calculated interaction energies, ΔE, were interpreted in terms of the highest occupied molecular orbital (HOMO) energies of the isolated collector ions. The results show that the HOMOs are strongly localized to the sulfur atoms and the HOMO energies can be used as a reactivity descriptor for the flotation ability of the thiol collectors. Using the HOMO and ΔE energies, the reactivity order of the collectors is found to be (C 2 H 5 ) 2 NCS 2 - > C 2 H 5 NHCS 2 - > C 2 H 5 OCS 2 - > C 2 H 5 SCS 2 - > (C 2 H 5 O)(OH)PS 2 - . The theoretically obtained results are in good agreement with the experimental data reported

  1. Anandamide-ceramide interactions in a membrane environment: Molecular dynamic simulations data.

    Science.gov (United States)

    Di Scala, Coralie; Mazzarino, Morgane; Yahi, Nouara; Varini, Karine; Garmy, Nicolas; Fantini, Jacques; Chahinian, Henri

    2017-10-01

    Anandamide is a lipid neurotransmitter that interacts with various plasma membrane lipids. The data here consists of molecular dynamics simulations of anandamide, C18-ceramide and cholesterol performed in vacuo and within a hydrated palmitoyl-oleoyl-phosphatidylcholine (POPC)/cholesterol membrane. Several models of anandamide/cholesterol and anandamide/ceramide complexes are presented. The energy of interaction and the nature of the intermolecular forces involved in each of these complexes are detailed. The impact of water molecules hydrating the POPC/cholesterol membrane for the stability of the anandamide/cholesterol and anandamide/ceramide complexes is also analyzed. From a total number of 1920 water molecules stochatiscally merged with the lipid matrix, 48 were eventually redistributed around the polar head groups of the anandamide/ceramide complex, whereas only 15 reached with the anandamide/cholesterol complex. The interpretation of this dataset is presented in the accompanying article "Ceramide binding to anandamide increases its half-life and potentiates its cytotoxicity in human neuroblastoma cells" [1].

  2. Molecular Determinants for Substrate Interactions with the Glycine Transporter GlyT2.

    Science.gov (United States)

    Carland, Jane E; Thomas, Michael; Mostyn, Shannon N; Subramanian, Nandhitha; O'Mara, Megan L; Ryan, Renae M; Vandenberg, Robert J

    2018-03-21

    Transporters in the SLC6 family play key roles in regulating neurotransmission and are the targets for a wide range of therapeutics. Important insights into the transport mechanisms and the specificity of drug interactions of SLC6 transporters have been obtained from the crystal structures of a bacterial homologue of the family, LeuT Aa , and more recently the Drosophila dopamine transporter and the human serotonin transporter. However, there is disputed evidence that the bacterial leucine transporter, LeuT Aa , contains two substrate binding sites that work cooperatively in the mechanism of transport, with the binding of a second substrate being required for the release of the substrate from the primary site. An alternate proposal is that there may be low affinity binding sites that serve to direct the flow of substrates to the primary site. We have used a combination of molecular dynamics simulations of substrate interactions with a homology model of GlyT2, together with radiolabeled amino acid uptake assays and electrophysiological analysis of wild-type and mutant transporters, to provide evidence that substrate selectivity of GlyT2 is determined entirely by the primary substrate binding site and, furthermore, if a secondary site exists then it is a low affinity nonselective amino acid binding site.

  3. Molecular Modeling of Myrosinase from Brassica oleracea: A Structural Investigation of Sinigrin Interaction

    Directory of Open Access Journals (Sweden)

    Sathishkumar Natarajan

    2015-12-01

    Full Text Available Myrosinase, which is present in cruciferous plant species, plays an important role in the hydrolysis of glycosides such as glucosinolates and is involved in plant defense. Brassicaceae myrosinases are diverse although they share common ancestry, and structural knowledge about myrosinases from cabbage (Brassica oleracea was needed. To address this, we constructed a three-dimensional model structure of myrosinase based on Sinapis alba structures using Iterative Threading ASSEmbly Refinement server (I-TASSER webserver, and refined model coordinates were evaluated with ProQ and Verify3D. The resulting model was predicted with β/α fold, ten conserved N-glycosylation sites, and three disulfide bridges. In addition, this model shared features with the known Sinapis alba myrosinase structure. To obtain a better understanding of myrosinase–sinigrin interaction, the refined model was docked using Autodock Vina with crucial key amino acids. The key nucleophile residues GLN207 and GLU427 were found to interact with sinigrin to form a hydrogen bond. Further, 20-ns molecular dynamics simulation was performed to examine myrosinase–sinigrin complex stability, revealing that residue GLU207 maintained its hydrogen bond stability throughout the entire simulation and structural orientation was similar to that of the docked state. This conceptual model should be useful for understanding the structural features of myrosinase and their binding orientation with sinigrin.

  4. Analytic nuclear forces and molecular properties from full configuration interaction quantum Monte Carlo

    International Nuclear Information System (INIS)

    Thomas, Robert E.; Overy, Catherine; Opalka, Daniel; Alavi, Ali; Knowles, Peter J.; Booth, George H.

    2015-01-01

    Unbiased stochastic sampling of the one- and two-body reduced density matrices is achieved in full configuration interaction quantum Monte Carlo with the introduction of a second, “replica” ensemble of walkers, whose population evolves in imaginary time independently from the first and which entails only modest additional computational overheads. The matrices obtained from this approach are shown to be representative of full configuration-interaction quality and hence provide a realistic opportunity to achieve high-quality results for a range of properties whose operators do not necessarily commute with the Hamiltonian. A density-matrix formulated quasi-variational energy estimator having been already proposed and investigated, the present work extends the scope of the theory to take in studies of analytic nuclear forces, molecular dipole moments, and polarisabilities, with extensive comparison to exact results where possible. These new results confirm the suitability of the sampling technique and, where sufficiently large basis sets are available, achieve close agreement with experimental values, expanding the scope of the method to new areas of investigation

  5. Entanglement loss in molecular quantum-dot qubits due to interaction with the environment

    Science.gov (United States)

    Blair, Enrique P.; Tóth, Géza; Lent, Craig S.

    2018-05-01

    We study quantum entanglement loss due to environmental interaction in a condensed matter system with a complex geometry relevant to recent proposals for computing with single electrons at the nanoscale. We consider a system consisting of two qubits, each realized by an electron in a double quantum dot, which are initially in an entangled Bell state. The qubits are widely separated and each interacts with its own environment. The environment for each is modeled by surrounding double quantum dots placed at random positions with random orientations. We calculate the unitary evolution of the joint system and environment. The global state remains pure throughout. We examine the time dependence of the expectation value of the bipartite Clauser–Horne–Shimony–Holt (CHSH) and Brukner–Paunković–Rudolph–Vedral (BPRV) Bell operators and explore the emergence of correlations consistent with local realism. Though the details of this transition depend on the specific environmental geometry, we show how the results can be mapped on to a universal behavior with appropriate scaling. We determine the relevant disentanglement times based on realistic physical parameters for molecular double-dots.

  6. Molecular interactions of mussel protective coating protein, mcfp-1, from Mytilus californianus.

    Science.gov (United States)

    Lu, Qingye; Hwang, Dong Soo; Liu, Yang; Zeng, Hongbo

    2012-02-01

    Protective coating of the byssus of mussels (Mytilus sp.) has been suggested as a new paradigm of medical coating due to its high extensibility and hardness co-existence without their mutual detriment. The only known biomacromolecule in the extensible and tough coating on the byssus is mussel foot protein-1 (mfp-1), which is made up with positively charged residues (~20 mol%) and lack of negatively charged residues. Here, adhesion and molecular interaction mechanisms of Mytilus californianus foot protein-1 (mcfp-1) from California blue mussel were investigated using a surface forces apparatus (SFA) in buffer solutions of different ionic concentrations (0.2-0.7 M) and pHs (3.0-5.5). Strong and reversible cohesion between opposed positively charged mcfp-1 films was measured in 0.1 M sodium acetate buffer with 0.1 M KNO(3). Cohesion of mcfp-1 was gradually reduced with increasing the ionic strength, but was not changed with pH variations. Oxidation of 3,4-dihydroxyphenylalanine (DOPA) residues of mcfp-1, a key residue for adhesive and coating proteins of mussel, didn't change the cohesion strength of mcfp-1 films, but the addition of chemicals with aromatic groups (i.e., aspirin and 4-methylcatechol) increased the cohesion. These results suggest that the cohesion of mcfp-1 films is mainly mediated by cation-π interactions between the positively charged residues and benzene rings of DOPA and other aromatic amino acids (~20 mol% of total amino acids of mcfp-1), and π-π interactions between the phenyl groups in mcfp-1. The adhesion mechanism obtained for the mcfp-1 proteins provides important insight into the design and development of functional biomaterials and coatings mimicking the extensible and robust mussel cuticle coating. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Single NdPc{sub 2} molecules on surfaces. Adsorption, interaction, and molecular magnetism

    Energy Technology Data Exchange (ETDEWEB)

    Fahrendorf, Sarah

    2013-01-24

    They have huge potential for application in molecular-spin-transistors, molecular-spinvalves, and molecular quantum computing. SMMs are characterized by high spin ground states with zero-field splitting leading to high relaxation barriers and long relaxation times. A relevant class of molecules are the lanthanide double-decker phthalocyanines (LaPc{sub 2}) with only one metal atom sandwiched between two organic phthalocyanine (Pc) ligands. For envisaged spintronic applications it is important to understand the interaction between the molecules and the substrate and its influence on the electronic and magnetic properties. The subject of this thesis is the investigation of the adsorbed neodymium double-decker phthalocyanine (NdPc{sub 2}) by means of low temperature scanning tunneling microscopy and spectroscopy (STM and STS). The molecules are deposited by sublimation onto different substrates. It is observed that a large fraction of the double-decker molecules decomposes during deposition. The decomposition probability strongly depends on the chosen substrate. Therefore it is concluded that the substrate modifies the electronic structure of the molecule leading to a stabilization or destabilization of the molecular entity. Charge transfer from the surface to the molecule is identified as a potential stabilizing mechanism. The electronic and magnetic properties are investigated in detail for adsorbed NdPc{sub 2} molecules on Cu(100). The results of the experimental study are compared to state-of-the-art density functional theory calculations performed by our colleagues from the Peter Gruenberg Institute (PGI-1) at the Forschungszentrum Juelich. Interestingly, the lower Pc ring of the molecule hybridizes intensely with the substrate leading to strong chemisorption of the molecule, while the upper Pc ring keeps its molecular type electronic states, which can be energetically shifted by an external electric field. Importantly, it is possible to get direct access to the

  8. Single NdPc2 molecules on surfaces. Adsorption, interaction, and molecular magnetism

    International Nuclear Information System (INIS)

    Fahrendorf, Sarah

    2013-01-01

    They have huge potential for application in molecular-spin-transistors, molecular-spinvalves, and molecular quantum computing. SMMs are characterized by high spin ground states with zero-field splitting leading to high relaxation barriers and long relaxation times. A relevant class of molecules are the lanthanide double-decker phthalocyanines (LaPc 2 ) with only one metal atom sandwiched between two organic phthalocyanine (Pc) ligands. For envisaged spintronic applications it is important to understand the interaction between the molecules and the substrate and its influence on the electronic and magnetic properties. The subject of this thesis is the investigation of the adsorbed neodymium double-decker phthalocyanine (NdPc 2 ) by means of low temperature scanning tunneling microscopy and spectroscopy (STM and STS). The molecules are deposited by sublimation onto different substrates. It is observed that a large fraction of the double-decker molecules decomposes during deposition. The decomposition probability strongly depends on the chosen substrate. Therefore it is concluded that the substrate modifies the electronic structure of the molecule leading to a stabilization or destabilization of the molecular entity. Charge transfer from the surface to the molecule is identified as a potential stabilizing mechanism. The electronic and magnetic properties are investigated in detail for adsorbed NdPc 2 molecules on Cu(100). The results of the experimental study are compared to state-of-the-art density functional theory calculations performed by our colleagues from the Peter Gruenberg Institute (PGI-1) at the Forschungszentrum Juelich. Interestingly, the lower Pc ring of the molecule hybridizes intensely with the substrate leading to strong chemisorption of the molecule, while the upper Pc ring keeps its molecular type electronic states, which can be energetically shifted by an external electric field. Importantly, it is possible to get direct access to the spin

  9. Comprehensive Characterization of Minichromosome Maintenance Complex (MCM) Protein Interactions Using Affinity and Proximity Purifications Coupled to Mass Spectrometry.

    Science.gov (United States)

    Dubois, Marie-Line; Bastin, Charlotte; Lévesque, Dominique; Boisvert, François-Michel

    2016-09-02

    The extensive identification of protein-protein interactions under different conditions is an important challenge to understand the cellular functions of proteins. Here we use and compare different approaches including affinity purification and purification by proximity coupled to mass spectrometry to identify protein complexes. We explore the complete interactome of the minichromosome maintenance (MCM) complex by using both approaches for all of the different MCM proteins. Overall, our analysis identified unique and shared interaction partners and proteins enriched for distinct biological processes including DNA replication, DNA repair, and cell cycle regulation. Furthermore, we mapped the changes in protein interactions of the MCM complex in response to DNA damage, identifying a new role for this complex in DNA repair. In summary, we demonstrate the complementarity of these approaches for the characterization of protein interactions within the MCM complex.

  10. Effects of nonfiction guided interactive read-alouds and think-alouds on fourth grader's depth of content area science vocabulary knowledge and comprehension

    Science.gov (United States)

    Hanna, Tania Tamara

    Effects of nonfiction guided interactive read-alouds and think-alouds as a supplement to basal science textbooks on three vocabulary measures, definitions, examples, and characteristics, and one multiple-choice comprehension measure were assessed for 127 fourth graders over three time periods: pretest, posttest, and a 2-week delayed posttest. Two of three fourth-grade elementary science teachers implemented a series of 12 content-enhanced guided interactive scripted lessons. Two of these teachers implemented two treatments each. The first condition employed basal science textbooks as the text for guided interactive read-alouds and think-alouds while the second treatment employed basal science textbooks in conjunction with nonfiction text sets as the texts for guided interactive read-alouds and think-alouds. The third teacher, guided by traditional lesson plans, provided students with silent independent reading instruction using basal science textbooks. Multivariate analyses of variance and analyses of variance tests showed that mean scores for both treatment groups significantly improved on definitions and characteristics measures at posttest and either stabilized or slightly declined at delayed posttest. The treatment-plus group lost considerably on the examples posttest measure. The treatment group improved mean scores on the examples posttest measure, outperforming the treatment-plus group and the control group. Alternately, the control group significantly improved on the delayed posttest examples measure. Additionally, the two groups implementing guided interactive read-alouds and think-alouds performed better than the independent reading group on multiple-choice comprehension measures at posttest and sustained those gains 2 weeks later on delayed posttests. Findings maintain the incremental nature of vocabulary acquisition and development research and emphasize the roles of listening and speaking as critical features for integrating vocabulary into long

  11. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    Directory of Open Access Journals (Sweden)

    Lioshina L. G.

    2009-02-01

    Full Text Available The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with Azospirillum

  12. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    OpenAIRE

    Lioshina L. G.

    2009-01-01

    The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with...

  13. Two-time temperature Green functions in kinetic theory and molecular hydrodynamics. 3. Account of interactions of hydrodynamic fluctuations

    International Nuclear Information System (INIS)

    Tserkovnikov, Yu.A.

    2001-01-01

    The regular method for deriving the equations for the Green functions in the tasks on the molecular hydrodynamics and kinetics, making it possible to account consequently the contribution into the generalized kinetics coefficients, conditioned by interaction of two, three and more hydrodynamic modes. In contrast to the general theory of perturbations by the interaction constant the consequent approximations are accomplished by the degree of accounting for the higher correlations, described by the irreducible functions [ru

  14. Computational study of the human dystrophin repeats: interaction properties and molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Baptiste Legrand

    Full Text Available Dystrophin is a large protein involved in the rare genetic disease Duchenne muscular dystrophy (DMD. It functions as a mechanical linker between the cytoskeleton and the sarcolemma, and is able to resist shear stresses during muscle activity. In all, 75% of the dystrophin molecule consists of a large central rod domain made up of 24 repeat units that share high structural homology with spectrin-like repeats. However, in the absence of any high-resolution structure of these repeats, the molecular basis of dystrophin central domain's functions has not yet been deciphered. In this context, we have performed a computational study of the whole dystrophin central rod domain based on the rational homology modeling of successive and overlapping tandem repeats and the analysis of their surface properties. Each tandem repeat has very specific surface properties that make it unique. However, the repeats share enough electrostatic-surface similarities to be grouped into four separate clusters. Molecular dynamics simulations of four representative tandem repeats reveal specific flexibility or bending properties depending on the repeat sequence. We thus suggest that the dystrophin central rod domain is constituted of seven biologically relevant sub-domains. Our results provide evidence for the role of the dystrophin central rod domain as a scaffold platform with a wide range of surface features and biophysical properties allowing it to interact with its various known partners such as proteins and membrane lipids. This new integrative view is strongly supported by the previous experimental works that investigated the isolated domains and the observed heterogeneity of the severity of dystrophin related pathologies, especially Becker muscular dystrophy.

  15. Exploring the mechanism of interaction between sulindac and human serum albumin: Spectroscopic and molecular modeling methods

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xiao-Ping; Hou, Ya-He [Department of Material Engineering, Xuzhou College of Industrial Technology, Xuzhou, Jiangsu 221140 (China); Wang, Li [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); Zhang, Ye-Zhong, E-mail: zhangfluorescence@126.com [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); Liu, Yi, E-mail: prof.liuyi@263.net [Department of Chemistry, College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou, Hubei 434023 (China); College of Chemistry and Molecular Sciences and State Key Laboratory of Virology, Wuhan University, Wuhan 430072 (China)

    2013-06-15

    In the present study, a combination of fluorescence, molecular modeling and circular dichroism (CD) approaches had been employed to investigate the interaction between sulindac and human serum albumin (HSA). Results of mechanism discussion demonstrated that the fluorescence quenching of HSA by sulindac was a static quenching procedure. Binding parameters calculated from the modified Stern–Volmer equation showed that sulindac bound to HSA with the binding affinities in the order of 10{sup 5} L mol{sup −1}. The thermodynamic parameters (ΔH=−18.58 kJ mol{sup −1}; ΔS=37.26 J mol{sup −1} K{sup −1}) obtained by the van′t Hoff equation revealed that hydrophobic forces played a leading role in the formation of sulindac–HSA complex, but hydrogen bonds could not be omitted. Site marker competitive experiments revealed a displacement of warfarin by sulindac, which indicated that the binding site of sulindac to HSA located in the sub-domain IIA (Sudlow′s site I). The molecular docking study confirmed the specific binding mode and binding site obtained by fluorescence and site marker competitive experiments. CD and three-dimensional fluorescence spectroscopy were used to investigate the changes of HSA secondary structure and microenvironment in the presence of sulindac. Alterations of HSA conformation were observed with the reduction of α-helix from 60.1% (free HSA) to 57.3%, manifesting a slight unfolding of the polypeptides of protein. -- Highlights: ► The quenching mechanism between sulindac and HSA is a static process. ► The binding of sulindac to HSA takes place in sub-domain IIA (Sudlow′s site I). ► The binding is spontaneous and hydrophobic force plays major role in stabilizing the complex. ► CD and 3-D fluorescence spectra prove the change of the microenvironment and conformation of HSA.

  16. Effects of Weak Intermolecular Interactions on the Molecular Isomerism of Tricobalt Metal Chains

    International Nuclear Information System (INIS)

    Poulsen, R.; Overgaard, J.; Schulman, A.; Stergaard, C.; Murillo, C.; Spackman, M.; Iversen, B.

    2009-01-01

    Depending on the number of interstitial solvent molecules, n, crystals of the linear chain compound Co3(dipyridylamide)4Cl2·nCH2Cl2 adopt either symmetrical or unsymmetrical metal chain structures. We explore here the possible reasons for such behavior using Hirshfeld surface analysis of intermolecular interactions as well as the charge density determined from 100(1) K X-ray diffraction data on the unsymmetrical complex Co3(dipyridylamide)4Cl2·2.11CH2Cl2, u-1, and crystal structures of u-1 determined from single crystal synchrotron X-ray diffraction data at 20, 150, and 300 K. The new crystal structures are compared with previous structural results on a crystal with slightly different solvent content. This change in solvent content only affects the bond distances to atom Co(3), which are also strongly affected by temperature changes due to a spin crossover transition. Large differences in intermolecular interactions are revealed by the Hirshfeld surface analysis between symmetrical (s-1) and unsymmetrical (u-1) crystal solvates, suggesting that the molecular isomerism is strongly influenced by crystal packing effects. Topological analysis of the static electron density of u-1 suggests that there is direct metal-metal bonding for both the shorter Co(1)-Co(2) and the longer Co(2)-Co(3) contact. The approximate description of the system as a (Co2)2+-dimer and an isolated Co2+-ion is reflected in the character of the metal-ligand interactions, which are more ionic for the isolated Co(3) atom, and the topological charges Co(1)+0.50, Co(2)+0.77, and Co(3)+1.36. The two termini of u-1 are found to be very different, both in terms of structural surroundings as well as topology. The central Co(2) atom is similar to a cobalt atom in a tetragonally distorted octahedral environment resulting in preferred occupancy in the t2g orbitals. The Co(1) atom has significant deformation in the xz and yz planes (z along the chain axis, x and y toward ligands) reflecting covalent

  17. Surface force analysis of molecular interfacial interactions of proteins and lipids with polymeric biomaterials

    International Nuclear Information System (INIS)

    Hamilton-Brown, P.; Griesser, H.J.; Meagher, L.

    2001-01-01

    Full text: Adverse biological responses to biomedical devices are often caused by the irreversible accumulation of biological deposits onto the surfaces of devices. Such deposits cause blocking of artificial blood vessels, fibrous encapsulation of soft tissue regenerative devices, 'fouling' of contact lenses, secondary cataracts on intraocular lenses, and other undesirable events that interfere with the intended functions of biomedical devices. The formation of deposits is triggered by an initial stage in which various proteins and lipids rapidly adsorb onto the synthetic material surface; further biological molecules and ultimately cellular entities (e.g., host cells, bacteria) then settle onto the initial adsorbed layer. Hence, to avoid or control the accumulation of biological deposits, molecular understanding is required of the initial adsorption processes. Such adsorption is caused by attractive interfacial forces, which we are characterising by the use of a novel method. In the present study, polymeric thin film coatings, polyethylene oxide (PEO), and polysaccharide coatings have been analysed in terms of their surface forces and the ensuing propensity for protein and lipid adsorption. Interfacial forces are measured using atomic force microscopy (AFM) with a colloid-modified tip in a liquid cell using solutions of physiological pH and ionic strength. The chemical composition and uniformity of the coatings was characterised by X-ray Photon Spectroscopy (XPS). For a polymeric solid coating, repulsive forces have been measured against a silica colloid probe, and the dominant surface force is electrostatic. For the highly hydrated, 'soft' PEO and polysaccharide coatings, on the other hand, steric/entropic forces are also significant and contribute to interfacial interactions with proteins and lipids. In one system we have observed a time dependence of the electrostatic surface potential, which affects interaction with charged proteins. Force measurements were

  18. Interaction of bovine serum albumin with a psychotropic drug alprazolam: Physicochemical, photophysical and molecular docking studies

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Moumita; Paul, Shiv Shankar; Mukherjea, Kalyan K., E-mail: k_mukherjea@yahoo.com

    2013-10-15

    The interaction between alprazolam (Alp) and bovine serum albumin (BSA) has been investigated under physiological conditions by UV–vis, steady state as well as time-resolved fluorescence, circular dichroism (CD) spectroscopic and molecular docking studies. The binding constant K of Alp to BSA was found to be 1.8×10{sup 5} L mol{sup −1} from absorption data. Fluorometric studies suggested the formation of the Alp–BSA complex, while time-resolved fluorescence studies showed that the binding of Alp by BSA was mainly static and the effective rate constant is found to be 2.33×10{sup 13} L mol{sup −1} s{sup −1}. According to the modified Stern–Volmer equation, the Stern–Volmer quenching constants (K{sub SV}) between Alp and BSA at four different temperatures 295, 303, 308, 313 K were obtained to be 1.19×10{sup 5}, 1.05×10{sup 5}, 0.99×10{sup 5} and 0.90×10{sup 5} L mol{sup −1}, respectively. The change in enthalpy (ΔH) and entropy (ΔS) were calculated to be −11.66 and 57.64 J mol{sup −1} K{sup −1}, respectively, indicating that the interaction was hydrophobic in nature. Site marker competitive experiments suggested that the binding of Alp to BSA primarily took place in sub-domain IIA, whereas the binding distance (r) between Alp and the tryptophan residue of BSA was obtained to be 1.87 nm by Förster's theory of non-radiative energy transfer. The conformational studies by CD spectroscopy showed that the presence of Alp decreased the α-helical content of BSA and induced the unfolding of the polypeptide of the protein. The change in conformation was also supported by excitation–emission matrix spectroscopy (EEMS) studies. The molecular docking experiment supports the above results and effectively proves the binding of Alp to BSA. -- Highlights: • Alprazolam: a benzodiazepine drug with anxiolytic and anticonvulsant properties. • Alprazolam induces conformational change on the native as well as urea denatured BSA. • Alprazolam may

  19. Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: Advances toward treatment of hepatitis B virus infections

    Science.gov (United States)

    Shahabadi, Nahid; Falsafi, Monireh

    The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33 ± 0.2 × 104 L mol-1and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH = 34.4 kJ mol-1; ΔS = 184.32 J mol-1 K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

  20. Three-dimensional interactive Molecular Dynamics program for the study of defect dynamics in crystals

    Science.gov (United States)

    Patriarca, M.; Kuronen, A.; Robles, M.; Kaski, K.

    2007-01-01

    The study of crystal defects and the complex processes underlying their formation and time evolution has motivated the development of the program ALINE for interactive molecular dynamics experiments. This program couples a molecular dynamics code to a Graphical User Interface and runs on a UNIX-X11 Window System platform with the MOTIF library, which is contained in many standard Linux releases. ALINE is written in C, thus giving the user the possibility to modify the source code, and, at the same time, provides an effective and user-friendly framework for numerical experiments, in which the main parameters can be interactively varied and the system visualized in various ways. We illustrate the main features of the program through some examples of detection and dynamical tracking of point-defects, linear defects, and planar defects, such as stacking faults in lattice-mismatched heterostructures. Program summaryTitle of program:ALINE Catalogue identifier:ADYJ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYJ_v1_0 Program obtainable from: CPC Program Library, Queen University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Computers:DEC ALPHA 300, Intel i386 compatible computers, G4 Apple Computers Installations:Laboratory of Computational Engineering, Helsinki University of Technology, Helsinki, Finland Operating systems under which the program has been tested:True64 UNIX, Linux-i386, Mac OS X 10.3 and 10.4 Programming language used:Standard C and MOTIF libraries Memory required to execute with typical data:6 Mbytes but may be larger depending on the system size No. of lines in distributed program, including test data, etc.:16 901 No. of bytes in distributed program, including test data, etc.:449 559 Distribution format:tar.gz Nature of physical problem:Some phenomena involving defects take place inside three-dimensional crystals at times which can be hardly predicted. For this reason they are

  1. A rapid NGS strategy for comprehensive molecular diagnosis of Birt-Hogg-Dubé syndrome in patients with primary spontaneous pneumothorax.

    Science.gov (United States)

    Zhang, Xinxin; Ma, Dehua; Zou, Wei; Ding, Yibing; Zhu, Chengchu; Min, Haiyan; Zhang, Bin; Wang, Wei; Chen, Baofu; Ye, Minhua; Cai, Minghui; Pan, Yanqing; Cao, Lei; Wan, Yueming; Jin, Yu; Gao, Qian; Yi, Long

    2016-05-27

    Primary spontaneous pneumothorax (PSP) or pulmonary cysts is one of the manifestations of Birt-Hogg-Dube syndrome (BHDS) that is caused by heterozygous mutations in FLCN gene. Most of the mutations are SNVs and small indels, and there are also approximately 10 % large intragenic deletions and duplications of the mutations. These molecular findings are generally obtained by disparate methods including Sanger sequencing and Multiple Ligation-dependent Probe Amplification in the clinical laboratory. In addition, as a genetically heterogeneous disorder, PSP may be caused by mutations in multiple genes include FBN1, COL3A1, CBS, SERPINA1 and TSC1/TSC2 genes. For differential diagnosis, these genes should also be screened which makes the diagnostic procedure more time-consuming and labor-intensive. Forty PSP patients were divided into 2 groups. Nineteen patients with different pathogenic mutations of FLCN previously identified by conventional Sanger sequencing and MLPA were included in test group, 21 random PSP patients without any genetic screening were included in blinded sample group. 7 PSP genes including FLCN, FBN1, COL3A1, CBS, SERPINA1 and TSC1/TSC2 were designed and enriched by Haloplex system, sequenced on a Miseq platform and analyzed in the 40 patients to evaluate the performance of the targeted-NGS method. We demonstrated that the full spectrum of genes associated with pneumothorax including FLCN gene mutations can be identified simultaneously in multiplexed sequence data. Noteworthy, by our in-house copy number analysis of the sequence data, we could not only detect intragenic deletions, but also determine approximate deletion junctions simultaneously. NGS based Haloplex target enrichment technology is proved to be a rapid and cost-effective screening strategy for the comprehensive molecular diagnosis of BHDS in PSP patients, as it can replace Sanger sequencing and MLPA by simultaneously detecting exonic and intronic SNVs, small indels, large intragenic

  2. A comprehensive comparison of four species of Onchidiidae provides insights on the morphological and molecular adaptations of invertebrates from shallow seas to wetlands

    Science.gov (United States)

    Wang, Dongfeng; Li, Jie; Liu, Xin; Wu, Xin

    2018-01-01

    The Onchidiidae family is ideal for studying the evolution of marine invertebrate species from sea to wetland environments. However, comparative studies of Onchidiidae species are rare. A total of 40 samples were collected from four species (10 specimens per onchidiid), and their histological and molecular differences were systematically evaluated to elucidate the morphological foundations underlying the adaptations of these species. A histological analysis was performed to compare the structures of respiratory organs (gill, lung sac, dorsal skin) among onchidiids, and transcriptome sequencing of four representative onchidiids was performed to investigate the molecular mechanisms associated with their respective habitats. Twenty-six SNP markers of Onchidium reevesii revealed some DNA polymorphisms determining visible traits. Non-muscle myosin heavy chain II (NMHC II) and myosin heavy chain (MyHC), which play essential roles in amphibian developmental processes, were found to be differentially expressed in different onchidiids and tissues. The species with higher terrestrial ability and increased integrated expression of Os-MHC (NMHC II gene) and the MyHC gene, illustrating that the expression levels of these genes were associated with the evolutionary degree. This study provides a comprehensive analysis of the adaptions of a diverse and widespread group of invertebrates, the Onchidiidae. Some onchidiids can breathe well through gills and skin when under seawater, and some can breathe well through lung sacs and skin when in wetlands. A histological comparison of respiratory organs and the relative expression levels of two genes provided insights into the adaptions of onchidiids that allowed their transition from shallow seas to wetlands. This work provides a valuable reference and might encourage further study. PMID:29698429

  3. Reactivities of some thiol collectors and their interactions with Ag (+1) ion by molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Yekeler, Hulya; Yekeler, Meftuni

    2004-09-15

    The most commonly used collectors for sulfide minerals in the mining industry are the thiol collectors for the recovery of these minerals from their associated gangues by froth flotation. For this reason, a great deal of attention has been paid to understand the attachment mechanism of thiol collectors to metal sulfide surfaces. The density functional theory (DFT) calculations at the B3LYP/3-21G* and B3LYP/6-31++G** levels were employed to propose the flotation responses of these thiol collectors, namely, diethyl dithiocarbamate, ethyl dithiocarbamate, ethyl dithiocarbonate, ethyl trithiocarbonate and ethyl dithiophosphate ions, and to study the interaction energies of these collectors with Ag (+1) ion in connection to acanthite (Ag{sub 2}S) mineral. The calculated interaction energies, {delta}E, were interpreted in terms of the highest occupied molecular orbital (HOMO) energies of the isolated collector ions. The results show that the HOMOs are strongly localized to the sulfur atoms and the HOMO energies can be used as a reactivity descriptor for the flotation ability of the thiol collectors. Using the HOMO and {delta}E energies, the reactivity order of the collectors is found to be (C{sub 2}H{sub 5}){sub 2}NCS{sub 2}{sup -} > C{sub 2}H{sub 5}NHCS{sub 2}{sup -} > C{sub 2}H{sub 5}OCS{sub 2}{sup -} > C{sub 2}H{sub 5}SCS{sub 2}{sup -} > (C{sub 2}H{sub 5}O)(OH)PS{sub 2}{sup -}. The theoretically obtained results are in good agreement with the experimental data reported.

  4. Molecular modeling study for interaction between Bacillus subtilis Obg and Nucleotides.

    Directory of Open Access Journals (Sweden)

    Yuno Lee

    Full Text Available The bacterial Obg proteins (Spo0B-associated GTP-binding protein belong to the subfamily of P-loop GTPase proteins that contain two equally and highly conserved domains, a C-terminal GTP binding domain and an N-terminal glycine-rich domain which is referred as the "Obg fold" and now it is considered as one of the new targets for antibacterial drug. When the Obg protein is associated with GTP, it becomes activated, because conformation of Obg fold changes due to the structural changes of GTPase switch elements in GTP binding site. In order to investigate the effects and structural changes in GTP bound to Obg and GTPase switch elements for activation, four different molecular dynamics (MD simulations were performed with/without the three different nucleotides (GTP, GDP, and GDP + Pi using the Bacillus subtilis Obg (BsObg structure. The protein structures generated from the four different systems were compared using their representative structures. The pattern of C(alpha-C(alpha distance plot and angle between the two Obg fold domains of simulated apo form and each system (GTP, GDP, and GDP+Pi were significantly different in the GTP-bound system from the others. The switch 2 element was significantly changed in GTP-bound system. Also root-mean-square fluctuation (RMSF analysis revealed that the flexibility of the switch 2 element region was much higher than the others. This was caused by the characteristic binding mode of the nucleotides. When GTP was bound to Obg, its gamma-phosphate oxygen was found to interact with the key residue (D212 of the switch 2 element, on the contrary there was no such interaction found in other systems. Based on the results, we were able to predict the possible binding conformation of the activated form of Obg with L13, which is essential for the assembly with ribosome.

  5. Molecular dynamics modeling the synthetic and biological polymers interactions pre-studied via docking

    Science.gov (United States)

    Tsvetkov, Vladimir B.; Serbin, Alexander V.

    2014-06-01

    In previous works we reported the design, synthesis and in vitro evaluations of synthetic anionic polymers modified by alicyclic pendant groups (hydrophobic anchors), as a novel class of inhibitors of the human immunodeficiency virus type 1 ( HIV-1) entry into human cells. Recently, these synthetic polymers interactions with key mediator of HIV-1 entry-fusion, the tri-helix core of the first heptad repeat regions [ HR1]3 of viral envelope protein gp41, were pre-studied via docking in terms of newly formulated algorithm for stepwise approximation from fragments of polymeric backbone and side-group models toward real polymeric chains. In the present article the docking results were verified under molecular dynamics ( MD) modeling. In contrast with limited capabilities of the docking, the MD allowed of using much more large models of the polymeric ligands, considering flexibility of both ligand and target simultaneously. Among the synthesized polymers the dinorbornen anchors containing alternating copolymers of maleic acid were selected as the most representative ligands (possessing the top anti-HIV activity in vitro in correlation with the highest binding energy in the docking). To verify the probability of binding of the polymers with the [HR1]3 in the sites defined via docking, various starting positions of polymer chains were tried. The MD simulations confirmed the main docking-predicted priority for binding sites, and possibilities for axial and belting modes of the ligands-target interactions. Some newly MD-discovered aspects of the ligand's backbone and anchor units dynamic cooperation in binding the viral target clarify mechanisms of the synthetic polymers anti-HIV activity and drug resistance prevention.

  6. Molecular interactions between selected sodium salts of bile acids and morphine hydrochloride.

    Science.gov (United States)

    Poša, Mihalj; Csanádi, János; Kövér, Katalin E; Guzsvány, Valéria; Batta, Gyula

    2012-06-01

    The objective of this study was to understand the prolonged analgesic action of morphine hydrochloride observed in the presence of sodium 12-oxochenodeoxycholanate. Based on literature, this phenomenon may be due to the formation of aggregates in the cell between the molecules of bile acids and morphine. In addition to the sodium 12-oxochenodeoxycholanate, the present investigation also included salts of cholic and 7-oxodeoxycholic acids. Saturation transfer difference NMR experiments showed that morphine binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt approaches the critical micellar concentration (CMC). The spin-lattice relaxation times (T(1)) of the affected protons decrease significantly in the presence of micellar solutions of the bile acid salts, and the most pronounced change in T(1) was observed for sodium 7-oxodeoxycholate. Diffusion-ordered NMR experiments suggested that morphine hydrochloride can interact only with sodium 7-oxochenodeoxycholate. It can be supposed that the molecular ratio of sodium 7-oxodeoxycholate and morphine hydrochloride in the mixed micelle is 2:1. The CMC values of mixed micelles do not differ from the CMC values of the micelle constituents, which suggests that the binding of morphine hydrochloride does not perturb the hydrophobic domain of the bile acid molecule. In the presence of bile acids, the transfer rate constant (k(12)) of morphine hydrochloride from the buffered aqueous solution to chloroform (model of the cell membrane) shows a decrease. A significant decrease of the k(12) was also observed in the presence of micellar solutions. Kinetic measurements indicated that, in addition to micellar interaction between morphine hydrochloride and sodium salts of bile acids, a complex may also be formed in chloroform via hydrogen bonds formed between the drug and bile acid molecules. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Molecular dynamics investigation of nanoscale substrate topography and its interaction with liquids

    Science.gov (United States)

    Cordeiro Rodrigues, Jhonatam

    Nanotechnology has been presenting successful applications in several areas. However, experimentation with nanoscale materials is costly and limited in analysis capability. This research investigates the use of molecular dynamics (MD) simulations to model and study nanomaterials and manufacturing processes. MD simulations are employed to reduce cost, optimize design, increase productivity and allow for the investigation of material interactions not yet observable through experimentation. This work investigates the interaction of water with substrates at the nanoscale. The effect of temperature, droplet impingement velocities and size, as well as substrate material, are investigated at the nanoscale. Several substrate topography designs were modeled to reveal their influence on the wettability of the substrate. Nanoscale gold and silicon substrates are more hydrophilic at higher temperatures than at room temperature. The reduction in droplet diameter increases its wettability. High impingement velocity of droplets does not influence final wettability of substrates but induces higher diffusion rates of droplets in a heated environment. Droplets deposited over a gradient of surface exposure presents spontaneous movement. The Leidenfrost effect was investigated at the nanoscale. Droplets of 4 and 10nm in diameter presented behaviors pertinent to the Leidenfrost effect at 373K, significantly lower than at micro scale and of potential impact to the field. Topographical features were manipulated using superhydrophobic coating resulting in micro whiskers. Nanoimprint lithography (NIL) was used to manufacture substrate topographies at the nanoscale. Water droplets were deposited on the substrates and their wettability was measured using droplet contact angles. Lower surface area exposure resulted in higher contact angles. The experimental relationships between surface topography and substrate wettability were used to validate the insights gained from MD simulations for

  8. Toward Molecular Magnets of Organic Origin via Anion-π Interaction Involving m-Aminyl Diradical: A Theoretical Study

    DEFF Research Database (Denmark)

    Bhattacharya, Debojit; Shil, Suranjan; Misra, Anirban

    2016-01-01

    Here we study a set of novel magnetic organic molecular species with different halide ions (fluoride, chloride, bromide) absorbed ∼2 Å above or below the center of an aromatic π-ring in an m-aminyl diradical. Focus is on the nature of anion-π interaction and its impact on magnetic properties, spe...

  9. The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

    Directory of Open Access Journals (Sweden)

    Matthias Stein

    Full Text Available Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

  10. Interaction-induced light scattering in a fullerene surrounded by an ultrathin argon 'atmosphere': Molecular dynamics simulation

    International Nuclear Information System (INIS)

    Dawid, A.; Gburski, Z.

    2003-01-01

    Using the molecular dynamics method, we have calculated the interaction-induced polarizability correlation functions and spectra of the depolarized light scattering in a C 60 fullerene molecule surrounded by an argon atmosphere. The liquid phase of (C 60 )Ar n (n=36, 40, 44) system has been studied

  11. Molecular aspects of the interaction between Mason-Pfizer monkey virus matrix protein and artificial phospholipid membrane

    Czech Academy of Sciences Publication Activity Database

    Junková, P.; Prchal, J.; Spiwok, V.; Pleskot, Roman; Kadlec, Jan; Krásný, L.; Hynek, R.; Hrabal, R.; Ruml, T.

    2016-01-01

    Roč. 84, č. 11 (2016), s. 1717-1727 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : covalent labelling * mass spectrometry * multiscale molecular dynamics * protein-membrane interaction * phosphatidylinositol-(4,5)-bisphosphate * liposomes Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  12. Predicting the influence of long-range molecular interactions on macroscopic-scale diffusion by homogenization of the Smoluchowski equation

    Energy Technology Data Exchange (ETDEWEB)

    Kekenes-Huskey, P. M., E-mail: pkekeneshuskey@ucsd.edu [Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0636 (United States); Gillette, A. K. [Department of Mathematics, University of Arizona, Tucson, Arizona 85721-0089 (United States); McCammon, J. A. [Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0636 (United States); Department of Chemistry, Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093-0636 (United States)

    2014-05-07

    The macroscopic diffusion constant for a charged diffuser is in part dependent on (1) the volume excluded by solute “obstacles” and (2) long-range interactions between those obstacles and the diffuser. Increasing excluded volume reduces transport of the diffuser, while long-range interactions can either increase or decrease diffusivity, depending on the nature of the potential. We previously demonstrated [P. M. Kekenes-Huskey et al., Biophys. J. 105, 2130 (2013)] using homogenization theory that the configuration of molecular-scale obstacles can both hinder diffusion and induce diffusional anisotropy for small ions. As the density of molecular obstacles increases, van der Waals (vdW) and electrostatic interactions between obstacle and a diffuser become significant and can strongly influence the latter's diffusivity, which was neglected in our original model. Here, we extend this methodology to include a fixed (time-independent) potential of mean force, through homogenization of the Smoluchowski equation. We consider the diffusion of ions in crowded, hydrophilic environments at physiological ionic strengths and find that electrostatic and vdW interactions can enhance or depress effective diffusion rates for attractive or repulsive forces, respectively. Additionally, we show that the observed diffusion rate may be reduced independent of non-specific electrostatic and vdW interactions by treating obstacles that exhibit specific binding interactions as “buffers” that absorb free diffusers. Finally, we demonstrate that effective diffusion rates are sensitive to distribution of surface charge on a globular protein, Troponin C, suggesting that the use of molecular structures with atomistic-scale resolution can account for electrostatic influences on substrate transport. This approach offers new insight into the influence of molecular-scale, long-range interactions on transport of charged species, particularly for diffusion-influenced signaling events

  13. A methodological proposal for comprehensive research: Communicative interactions in a virtual learning environment [Propuesta metodológica para la investigación comprensiva: Interacciones comunicativas en un entorno virtual de aprendizaje

    OpenAIRE

    Lopera C.V.; Vasquez S.A.

    2011-01-01

    To understand the communicative interactions that come up in the relationships of students in a virtual learning environment, the project "Communicative interactions in a virtual learning environment" was developed within a comprehensive research framework that refers to the structure of epistemological and methodological decisions and acts that allows a person to comprehensively access to the sense of life practices. Departing from an etnomethodological focus, the data obtaining, the analysi...

  14. Molecular interactions involved in proton-dependent gating in KcsA potassium channels

    Science.gov (United States)

    Posson, David J.; Thompson, Ameer N.; McCoy, Jason G.

    2013-01-01

    The bacterial potassium channel KcsA is gated open by the binding of protons to amino acids on the intracellular side of the channel. We have identified, via channel mutagenesis and x-ray crystallography, two pH-sensing amino acids and a set of nearby residues involved in molecular interactions that influence gating. We found that the minimal mutation of one histidine (H25) and one glutamate (E118) near the cytoplasmic gate completely abolished pH-dependent gating. Mutation of nearby residues either alone or in pairs altered the channel’s response to pH. In addition, mutations of certain pairs of residues dramatically increased the energy barriers between the closed and open states. We proposed a Monod–Wyman–Changeux model for proton binding and pH-dependent gating in KcsA, where H25 is a “strong” sensor displaying a large shift in pKa between closed and open states, and E118 is a “weak” pH sensor. Modifying model parameters that are involved in either the intrinsic gating equilibrium or the pKa values of the pH-sensing residues was sufficient to capture the effects of all mutations. PMID:24218397

  15. Effects of electron-phonon interaction on thermal and electrical transport through molecular nano-conductors

    Energy Technology Data Exchange (ETDEWEB)

    Lü, Jing-Tao, E-mail: jtlu@hust.edu.cn [School of Physics, Huazhong University of Science and Technology, 430074 Wuhan (China); Zhou, Hangbo [Department of Physics and Center for Computational Science and Engineering, National University of Singapore, 117551 Singapore (Singapore); NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 117456 Singapore (Singapore); Jiang, Jin-Wu [Shanghai Institute of Applied Mathematics and Mechanics, Shanghai Key Laboratory of Mechanics in Energy Engineering, Shanghai University, 200072 Shanghai (China); Wang, Jian-Sheng [Department of Physics and Center for Computational Science and Engineering, National University of Singapore, 117551 Singapore (Singapore)

    2015-05-15

    The topic of this review is the effects of electron-phonon interaction (EPI) on the transport properties of molecular nano-conductors. A nano-conductor connects to two electron leads and two phonon leads, possibly at different temperatures or chemical potentials. The EPI appears only in the nano-conductor. We focus on its effects on charge and energy transport. We introduce three approaches. For weak EPI, we use the nonequilibrium Green’s function method to treat it perturbatively. We derive the expressions for the charge and heat currents. For weak system-lead couplings, we use the quantum master equation approach. In both cases, we use a simple single level model to study the effects of EPI on the system’s thermoelectric transport properties. It is also interesting to look at the effect of currents on the dynamics of the phonon system. For this, we derive a semi-classical generalized Langevin equation to describe the nano-conductor’s atomic dynamics, taking the nonequilibrium electron system, as well as the rest of the atomic degrees of freedom as effective baths. We show simple applications of this approach to the problem of energy transfer between electrons and phonons.

  16. Self-interaction corrected density functional calculations of molecular Rydberg states

    International Nuclear Information System (INIS)

    Gudmundsdóttir, Hildur; Zhang, Yao; Weber, Peter M.; Jónsson, Hannes

    2013-01-01

    A method is presented for calculating the wave function and energy of Rydberg excited states of molecules. A good estimate of the Rydberg state orbital is obtained using ground state density functional theory including Perdew-Zunger self-interaction correction and an optimized effective potential. The total energy of the excited molecule is obtained using the Delta Self-Consistent Field method where an electron is removed from the highest occupied orbital and placed in the Rydberg orbital. Results are presented for the first few Rydberg states of NH 3 , H 2 O, H 2 CO, C 2 H 4 , and N(CH 3 ) 3 . The mean absolute error in the energy of the 33 molecular Rydberg states presented here is 0.18 eV. The orbitals are represented on a real space grid, avoiding the dependence on diffuse atomic basis sets. As in standard density functional theory calculations, the computational effort scales as NM 2 where N is the number of orbitals and M is the number of grid points included in the calculation. Due to the slow scaling of the computational effort with system size and the high level of parallelism in the real space grid approach, the method presented here makes it possible to estimate Rydberg electron binding energy in large molecules

  17. Ultrasonic study on molecular interactions in binary mixtures of formamide with 1-propanol or 2-propanol

    Institute of Scientific and Technical Information of China (English)

    Manju Rani; Suman Gahlyan; Ankur Gaur; Sanjeev Maken

    2015-01-01

    Ultrasonic speeds have been measured at 298.15 K and 308.15 K for mixtures of formamide+1-propanol or 2-propanol. For an equimolar mixture, excess molar compressibility follows the sequence of 1-propanol N 2-propanol. The ultrasonic speed data are correlated by various correlations such as Nomoto's relation, van Dael's mixing relation and impedance dependence relation, and analyzed in terms of Jacobson's free length theory and Schaaff's collision factor theory. Excess isentropic compressibility is calculated from ex-perimental ultrasonic speed data and previously reported excess volume data. The excess molar ultrasonic speed and isentropic compressibility values are fitted to Redlich–Kister polynomial equation. Other proper-ties such as molecular association, avallable volume, free volume, and intermolecular free length are also calculated. The excess isentropic compressibility data are also interpreted in terms of graph theoretical ap-proach. The calculated isentropic compressibility values are well consistent with the experimental data. It is found that the interaction between formamide and propanol increases when hydroxyl group attached to a carbon atom has more–CH3 groups.

  18. Interaction of amyloid inhibitor proteins with amyloid beta peptides: insight from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Payel Das

    Full Text Available Knowledge of the detailed mechanism by which proteins such as human αB- crystallin and human lysozyme inhibit amyloid beta (Aβ peptide aggregation is crucial for designing treatment for Alzheimer's disease. Thus, unconstrained, atomistic molecular dynamics simulations in explicit solvent have been performed to characterize the Aβ17-42 assembly in presence of the αB-crystallin core domain and of lysozyme. Simulations reveal that both inhibitor proteins compete with inter-peptide interaction by binding to the peptides during the early stage of aggregation, which is consistent with their inhibitory action reported in experiments. However, the Aβ binding dynamics appear different for each inhibitor. The binding between crystallin and the peptide monomer, dominated by electrostatics, is relatively weak and transient due to the heterogeneous amino acid distribution of the inhibitor surface. The crystallin-bound Aβ oligomers are relatively long-lived, as they form more extensive contact surface with the inhibitor protein. In contrast, a high local density of arginines from lysozyme allows strong binding with Aβ peptide monomers, resulting in stable complexes. Our findings not only illustrate, in atomic detail, how the amyloid inhibitory mechanism of human αB-crystallin, a natural chaperone, is different from that of human lysozyme, but also may aid de novo design of amyloid inhibitors.

  19. Molecular Aspects of Dopaminergic Neurodegeneration: Gene-Environment Interaction in Parkin Dysfunction

    Directory of Open Access Journals (Sweden)

    Syed Z. Imam

    2011-12-01

    Full Text Available Parkinson’s disease (PD is a common neurodegenerative movement disorder that is characterized pathologically by a progressive loss of midbrain dopaminergic neurons and by protein inclusions, designated Lewy bodies and Lewy neurites. PD is one of the most common neurodegenerative diseases, affecting almost 1% of the population over 60 years old. Although the symptoms and neuropathology of PD have been well characterized, the underlying mechanisms and causes of the disease are still not clear. Genetic mutations can provide important clues to disease mechanism, but most PD cases are sporadic rather than familial; environmental factors have long been suspected to contribute to the disease. Although more than 90% of PD cases occur sporadically and are thought to be due, in part, to oxidative stress and mitochondrial dysfunction, the study of genetic mutations has provided great insight into the molecular mechanisms of PD. Furthermore, rotenone, a widely used pesticide, and paraquat and maneb cause a syndrome in rats and mice that mimics, both behaviorally and neurologically, the symptoms of PD. In the current review, we will discuss various aspects of gene-environment interaction that lead to progressive dopaminergic neurodegenration, mainly focusing on our current finding based on stress-mediated parkin dysfunction.

  20. Electrostatic solvation free energies of charged hard spheres using molecular dynamics with density functional theory interactions

    Science.gov (United States)

    Duignan, Timothy T.; Baer, Marcel D.; Schenter, Gregory K.; Mundy, Chistopher J.

    2017-10-01

    Determining the solvation free energies of single ions in water is one of the most fundamental problems in physical chemistry and yet many unresolved questions remain. In particular, the ability to decompose the solvation free energy into simple and intuitive contributions will have important implications for models of electrolyte solution. Here, we provide definitions of the various types of single ion solvation free energies based on different simulation protocols. We calculate solvation free energies of charged hard spheres using density functional theory interaction potentials with molecular dynamics simulation and isolate the effects of charge and cavitation, comparing to the Born (linear response) model. We show that using uncorrected Ewald summation leads to unphysical values for the single ion solvation free energy and that charging free energies for cations are approximately linear as a function of charge but that there is a small non-linearity for small anions. The charge hydration asymmetry for hard spheres, determined with quantum mechanics, is much larger than for the analogous real ions. This suggests that real ions, particularly anions, are significantly more complex than simple charged hard spheres, a commonly employed representation.

  1. Molecular dynamics study of interstitial-solute interactions in irradiated alloys

    International Nuclear Information System (INIS)

    Lam, N.Q.; Doan, N.V.; Adda, Y.

    1980-01-01

    The molecular dynamics technique has been used, in conjunction with the interionic potentials of Dagens et al, to study the stability, configuration, binding, and induced migration of mixed dumbbells in an irradiated Al-Zn alloy. For the purpose of comparisons, self-interstitials in pure Al were also investigated. The Al-Al and Al-Zn interactions were described by pair potentials which extended to ninth-neighbour distances. Both the self-interstitial dumbbell and the mixed dumbbell were found to be stable in the configuration. The formation energy of the self-interstitial is 2.89 eV and the mixed-dumbbell binding energy is 0.38 eV. As a result of this strong binding, the threshold energy required to induce the migration of the mixed dumbbell is about 1.2 eV, which is significantly larger than the minimum energy of about 0.15 eV transferred to a self-interstitial to induce its jumps in pure Al. Caging motions of the mixed dumbbell were observed. The present computer-simulation results are compared with experimental measurements. (author)

  2. Effects of electron-phonon interaction on thermal and electrical transport through molecular nano-conductors

    International Nuclear Information System (INIS)

    Lü, Jing-Tao; Zhou, Hangbo; Jiang, Jin-Wu; Wang, Jian-Sheng

    2015-01-01

    The topic of this review is the effects of electron-phonon interaction (EPI) on the transport properties of molecular nano-conductors. A nano-conductor connects to two electron leads and two phonon leads, possibly at different temperatures or chemical potentials. The EPI appears only in the nano-conductor. We focus on its effects on charge and energy transport. We introduce three approaches. For weak EPI, we use the nonequilibrium Green’s function method to treat it perturbatively. We derive the expressions for the charge and heat currents. For weak system-lead couplings, we use the quantum master equation approach. In both cases, we use a simple single level model to study the effects of EPI on the system’s thermoelectric transport properties. It is also interesting to look at the effect of currents on the dynamics of the phonon system. For this, we derive a semi-classical generalized Langevin equation to describe the nano-conductor’s atomic dynamics, taking the nonequilibrium electron system, as well as the rest of the atomic degrees of freedom as effective baths. We show simple applications of this approach to the problem of energy transfer between electrons and phonons

  3. Understanding trophic interactions of Orius spp. (Hemiptera: Anthocoridae) in lettuce crops by molecular methods.

    Science.gov (United States)

    Gomez-Polo, Priscila; Alomar, Oscar; Castañé, Cristina; Aznar-Fernández, Thaïs; Lundgren, Jonathan G; Piñol, Josep; Agustí, Nuria

    2016-02-01

    The aphid Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae) and the thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) are common pests in Mediterranean lettuce crops, where Orius spp. are common generalist predators. Predation by Orius spp. was studied in a lettuce plot by conventional polymerase chain reaction (PCR) and real-time PCR analyses using specific primers of both main pests. Also, high-throughput sequencing was used to have a wider approach of the diet of these predators in natural field conditions. Molecular analyses indicated a higher predation on N. ribisnigri in spring and on F. occidentalis in summer. Predation on alternative prey, like Collembola, was also found in both seasons. Real-time PCR was more sensitive than conventional PCR in showing the target trophic links, whereas high-throughput sequencing revealed predation on other natural enemies - intraguild predation (IGP), showing other trophic interactions of Orius majusculus within the studied ecosystem. This study gives important information about the trophic relationships present in Mediterranean lettuce crops in different periods of the year. The detected predation by Orius spp. on alternative prey, as well as on other natural enemies, should be further investigated to clarify whether it adds or detracts to the biological control of N. ribisnigri and F. occidentalis. © 2015 Society of Chemical Industry.

  4. MDM2-MDM4 molecular interaction investigated by atomic force spectroscopy and surface plasmon resonance.

    Science.gov (United States)

    Moscetti, Ilaria; Teveroni, Emanuela; Moretti, Fabiola; Bizzarri, Anna Rita; Cannistraro, Salvatore

    Murine double minute 2 (MDM2) and 4 (MDM4) are known as the main negative regulators of p53, a tumor suppressor. They are able to form heterodimers that are much more effective in the downregulation of p53. Therefore, the MDM2-MDM4 complex could be a target for promising therapeutic restoration of p53 function. To this aim, a deeper understanding of the molecular mechanisms underlining the heterodimerization is needed. The kinetic and thermodynamic characterization of the MDM2-MDM4 complex was performed with two complementary approaches: atomic force spectroscopy and surface plasmon resonance. Both techniques revealed an equilibrium dissociation constant (KD ) in the micromolar range for the MDM2-MDM4 heterodimer, similar to related complexes involved in the p53 network. Furthermore, the MDM2-MDM4 complex is characterized by a relatively high free energy, through a single energy barrier, and by a lifetime in the order of tens of seconds. New insights into the MDM2-MDM4 interaction could be highly important for developing innovative anticancer drugs focused on p53 reactivation.

  5. The molecular mechanism of bisphenol A (BPA as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD simulations.

    Directory of Open Access Journals (Sweden)

    Lanlan Li

    Full Text Available Bisphenol A (BPA can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these