WorldWideScience

Sample records for acid molecular switches

  1. Monitoring Gene Expression In Vivo with Nucleic Acid Molecular Switches

    Energy Technology Data Exchange (ETDEWEB)

    David C. Ward; Patricia Bray-Ward

    2005-01-26

    The overall objectives of this project were (1) to develop allosteric ribozymes capable of acting as molecular switches for monitoring the levels of both wild-type and mutant mRNA species in living cells and whole animals and (2) to develop highly efficient reagents to deliver nucleic acid molecular switches into living cells, tissues and animals with the ultimate goal of expression profiling specific mRNAs of diagnostic or prognostic value within tumors in animals. During the past year, we have moved our laboratory to Nevada and in the moving process we have lost electronic and paper copies of prior progress reports concerning the construction and biological properties of the molecular switches. Since there was minimal progress during the last year on molecular switches, we are relying on past project reports to provide a summary of our data on this facet of the grant. Here we are summarizing the work done on the delivery reagents and their application to inducing mutations in living cells, which will include work done during the no cost extension.

  2. Chiral induction in phenanthroline-derived oligoamide foldamers: an acid- and base-controllable switch in helical molecular strands.

    Science.gov (United States)

    Hu, Hai-Yu; Xiang, Jun-Feng; Yang, Yong; Chen, Chuan-Feng

    2008-03-20

    A series of phenanthroline-derived oligoamides bearing a chiral (R)-phenethylamino end group were synthesized that displayed chiral helical induction and subsequently formed one-hand helical foldamers in solution. Moreover, an acid- and base-controllable switch in the helical molecular strands was observed, which has been demonstrated by NMR, UV-vis, and circular dichroism spectroscopy.

  3. Molecular Rotors as Switches

    Directory of Open Access Journals (Sweden)

    Kang L. Wang

    2012-08-01

    Full Text Available The use of a functional molecular unit acting as a state variable provides an attractive alternative for the next generations of nanoscale electronics. It may help overcome the limits of conventional MOSFETd due to their potential scalability, low-cost, low variability, and highly integratable characteristics as well as the capability to exploit bottom-up self-assembly processes. This bottom-up construction and the operation of nanoscale machines/devices, in which the molecular motion can be controlled to perform functions, have been studied for their functionalities. Being triggered by external stimuli such as light, electricity or chemical reagents, these devices have shown various functions including those of diodes, rectifiers, memories, resonant tunnel junctions and single settable molecular switches that can be electronically configured for logic gates. Molecule-specific electronic switching has also been reported for several of these device structures, including nanopores containing oligo(phenylene ethynylene monolayers, and planar junctions incorporating rotaxane and catenane monolayers for the construction and operation of complex molecular machines. A specific electrically driven surface mounted molecular rotor is described in detail in this review. The rotor is comprised of a monolayer of redox-active ligated copper compounds sandwiched between a gold electrode and a highly-doped P+ Si. This electrically driven sandwich-type monolayer molecular rotor device showed an on/off ratio of approximately 104, a read window of about 2.5 V, and a retention time of greater than 104 s. The rotation speed of this type of molecular rotor has been reported to be in the picosecond timescale, which provides a potential of high switching speed applications. Current-voltage spectroscopy (I-V revealed a temperature-dependent negative differential resistance (NDR associated with the device. The analysis of the device

  4. A sensitive SERS assay for detecting proteins and nucleic acids using a triple-helix molecular switch for cascade signal amplification.

    Science.gov (United States)

    Ye, Sujuan; Wu, Yanying; Zhang, Wen; Li, Na; Tang, Bo

    2014-08-25

    A novel surface-enhanced Raman scattering (SERS) detection system is developed for proteins and nucleic acids based on a triple-helix molecular switch for multiple cycle signal amplification, achieving high sensitivity, universality, rapid analysis, and high selectivity.

  5. Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

    Science.gov (United States)

    Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

    2017-01-01

    Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials. PMID:28084463

  6. Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

    Science.gov (United States)

    Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

    2017-01-01

    Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials.

  7. EDITORIAL: Molecular switches at surfaces Molecular switches at surfaces

    Science.gov (United States)

    Weinelt, Martin; von Oppen, Felix

    2012-10-01

    In nature, molecules exploit interaction with their environment to realize complex functionalities on the nanometer length scale. Physical, chemical and/or biological specificity is frequently achieved by the switching of molecules between microscopically different states. Paradigmatic examples are the energy production in proton pumps of bacteria or the signal conversion in human vision, which rely on switching molecules between different configurations or conformations by external stimuli. The remarkable reproducibility and unparalleled fatigue resistance of these natural processes makes it highly desirable to emulate nature and develop artificial systems with molecular functionalities. A promising avenue towards this goal is to anchor the molecular switches at surfaces, offering new pathways to control their functional properties, to apply electrical contacts, or to integrate switches into larger systems. Anchoring at surfaces allows one to access the full range from individual molecular switches to self-assembled monolayers of well-defined geometry and to customize the coupling between molecules and substrate or between adsorbed molecules. Progress in this field requires both synthesis and preparation of appropriate molecular systems and control over suitable external stimuli, such as light, heat, or electrical currents. To optimize switching and generate function, it is essential to unravel the geometric structure, the electronic properties and the dynamic interactions of the molecular switches on surfaces. This special section, Molecular Switches at Surfaces, collects 17 contributions describing different aspects of this research field. They analyze elementary processes, both in single molecules and in ensembles of molecules, which involve molecular switching and concomitant changes of optical, electronic, or magnetic properties. Two topical reviews summarize the current status, including both challenges and achievements in the field of molecular switches on

  8. Molecular DNA switches and DNA chips

    Science.gov (United States)

    Sabanayagam, Chandran R.; Berkey, Cristin; Lavi, Uri; Cantor, Charles R.; Smith, Cassandra L.

    1999-06-01

    We present an assay to detect single-nucleotide polymorphisms on a chip using molecular DNA switches and isothermal rolling- circle amplification. The basic principle behind the switch is an allele-specific oligonucleotide circularization, mediated by DNA ligase. A DNA switch is closed when perfect hybridization between the probe oligonucleotide and target DNA allows ligase to covalently circularize the probe. Mismatches around the ligation site prevent probe circularization, resulting in an open switch. DNA polymerase is then used to preferentially amplify the closed switches, via rolling-circle amplification. The stringency of the molecular switches yields 102 - 103 fold discrimination between matched and mismatched sequences.

  9. Molecular switches and motors on surfaces.

    Science.gov (United States)

    Pathem, Bala Krishna; Claridge, Shelley A; Zheng, Yue Bing; Weiss, Paul S

    2013-01-01

    Molecular switches and motors respond structurally, electronically, optically, and/or mechanically to external stimuli, testing and potentially enabling extreme miniaturization of optoelectronic devices, nanoelectromechanical systems, and medical devices. The assembly of motors and switches on surfaces makes it possible both to measure the properties of individual molecules as they relate to their environment and to couple function between assembled molecules. In this review, we discuss recent progress in assembling molecular switches and motors on surfaces, measuring static and dynamic structures, understanding switching mechanisms, and constructing functional molecular materials and devices. As demonstrative examples, we choose a representative molecule from three commonly studied classes including molecular switches, photochromic molecules, and mechanically interlocked molecules. We conclude by offering perspectives on the future of molecular switches and motors on surfaces.

  10. Chiroptical Molecular Switches 1; Principles and Syntheses.

    NARCIS (Netherlands)

    Lange, Ben de; Jager, Wolter F.; Feringa, Bernard

    1992-01-01

    The concept and the synthesis of the basic molecules for a chiroptical molecular switch are described. This molecular switch is based on photochemical interconversion of two bistable forms of chiral sterically overcrowded olefins. A large variety of these alkenes with different properties have been

  11. Fine tuning of molecular rotor function in photochemical molecular switches

    NARCIS (Netherlands)

    ter Wiel, Matthijs K. J.; Feringa, Ben L.

    2009-01-01

    Molecular switches are used as scaffolds for the construction of controlled molecular rotors. The internal position of the switching entity in the molecule controls the dynamic behaviour of the rotor moiety in the molecule. Six new molecular motors with o-xylyl rotor moieties were prepared on the ba

  12. Designs for the self-assembly of open and closed macromolecular structures and a molecular switch using DNA methyltransferases to order proteins on nucleic acid scaffolds

    Science.gov (United States)

    Smith, Steven S.

    2002-06-01

    The methyltransferase-directed addressing of fusion proteins to DNA scaffolds offers an approach to the construction of protein/nucleic acid biostructures with potential in a variety of applications. The technology is currently only limited by the yield of high occupancy structures. However, current evidence shows that DNA scaffolds that contain three or four targeted proteins can be reliably constructed. This permits a variety of macromolecular designs, several of which are given in this paper. Designs for open and closed two-dimensional and three-dimensional assemblies and a design for a molecular switch are discussed. The closed two-dimensional assembly takes the form of a square, and could find application as a component of other systems including a macromolecular rotaxane. The closed three-dimensional system takes the form of a trigonal bipyramid and could find application as a macromolecular carcerand. The molecular switch could find application as a peptide biosensor. Guidelines for the construction and structural verification of these designs are reported.

  13. Acid/Base and H2PO4(-) Controllable High-Contrast Optical Molecular Switches with a Novel BODIPY Functionalized [2]Rotaxane.

    Science.gov (United States)

    Arumugaperumal, Reguram; Srinivasadesikan, Venkatesan; Ramakrishnam Raju, Mandapati V; Lin, Ming-Chang; Shukla, Tarun; Singh, Ravinder; Lin, Hong-Cheu

    2015-12-09

    A novel multifunctional mechanically interlocked switchable [2]rotaxane R4 containing two molecular stations and rotaxane arms terminated with boron-dipyrromethene (BODIPY) fluorophores and its derivatives were synthesized for the first time by CuAAC click reaction. The shuttling motion of macrocycle between the dibenzylammonium and triazolium recognition sites and the distance dependent photoinduced electron transfer process of R4 is demonstrated by utilizing external chemical stimuli (acid/base). Interestingly, the reversible self-assembly process of R4 was recognized by the acid-base molecular switch strategy. Notably, two symmetrical triazolium groups acted as molecular stations, H2PO4(-) receptors, and H-bonded donors. Both [2]rotaxane R4 and thread R2 demonstrated excellent optical responses and high selectivity toward H2PO4(-) ion. The specific motion and guest-host interactions of mechanically interlocked machines (MIMs) were also further explored by quantum mechanical calculations. The thread R2 also demonstrated to enable the detection of H2PO4(-) in RAW 264.7 cells successfully.

  14. Molecular mechanism of R-bicalutamide switching from androgen receptor antagonist to agonist induced by amino acid mutations using molecular dynamics simulations and free energy calculation

    Science.gov (United States)

    Liu, Hongli; Han, Rui; Li, Jiazhong; Liu, Huanxiang; Zheng, Lifang

    2016-12-01

    R-bicalutamide, a first generation antiandrogen, was used to treat prostate cancer for decades. Although it is very effective at the beginning, resistance appears after 2-3 years of treatment. Mutation of androgen receptor (AR) is considered a main reason for drug resistance. It is reported that AR W741C, W741L, W741C_T877A, T877A, F876L, F876L_T877A and L701H mutations can convert R-bicalutamide from AR antagonist to agonist, but the switching mechanisms are not clear. In this study, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM-GBSA) calculations were performed to analyze the interaction mechanisms between R-bicalutamide and wild type/mutant ARs. The results indicate that helix H12, which lies on the top of AR LBD like a cover, plays a vital role in R-bicalutamide binding. When interacting with AR, the B-ring of R-bicalutamide pushes H12 aside, distorting the coactivator binding site (AF2) resulting in the inactivation of transcription. Several residue mutations appear to enlarge the distance between the B-ring of R-bicalutamide and H12, reducing steric clash, which is conducive to a closed H12 conformation, leading to the formation of the coactivator binding site AF2 and increased transcription. Hydrogen bond and per-residue free energy decomposition analyses are also investigated to explore the interacting mechanisms, and M895 is found to be a key residue in the antagonist mechanism. The obtained molecular mechanisms will aid rational screening and design of novel AR antagonists, even to mutant AR.

  15. A nanoplasmonic switch based on molecular machines

    KAUST Repository

    Zheng, Yue Bing

    2009-06-01

    We aim to develop a molecular-machine-driven nanoplasmonic switch for its use in future nanophotonic integrated circuits (ICs) that have applications in optical communication, information processing, biological and chemical sensing. Experimental data show that an Au nanodisk array, coated with rotaxane molecular machines, switches its localized surface plasmon resonances (LSPR) reversibly when it is exposed to chemical oxidants and reductants. Conversely, bare Au nanodisks and disks coated with mechanically inert control compounds, do not display the same switching behavior. Along with calculations based on time-dependent density functional theory (TDDFT), these observations suggest that the nanoscale movements within surface-bound "molecular machines" can be used as the active components in plasmonic devices. ©2009 IEEE.

  16. Active Molecular Plasmonics: Controlling Plasmon Resonances with Molecular Switches

    KAUST Repository

    Zheng, Yue Bing

    2009-02-11

    A gold nanodisk array, coated with bistable, redox-controllable [2]rotaxane molecules, when exposed to chemical oxidants and reductants, undergoes switching of its plasmonic properties reversibly. By contrast, (i) bare gold nanodisks and (ii) disks coated with a redox-active, but mechanically inert, control compound do not display surface-plasmon-based switching. Along with calculations based on time-dependent density functional theory, these experimental observations suggest that the nanoscale movements within surface-bound “molecular machines” can be used as the active components in plasmonic devices.

  17. An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes

    DEFF Research Database (Denmark)

    Papaleo, Elena; Ranzani, Valeria; Tripodi, Farida;

    2011-01-01

    elements in one of the larger families of E2 enzymes: an acidic insertion in β4α2 loop in the proximity of the catalytic cysteine and two conserved key serine residues within the catalytic domain, which are phosphorylated by CK2. Our investigations, using yeast Cdc34 as a model, through 2.5 µs molecular......E2 ubiquitin-conjugating enzymes are crucial mediators of protein ubiquitination, which strongly influence the ultimate fate of the target substrates. Recently, it has been shown that the activity of several enzymes of the ubiquitination pathway is finely tuned by phosphorylation, an ubiquitous...... mechanism for cellular regulation, which modulates protein conformation. In this contribution, we provide the first rationale, at the molecular level, of the regulatory mechanism mediated by casein kinase 2 (CK2) phosphorylation of E2 Cdc34-like enzymes. In particular, we identify two co-evolving signature...

  18. The Art of Building Small : From Molecular Switches to Molecular Motors

    NARCIS (Netherlands)

    Feringa, Bernard

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  19. The art of building small : From molecular switches to molecular motors

    NARCIS (Netherlands)

    Feringa, Ben L.

    2007-01-01

    Molecular switches and motors are essential components of artificial molecular machines. In this perspective, we discuss progress in our design, synthesis, and functioning of photochemical and electrochemical switches and chemical and light-driven molecular motors. Special emphasis is given to the c

  20. Tetrapodal molecular switches and motors: synthesis and photochemistry.

    Science.gov (United States)

    Chen, Kuang-Yen; Wezenberg, Sander J; Carroll, Gregory T; London, Gábor; Kistemaker, Jos C M; Pijper, Thomas C; Feringa, Ben L

    2014-08-01

    The design, synthesis, and dynamic behavior of a series of novel tetrapodal molecular switches and motors containing common functional groups for attachment to various inorganic and organic surfaces are presented. Using a Diels-Alder reaction, an anthracene unit with four functionalized alkyl substituents ("legs") was coupled to maleimide-functionalized molecular switches or motors under ambient conditions. Terminal functional groups at the "legs" include thioacetates and azides, making these switches and motors ideal candidates for attachment to metallic or alkyne-functionalized surfaces. UV/vis absorption spectroscopy shows that the molecular switches and motors retain their ability to undergo reversible photoinduced and/or thermally induced structural changes after attachment to the tetrapodal anthracene.

  1. Electronic transport properties of a quinone-based molecular switch

    Science.gov (United States)

    Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

    2016-09-01

    In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

  2. Polymer Alignment Behavior with Molecular Switching of Ferroelectric Liquid Crystal

    Science.gov (United States)

    Murashige, Takeshi; Fujikake, Hideo; Sato, Hiroto; Kikuchi, Hiroshi; Kurita, Taiichiro; Sato, Fumio

    2007-01-01

    This paper describes the molecular alignment behavior of polymer networks with switching of a ferroelectric liquid crystal (FLC) in a molecularly aligned FLC/polymer composite film. The polymer alignment in the composite film, which was slowly formed by photopolymerization-induced phase separation of a heated nematic-phase solution of FLC and monomers, was observed by polarization Raman spectral microscopy. Raman peak intensities originating from the polymers were changed with those from the FLC, when the applied voltage polarity was changed. The trace patterns of the Raman peak intensity with in-plane rotation of the composite film indicated that the formed flexible polymers can follow FLC molecular switching.

  3. Synthetic light-activated molecular switches and motors on surfaces

    NARCIS (Netherlands)

    Katsonis, Nathalie; Lubomska, Monika; Pollard, Michael M.; Feringa, Ben L.; Rudolf, Petra

    2007-01-01

    Recent advances in synthetic methods and analysis techniques provide a basis for the construction and characterization of organized arrays of molecular switches and motors on surfaces. Among them, molecular systems that can be controlled by light are particularly promising because of their ease of a

  4. Molecular magnetic switch for a metallofullerene

    OpenAIRE

    Bo WU; Wang, Taishan; Feng, Yongqiang; Zhang, Zhuxia; Jiang,Li; Wang, Chunru

    2015-01-01

    The endohedral fullerenes lead to well-protected internal species by the fullerene cages, and even highly reactive radicals can be stabilized. However, the manipulation of the magnetic properties of these radicals from outside remains challenging. Here we report a system of a paramagnetic metallofullerene Sc3C2@C80 connected to a nitroxide radical, to achieve the remote control of the magnetic properties of the metallofullerene. The remote nitroxide group serves as a magnetic switch for the e...

  5. Molecular magnetic switch for a metallofullerene

    Science.gov (United States)

    Wu, Bo; Wang, Taishan; Feng, Yongqiang; Zhang, Zhuxia; Jiang, Li; Wang, Chunru

    2015-01-01

    The endohedral fullerenes lead to well-protected internal species by the fullerene cages, and even highly reactive radicals can be stabilized. However, the manipulation of the magnetic properties of these radicals from outside remains challenging. Here we report a system of a paramagnetic metallofullerene Sc3C2@C80 connected to a nitroxide radical, to achieve the remote control of the magnetic properties of the metallofullerene. The remote nitroxide group serves as a magnetic switch for the electronic spin resonance (ESR) signals of Sc3C2@C80 via spin–spin interactions. Briefly, the nitroxide radical group can ‘switch off’ the ESR signals of the Sc3C2@C80 moiety. Moreover, the strength of spin–spin interactions between Sc3C2@C80 and the nitroxide group can be manipulated by changing the distance between these two spin centres. In addition, the ESR signals of the Sc3C2@C80 moiety can be switched on at low temperatures through weakened spin–lattice interactions. PMID:25732144

  6. Phosphorylation: The Molecular Switch of Double-Strand Break Repair

    Directory of Open Access Journals (Sweden)

    K. C. Summers

    2011-01-01

    Full Text Available Repair of double-stranded breaks (DSBs is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ, homologous recombination (HR, or the inclusive DNA damage response (DDR. These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

  7. A pH-sensitive peptide-containing lasso molecular switch.

    Science.gov (United States)

    Clavel, Caroline; Fournel-Marotte, Karine; Coutrot, Frédéric

    2013-09-17

    The synthesis of a peptide-containing lasso molecular switch by a self-entanglement strategy is described. The interlocked rotaxane molecular machine consists of a benzometaphenylene[25]crown-8 (BMP25C8) macrocycle surrounding a molecular axle. This molecular axle contains a tripeptidic sequence and two molecular stations: a N-benzyltriazolium and a pH-sensitive anilinium station. The tripeptide is located between the macrocycle and the triazolium station, so that its conformation can be tailored depending on the shuttling of the macrocycle from one station to the other. At acidic pH, the macrocycle resides around the anilinium moiety, whereas it shuttles around the triazolium station after deprotonation. This molecular machinery thus forces the lasso to adopt a tightened or a loosened conformation.

  8. Dissipation enhanced vibrational sensing in an olfactory molecular switch

    Energy Technology Data Exchange (ETDEWEB)

    Chęcińska, Agata; Heaney, Libby [Centre for Quantum Technologies, National University of Singapore, Singapore 117543 (Singapore); Pollock, Felix A. [Atomic and Laser Physics, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU (United Kingdom); Nazir, Ahsan [Photon Science Institute and School of Physics and Astronomy, University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Centre for Quantum Dynamics, Imperial College London, London SW7 2AZ (United Kingdom)

    2015-01-14

    Motivated by a proposed olfactory mechanism based on a vibrationally activated molecular switch, we study electron transport within a donor-acceptor pair that is coupled to a vibrational mode and embedded in a surrounding environment. We derive a polaron master equation with which we study the dynamics of both the electronic and vibrational degrees of freedom beyond previously employed semiclassical (Marcus-Jortner) rate analyses. We show (i) that in the absence of explicit dissipation of the vibrational mode, the semiclassical approach is generally unable to capture the dynamics predicted by our master equation due to both its assumption of one-way (exponential) electron transfer from donor to acceptor and its neglect of the spectral details of the environment; (ii) that by additionally allowing strong dissipation to act on the odorant vibrational mode, we can recover exponential electron transfer, though typically at a rate that differs from that given by the Marcus-Jortner expression; (iii) that the ability of the molecular switch to discriminate between the presence and absence of the odorant, and its sensitivity to the odorant vibrational frequency, is enhanced significantly in this strong dissipation regime, when compared to the case without mode dissipation; and (iv) that details of the environment absent from previous Marcus-Jortner analyses can also dramatically alter the sensitivity of the molecular switch, in particular, allowing its frequency resolution to be improved. Our results thus demonstrate the constructive role dissipation can play in facilitating sensitive and selective operation in molecular switch devices, as well as the inadequacy of semiclassical rate equations in analysing such behaviour over a wide range of parameters.

  9. Molecular switching analyzed with sub-molecular precision: CuPc on Cu(111)

    Energy Technology Data Exchange (ETDEWEB)

    Schaffert, Johannes; Cottin, Maren; Sonntag, Andreas; Karacuban, Hatice; Bobisch, Christian; Moeller, Rolf [Faculty of Physics, Center for Nanointegration Duisburg-Essen, University of Duisburg-Essen, 47048 Duisburg (Germany); Lorente, Nicolas [Centro de Investigacion en Nanociencia y Nanotecnologia, Campus de la Universitat Autonoma de Barcelona, 08193 Bellaterra (Spain)

    2011-07-01

    The current fluctuations in Scanning Tunneling Microscopy and Spectroscopy have been analyzed in real time using special analogue electronics. This type of Scanning Action Microscopy technique allows to map topography and switching processes simultaneously. For the Cu-Phthalocyanine (CuPc) molecule on Cu(111), switching between two states is observed. The switching frequency, the switching amplitude and the ratio between the residence times in the observed states can be studied with Angstrom spacial resolution. Spectroscopic data obtained at 7 K yields information about the involved electronic states. Based on the experimental data as well as DFT calculations a model is presented. The CuPc molecule switches between different adsorption configurations, which are attributed to different angles of molecular rotation on the Cu(111) surface.

  10. Light-Triggered Control of Plasmonic Refraction and Group Delay by Photochromic Molecular Switches

    DEFF Research Database (Denmark)

    Großmann, Malte; Klick, Alwin; Lemke, Christoph

    2015-01-01

    An interface supporting plasmonic switching is prepared from a gold substrate coated with a polymerfilm doped with photochromic molecular switches. A reversible light-induced change in the surface plasmon polariton dispersion curve of the interface is experimentally demonstrated, evidencing...... reversible switching of the surface plasmon polariton group and phase velocity. The switching capabilities of the interface are furthermore successfully applied to achieve focus control of a plasmonic lens. The results imply the realization of nonvolatile and reversible plasmonic switching units providing...

  11. Switching Dynamics in Reaction Networks Induced by Molecular Discreteness

    CERN Document Server

    Togashi, Y; Kaneko, Kunihiko; Togashi, Yuichi

    2006-01-01

    To study the fluctuations and dynamics in chemical reaction processes, stochastic differential equations based on the rate equation involving chemical concentrations are often adopted. When the number of molecules is very small, however, the discreteness in the number of molecules cannot be neglected since the number of molecules must be an integer. This discreteness can be important in biochemical reactions, where the total number of molecules is not significantly larger than the number of chemical species. To elucidate the effects of such discreteness, we study autocatalytic reaction systems comprising several chemical species through stochastic particle simulations. The generation of novel states is observed; it is caused by the extinction of some molecular species due to the discreteness in their number. We demonstrate that the reaction dynamics are switched by a single molecule, which leads to the reconstruction of the acting network structure. We also show the strong dependence of the chemical concentra...

  12. Electronic Transport Properties of a Naphthopyran-Based Optical Molecular Switch:an ab initio Study

    Institute of Scientific and Technical Information of China (English)

    XIA Cai-Juan; LIU De-Sheng; ZHANG Ying-Tang

    2011-01-01

    The electronic transport properties of a. Naphthopyran-based molecular optical switch are investigated by using the nonequilibrium Green's Function formalism combined with first-principles density functional theory. The molecule that comprises the switch can convert between its open and closed forms upon photoexcitation. Theoretical results show that the current through the open form is significantly larger than that through the closed form, which is different from other optical switches based on ring-opening reactions of the molecular bridge. The maximum on-off ratio (about 90) can be obtained at 1.4 V. The physical origin of the switching behavior is interpreted based on the spatial distributions of molecular orbitals and the HOMO-LUMO gap. Our result shows that the naphthopyran-based molecule is a good candidate for optical molecular switches and will be useful in the near future.%@@ ronic transport properties of a naphthopyran-based molecular optical switch are investigated by using the nonequilibrium Green's function formalism combined with first-principles density functional theory.The molecule that comprises the switch can convert between its open and closed forms upon photoexcitation.Theoretical results show that the current through the open form is significantly larger than that through the closed form,which is different from other optical switches based on ring-opening reactions of the molecular bridge.The maximum on-off ratio(about 90)can be obtained at 1.4 V.The physical origin of the switching behavior is interpreted based on the spatial distributions of molecular orbitals and the HOMO-LUMO gap.Our result shows that the naphthopyran-based molecule is a good candidate for optical molecular switches and will be useful in the near future.

  13. Production of high molecular weight polylactic acid

    Science.gov (United States)

    Bonsignore, Patrick V.

    1995-01-01

    A degradable high molecular weight poly(lactic acid). A poly(lactic acid) has a terminal end group of one of carboxyl or hydroxyl groups with low molecular weight poly(lactic acid) units coupled with linking agents of di-isocyanates, bis-epoxides, bis-oxazolines and bis-ortho esters. The resulting high molecular weight poly(lactic acid) can be used for applications taking advantage of the improved physical properties.

  14. A pH-sensitive lasso-based rotaxane molecular switch.

    Science.gov (United States)

    Clavel, Caroline; Romuald, Camille; Brabet, Emile; Coutrot, Frédéric

    2013-02-25

    The synthesis of a pH-sensitive two-station [1]rotaxane molecular switch by self-entanglement of a non-interlocked hermaphrodite molecule, containing an anilinium and triazole moieties, is reported. The anilinium was chosen as the best template for the macrocycle benzometaphenylene[25]crown-8 (BMP25C8) and allowed the self-entanglement of the molecule. The equilibrium between the hermaphrodite molecule and the pseudo[1]rotaxane was studied by (1)H NMR spectroscopy: the best conditions of self-entanglement were found in the less polar solvent CD(2)Cl(2) and at high dilution. The triazole moiety was then benzylated to afford a benzyltriazolium moiety, which then played a dual role. On one hand, it acts as a bulky gate to trap the BMP25C8, thus to avoid any self-disentanglement of the molecular architecture. On another hand, it acts as a second molecular station for the macrocycle. At acidic pH, the BMP25C8 resides around the best anilinium molecular station, displaying the lasso [1]rotaxane in a loosened conformation. The deprotonation of the anilinium molecular station triggers the shuttling of the BMP25C8 around the triazolium moiety, therefore tightening the lasso.

  15. An Electrically Driven and Readable Molecular Monolayer Switch Based on a Solid Electrolyte.

    Science.gov (United States)

    Marchante, Elena; Crivillers, Núria; Buhl, Moritz; Veciana, Jaume; Mas-Torrent, Marta

    2016-01-01

    The potential application of molecular switches as active elements in information storage has been demonstrated through numerous works. Importantly, such switching capabilities have also been reported for self-assembled monolayers (SAMs). SAMs of electroactive molecules have recently been exploited as electrochemical switches. Typically, the state of these switches could be read out through their optical and/or magnetic response. These output reading processes are difficult to integrate into devices, and furthermore, there is a need to use liquid environments for switching the redox-active molecular systems. In this work, both of these challenges were overcome by using an ionic gel as the electrolyte medium, which led to an unprecedented solid-state device based on a single molecular layer. Moreover, electrochemical impedance has been successfully exploited as the output of the system.

  16. Asymmetric stochastic switching driven by intrinsic molecular noise.

    Directory of Open Access Journals (Sweden)

    David Frigola

    Full Text Available Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.

  17. Molecular modeling and molecular dynamics simulation of the polarization switching phenomena in the ferroelectric polymers PVDF at the nanoscale

    Energy Technology Data Exchange (ETDEWEB)

    Bystrov, V.S., E-mail: bystrov@ua.pt [Department of Materials and Ceramic Engineering and CICECO, University of Aveiro, 3810-193 Aveiro (Portugal); Institute of Mathematical Problems of Biology RAS, 142290, Pushchino (Russian Federation)

    2014-01-01

    The molecular modeling and molecular dynamics of polarization switching for the ferroelectric films model of polyvinylidene fluoride (PVDF) are investigated at the nanoscale. We consider a molecular model of PVDF film, consisting of two and four a chains [–CH2–CF2–]{sub n} limited by n=6 elementary units. The first-principle approach is applied to the switching and kinetics of these models. Two types of behavior were established for PVDF chains: simultaneous and sequential rotation in high and low electric fields. Kinetics of sequential polarization switching shows a homogeneous critical behavior in the low electric field with a critical point at Landau–Ginzburg–Devonshire (LGD) coercive field E=E{sub C}. This type of kinetics demonstrates a kink-like behavior for polarization solitary wave propagation. The simultaneous type of kinetics demonstrates the total domain-like polarization switching, corresponding to exponential behavior of switching time in high electric field as for bulk samples. Corresponding LGD intrinsic coercive field for a two-chain and four-chains model is E{sub C}∼2.0 GV/m with revealing size effect. Obtained results show common quantum nature of PVDF chains switching phenomena—the quantum interaction of the PVDF molecular orbitals under applied electric field at the nanoscale level. The results obtained are compared with experimental data.

  18. The stochastic behavior of a molecular switching circuit with feedback

    Directory of Open Access Journals (Sweden)

    Smith Eric

    2007-05-01

    Full Text Available Abstract Background Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component. Results Multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration, which is the case we consider. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory within a statistical mechanics framework. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. In the second-order case, the circuit never leaves the bistable regime upon increasing the number of substrate molecules at constant kinase to phosphatase ratio. Conclusion The number of substrate molecules is a key parameter controlling both the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. The relevance of the concept of memory depends on the degree of switch symmetry, as memory presupposes information to be remembered, which is highest for equal residence times in the switched states. Reviewers This article was reviewed by Artem Novozhilov (nominated by Eugene Koonin, Sergei Maslov, and Ned Wingreen.

  19. Electrically controllable molecular spin crossover switching in Fe(phen)2 (NCS)2 thin film

    Science.gov (United States)

    Mondal, Chaitali; Mandal, Swapan K.

    2016-10-01

    Spin crossover molecular complex Fe(phen)2(NCS)2 in thin film form (20-300 nm) is obtained by simple dip-coating technique on glass substrates. The growth of the molecular films is confirmed by optical and X-ray diffraction data. The morphology of the samples shows distributed nanocrystals with an average size ca. 12 nm. We measure the current (I)-voltage (V) characteristics of a device with 300 nm film thickness and show that application of electric field can induce spin state switching. The electric field experienced by individual nanocrystals separated by nanometric gap is supposed to be quite high and is plausibly playing the crucial role in instigating switching in molecular nanocrystals. The result is quite significant towards developing room temperature molecular spin cross-over switching devices in the nanoscale limit.

  20. Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure. Heart failure was induced in rats by myocardial infarction, and mitochondria were isolated from hearts by differential centrifugation. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry, a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts. Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism. Among those, the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunits while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex. These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.

  1. Amino acid properties conserved in molecular evolution.

    Directory of Open Access Journals (Sweden)

    Witold R Rudnicki

    Full Text Available That amino acid properties are responsible for the way protein molecules evolve is natural and is also reasonably well supported both by the structure of the genetic code and, to a large extent, by the experimental measures of the amino acid similarity. Nevertheless, there remains a significant gap between observed similarity matrices and their reconstructions from amino acid properties. Therefore, we introduce a simple theoretical model of amino acid similarity matrices, which allows splitting the matrix into two parts - one that depends only on mutabilities of amino acids and another that depends on pairwise similarities between them. Then the new synthetic amino acid properties are derived from the pairwise similarities and used to reconstruct similarity matrices covering a wide range of information entropies. Our model allows us to explain up to 94% of the variability in the BLOSUM family of the amino acids similarity matrices in terms of amino acid properties. The new properties derived from amino acid similarity matrices correlate highly with properties known to be important for molecular evolution such as hydrophobicity, size, shape and charge of amino acids. This result closes the gap in our understanding of the influence of amino acids on evolution at the molecular level. The methods were applied to the single family of similarity matrices used often in general sequence homology searches, but it is general and can be used also for more specific matrices. The new synthetic properties can be used in analyzes of protein sequences in various biological applications.

  2. The Development and Study of Molecular Electronic Switches and their Field-Effect Transistor (FET) Device Properties

    Science.gov (United States)

    2015-02-27

    reviewed journals: Final Report: The Development and Study of Molecular Electronic Switches and their Field -Effect Transistor (FET) Device Properties...fabrication of nanostructures can serve as building blocks for molecular switching devices, organic light-emitting diodes (OLEDs), photovoltaic, field ...arrays, and photovoltaic cells. We are currently synthesizing the iodo-substituted perylene diimide (6) that will be cross -coupled to the above switch

  3. Electrospun Nanofibers from a Tricyanofuran-Based Molecular Switch for Colorimetric Recognition of Ammonia Gas.

    Science.gov (United States)

    Khattab, Tawfik A; Abdelmoez, Sherif; Klapötke, Thomas M

    2016-03-14

    A chromophore based on tricyanofuran (TCF) with a hydrazone (H) recognition moiety was developed. Its molecular-switching performance is reversible and has differential sensitivity towards aqueous ammonia at comparable concentrations. Nanofibers were fabricated from the TCF-H chromophore by electrospinning. The film fabricated from these nanofibers functions as a solid-state optical chemosensor for probing ammonia vapor. Recognition of ammonia vapor occurs by proton transfer from the hydrazone fragment of the chromophore to the ammonia nitrogen atom and is facilitated by the strongly electron withdrawing TCF fragment. The TCF-H chromophore was added to a solution of poly(acrylic acid), which was electrospun to obtain a nanofibrous sensor device. The morphology of the nanofibrous sensor was determined by SEM, which showed that nanofibers with a diameter range of 200-450 nm formed a nonwoven mat. The resultant nanofibrous sensor showed very good sensitivity in ammonia-vapor detection. Furthermore, very good reversibility and short response time were also observed.

  4. A cytosolic carbonic anhydrase molecular switch occurs in the gills of metamorphic sea lamprey

    Science.gov (United States)

    Ferreira-Martins, D.; McCormick, Stephen; Campos, A.; Lopes-Marques, M.; Osorio, H.; Coimbra, J.; Castro, L.F.C.; Wilson, Jonthan M

    2016-01-01

    Carbonic anhydrase plays a key role in CO2 transport, acid-base and ion regulation and metabolic processes in vertebrates. While several carbonic anhydrase isoforms have been identified in numerous vertebrate species, basal lineages such as the cyclostomes have remained largely unexamined. Here we investigate the repertoire of cytoplasmic carbonic anhydrases in the sea lamprey (Petromyzon marinus), that has a complex life history marked by a dramatic metamorphosis from a benthic filter-feeding ammocoete larvae into a parasitic juvenile which migrates from freshwater to seawater. We have identified a novel carbonic anhydrase gene (ca19) beyond the single carbonic anhydrase gene (ca18) that was known previously. Phylogenetic analysis and synteny studies suggest that both carbonic anhydrase genes form one or two independent gene lineages and are most likely duplicates retained uniquely in cyclostomes. Quantitative PCR of ca19 and ca18 and protein expression in gill across metamorphosis show that the ca19 levels are highest in ammocoetes and decrease during metamorphosis while ca18 shows the opposite pattern with the highest levels in post-metamorphic juveniles. We propose that a unique molecular switch occurs during lamprey metamorphosis resulting in distinct gill carbonic anhydrases reflecting the contrasting life modes and habitats of these life-history stages.

  5. Sox2 transcription network acts as a molecular switch to regulate properties of neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Koji; Shimozaki

    2014-01-01

    Neural stem cells(NSCs) contribute to ontogeny by producing neurons at the appropriate time and location. Neurogenesis from NSCs is also involved in various biological functions in adults. Thus, NSCs continue to exert their effects throughout the lifespan of the organism. The mechanism regulating the core functional properties of NSCs is governed by intra- and extracellular signals. Among the transcription factors that serve as molecular switches, Sox2 is considered a key factor in NSCs. Sox2 forms a core network with partner factors, thereby functioning as a molecular switch. This review discusses how the network of Sox2 partner and target genes illustrates the molecular characteristics of the mechanism underlying the self-renewal and multipotency of NSCs.

  6. Molecular Interaction of Pinic Acid with Sulfuric Acid

    DEFF Research Database (Denmark)

    Elm, Jonas; Kurten, 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...... from the corresponding ΔG values. The first two additions of sulfuric acid to pinic acid are found to be favorable with ΔG values of -9.06 and -10.41 kcal/mol. Addition of a third sulfuric acid molecule is less favorable and leads to a structural rearrangement forming a bridged sulfuric acid-pinic acid...... 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...

  7. Investigation of a metal-organic interface. Realization and understanding of a molecular switch

    Energy Technology Data Exchange (ETDEWEB)

    Neucheva, Olga [Forschungszentrum Juelich (DE). Institute of Bio- and Nanosystems (IBN), Functional Nanostructures at Surfaces (IBN-3)

    2010-07-01

    The field of molecular organic electronics is an emerging and very dynamic area. The continued trend to miniaturisation, combined with increasing complexity and cost of production in conventional semiconductor electronics, forces companies to turn their attention to alternatives that promise the next levels of scale at significantly lower cost. After consumer electronic devices based on organic transistors, such as TVs and book readers, have already been presented, molecular electronics is expected to offer the next breakthrough in feature size. Unfortunately, most of the organic/metal interfaces contain intrinsic defects that break the homogeneity of the interface properties. In this thesis, the electronic and structural properties of such defects were examined in order to understand the influence of the inhomogeneities on the quality of the interface layer. However, the main focus of this work was the investigation of the local properties of a single molecule. Taking advantage of the Scanning Tunnelling Microscope's (STM's) ability to act as a local probe, a single molecular switch was realized and studied. Moreover, in close collaboration with theory groups, the underlying mechanism driving the switching process was identified and described. Besides the investigation of the switching process, the ability of the STM to build nanostructures of different shapes from large organic molecules was shown. Knowing the parameters for realization and control of the switching process and for building the molecular corrals, the results of this investigation enable the reconstruction of the studied molecular ensemble and its deployment in electric molecular circuits, constituting a next step towards further miniaturization of electronic devices. (orig.)

  8. The importance of the rotor in hydrazone-based molecular switches

    Directory of Open Access Journals (Sweden)

    Xin Su

    2012-06-01

    Full Text Available The pH-activated E/Z isomerization of a series of hydrazone-based systems having different functional groups as part of the rotor (R = COMe, CN, Me, H, was studied. The switching efficiency of these systems was compared to that of a hydrazone-based molecular switch (R = COOEt whose E/Z isomerization is fully reversible. It was found that the nature of the R group is critical for efficient switching to occur; the R group should be a moderate H-bond acceptor in order to (i provide enough driving force for the rotor to move upon protonation, and (ii stabilize the obtained Z configuration, to achieve full conversion.

  9. Ab initio theory for current-induced molecular switching: Melamine on Cu(001)

    KAUST Repository

    Ohto, Tatsuhiko

    2013-05-28

    Melamine on Cu(001) is mechanically unstable under the current of a scanning tunneling microscope tip and can switch among configurations. However, these are not equally accessible, and the switching critical current depends on the bias polarity. In order to explain such rich phenomenology, we have developed a scheme to evaluate the evolution of the reaction paths and activation barriers as a function of bias, which is rooted in the nonequilibrium Green\\'s function method implemented within density functional theory. This, combined with the calculation of the inelastic electron tunneling spectroscopy signal, allows us to identify the vibrational modes promoting the observed molecular conformational changes. Finally, once our ab initio results are used within a resonance model, we are able to explain the details of the switching behavior, such as its dependence on the bias polarity, and the noninteger power relation between the reaction rate constants and both the bias voltage and the electric current. © 2013 American Physical Society.

  10. Electronic Transport Properties of an Anthraquinone-Based Molecular Switch with Carbon Nanotube Electrodes

    Institute of Scientific and Technical Information of China (English)

    ZHAO Peng; LIU De-Sheng

    2012-01-01

    Based on the nonequilibrium Green's function method and density functional theory calculations,we theoretically investigate the electronic transport properties of an anthraquinone-based molecular switch with carbon nanotube electrodes.The molecules that comprise the switch can convert between reduced hydroquinone (HQ) and oxidized anthraquinne (AQ) states via redox reactions.Our results show that the on-off ratio is increased one order of magnitude when compared to the case of gold electrodes.Moreover,an obvious negative differential resistance behavior at much low bias (0.07 V) is observed in the HQ form.%Based on the nonequilihrium Green's function method and density functional theory calculations, we theoretically investigate the electronic transport properties of an anthraquinone-based molecular switch with carbon nanotube electrodes. The molecules that comprise the switch can convert between reduced hydroquinone (HQ) and oxidized anthraquinne (AQ) states via redox reactions. Our results show that the on-off ratio is increased one order of magnitude when compared to the case of gold electrodes. Moreover, an obvious negative differential resistance behavior at much low bias (0.07 V) is observed in the HQ form.

  11. The theoretical investigation of one of the derivatives of 1, 2-dithienylcyclopentene as a molecular switch.

    Science.gov (United States)

    Safarpour, Mohammad Ali; Hashemianzadeh, Seyed Majid; Kasaeian, Azam

    2008-04-01

    The structural and electronic properties of a three-state molecular switch-an active device in a nano-electronic circuit-were studied using the B3LYP/6-31G* method. Due to its chemical stability, high conductivity upon doping, and non-linear optical properties, polythiophene is among the most widely studied conjugated organic polymers, both experimentally and theoretically. The aim of the present work was to theoretically study a very complex case: a three-state switch synthesized and experimentally investigated by Nishida et al. (Org Lett 6:2523-2526, 2004). An initial set of test calculations showed B3LYP level of theory and 6-31G* basis set to be the most appropriate for our purpose, i.e., the study of the structure, charge and spin distributions, as well as electrical characteristics such as electric polarizability, HOMO-LUMO gap (HLG) and electric dipole moment, for one of the 1,2-dithienylcyclopentene derivatives. Also, natural bond orbital analyses were performed to calculate local charges and charge transfers in order to study the capability of the molecule as a molecular switch. The results reported here are of general significance, and demonstrate that it is possible to use certain structural and electrical properties to understand and design electro-photochromic compounds showing a switching function in cases where stable forms can be exchanged by light or electron transfer. Figure Model of a thiophene wire incorporating a redox active unit.

  12. Transport dynamics of molecular motors that switch between an active and inactive state.

    Science.gov (United States)

    Pinkoviezky, I; Gov, N S

    2013-08-01

    Molecular motors are involved in key transport processes in the cell. Many of these motors can switch from an active to a nonactive state, either spontaneously or depending on their interaction with other molecules. When active, the motors move processively along the filaments, while when inactive they are stationary. We treat here the simple case of spontaneously switching motors, between the active and inactive states, along an open linear track. We use our recent analogy with vehicular traffic, where we go beyond the mean-field description. We map the phase diagram of this system, and find that it clearly breaks the symmetry between the different phases, as compared to the standard total asymmetric exclusion process. We make several predictions that may be testable using molecular motors in vitro and in living cells.

  13. Research Update: Molecular electronics: The single-molecule switch and transistor

    Directory of Open Access Journals (Sweden)

    Kai Sotthewes

    2014-01-01

    Full Text Available In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage drop across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.

  14. Biodegradation of high molecular weight polylactic acid

    Science.gov (United States)

    Stloukal, Petr; Koutny, Marek; Sedlarik, Vladimir; Kucharczyk, Pavel

    2012-07-01

    Polylactid acid seems to be an appropriate replacement of conventional non-biodegradable synthetic polymer primarily due to comparable mechanical, thermal and processing properties in its high molecular weight form. Biodegradation of high molecular PLA was studied in compost for various forms differing in their specific surface area. The material proved its good biodegradability under composting conditions and all investigated forms showed to be acceptable for industrial composting. Despite expectations, no significant differences in resulting mineralizations were observed for fiber, film and powder sample forms with different specific surface areas. The clearly faster biodegradation was detected only for the thin coating on porous material with high specific surface area.

  15. Molecular switches under TGFβ signalling during progression from cardiac hypertrophy to heart failure.

    Science.gov (United States)

    Heger, J; Schulz, R; Euler, G

    2016-01-01

    Cardiac hypertrophy is a mechanism to compensate for increased cardiac work load, that is, after myocardial infarction or upon pressure overload. However, in the long run cardiac hypertrophy is a prevailing risk factor for the development of heart failure. During pathological remodelling processes leading to heart failure, decompensated hypertrophy, death of cardiomyocytes by apoptosis or necroptosis and fibrosis as well as a progressive dysfunction of cardiomyocytes are apparent. Interestingly, the induction of hypertrophy, cell death or fibrosis is mediated by similar signalling pathways. Therefore, tiny changes in the signalling cascade are able to switch physiological cardiac remodelling to the development of heart failure. In the present review, we will describe examples of these molecular switches that change compensated hypertrophy to the development of heart failure and will focus on the importance of the signalling cascades of the TGFβ superfamily in this process. In this context, potential therapeutic targets for pharmacological interventions that could attenuate the progression of heart failure will be discussed.

  16. Transient photocurrent in molecular junctions: singlet switching on and triplet blocking.

    Science.gov (United States)

    Petrov, E G; Leonov, V O; Snitsarev, V

    2013-05-14

    The kinetic approach adapted to describe charge transmission in molecular junctions, is used for the analysis of the photocurrent under conditions of moderate light intensity of the photochromic molecule. In the framework of the HOMO-LUMO model for the single electron molecular states, the analytic expressions describing the temporary behavior of the transient and steady state sequential (hopping) as well as direct (tunnel) current components have been derived. The conditions at which the current components achieve their maximal values are indicated. It is shown that if the rates of charge transmission in the unbiased molecular diode are much lower than the intramolecular singlet-singlet excitation/de-excitation rate, and the threefold degenerated triplet excited state of the molecule behaves like a trap blocking the charge transmission, a possibility of a large peak-like transient switch-on photocurrent arises.

  17. Proteomic analysis of mitochondria reveals a metabolic switch from fatty acid oxidation to glycolysis in the failing heart

    Institute of Scientific and Technical Information of China (English)

    WANG Jun; WANG TingZhong; LIU Ping; FAN FenLing; GUAN YouFei; MA AiQun; BAI Ling; LI Jing; SUN ChaoFeng; ZHAO Jin; CUI ChangCong; HAN Ke; LIU Yu; ZHUO XiaoZhen

    2009-01-01

    This work characterizes the mitochondrial proteomic profile in the failing heart and elucidates the molecular basis of mitochondria in heart failure.Heart failure was induced in rats by myocardial infarction,and mitochondria were isolated from hearts by differential centrifugation.Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry,a system biology approach was employed to investigate differences in mitochondrial proteins between normal and failing hearts.Mass spectrometry identified 27 proteins differentially expressed that involved in energy metabolism.Among those,the up-regulated proteins included tricarboxylic acid cycle enzymes and pyruvate dehydrogenase complex subunita while the down-regulated proteins were involved in fatty acid oxidation and the OXPHOS complex.These results suggest a substantial metabolic switch from free fatty acid oxidation to glycolysis in heart failure and provide molecular evidence for alterations in the structural and functional parameters of mitochondria that may contribute to cardiac dysfunction during ischemic injury.

  18. Photo-driven molecular switch based on the photochromism and solvatochromism of diarylethene dialdehyde

    Institute of Scientific and Technical Information of China (English)

    BIN YueJing; ZHAO FuQun; CHEN ZiHui; ZHANG FuShi

    2008-01-01

    The two distinct characters of diarylethene dialdehyde derivative-photochromism and solvatochrom-ism are displayed in particular circumstances. The fluorescence of phosphorus (Ⅲ) tetrabenzotri-azacorrole can be reversibly regulated by the three kinds of status of the diarylethene dialdehyde, col-orless ring-opened form, red ring-closed form, and blue ring-closed form, which is gated by visible light, ultraviolet light and ethanol individually or jointly. Based on this effect, a novel molecular INH logic switch is proposed.

  19. Molecular mechanism of 7TM receptor activation--a global toggle switch model

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Frimurer, Thomas M; Holst, Birgitte;

    2006-01-01

    The multitude of chemically highly different agonists for 7TM receptors apparently do not share a common binding mode or active site but nevertheless act through induction of a common molecular activation mechanism. A global toggle switch model is proposed for this activation mechanism to reconcile...... to this model, a vertical see-saw movement of TM-VI-and to some degree TM-VII-around a pivot corresponding to the highly conserved prolines will occur during receptor activation, which may involve the outer segment of TM-V in an as yet unclear fashion. Small-molecule agonists can stabilize such a proposed...

  20. Multitarget Molecular Hybrids of Cinnamic Acids

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2014-12-01

    Full Text Available In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX inhibition and analgesic activity (IC50 = 0.34 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ and the highest anti-proteolytic activity (IC50= 5 μΜ. The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91% and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.

  1. Identification of dynamical hinge points of the L1 ligase molecular switch.

    Science.gov (United States)

    Giambasu, George M; Lee, Tai-Sung; Sosa, Carlos P; Robertson, Michael P; Scott, William G; York, Darrin M

    2010-04-01

    The L1 ligase is an in vitro selected ribozyme that uses a noncanonically base-paired ligation site to catalyze regioselectively and regiospecifically the 5' to 3' phosphodiester bond ligation, a reaction relevant to origin of life hypotheses that invoke an RNA world scenario. The L1 ligase crystal structure revealed two different conformational states that were proposed to represent the active and inactive forms. It remains an open question as to what degree these two conformers persist as stable conformational intermediates in solution, and along what pathway are they able to interconvert. To explore these questions, we have performed a series of molecular dynamics simulations in explicit solvent of the inactive-active conformational switch in L1 ligase. Four simulations were performed departing from both conformers in both the reactant and product states, in addition to a simulation where local unfolding in the active state was induced. From these simulations, along with crystallographic data, a set of four virtual torsion angles that span two evolutionarily conserved and restricted regions were identified as dynamical hinge points in the conformational switch transition. The ligation site visits three distinct states characterized by hydrogen bond patterns that are correlated with the formation of specific contacts that may promote catalysis. The insights gained from these simulations contribute to a more detailed understanding of the coupled catalytic/conformational switch mechanism of L1 ligase that may facilitate the design and engineering of new catalytic riboswitches.

  2. A molecular beacon-based DNA switch for reversible pH sensing in vesicles and live cells.

    Science.gov (United States)

    Narayanaswamy, Nagarjun; Nair, Raji R; Suseela, Y V; Saini, Deepak Kumar; Govindaraju, T

    2016-07-01

    In this Communication, a molecular beacon-based DNA switch (LMB) is developed as an efficient and reversible pH sensing probe. Remarkably, LMB exhibited reversible structural transition between the closed (molecular beacon) and open (A-motif) states very efficiently in synthetic vesicles and live cells without the need for any transfection agents.

  3. Switching the BZ reaction with a strong-acid-free gel.

    Science.gov (United States)

    Hara, Yusuke; Yamaguchi, Yoshinori; Mayama, Hiroyuki

    2014-01-16

    In the present study, a novel gel with a semi-interpenetrating polymer network (semi-IPN) that undergo the Belousov-Zhabotinsky (BZ) reaction without the addition of a strong acid (HNO3 or H2SO4) was developed. The required concentrations of the BZ substrates, sodium bromate (NaBrO3) and malonic acid (MA), under these conditions were higher than under the normal BZ reaction conditions, involving the addition of a strong acid. The period of the BZ reaction with the novel gel (semi-IPN BZ gel) decreased with increasing concentrations of NaBrO3 and MA. Moreover, the connection of the semi-IPN BZ gel to a conventional BZ gel facilitated the reaction in the latter through the propagation of the intermediates from the former to the latter. The BZ reaction stopped when the conventional BZ gel was disconnected from the semi-IPN BZ gel. These results demonstrate that the BZ reaction in the conventional BZ gel underwent on-off switching, controlled by its attachment to the semi-IPN BZ gel. This on-off switching mechanism would be valuable in controlling actuators and robots without strong acids.

  4. Molecular and Supramolecular Information Processing From Molecular Switches to Unconventional Computing

    CERN Document Server

    Katz, Evgeny

    2012-01-01

    Edited by a renowned and much cited chemist, this book covers the whole span of molecular computers that are based on non-biological systems. The contributions by all the major scientists in the field provide an excellent overview of the latest developments in this rapidly expanding area. A must-have for all researchers working on this very hot topic. Perfectly complements Biomolecular Information Processing, also by Prof. Katz, and available as a two-volume set.

  5. Photoisomerization dynamics of a rhodopsin-based molecule (potential molecular switch) with high quantum yields

    Science.gov (United States)

    Allen, Roland; Jiang, Chen-Wei; Zhang, Xiu-Xing; Fang, Ai-Ping; Li, Hong-Rong; Xie, Rui-Hua; Li, Fu-Li

    2015-03-01

    It is worthwhile to explore the detailed reaction dynamics of various candidates for molecular switches, in order to understand, e.g., the differences in quantum yields and switching times. Here we report density-functional-based simulations for the rhodopsin-based molecule 4-[4-Methylbenzylidene]-5-p-tolyl-3,4-dihydro-2H-pyrrole (MDP), synthesized by Sampedro et al. We find that the photoisomerization quantum yields are remarkably high: 82% for cis-to-trans, and 68% for trans-to-cis. The lifetimes of the S1 excited state in cis-MDP in our calculations are in the range of 900-1800 fs, with a mean value of 1270 fs, while the range of times required for full cis-to-trans isomerization are 1100-2000 fs, with a mean value of 1530 fs. In trans-MDP, the calculated S1 excited state lifetimes are 860-2140 fs, with a mean value of 1330 fs, and with the full trans-to-cis isomerization completed about 200 fs later. In both cases, the dominant reaction mechanism is rotation around the central C =C bond (connected to the pyrroline ring), and de-excitation occurs at an avoided crossing between the ground state and the lowest singlet state, near the midpoint of the rotational pathway. Research Fund for the Doctoral Program of Higher Education of China; Fundamental Research Funds for the Central Universities; Robert A. Welch Foundation; National Natural Science Foundation of China.

  6. NBS-LRR Proteins and Their Partners: Molecular Switches of Plant Defense

    Institute of Scientific and Technical Information of China (English)

    LIU Chunyan; QIU Hongmei; WANG Jialin; WANG Jing; CHEN Qingshan; HU Guohua

    2008-01-01

    Specificity of the plant innate immune system is often conferred by resistance (R) proteins. Most plant disease resistance (R) proteins contain a series of leucine-rich repeats (LRRs), a nucleotide-binding site (NBS), and a putative amino-terminal signaling domain. They are termed NBS-LRR proteins. The LRRs are mainly involved in recognition, and the amino-terminal domain determines signaling specificity, whereas the NBS domain presumably functions as a molecular switch. During the past years, the most important discoveries are the role of partners in NBS-LRR gene mediated defenses, mounting support for the so-called "guard hypothesis" of R gene function, and providing evidence for intramolecular interactions and intelmolecular interactions within NBS-LRR proteins as a mode of signaling regulation. The outcome of these interactions determines whether a plant activates its defense responses.

  7. Photoinduced reversible switching of porosity in molecular crystals based on star-shaped azobenzene tetramers.

    Science.gov (United States)

    Baroncini, Massimo; d'Agostino, Simone; Bergamini, Giacomo; Ceroni, Paola; Comotti, Angiolina; Sozzani, Piero; Bassanetti, Irene; Grepioni, Fabrizia; Hernandez, Taylor M; Silvi, Serena; Venturi, Margherita; Credi, Alberto

    2015-08-01

    The development of solid materials that can be reversibly interconverted by light between forms with different physico-chemical properties is of great interest for separation, catalysis, optoelectronics, holography, mechanical actuation and solar energy conversion. Here, we describe a series of shape-persistent azobenzene tetramers that form porous molecular crystals in their E-configuration, the porosity of which can be tuned by changing the peripheral substituents on the molecule. Efficient E→Z photoisomerization of the azobenzene units takes place in the solid state and converts the crystals into a non-porous amorphous melt phase. Crystallinity and porosity are restored upon Z→E isomerization promoted by visible light irradiation or heating. We demonstrate that the photoisomerization enables reversible on/off switching of optical properties such as birefringence as well as the capture of CO2 from the gas phase. The linear design, structural versatility and synthetic accessibility make this new family of materials potentially interesting for technological applications.

  8. Total synthesis of marinomycin A using salicylate as a molecular switch to mediate dimerization

    Science.gov (United States)

    Evans, P. Andrew; Huang, Mu-Hua; Lawler, Michael J.; Maroto, Sergio

    2012-08-01

    Antibiotics play a significant role in human health because of their ability to treat life-threatening bacterial infections. The growing problems with antibiotic resistance have made the development of new antibiotics a World Health Organization priority. Marinomycin A is a member of a new class of bis-salicylate-containing polyene macrodiolides, which have potent antibiotic activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Herein, we describe a triply convergent synthesis of this agent using the salicylate as a novel molecular switch for the chemoselective construction of the macrodiolide. This strategy raises new questions regarding the biosynthetic role of the salicylate and its potential impact on the mechanism of action of these types of agents. For instance, in contrast to penicillin, which enhances the electrophilicity of the cyclic amide through ring strain, salicylates reduce the electrophilicity of the aryl ester through an intramolecular resonance-assisted hydrogen bond to provide an amide surrogate.

  9. Photochromic Spatiotemporal Control of Bubble-Propelled Micromotors by a Spiropyran Molecular Switch.

    Science.gov (United States)

    Moo, James Guo Sheng; Presolski, Stanislav; Pumera, Martin

    2016-03-22

    Controlling the environment in which bubble-propelled micromotors operate represents an attractive strategy to influence their motion, especially when the trigger is as simple as light. We demonstrate that spiropyrans, which isomerize to amphiphilic merocyanines under UV irradiation, can act as molecular switches that drastically affect the locomotion of the micrometer-sized engines. The phototrigger could be either a point or a field source, thus allowing different modes of control to be executed. A whole ensemble of micromotors was repeatedly activated and deactivated by just altering the spiropyran-merocyanine ratio with light. Moreover, the velocity of individual micromotors was altered using a point irradiation source that caused only localized changes in the environment. Such selective manipulation, achieved here with an optical microscope and a photochromic additive in the medium, reveals the ease of the methodology, which can allow micro- and nanomotors to reach their full potential of not just stochastic, but directional controlled motion.

  10. 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.

  11. Controlling the color of cholesteric liquid-crystalline films by photoirradiation of a chiroptical molecular switch used as dopant

    NARCIS (Netherlands)

    van Delden, RA; Huck, NPM; Feringa, BL; Delden, Richard A. van; Gelder, Marc B. van; Huck, Nina P.M.

    2003-01-01

    Using thin films of a cholesteric mixture of acrylates 2 and 3 doped with the chiroptical molecular switch (M)-trans-1, photo-control of the reflection color between red and green is possible. This doped liquid-crystal (LC) film can be used for photoinduced writing, color reading, and photoinduced l

  12. Synthesis of Hymecromone Derivatives Containing Chiral 1,1'-Bi-2-naphthyl Moiety for Dual-mode Molecular Switch

    Institute of Scientific and Technical Information of China (English)

    Zi Xing SHAN; Chun Guang XIAO

    2004-01-01

    Some hymecromone derivatives containing chiral 1,1(-bi-2-naphthyl moiety were synthesized and their photodimerizations were investigated.It was found that fluorescence intensity and optical rotation of the new chiral hymecromone derivatives could be regulated by light.This property has potential significance for developing a new type of dual-mode molecular switch.

  13. Proton induced tautomeric switching in N-rich aromatics with tunable acid-base character

    Science.gov (United States)

    Centore, Roberto; Manfredi, Carla; Fusco, Sandra; Maglione, Cira; Carella, Antonio; Capobianco, Amedeo; Peluso, Andrea; Colonna, Daniele; Di Carlo, Aldo

    2015-08-01

    The acid-base properties of selected derivatives of the [1,2,4]triazolo[3,2-c][1,2,4]triazole fused aromatic system have been investigated by UV-vis spectroscopy. Neutral heterobicycles (HL) exhibit amphoteric behavior (they can deliver the N-H proton forming the conjugated base L- and can accept up to two protons, forming the species H2L+ and H3L++) and show an unprecedented tautomeric switching upon protonation, as revealed by single crystal X-ray analysis and confirmed by theoretical calculations. By varying the groups attached at the heterocycle, a remarkable shift of pKai values, up to 5-6 units, is observed. In particular, with strong electron attractor groups at position 7 (e.g. p-nitrophenyl or pentafluorophenyl) the neutral compounds are stronger acids than phenol or p-nitrophenol.

  14. Tip-induced domain structures and polarization switching in ferroelectric amino acid glycine

    Science.gov (United States)

    Seyedhosseini, E.; Bdikin, I.; Ivanov, M.; Vasileva, D.; Kudryavtsev, A.; Rodriguez, B. J.; Kholkin, A. L.

    2015-08-01

    Bioorganic ferroelectrics and piezoelectrics are becoming increasingly important in view of their intrinsic compatibility with biological environment and biofunctionality combined with strong piezoelectric effect and a switchable polarization at room temperature. Here, we study tip-induced domain structures and polarization switching in the smallest amino acid β-glycine, representing a broad class of non-centrosymmetric amino acids. We show that β-glycine is indeed a room-temperature ferroelectric and polarization can be switched by applying a bias to non-polar cuts via a conducting tip of atomic force microscope (AFM). Dynamics of these in-plane domains is studied as a function of an applied voltage and pulse duration. The domain shape is dictated by polarization screening at the domain boundaries and mediated by growth defects. Thermodynamic theory is applied to explain the domain propagation induced by the AFM tip. Our findings suggest that the properties of β-glycine are controlled by the charged domain walls which in turn can be manipulated by an external bias.

  15. Tip-induced domain structures and polarization switching in ferroelectric amino acid glycine

    Energy Technology Data Exchange (ETDEWEB)

    Seyedhosseini, E., E-mail: Seyedhosseini@ua.pt; Ivanov, M. [CICECO-Aveiro Institute of Materials and Department of Physics, University of Aveiro, 3810-193 Aveiro (Portugal); Bdikin, I. [TEMA and Department of Mechanical Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Vasileva, D. [Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation); Kudryavtsev, A. [Moscow State Institute of Radioengineering, Electronics and Automation, 119454 Moscow (Russian Federation); Rodriguez, B. J. [Conway Institute of Biomolecular and Biomedical Research and School of Physics, University College Dublin, Dublin (Ireland); Kholkin, A. L. [CICECO-Aveiro Institute of Materials and Department of Physics, University of Aveiro, 3810-193 Aveiro (Portugal); Institute of Natural Sciences, Ural Federal University, 620000 Ekaterinburg (Russian Federation)

    2015-08-21

    Bioorganic ferroelectrics and piezoelectrics are becoming increasingly important in view of their intrinsic compatibility with biological environment and biofunctionality combined with strong piezoelectric effect and a switchable polarization at room temperature. Here, we study tip-induced domain structures and polarization switching in the smallest amino acid β-glycine, representing a broad class of non-centrosymmetric amino acids. We show that β-glycine is indeed a room-temperature ferroelectric and polarization can be switched by applying a bias to non-polar cuts via a conducting tip of atomic force microscope (AFM). Dynamics of these in-plane domains is studied as a function of an applied voltage and pulse duration. The domain shape is dictated by polarization screening at the domain boundaries and mediated by growth defects. Thermodynamic theory is applied to explain the domain propagation induced by the AFM tip. Our findings suggest that the properties of β-glycine are controlled by the charged domain walls which in turn can be manipulated by an external bias.

  16. Isolation of Ion-Driven Conformations in Diphenylacetylene Molecular Switches Using Cryogenic Infrared Spectroscopy

    Science.gov (United States)

    Wolk, Arron B.; Garand, Etienne; Jones, Ian M.; Kamrath, Michael Z.; Hamilton, Rew; Johnson, Mark A.

    2012-06-01

    We report the infrared predissociation spectra of a family of ionic diphenylacetylene molecular switch complexes. The electrosprayed complexes were trapped and cooled in a cryogenic (10K) quadrupole ion trap and tagged with molecular deuterium. The infrared spectra of the vibrationally cold species reveal sharp transitions over a wide energy range (800 - 3800 cm-1), facilitating comparison to harmonic spectra. The evolution of the band pattern upon derivatization of the complexes exposes the signatures of the amide, urea, and carbonyl functionalities, enabling unambiguous identification of the non-covalent interactions that control the secondary structure of the molecule. Complexation with the tetramethylammonium cation reveals a conformation analogous to that of the neutral molecule, while halide ion attachment induces a conformational change similar to that observed earlier in solution. In several cases, both the donor and acceptor groups involved in the multidentate H-bonds are observed, providing a microscopic mechanical picture of the interactions at play. I. Jones, and A. Hamilton, Angew. Chem. Intl. Edit. 50, 4597 (2011).

  17. Ultrafast quenching of ring closure in molecular switches, self-assembled on gold nanoparticles

    NARCIS (Netherlands)

    Hania, Ralph; Pugžlys, Audrius; Kudernac, Tibor; Jonkman, Harry; Duppen, Koos; DeSilvestri, S.; Kobayashi, T.; Kobayashi, T.; Nelson, K.A.; Okada, T.

    2005-01-01

    We report the ultrafast quenching of the ring-closure reaction in BTE-based photochromic switches self-assembled on gold nanoparticles. The photoinduced population dynamics of the switches reveals that the electronic states of the switch molecules are strongly mixed with the states of the gold parti

  18. A predictive model of intein insertion site for use in the engineering of molecular switches.

    Directory of Open Access Journals (Sweden)

    James Apgar

    Full Text Available Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54. In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch.

  19. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz]2+

    Science.gov (United States)

    de La Cadena, Alejandro; Davydova, Dar'Ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-09-01

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz]2+ by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz]2+ in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a 3MLCT state suggests that the [Ru(bpy)2dppz]2+ complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.

  20. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz](2.).

    Science.gov (United States)

    De la Cadena, Alejandro; Davydova, Dar'ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-09-20

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz](2+) by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz](2+) in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a (3)MLCT state suggests that the [Ru(bpy)2dppz](2+) complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.

  1. Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz]2+

    Science.gov (United States)

    De la Cadena, Alejandro; Davydova, Dar’ya; Tolstik, Tatiana; Reichardt, Christian; Shukla, Sapna; Akimov, Denis; Heintzmann, Rainer; Popp, Jürgen; Dietzek, Benjamin

    2016-01-01

    An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz]2+ by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz]2+ in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a 3MLCT state suggests that the [Ru(bpy)2dppz]2+ complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment. PMID:27644587

  2. Molecular Simulation of Naphthenic Acid Removal on Acidic Catalyst Ⅱ. Experimental results of catalytic decarboxylation over acidic catalysts

    Institute of Scientific and Technical Information of China (English)

    Fu Xiaoqin; Tian Songbai; Hou Shuandi; Longjun; Wang Xieqing

    2008-01-01

    The energy barriers of thermal decarboxylation reactions of petroleum acids and catalytic decarboxylation reactions of Br(o)nsted acid and Lewis acid were analyzed using molecular simulation technology.Compared with thermal decarboxylation reactions of petroleum acids, the decarboxylation reactions by acid catalysts were easier to occur. The decarboxylaton effect by Lewis acid was better than Br(o)nsted acid. The mechanisms of catalytic decarboxylation over acid catalyst were also verified by experiments on a fixed bed and a fluidized bed, the experimental results showed that the rate of acid removal could reach up to 97% over the acidic catalyst at a temperature above 400℃.

  3. Synthesis and Characterization of Molecularly Imprinted Polymers for Phenoxyacetic Acids

    Directory of Open Access Journals (Sweden)

    Canping Pan

    2008-01-01

    Full Text Available 2-methylphenoxyacetic acid (2-MPA, 2-methyl-4-chlorophenxyacetic acid (MCPA and 4-chlorophenoxyacetic acid (4-CPA were imprinted to investigate the cross-selectivities of molecularly imprinted polymers (MIPs. The result indicates that 2-MPA, which is similar in shape, size and functionality with phenoxyacetic herbicides, are suitable to be used as a suitable template to prepare the MIPs for retaining phenoxyacetic herbicides. To study the ion-pair interactions between template molecules and functional monomer 4-vinylpiridine (4-VP, computational molecular modeling was employed. The data indicate that the cross-selectivities of MIPs for phenoxyacetic acid herbicides depend on the binding energies of complexes.

  4. A novel colorimetric triple-helix molecular switch aptasensor for ultrasensitive detection of tetracycline.

    Science.gov (United States)

    Ramezani, Mohammad; Mohammad Danesh, Noor; Lavaee, Parirokh; Abnous, Khalil; Mohammad Taghdisi, Seyed

    2015-08-15

    Detection methods of antibiotic residues in blood serum and animal derived foods are of great interest. In this study a colorimetric aptasensor was designed for sensitive, selective and fast detection of tetracycline based on triple-helix molecular switch (THMS) and gold nanoparticles (AuNPs). As a biosensor, THMS shows distinct advantages including high stability, sensitivity and preserving the selectivity and affinity of the original aptamer. In the absence of tetracycline, THMS is stable, leading to the aggregation of AuNPs by salt and an obvious color change from red to blue. In the presence of tetracycline, aptamer binds to its target, signal transduction probe (STP) leaves the THMS and adsorbs on the surface of AuNPs. So the well-dispersed AuNPs remain stable against salt-induced aggregation with a red color. The presented aptasensor showed high selectivity toward tetracyclines with a limit of detection as low as 266 pM for tetracycline. The designed aptasensor was successfully applied to detect tetracycline in serum and milk.

  5. Temperature control of molecular circuit switch responsible for virulent phenotype expression in uropathogenic Escherichia coli

    Science.gov (United States)

    Samoilov, Michael

    2010-03-01

    The behavior and fate of biological organisms are to a large extent dictated by their environment, which can be often viewed as a collection of features and constraints governed by physics laws. Since biological systems comprise networks of molecular interactions, one such key physical property is temperature, whose variations directly affect the rates of biochemical reactions involved. For instance, temperature is known to control many gene regulatory circuits responsible for pathogenicity in bacteria. One such example is type 1 fimbriae (T1F) -- the foremost virulence factor in uropathogenic E. coli (UPEC), which accounts for 80-90% of all community-acquired urinary tract infections (UTIs). The expression of T1F is randomly `phase variable', i.e. individual cells switch between virulent/fimbriate and avirulent/afimbriate phenotypes, with rates regulated by temperature. Our computational investigation of this process, which is based on FimB/FimE recombinase-mediated inversion of fimS DNA element, offers new insights into its discrete-stochastic kinetics. In particular, it elucidates the logic of T1F control optimization to the host temperature and contributes further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs.

  6. Molecular Design of Ionization-Induced Proton Switching Element Based on Fluorinated DNA Base Pair.

    Science.gov (United States)

    Tachikawa, Hiroto; Kawabata, Hiroshi

    2016-03-10

    To design theoretically the high-performance proton switching element based on DNA base pair, the effects of fluorine substitution on the rate of proton transfer (PT) in the DNA model base pair have been investigated by means of direct ab initio molecular dynamics (AIMD) method. The 2-aminopyridine dimer, (AP)2, was used as the model of the DNA base pair. One of the hydrogen atoms of the AP molecule in the dimer was substituted by a fluorine (F) atom, and the structures of the dimer, expressed by F-(AP)2, were fully optimized at the MP2/6-311++G(d,p) level. The direct AIMD calculations showed that the proton is transferred within the base pair after the vertical ionization. The rates of PT in F-(AP)2(+) were calculated and compared with that of (AP)2(+) without an F atom. It was found that PT rate is accelerated by the F-substitution. Also, the direction of PT between F-AP and AP molecules can be clearly controlled by the position of F-substitution (AP)2 in the dimer.

  7. Target-responsive structural switching for nucleic acid-based sensors.

    Science.gov (United States)

    Li, Di; Song, Shiping; Fan, Chunhai

    2010-05-18

    Interest in the development of sensitive, selective, rapid, and cost-effective biosensors for biomedical analysis, environmental monitoring, and the detection of bioterrorism agents is rapidly increasing. A classic biosensor directly transduces ligand-target binding events into a measurable physical readout. More recently, researchers have proposed novel biosensing strategies that couple ligand-induced structural switching of biomolecules with advanced optical and electronic transducers. This approach has proven to be a highly general platform for the development of new biosensors. In this Account, we describe a series of electrochemical and optical nucleic acid sensors that use target-responsive DNA structures. By employing surface-confined DNA structures with appropriate redox labels, we can monitor target-induced structural switching of DNA or aptamer-specific small molecule probes by measuring electrochemical currents that are directly associated with the distance between the redox label and the electrode surface. We have also demonstrated significant improvements in sensing performance through optimization of the DNA self-assembly process at electrode surfaces or the introduction of nanomaterial-based signal amplification. Alternatively, gold nanoparticles interact differently with folded and unfolded DNA structures, which provides a visual method for detecting target-induced structural switching based on the plasmonic change of gold nanoparticles. This novel method using gold nanoparticles has proven particularly suitable for the detection of a range of small-molecule targets (e.g., cocaine) and environmentally toxic metal ions (e.g., Hg(2+)). Rational sequence design of DNA aptamers improves the sensitivity and increases the reaction kinetics. Recently, we have also designed microfluidic devices that allow rapid and portable mercury detection with the naked eye. This Account focuses on the use of bulk and nanoscale gold and DNA/aptamer molecules. We expect

  8. Gallic acid: molecular rival of cancer.

    Science.gov (United States)

    Verma, Sharad; Singh, Amit; Mishra, Abha

    2013-05-01

    Gallic acid, a predominant polyphenol, has been shown to inhibit carcinogenesis in animal models and in vitro cancerous cell lines. The inhibitory effect of gallic acid on cancer cell growth is mediated via the modulation of genes which encodes for cell cycle, metastasis, angiogenesis and apoptosis. Gallic acid inhibits activation of NF-κB and Akt signaling pathways along with the activity of COX, ribonucleotide reductase and GSH. Moreover, gallic acid activates ATM kinase signaling pathways to prevent the processes of carcinogenesis. The data so far available, both from in vivo and in vitro studies, indicate that this dietary polyphenol could be promising agent in the field of cancer chemoprevention.

  9. Isomerization of Orthogonal Molecular Switches Encapsulated within Micelles Solubilizing Carbon Nanotubes

    DEFF Research Database (Denmark)

    Kreft, Stefanie K.; Petersen, Michael Åxman; Nielsen, Mogens Brøndsted

    2015-01-01

    We study the effects of the proximity of the orthogonal dipole-switching moiety dihydroazulene/vinylheptafulvene (DHA/VHF) to carbon nanotubes (CNTs). The switches are introduced into a micelle surrounding the CNTs, thereby achieving very close proximity between the molecules and the CNTs...... for the first time. The change of the molecules' configuration is not hindered by its encapsulation: We report the reversible switching of molecules inside CNT surrounding micelles. The orthogonality of the switch also allows us for the first time to observe the effect of the molecule on the emission spectra...

  10. Ultrafast quantum spin-state switching in the Co-octaethylporphyrin molecular magnet with a terahertz pulsed magnetic field

    Science.gov (United States)

    Farberovich, Oleg V.; Mazalova, Victoria L.

    2016-05-01

    Molecular spin crossover switches are the objects of intense theoretical and experimental studies in recent years. This interest is due to the fact that these systems allow one to control their spin state by applying an external photo-, thermo-, piezo-, or magnetic stimuli. The greatest amount of research is currently devoted to the study of the effect of the photoexcitation on the bi-stable states of spin crossover single molecular magnets (SMMs). The main limitation of photo-induced bi-stable states is their short lifetime. In this paper we present the results of a study of the spin dynamics of the Co-octaethylporphyrin (CoOEP) molecule in the Low Spin (LS) state and the High Spin (HS) state induced by applying the magnetic pulse of 36.8 T. We show that the spin switching in case of the HS state of the CoOEP molecule is characterized by a long lifetime and is dependent on the magnitude and duration of the applied field. Thus, after applying an external stimuli the system in the LS state after the spin switching reverts to its ground state, whereas the system in the HS state remains in the excited state for a long time. We found that the temperature dependency of magnetic susceptibility shows an abrupt thermal spin transition between two spin states at 40 K. Here the proposed theoretical approach opens the way to create modern devices for spintronics with the controllable spin switching process.

  11. Simultaneous determination of amino acids and carbohydrates in culture media of Clostridium thermocellum by valve-switching ion chromatography.

    Science.gov (United States)

    Fa, Yun; Yang, Haiyan; Ji, Chengshuai; Cui, He; Zhu, Xinshu; Du, Juan; Gao, Jun

    2013-10-10

    An improved method for the simultaneous determination of 20 amino acids and 7 carbohydrates using one-valve switching after injection, ion chromatography, and integrated pulsed amperometric detection is proposed. The resolution of the amino acids and carbohydrates in the cation trap column was investigated. In addition, parameters including flow liquid type, flow rate, concentration, and valve-switch timing were optimized. The method is time-saving, effective, and accurate for the simultaneous separation of amino acids and carbohydrates, with a mean correlation coefficient of >0.99 and repeatability of 0.5-4.6% for eight replicates. The method was successfully applied in the analysis of amino acids and carbohydrates in aseptic media and in extracellular culture media of three phenotypes of Clostridium thermocellum.

  12. Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

    Science.gov (United States)

    Bellomaria, A; Nepravishta, R; Mazzanti, U; Marchetti, M; Piccioli, P; Paci, M

    2014-10-15

    Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments.

  13. Programmable DNA triple-helix molecular switch in biosensing applications: from in homogenous solutions to in living cells.

    Science.gov (United States)

    Tang, Pinting; Zheng, Jing; Tang, Jianru; Ma, Dandan; Xu, Weijian; Li, Jishan; Cao, Zhong; Yang, Ronghua

    2017-02-21

    Herein, we demonstrated a new gold nanoparticles (AuNPs)-integrated programmable triple-helix molecular switch (THMS) to realize the biosensing of multiple targets from in homogenous solution to in living cells. The results demonstrated that this proposed programmable THMS could be successfully used for imaging multiple messenger RNA (mRNA) in living cells and it significantly extends the scope of the THMS sensing platform.

  14. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway

    DEFF Research Database (Denmark)

    Amit, Sharon; Hatzubai, Ada; Birman, Yaara;

    2002-01-01

    The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin a......, thereby precluding the initiation of the cascade. Thus, a single, CKI-dependent phosphorylation event serves as a molecular switch for the Wnt pathway. Udgivelsesdato: 2002-May-1...

  15. Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Papetti, Moreno; Rigbolt, Kristoffer T G

    2016-01-01

    identified RAB7 phosphorylation and RCP recruitment to EGFR as switches for EGF and TGF-α outputs, controlling receptor trafficking, signaling duration, proliferation, and migration. By manipulating RCP levels or phosphorylation of RAB7 in EGFR-positive cancer cells, we were able to switch a TGF...

  16. Aptamer contained triple-helix molecular switch for rapid fluorescent sensing of acetamiprid.

    Science.gov (United States)

    Liu, Xin; Li, Ying; Liang, Jing; Zhu, Wenyue; Xu, Jingyue; Su, Ruifang; Yuan, Lei; Sun, Chunyan

    2016-11-01

    In this study, an aptamer-based fluorescent sensing platform using triple-helix molecular switch (THMS) was developed for the pesticide screening represented by acetamiprid. The THMS was composed of two tailored DNA probes: a label-free central target specific aptamer sequence flanked by two arm segments acting as a recognition probe; a hairpin-shaped structure oligonucleotide serving as a signal transduction probe (STP), labeled with a fluorophore and a quencher at the 3' and 5'-end, respectively. In the absence of acetamiprid, complementary bindings of two arm segments of the aptamers with the loop sequence of STP enforce the formation of THMS with the "open" configuration of STP, and the fluorescence of THMS is on. In the presence of target acetamiprid, the aptamer-target binding results in the formation of a structured aptamer/target complex, which disassembles the THMS and releases the STP. The free STP is folded to a stem loop structure, and the fluorescence is quenched. The quenched fluorescence intensity was proportional to the concentration of acetamiprid in the range from 100 to 1200nM, with the limit of detection (LOD) as low as 9.12nM. In addition, this THMS-based method has been successfully used to test and quantify acetamiprid in Chinese cabbage with satisfactory recoveries, and the results were in full agreement with those from LC-MS. The aptamer-based THMS presents distinct advantages, including high stability, remarkable sensitivity, and preservation of the affinity and specificity of the original aptamer. Most importantly, this strategy is convenient and generalizable by virtue of altering the aptamer sequence without changing the triple-helix structure. So, it is expected that this aptamer-based fluorescent assay could be extensively applied in the field of food safety inspection.

  17. Molecular screening of wine lactic acid bacteria degrading hydroxycinnamic acids.

    Science.gov (United States)

    de las Rivas, Blanca; Rodríguez, Héctor; Curiel, José Antonio; Landete, José María; Muñoz, Rosario

    2009-01-28

    The potential to produce volatile phenols from hydroxycinnamic acids was investigated for lactic acid bacteria (LAB) isolated from Spanish grape must and wine. A PCR assay was developed for the detection of LAB that potentially produce volatile phenols. Synthetic degenerate oligonucleotides for the specific detection of the pdc gene encoding a phenolic acid decarboxylase were designed. The pdc PCR assay amplifies a 321 bp DNA fragment from phenolic acid decarboxylase. The pdc PCR method was applied to 85 strains belonging to the 6 main wine LAB species. Lactobacillus plantarum, Lactobacillus brevis, and Pediococcus pentosaceus strains produce a positive response in the pdc PCR assay, whereas Oenococcus oeni, Lactobacillus hilgardii, and Leuconostoc mesenteroides strains did not produce the expected PCR product. The production of vinyl and ethyl derivatives from hydroxycinnamic acids in culture media was determined by high-performance liquid chromatography. A relationship was found between pdc PCR amplification and volatile phenol production, so that the LAB strains that gave a positive pdc PCR response produce volatile phenols, whereas strains that did not produce a PCR amplicon did not produce volatile phenols. The proposed method could be useful for a preliminary identification of LAB strains able to produce volatile phenols in wine.

  18. A theoretical investigation on anomalous switching of single-stranded deoxyribonucleic acid (ssDNA) monolayers by water vapor

    Institute of Scientific and Technical Information of China (English)

    赵新军; 高志福; 蒋中英

    2015-01-01

    In this paper, we use a molecular theory to study the anomalous switching of ssDNA monolayers. Here, both ssDNA–water and water–water hydrogen bonds and their explicit coupling to the ssDNA conformations are considered. We find that hydrogen bonding becomes a key element in inducing the anomalous switching of ssDNA monolayers. This finding accords well with the experimental observations. Based on our theoretical model, we predict that the anomalous switching induced by water vapor will be applicable to a wide range of hydrogen bonds polymers, and ssDNA–water hydrogen bonds and water–water hydrogen bonds hybridization will lead to the hydrogen-bond network formation of 3D ssDNA monolayers.

  19. Palladium-atom catalyzed formic acid decomposition and the switch of reaction mechanism with temperature.

    Science.gov (United States)

    He, Nan; Li, Zhen Hua

    2016-04-21

    Formic acid decomposition (FAD) reaction has been an innovative way for hydrogen energy. Noble metal catalysts, especially palladium-containing nanoparticles, supported or unsupported, perform well in this reaction. Herein, we considered the simplest model, wherein one Pd atom is used as the FAD catalyst. With high-level theoretical calculations of CCSD(T)/CBS quality, we investigated all possible FAD pathways. The results show that FAD catalyzed by one Pd atom follows a different mechanism compared with that catalyzed by surfaces or larger clusters. At the initial stage of the reaction, FAD follows a dehydration route and is quickly poisoned by CO due to the formation of very stable PdCO. PdCO then becomes the actual catalyst for FAD at temperatures approximately below 1050 K. Beyond 1050 K, there is a switch of catalyst from PdCO to Pd atom. The results also show that dehydration is always favoured over dehydrogenation on either the Pd-atom or PdCO catalyst. On the Pd-atom catalyst, neither dehydrogenation nor dehydration follows the formate mechanism. In contrast, on the PdCO catalyst, dehydrogenation follows the formate mechanism, whereas dehydration does not. We also systematically investigated the performance of 24 density functional theory methods. We found that the performance of the double hybrid mPW2PLYP functional is the best, followed by the B3LYP, B3PW91, N12SX, M11, and B2PLYP functionals.

  20. Electropolymerized Molecularly Imprinted Polypyrrole Film for Sensing of Clofibric Acid

    Directory of Open Access Journals (Sweden)

    Bianca Schweiger

    2015-02-01

    Full Text Available Piezoelectric quartz crystals and analogous gold substrates were electrochemically coated with molecularly imprinted polypyrrole films for pulsed amperometric detection (PAD of clofibric acid, a metabolite of clofibrate. Cyclic voltammetry data obtained during polymerization and deposited weight estimations revealed a decrease of the polymerization rate with increasing clofibric acid concentration. XPS measurements indicated that clofibric acid could be removed after imprinting with an aqueous ethanol solution, which was further optimized by using PAD. Zeta potential and contact angle measurements revealed differences between molecularly imprinted (MIP and non-imprinted polymer (NIP layers. Binding experiments with clofibric acid and other substances showed a pronounced selectivity of the MIP for clofibric acid vs. carbamazepine, but the response of MIP and NIP to 2,4-dichlorophenoxyacetic acid was higher than that for clofibric acid. A smooth surface, revealed by AFM measurements, with roughness of 6–8 nm for imprinted and non-imprinted layers, might be a reason for an excessively low density of specific binding sites for clofibric acid. Furthermore, the decreased polymerization rate in the presence of clofibric acid might not result in well-defined polymer structures, which could be the reason for the lower sensitivity.

  1. Ab initio study of transport properties of an all-carbon molecular switch based on C20 molecule

    Institute of Scientific and Technical Information of China (English)

    OUYANG Fang-ping; XU Hui

    2007-01-01

    Choosing closed-ended armchair (5, 5) singlewall carbon nanotubes (CCNTs) as electrodes, we have investigated the electron transport properties across a carbon molecular junction consisting of a C20 molecule sandwiched between two semi-infinite carbon nanotubes. It is shown that the Landauer conductance of this carbon hybrid system can be tuned within several orders of magnitude not only by varying the tube-C20 distance, but more importantly by changing the orientation of the C20 molecule and rotating the C20 molecule or one of the tubes around the symmetry axis of the system at fixed distances. This fact could make this all-carbon molecular system a possible candidate for a nanoelectronic switching device. Moreover, our study also reveals that molecular configuration selection and structural relaxation would play an important role in the design of such devices.

  2. Reversible molecular switching at a metal surface: A case study of tetra- tert-butyl-azobenzene on Au(1 1 1)

    Science.gov (United States)

    Wolf, Martin; Tegeder, Petra

    2009-06-01

    Molecular switches represent a fascinating class of functional molecules, whose properties can be reversibly changed between different molecular states by excitation with light or other external stimuli. Using surface science concepts like self assembly to align such molecules in a well-defined geometry at solid surfaces, new functional properties may arise, which are relevant for different fields like, e.g., molecular electronics, sensing or biocompatible interfaces. For a microscopic understanding of molecular switching at surfaces, it is essential to obtain detailed knowledge on the underlying elementary processes, for instance the excitation mechanism in photoinduced switching. Here we present a case study of a specifically designed azobenzene derivative on a metal surface, namely tetra- tert-butyl-azobenzene (TBA) adsorbed on Au(1 1 1), which is so far one of the best studied system for which reversible conformational changes have been demonstrated. TBA/Au(1 1 1) can thus be viewed as model system in order to gain deeper insights into molecular switching processes at metal surfaces. We have studied the photoinduced and thermally activated reversible switching of TBA in direct contact with a Au(1 1 1) surface using two-photon photoemission (2PPE) and high-resolution electron energy loss spectroscopy (HREELS). The trans/cis-isomerization of TBA is accompanied by reversible changes in the geometrical and electronic structure of the molecules, allowing to gain mechanistic and quantitative insight into the switching process. In particular, the cross sections for the photoisomerization, the ratio between the cis- and trans-TBA in the photostationary state, and the activation energy for the thermally induced cis→trans reaction have been determined and are found to be strongly reduced compared to the corresponding quantities in the liquid phase. Furthermore, the mechanism of optical excitation and molecular switching of TBA on Au(1 1 1) has been identified to arise

  3. Single electron bipolar conductance switch driven by the molecular Aharonov-Bohm effect.

    Science.gov (United States)

    Lee, Joonhee; Tallarida, Nicholas; Rios, Laura; Perdue, Shawn M; Apkarian, Vartkess Ara

    2014-06-24

    We demonstrate a conductance switch controlled by the spin-vibronic density of an odd electron on a single molecule. The junction current is modulated by the spin-flip bistability of the electron. Functional images are provided as wiring diagrams for control of the switch's frequency, amplitude, polarity, and duty-cycle. The principle of operation relies on the quantum mechanical phase associated with the adiabatic circulation of a spin-aligned electron around a conical intersection. The functional images quantify the governing vibronic Hamiltonian.

  4. The Role of Concentration and Solvent Character in the Molecular Organization of Humic Acids

    Directory of Open Access Journals (Sweden)

    Martina Klučáková

    2016-10-01

    Full Text Available The molecular organization of humic acids in different aqueous solutions was studied over a wide concentration range (0.01–10 g·dm−3. Solutions of humic acids were prepared in three different media: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic sample. Potentiometry, conductometry, densitometry, and high resolution ultrasound spectrometry were used in order to investigate conformational changes in the humic systems. The molecular organization of humic acids in the studied systems could be divided into three concentration ranges. The rearrangements were observed at concentrations of ~0.02 g·dm−3 and ~1 g·dm−3. The first “switch-over point” was connected with changes in the hydration shells of humic particles resulting in changes in their elasticity. The compressibility of water in the hydration shells is less than the compressibility of bulk water. The transfer of hydration water into bulk water increased the total compressibility of the solution, reducing the ultrasonic velocity. The aggregation of humic particles and the formation of rigid structures in systems with concentrations higher than 1 g·dm−3 was detected.

  5. Electrostatic Switch Function in the Mechanism of Protein Kinase A Iα Activation: Results of the Molecular Dynamics Simulation

    Science.gov (United States)

    Rogacheva, Olga N.; Shchegolev, Boris F.

    2017-01-01

    We used molecular dynamics to find the average path of the A-domain H → B conformational transition in protein kinase A Iα. We obtained thirteen productive trajectories and processed them sequentially using factor and cross-correlation analyses. The conformational transition is presented as partly deterministic sequence of six events. Event B represents H → B transition of the phosphate binding cassette. Main participants of this event form electrostatic switch cAMP(O6)–A202(N-H)–G199(C=O). Through this switch, cAMP transmits information about its binding to hydrophobic switch L203–Y229 and thus triggers conformational transition of A-domain. Events C and D consist in N3A-motif displacement towards phosphate binding cassette and B/C-helix rotation. Event E involves an increase in interaction energy between Y229 and β-subdomain. Taken together, events B, E, and D correspond to the hinge movement towards β-barrel. Transition of B/C-helix turn (a.a. 229–234) from α-form to π-form accounts for event F. Event G implies that π-helical turn is replaced by kink. Emerging in the resulting conformation, electrostatic interaction R241–E200 facilitates kink formation. The obtained data on the mechanism of cAMP-dependent activation of PKA Iα may contribute to new approaches to designing pharmaceuticals based on cAMP analogs.

  6. Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell

    Science.gov (United States)

    Sotiropoulou, Georgia; Pampalakis, Georgios; Lianidou, Evi; Mourelatos, Zissimos

    2009-01-01

    Transformation of normal cells into malignant tumors requires the acquisition of six hallmark traits, e.g., self-sufficiency in growth signals, insensitivity to antigrowth signals and self-renewal, evasion of apoptosis, limitless replication potential, angiogenesis, invasion, and metastasis, which are common to all cancers (Hanahan and Weinberg 2000). These new cellular traits evolve from defects in major regulatory microcircuits that are fundamental for normal homeostasis. The discovery of microRNAs (miRNAs) as a new class of small non-protein-coding RNAs that control gene expression post-transcriptionally by binding to various mRNA targets suggests that these tiny RNA molecules likely act as molecular switches in the extensive regulatory web that involves thousands of transcripts. Most importantly, accumulating evidence suggests that numerous microRNAs are aberrantly expressed in human cancers. In this review, we discuss the emergent roles of microRNAs as switches that function to turn on/off known cellular microcircuits. We outline recent compelling evidence that deregulated microRNA-mediated control of cellular microcircuits cooperates with other well-established regulatory mechanisms to confer the hallmark traits of the cancer cell. Furthermore, these exciting insights into aberrant microRNA control in cancer-associated circuits may be exploited for cancer therapies that will target deregulated miRNA switches. PMID:19561119

  7. Electrochemical control of quantum interference in anthraquinone-based molecular switches

    DEFF Research Database (Denmark)

    Markussen, Troels; Schiøtz, Jakob; Thygesen, Kristian Sommer

    2010-01-01

    Using first-principles calculations we analyze the electronic transport properties of a recently proposed anthraquinone-based electrochemical switch. Robust conductance on/off ratios of several orders of magnitude are observed due to destructive quantum interference present in the anthraquinone...

  8. Transition metal functionalized photo- and redox-switchable diarylethene based molecular switches

    NARCIS (Netherlands)

    Harvey, Emma C.; Feringa, Ben L.; Vos, Johannes G.; Browne, Wesley R.; Pryce, Mary T.

    2015-01-01

    In this review recent progress in combining metal carbonyl and bipyridyl transition metal complexes with dithienylethene photochromic switches is discussed. A key challenge in designing such systems is to allow for interaction between the various components, but without loss in photochemical activit

  9. Molecular Basis for Mycophenolic Acid Biosynthesis in Penicillium brevicompactum

    DEFF Research Database (Denmark)

    Regueira, Torsten Ulrik Bak; Kildegaard, Kanchana Rueksomtawin; Hansen, Bjarne Gram;

    2011-01-01

    Mycophenolic acid (MPA) is the active ingredient in the increasingly important immunosuppressive pharmaceuticals CellCept (Roche) and Myfortic (Novartis). Despite the long history of MPA, the molecular basis for its biosynthesis has remained enigmatic. Here we report the discovery of a polyketide...

  10. Incorporation of oxygen into abscisic Acid and phaseic Acid from molecular oxygen.

    Science.gov (United States)

    Creelman, R A; Zeevaart, J A

    1984-05-01

    Abscisic acid accumulates in detached, wilted leaves of Xanthium strumarium. When these leaves are subsequently rehydrated, phaseic acid, a catabolite of abscisic acid, accumulates. Analysis by gas chromatography-mass spectrometry of phaseic acid isolated from stressed and subsequently rehydrated leaves placed in an atmosphere containing 20% (18)O(2) and 80% N(2) indicates that one atom of (18)O is incorporated in the 6'-hydroxymethyl group of phaseic acid. This suggests that the enzyme that converts abscisic acid to phaseic acid is an oxygenase.Analysis by gas chromatography-mass spectrometry of abscisic acid isolated from stressed leaves kept in an atmosphere containing (18)O(2) indicates that one atom of (18)O is present in the carboxyl group of abscisic acid. Thus, when abscisic acid accumulates in water-stressed leaves, only one of the four oxygens present in the abscisic acid molecule is derived from molecular oxygen. This suggests that either (a) the oxygen present in the 1'-, 4'-, and one of the two oxygens at the 1-position of abscisic acid arise from water, or (b) there exists a stored precursor with oxygen atoms already present in the 1'- and 4'-positions of abscisic acid which is converted to abscisic acid under conditions of water stress.

  11. Molecular modeling of nucleic Acid structure: electrostatics and solvation.

    Science.gov (United States)

    Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

    2014-12-19

    This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit.

  12. Mode switching of a self-propelled camphor disk sensitive to the photoisomerization of a molecular layer on water.

    Science.gov (United States)

    Nakata, Satoshi; Miyaji, Tatsuya; Matsuda, Yui; Yoshii, Miyu; Abe, Manabu

    2014-07-01

    A simple self-propelled motor on a 4-[[(dodecyloxy)benz-4-yl]azo]benzoic acid (DBA) molecular layer was investigated from the viewpoint of motor control depending on the molecular structure. The nature of the self-motion of a camphor disk on the DBA molecular layer changed depending on the surface pressure (π)-area (A) isotherm of DBA, which in turn changed by the photoisomerization between UV and green lights. The characteristic motion of the camphor disk is discussed in relation to the π-A isotherm of DBA, which changes depending on the photoisomerization as the driving force of motion.

  13. Hydrogen bond switching among flavin and amino acid side chains in the BLUF photoreceptor observed by ultrafast infrared spectroscopy.

    Science.gov (United States)

    Bonetti, Cosimo; Mathes, Tilo; van Stokkum, Ivo H M; Mullen, Katharine M; Groot, Marie-Louise; van Grondelle, Rienk; Hegemann, Peter; Kennis, John T M

    2008-11-15

    BLUF domains constitute a recently discovered class of photoreceptor proteins found in bacteria and eukaryotic algae. BLUF domains are blue-light sensitive through a FAD cofactor that is involved in an extensive hydrogen-bond network with nearby amino acid side chains, including a highly conserved tyrosine and glutamine. The participation of particular amino acid side chains in the ultrafast hydrogen-bond switching reaction with FAD that underlies photoactivation of BLUF domains is assessed by means of ultrafast infrared spectroscopy. Blue-light absorption by FAD results in formation of FAD(*-) and a bleach of the tyrosine ring vibrational mode on a picosecond timescale, showing that electron transfer from tyrosine to FAD constitutes the primary photochemistry. This interpretation is supported by the absence of a kinetic isotope effect on the fluorescence decay on H/D exchange. Subsequent protonation of FAD(*-) to result in FADH(*) on a picosecond timescale is evidenced by the appearance of a N-H bending mode at the FAD N5 protonation site and of a FADH(*) C=N stretch marker mode, with tyrosine as the likely proton donor. FADH(*) is reoxidized in 67 ps (180 ps in D(2)O) to result in a long-lived hydrogen-bond switched network around FAD. This hydrogen-bond switch shows infrared signatures from the C-OH stretch of tyrosine and the FAD C4=O and C=N stretches, which indicate increased hydrogen-bond strength at all these sites. The results support a previously hypothesized rotation of glutamine by approximately 180 degrees through a light-driven radical-pair mechanism as the determinant of the hydrogen-bond switch.

  14. Analysis of proteins responsive to acetic acid in Acetobacter: molecular mechanisms conferring acetic acid resistance in acetic acid bacteria.

    Science.gov (United States)

    Nakano, Shigeru; Fukaya, Masahiro

    2008-06-30

    Acetic acid bacteria are used for industrial vinegar production because of their remarkable ability to oxidize ethanol and high resistance to acetic acid. Although several molecular machineries responsible for acetic acid resistance in acetic acid bacteria have been reported, the entire mechanism that confers acetic acid resistance has not been completely understood. One of the promising methods to elucidate the entire mechanism is global analysis of proteins responsive to acetic acid by two-dimensional gel electrophoresis. Recently, two proteins whose production was greatly enhanced by acetic acid in Acetobacter aceti were identified to be aconitase and a putative ABC-transporter, respectively; furthermore, overexpression or disruption of the genes encoding these proteins affected acetic acid resistance in A. aceti, indicating that these proteins are involved in acetic acid resistance. Overexpression of each gene increased acetic acid resistance in Acetobacter, which resulted in an improvement in the productivity of acetic acid fermentation. Taken together, the results of the proteomic analysis and those of previous studies indicate that acetic acid resistance in acetic acid bacteria is conferred by several mechanisms. These findings also provide a clue to breed a strain having high resistance to acetic acid for vinegar fermentation.

  15. Supramolecular assemblies and molecular recognition of amphiphilic schiff bases with barbituric acid in organized molecular films.

    Science.gov (United States)

    Jiao, Tifeng; Liu, Minghua

    2005-02-24

    A bolaform Schiff base, N,N'-bis(salicylidene)-1,10-decanediamine (BSC10), has been synthesized and its interfacial hydrogen bond formation or molecular recognition with barbituric acid was investigated in comparison with that of a single chain Schiff base, 2-hydroxybenzaldehyde-octadecylamine (HBOA). It has been found that while HBOA formed a monolayer at the air/water interface, the bolaform Schiff base formed a multilayer film with ordered layer structure on water surface. When the Schiff bases were spread on the subphase containing barbituric acid, both of the Schiff bases could form hydrogen bonds with barbituric acid in situ in the spreading films. As a result, an increase of the molecular areas in the isotherms was observed. The in situ H-bonded films could be transferred onto solid substrates, and the transferred multilayer films were characterized by various methods such as UV-vis and FT-IR spectrosopies. Spectral changes were observed for the films deposited from the barbituric acid subphase, which supported the hydrogen bond formation between the Schiff bases and barbituric acid. By measuring the MS-TOF of the deposited films dissolved in CHCl3 solution, it was concluded that a 2:1 complex of HBOA with barbituric acid and a 1:2 complex of BSC10 with barbituric acid were formed. On the other hand, when the multilayer films of both Schiff bases were immersed in an aqueous solution of barbituric acid, a similar molecular recognition through the hydrogen bond occurred. A clear conformational change of the alkyl spacer in the bolaform Schiff base was observed during the complex formation with the barbituric acid.

  16. Troger's base molecular scaffolds in dicarboxylic acid recognition.

    Science.gov (United States)

    Goswami, S; Ghosh, K; Dasgupta, S

    2000-04-07

    Artificial receptors (1-5) have been designed and synthesized from simple precursors. The chain length selectivity studies of dicarboxylic acids within the cavities of new fluorescent Troger's base molecular frameworks (1-3) have been carried out with a critical examination of their role of rigidity as well as flexibility in selective binding in comparison to receptor 5. The chiral resolution of the racemic Troger's base receptors (1 and 2) by chiral recognition with (+)- camphoric acid using hydrogen-bonding interactions has been studied.

  17. Molecular Dynamic Studies on Langmuir Monolayers of Stearic Acid

    Institute of Scientific and Technical Information of China (English)

    KONG Chui-peng; ZHANG Hong-xing; ZHAO Zeng-xia; ZHENG Qing-chuan

    2013-01-01

    Compression isotherm for stearic acid was obtained by means of molecular dynamic simulation and compared to experimentally measured values for the Langmuir monolayers.Compared to the previous simulation,the present simulation has provided a method to reproduce the compression of the monolayer.The result is consistent with other experimental results.By analyzing the alkyl tails,the configuration of stearic acid molecules during the compression process was studied and a uniform monolayer was obtained after compression.Stearic acid molecules were observed to form fine organized monolayer from completely random structure.Hexatic order of the arrangement has been identified for the distribution of stearic acid molecules in the monolayer.At the end of the compression,the stearic acid molecules were tightly packed in the gap of two other molecules.At last,the hydrogen bonds in the system were analyzed.The main hydrogen bonds were from stearic acid-water interaction and their intensities constantly decreased with the decreased of surface area per molecule.The weak hydrogen bond interaction between stearic acid molecules may be the reason of easy collapse.

  18. Hydration of amino acids: FTIR spectra and molecular dynamics studies.

    Science.gov (United States)

    Panuszko, Aneta; Adamczak, Beata; Czub, Jacek; Gojło, Emilia; Stangret, Janusz

    2015-11-01

    The hydration of selected amino acids, alanine, glycine, proline, valine, isoleucine and phenylalanine, has been studied in aqueous solutions by means of FTIR spectra of HDO isotopically diluted in H2O. The difference spectra procedure and the chemometric method have been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. To support interpretation of obtained spectral results, molecular dynamics simulations of amino acids were performed. The structural-energetic characteristic of these solute-affected water molecules shows that, on average, water affected by amino acids forms stronger and shorter H-bonds than those in pure water. Differences in the influence of amino acids on water structure have been noticed. The effect of the hydrophobic side chain of an amino acid on the solvent interactions seems to be enhanced because of the specific cooperative coupling of water strong H-bond chain, connecting the carboxyl and amino groups, with the clathrate-like H-bond network surrounding the hydrocarbon side chain. The parameter derived from the spectral data, which corresponds to the contributions of the population of weak hydrogen bonds of water molecules which have been substituted by the stronger ones in the hydration sphere of amino acids, correlated well with the amino acid hydrophobicity indexes.

  19. pH-responsive self-duplex of (Py)A-substituted oligodeoxyadenylate in graphene oxide solution as a molecular switch.

    Science.gov (United States)

    Yi, Jeong Wu; Park, Jaesung; Kim, Kwang S; Kim, Byeang Hyean

    2011-11-07

    In this paper, we demonstrated a highly discriminated and reliable molecular switch based on the interaction between the self-duplex of (Py)A-substituted oligodeoxyadenylate and graphene oxide in aqueous solution. This system showed a clear on/off state through the association and dissociation of (Py)A-modified oligodeoxynucleotide with graphene oxide in manipulated pH conditions, high amplitude efficiency for at least 50 cycles, and rapid response within seconds. Our molecular switch system has high reproducibility and simple operation by using pH stimulus.

  20. Unusually Large Young's Muduli of Amino Acid Molecular Crystals

    Science.gov (United States)

    Azuri, Ido; Meirzadeh, Elena; Ehre, David; Cohen, Sidney R.; Rappe, Andrew M.; Lahav, Meir; Lubomirsky, Igor; Kronik, Leeor

    Young's moduli of selected amino acid molecular crystals were studied both experimentally and computationally using nanoindentation and dispersion-corrected density functional theory. The Young modulus is found to be strongly facet-dependent, with some facets exhibiting exceptionally high values (as large as 44 GPa). The magnitude of Young's modulus is strongly correlated with the relative orientation between the underlying hydrogen-bonding network and the measured facet. Furthermore, we show computationally that the Young modulus can be as large as 70-90 GPa if facets perpendicular to the primary direction of the hydrogen-bonding network can be stabilized. This value is remarkably high for a molecular solid and suggests the design of hydrogen-bond networks as a route for rational design of ultra-stiff molecular solids. Angew. Chem. Int. Ed.. doi: 10.1002/anie.201505813.

  1. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han

    2014-01-01

    Full Text Available Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA and oleanolic acid (OA at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0 to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT, and diacylglycerol acyltransferase (DGAT in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

  2. First Acetic Acid Survey with CARMA in Hot Molecular Cores

    CERN Document Server

    Shiao, Y -S Jerry; Remijan, Anthony J; Snyder, Lewis E; Friedel, Douglas N

    2010-01-01

    Acetic acid (CH$_3$COOH) has been detected mainly in hot molecular cores where the distribution between oxygen (O) and nitrogen (N) containing molecular species is co-spatial within the telescope beam. Previous work has presumed that similar cores with co-spatial O and N species may be an indicator for detecting acetic acid. However, does this presumption hold as higher spatial resolution observations become available of large O and N-containing molecules? As the number of detected acetic acid sources is still low, more observations are needed to support this postulate. In this paper, we report the first acetic acid survey conducted with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at 3 mm wavelengths towards G19.61-0.23, G29.96-0.02 and IRAS 16293-2422. We have successfully detected CH$_3$COOH via two transitions toward G19.61-0.23 and tentatively confirmed the detection toward IRAS 16293-2422 A. The determined column density of CH$_3$COOH is 2.0(1.0)$\\times 10^{16}$ cm$^{-2}$ and the...

  3. Analysis of trace inorganic anions in weak acid salts by single pump cycling-column-switching ion chromatography.

    Science.gov (United States)

    Huang, Zhongping; Ni, Chengzhu; Zhu, Zhuyi; Pan, Zaifa; Wang, Lili; Zhu, Yan

    2015-05-01

    The application of ion chromatography with the single pump cycling-column-switching technique was described for the analysis of trace inorganic anions in weak acid salts within a single run. Due to the hydrogen ions provided by an anion suppressor electrolyzing water, weak acid anions could be transformed into weak acids, existing as molecules, after passing through the suppressor. Therefore, an anion suppressor and ion-exclusion column were adopted to achieve on-line matrix elimination of weak acid anions with high concentration for the analysis of trace inorganic anions in weak acid salts. A series of standard solutions consisting of target anions of various concentrations from 0.005 to 10 mg/L were analyzed, with correlation coefficients r ≥ 0.9990. The limits of detection were in the range of 0.67 to 1.51 μg/L, based on the signal-to-noise ratio of 3 and a 25 μL injection volume. Relative standard deviations for retention time, peak area, and peak height were all less than 2.01%. A spiking study was performed with satisfactory recoveries between 90.3 and 104.4% for all anions. The chromatographic system was successfully applied to the analysis of trace inorganic anions in five weak acid salts.

  4. Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis

    Directory of Open Access Journals (Sweden)

    Wang Jean H

    2011-12-01

    Full Text Available Abstract Background The lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus. Results If either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is not blocked. Conclusions After gastrulation, retinoic acid is required for lung but not thyroid differentiation in Xenopus while Fgf signalling is needed for lung but only for early expression of pax2 in the thyroid. Exposure to retinoic acid can cause the presumptive thyroid to switch to a lung developmental program.

  5. A solid-state electrochemiluminescence biosensing switch for detection of DNA hybridization based on ferrocene-labeled molecular beacon

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaoying [School of Public Health, Southeast University, Nanjing 210009 (China); He Pingang, E-mail: pghe@chem.ecnu.edu.c [Department of Chemistry, East China Normal University, Shanghai 200062 (China); Fang Yuzhi, E-mail: yzfang@chem.ecnu.edu.c [Department of Chemistry, East China Normal University, Shanghai 200062 (China)

    2010-08-15

    A solid-state electrochemiluminescence (ECL) biosensing switch incorporating quenching of ECL of ruthenium(II) tris-(bipyridine) (Ru(bpy){sub 3}{sup 2+}) by ferrocene (Fc) has been successfully developed for DNA hybridization detection. The important issue for this biosensing system is based on the ferrocene-labeled molecular beacon (Fc-MB), i.e. using the special Fc-MB to react with the target DNA and then change its structure, resulting in an ECL intensity change. Under the optimal conditions, the difference of ECL intensity before and after the hybridization reaction ({Delta}I{sub ECL}) was linearly related to the concentration of the complementary sequence in the range of 10 fM-10 pM and the detection limit was down to 1.0 fM.

  6. Dual origin of defect magnetism in graphene and its reversible switching by molecular doping.

    Science.gov (United States)

    Nair, R R; Tsai, I-L; Sepioni, M; Lehtinen, O; Keinonen, J; Krasheninnikov, A V; Castro Neto, A H; Katsnelson, M I; Geim, A K; Grigorieva, I V

    2013-01-01

    Control of magnetism by applied voltage is desirable for spintronics applications. Finding a suitable material remains an elusive goal, with only a few candidates found so far. Graphene is one of them and attracts interest because of its weak spin-orbit interaction, the ability to control electronic properties by the electric field effect and the possibility to introduce paramagnetic centres such as vacancies and adatoms. Here we show that the magnetism of adatoms in graphene is itinerant and can be controlled by doping, so that magnetic moments are switched on and off. The much-discussed vacancy magnetism is found to have a dual origin, with two approximately equal contributions; one from itinerant magnetism and the other from dangling bonds. Our work suggests that graphene's spin transport can be controlled by the field effect, similar to its electronic and optical properties, and that spin diffusion can be significantly enhanced above a certain carrier density.

  7. Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B

    2013-01-01

    The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation......, whereas FGF-10 promotes receptor recycling and cell migration. By combining mass-spectrometry-based quantitative proteomics with fluorescence microscopy and biochemical methods, we find that FGF-10 specifically induces the rapid phosphorylation of tyrosine (Y) 734 on FGFR2b, which leads to PI3K and SH3BP4...... recruitment. This complex is crucial for FGFR2b recycling and responses, given that FGF-10 stimulation of either FGFR2b_Y734F mutant- or SH3BP4-depleted cells switches the receptor endocytic route to degradation, resulting in decreased breast cancer cell migration and the inhibition of epithelial branching...

  8. Molecular Simulation of Naphthenic Acid Removal on Acidic Catalyst (Ⅰ) Mechanism of Catalytic Decarboxylation

    Institute of Scientific and Technical Information of China (English)

    Fu Xiaoqin; Dai Zhenyu; Tian Songbai; Hou Suandi; Wang Xieqing

    2008-01-01

    In this paper, the charge distribution, the chemical bond order and the reactive performance of carboxylic acid model compounds on acidic catalyst were investigated by using molecular simulation technology. The simulation results showed that the bond order of C-O was higher than that of C-C,and C-C bond connected to the carbon atom in the carboxyl radical had the lowest bond order. The charge distributions of model naphthenic acids were similar in characteristics that the negative charges were concentrated on carboxyls. According to the simulation results, the mechanisms of catalytic decarboxylation over acidic solid catalyst were proposed, and a new route was put forward regarding removal of the naphthenic acid from crude oil through catalytic decarboxylation.

  9. Establishing the ellipsoidal geometry of a benzoic acid-based amphiphile via dimer switching: insights from intramolecular rotation and facial H-bond torsion.

    Science.gov (United States)

    Ramesh, Nivarthi; Sarangi, Nirod Kumar; Patnaik, Archita

    2013-05-01

    Soft molecular ellipsoids conceived from 3,4-di(dodecyloxy)benzoic acid (DDBA) amphiphile draw attention to monomer structure design, intramolecular -COOH headgroup twist (ϕ°) and cyclic-acyclic dimer switching through facial H-bond torsion (ψ°). Generically, precipitation in hydrogen bonded systems has been the prime phenomenon once the critical aggregation concentrations were reached in the bulk solution. DDBA was no exception to this generalization. It formed precipitates in chloroform and methanol with no specific geometry but with cyclic dimer motifs in them. On the contrary, surface pressure modulated interfacial aggregation with ellipsoidal geometry followed acyclic dimerization (catemer motif) with various levels of headgroup torsion, established through real-time polarization modulated infrared reflection-absorption spectroscopy (IRRAS) and density functional theory (DFT) calculations, that estimated the energy costs for these unexplored pathways. The reaction coordinates ϕ° and ψ° in consonance with 2D surface pressure modulation thus directed the shape anisotropy during the dynamic self-assembly of DDBA. Changes in subphase pH and metal ionic environment had a derogatory effect on the ellipsoid formation, the structural requirement for which strictly followed a stringent need for twin alkyl chains in an asymmetric unit cell, as 4-dodecyloxybenzoic acid (MABA) with a single alkyl chain formed exclusively spherical assemblies with no dimer modulation. The investigation thus reports unexplored energy pathways toward ellipsoidal geometry of the amphiphile in the course of its interfacial aggregation.

  10. Molecular products from the thermal degradation of glutamic acid.

    Science.gov (United States)

    Kibet, Joshua K; Khachatryan, Lavrent; Dellinger, Barry

    2013-08-14

    The thermal behavior of glutamic acid was investigated in N2 and 4% O2 in N2 under flow reactor conditions at a constant residence time of 0.2 s, within a total pyrolysis time of 3 min at 1 atm. The identification of the main pyrolysis products has been reported. Accordingly, the principal products for pyrolysis in order of decreasing abundance were succinimide, pyrrole, acetonitrile, and 2-pyrrolidone. For oxidative pyrolysis, the main products were succinimide, propiolactone, ethanol, and hydrogen cyanide. Whereas benzene, toluene, and a few low molecular weight hydrocarbons (propene, propane, 1-butene, and 2-butene) were detected during pyrolysis, no polycyclic aromatic hydrocarbons (PAHs) were detected. Oxidative pyrolysis yielded low molecular weight hydrocarbon products in trace amounts. The mechanistic channels describing the formation of the major product succinimide have been explored. The detection of succinimide (major product) and maleimide (minor product) from the thermal decomposition of glutamic acid has been reported for the first time in this study. Toxicological implications of some reaction products (HCN, acetonitrile, and acyrolnitrile), which are believed to form during heat treatment of food, tobacco burning, and drug processing, have been discussed in relation to the thermal degradation of glutamic acid.

  11. Thermal modulation of the monomer/excimer fluorescence for bispyrene molecules through the gel solution transition of an organogel: A thermo-driven molecular fluorescence switch

    Science.gov (United States)

    Wang, Cheng; Wang, Zhuo; Zhang, Deqing; Zhu, Daoben

    2006-09-01

    Reversible modulation of the monomer/excimer emission was observed for bispyrene molecules 1 and 2 through the solution-gel phase transition (with gelator 3 as the LMWG) and accordingly a thermo-driven molecular fluorescence switch can be established.

  12. Lewis acid enhanced switching of the 1,1-dicyanodihydroazulene/vinylheptafulvene photo/thermoswitch

    DEFF Research Database (Denmark)

    Parker, Christian Richard; Tortzen, Christian Gregers; Broman, Søren Lindbæk;

    2011-01-01

    Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion.......Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion....

  13. Molecular-Mechanical Switching at the Nanoparticle-Solvent Interface: Practice and Theory

    Energy Technology Data Exchange (ETDEWEB)

    Coskun, Ali [Northwestern Univ., Evanston, IL (United States); Wesson, Paul J. [Northwestern Univ., Evanston, IL (United States); Klajn, Rafal [Northwestern Univ., Evanston, IL (United States); Trabolsi, Ali [Northwestern Univ., Evanston, IL (United States); Fang, Lei [Northwestern Univ., Evanston, IL (United States); Olson, Mark A. [Northwestern Univ., Evanston, IL (United States); Dey, Sanjeev K. [Northwestern Univ., Evanston, IL (United States); Grzybowski, Bartosz A. [Northwestern Univ., Evanston, IL (United States); Stoddart, J. Fraser [Northwestern Univ., Evanston, IL (United States)

    2010-01-01

    A range (Au, Pt, Pd) of metal nanoparticles (MNPs) has been prepared and functionalized with (a) redox-active stalks containing tetrathiafulvalene (TTF) units, (b) [2]pseudorotaxanes formed between these stalks and cyclobis(paraquat-p-phenylene) (CBPQT4+) rings, and (c) bistable [2]rotaxane molecules where the dumbbell component contains a 1,5-dioxynaphthalene (DNP) unit, as well as a TTF unit, encircled by a CBPQT4+ ring. It transpires that the molecules present in (a) and (c) and the supermolecules described in (b) retain their switching characteristics, previously observed in solution, when they are immobilized onto MNPs. Moreover, their oxidation potentials depend on the fraction, χ, of the molecules or supermolecules on the surface of the nanoparticles. A variation in χ affects the oxidation potentials of the TTF units to the extent that switching can be subjected to fine tuning as a result. Specifically, increasing χ results in positive shifts (i) in the oxidation potentials of the TTF unit in (a)-(c) and (ii) the reduction potentials of the CBPQT4+ rings in (c). These shifts can be attributed to an increase in the electrostatic potential surrounding the MNPs. Both the magnitude and the direction of these shifts are reproduced by a model, based on the Poisson-Boltzmann equation coupled with charge-regulating boundary conditions. Furthermore, the kinetics of relaxation from the metastable state coconformation (MSCC) to the ground-state coconformation (GSCC) of the bistable [2]rotaxane molecules also depends on χ, as well as on the nanoparticle diameter. Increasing either of these parameters accelerates the rate of relaxation from the MSCC to the GSCC. This rate is a function of (i) the activation energy for the relaxation process associated with the bistable [2]rotaxane molecules in solution and (ii) the electrostatic potential surrounding the MNPs. The electrostatic potential depends on (i) the diameter of the MNPs, (ii

  14. Caveolin isoform switching as a molecular, structural, and metabolic regulator of microglia

    OpenAIRE

    2013-01-01

    Microglia are ramified cells that serve as central nervous system (CNS) guardians, capable of proliferation, migration, and generation of inflammatory cytokines. In non-pathological states, these cells exhibit ramified morphology with processes intermingling with neurons and astrocytes. Under pathological conditions, they acquire a rounded amoeboid morphology and proliferative and migratory capabilities. Such morphological changes require cytoskeleton rearrangements. The molecular control poi...

  15. Molecular dynamics simulation of anionic clays containing glutamic acid

    Science.gov (United States)

    Xu, Qian; Ni, Zheming; Yao, Ping; Li, Yuan

    2010-08-01

    Supra-molecular structure of glutamic acid intercalated ZnAl layered double hydroxides (Glu-ZnAl-LDH) was modeled by molecular dynamics (MD) methods. Hydrogen bonding, hydration and swelling properties of Glu-LDH have been investigated. For Nw layers and anions. When A-W type H-bonds gradually reached a saturation state, water molecules continued to form hydrogen bonds with the hydroxyls of the layers. The L-W type H-bonds gradually substituted the L-A type H-bonds and Glu anions moved to the center of an interlayer and then separated with the layers. Last, a well-ordered structural water layer was formed on the surface hydroxyls of Glu-LDH. The lower releasing content of Glu-LDH maybe was influenced by the lower balance hydration energy and existence of L-A type H-bonds in high water content.

  16. A rapid drug release system with a NIR light-activated molecular switch for dual-modality photothermal/antibiotic treatments of subcutaneous abscesses.

    Science.gov (United States)

    Chiang, Wei-Lun; Lin, Tzu-Tsen; Sureshbabu, Radhakrishnan; Chia, Wei-Tso; Hsiao, Hsu-Chan; Liu, Hung-Yi; Yang, Chih-Man; Sung, Hsing-Wen

    2015-02-10

    Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a "molecular switch" in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.

  17. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans, E-mail: hans.brandstetter@sbg.ac.at [University of Salzburg, Billrothstrasse 11, 5020 Salzburg (Austria)

    2014-07-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed.

  18. Molecular targeting of acid ceramidase: implications to cancer therapy.

    Science.gov (United States)

    Zeidan, Youssef H; Jenkins, Russell W; Korman, John B; Liu, Xiang; Obeid, Lina M; Norris, James S; Hannun, Yusuf A

    2008-08-01

    Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.

  19. Porphyrinic metal-organic framework as electrochemical probe for DNA sensing via triple-helix molecular switch.

    Science.gov (United States)

    Ling, Pinghua; Lei, Jianping; Ju, Huangxian

    2015-09-15

    An electrochemical DNA sensor was developed based on the electrocatalysis of porphyrinic metal-organic framework (MOF) and triple-helix molecular switch for signal transduction. The streptavidin functionalized zirconium-porphyrin MOF (PCN-222@SA) was prepared as signal nanoprobe via covalent method and demonstrated high electrocatalysis for O2 reduction. Due to the large steric effect, the designed nanoprobe was blocked for the interaction with the biotin labeled triple-helix immobilized on the surface of glassy carbon electrode. In the presence of target DNA, the assistant DNA in triple-helix will hybridize with target DNA, resulting in the disassembly of triple-helix molecular. Consequently, the end biotin away from the electrode was ''activated'' for easy access to the signal nanoprobe, PCN-222@SA, on the basis of biotin-streptavidin biorecognition. The introduction of signal nanoprobe to a sensor surface led to a significantly amplified electrocatalytic current towards oxygen reduction. Integrating with DNA recycling amplification of Exonuclease III, the sensitivity of the biosensor was improved significantly with detection limit of 0.29 fM. Moreover, the present method has been successfully applied to detect DNA in complex serum matrix. This porphyrinic MOF-based strategy has promising application in the determination of various analytes for signal transduction and has great potential in bioassays.

  20. Molecular and Therapeutic Potential and Toxicity of Valproic Acid

    Directory of Open Access Journals (Sweden)

    Sébastien Chateauvieux

    2010-01-01

    Full Text Available Valproic acid (VPA, a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.

  1. Molecular mechanisms of acid-base sensing by the kidney.

    Science.gov (United States)

    Brown, Dennis; Wagner, Carsten A

    2012-05-01

    A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

  2. Amino acid detection using fluoroquinolone–Cu{sup 2+} complex as a switch-on fluorescent probe by competitive complexation without derivatization

    Energy Technology Data Exchange (ETDEWEB)

    Farokhcheh, Alireza; Alizadeh, Naader, E-mail: alizaden@modares.ac.ir

    2014-01-15

    In this work, we describe the use of fluoroquinolone–Cu{sup 2+} complex as a competitive switch-on fluorescence probe for amino acid determination without derivatization. The fluorescence intensity of this probe, which has been reduced due to effective quenching by Cu{sup 2+} ion, increases drastically by an addition of amino acid (glycine, phenylalanine, sarcosine, aspargine, alanine, proline, arginine, aspartic acid, glutamic acid, lysine, leucine and isoleucine). The overall stability constants of Cu{sup 2+} ion complexes with amino acids were determined by fluorometric titration of fluoroquinolone-Cu{sup 2+} complex with the amino acid solution. Furthermore, the probe shows high calibration sensitivity toward aspartic acid. The fluorescence signal depends linearly on the amino acid concentration within the range of concentration from 1.2×10{sup −7} to 1.1×10{sup −5} mol L{sup −1} for aspartic acid. The detection limit was found 2.7×10{sup −8} mol L{sup −1} with the relative standard deviation (RSD%) about 2.1% (five replicate). -- Highlights: • Amino acids are detected by using fluoroquinolone–Cu{sup 2+} complex as fluorescent probe. • Amino acids were detected based on a competitive complexation reaction. • Probe has been able to recognize amino acids through switch-on fluorescence behavior. • Ultra-trace level of aspartic and glutamic acid is determined without derivatization.

  3. Preparation of low-molecular-weight hyaluronic acid by ozone treatment.

    Science.gov (United States)

    Wu, Yue

    2012-06-20

    Recently, low-molecular-weight hyaluronic acid has been reported to have novel features, such as free radical scavenging activities, antioxidant activities, promotion of excisional wound healing, etc. In the present work, degradation of native hyaluronic acid by ozone treatment was performed for preparation of low-molecular-weight hyaluronic acid. The molecular weight of native hyaluronic acid was reduced from 1535 to 87 kDa for 120 min at 40°C. The rate of reduction of molecular weight was 94.33%. The FT-IR, 13C NMR, and UV-vis spectra suggested that there was no obvious modification of chemical structure of low-molecular-weight hyaluronic acid. The use of degradation of native hyaluronic acid by ozone treatment can be a useful alternative for production of low-molecular-weight hyaluronic acid.

  4. Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

    Directory of Open Access Journals (Sweden)

    Kuan-Hao Tsui

    2012-01-01

    Full Text Available Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR, cytochrome P450 cholesterol side-chain cleavage (P450scc, and 3β-hydroxysteroid dehydrogenase (3β-HSD. We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.

  5. Inducible molecular switches for the study of long-term potentiation.

    Science.gov (United States)

    Hédou, Gaël; Mansuy, Isabelle M

    2003-04-29

    This article reviews technical and conceptual advances in unravelling the molecular bases of long-term potentiation (LTP), learning and memory using genetic approaches. We focus on studies aimed at testing a model suggesting that protein kinases and protein phosphatases balance each other to control synaptic strength and plasticity. We describe how gene 'knock-out' technology was initially exploited to disrupt the Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) gene and how refined knock-in techniques later allowed an analysis of the role of distinct phosphorylation sites in CaMKII. Further to gene recombination, regulated gene expression using the tetracycline-controlled transactivator and reverse tetracycline-controlled transactivator systems, a powerful new means for modulating the activity of specific molecules, has been applied to CaMKIIalpha and the opposing protein phosphatase calcineurin. Together with electro-physiological and behavioural evaluation of the engineered mutant animals, these genetic methodologies have helped gain insight into the molecular mechanisms of plasticity and memory. Further technical developments are, however, awaited for an even higher level of finesse.

  6. Design and Synthesis of Chiral Molecular Tweezers Based on Deoxycholic Acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A series of new chiral molecular tweezers have been designed and synthesized by using deoxycholic acid as spacer and aromatic amines as arms.Instead of using toxic phosgene,the triphosgene was employed in synthesis of the molecular tweezers receptors.These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

  7. Molecular rectification and conductance switching in carbon-based molecular junctions by structural rearrangement accompanying electron injection.

    Science.gov (United States)

    McCreery, Richard; Dieringer, Jon; Solak, Ali Osman; Snyder, Brian; Nowak, Aletha M; McGovern, William R; DuVall, Stacy

    2003-09-01

    Molecular junctions were fabricated consisting of a 3.7 nm thick layer of nitroazobenzene (NAB) molecules between a pyrolyzed photoresist substrate (PPF) and a titanium top contact which was protected from oxidation by a layer of gold. Raman spectroscopy, XPS, and AFM revealed that the NAB layer was 2-3 molecules thick and was bonded to the two conducting contacts by C-C and N-Ti covalent bonds. The current/voltage behavior of the PPF/NAB(3.7)/Ti junctions showed strong and reproducible rectification, with the current at +2 V exceeding that at -2 V by a factor of 600. The observed current density at +3 V was 0.71 A/cm(2), or about 10(5) e(-)/s/molecule. The i/V response was strongly dependent on temperature and scan rate, with the rectification ratio decreasing for lower temperature and faster scans. Junction conductivity increased with time over several seconds at room temperature in response to positive voltage pulses, with the rate of increase larger for more positive potentials. Voltage pulses to positive potentials and back to zero volts revealed that electrons are injected from the Ti to the NAB, to the extent of about 0.1-1 e(-)/molecule for a +3 V pulse. These electrons cause an activated transition of the NAB into a more conductive quinoid state, which in turn causes an increase in conductivity. The transition to the quinoid state involves nuclear rearrangement which occurs on a submillisecond to several second time scale, depending on the voltage applied. The quinoid state is stable as long as the applied electric field is present, but reverts back to NAB within several minutes after the field is relaxed. The results are interpreted in terms of a thermally activated, potential dependent electron transfer into the 3.7 nm NAB layer, which brings about a conductivity increase of several orders of magnitude.

  8. Micelle-assisted signaling of peracetic acid by the oxidation of pyreneboronic acid via monomer-excimer switching.

    Science.gov (United States)

    Choi, Jiyoung; Lee, Hyo Jin; Cho, Min Jeoung; Chang, Suk-Kyu

    2015-08-15

    A simple fluorescent probe for the industrial oxidant peracetic acid (PAA) was investigated. PAA-assisted oxidative conversion of pyrene-1-boronic acid into 1-hydroxypyrene was used as the signaling tool. Pyreneboronic acid was found to display selective signaling behavior, being more responsive to PAA than to other commonly used practical oxidants such as H2O2 and HOCl. The changes in pyrene monomer fluorescence to excimer were used in the quantitative analysis of PAA. When using the surfactant hexadecyltrimethylammonium bromide as a micellar additive, the signaling of PAA was markedly enhanced. Selective fluorescence signaling of PAA by pyrene-1-boronic acid with a detection limit of 1.5×10(-6)M in aqueous environment was successfully achieved.

  9. Laser control of double proton transfer in porphycenes. Towards an ultrafast switch for photonic molecular wires

    CERN Document Server

    Abdel-Latif, Mahmoud K

    2010-01-01

    Electronic excitation energy transfer along a molecular wire depends on the relative orientation of the electronic transition dipole moments of neighboring chromophores. In porphycenes this orientation is changed upon double proton transfer in the electronic ground state. We explore the possibility to trigger such a double proton transfer reaction by means of an infrared pump-dump laser control scheme. To this end a quantum chemical characterization of an asymmetrically substituted porphycene is performed using density functional theory. Ground state geometries, the topology of the potential energy surface for double proton transfer, and S0->S1 transition energies are compared with the parent compound porphycene and a symmetric derivative. Employing a simple two-dimensional model for the double proton transfer, which incorporates sequential and concerted motions, quantum dynamics simulations of the laser driven dynamics are performed which demonstrate tautomerization control. Based on the orientation of the t...

  10. Plasma membranes as heat stress sensors: from lipid-controlled molecular switches to therapeutic applications.

    Science.gov (United States)

    Török, Zsolt; Crul, Tim; Maresca, Bruno; Schütz, Gerhard J; Viana, Felix; Dindia, Laura; Piotto, Stefano; Brameshuber, Mario; Balogh, Gábor; Péter, Mária; Porta, Amalia; Trapani, Alfonso; Gombos, Imre; Glatz, Attila; Gungor, Burcin; Peksel, Begüm; Vigh, László; Csoboz, Bálint; Horváth, Ibolya; Vijayan, Mathilakath M; Hooper, Phillip L; Harwood, John L; Vigh, László

    2014-06-01

    The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

  11. A sensitive and versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch.

    Science.gov (United States)

    Wang, Xiuzhong; Jiang, Aiwen; Hou, Ting; Li, Feng

    2014-12-07

    In the present study, a versatile "signal-on" electrochemical aptasensor based on a triple-helix molecular switch has been developed. An aptamer probe is designed to hybridize with the methylene blue (MB)-modified DNA capture probe immobilized on the gold electrode to form rigid triple-helix DNA, impeding the efficient electron transfer of MB to the electrode and resulting in the decreased oxidation peak current of MB. However, upon introduction of the perfectly matched target, for example, human α-thrombin (Tmb), the interaction between Tmb and the aptamer probe leads to the dissociation of the triple-helix DNA structure and thereby liberates the MB-modified end of the capture probe, allowing the MB to collide with the electrode surface and resulting in an increase of the oxidation peak currents of MB. Therefore, the sensitive signal-on detection of Tmb is realized, and the detection limit of Tmb is 0.12 nM. The proposed approach also demonstrates excellent regenerability, reproducibility and stability. Additionally, it also has the advantages of simplicity in design and easy operation. The success in the present biosensor provides a promising alternative to the electrochemical detection of a variety of analytes and may have potential applications in point-of-care testing and clinical diagnosis.

  12. Assessing computationally efficient isomerization dynamics: Delta-SCF density-functional theory study of azobenzene molecular switching

    CERN Document Server

    Maurer, Reinhard J; 10.1063/1.3664305

    2012-01-01

    We present a detailed comparison of the S0, S1 (n -> \\pi*) and S2 (\\pi -> \\pi*) potential energy surfaces (PESs) of the prototypical molecular switch azobenzene as obtained by Delta-self-consistent-field (Delta-SCF) Density-Functional Theory (DFT), time-dependent DFT (TD-DFT) and approximate Coupled Cluster Singles and Doubles (RI-CC2). All three methods unanimously agree in terms of the PES topologies, which are furthermore fully consistent with existing experimental data concerning the photo-isomerization mechanism. In particular, sum-method corrected Delta-SCF and TD-DFT yield very similar results for S1 and S2, when based on the same ground-state exchange-correlation (xc) functional. While these techniques yield the correct PES topology already on the level of semi-local xc functionals, reliable absolute excitation energies as compared to RI-CC2 or experiment require an xc treatment on the level of long-range corrected hybrids. Nevertheless, particularly the robustness of Delta-SCF with respect to state c...

  13. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  14. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance.

    Science.gov (United States)

    Bertolin, Giulia; Ferrando-Miguel, Rosa; Jacoupy, Maxime; Traver, Sabine; Grenier, Karl; Greene, Andrew W; Dauphin, Aurélien; Waharte, François; Bayot, Aurélien; Salamero, Jean; Lombès, Anne; Bulteau, Anne-Laure; Fon, Edward A; Brice, Alexis; Corti, Olga

    2013-11-01

    Loss-of-function mutations in PARK2/PARKIN and PINK1 cause early-onset autosomal recessive Parkinson disease (PD). The cytosolic E3 ubiquitin-protein ligase PARK2 cooperates with the mitochondrial kinase PINK1 to maintain mitochondrial quality. A loss of mitochondrial transmembrane potential (ΔΨ) leads to the PINK1-dependent recruitment of PARK2 to the outer mitochondrial membrane (OMM), followed by the ubiquitination and proteasome-dependent degradation of OMM proteins, and by the autophagy-dependent clearance of mitochondrial remnants. We showed here that blockade of mitochondrial protein import triggers the recruitment of PARK2, by PINK1, to the TOMM machinery. PD-causing PARK2 mutations weakened or disrupted the molecular interaction between PARK2 and specific TOMM subunits: the surface receptor, TOMM70A, and the channel protein, TOMM40. The downregulation of TOMM40 or its associated core subunit, TOMM22, was sufficient to trigger OMM protein clearance in the absence of PINK1 or PARK2. However, PARK2 was required to promote the degradation of whole organelles by autophagy. Furthermore, the overproduction of TOMM22 or TOMM40 reversed mitochondrial clearance promoted by PINK1 and PARK2 after ΔΨ loss. These results indicated that the TOMM machinery is a key molecular switch in the mitochondrial clearance program controlled by the PINK1-PARK2 pathway. Loss of functional coupling between mitochondrial protein import and the neuroprotective degradation of dysfunctional mitochondria may therefore be a primary pathogenic mechanism in autosomal recessive PD.

  15. A novel purification process for dodecanedioic acid by molecular distillation

    Institute of Scientific and Technical Information of China (English)

    Jiang Yu; Xigang Yuan; Aiwu Zeng

    2015-01-01

    A novel purification process is involved to obtain the high purity [N 99%(by mass)] dodecanedioic acid (DC12). It involves a re-crystal ization followed by molecular distil ation from the crude product. The objective of this study is to investigate general conditions, feed rate, distil ing temperature and vacuum, necessary for centrifugal distil-lation of DC12. Under the optimum conditions, distilling temperature 180 °C, pressure 30 Pa and feed flow rate 700 ml·h−1, the purity of DC12 in the residence reached 97.55%with a yield of 53.18%by the analysis of gas chromatography. Multiple-pass distillation made a considerable contribution by improving the purity to 99.22%. Additionally, the effect of pretreatment (re-crystallization) on distillation process was revealed through a series of comparative experiments.

  16. Estudio de un modelo de red neuronal artificial del switch molecular del bacteriófago Lambda

    Directory of Open Access Journals (Sweden)

    Rodríguez Tobón Guillermo León

    2006-06-01

    Full Text Available La maquinaria molecular de las células consiste de una enorme red de moléculas que interactúan unas con
    otras de manera compleja. En estos sistemas la información es procesada por medio de variaciones en las
    concentraciones y localización de estas moléculas en respuesta a estímulos de origen intra o extra celular. Una
    de las tendencias más importantes de la biología molecular actual, gira en torno a la comprensión de los procesos de procesamiento de la información por medio de la elaboración de modelos dinámicos sistémicos de los sistemas moleculares biológicos. En los últimos años, grandes adelantos han tenido lugar en el campo del desarrollo e implementación de algoritmos que permiten realizar simulaciones del comportamiento de diversos sistemas moleculares tales como las vías de señalización intracelular, control del metabolismo y expresión genética. En un modelo dinámico sistémico cualquier cantidad de interés, mientras que la medición de las mismas cantidades in vivo requiere la elaboración y ejecución de experimentos muy laboriosos y costosos. La aplicación de las técnicas de modelamiento y simulación en el campo de la biología molecular ayuda al mejoramiento en el entendimiento de los procesos biológicos. Los aspectos moleculares del sistema regulatorio del bacteriófago lambda, ha sido por mucho tiempo el centro de atención de las investigaciones que tratan de dilucidar las bases moleculares de los procesos implicados en el control de expresión genética en procariotas. Aspectos tanto cuantitativos como cualitativos del comportamiento del switch del bacteriófago lambda han sido caracterizados experimentalmente. Sin embargo, un completo  entendimiento de la robustez y estabilidad del sistema regulatorio del mismo está aún por obtenerse. En el presente trabajo se propone  una modificación del modelo dinámico, el cual tiene como elemento principal la dinámica reguladora del operador

  17. Characterization of Hydroxyphthioceranoic and Phthioceranoic Acids by Charge-Switch Derivatization and CID Tandem Mass Spectrometry

    Science.gov (United States)

    Hsu, Fong-Fu

    2016-04-01

    Hydroxyphthioceranoic (HPA) and phthioceranoic (PA) acids are polymethylated long chain fatty acids with and without a hydroxyl group attached to the carbon next to the terminal methyl-branched carbon distal to the carboxylic end of the long-chain fatty acid, respectively. They are the major components of the sulfolipids found in the cell wall of Mycobacterium tuberculosis (M. tuberculosis) strain H37Rv. In this report, I describe CID linear ion-trap MSn mass spectrometric approaches combined with charge-reverse derivatization strategy toward characterization of these complex lipids, which were released from sulfolipids by alkaline hydrolysis and sequentially derivatized to the N-(4-aminomethylphenyl) pyridinium (AMPP) derivatives. This method affords complete characterization of HPA and PA, including the location of the hydroxyl group and the multiple methyl side chains. The study also led to the notion that the hydroxyphthioceranoic acid in sulfolipid consists of two (for hC24) to 12 (for hC52) methyl branches, and among them 2,4,6,8,10,12,14,16-octamethyl-17-hydroxydotriacontanoic acid (hC40) is the most prominent, while phthioceranoic acids are the minor constituents. These results confirm our previous findings that sulfolipid II, a family of homologous 2-stearoyl(palmitoyl)-3,6,6'-tris(hydroxyphthioceranoy1)-trehalose 2'-sulfates is the predominant species, and sulfolipid I, a family of homologous 2-stearoyl(palmitoyl)-3-phthioceranoyl-6,6'-bis(hydroxyphthioceranoy1)-trehalose 2'-sulfates is the minor species in the cell wall of M. tuberculosis.

  18. Solution-phase laser processing of π-conjugated polymers: Switching between different molecular states

    Science.gov (United States)

    Takada, K.; Tomioka, A.

    2012-04-01

    Liquid-phase laser processing, where the laser-irradiated target material is immersed in water for cooling, has been reported as a promising processing technique for thermally fragile organic materials. Although nanometer-sized particles have been reported to be obtained with the liquid-phase laser processing, the physical property did not change because quantum-mechanical size effect does not exhibit itself in the zero-radius Frenkel excitons. In the present study, we step further to use solution droplets as a target material, where organic molecules are molecularly dispersed in organic solvent and, therefore, expected to easily alter the conformation and the energy state upon laser irradiation. Small volume organic solvent is quickly evaporated upon laser irradiation, letting the bare organic molecule placed in water and rapidly cooled. To prevent the chemical decomposition of the target π-conjugated molecule, the specimen was resonantly irradiated by a ns-pulse green laser, not by a conventional UV laser. When the solid state spin-coat film made from MEH-PPV chloroform solution was used as a irradiation target immersed in water, resulting MEH-PPV particles showed similar photoluminescence (PL) like the PL of the spin-coat film and PL of the chloroform solution, including the 0→1, 0→2 vibrational transitions: this indicates that the energy levels were not modified from the spin-coat film. In comparison, when tiny droplets of MEH-PPV chloroform solution (orange color) were suspended in water, laser irradiation gave rise to yellow MEH-PPV particles which showed 550 nm and 530 nm PL (type B), blue-shifted from the spin-coat film PL 580 nm (type A), suggesting a successful phase transition of MEH-PPV polymer to type B. Further solution-phase laser processing left the type B state unchanged. The irreversible phase transition from type A to type B suggests that the type B ground state has lower energy than type A, which is consistent with the blue-shifted PL of

  19. Molecular complexes of alprazolam with carboxylic acids, boric acid, boronic acids, and phenols. Evaluation of supramolecular heterosynthons mediated by a triazole ring.

    Science.gov (United States)

    Varughese, Sunil; Azim, Yasser; Desiraju, Gautam R

    2010-09-01

    A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor with the acidic coformers. The hydrogen bond patterns exhibited with aromatic carboxylic acids were found to depend on the nature and position of the substituents. Being a strong acid, 2,6-dihydroxybenzoic acid forms a salt with alprazolam. With aliphatic dicarboxylic acids alprazolam forms hydrates and the water molecules play a central role in synthon formation and crystal packing. The triazole ring makes two distinct heterosynthons in the molecular complex with boric acid. Boronic acids and phenols form consistent hydrogen bond patterns, and these are seemingly independent of the substitutional effects. Boronic acids form noncentrosymmetric cyclic synthons, while phenols form O--H...N hydrogen bonds with the triazole ring.

  20. Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

    Directory of Open Access Journals (Sweden)

    Megan Leander

    Full Text Available Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS, a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (RhpMS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock

  1. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn- thesizing new chiral resolving agents.

  2. Investigation of molecular interactions in the complex formation of tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid

    Institute of Scientific and Technical Information of China (English)

    TAN Bin; ZHAI Zheng; LUO GuangSheng; WANG JiaDing

    2008-01-01

    The molecular interactions in the complex formation of two tartaric acid derivatives with di(2-ethylhexyl) phosphoric acid are investigated. The complex formation with a 1:1 stoichiometry between tartaric acid derivatives and D2EHPA can be obtained through UV-Vis titration, NMR chemical shifts and molecular dynamic simulations. Furthermore, the differences of the two complexes on the binding constants and strength of hydrogen bonds can also be determined. Such research will ideally provide insight into ways of regulating the complex forming properties of tartaric acid derivatives for composing or syn-thesizing new chiral resolving agents.

  3. Molecular Orbital Rule for Quantum Interference in Weakly Coupled Dimers: Low-Energy Giant Conductivity Switching Induced by Orbital Level Crossing.

    Science.gov (United States)

    Nozaki, Daijiro; Lücke, Andreas; Schmidt, Wolf Gero

    2017-02-16

    Destructive quantum interference (QI) in molecular junctions has attracted much attention in recent years. It can tune the conductance of molecular devices dramatically, which implies numerous potential applications in thermoelectric and switching applications. There are several schemes that address and rationalize QI in single molecular devices. Dimers play a particular role in this respect because the QI signal may disappear, depending on the dislocation of monomers. We derive a simple rule that governs the occurrence of QI in weakly coupled dimer stacks of both alternant and nonalternant polyaromatic hydrocarbons (PAHs) and extends the Tada-Yoshizawa scheme. Starting from the Green's function formalism combined with the molecular orbital expansion approach, it is shown that QI-induced antiresonances and their energies can be predicted from the amplitudes of the respective monomer terminal molecular orbitals. The condition is illustrated for a toy model consisting of two hydrogen molecules and applied within density functional calculations to alternant dimers of oligo(phenylene-ethynylene) and nonalternant PAHs. Minimal dimer structure modifications that require only a few millielectronvolts and lead to an energy crossing of the essentially preserved monomer orbitals are shown to result in giant conductance switching ratios.

  4. Amino Acid Molecular Units: Building Primary and Secondary Protein Structures

    Directory of Open Access Journals (Sweden)

    Aparecido R. Silva

    2008-05-01

    Full Text Available In order to guarantee the learning quality and suitable knowledge  use  about structural biology, it is fundamental to  exist, since the beginning of  students’ formation, the possibility of clear visualization of biomolecule structures. Nevertheless, the didactic books can only bring  schematic  drawings; even more elaborated figures and graphic computation  do not permit the necessary interaction.  The representation of three-dimensional molecular structures with ludic models, built with representative units, have supplied to the students and teachers a successfully experience to  visualize such structures and correlate them to the real molecules.  The design and applicability of the representative units were discussed with researchers and teachers before mould implementation.  In this stage  it  will be presented the  developed  kit  containing the  representative  plastic parts of the main amino acids.  The kit can demonstrate the interaction among the amino acids  functional groups  (represented by colors, shapes,  sizes and  the peptidic bonds between them  facilitating the assembly and visuali zation of the primary and secondary protein structure.  The models were designed for  Ca,  amino,  carboxyl groups  and  hydrogen. The  lateral chains have  well defined models that represent their geometrical shape.  The completed kit set  will be presented in this meeting (patent requested.  In the last phase of the project will be realized  an effective evaluation  of the kit  as a facilitative didactic tool of the teaching/learning process in the Structural Molecular Biology area.

  5. Role of accelerated segment switch in exons to alter targeting (ASSET in the molecular evolution of snake venom proteins

    Directory of Open Access Journals (Sweden)

    Kini R Manjunatha

    2009-06-01

    Full Text Available Abstract Background Snake venom toxins evolve more rapidly than other proteins through accelerated changes in the protein coding regions. Previously we have shown that accelerated segment switch in exons to alter targeting (ASSET might play an important role in its functional evolution of viperid three-finger toxins. In this phenomenon, short sequences in exons are radically changed to unrelated sequences and hence affect the folding and functional properties of the toxins. Results Here we analyzed other snake venom protein families to elucidate the role of ASSET in their functional evolution. ASSET appears to be involved in the functional evolution of three-finger toxins to a greater extent than in several other venom protein families. ASSET leads to replacement of some of the critical amino acid residues that affect the biological function in three-finger toxins as well as change the conformation of the loop that is involved in binding to specific target sites. Conclusion ASSET could lead to novel functions in snake venom proteins. Among snake venom serine proteases, ASSET contributes to changes in three surface segments. One of these segments near the substrate binding region is known to affect substrate specificity, and its exchange may have significant implications for differences in isoform catalytic activity on specific target protein substrates. ASSET therefore plays an important role in functional diversification of snake venom proteins, in addition to accelerated point mutations in the protein coding regions. Accelerated point mutations lead to fine-tuning of target specificity, whereas ASSET leads to large-scale replacement of multiple functionally important residues, resulting in change or gain of functions.

  6. Design and Synthesis of Novel Molecular Tweezers Derived from Chenodeoxycholic Acid

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang ZHAO; Qi Ming MU; Shu Hua CHEN

    2004-01-01

    A novel type of chiral molecular tweezers has been designed and synthesized by using chenodeoxy cholic acid as spacer and the aromatic compounds as arm. Their structures were characterized by 1HNMR, IR, MS spectra and elemental analysis. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.

  7. Molecular modeling of protonic acid doping of emeraldine base polyaniline for chemical sensors

    NARCIS (Netherlands)

    Chen, X.; Yuan, C.A.; Wong, C.K.Y.; Ye, H.; Leung, S.Y.Y.; Zhang, G.

    2012-01-01

    We proposed a molecular modeling methodology to study the protonic acid doping of emeraldine base polyaniline which can used in gas detection. The commercial forcefield COMPASS was used for the polymer and protonic acid molecules. The molecular model, which is capable of representing the polyaniline

  8. Capillary Electrochromatography of Molecularly Imprinted Monolithic Column Using p-Hydroxybenzoic Acid as Templates

    Institute of Scientific and Technical Information of China (English)

    Zhao Sheng LIU; Yan Li XU; Chao YAN; Ru Yu GAO

    2004-01-01

    Molecularly imprinted polymers using p-hydroxybenzoic acid as templates was synthesized by an in situ polymerization reaction and rendered capillary monolithic column was used in capillary electrochromatographic mode. Good molecular recognition was achieved forphydroxybenzoic acid and good resolution of isomers can be realized.

  9. A column-switching liquid chromatography-tandem mass spectrometry method for quantitation of 2-cyanoethylmercapturic acid and 2-hydroxyethylmercapturic acid in Chinese smokers.

    Science.gov (United States)

    Hou, Hongwei; Xiong, Wei; Gao, Na; Zhang, Xiaotao; Tang, Gangling; Hu, Qingyuan

    2012-11-01

    The acrylonitrile metabolites 2-cyanoethylmercapturic acid (CEMA) and 2-hydroxyethylmercapturic acid (HEMA) have been determined in human urine using an automated column-switching procedure. A diluted sample was centrifuged just prior to being injected into a reusable precolumn packed with a restricted access material and coupled to a liquid chromatography-tandem mass spectrometry system. This method achieved satisfactory reproducibility and accuracy. Average intra- and interday variations (% relative standard deviations) ranged from 2.4 to 3.8% for CEMA and from 2.7 to 10.5% for HEMA. The limits of quantification were 0.003 and 0.099ng/ml for CEMA and HEMA, respectively. It was used to study the uptake of acrylonitrile from smoke constituents by both nonsmokers and smokers of different tar yield cigarettes under ISO 3308 smoking condition. Metabolite concentrations in smoker urine samples were approximately 12 times higher compared with those in nonsmokers for CEMA and 3 times higher for HEMA. Urinary CEMA levels show a clear dose-response relationship with daily cigarette consumption and urinary cotinine. CEMA can also discriminate between smokers of different ISO cigarettes. Because HEMA is not specific, it is only slightly related to smoking and acrylonitrile exposure. The validated biomarker CEMA will continue to be useful for studies of acrylonitrile uptake by smokers.

  10. Synthesis, Crystal Structure, and Hirshfeld Surface Analysis of Ciprofloxacin-Salicylic Acid Molecular Salt

    OpenAIRE

    Ravikumar Nagalapalli; Shankar Yaga Bheem

    2014-01-01

    In the present study, ciprofloxacin-salicylic acid molecular salt has been synthesized and preliminarily characterized by FT-IR spectroscopy. The single crystal X-ray diffraction (SCXRD) reveals the proton transfer from carboxylic acid group of salicylic acid to piperazine moiety in ciprofloxacin confirming the formation of new molecular salt. The molecular packing of the molecular salt is mainly supported by N+–H⋯O−, O–H⋯O, C–H⋯F, C–H⋯π, and π-π interactions. The 3D Hirshfeld surfaces and th...

  11. Synthesis, Crystal Structure, and Hirshfeld Surface Analysis of Ciprofloxacin-Salicylic Acid Molecular Salt

    Directory of Open Access Journals (Sweden)

    Ravikumar Nagalapalli

    2014-01-01

    Full Text Available In the present study, ciprofloxacin-salicylic acid molecular salt has been synthesized and preliminarily characterized by FT-IR spectroscopy. The single crystal X-ray diffraction (SCXRD reveals the proton transfer from carboxylic acid group of salicylic acid to piperazine moiety in ciprofloxacin confirming the formation of new molecular salt. The molecular packing of the molecular salt is mainly supported by N+–H⋯O−, O–H⋯O, C–H⋯F, C–H⋯π, and π-π interactions. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated for intermolecular hydrogen bonding interactions.

  12. Folic acid supplementation during early hepatocarcinogenesis: cellular and molecular effects.

    Science.gov (United States)

    Chagas, Carlos Eduardo Andrade; Bassoli, Bruna Kempfer; de Souza, Camila Alexandre Soares; Deminice, Rafael; Jordão Júnior, Alceu Afonso; Paiva, Sérgio Alberto Rupp; Dagli, Maria Lúcia Zaidan; Ong, Thomas Prates; Moreno, Fernando Salvador

    2011-11-01

    Folic acid (FA) supplementation during carcinogenesis is controversial. Considering the impact of liver cancer as a public health problem and mandatory FA fortification in several countries, the role of FA supplementation in hepatocarcinogenesis should be elucidated. We evaluated FA supplementation during early hepatocarcinogenesis. Rats received daily 0.08 mg (FA8 group) or 0.16 mg (FA16 group) of FA/100 g body weight or water (CO group, controls). After a 2-week treatment, animals were subjected to the "resistant hepatocyte" model of hepatocarcinogenesis (initiation with diethylnitrosamine, selection/promotion with 2-acetylaminofluorene and partial hepatectomy) and euthanized after 8 weeks of treatment. Compared to the CO group, the FA16 group presented: reduced (p PNL); reduced (p PNL; decreased (p PNL. Regarding all these parameters, no differences (p > 0.05) were observed between CO and FA8 groups. FA-treated groups presented increased hepatic levels of S-adenosylmethionine but only FA16 group presented increased S-adenosylmethionine/S-adenosylhomocysteine ratio. No differences (p > 0.05) were observed between experimental groups regarding apoptosis in persistent and remodeling GST-P positive PNL, and global DNA methylation pattern in microdissected PNL. Altogether, the FA16 group, but not the FA8 group, presented chemopreventive activity. Reversion of PNL phenotype and inhibition of DNA damage and of c-myc expression represent relevant FA cellular and molecular effects.

  13. Development and Evaluation of Amino Acid Molecular Models

    Directory of Open Access Journals (Sweden)

    Aparecido R. Silva

    2007-05-01

    Full Text Available The comprehension of structure and function of proteins has a tight relationshipwith the development of structural biology. However, biochemistry students usuallyfind difficulty to visualize the structures when they use only schematic drawings ofdidactic books. The representation of three-dimensional structures of somebiomolecules with ludic models, built with representative units, have supplied tothe students and teachers a successfully experience to better visualize andcorrelate the structures to the real molecules. The present work shows thedeveloped models and the process to produce the representative units of the mainamino acids in industrial scale. The design and applicability of the representativeunits were discussed with many teachers and some suggestions wereimplemented to the models. The preliminary evaluation and perspective ofutilization by researchers show that the work is in the right direction. At the actualstage, the models are defined, prototypes were made and will be presented in thismeeting. The moulds for the units are at the final stage of construction and trial inspecialized tool facilities. The last term will consist of an effective evaluation of thedidactic tool for the teaching/learning process in Structural Molecular Biology. Theevaluation protocol is being elaborated containing simple and objective questions,similar to those used in research on science teaching.

  14. Study on fluorescence spectra of molecular association of acetic acid-water

    Institute of Scientific and Technical Information of China (English)

    Caiqin Han; Ying Liu; Yang Yang; Xiaowu Ni; Jian Lu; Xiaosen Luo

    2009-01-01

    Fluorescence spectra of acetic acid-water solution excited by ultraviolet (UV) light are studied, and the relationship between fluorescence spectra and molecular association of acetic acid is discussed. The results indicate that when the exciting light wavelength is longer than 246 nm, there are two fluorescence peaks located at 305 and 334 nm, respectively. By measuring the excitation spectra, the optimal wavelengths of the two fluorescence peaks are obtained, which are 258 and 284 nm, respectively. Fluorescence spectra of acetic acid-water solution change with concentrations, which is primarily attributed to changes of molecular association of acetic acid in aqueous solution. Through theoretical analysis, three variations of molecular association have been obtained in acetic acid-water solution, which are the hydrated monomers, the linear dimers, and the water separated dimers. This research can provide references to studies of molecular association of acetic acid-water, especially studies of hydrogen bonds.

  15. Effects of molecular chirality on self-assembly and switching in liquid crystals at the cross-over between rod-like and bent shapes.

    Science.gov (United States)

    Ocak, Hale; Poppe, Marco; Bilgin-Eran, Belkız; Karanlık, Gürkan; Prehm, Marko; Tschierske, Carsten

    2016-09-21

    A bent-core compound derived from a 4-cyanoresorcinol core unit with two terephthalate based rod-like wings and carrying chiral 3,7-dimethyloctyloxy side chains has been synthesized in racemic and enantiomerically pure form and characterized by polarizing microscopy, differential scanning calorimetry, X-ray diffraction and electro-optical investigations to study the influence of molecular chirality on the superstructural chirality and polar order in lamellar liquid crystalline phases. Herein we demonstrate that the coupling of molecular chirality with superstructural layer chirality in SmCsPF domain phases (forming energetically distinct diastereomeric pairs) can fix the tilt direction and thus stabilize synpolar order, leading to bistable ferroelectric switching in the SmC* phases of the (S)-enantiomer, whereas tristable modes determine the switching of the racemate. Moreover, the mechanism of electric field induced molecular reorganization changes from a rotation around the molecular long axis in the racemate to a rotation on the tilt-cone for the (S)-enantiomer. At high temperature the enantiomer behaves like a rod-like molecule with a chirality induced ferroelectric SmC* phase and an electroclinic effect in the SmA'* phase. At reduced temperature sterically induced polarization, due to the bent molecular shape, becomes dominating, leading to much higher polarization values, thus providing access to high polarization ferroelectric materials with weakly bent compounds having only "weakly chiral" stereogenic units. Moreover, the field induced alignment of the SmCsPF(()*()) domains gives rise to a special kind of electroclinic effect appearing even in the absence of molecular chirality. Comparison with related compounds indicates that the strongest effects of chirality appear for weakly bent molecules with a relatively short coherence length of polar order, whereas for smectic phases with long range polar order the effects of the interlayer interfaces can override

  16. Synthesis, molecular structure, spectroscopic investigations and computational study of a potential molecular switch of 2-([1,1'-biphenyl]-4-yl)-2-methyl-6-(4-nitrophenyl)-4-phenyl-1,3 diazabicyclo [3.1.0]hex-3-ene

    Indian Academy of Sciences (India)

    AYOUB KANAANI; DAVOOD AJLOO; HAMZEH I KIYAN; FRESHTE SHAHERI; MAJID AMIRI

    2016-08-01

    This work presents a combined experimental and theoretical study on a photochromic compound, 2-([1,1'-biphenyl]-4-yl)-2-methyl-6-(4-nitrophenyl)-4-phenyl-1,3 diazabicyclo [3.1.0]hex-3-ene, existing in closed form (‘A’) and open form (‘B’). The spectroscopic properties of the title compound have beeninvestigated by using IR, UV–Vis and ¹H NMR techniques. The molecular geometry and spectroscopic data of the title compound have been calculated by using the density functional method (B3LYP) invoking 6-311G(d,p) basis set. UV-Vis spectra of the two forms were recorded. The excitation energies, oscillator strength, etc., were calculated by time-dependent density functional theory (TD-DFT). Furthermore, molecular electrostatic potential map (MEP), frontier molecular orbital analysis (HOMO–LUMO), total density of state (TDOS) and reactivity descriptors were found and discussed. We applied a first-principles computational approach to study a light-sensitive molecular switch. We find that the conductance of the two isomers varies dramatically, which suggests that this system has potential use as a molecular switch.

  17. Effect of Molecular Structure on the Performance of Polyacrylic Acid Superplasticizer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rongguo; GUO Huiling; LEI Jiaheng; ZHANG Anfu; GU Huajun

    2007-01-01

    The effects of structure parameters, such as molecular structure, segment kinds, molecular weight, and organic functional groups, on the performance of polyacrylic acid superplasticizer were discussed. According to the differences of chain sections, functional groups, etc, polyacrylic acid superplasticizer could be divided into A, B, C three parts. Among them, A chain section included sulfonic acid groups, B chain section carboxyl groups, C chain section polyester. Polyacrylic acid superplasticizers with different matching of A, B, C chain sections, different length of C chain section and different molecular weights were synthesized by acrylic acid, polyethylene glycol, sodium methyl allylsulfonate; the relation between the molecular structure and performance was also studied. The expetimental results indicate that the water-reduction ratio increases obviously with the increment of the proportion of sodium methyl allylsulfonate chain section in the molecular; the slump retention increases greatly with the increment of the proportion of acrylic acid chain section; the dispersion of cement particles increases with the increment of the chain length of polyethylene glycol; when the molecular weight is in the range of 5000, the dispersion and slump retentibity increase with the increment of the average molecular weight of polymers.

  18. Wet oxidation kinetics of refractory low molecular mass carboxylic acids

    Energy Technology Data Exchange (ETDEWEB)

    Shende, R.V.; Levec, J.

    1999-10-01

    Wet oxidation kinetics of aqueous solutions of formic, acetic, oxalic, and glyoxalic acids was studied in a titanium autoclave at a temperature range of 150--320 C and oxygen partial pressures between 8 and 60 bar. Oxidation reactions obeyed a first-order kinetics with respect to concentration of all substrates. On the basis of acid concentration decay, the activation energy for acetic, oxalic, and glyoxalic acid oxidation was 178, 137, and 97 kJ/mol, respectively; whereas on the total organic carbon (TOC) conversion basis, these values were slightly higher, namely 182, 141, and 104 kJ/mol. The activation energy for formic acid took a unique value of 149 kJ/mol regardless of the type of concentration used. The rate of oxidation was proportional to a square root of oxygen concentration (partial pressure) for acetic, formic, and oxalic acids, whereas it was linearly proportional for glyoxalic acid. When sufficiently high oxygen partial pressure was applied ({ge}22 bar), the individual acid conversion in a mixture of these acids was well predicted by the rate expression derived for that acid. The lumped TOC concentration of mixtures did not obey a first-order kinetic behavior, although underlying TOC kinetics for each individual acid was linear. The oxidation results are also discussed in a view of speculated reaction pathways and the reactor material.

  19. Structural polymorphism of the major capsid protein of a double-stranded RNA virus: an amphipathic alpha helix as a molecular switch.

    Science.gov (United States)

    Saugar, Irene; Luque, Daniel; Oña, Ana; Rodríguez, José F; Carrascosa, José L; Trus, Benes L; Castón, José R

    2005-07-01

    The infectious bursal disease virus T=13 viral particle is composed of two major proteins, VP2 and VP3. Here, we show that the molecular basis of the conformational flexibility of the major capsid protein precursor, pVP2, is an amphipatic alpha helix formed by the sequence GFKDIIRAIR. VP2 containing this alpha helix is able to assemble into the T=13 capsid only when expressed as a chimeric protein with an N-terminal His tag. An amphiphilic alpha helix, which acts as a conformational switch, is thus responsible for the inherent structural polymorphism of VP2. The His tag mimics the VP3 C-terminal region closely and acts as a molecular triggering factor. Using cryo-electron microscopy difference imaging, both polypeptide elements were detected on the capsid inner surface. We propose that electrostatic interactions between these two morphogenic elements are transmitted to VP2 to acquire the competent conformations for capsid assembly.

  20. Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved in intestinal inflammation

    OpenAIRE

    Knoch, Bianca; Matthew P.G. Barnett; McNabb, Warren C.; Roy, Nicole C.

    2009-01-01

    The use of «omic» techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acid...

  1. High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

    OpenAIRE

    Maharjan, Anu S; Darrell Pilling; Gomer, Richard H.

    2011-01-01

    BACKGROUND: Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da). METHODS AND FINDINGS: In this report, we show that HMWHA potentiates the differentiation of human monocytes into ...

  2. Nucleic Acids Research annual Database Issue and the NAR online Molecular Biology Database Collection in 2009.

    Science.gov (United States)

    Galperin, Michael Y; Cochrane, Guy R

    2009-01-01

    The current issue of Nucleic Acids Research includes descriptions of 179 databases, of which 95 are new. These databases (along with several molecular biology databases described in other journals) have been included in the Nucleic Acids Research online Molecular Biology Database Collection, bringing the total number of databases in the collection to 1170. In this introductory comment, we briefly describe some of these new databases and review the principles guiding the selection of databases for inclusion in the Nucleic Acids Research annual Database Issue and the Nucleic Acids Research online Molecular Biology Database Collection. The complete database list and summaries are available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  3. Molecular Determinants of the Response of Tumor Cells to Boswellic Acids

    Directory of Open Access Journals (Sweden)

    Thomas Efferth

    2011-08-01

    Full Text Available Frankincense (Boswellia serrata, B. carterii is used as traditional remedy to treat inflammatory diseases. The molecular effects of the active ingredients, the boswellic acids, on the immune system have previously been studied and verified in several clinical studies. Boswellic acids also inhibit cancer cell growth in vitro and in vivo. The molecular basis of the cytotoxicity of boswellic acids is, however, not fully understood as yet. By mRNA-based microarray, COMPARE, and hierarchical cluster analyses, we identified a panel of genes from diverse functional groups, which were significantly associated with sensitivity or resistance of a- or b-boswellic acids, such as transcription factors, signal transducers, growth regulating genes, genes involved in RNA and protein metabolism and others. This indicates that boswellic acids exert profound cytotoxicity on cancer cells by a multiplicity of molecular mechanisms.

  4. Molecular Determinants of the Response of Tumor Cells to Boswellic Acids

    Science.gov (United States)

    Eichhorn, Tolga; Greten, Henry Johannes; Efferth, Thomas

    2011-01-01

    Frankincense (Boswellia serrata, B. carterii) is used as traditional remedy to treat inflammatory diseases. The molecular effects of the active ingredients, the boswellic acids, on the immune system have previously been studied and verified in several clinical studies. Boswellic acids also inhibit cancer cell growth in vitro and in vivo. The molecular basis of the cytotoxicity of boswellic acids is, however, not fully understood as yet. By mRNA-based microarray, COMPARE, and hierarchical cluster analyses, we identified a panel of genes from diverse functional groups, which were significantly associated with sensitivity or resistance of α- or β-boswellic acids, such as transcription factors, signal transducers, growth regulating genes, genes involved in RNA and protein metabolism and others. This indicates that boswellic acids exert profound cytotoxicity on cancer cells by a multiplicity of molecular mechanisms.

  5. Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC zeta-GLUT4-glucose pathway in cardiomyoblasts.

    Science.gov (United States)

    Chen, Yeh-Peng; Tsai, Chia-Wen; Shen, Chia-Yao; Day, Cecilia-Hsuan; Yeh, Yu-Lan; Chen, Ray-Jade; Ho, Tsung-Jung; Padma, V Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2016-05-01

    Metabolic regulation is inextricably linked with cardiac function. Fatty acid metabolism is a significant mechanism for creating energy for the heart. However, cardiomyocytes are able to switch the fatty acids or glucose, depending on different situations, such as ischemia or anoxia. Lipotoxicity in obesity causes impairments in energy metabolism and apoptosis in cardiomyocytes. We utilized the treatment of H9c2 cardiomyoblast cells palmitic acid (PA) as a model for hyperlipidemia to investigate the signaling mechanisms involved in these processes. Our results show PA induces time- and dose-dependent lipotoxicity in H9c2 cells. Moreover, PA enhances cluster of differentiation 36 (CD36) and reduces glucose transporter type 4 (GLUT4) pathway protein levels following a short period of treatment, but cells switch from CD36 back to the GLUT4 pathway after during long-term exposure to PA. As sirtuin 1 (SIRT1) and protein kinase Cζ (PKCζ) play important roles in CD36 and GLUT4 translocation, we used the SIRT1 activator resveratrol and si-PKCζ to identify the switches in metabolism. Although PA reduced CD36 and increased GLUT4 metabolic pathway proteins, when we pretreated cells with resveratrol to activate SIRT1 or transfected si-PKCζ, both were able to significantly increase CD36 metabolic pathway proteins and reduce GLUT4 pathway proteins. High-fat diets affect energy metabolism pathways in both normal and aging rats and involve switching the energy source from the CD36 pathway to GLUT4. In conclusion, PA and high-fat diets cause lipotoxicity in vivo and in vitro and adversely switch the energy source from the CD36 pathway to the GLUT4 pathway.

  6. Design and synthesis of novel chiral molecular tweezers based on deoxycholic acid

    Institute of Scientific and Technical Information of China (English)

    Zhi Gang Zhao; Xing Li Liu; Yi Zhong

    2008-01-01

    A novel type of chiral molecular tweezers has been designed and synthesized by using deoxycholic acid as backbone and ethanoyl and the chiral unsymmetrical urea unit as arms. Their structures were characterized by 1H NMR, IR, MS spectra and elemental analysis. These molecular tweezers showed good binding ability for neutral molecules and chiral molecules.

  7. An intrinsic propensity of murine peritoneal B1b cells to switch to IgA in presence of TGF-β and retinoic acid.

    Directory of Open Access Journals (Sweden)

    Bishnudeo Roy

    Full Text Available AIMS: In the present study we have investigated the comparative switching propensity of murine peritoneal and splenic B cell subpopulations to IgA in presence of retinoic acid (RA and TGF-β. METHODS AND RESULTS: To study the influence of RA and TGF-β on switching of B cell subpopulations to IgA, peritoneal (B1a, B1b and B2 cells and splenic (B1a, marginal zone, and B2 B cells from normal BALB/c mice were FACS purified, cultured for 4 days in presence of RA and TGF-β and the number of IgA producing cells was determined by ELISPOT assay or FACS analysis. In presence of TGF-β, peritoneal B1b cells switched to IgA more potently than other peritoneal B cell subpopulations. When TGF-β was combined with retinoic acid (RA, switching to IgA was even more pronounced. Under these conditions, "innate" B cells like peritoneal and splenic B1 cells and MZ B cells produced IgA more readily than B2 cells. Additionally, high frequency of nucleotide exchanges indicating somatic hypermutation in VH regions was observed. Besides IgA induction, RA treatment of sorted PEC and splenic B cells led to expression of gut homing molecules - α4β7 and CCR9. Intraperitoneal transfer of RA-treated B1 cells into Rag1(-/- recipients resulted in IgA in serum and gut lavage, most efficiently amongst B1b cell recipients. CONCLUSION: Present study demonstrates the differential and synergistic effect of RA and TGF-β on switching of different B cell subpopulations to IgA and establishes the prominence of peritoneal B1b cells in switching to IgA under the influence of these two factors. Our study extends our knowledge about the existing differences among B cell subpopulations with regards to IgA production and indicates towards their differential contribution to gut associated humoral immunity.

  8. Computational study on 3D structure of L-aspartic acid and L-glutamic acid: molecular descriptors and properties

    Directory of Open Access Journals (Sweden)

    Stefaniu Amalia

    2016-06-01

    Full Text Available The aim of this work is to provide a comprehensive and complex analysis of molecular descriptors and properties of two similar amino acids, L-Aspartic acid and L-Glutamic acid, using a software tool for calculations and properties predictions. As amino acids are model compounds for predicting the physical-chemical properties and behavior of biological, larger molecules as peptides or proteins, researches were focused on providing accurate mechanical calculations using: molecular/mechanical methods. Our study aims to initiate a linear scaling approach, by dividing a large system into small subsystems and performing the calculations for each, individually, then, embedding and correcting the information globally. The calculations were performed on the 3D structure of the studied amino acids that were first generated, as CPK model, and optimized by energy minimization. A comparative assay on their topological, molecular descriptors and properties was conducted, in vacuum and in water, using the Hartree-Fock model and second-order Møller-Plesset perturbation theory MP2 for predicting structure, energy and property calculations with Spartan’14 software. Values of molecular properties such as area, volume, polar surface area, polarizability, ovality, logP, dipole moment, HOMO-LUMO gap, distances and angles between atoms, were obtained. The results have been interpreted in terms of electronic effects of side chain groups, molecular deformability, steric factors and reactivity. This approach can be extended to other amino acids in order to predict protein-ligand interactions, important aspects in drug design studies and protein engineering.

  9. Molecular mechanisms behind the antimicrobial activity of hop iso-α-acids in Lactobacillus brevis.

    Science.gov (United States)

    Schurr, Benjamin C; Hahne, Hannes; Kuster, Bernhard; Behr, Jürgen; Vogel, Rudi F

    2015-04-01

    The main bittering component in beer, hop iso-α-acids, have been characterised as weak acids, which act as ionophores impairing microbial cells' function under acidic conditions as present in beer. Besides medium pH, divalent cations play a central role regarding the efficacy of the antimicrobial effect. The iso-α-acids' non-bitter derivatives humulinic acids can be found in isomerised hop extracts and can be generated during hop storage. Therefore, they have been under investigation concerning their influence on beer sensory properties. This study sketches the molecular mechanism behind iso-α-acids' antimicrobial activity in Lactobacillus (L.) brevis regarding their ionophore activity versus the dependence of the inhibitory potential on manganese binding, and suggests humulinic acids as novel tasteless food preservatives. We designed and synthesised chemically modified iso-α-acids to enhance the basic understanding of the molecular mechanism of antimicrobial iso-α-acids. It could be observed that a manganese-binding dependent transmembrane redox reaction (oxidative stress) plays a crucial role in inhibition. Privation of an acidic hydroxyl group neither erased ionophore activity, nor did it entirely abolish antimicrobial activity. Humulinic acids proved to be highly inhibitory, even outperforming iso-α-acids.

  10. Effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a statin-treated patient with elevated triglycerides.

    Science.gov (United States)

    Kedia, Anurag W; Lynch, Erin

    2015-01-01

    In patients with dyslipidemia, elevated triglyceride (TG) levels, or TG-rich lipoproteins, and cardiovascular risk may remain despite statin therapy. Prescription omega-3 fatty acid formulations containing the ethyl esters of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (omega-3-acid ethyl esters; Lovaza®) or high-purity EPA ethyl ester (icosapent ethyl; Vascepa®) are TG-lowering treatments that may be administered in addition to statins. Here we describe the effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a 44-year-old obese man with dyslipidemia, hypertension, and hypothyroidism. The patient was receiving stable treatment with medications, including atorvastatin 40 mg/day and extended-release niacin 1000 mg/day. Owing to persistently elevated TG levels and other cardiovascular risk factors, the patient was initiated on omega-3-acid ethyl esters 4 g/day. After approximately 2 years on omega-3-acid ethyl esters, his total cholesterol (TC) level was 184 mg/dL, low-density lipoprotein cholesterol (LDL-C) level was 81 mg/dL, TG level was elevated at 307 mg/dL despite statin therapy, and non-high-density lipoprotein cholesterol (non-HDL-C) level was 144 mg/dL. After the switch to icosapent ethyl, TC level decreased by 34% to 121 mg/dL, LDL-C level decreased by 28% to 58 mg/dL, TG level decreased by 41% to 180 mg/dL, and non-HDL-C level decreased by 44% to 81 mg/dL. Switching from omega-3-acid ethyl esters containing both EPA and DHA to icosapent ethyl containing high-purity EPA resulted in beneficial and substantial changes in the lipid profile with a notable reduction of TG levels along with additional reductions in LDL-C levels in a statin-treated obese patient with persistently high TG levels. Treatment with icosapent ethyl was well tolerated.

  11. Phosphorus release from phosphate rock and iron phosphate by low-molecular-weight organic acids

    Institute of Scientific and Technical Information of China (English)

    XU Ren-kou; ZHU Yong-guan; David Chittleborough

    2004-01-01

    Low-molecular-weight(LMW) organic acids widely exist in soils, particularly in the rhizosphere. A series of batch experiments were carried out to investigate the phosphorus release from rock phosphate and iron phosphate by Iow-molecular-weight organic acids.Results showed that citric acid had the highest capacity to solubilize P from both rock and iron phosphate. P solubilization from rock phosphate and iron phosphate resulted in net proton consumption. P release from rock phosphate was positively correlated with the pKa values. P release from iron phosphate was positively correlated with Fe-organic acid stability constants except for aromatic acids, but was not correlated with PKa. Increase in the concentrations of organic acids enhanced P solubilization from both rock and iron phosphate almost linearrly. Addition of phenolic compounds further increased the P release from iron phosphate. Initial solution pH had much more substantial effect on P release from rock phosphate than from iron phosphate.

  12. A Metabolic Switch

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    Our muscles are metabolically flexible, i.e., they are capable of `switching' between two types of oxidation: (1) when fasting, a predominantly lipid oxidation with high rates of fatty acid uptake, and (2) when fed, suppression of lipid oxidation in favour of increased glucose uptake, oxidation...... and storage, in response to insulin. One of the many manifestations of obesity and Type 2 diabetes is an insulin resistance of the skeletal muscles, which suppresses this metabolic switch. This talk describes recent development of a low-dimensional system of ODEs that model the metabolic switch, displaying...

  13. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Stensbøl, T B;

    1997-01-01

    using rat brain ionotropic glutamate receptors, and in functional assays using cloned metabotropic glutamate (mGlu) receptors. As a notable result of these studies, (2S,4R)-4-methylglutamic acid and (2S,4S)-4-methylglutamic acid were shown to be selective for kainic acid receptors and mGlu receptors......The pharmacology of (2S,4R)-4-methylglutamic acid, (2S,4S)-4-methylglutamic acid and (S)- and (R)-4-methyleneglutamic acids (obtained in high chemical and enantiomeric purity from racemic 4-methyleneglutamic acid by chiral HPLC using a Crownpak CR(+) column), was examined in binding experiments...... (subtypes 1alpha and 2), respectively, whereas (S)-4-methyleneglutamic acid showed high but rather non-selective affinity for the (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), kainic acid, NMDA and mGlu receptors (subtypes 1alpha and 2). Although none of the compounds were specific...

  14. Molecular targets of omega 3 and conjugated linoleic fatty acids – micromanaging cellular response

    Directory of Open Access Journals (Sweden)

    Francesco eVisioli

    2012-02-01

    Full Text Available Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and CLA, as paradigmatic molecules that can be explored both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.

  15. Effect of Low-Molecular-Weight Organic Acids on Cl- Adsorption by Variable Charge Soils

    Institute of Scientific and Technical Information of China (English)

    XU Ren-Kou; ANG Ma-Li; WANG Qiang-Sheng; JI Guo-Liang1

    2004-01-01

    Low-molecular-weight (LMW) organic acids exist widely in soils and have been implicated in many soil processes.The objective of the present paper was to evaluate effect of two LMW organic acids, citric acid and oxalic acid, on Cl- adsorption by three variable charge soils, a latosol, a lateritic red soil and a red soil, using a batch method. The results showed that the presence of citric acid and oxalic acid led to a decrease in Cl- adsorption with larger decreases for citric acid. Among the different soils Gl- adsorption in the lateritic red soil and the red soil was more affected by both the LMW organic acids than that in the latosol.

  16. Potential origin and formation for molecular components of humic acids in soils

    Science.gov (United States)

    DiDonato, Nicole; Chen, Hongmei; Waggoner, Derek; Hatcher, Patrick G.

    2016-04-01

    Soil humic acids are the base soluble/acid insoluble organic components of soil organic matter. Most of what we know about humic acids comes from studies of their bulk molecular properties or analysis of individual fractions after extraction from soils. This work attempts to better define humic acids and explain similarities and differences for several soils varying in degrees of humification using advanced molecular level techniques. Our investigation using electrospray ionization coupled to Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) and nuclear magnetic resonance spectroscopy (NMR) has given new insight into the distinctive molecular characteristics of humic acids which suggest a possible pathway for their formation. Humic acids from various ecosystems, climate regions and soil textural classes are distinguished by the presence of three predominant molecular components: lignin-like molecules, carboxyl-containing aliphatic molecules and condensed aromatic molecules that bear similarity to black carbon. Results show that humification may be linked to the relative abundance of these three types of molecules as well as the relative abundance of carboxyl groups in each molecular type. This work also demonstrates evidence for lignin as the primary source of soil organic matter, particularly condensed aromatic molecules often categorized as black carbon and is the first report of the non-pyrogenic source for these compounds in soils. We also suggest that much of the carboxyl-containing aliphatic molecules are sourced from lignin.

  17. In-silico design of computational nucleic acids for molecular information processing.

    Science.gov (United States)

    Ramlan, Effirul Ikhwan; Zauner, Klaus-Peter

    2013-05-07

    Within recent years nucleic acids have become a focus of interest for prototype implementations of molecular computing concepts. During the same period the importance of ribonucleic acids as components of the regulatory networks within living cells has increasingly been revealed. Molecular computers are attractive due to their ability to function within a biological system; an application area extraneous to the present information technology paradigm. The existence of natural information processing architectures (predominately exemplified by protein) demonstrates that computing based on physical substrates that are radically different from silicon is feasible. Two key principles underlie molecular level information processing in organisms: conformational dynamics of macromolecules and self-assembly of macromolecules. Nucleic acids support both principles, and moreover computational design of these molecules is practicable. This study demonstrates the simplicity with which one can construct a set of nucleic acid computing units using a new computational protocol. With the new protocol, diverse classes of nucleic acids imitating the complete set of boolean logical operators were constructed. These nucleic acid classes display favourable thermodynamic properties and are significantly similar to the approximation of successful candidates implemented in the laboratory. This new protocol would enable the construction of a network of interconnecting nucleic acids (as a circuit) for molecular information processing.

  18. Switch wear leveling

    Science.gov (United States)

    Wu, Hunter; Sealy, Kylee; Gilchrist, Aaron

    2015-09-01

    An apparatus for switch wear leveling includes a switching module that controls switching for two or more pairs of switches in a switching power converter. The switching module controls switches based on a duty cycle control technique and closes and opens each switch in a switching sequence. The pairs of switches connect to a positive and negative terminal of a DC voltage source. For a first switching sequence a first switch of a pair of switches has a higher switching power loss than a second switch of the pair of switches. The apparatus includes a switch rotation module that changes the switching sequence of the two or more pairs of switches from the first switching sequence to a second switching sequence. The second switch of a pair of switches has a higher switching power loss than the first switch of the pair of switches during the second switching sequence.

  19. Exciter switch

    Science.gov (United States)

    Mcpeak, W. L.

    1975-01-01

    A new exciter switch assembly has been installed at the three DSN 64-m deep space stations. This assembly provides for switching Block III and Block IV exciters to either the high-power or 20-kW transmitters in either dual-carrier or single-carrier mode. In the dual-carrier mode, it provides for balancing the two drive signals from a single control panel located in the transmitter local control and remote control consoles. In addition to the improved switching capabilities, extensive monitoring of both the exciter switch assembly and Transmitter Subsystem is provided by the exciter switch monitor and display assemblies.

  20. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  1. Photoelectron spectroscopy of self-assembled monolayers of molecular switches on noble metal surfaces; Photoelektronenspektroskopie selbstorganisierter Adsorbatschichten aus molekularen Schaltern auf Edelmetalloberflaechen

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, Nils

    2012-09-12

    Self-assembled monolayers (SAMs) of butanethiolate (C4) on single crystalline Au(111) surfaces were prepared by adsorption from solution. The thermally activated desorption behaviour of the C4 molecules from the gold substrate was examined by qualitative thermal desorption measurements (TDM), through this a desorption temperature T{sub Des}=473 K could be determined. With this knowledge, it was possible to produce samples of very good surface quality, by thermal treatment T{sub Sample}molecular switch 3-(4-(4-Hexyl-phenylazo)-phenoxy)-propane-1-thiol (ABT), deposited by self-assembly from solution on Au(111), was examined using laser-based photoelectron spectroscopy. Differences in the molecular dipole moment characteristic for the trans and the cis isomer of ABT were observed via changes in the sample work function, accessible by detection of the threshold energy for photoemission. A quantitative

  2. New concepts in molecular imaging: non-invasive MRI spotting of proteolysis using an Overhauser effect switch.

    Directory of Open Access Journals (Sweden)

    Philippe Mellet

    Full Text Available BACKGROUND: Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans. CONCLUSIONS/SIGNIFICANCE: The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.

  3. 全氟环戊二芳基乙烯多功能分子开关的研究进展%Progress in multifunctional molecular switches of perfluorocylopentene derivatives

    Institute of Scientific and Technical Information of China (English)

    范丛斌; 章洛汗; 蒲守智

    2011-01-01

    全氟环戊二芳基乙烯是近年来国内外备受关注的一类光致变色化合物.其优良的热稳定性、抗疲劳性,使其很有可能成为一种新型的超高密度信息存储、分子开关及光通信材料.主要介绍了该类化合物的结构异构所表现的不同特性的光/热控分子开关、电化学开关、荧光开关、手性开关和液晶等分子开关,并展望了该类化合物的发展前景.%Perfluorocyctopentene derivative is one of photochromic compounds, which has attracted considerable interest of research because of their thermally irreversible and fatigue resistance properties for use in optoelectronic devices such as ultrahigh-density optical data storage, molecular switches and optical communication. This article describes recent development of multifunctional-switchable perfluorocyclopentene derivatives,which show different isomer properties including photo/hot irradiation molecular switches, electrochemical switches, fluorescent photo-switches, photoirradiation chiral switches and liquid crystalline switches. Future development is prospected finally.

  4. Hyaluronic acid-coated chitosan nanoparticles: molecular weight-dependent effects on morphology and hyaluronic acid presentation.

    Science.gov (United States)

    Almalik, Abdulaziz; Donno, Roberto; Cadman, Christopher J; Cellesi, Francesco; Day, Philip J; Tirelli, Nicola

    2013-12-28

    Chitosan nanoparticles are popular carriers for the delivery of macromolecular payloads, e.g. nucleic acids. In this study, nanoparticles were prepared via complexation with triphosphate (TPP) anions and were successively coated with hyaluronic acid (HA). Key variables of the preparative process (e.g. chitosan and HA molecular weight) were optimised in view of the maximisation of loading with DNA, of the Zeta potential and of the dimensional stability, and the resulting particles showed excellent storage stability. We have focused on the influence of chitosan molecular weight on nanoparticle properties. Larger molecular weight increased their porosity (=decreased cross-link density), and this caused also larger dimensional changes in response to variations in osmotic pressure or upon drying. The dependency of nanoparticle porosity on chitosan molecular weight had a profound effect on the adsorption of HA on the nanoparticles; HA was apparently able to penetrate deeply into the more porous high molecular weight (684 kDa) chitosan nanoparticles, while it formed a corona around those composed of more densely cross-linked low molecular weight (25 kDa) chitosan. Atomic Force Microscopy (AFM) allowed not only to highlight the presence of this corona, but also to estimate its apparent thickness to about 20-30 nm (in a dry state). The different morphology has a significant effect on the way HA is presented to biomolecules, and this has specific relevance in relation to interactions with HA receptors (e.g. CD44) that influence kinetics and mechanism of nanoparticle uptake. Finally, it is worth to mention that chitosan molecular weight did not appear to greatly affect the efficiency of nanoparticle loading with DNA, but significantly influenced its chitosanase-triggered release, with high molecular chitosan nanoparticles seemingly more prone to degradation by this enzyme.

  5. Dissolution of Aluminum in Variably Charged Soils as Affected by Low-Molecular-Weight Organic Acids

    Institute of Scientific and Technical Information of China (English)

    LI Jiu-Yu; XU Ren-Kou; JI Guo-Liang

    2005-01-01

    Low-molecular-weight (LMW) organic acids exist widely in soils and play an important role in soil processes such as mineral weathering, nutrient mobilization and Al detoxification. In this research, a batch experiment was conducted to examine the effects of LMW organic acids on dissolution of aluminum in two variably charged soils, an Ultisol and an Oxisol. The results showed that the LMW organic acids enhanced the dissolution of Al in the two investigated soils in the following order: citric > oxalic > malonic > malic > tartaric > salicylic > lactic > maleic. This was generally in agreement with the magnitude of the stability constants for the Al-organic complexes. The effects of LMW organic acids on Al dissolution were greater in the Ultisol than in the Oxisol as compared to their controls. Also, the accelerating effects of citric and oxalic acids on dissolution of Al increased with an increase in pH, while the effects of lactic and salicylic acids decreased. Additionally, when the organic acid concentration was less than 0.2 mmol L-1, the dissolution of Al changed little with increase in acid concentration. However, when the organic acid concentration was greater than 0.2 mmol L-1,the dissolution of Al increased with increase in acid concentration. In addition to the acid first dissociation constant and stability constant of Al-organic complexes, the promoting effects of LMW organic acids on dissolution of Al were also related to their sorption-desorption equilibrium in the soils.

  6. Molecularly imprinted polymer microspheres for solid-phase extraction of protocatechuic acid in Rhizoma homalomenae.

    Science.gov (United States)

    Chen, Fang-Fang; Wang, Guo-Ying; Shi, Yan-Ping

    2011-10-01

    Molecularly imprinted polymers (MIPs) had been prepared by precipitation polymerization method using acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, acetonitrile as the porogen solvent and protocatechuic acid (PA), one of phenolic acids, as the template molecule. The MIPs were characterized by scanning electron microscopy and Fourier transform infrared, and their performance relative to non-imprinted polymers was assessed by equilibrium binding experiments. Six structurally similar phenolic acids, including p-hydroxybenzoic acid, gallic acid, salicylic acid, syringic acid, vanillic acid, ferulic acid were selected to assess the selectivity and recognition capability of the MIPs. The MIPs were applied to extract PA from the traditional Chinese medicines as a solid-phase extraction sorbent. The resultant cartridge showed that the MIPs have a good extraction performance and were able to selectively extract almost 82% of PA from the extract of Rhizoma homalomenae. Thus, the proposed molecularly imprinted-solid phase extraction-high performance liquid chromatography method can be successfully used to extract and analyse PA in traditional Chinese medicines.

  7. Synthesis and Characterization of Molecular Imprinting Polymer Microspheres of Cinnamic Acid: Extraction of Cinnamic Acid from Spiked Blood Plasma

    Directory of Open Access Journals (Sweden)

    Alvin Leong Joke Chow

    2016-01-01

    Full Text Available The molecular imprinting technique is used to create the molecularly imprinted polymers (MIPs with higher binding capacity towards the template. In this research precipitation polymerization method with noncovalent approach was used to synthesize imprinted polymer microspheres. The polymerization reaction was conducted in a flask containing acetonitrile as a porogen, cinnamic acid as a template (T, acrylic acid (AA as a monomer, divinylbenzene (DVB as a cross-linker, and azobisisobutyronitrile as an initiator. The polymer particles were characterized by using SEM and FTIR. The rebinding efficiency was conducted by batch binding assay and the results were monitored by using HPLC. The batch binding results suggested MIP1 (T : AA : DVB, 1 : 6 : 20 molar ratio is most suitable composition for the rebinding of cinnamic acid. The highly selective polymer (MIP1 was used for the extraction of cinnamic acid from human plasma. The extraction efficiency of imprinted polymer of cinnamic acid from spiked plasma was above 75%.

  8. Molecular self-assembly using peptide nucleic acids.

    Science.gov (United States)

    Berger, Or; Gazit, Ehud

    2017-01-01

    Peptide nucleic acids (PNAs) are extensively studied for the control of genetic expression since their design in the 1990s. However, the application of PNAs in nanotechnology is much more recent. PNAs share the specific base-pair recognition characteristic of DNA together with material-like properties of polyamides, both proteins and synthetic polymers, such as Kevlar and Nylon. The first application of PNA was in the form of PNA-amphiphiles, resulting in the formation of either lipid integrated structures, hydrogels or fibrillary assemblies. Heteroduplex DNA-PNA assemblies allow the formation of hybrid structures with higher stability as compared with pure DNA. A systematic screen for minimal PNA building blocks resulted in the identification of guanine-containing di-PNA assemblies and protected guanine-PNA monomer spheres showing unique optical properties. Finally, the co-assembly of PNA with thymine-like three-faced cyanuric acid allowed the assembly of poly-adenine PNA into fibers. In summary, we believe that PNAs represent a new and important family of building blocks which converges the advantages of both DNA- and peptide-nanotechnologies.

  9. Selective recognition and separation of amino acids by molecularly imprinted polymers

    OpenAIRE

    Trikka, F.A.; Papi, R. M.; Kyriakidis, D A

    2008-01-01

    Journal URL: http://www.springer.at/amino_acids Molecularly imprinted polymers (MIPs) are smart tailored-made materials used for the sensitive and selective recognition of small molecules and=or biologically important substances. The target molecule acting as a molecular template is copolymerized with an excess of afunctional monomer and a cross-linker. The template is entrapped in the formed polymer and following its removal complementary cavities in structure and in properties to the ...

  10. Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.

    Science.gov (United States)

    Lamb, Jeffrey P; Engers, Darren W; Niswender, Colleen M; Rodriguez, Alice L; Venable, Daryl F; Conn, P Jeffrey; Lindsley, Craig W

    2011-05-01

    This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.

  11. Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors

    DEFF Research Database (Denmark)

    Bräuner-Osborne, Hans; Nielsen, B; Krogsgaard-Larsen, P

    1998-01-01

    We have studied the effects of the enantiomers of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) and analogues substituted with a methyl, bromo or butyl group in the four position of the ring at cloned metabotropic glutamate (mGlu) receptors expressed in Chinese hamster...... ovary (CHO) cells. In contrast to the parent compound ibotenic acid, which is a potent group I and II agonist, the (S)-forms of homoibotenic acid and its analogues are selective and potent group I antagonists whereas the (R)-forms are inactive both as agonists and antagonists at group I, II, and III m......Glu receptors. Interestingly, (S)-homoibotenic acid and the analogues display equal potency at both mGlu1alpha and mGlu5a with Ki values in the range of 97 to 490 microM, (S)-homoibotenic acid and (S)-2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid [(S)-4-butylhomoibotenic acid] displaying the lowest...

  12. Complexation and molecular modeling studies of europium(III)-gallic acid-amino acid complexes.

    Science.gov (United States)

    Taha, Mohamed; Khan, Imran; Coutinho, João A P

    2016-04-01

    With many metal-based drugs extensively used today in the treatment of cancer, attention has focused on the development of new coordination compounds with antitumor activity with europium(III) complexes recently introduced as novel anticancer drugs. The aim of this work is to design new Eu(III) complexes with gallic acid, an antioxida'nt phenolic compound. Gallic acid was chosen because it shows anticancer activity without harming health cells. As antioxidant, it helps to protect human cells against oxidative damage that implicated in DNA damage, cancer, and accelerated cell aging. In this work, the formation of binary and ternary complexes of Eu(III) with gallic acid, primary ligand, and amino acids alanine, leucine, isoleucine, and tryptophan was studied by glass electrode potentiometry in aqueous solution containing 0.1M NaNO3 at (298.2 ± 0.1) K. Their overall stability constants were evaluated and the concentration distributions of the complex species in solution were calculated. The protonation constants of gallic acid and amino acids were also determined at our experimental conditions and compared with those predicted by using conductor-like screening model for realistic solvation (COSMO-RS) model. The geometries of Eu(III)-gallic acid complexes were characterized by the density functional theory (DFT). The spectroscopic UV-visible and photoluminescence measurements are carried out to confirm the formation of Eu(III)-gallic acid complexes in aqueous solutions.

  13. The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120)

    OpenAIRE

    Hudson, Brian D.; Shimpukade, Bharat; Milligan, Graeme; Ulven, Trond

    2014-01-01

    The long-chain fatty acid receptor FFA4(previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. The current study examines for the first time the detailed mode of binding of both a long-chain fatty acid and synthetic agonist ligands at FFA4 by integrating molecular modeling, receptor mutagenesis, and ligand structure-activity relationship approaches in an iterative format. In doing so, residues required for binding of fat...

  14. Nucleic acids--genes, drugs, molecular lego and more.

    Science.gov (United States)

    Häner, Robert

    2010-01-01

    Chemically modified nucleic acids find widespread use as tools in research, as diagnostic reagents and even as pharmaceutical compounds. On the background of antisense research and development, the synthesis and evaluation of modified oligonucleotides was intensively pursued in the early to mid nineties in corporate research of former Ciba. Most of these efforts concentrated on the development of sugar and/or backbone-modified derivatives for pharmaceutical applications. Additionally, oligonucleotide metal conjugates were investigated with the goal to develop artificial ribonucleases. Since the turn of the millennium also the potential of non-nucleosidic and non-hydrogen bonding building blocks has increasingly been recognized. Such derivatives possess unique properties that may have an impact in the fields of materials and genetic research. In this brief account, we take a personal look back on some past as well as some recent results.

  15. Molecularly imprinted titania nanoparticles for selective recognition and assay of uric acid

    Science.gov (United States)

    Mujahid, Adnan; Khan, Aimen Idrees; Afzal, Adeel; Hussain, Tajamal; Raza, Muhammad Hamid; Shah, Asma Tufail; uz Zaman, Waheed

    2015-06-01

    Molecularly imprinted titania nanoparticles are su ccessfully synthesized by sol-gel method for the selective recognition of uric acid. Atomic force microscopy is used to study the morphology of uric acid imprinted titania nanoparticles with diameter in the range of 100-150 nm. Scanning electron microscopy images of thick titania layer indicate the formation of fine network of titania nanoparticles with uniform distribution. Molecular imprinting of uric acid as well as its subsequent washing is confirmed by Fourier transformation infrared spectroscopy measurements. Uric acid rebinding studies reveal the recognition capability of imprinted particles in the range of 0.01-0.095 mmol, which is applicable in monitoring normal to elevated levels of uric acid in human blood. The optical shift (signal) of imprinted particles is six times higher in comparison with non-imprinted particles for the same concentration of uric acid. Imprinted titania particles have shown substantially reduced binding affinity toward interfering and structurally related substances, e.g. ascorbic acid and guanine. These results suggest the possible application of titania nanoparticles in uric acid recognition and quantification in blood serum.

  16. Improved Inhibition of Telomerase by Short Twisted Intercalating Nucleic Acids under Molecular Crowding Conditions

    DEFF Research Database (Denmark)

    Agarwal, Tani; Pradhan, Devranjan; Géci, Imrich;

    2012-01-01

    crowding conditions mimicking physiological milieu, stabilization of the telomeric G-quadruplex is often lost. We attempted to demonstrate the enhanced G-quadruplex stabilizing ability under molecular conditions by using twisted intercalating nucleic acids (TINA)-modified oligonucleotides. We have shown......-based telomerase repeat amplification assay (TRAP) assay as well as nondenaturing polyacrylamide gel electrophoresis-based TRAP, we demonstrate remarkable enhancement in their anti-telomerase activity even under molecular crowding conditions. This is the first time in which a G-quadruplex stabilizing agent has...... demonstrated enhanced activity even under molecular crowding conditions....

  17. Molecular Weight Distributions of Cotton Cellulose Treated with a Polycarboxylic Acid at Different pH

    Institute of Scientific and Technical Information of China (English)

    MAO Zhi-ping; Charles Q. Yang

    2004-01-01

    In last paper, the average molecular weight of a control cotton fabric and cotton fabrics treated with the polycarboxylic acid at different pH were measured. The result doesn't support the hypothesis that the pH of the finishing bath can affect the depolymerization of the finished cotton fabric. In order to understand more about it, the molecular weight distributions of the control and finished cotton fabrics were measured and the reason was fund. From the ratio and the molecular weight of the low molecular part one can see that the pH of the finishing bath can affect the depolymerization of the finished cotton fabrics. The phenomenon that the average molecular weights of the cotton fabric crosslinked with BTCA at different pH are almost same is attributed to that the crosslinks are not broken completely when treated with 0.5M NaOH solution at 50℃ for 144h.

  18. Combined spectroscopy and molecular modeling studies on the binding of galbanic acid and MMP9.

    Science.gov (United States)

    Kiani, Amir; Almasi, Khadijeh; Shokoohinia, Yalda; Sadrjavadi, Komail; Nowroozi, Amin; Shahlaei, Mohsen

    2015-11-01

    The molecular mechanism of galbanic acid (GBA) binding to matrix metalloproteinase 9 (MMP9) was investigated by fluorescence quenching, absorption spectroscopy, FT-IR, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of MMP9 was quenched by GBA. The titration of MMP9 by various amount of GBA was also followed by UV-Vis absorption spectroscopy. The results revealed that GBA, as a biologically active sesquiterpene coumarin derivative, has an ability to bind strongly to MMP9. Molecular docking results indicated that the main active binding site for GBA has been located in a hydrophobic cavity in the vicinity of Zn atom. Moreover, MD simulation results suggested that GBA as a coumarin derivative can interact with MMP9, without affecting the secondary structure of MMP9. MD simulations, molecular docking as computational methods from one hand and experimental data from other hand reciprocally supported each other.

  19. Phosphorylation state of CREB in the rat hippocampus: a molecular switch between spatial novelty and spatial familiarity?

    Science.gov (United States)

    Moncada, Diego; Viola, Haydée

    2006-07-01

    The activation of cAMP response element-binding protein (CREB) after a learning experience is a common feature in the formation of several associative memories. We recently demonstrated that the increase in the hippocampal phosphorylated CREB (pCREB) levels 1 h after a short exploration of an open field (OF) was associated to detection of spatial novelty and was not related to the memory formation of habituation in this non-associative learning paradigm. Moreover, after a long training of three OF sessions, hippocampal pCREB levels were below to that observed in control rats. The present results show that such decrease does not correlate with memory retrieval or improvement in long-term memory of habituation. Instead, it is associated with the familiarity to the arena. Our experiments revealed that the relevant variable to induce CREB deactivation was the prolonged exploration of the arena (30 min). A 15 min OF exploration was ineffective. Furthermore, the last 5 min period of a prolonged exploration was crucial to change CREB phosphorylation state: when exploration took place in a novel arena the level of pCREB increased; in contrast, when it was performed in the familiar OF, pCREB levels decreased. Taken as a whole, our results suggest that CREB phosphorylation state in the hippocampus switches in response to exposure to a novel or to a familiar spatial environment.

  20. Hybrid MPI/OpenMP Implementation of the ORAC Molecular Dynamics Program for Generalized Ensemble and Fast Switching Alchemical Simulations.

    Science.gov (United States)

    Procacci, Piero

    2016-06-27

    We present a new release (6.0β) of the ORAC program [Marsili et al. J. Comput. Chem. 2010, 31, 1106-1116] with a hybrid OpenMP/MPI (open multiprocessing message passing interface) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium technology aimed at evaluating the binding free energy in drug-receptor system on high performance computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level. The efficiency, simplicity, and inherent parallel nature of the ORAC implementation of the FS-DAM algorithm, project the code as a possible effective tool for a second generation high throughput virtual screening in drug discovery and design. The code, along with documentation, testing, and ancillary tools, is distributed under the provisions of the General Public License and can be freely downloaded at www.chim.unifi.it/orac .

  1. Femtosecond Laser Spectroscopy of the Rhodopsin Photochromic Reaction: A Concept for Ultrafast Optical Molecular Switch Creation (Ultrafast Reversible Photoreaction of Rhodopsin

    Directory of Open Access Journals (Sweden)

    Olga Smitienko

    2014-11-01

    Full Text Available Ultrafast reverse photoreaction of visual pigment rhodopsin in the femtosecond time range at room temperature is demonstrated. Femtosecond two-pump probe experiments with a time resolution of 25 fs have been performed. The first рump pulse at 500 nm initiated cis-trans photoisomerization of rhodopsin chromophore, 11-cis retinal, which resulted in the formation of the primary ground-state photoproduct within a mere 200 fs. The second pump pulse at 620 nm with a varying delay of 200 to 3750 fs relative to the first рump pulse, initiated the reverse phototransition of the primary photoproduct to rhodopsin. The results of this photoconversion have been observed on the differential spectra obtained after the action of two pump pulses at a time delay of 100 ps. It was found that optical density decreased at 560 nm in the spectral region of bathorhodopsin absorption and increased at 480 nm, where rhodopsin absorbs. Rhodopsin photoswitching efficiency shows oscillations as a function of the time delay between two рump pulses. The quantum yield of reverse photoreaction initiated by the second pump pulse falls within the range 15% ± 1%. The molecular mechanism of the ultrafast reversible photoreaction of visual pigment rhodopsin may be used as a concept for the development of an ultrafast optical molecular switch.

  2. Molecular basis for amino acid sensing by family C G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Bräuner-Osborne, Hans

    2009-01-01

    -alpha;-amino acid receptor G-protein-coupled receptor family C, group 6, subtype A (GPRC6A) and seven orphan receptors. Aside from the orphan receptors, the family C GPCRs are dimeric receptors characterized by a large extracellular Venus flytrap domain which bind the endogenous agonists. Except from the GABA(B1......-2) and T1R2-3 receptor, all receptors are either activated or positively modulated by amino acids. In this review, we outline mutational, biophysical and structural studies which have elucidated the interaction of the amino acids with the Venus flytrap domains, molecular mechanisms of receptor selectivity...

  3. Photoinduced switching to metallic states in the two-dimensional organic Mott insulator dimethylphenazine-tetrafluorotetracyanoquinodimethane with anisotropic molecular stacks

    Science.gov (United States)

    Matsuzaki, Hiroyuki; Ohkura, Masa-aki; Ishige, Yu; Nogami, Yoshio; Okamoto, Hiroshi

    2015-06-01

    A photoinduced phase transition was investigated in an organic charge-transfer (CT) complex M2P -TCNQ F4 , [M2P : 5,10-dihydro-5,10-dimethylphenazine, donor (D) molecule; TCNQ F4 : 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, acceptor (A) molecule] by means of femtosecond pump-probe reflection spectroscopy. This is an ionic compound and has a peculiar two-dimensional (2D) molecular arrangement; the same A (or D) molecules arrange along the [100] direction, and A and D molecules alternately arrange along the [111] direction. It results in a strongly anisotropic two-dimensional electronic structure. This compound shows a structural and magnetic phase transition at 122 K below which the two neighboring molecules are dimerized along both the [100] and [111] directions. We demonstrate that two kinds of photoinduced phase transitions occur by irradiation of a femtosecond laser pulse; in the high-temperature lattice-uniform phase, a quasi-one-dimensional (1D) metallic state along the AA(DD) stack is generated, and in the low-temperature lattice-dimerized phase, a quasi-2D metallic state is initially produced and molecular dimerizations are subsequently released. Mixed-stack CT compounds consisting of DA stacks are generally insulators or semiconductors in the ground state. Here, such a dynamical metallization in the DA stack is demonstrated. The release of the dimerizations drives several kinds of coherent oscillations which play an important role in the stabilization of the lattice-dimerized phase. The mechanisms of those photoinduced phase transitions are discussed in terms of the magnitudes of the anisotropic bandwidths and molecular dimerizations along two different directions of the molecular stacks.

  4. UPGRADING OF BIO-OIL MOLECULAR DISTILLATION FRACTION WITH SOLID ACID CATALYST

    Directory of Open Access Journals (Sweden)

    Zuogang Guo

    2011-05-01

    Full Text Available Molecular distillation technology has been adopted to obtain a bio-oil fraction rich in carboxylic acids and ketones. This unique bio-oil fraction was then upgraded with a La-promoted solid acid catalyst. Three washing pretreatments were used to prepare catalysts A, B, and C, with the intention of reducing the amounts of residual sulfuric acid. Model reactions were used to estimate their catalytic activities and the residual amounts of sulfuric acid. Catalyst B, with washing after calcination, displayed higher catalytic activity (80.83% and lower residual amount of sulfuric acid (50 μmol/g. The catalysts were characterized by techniques such as BET, XRD, and SEM to explain the differences in their catalytic activities. The optimum catalyst B was used in the upgrading of the bio-oil molecular distillation fraction. After upgrading, the corrosivity of the bio-oil fraction declined and its storage stability was improved. The carboxylic acid content in the upgraded bio-oil fraction decreased from 18.39% to 2.70%, while the ester content increased from 0.72% to 31.17%. The conversion of corrosive carboxylic acids to neutral esters reduced the corrosivity of the bio-oil fraction. Moreover, the ketones with unsaturated carbon-carbon double bonds (such as 2-cyclopenten-1-one, 3-methyl-2-cyclopenten-1-one, etc. were converted into saturated compounds, which improved the stability of the bio-oil fraction.

  5. Relationship between molecular descriptors and the enthalpies of sublimation of natural amino acids

    Science.gov (United States)

    Badelin, V. G.; Tyunina, V. V.; Girichev, G. V.; Tyunina, E. Yu.

    2016-07-01

    A multiparameter correlation between the enthalpies of sublimation and molecular descriptors of natural amino acids is proposed, based on generalized experimental and literature data on the heat effects of sublimation. The contributions from Van der Waals interactions, hydrogen bond formation, and electrostatic effects into enthalpy of sublimation has been evaluated using regression coefficients.

  6. Unbinding of Retinoic Acid from its Receptor Studied by Steered Molecular Dynamics

    CERN Document Server

    Kosztin, D; Schulten, K; Kosztin, Dorina; Izrailev, Sergei; Schulten, Klaus

    1999-01-01

    Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by conformational changes in the protein which induce transactivation or transrepression of the target genes. In this paper we present a study of the hormone binding/unbinding process in order to clarify the role of some of the amino acid contacts and identify possible pathways of the all-trans retinoic acid binding/unbinding to/from human retinoic acid receptor (hRAR)-g. Three possible pathways were explored using steered molecular dynamics simulations. Unbinding was induced on a time scale of 1 ns by applying external forces to the hormone. The simulations suggest that the hormone may employ one pathway for binding and an alternative "back door" pathway for unbinding.

  7. Rheology, oxygen transfer, and molecular weight characteristics of poly(glutamic acid) fermentation by Bacillus subtilis.

    Science.gov (United States)

    Richard, Andrew; Margaritis, Argyrios

    2003-05-01

    Poly(glutamic acid) (PGA) is a water-soluble, biodegradable biopolymer that is produced by microbial fermentation. Recent research has shown that PGA can be used in drug delivery applications for the controlled release of paclitaxel (Taxol) in cancer treatment. A fundamental understanding of the key fermentation parameters is necessary to optimize the production and molecular weight characteristics of poly(glutamic acid) by Bacillus subtilis for paclitaxel and other applications of pharmaceuticals for controlled release. Because of its high molecular weight, PGA fermentation broths exhibit non-Newtonian rheology. In this article we present experimental results on the batch fermentation kinetics of PGA production, mass transfer of oxygen, specific oxygen uptake rate, broth rheology, and molecular weight characterization of the PGA biopolymer.

  8. Plant Adaptation to Acid Soils: The Molecular Basis for Crop Aluminum Resistance.

    Science.gov (United States)

    Kochian, Leon V; Piñeros, Miguel A; Liu, Jiping; Magalhaes, Jurandir V

    2015-01-01

    Aluminum (Al) toxicity in acid soils is a significant limitation to crop production worldwide, as approximately 50% of the world's potentially arable soil is acidic. Because acid soils are such an important constraint to agriculture, understanding the mechanisms and genes conferring resistance to Al toxicity has been a focus of intense research interest in the decade since the last article on crop acid soil tolerance was published in this journal. An impressive amount of progress has been made during that time that has greatly increased our understanding of the diversity of Al resistance genes and mechanisms, how resistance gene expression is regulated and triggered by Al and Al-induced signals, and how the proteins encoded by these genes function and are regulated. This review examines the state of our understanding of the physiological, genetic, and molecular bases for crop Al tolerance, looking at the novel Al resistance genes and mechanisms that have been identified over the past ten years. Additionally, it examines how the integration of molecular and genetic analyses of crop Al resistance is starting to be exploited for the improvement of crop plants grown on acid soils via both molecular-assisted breeding and biotechnology approaches.

  9. Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

    Science.gov (United States)

    Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

    2001-10-01

    Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

  10. A log-normal distribution model for the molecular weight of aquatic fulvic acids

    Science.gov (United States)

    Cabaniss, S.E.; Zhou, Q.; Maurice, P.A.; Chin, Y.-P.; Aiken, G.R.

    2000-01-01

    The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a lognormal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured M(n) and M(w) and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several types of molecular weight data, including the shapes of high- pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a log-normal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured Mn and Mw and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several type's of molecular weight data, including the shapes of high-pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.

  11. A sulfuric-lactic acid process for efficient purification of fungal chitosan with intact molecular weight.

    Science.gov (United States)

    Naghdi, Mitra; Zamani, Akram; Karimi, Keikhosro

    2014-02-01

    The most recent method of fungal chitosan purification, i.e., two steps of dilute sulfuric acid treatment, pretreatment of cell wall at room temperature for phosphate removal and extraction of chitosan from the phosphate free cell wall at high temperature, significantly reduces the chitosan molecular weight. This study was aimed at improvement of this method. In the pretreatment step, to choose the best conditions, cell wall of Rhizopus oryzae, containing 9% phosphate, 10% glucosamine, and 21% N-acetyl glucosamine, was treated with sulfuric, lactic, acetic, nitric, or hydrochloric acid, at room temperature. Sulfuric acid showed the best performance in phosphate removal (90%) and cell wall recovery (89%). To avoid depolymerisation of chitosan, hot sulfuric acid extraction was replaced with lactic acid treatment at room temperature, and a pure fungal chitosan was obtained (0.12 g/g cell wall). Similar pretreatment and extraction processes were conducted on pure shrimp chitosan and resulted in a chitosan recovery of higher than 87% while the reduction of chitosan viscosity was less than 15%. Therefore, the sulfuric-lactic acid method purified the fungal chitosan without significant molecular weight manipulation.

  12. Tuning the temperature dependence for switching in dithienylethene photochromic switches.

    Science.gov (United States)

    Kudernac, Tibor; Kobayashi, Takao; Uyama, Ayaka; Uchida, Kingo; Nakamura, Shinichiro; Feringa, Ben L

    2013-08-29

    Diarylethene photochromic switches use light to drive structural changes through reversible electrocyclization reactions. High efficiency in dynamic photoswitching is a prerequisite for applications, as is thermal stability and the selective addressability of both isomers ring-opened and -closed diarylethenes. These properties can be optimized readily through rational variation in molecular structure. The efficiency with regard to switching as a function of structural variation is much less understood, with the exception of geometric requirements placed on the reacting atoms. Ultimately, increasing the quantum efficiency of photochemical switching in diarylethenes requires a detailed understanding of the excited-state potential energy surface(s) and the mechanisms involved in switching. Through studies of the temperature dependence, photoswitching and theoretical studies demonstrate the occurrence or absence of thermal activation barriers in three constitutional isomers that bear distinct π-conjugated systems. We found that a decrease in the thermal barriers correlates with an increase in switching efficiency. The origin of the barriers is assigned to the decrease in π-conjugation that is concomitant with the progress of the photoreaction. Furthermore, we show that balanced molecular design can minimize the change in the extent of π-conjugation during switching and lead to optimal bidirectional switching efficiencies. Our findings hold implications for future structural design of diarylethene photochromic switches.

  13. A Comparison of Low-Fluence 1064-nm Q-Switched Nd: YAG Laser with Topical 20% Azelaic Acid Cream and their Combination in Melasma in Indian Patients

    Science.gov (United States)

    Bansal, Charu; Naik, Hira; Kar, Hemanta K; Chauhan, Amrita

    2012-01-01

    Background: Melasma is an acquired symmetric hypermelanosis characterised by irregular light to gray-brown macules on sun-exposed skin with a predilection for the cheeks, forehead, upper lip, nose and chin. The management of melasma is challenging and requires meticulous use of available therapeutic options. Aims: To compare the therapeutic efficacy of low-fluence Q-switched Nd: YAG laser (QSNYL) with topical 20% azelaic acid cream and their combination in melasma in three study groups of 20 patients each. Materials and Methods: Sixty Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (group A = 20 patients of melasma treated with low-fluence QSNYL at weekly intervals, group B = 20 patients of melasma treated with twice daily application of 20% azelaic acid cream and group C = 20 patients of melasma treated with combination of both). Study period was of 12 weeks each. Response to treatment was assessed using melasma area and severity index score. Statistical Analysis: The statistical analysis was done using Chi-square test, paired and unpaired student t-test. Results: Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group C as compared to group A (P < 0.001) and group B (P < 0.001). Conclusions: This study shows the efficacy of low-fluence QSNYL, topical 20% azelaic acid cream and their combination in melasma. The combination of low-fluence QSNYL and topical 20% azelaic acid cream yields better results as compared to low-fluence QSNYL and azelaic acid alone. PMID:23378709

  14. A comparison of low-fluence 1064-nm Q-switched Nd: YAG laser with topical 20% azelaic acid cream and their combination in melasma in Indian patients

    Directory of Open Access Journals (Sweden)

    Charu Bansal

    2012-01-01

    Full Text Available Background: Melasma is an acquired symmetric hypermelanosis characterised by irregular light to gray-brown macules on sun-exposed skin with a predilection for the cheeks, forehead, upper lip, nose and chin. The management of melasma is challenging and requires meticulous use of available therapeutic options. Aims: To compare the therapeutic efficacy of low-fluence Q-switched Nd: YAG laser (QSNYL with topical 20% azelaic acid cream and their combination in melasma in three study groups of 20 patients each. Materials and Methods: Sixty Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (group A = 20 patients of melasma treated with low-fluence QSNYL at weekly intervals, group B = 20 patients of melasma treated with twice daily application of 20% azelaic acid cream and group C = 20 patients of melasma treated with combination of both. Study period was of 12 weeks each. Response to treatment was assessed using melasma area and severity index score. Statistical Analysis: The statistical analysis was done using Chi-square test, paired and unpaired student t-test. Results: Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group C as compared to group A ( P < 0.001 and group B ( P < 0.001. Conclusions: This study shows the efficacy of low-fluence QSNYL, topical 20% azelaic acid cream and their combination in melasma. The combination of low-fluence QSNYL and topical 20% azelaic acid cream yields better results as compared to low-fluence QSNYL and azelaic acid alone.

  15. Discovery of a regioselectivity switch in nitrating P450s guided by molecular dynamics simulations and Markov models

    Science.gov (United States)

    Dodani, Sheel C.; Kiss, Gert; Cahn, Jackson K. B.; Su, Ye; Pande, Vijay S.; Arnold, Frances H.

    2016-05-01

    The dynamic motions of protein structural elements, particularly flexible loops, are intimately linked with diverse aspects of enzyme catalysis. Engineering of these loop regions can alter protein stability, substrate binding and even dramatically impact enzyme function. When these flexible regions are unresolvable structurally, computational reconstruction in combination with large-scale molecular dynamics simulations can be used to guide the engineering strategy. Here we present a collaborative approach that consists of both experiment and computation and led to the discovery of a single mutation in the F/G loop of the nitrating cytochrome P450 TxtE that simultaneously controls loop dynamics and completely shifts the enzyme's regioselectivity from the C4 to the C5 position of L-tryptophan. Furthermore, we find that this loop mutation is naturally present in a subset of homologous nitrating P450s and confirm that these uncharacterized enzymes exclusively produce 5-nitro-L-tryptophan, a previously unknown biosynthetic intermediate.

  16. Molecular simulation of N-acetylneuraminic acid analogs and molecular dynamics studies of cholera toxin-Neu5Gc complex.

    Science.gov (United States)

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-01-01

    Cholera toxin (CT) is an AB5 protein complex secreted by the pathogen Vibrio cholera, which is responsible for cholera infection. N-acetylneuraminic acid (NeuNAc) is a derivative of neuraminic acid with nine-carbon backbone. NeuNAc is distributed on the cell surface mainly located in the terminal components of glycoconjugates, and also plays an important role in cell-cell interaction. In our current study, molecular docking and molecular dynamic (MD) simulations were implemented to identify the potent NeuNAc analogs with high-inhibitory activity against CT protein. Thirty-four NeuNAc analogs, modified in different positions C-1/C-2/C-4/C-5/C-7/C-8/C-9, were modeled and docked against the active site of CT protein. Among the 34 NeuNAc analogs, the analog Neu5Gc shows the least extra precision glide score of -9.52 and glide energy of -44.71 kcal/mol. NeuNAc analogs block the CT active site residues HIS:13, ASN:90, LYS:91, GLN:56, GLN:61, and TRP:88 through intermolecular hydrogen bonding. The MD simulation for CT-Neu5Gc docking complex was performed using Desmond. MD simulation of CT-Neu5Gc complex reveals the stable nature of docking interaction.

  17. Molecular approaches unravel the mechanism of acid soil tolerance in plants

    Institute of Scientific and Technical Information of China (English)

    Miao; Bian; Meixue; Zhou; Dongfa; Sun; Chengdao; Li

    2013-01-01

    Acid soil is a worldwide problem to plant production. Acid toxicity is mainly caused by a lack of essential nutrients in the soil and excessive toxic metals in the plant root zone. Of the toxic metals, aluminum(Al) is the most prevalent and most toxic. Plant species have evolved to variable levels of tolerance to aluminum enabling breeding of high Al-tolerant cultivars.Physiological and molecular approaches have revealed some mechanisms of Al toxicity in higher plants. Mechanisms of plant tolerance to Al stress include: 1) exclusion of Al from the root tips, and 2) absorbance, but tolerance of Al in root cells. Organic acid exudation to chelate Al is a feature shared by many higher plants. The future challenge for Al tolerance studies is the identification of novel tolerance mechanisms and the combination of different mechanisms to achieve higher tolerance. Molecular approaches have led to significant progress in explaining mechanisms and detection of genes responsible for Al tolerance.Gene-specific molecular markers offer better options for marker-assisted selection in breeding programs than linked marker strategies. This paper mainly focuses on recent progress in the use of molecular approaches in Al tolerance research.

  18. Macromolecular Crowding Studies of Amino Acids Using NMR Diffusion Measurements and Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Amninder S Virk

    2015-02-01

    Full Text Available Molecular crowding occurs when the total concentration of macromolecular species in a solution is so high that a considerable proportion of the volume is physically occupied and therefore not accessible to other molecules. This results in significant changes in the solution properties of the molecules in such systems. Macromolecular crowding is ubiquitous in biological systems due to the generally high intracellular protein concentrations. The major hindrance to understanding crowding is the lack of direct comparison of experimental data with theoretical or simulated data. Self-diffusion is sensitive to changes in the molecular weight and shape of the diffusing species, and the available diffusion space (i.e., diffusive obstruction. Consequently, diffusion measurements are a direct means for probing crowded systems including the self-association of molecules. In this work, nuclear magnetic resonance measurements of the self-diffusion of four amino acids (glycine, alanine, valine and phenylalanine up to their solubility limit in water were compared directly with molecular dynamics simulations. The experimental data were then analyzed using various models of aggregation and obstruction. Both experimental and simulated data revealed that the diffusion of both water and the amino acids were sensitive to the amino acid concentration. The direct comparison of the simulated and experimental data afforded greater insights into the aggregation and obstruction properties of each amino acid.

  19. Nucleosome switches.

    Science.gov (United States)

    Schwab, David J; Bruinsma, Robijn F; Rudnick, Joseph; Widom, Jonathan

    2008-06-06

    We present a statistical-mechanical model for the positioning of nucleosomes along genomic DNA molecules as a function of the strength of the binding potential and the chemical potential of the nucleosomes. We show that a significant section of the DNA is composed of two-level nucleosome switching regions where the nucleosome distribution undergoes a localized, first-order transition. The location of the nucleosome switches shows a strong correlation with the location of gene-regulation regions.

  20. Synthesis of high molecular weight polylactic acid from aqueous lactic acid co-catalyzed by tin(II)chloride dihydrate and succinic anhydride

    Institute of Scientific and Technical Information of China (English)

    LEI Ziqiang; BAI Yanbin; WANG Shoufeng

    2005-01-01

    Polylactic acid was synthesized from commercial available cheap aqueous lactic acid (85%―90% w/w) using succinic anhydride and SnCl2·2H2O as catalyst in the absence of organic solvents. As a result, polylactic acid with a molecular weight of 60000 was prepared in 10 h. The new procedure is much simple, cheap and outstanding in that the start material is aqueous lactic acid; the catalytic system is environmentally benign.

  1. Bistability in a Metabolic Network Underpins the De Novo Evolution of Colony Switching in Pseudomonas fluorescens

    DEFF Research Database (Denmark)

    Gallie, Jenna; Libby, Eric; Bertels, Frederic;

    2015-01-01

    levels favour nucleotide metabolism (capsule OFF), while cells with lower pyrimidine levels divert resources towards polymer biosynthesis (capsule ON). This decision point is present and functional in the wild-type strain. Finally, we present a simple mathematical model demonstrating that the molecular...... in central metabolism (carB) generates such a striking phenotype. We show that colony switching is underpinned by ON/OFF expression of capsules consisting of a colanic acid-like polymer. We use molecular genetics, biochemical analyses, and experimental evolution to establish that capsule switching results...

  2. Photochemical alkylation of inorganic selenium in the presence of low molecular weight organic acids.

    Science.gov (United States)

    Guo, Xuming; Sturgeon, Ralph E; Mester, Zoltán; Gardner, Graeme J

    2003-12-15

    Using a flow-through photochemical reactor and a low pressure mercury lamp as a UV source, alkyl selenium species are formed from inorganic selenium(IV) in the presence of low molecular weight organic acids (LMW acids). The volatile alkyl Se species were cryogenically trapped and identified by GC-MS and GC-ICP-MS. In the presence of formic, acetic, propionic and malonic acids, inorganic selenium(IV) is converted by UV irradiation to volatile selenium hydride and carbonyl, dimethylselenide and diethylselenide, respectively. Se(IV) was successfully removed from contaminated agricultural drainage waters (California, U.S.A.) using a batch photoreactor system Se. Photochemical alkylation may thus offer a promising means of converting toxic selenium salts, present in contaminated water, to less toxic dimethylselenide. The LMW acids and photochemical alkylation process may also be key to understanding the source of atmospheric selenium and are likely involved in its mobility in the natural anaerobic environment.

  3. The effect of photocatalytic oxidation on molecular size distribution profiles of humic acid.

    Science.gov (United States)

    Bekbolet, M; Sen-Kavurmaci, S

    2015-03-01

    The influence of photocatalytic degradation on molecular size fractionation (0.45 μm filtered, 100 kDa, 30 kDa and 3 kDa) of humic acid as a model compound of natural organic matter was investigated. The results were evaluated using UV-vis parameters, dissolved organic carbon (DOC) and excitation emission matrix (EEM) fluorescence spectral features. EEM fluorescence signatures displayed an irradiation period dependent transformation of humic-like fluorophores to fulvic-like fluorophores in accordance with the photocatalytic mineralization of HA. Molecular size distribution profiles expressed the formation of lower molecular size (oxidative degradation of humic acid of higher molecular size fractions (100 kDa and 30 kDa fractions). The fluorescence-derived index (fluorescence intensity (FI), represented by the ratio of the emission intensity at λemis = 450 nm to that at λemis = 500 nm, following the excitation at λexc = 370 nm) was also investigated. The use of EEM features has proven to be a useful tool for monitoring the effect of photocatalytic degradation on the structure and molecular size distribution profile of HA.

  4. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Directory of Open Access Journals (Sweden)

    Magd A. Kotb

    2012-07-01

    Full Text Available Ursodeoxycholic acid (UDCA is a steroid bile acid approved for primary biliary cirrhosis (PBC. UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively. “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day and toxic dose (28 mg/kg/day, and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

  5. Glucosidase II β-subunit, a novel substrate for caspase-3-like activity in rice, plays as a molecular switch between autophagy and programmed cell death

    Science.gov (United States)

    Cui, Jing; Chen, Bing; Wang, Hongjuan; Han, Yue; Chen, Xi; Zhang, Wei

    2016-01-01

    Endoplasmic reticulum (ER) stress activates unfolded protein response (UPR) and autophagy. However, prolonged, severe stresses activate programmed cell death (PCD) in both animal and plant cells. Compared to the well-studied UPR pathway, the molecular mechanisms of ER-stress-induced PCD are less understood. Here, we report the identification of Gas2, the glucosidase II β subunit in the ER, as a potential switch between PCD and autophagy in rice. MS analysis identified Gas2, GRP94, and HSP40 protein in a purified caspase-3-like activity from heat stressed rice cell suspensions. The three corresponding genes were down-regulated under DTT-induced ER stress. Gas2 and GRP94 were localized to the ER, while HSP40 localized to the cytoplasm. Compared to wild-type, a Gas2 RNAi cell line was much sensitive to DTT treatment and had high levels of autophagy. Both caspase-3 and heat-stressed cell suspension lysate could cleave Gas2, producing a 14 kDa N-terminal fragment. Conditional expression of corresponding C-terminal fragment resulted in enhanced caspase-3-like activity in the protoplasts under heat stress. We proposed that mild ER stress causes down-regulation of Gas2 and induces autophagy, while severe stress results in Gas2 cleavage by caspase-3-like activity and the cleavage product amplifies this activity, possibly participating in the initiation of PCD. PMID:27538481

  6. Molecular switch role of Akt in Polygonatum odoratum lectin-induced apoptosis and autophagy in human non-small cell lung cancer A549 cells.

    Science.gov (United States)

    Li, Chunyang; Chen, Jie; Lu, Bangmin; Shi, Zheng; Wang, Hailian; Zhang, Bin; Zhao, Kailiang; Qi, Wei; Bao, Jinku; Wang, Yi

    2014-01-01

    Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.

  7. Application of molecular techniques for identification and ennumeration of acetic acid bacteria

    OpenAIRE

    González Benito, Angel

    2005-01-01

    Application of molecular techniques for identification and enumeration of acetic acid bacteria:Los principales objetivos de la tesis son el desarrollo de técnicas de biología molecular rápidas y fiables para caracterizar bacterias acéticas.Las bacterias acéticas son las principales responsables del picado de los vinos y de la producción de vinagre. Sin embargo, existe un desconocimiento importante sobre su comportamiento y evolución. Las técnicas de enumeración y de identificación basadas en ...

  8. Real time monitoring of nucleic acids ligation based on molecular beacon

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel method has been developed to monitor the nucleic acids ligation process. Molecular beacon was employed here to convert the ligation information into fluorescence signal quickly and quantitatively. This method provides effective and original approach to researching the dynamic ligation process and the interactions between nucleic acids and ligase. An analytical method for T4 DNA ligase based on this way has been built up with a linear detection range from 2.3×10?4 U/mL to 0.23 U/mL. It is rapid and sensitive to detect 2.8×10?5 U T4 DNA ligase in 10 min.

  9. A comparative study on efficacy of high and low fluence Q-switched Nd:YAG laser and glycolic acid peel in melasma

    Directory of Open Access Journals (Sweden)

    Hemanta Kumar Kar

    2012-01-01

    Full Text Available Background: Melasma is acquired symmetric hypermelanosis characterized by light-to-deep brown pigmentation over cheeks, forehead, upper lip, and nose. Treatment of this condition is difficult and associated with high recurrence rates. With the advent of newer therapies, there is interest in the use of glycolic acid peels and Q-switched Nd:YAG laser (QSNYL in high and low fluence for this disorder. Aims: To compare the therapeutic efficacy of low fluence QSNYL, high fluence QSNYL, and glycolic acid peel in melasma in three study groups of 25 patients each. Methods: Seventy-five Indian patients diagnosed as melasma were included. These patients were randomly divided in three groups (Group A = 25 patients of melasma treated with low-fluence QSNYL at weekly intervals, Group B = 25 patients of melasma treated with glycolic acid peel at 2 weeks intervals, Group C = 25 patients of melasma treated with high-fluence QSNYL at 2 weeks intervals. Study period and follow-up period was of 12 weeks each. Out of the 75 patients included, 21 patients in Group A, 19 patients in Group B, and 20 patients in Group C completed the study. Response to treatment was assessed using melasma area and severity index score. Results: Significant improvement was recorded in all the three groups. The improvement was statistically highly significant in Group A as compared to Group C (P<0.005, significant in Group A as compared to Group B (P<0.05, and also in Group B when compared to Group C (P<0.05. Low-fluence QSNYL was associated with least side effects. Conclusions: This study shows the efficacy of low-fluence QSNYL and glycolic acid peel in melasma. These could be an effective treatment options compared to conventional methods for the treatment of melasma.

  10. Molecular identification of high and low affinity receptors for nicotinic acid.

    Science.gov (United States)

    Wise, Alan; Foord, Steven M; Fraser, Neil J; Barnes, Ashley A; Elshourbagy, Nabil; Eilert, Michelle; Ignar, Diane M; Murdock, Paul R; Steplewski, Klaudia; Green, Andrew; Brown, Andrew J; Dowell, Simon J; Szekeres, Philip G; Hassall, David G; Marshall, Fiona H; Wilson, Shelagh; Pike, Nicholas B

    2003-03-14

    Nicotinic acid has been used clinically for over 40 years in the treatment of dyslipidemia producing a desirable normalization of a range of cardiovascular risk factors, including a marked elevation of high density lipoprotein and a reduction in mortality. The precise mechanism of action of nicotinic acid is unknown, although it is believed that activation of a G(i)-G protein-coupled receptor may contribute. Utilizing available information on the tissue distribution of nicotinic acid receptors, we identified candidate orphan receptors. The selected orphan receptors were screened for responses to nicotinic acid, in an assay for activation of G(i)-G proteins. Here we describe the identification of the G protein-coupled receptor HM74 as a low affinity receptor for nicotinic acid. We then describe the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptor for nicotinic acid and other compounds with related pharmacology. The discovery of HM74A as a molecular target for nicotinic acid may facilitate the discovery of superior drug molecules to treat dyslipidemia.

  11. [Advancement in the research of early detection of bacterial nucleic acid in molecular diagnosis of sepsis].

    Science.gov (United States)

    Liu, Xiao; Ren, Hui; Peng, Dai-zhi

    2013-04-01

    Early diagnosis of sepsis helps make effective clinical decisions and improve the survival rate of patients with severe infection. However, the timely and accurate diagnosis of sepsis is still a great challenge in clinic. In order to settle the very problem, the scientists in the world have made a lot of exploration and research in the field of rapid molecular identification of pathogens. Nowadays, the nucleic acid detection of sepsis is mainly composed of 3 types of methodological strategies, either based on positive blood culture, single colonies, or directly on blood specimens. This paper presents a comprehensive overview of advances in the research of early detection of bacterial nucleic acid as molecular diagnosis of sepsis.

  12. Molecular characterization of lactic acid bacteria isolated from industrially fermented Greek table olives

    OpenAIRE

    Doulgeraki, Agapi; Pramateftaki, Paraskevi; Argyri, Anthoula; Nychas, George John; Tassou, Chrysoula; Panagou, Efstathios

    2012-01-01

    A total of 145 lactic acid bacteria (LAB) isolates have been recovered from fermented table olives and brine and characterized at strain level with molecular tools. Pulsed-Field Gel Electrophoresis (PFGE) of ApaI macrorestriction fragments was applied for strain differentiation. Species differentiation was based either on Denaturing Gradient Gel Electrophoresis (PCR-DGGE) (black olives) or on restriction analysis of the amplified 16S rRNA gene (PCR-ARDRA) (brine and green olives). Species ide...

  13. SFC在分子筛纯化系统切换控制中的应用%Application of SFC in switching-over control of molecular sieve purification system

    Institute of Scientific and Technical Information of China (English)

    付定君; 伍晓娟; 徐平林

    2011-01-01

    针对分子筛纯化系统切换控制的特点,结合横河CETUMCS3000控制系统中的顺序控制功能,介绍了SFC在分子筛纯化系统切换控制中的应用,以及一些组态经验和维护措施。%Application of SFC in switching-over control of molecular sieve purification system is briefed on basis of the features of switching-over control of molecular sieve purification system in combination with function of sequence control of Henghe CETUM CS3000 control system and experiences on configuration and maintenance measures are described.

  14. SYNTHESIS AND PROPERTIES OF HIGH MOLECULAR WEIGHT POLY(LACTIC ACID) AND ITS RESULTANT FIBERS

    Institute of Scientific and Technical Information of China (English)

    Wang-xi Zhang; Yan-zhi Wang

    2008-01-01

    Direct melt/solid polycondensation of lactic acid (LA) was carried out to obtain high molecular weight poly(lactic acid) (PLA) by a process using various catalysts in the first-step melt polycondensation, and followed solid polycondensation by using p-toulenesulfonic acid monohydrate (TSA) as the catalyst in the second step. Effects of various catalysts and reaction temperature on the molecular weight and crystallinity of resulting PLA polymers were examined. It was shown that SnCl2·2H2O/TSA, SnCl2·2H2O/succinic anhydride, and SnCl2·2H2O/maleic anhydride binary catalysts should be effective binary catalysts to obtain high molecular weight PLA of more than 1.2 × 105. A conventional melt spinning method was used to spin PLA fibers, which displayed tensile strength of (382.76±1.41) MPa and tensile modulus of (4.36±0.07) GPa.

  15. Disulfide bond reduction-triggered molecular hydrogels of folic acid-Taxol conjugates.

    Science.gov (United States)

    Yang, Chengbiao; Li, Dongxia; Fengzhao, Qianqi; Wang, Lianyong; Wang, Ling; Yang, Zhimou

    2013-09-25

    Molecular hydrogels of therapeutic agents are a novel kind of self-delivery system that can sustain release of drugs or pro-drugs. We have previously developed a molecular hydrogelator of folic acid (FA)-Taxol conjugate triggered by phosphatase. In this paper, we report a novel molecular hydrogelator system of FA-Taxol conjugates with improved synthetic strategy. The hydrogels are formed by the reduction of disulfide bond by glutathione (GSH). These hydrogels could sustain release of Taxol through ester bond hydrolysis. Compared with intravenous (i.v.) injection of clinically used Taxol® with four times the dosage, our hydrogel could inhibit tumor growth more efficiently by a single dose of intra-tumor (i.t.) administration. These observations suggested the big potential of this novel gelation system of Taxol for cancer therapy.

  16. Potential origin and formation for molecular components of humic acids in soils

    Science.gov (United States)

    Hatcher, Patrick; DiDonato, Nicole; Waggoner, Derek

    2016-04-01

    Humification is defined as the process by which plant and microbial debris are transformed in to humic substances. Proposed pathways for the formation of humic substances, include the lignin and lignin decomposition theories, the lignin-polyphenol theory as well as the melanoidin pathway. It is generally accepted that a combination of several of these pathways with some modifications may be responsible for producing humic substances. The current study examines humic acids from numerous soil samples to demonstrate their molecular composition. In addition we provide an explanation for the formation of these molecules that introduces a new perspective of the humification process. Our work utilizes advanced analytical techniques such as ESI-FTICR-MS and solid state NMR to more completely characterize humic acids at the molecular level. Methods Humic acids were extracted from soils using 0.5 M NaOH followed by treatment with a Dowex™ ion-exchange resin to remove sodium ions. Solid State 13C NMR spectra were obtained on a Bruker 400 MHz Avance II spectrometer equipped with a 4 mm solid state MAS probe. ESI-FTICR-MS analysis was conducted in the negative ion mode on a Bruker Daltonics 12 Tesla Apex Qe FTICR-MS instrument equipped with an Apollo II ESI source. Results: Soil humic acids from numerous soils were investigated in this study. The molecular formulas calculated from ultrahigh resolution mass spectra of well humified soils fall clearly into two predominant regions consisting of condensed aromatic molecules as well as high H/C, low O/C carboxyl-containing aliphatic molecules (CCAM). In contrast, the spectral data for humic acids from a poorly humified spodosol soil show a less dramatic separation of these regions, with relatively more molecular formula plotting in the lignin-like region and relatively fewer condensed aromatic molecules. From the mass spectral observations made for the humic acids, we can readily discern a relationship based on degree of

  17. Zeolite molecular sieves have dramatic acid-base effects on enzymes in nonaqueous media.

    Science.gov (United States)

    Fontes, Nuno; Partridge, Johann; Halling, Peter J; Barreiros, Susana

    2002-02-05

    Zeolite molecular sieves very commonly are used as in situ drying agents in reaction mixtures of enzymes in nonaqueous media. They often affect enzyme behavior, and this has been interpreted in terms of altered hydration. Here, we show that zeolites can also have dramatic acid-base effects on enzymes in low water media, resulting from their cation-exchange ability. Initial rates of transesterification catalyzed by cross-linked crystals of subtilisin were compared in supercritical ethane, hexane, and acetonitrile with water activity fixed by pre-equilibration. Addition of zeolite NaA (4 A powder) still caused remarkable rate enhancements (up to 20-fold), despite the separate control of hydration. In the presence of excess of an alternative solid-state acid-base buffer, however, zeolite addition had no effect. The more commonly used Merck molecular sieves (type 3 A beads) had similar but somewhat smaller effects. All zeolites have ion-exchange ability and can exchange H+ for cations such as Na+ and K+. These exchanges will tend to affect the protonation state of acidic groups in the protein and, hence, enzymatic activity. Zeolites pre-equilibrated in aqueous suspensions of varying pH-pNa gave very different enzyme activities. Their differing basicities were demonstrated directly by equilibration with an indicator dissolved in toluene. The potential of zeolites as acid-base buffers for low-water media is discussed, and their ability to overcome pH memory is demonstrated.

  18. Phenotypic, genetic and molecular characterization of a maize low phytic acid mutant (lpa241).

    Science.gov (United States)

    Pilu, R; Panzeri, D; Gavazzi, G; Rasmussen, S K; Consonni, G; Nielsen, E

    2003-10-01

    Phytic acid, myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the major storage compound of phosphorous (P) in plants, predominantly accumulating in seeds (up to 4-5% of dry weight) and pollen. In cereals, phytic acid is deposited in embryo and aleurone grain tissues as a mixed "phytate" salt of potassium and magnesium, although phytates contain other mineral cations such as iron and zinc. During germination, phytates are broken down by the action of phytases, releasing their P, minerals and myo-inositol which become available to the growing seedling. Phytic acid represents an anti-nutritional factor for animals, and isolation of maize low phytic acid ( lpa) mutants provides a novel approach to study its biochemical pathway and to tackle the nutritional problems associated with it. Following chemical mutagenesis of pollen, we have isolated a viable recessive mutant named lpa 241 showing about 90% reduction of phytic acid and about a tenfold increase in seed-free phosphate content. Although germination rate was decreased by about 30% compared to wild-type, developement of mutant plants was apparentely unaffected. The results of the genetic, biochemical and molecular characterization experiments carried out by SSR mapping, MDD-HPLC and RT-PCR are consistent with a mutation affecting the MIPS1S gene, coding for the first enzyme of the phytic acid biosynthetic pathway.

  19. Molecular size and amino acid composition of H-2d antigen solubilized in Nonidet P-40.

    Science.gov (United States)

    Rossowski, W; Kloczewiak, M; Radzikowski, C; Strzadala, L

    1976-01-01

    H-2d antigenic material solubilized by the detergent Nonidet P-40 from L-1210 mouse leukemia cells was isolated by gel filtration on Bio-Gel P-100. A single peak eluted in the void volume consisted of about 90% protein, 8% hexose and traces of sialic acids. In sedimentation velocity runs, the antigen sedimented as a single peak of 3-1 S. Molecular weight determined by sedimentation equilibrium as well as calculated from amino acid composition was found to be in the range of 53,000 daltons and approx. 45,000-51,000 when calculated from sodium dodecyl sulfate polyacrylamide gel electrophoresis. Secondary structure of H-2d glycoprotein was predicted from the amino acid composition. For NP-40-solubilized H-2d antigen, about 34% of helix, 13% beta sheet and 41% turns was found.

  20. Acid-catalyzed Furfuryl Alcohol Polymerization: Characterizations of Molecular Structure and Thermodynamic Properties

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taejin; Assary, Rajeev A; Marshall, Christopher L; Gosztola, David J.; Curtiss, Larry A; Stair, Peter C

    2011-07-22

    The liquid-phase polymerization of furfuryl alcohol catalyzed by sulfuric acid catalysts and the identities of molecular intermediates were investigated by using Raman spectroscopy and density functional theory calculation. At room temperature, with an acid catalyst, a vigorous furfuryl alcohol polymerization reaction was observed, whereas even at a high water concentration, furfuryl alcohol was very stable in the absence of an acid catalyst. Theoretical studies were carried out to investigate the thermodynamics of protonation of furfuryl alcohol, initiation of polymerization, and formation of conjugated dienes and diketonic species by using the B3LYP level of theory. A strong aliphatic C=C band observed in the calculated and measured Raman spectra provided crucial evidence to understand the polymerization reaction mechanism. It is confirmed that the formation of a conjugated diene structure rather than a diketone structure is involved in the furfuryl alcohol polymerization reaction.

  1. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

    Directory of Open Access Journals (Sweden)

    Sergio eGiannattasio

    2013-02-01

    Full Text Available Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications.

  2. Theoretical Structures of Triflic Acid-Water Clusters and the Molecular Mechanism of Proton Dissociation

    Energy Technology Data Exchange (ETDEWEB)

    Paddison, S.J.; Pratt, L.R.; Zawodzinski, T.A.

    1998-11-01

    Structural and energetic information required for recently proposed quasi-chemical theories of solution chemistry have been obtained for clusters of water with triflic acid, CF{sub 3}SO{sub 3}H(H{sub 2}O){sub n} for n=1-6. Quantum mechanical calculations on the clusters indicate that the acid proton does not dissociate with n=1 or 2 hydrating water molecules, but does dissociate for n>=3 water molecule partners. The computed minimum energy structures indicate that both ''Eigen'' (H{sub 9}O{sub 4}{sup +}) (n=3,4,6) and ''Zundel'' (H{sub 5}O{sub 2}{sup +}) (n=5) structures are likely to play a role in the molecular mechanism of acid dissociation in Nafion{reg_sign}.

  3. Differential coulometric oxidation following post column-switching high pressure liquid chromatography for fluorescence measurement of unmetabolized folic acid in human plasma.

    Science.gov (United States)

    Bailey, Steven W; Ayling, June E

    2013-11-08

    Although many countries have fortified their grain supplies with folic acid (FA) to decrease the incidence of neural tube defects, others have not due to concerns that this synthetic folate might have some adverse effects. Persistent unmetabolized FA has been found even in plasma from fasted subjects. To facilitate measurement of low levels of folic acid in human plasma, post-column coulometric oxidative cleavage was used to convert poorly fluorescent FA into a highly fluorescent compound determined to be 6-formyl-pterin. To minimize sample work-up and maximize recovery, column-switching HPLC transferred a window of eluate containing the FA from the first column (C8) onto a second column (phenyl-hexyl). The pH of two mobile phases were adjusted to be above and then below a pK of the FA α-carboxyl group, thus promoting separation from compounds coeluting from the C8-column. This permitted sample preparation using only a simple high recovery protein precipitation. Definitive identification of FA in human plasma was accomplished by duplicate injections of sample with the electrochemical voltage set above and below its half-potential. The LOD (S/N=3) was 0.10 nM. The intra- and inter-assay CV's were 2.3% and 5%, respectively. Comparison of these results with those obtained by HPLC/MS/MS with stable isotope internal standard showed a slope of 1.00 ± 0.019. This simple, sensitive, and repeatable assay facilitates a more thorough investigation of the response of various human populations to folic acid intake. Post-column differential coulometric electrochemistry can expand the variety of compounds amenable to fluorescence detection.

  4. High and low molecular weight hyaluronic acid differentially regulate human fibrocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Anu S Maharjan

    Full Text Available BACKGROUND: Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6 Da. During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5 Da. METHODS AND FINDINGS: In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4, or interleukin-13 (IL-13 to promote fibrocyte differentiation. CONCLUSIONS: We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13.

  5. Electrochemical Molecular Imprinted Sensors Based on Electrospun Nanofiber and Determination of Ascorbic Acid.

    Science.gov (United States)

    Zhai, Yunyun; Wang, Dandan; Liu, Haiqing; Zeng, Yanbo; Yin, Zhengzhi; Li, Lei

    2015-01-01

    In this study, electrochemical molecularly imprinted sensors were fabricated and used for the determination of ascorbic acid (AA). Nanofiber membranes of cellulose acetate (CA)/multi-walled carbon nanotubes (MWCNTs)/polyvinylpyrrolidone (PVP) (CA/MWCNTs/PVP) were prepared by electrospinning technique. After being transferred to a glass carbon electrode (GC), the nanofiber interface was further polymerized with pyrrole through electrochemical cyclic voltammetry (CV) technique. Meanwhile, target molecules (such as AA) were embedded into the polypyrrole through the hydrogen bond. The effects of monomer concentration (pyrrole), the number of scan cycles and scan rates of polymerization were optimized. Differential pulse voltammetry (DPV) tests indicated that the oxidation current of AA (the selected target) were higher than that of the structural analogues, which illustrated the selective recognition of AA by molecularly imprinted sensors. Simultaneously, the molecularly imprinted sensors had larger oxidation current of AA than non-imprinted sensors in the processes of rebinding. The electrochemical measurements showed that the molecularly imprinted sensors demonstrated good identification behavior for the detection of AA with a linear range of 10.0 - 1000 μM, a low detection limit down to 3 μM (S/N = 3), and a recovery rate range from 94.0 to 108.8%. Therefore, the electrochemical molecularly imprinted sensors can be used for the recognition and detection of AA without any time-consuming elution. The method presented here demonstrates the great potential for electrospun nanofibers and MWCNTs to construct electrochemical sensors.

  6. [Adsorption of aflatoxin on montmorillonite modified by low-molecular-weight humic acids].

    Science.gov (United States)

    Yao, Jia-Jia; Kang, Fu-Xing; Gao, Yan-Zheng

    2012-03-01

    The adsorption of a typical biogenic toxin aflatoxin B1 on montmorillonite modified by low-molecular-weight humic acids (M(r) aflatoxin B1 until amounting to the maximal capacity, and then the adsorbed aflatoxin B1 slowly released into solution and reached the sorption equilibrium state after 12 h. The sorption isotherm of aflatoxin B1 by montmorillonite could be well described by Langmiur model, while the sorption isotherm by humic acid-modified montmorillonite was well fitted by using the Freundlich model. The modification of the montmorillonite with humic acids obviously enhanced its adsorption capacity for aflatoxin B1, and the amounts of aflatoxin adsorbed by modified montmorillonite were obviously higher than those by montmorillonite. The sorption enhancement by humic acid modification was attributed to (1) the enlarged adsorption sites which owed to the surface collapse of crystal layers induced by organic acids, and (2) the binding of aflatoxin with the humic acid sorbed on mineral surface. In addition, the adsorption amounts of aflatoxin by montmorillonite and modified montmorillonite increased with the increase of pH values in solution, and more significant enhancement was observed for the latter than the former, which attributed to the release of humic acids from the modified montmorillonite with the high pH values in solution. This indicates that increasing the pH values resulted in the enhanced hydrophilic property and the release of the organic acids presented in modified montmorillonite, and more sorption sites were available for aflatoxin on the modified montmorillonite. Results of this work would strengthen our understanding of the behavior and fate of biological contaminants in the environment.

  7. Binding Preferences of Amino Acids for Gold Nanoparticles: A Molecular Simulation Study.

    Science.gov (United States)

    Shao, Qing; Hall, Carol K

    2016-08-09

    A better understanding of the binding preference of amino acids for gold nanoparticles of different diameters could aid in the design of peptides that bind specifically to nanoparticles of a given diameter. Here we identify the binding preference of 19 natural amino acids for three gold nanoparticles with diameters of 1.0, 2.0, and 4.0 nm, and investigate the mechanisms that govern these preferences. We calculate potentials of mean force between 36 entities (19 amino acids and 17 side chains) and the three gold nanoparticles in explicit water using well-tempered metadynamics simulations. Comparing these potentials of mean force determines the amino acids' nanoparticle binding preferences and if these preferences are controlled by the backbone, the side chain, or both. Twelve amino acids prefer to bind to the 4.0 nm gold nanoparticle, and seven prefer to bind to the 2.0 nm one. We also use atomistic molecular dynamics simulations to investigate how water molecules near the nanoparticle influence the binding of the amino acids. The solvation shells of the larger nanoparticles have higher water densities than those of the smaller nanoparticles while the orientation distributions of the water molecules in the shells of all three nanoparticles are similar. The nanoparticle preferences of the amino acids depend on whether their binding free energy is determined mainly by their ability to replace or to reorient water molecules in the nanoparticle solvation shell. The amino acids whose binding free energy depends mainly on the replacement of water molecules are likely to prefer to bind to the largest nanoparticle and tend to have relatively simple side chain structures. Those whose binding free energy depends mainly on their ability to reorient water molecules prefer a smaller nanoparticle and tend to have more complex side chain structures.

  8. First Palladium-Catalyzed Addition of Organoboronic Acids to Allenes: A Magic Regioselectivity Switch by Using a Base or an Acid

    Institute of Scientific and Technical Information of China (English)

    MA Sheng-Ming; JIAO Ning

    2003-01-01

    @@ Organoboronic acids enjoy high prestige in the metal-catalyzed C-C bond formations. The most notable progress is the rhodium- and nickel-catalyzed conjugate addition with unsaturated carbon-carbon bond, aldehydes, N-sulfonyl imines reported by Miyaura, Hayashi and Shirakawa.[1

  9. The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

    Directory of Open Access Journals (Sweden)

    Kenrick A Vassall

    global structure of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.

  10. The effects of threonine phosphorylation on the stability and dynamics of the central molecular switch region of 18.5-kDa myelin basic protein.

    Science.gov (United States)

    Vassall, Kenrick A; Bessonov, Kyrylo; De Avila, Miguel; Polverini, Eugenia; Harauz, George

    2013-01-01

    of the peptides through altered electrostatic interactions. The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.

  11. Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

    Science.gov (United States)

    Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

    2014-11-19

    A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

  12. Molecular Cloning and Pharmacological Properties of an Acidic PLA2 from Bothrops pauloensis Snake Venom

    Directory of Open Access Journals (Sweden)

    Francis Barbosa Ferreira

    2013-12-01

    Full Text Available In this work, we describe the molecular cloning and pharmacological properties of an acidic phospholipase A2 (PLA2 isolated from Bothrops pauloensis snake venom. This enzyme, denominated BpPLA2-TXI, was purified by four chromatographic steps and represents 2.4% of the total snake venom protein content. BpPLA2-TXI is a monomeric protein with a molecular mass of 13.6 kDa, as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF analysis and its theoretical isoelectric point was 4.98. BpPLA2-TXI was catalytically active and showed some pharmacological effects such as inhibition of platelet aggregation induced by collagen or ADP and also induced edema and myotoxicity. BpPLA2-TXI displayed low cytotoxicity on TG-180 (CCRF S 180 II and Ovarian Carcinoma (OVCAR-3, whereas no cytotoxicity was found in regard to MEF (Mouse Embryonic Fibroblast and Sarcoma 180 (TIB-66. The N-terminal sequence of forty-eight amino acid residues was determined by Edman degradation. In addition, the complete primary structure of 122 amino acids was deduced by cDNA from the total RNA of the venom gland using specific primers, and it was significantly similar to other acidic D49 PLA2s. The phylogenetic analyses showed that BpPLA2-TXI forms a group with other acidic D49 PLA2s from the gender Bothrops, which are characterized by a catalytic activity associated with anti-platelet effects.

  13. Interpretation of pH-activity profiles for acid-base catalysis from molecular simulations.

    Science.gov (United States)

    Dissanayake, Thakshila; Swails, Jason M; Harris, Michael E; Roitberg, Adrian E; York, Darrin M

    2015-02-17

    The measurement of reaction rate as a function of pH provides essential information about mechanism. These rates are sensitive to the pK(a) values of amino acids directly involved in catalysis that are often shifted by the enzyme active site environment. Experimentally observed pH-rate profiles are usually interpreted using simple kinetic models that allow estimation of "apparent pK(a)" values of presumed general acid and base catalysts. One of the underlying assumptions in these models is that the protonation states are uncorrelated. In this work, we introduce the use of constant pH molecular dynamics simulations in explicit solvent (CpHMD) with replica exchange in the pH-dimension (pH-REMD) as a tool to aid in the interpretation of pH-activity data of enzymes and to test the validity of different kinetic models. We apply the methods to RNase A, a prototype acid-base catalyst, to predict the macroscopic and microscopic pK(a) values, as well as the shape of the pH-rate profile. Results for apo and cCMP-bound RNase A agree well with available experimental data and suggest that deprotonation of the general acid and protonation of the general base are not strongly coupled in transphosphorylation and hydrolysis steps. Stronger coupling, however, is predicted for the Lys41 and His119 protonation states in apo RNase A, leading to the requirement for a microscopic kinetic model. This type of analysis may be important for other catalytic systems where the active forms of the implicated general acid and base are oppositely charged and more highly correlated. These results suggest a new way for CpHMD/pH-REMD simulations to bridge the gap with experiments to provide a molecular-level interpretation of pH-activity data in studies of enzyme mechanisms.

  14. Molecular cloning and pharmacological properties of an acidic PLA2 from Bothrops pauloensis snake venom.

    Science.gov (United States)

    Ferreira, Francis Barbosa; Gomes, Mário Sérgio Rocha; de Souza, Dayane Lorena Naves; Gimenes, Sarah Natalie Cirilo; Castanheira, Letícia Eulalio; Borges, Márcia Helena; Rodrigues, Renata Santos; Yoneyama, Kelly Aparecida Geraldo; Brandeburgo, Maria Inês Homsi; Rodrigues, Veridiana M

    2013-12-04

    In this work, we describe the molecular cloning and pharmacological properties of an acidic phospholipase A(2) (PLA(2)) isolated from Bothrops pauloensis snake venom. This enzyme, denominated BpPLA(2)-TXI, was purified by four chromatographic steps and represents 2.4% of the total snake venom protein content. BpPLA(2)-TXI is a monomeric protein with a molecular mass of 13.6 kDa, as demonstrated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis and its theoretical isoelectric point was 4.98. BpPLA(2)-TXI was catalytically active and showed some pharmacological effects such as inhibition of platelet aggregation induced by collagen or ADP and also induced edema and myotoxicity. BpPLA(2)-TXI displayed low cytotoxicity on TG-180 (CCRF S 180 II) and Ovarian Carcinoma (OVCAR-3), whereas no cytotoxicity was found in regard to MEF (Mouse Embryonic Fibroblast) and Sarcoma 180 (TIB-66). The N-terminal sequence of forty-eight amino acid residues was determined by Edman degradation. In addition, the complete primary structure of 122 amino acids was deduced by cDNA from the total RNA of the venom gland using specific primers, and it was significantly similar to other acidic D49 PLA(2)s. The phylogenetic analyses showed that BpPLA(2)-TXI forms a group with other acidic D49 PLA(2)s from the gender Bothrops, which are characterized by a catalytic activity associated with anti-platelet effects.

  15. Preparation of Higher Molecular Weight Poly (L-lactic Acid by Chain Extension

    Directory of Open Access Journals (Sweden)

    Chenguang Liu

    2013-01-01

    Full Text Available High molecular weight poly (lactic acid (PLA was obtained by chain extending with hexamethylene diisocyanate (HDI. The influences of the amount of chain extender, reaction time, and molecular weight changes of prepolymers on the poly(lactic acid were investigated. PLA prepolymer with a viscosity, average molecular weight (Mη of 2 × 104 g/mol was synthesized from l-lactide using stannous octoate as the catalyst. After 20 min of chain extension at 175°C, the resulting polymer had Mw of 20.3 × 104 g/mol and Mn of 10.5 × 104 g/mol. Both FT-IR and 1H-NMR verified that the structure of PLA did not change either before chain extending or after. The optically active characterized that the chain extending-product was left handed. DSC and XRD results showed that both the Tg and the crystallinity of PLA were lowered by chain-extension reaction. The crystalline transformation happened in PLA after chain extending, crystalline α′ form to α form.

  16. Synthesis of Molecularly Imprinted Polymers for Amino Acid Derivates by Using Different Functional Monomers

    Directory of Open Access Journals (Sweden)

    Sonia Scorrano

    2011-03-01

    Full Text Available Fmoc-3-nitrotyrosine (Fmoc-3-NT molecularly imprinted polymers (MIPs were synthesized to understand the influence of several functional monomers on the efficiency of the molecular imprinting process. Acidic, neutral and basic functional monomers, such as acrylic acid (AA, methacrylic acid (MAA, methacrylamide (MAM, 2-vinylpyridine (2-VP, 4-vinylpyridine (4-VP, have been used to synthesize five different polymers. In this study, the MIPs were tested in batch experiments by UV-visible spectroscopy in order to evaluate their binding properties. The MIP prepared with 2-VP exhibited the highest binding affinity for Fmoc-3NT, for which Scatchard analysis the highest association constant (2.49 × 104 M−1 was obtained. Furthermore, titration experiments of Fmoc-3NT into acetonitrile solutions of 2-VP revealed a stronger bond to the template, such that a total interaction is observed. Non-imprinted polymers as control were prepared and showed no binding affinities for Fmoc-3NT. The results are indicative of the importance of ionic bonds formed between the –OH residues of the template molecule and the pyridinyl groups of the polymer matrix. In conclusion, 2-VP assists to create a cavity which allows better access to the analytes.

  17. Synthesis and Molecular Structures of (E-non-2-enoic Acid and (E-dec-2-enoic Acid

    Directory of Open Access Journals (Sweden)

    Marcel Sonneck

    2015-10-01

    Full Text Available The molecular structures of (E-non-2-enoic acid (C9 and (E-dec-2-enoic acid (C10 are reported. The title compounds were crystallized by slow evaporation of ethanolic solutions at −30 °C. C9 crystallizes in the monoclinic space group P21/c and C10 in the triclinic space group P-1, each with 4 molecules in the unit cell. The unit cell parameters for C9 are: a = 10.6473(4 Å, b = 5.2855(2 Å, c = 17.0313(7 Å; β = 106.0985(10° and V = 920.87(6 Å3. The unit cell parameters for C10 are: a = 4.1405(2 Å, b = 15.2839(6 Å, c = 17.7089(7 Å; α = 68.3291(11°, β = 83.3850(13°, γ = 85.0779(12° and V = 1033.39(8 Å3.

  18. Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains

    Directory of Open Access Journals (Sweden)

    Kuypers Frans A

    2006-07-01

    Full Text Available Abstract Background The formation of acyl-CoA by the action of acyl-CoA synthetases plays a crucial role in membrane lipid turnover, including the plasma membrane of erythrocytes. In human, five Acyl-CoA Synthetase Long-chain (ACSL genes have been identified with as many as 3 different transcript variants for each. Results Acyl-CoA Synthetase Long-chain member 6 (ACSL6 is responsible for activation of long-chain fatty acids in erythrocytes. Two additional transcript variants were also isolated from brain and testis. We report the expression in reticulocytes of two new variants and of the one isolated from brain. All three represented different spliced variants of a mutually exclusive exon pair. They encode a slightly different short motif which contains a conserved structural domain, the fatty acid Gate domain. The motifs differ in the presence of either the aromatic residue phenylalanine (Phe or tyrosine (Tyr. Based on homology, two new isoforms for the closely related ACSL1 were predicted and characterized. One represented a switch of the Phe- to the Tyr-Gate domain motif, the other resulted from the exclusion of both. Swapping of this motif also appears to be common in all mammalian ACSL member 1 and 6 homologs. Conclusion We propose that a Phe to Tyr substitution or deletion of the Gate domain, is the structural reason for the conserved alternative splicing that affects these motifs. Our findings support our hypothesis that this region is structurally important to define the activity of these enzymes.

  19. Effect of molecular weight and glass transition on relaxation and release behaviour of poly(DL-lactic acid) tablets

    NARCIS (Netherlands)

    Steendam, R.; Van Steenbergen, M.J.; Hennink, W.E.; Frijlink, H.W.; Lerk, C.F.

    2001-01-01

    Different molecular weight grades of poly(DL-lactic acid) were applied as release controlling excipients in tablets for oral drug administration. The role of molecular weight and glass transition in the mechanism of water-induced volume expansion and drug release of PDLA tablets was investigated. Mo

  20. Microwave assisted one-pot synthesis of novel molecular clefts with only one chiral arm based on deoxycholic acid

    Institute of Scientific and Technical Information of China (English)

    Bi Tao Zeng; Zhi Gang Zhao; Xing Li Liu; Yun Shi

    2008-01-01

    A rapid, safe, and efficient method for the synthesis of novel molecular clefts based" on deoxycholic acid was reported. Sevennew molecular clefts have been synthesized in good yields (89-98%). This method proved to be extremely simple and highlyefficient. The structures of these receptors were confirmed by 1H NMR, IR, MS spectra and elemental analysis.

  1. Molecular mechanism of flip-flop in triple-layer oleic-acid membrane: correlation between oleic acid and water.

    Science.gov (United States)

    Ngo, Van A; Kalia, Rajiv K; Nakano, Aiichiro; Vashishta, Priya

    2012-11-15

    We perform all-atom molecular dynamics simulations to study a pure oleic acid (OA) membrane in water that results in a triple-layer structure. We compute the pressure profiles to examine the hydrophobic and hydrophilic regions, and to estimate the surface tension (≈34.5 mN/m), which is similar to those of lipid membranes. We observe that the membrane of OAs having a large diffusion coefficient (0.4 × 10(-7) cm(2)/s) along the normal to the membrane is an ideal model to study oleic acid flip-flop. In the model, the membrane contains a middle layer serving as an intermediate for water and OAs to easily migrate (flip-flop) from one to other leaflets. Water molecules surrounding OA head-groups help to reduce the barriers at the hydrophobic interface to trigger flip-flop events. Within 500 ns, we observe 175 flip-flop events of OAs and 305 events of water traversing the membrane. The ratio of water passing rate (k(H(2)O) = 0.673 ns(-1)) to OA flip-flop rate (k(OA) = 0.446 ns(-1)) is 3/2. The ratio of the totally correlated water-OA events to the totally uncorrelated water-OA events, n(cor)/n(uncor), is also 3/2. The probability of the totally and partially correlated events is 69%. The results indicate that the trans-membrane movement of water and OAs is cooperative and correlated, and agrees with experimentally measured absorption rates. They support the idea that OA flip-flop is more favorable than transport by means of functional proteins. This study might provide further insight into how primitive cell membranes work, and how the interplay and correlation between water and fatty acids may occur.

  2. Molecular Modeling of Ammonium, Calcium, Sulfur, and Sodium Lignosulphonates in Acid and Basic Aqueous Environments

    Science.gov (United States)

    Salazar Valencia, P. J.; Bolívar Marinez, L. E.; Pérez Merchancano, S. T.

    2015-12-01

    Lignosulphonates (LS), also known as lignin sulfonates or sulfite lignin, are lignins in sulfonated forms, obtained from the "sulfite liquors," a residue of the wood pulp extraction process. Their main utility lies in its wide range of properties, they can be used as additives, dispersants, binders, fluxing, binder agents, etc. in fields ranging from food to fertilizer manufacture and even as agents in the preparation of ion exchange membranes. Since they can be manufactured relatively easy and quickly, and that its molecular size can be manipulated to obtain fragments of very low molecular weight, they are used as transport agents in the food industry, cosmetics, pharmaceutical and drug development, and as molecular elements for the treatment of health problems. In this paper, we study the electronic structural and optical characteristics of LS incorporating ammonium, sulfur, calcium, and sodium ions in acidic and basic aqueous media in order to gain a better understanding of their behavior and the very interesting properties exhibit. The studies were performed using the molecular modeling program HyperChem 5 using the semiempirical method PM3 of the NDO Family (neglect of differential overlap), to calculate the structural properties. We calculated the electronic and optical properties using the semiempirical method ZINDO / CI.

  3. Molecular characterisation of the nucleic acids recovered from aged forensic samples.

    Science.gov (United States)

    Previderè, Carlo; Micheletti, Piero; Perossa, Romina; Grignani, Pierangela; Fattorini, Paolo

    2002-12-01

    The molecular composition of the genetic substrate recovered from seven aged forensic samples has been extensively investigated. A simple enzymatic test based on DNAseI incubation of the extracts showed that the UV-fluorescent material from the forensic specimens is composed of nucleic acids, with the DNA fraction representing at least 90% of the total amount. Since spectrophotometric determinations of the extracts showed unreliable results due to anomalous OD(260)/OD(280) ratios, quantification of the nuclease-sensitive genetic material was performed by a slightly modified agarose plate method. The first quantitative data on exogenous contamination in aged forensic samples are provided by slot-blot hybridisation of the extracts to human, bacterial and fungal probes. Only limited amounts of human and contaminant DNA were detected in the samples. The molecular integrity of the primary structure of these aged DNA samples was analysed by reversed-phase HPLC/MS. The data show a good correlation between the degree of chemical damage and the ability to hybridise to molecular probes. The ability to achieve specific genetic profiles was assessed by multiplex PCR amplification of STR loci. Our data show that accurate determination of the molecular composition of the DNA recovered from forensic samples can be extremely useful for a reliable evaluation of the PCR typing results.

  4. Proteomics identifies molecular networks affected by tetradecylthioacetic acid and fish oil supplemented diets

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; León, Ileana R.; Kulej, Katarzyna

    2013-01-01

    - high fat diet that is thought to contribute to the development of metabolic syndrome - a condition that is strongly associated with diabetes, obesity and heart failure. Fish oil and TTA are known to have beneficial effects for the fatty acid metabolism and have been shown to alleviate some...... of the symptoms of the metabolic syndrome. To date very little is known about the molecular mechanisms behind these beneficial effects and the potential pitfalls of the consumption of those two compounds. Only studies of each compound separately and using only small scale molecular biology approaches have been...... carried out. The results of this work provide an excellent starting point for further studies that will help to understand the metabolic effects of fish oil and TTA and will hopefully help to design dietary programs directed towards reduction of the prevalence of metabolic syndrome and associated diseases....

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

    Energy Technology Data Exchange (ETDEWEB)

    Katti, Dinesh R., E-mail: Dinesh.Katti@ndsu.edu; 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{sub 4}{sup 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{sub 4}{sup 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.

  6. Synthesis, molecular modeling and biological evaluation of two new chicoric acid analogs.

    Science.gov (United States)

    Righi, Giuliana; Pelagalli, Romina; Isoni, Valerio; Tirotta, Ilaria; Dallocchio, Roberto; Dessì, Alessandro; Macchi, Beatrice; Frezza, Caterina; Rossetti, Ilaria; Bovicelli, Paolo

    2017-02-01

    Two conformationally constrained compounds similar to chicoric acid but lacking the catechol and carboxyl groups were prepared. In these analogues, the single bond between the two caffeoyl fragments has been replaced with a chiral oxirane ring and both aromatic residues modified protecting completely or partially the catechol moiety as methyl ether. Preliminary molecular modelling studies carried out on the two analogues showed interactions near the active site of HIV integrase; however, in comparison with raltegravir, the biological evaluation confirmed that CAA-1 and CAA-2 were unable to inhibit infection at lower concentration.

  7. Catalytic Hydrogenation over Palladium Complex of Molecular Complex of Poly(4-vinylpyridine) with Acetic Acid

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The palladium complex of the molecular complex of poly(4-vinylpyridine) with acetic acid(PVP/HAc-Pd) was prepared. Its catalytic activity for the hydrogenation of nitrobenzene was found much higher than that of the corresponding palladium complex of poly(4-vinylpyridine). In the presence of a strong inorganic alkali, especially potassium hydroxide, the catalytic activity is greatly improved. The suitable hydrogenation condition for PVP/HAc-Pd is to use 0.1 mol/L ethanol solution of potassium hydroxide as the hydrogenation medium and the hydrogenation is carried out at 45 ℃.

  8. New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

    OpenAIRE

    Assem Barakat; Abdullah Mohammed Al-Majid; Saied M. Soliman; Gehad Lotfy; Ghabbour, Hazem A; Hoong-Kun Fun; Abdul Wadood; Ismail Warad; Joseph C. Sloop

    2015-01-01

    The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4-fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular stru...

  9. Sector Switching

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Much of the literature on industry evolution has found firm dynamics to be an important source of sector-level productivity growth. In this paper, we ask whether the delineation of entry and exit firms matters in assessing the impact of firm turnover. Using detailed firm level data from Vietnam......-level determinants of firm exit and switching, which need to be carefully considered in the search for effective policy...

  10. Sector Switching

    DEFF Research Database (Denmark)

    Newman, Carol; Rand, John; Tarp, Finn

    Much of the literature on industry evolution has found firm dynamics to be an important source of sector-level productivity growth. In this paper, we ask whether the delineation of entry and exit firms matters in assessing the impact of firm turnover. Using detailed firm level data from Vietnam, ......-level determinants of firm exit and switching, which need to be carefully considered in the search for effective policy...

  11. Possible molecular targets for therapeutic applications of caffeic acid phenethyl ester in inflammation and cancer

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2015-03-01

    Full Text Available Of the various derivatives of caffeic acid, caffeic acid phenethyl ester (CAPE is a hydrophobic, bioactive polyphenolic ester obtained from propolis extract. The objective in writing this review article was to summarize all published studies on therapeutics of CAPE in inflammation and cancer to extract direction for future research. The possible molecular targets for the action of CAPE, include various transcription factors such as nuclear factor-κB, tissue necrosis factor-α, interleukin-6, cyclooxygenase-2, Nrf2, inducible nitric oxide synthase, nuclear factor of activated T cells, hypoxia-inducible factor-1α, and signal transducers and activators of transcription. Based on the valuable data on its therapeutics in inflammation and cancer, clinical studies of CAPE should also be conducted to explore its toxicities, if any.

  12. Molecular dynamics simulations of the adsorption of amino acids on the hydroxyapatite {100}-water interface

    Institute of Scientific and Technical Information of China (English)

    Zhi-sen ZHANG; Hai-hua PAN; Rui-kang TANG

    2008-01-01

    The understanding of interfaces and interaction of organic molecules and inorganic materials are the important issues in biomineralization. Experimentally, it has been found that amino acids (AA) can regulate the morphology of hydroxyapatite (HAP) crystals significantly. In this study, molecular dynamics simulation is employed to investigate the detailed adsorption behavior of polar, ionic, and hydrophobic AA on the {100} face of HAP at the atomic level. The results indicate that various AA are adsorbed on the HAP crystal surface mainly by amino and carboxylate groups at the specific sites. Multiple inter-action points are found for polar and ionic AA. The adsorbed AA molecules occupy the Ca and P sites of the HAP surfaces which may inhibit and regulate the HAP growth. The adsorbed amino acid layer can also change the interfacial hydration layer and influence the transporta-tion of ions in and out of HAP, which may be another strategy of biological control in biomineralization.

  13. A classical reactive potential for molecular clusters of sulphuric acid and water

    CERN Document Server

    Stinson, Jake L; Ford, Ian J

    2016-01-01

    We present a two-state empirical valence bond (EVB) potential describing interactions between sulphuric acid and water molecules and designed to model proton transfer between them within a classical dynamical framework. The potential has been developed in order to study the properties of molecular clusters of these species, which are thought to be relevant to atmospheric aerosol nucleation. The particle swarm optimisation method has been used to fit the parameters of the EVB model to density functional theory (DFT) calculations. Features of the parametrised model and DFT data are compared and found to be in satisfactory agreement. In particular, it is found that a single sulphuric acid molecule will donate a proton when clustered with four water molecules at 300 K and that this threshold is temperature dependent.

  14. Amino acids as co-amorphous stabilizers for poorly water-soluble drugs--Part 2: molecular interactions.

    Science.gov (United States)

    Löbmann, Korbinian; Laitinen, Riikka; Strachan, Clare; Rades, Thomas; Grohganz, Holger

    2013-11-01

    The formation of co-amorphous drug-drug mixtures has proved to be a powerful approach to stabilize the amorphous form and at the same time increase the dissolution of poorly water-soluble drugs. Molecular interactions in these co-amorphous formulations can play a crucial role in stabilization and dissolution enhancement. In this regard, Fourier-transform infrared spectroscopy (FTIR) is a valuable tool to analyze the molecular near range order of the compounds in the co-amorphous mixtures. In this study, several co-amorphous drugs--low molecular weight excipient blends--have been analyzed with FTIR spectroscopy. Molecular interactions of the drugs carbamazepine and indomethacin with the amino acids arginine, phenylalanine, and tryptophan were investigated. The amino acids were chosen from the biological target site of both drugs and prepared as co-amorphous formulations together with the drugs by vibrational ball milling. A detailed analysis of the FTIR spectra of these formulations revealed specific peak shifts in the vibrational modes of functional groups of drug and amino acid, as long as one amino acid from the biological target site was present in the blends. These peak shifts indicate that the drugs formed specific molecular interactions (hydrogen bonding and π-π interactions) with the amino acids. In the drug-amino acid mixtures that contained amino acids which were not present at the biological target site, no such interactions were identified. This study shows the potential of amino acids as small molecular weight excipients in co-amorphous formulations to stabilize the amorphous form of a poorly water-soluble drug through strong and specific molecular interactions with the drug.

  15. Selective oxidation of glycerol to formic acid in highly concentrated aqueous solutions with molecular oxygen using V-substituted phosphomolybdic acids

    KAUST Repository

    Zhang, Jizhe

    2014-01-01

    Formic acid is an important commodity chemical as well as a promising medium for hydrogen storage and hydrogen production. In this paper, we report that formic acid can be produced through selective oxidation of glycerol, a low-cost by-product of biodiesel, by using vanadium-substituted phosphomolybdic acids as catalysts and molecular oxygen as the oxidant. Significantly, this catalytic system allows for high-concentration conversions and thus leads to exceptional efficiency. Specifically, 3.64 g of formic acid was produced from 10 g of glycerol/water (50/50 in weight) solution. © 2014 the Partner Organisations.

  16. The 2016 database issue of Nucleic Acids Research and an updated molecular biology database collection.

    Science.gov (United States)

    Rigden, Daniel J; Fernández-Suárez, Xosé M; Galperin, Michael Y

    2016-01-04

    The 2016 Database Issue of Nucleic Acids Research starts with overviews of the resources provided by three major bioinformatics centers, the U.S. National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EMBL-EBI) and Swiss Institute for Bioinformatics (SIB). Also included are descriptions of 62 new databases and updates on 95 databases that have been previously featured in NAR plus 17 previously described elsewhere. A number of papers in this issue deal with resources on nucleic acids, including various kinds of non-coding RNAs and their interactions, molecular dynamics simulations of nucleic acid structure, and two databases of super-enhancers. The protein database section features important updates on the EBI's Pfam, PDBe and PRIDE databases, as well as a variety of resources on pathways, metabolomics and metabolic modeling. This issue also includes updates on popular metagenomics resources, such as MG-RAST, EBI Metagenomics, and probeBASE, as well as a newly compiled Human Pan-Microbe Communities database. A significant fraction of the new and updated databases are dedicated to the genetic basis of disease, primarily cancer, and various aspects of drug research, including resources for patented drugs, their side effects, withdrawn drugs, and potential drug targets. A further six papers present updated databases of various antimicrobial and anticancer peptides. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been updated with the addition of 88 new resources and removal of 23 obsolete websites, which brought the current listing to 1685 databases.

  17. Neurotransmitter Switching? No Surprise.

    Science.gov (United States)

    Spitzer, Nicholas C

    2015-06-03

    Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed.

  18. Solid lipid nanoparticles as nucleic acid delivery system: properties and molecular mechanisms.

    Science.gov (United States)

    de Jesus, Marcelo B; Zuhorn, Inge S

    2015-03-10

    Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure-function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

  19. Glycolipid core structure switching from globo- to lacto- and ganglio-series during retinoic acid-induced differentiation of TERA-2-derived human embryonal carcinoma cells.

    Science.gov (United States)

    Fenderson, B A; Andrews, P W; Nudelman, E; Clausen, H; Hakomori, S

    1987-07-01

    We have analyzed the glycolipid markers of a recently cloned human embryonal carcinoma (EC) cell line, NTERA-2, which differentiates extensively into a variety of somatic cell types when exposed to retinoic acid. These tumor cells provide a model system that can be used to study the ontogeny of glycolipid diversity during human embryonic development. Glycolipid antigens were identified by cell surface immunofluorescence and thin-layer chromatography immunostaining using a comprehensive set of anticarbohydrate monoclonal antibodies. Undifferentiated NTERA-2 cells were found to express predominantly globo-series glycolipids, including Gb3, Gb5 (IV3GalGb4), globo-ganglioside (IV3NeuAc alpha 2----3GalGb4), globo-H (IV3Fuc alpha 1----2GalGb4), and globo-A (IV3GalNAc alpha 1----3[Fuc alpha 1----2]GalGb4). When NTERA-2 cells were induced to differentiate by culturing in the presence of 10(-5) M retinoic acid, a remarkable shift of cellular glycolipids from globo-series to lacto- and ganglio-series was observed: Globo-series structures declined, particularly during the period 7-20 days after first exposure to retinoic acid, while lacto-series structures, including fucosyl alpha 1----3 type 2 chain (Lex) and sialosyl type 2 chain, and ganglio-series structures, including GM3, GD3, 9-O-acetyl-GD3, GM2, GD2, and GT3, increased. The presence of globo-A and globo-H as the major ABH blood group antigens in undifferentiated NTERA-2 cells suggests that globo-series blood group antigens are embryonic antigens, synthesis of which switches to lacto-series during human development. Two-color immunofluorescence analysis indicated preferential expression of several ganglio- and lacto-series antigens on different subsets of differentiated cells and permitted the relationship of these subsets to the development of neurons in NTERA-2 cultures to be determined. The results suggest that glycosyltransferase, particularly those involved in controlling glycoconjugate core structure assembly

  20. Vapor-pressure osmometric study of the molecular weight and aggregation tendency of a reference-soil fulvic acid

    Science.gov (United States)

    Marinsky, J.A.; Reddy, M.M.

    1990-01-01

    The molecular weight and aggregation tendency of a reference-soil fulvic acid in Armadale horizon Bh were determined by vapor-pressure osmometry using tetrahydrofuran and water as solvents. With tetrahydrofuran, number-average molecular weight values of 767 ?? 34 and 699 ?? 8 daltons were obtained from two separate sets of measurements. Two sets of measurements with water also yielded values within this range (754 ?? 70 daltons) provided that the fulvic acid concentration in water did not exceed 7 mg ml-1; at higher concentrations (9.1-13.7 mg ml-1) a number-average molecular weight of 956 ?? 25 daltons was resolved, providing evidence of molecular aggregation. Extension of these studies to 80% neutralized fulvic acid showed that a sizeable fraction of the sodium counter ion is not osmotically active.

  1. Hybrid molecularly imprinted poly(methacrylic acid-TRIM)-silica chemically modified with (3-glycidyloxypropyl)trimethoxysilane for the extraction of folic acid in aqueous medium

    Energy Technology Data Exchange (ETDEWEB)

    Midori de Oliveira, Fernanda; Gava Segatelli, Mariana [Departamento de Química, Universidade Estadual de Londrina, Rod. Celso Garcia Cid, PR 445 Km 380, Campus Universitário, Londrina, PR CEP 86051-990 (Brazil); Tarley, César Ricardo Teixeira, E-mail: ctarleyquim@yahoo.com.br [Departamento de Química, Universidade Estadual de Londrina, Rod. Celso Garcia Cid, PR 445 Km 380, Campus Universitário, Londrina, PR CEP 86051-990 (Brazil); Instituto Nacional de Ciência e Tecnologia (INCT) de Bioanalítica, Universidade Estadual de Campinas (UNICAMP), Instituto de Química, Departamento de Química Analítica, Cidade Universitária Zeferino Vaz s/n, CEP 13083-970 Campinas, SP (Brazil)

    2016-02-01

    In the present study a hybrid molecularly imprinted poly(methacrylic acid-trimethylolpropane trimethacrylate)-silica (MIP) was synthesized and modified with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) with posterior opening of epoxy ring to provide hydrophilic properties of material in the extraction of folic acid from aqueous medium. The chemical and structural aggregates of hybrid material were characterized by means of Fourier Transform Infrared (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Thermogravimetric analysis (TGA) and textural data. Selectivity data of MIP were compared to non-imprinted polymer (NIP) through competitive sorption studies in the presence of caffeine, paracetamol or 4-aminobenzamide yielding relative selectivity coefficients (k′) higher than one unit, thus confirming the selective character of MIP even in the presence of structurally smaller compounds than the folic acid. The lower hydrophobic sorption by bovine serum albumin (BSA) in the MIP as compared to unmodified MIP proves the hydrophilicity of polymer surface by using GPTMS with opening ring. Under acid medium (pH 1.5) the sorption of folic acid onto MIP from batch experiments was higher than the one achieved for NIP. Equilibrium sorption of folic acid was reached at 120 min for MIP, NIP and MIP without GPTMS and kinetic sorption data were well described by pseudo-second-order, Elovich and intraparticle diffusion models. Thus, these results indicate the existence of different binding energy sites in the polymers and a complex mechanism consisting of both surface sorption and intraparticle transport of folic acid within the pores of polymers. - Highlights: • The molecularly imprinted hybrid polymer showed high adsorption capacity for folic acid. • The molecularly imprinted hybrid polymer showed high selectivity for folic acid. • The molecularly imprinted hybrid polymer modified with GPTMS excludes higher amount of BSA.

  2. Photoresponsive surface molecularly imprinted polymer on ZnO nanorods for uric acid detection in physiological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Qian [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Department of Science and Environmental Studies, The Hong Kong Institute of Education (Hong Kong); Li, Zai-yong; Wei, Yu-bo; Yang, Xia; Liu, Lan-tao [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Gong, Cheng-bin, E-mail: gongcbtq@swu.edu.cn [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Ma, Xue-bing [The Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Lam, Michael Hon-wah [Department of Biology and Chemistry, City University of Hong Kong (Hong Kong); Chow, Cheuk-fai, E-mail: cfchow@ied.edu.hk [Department of Science and Environmental Studies, The Hong Kong Institute of Education (Hong Kong)

    2016-09-01

    A photoresponsive surface molecularly imprinted polymer for uric acid in physiological fluids was fabricated through a facile and effective method using bio-safe and biocompatible ZnO nanorods as a support. The strategy was carried out by introducing double bonds on the surface of the ZnO nanorods with 3-methacryloxypropyltrimethoxysilane. The surface molecularly imprinted polymer on ZnO nanorods was then prepared by surface polymerization using uric acid as template, water-soluble 5-[(4-(methacryloyloxy)phenyl)diazenyl]isophthalic acid as functional monomer, and triethanolamine trimethacryl ester as cross-linker. The surface molecularly imprinted polymer on ZnO nanorods showed good photoresponsive properties, high recognition ability, and fast binding kinetics toward uric acid, with a dissociation constant of 3.22 × 10{sup −5} M in aqueous NaH{sub 2}PO{sub 4} buffer at pH = 7.0 and a maximal adsorption capacity of 1.45 μmol g{sup −1}. Upon alternate irradiation at 365 and 440 nm, the surface molecularly imprinted polymer on ZnO nanorods can quantitatively uptake and release uric acid. - Highlights: • Novel surface molecularly imprinted polymer on ZnO nanorods was synthesized. • ZnO-SMIP showed good selectivity toward uric acid in physiological fluids. • ZnO-SMIP displayed good photoresponsive properties.

  3. The allosteric switching mechanism in bacteriophage MS2

    Science.gov (United States)

    Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F.

    2016-07-01

    We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.

  4. Proton transport in triflic acid pentahydrate studied via ab initio path integral molecular dynamics.

    Science.gov (United States)

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2011-06-16

    Trifluoromethanesulfonic acid hydrates provide a well-defined system to study proton dissociation and transport in perfluorosulfonic acid membranes, typically used as the electrolyte in hydrogen fuel cells, in the limit of minimal water. The triflic acid pentahydrate crystal (CF(3)SO(3)H·5H(2)O) is sufficiently aqueous that it contains an extended three-dimensional water network. Despite it being extended, however, long-range proton transport along the network is structurally unfavorable and would require considerable rearrangement. Nevertheless, the triflic acid pentahydrate crystal system can provide a clear picture of the preferred locations of local protonic defects in the water network, which provides insights about related structures in the disordered, low-hydration environment of perfluorosulfonic acid membranes. Ab initio molecular dynamics simulations reveal that the proton defect is most likely to transfer to the closest water that has the expected presolvation and only contains water in its first solvation shell. Unlike the tetrahydrate of triflic acid (CF(3)SO(3)H·4H(2)O), there is no evidence of the proton preferentially transferring to a water molecule bridging two of the sulfonate groups. However, this could be an artifact of the crystal structure since the only such water molecule is separated from the proton by long O-O distances. Hydrogen bonding criteria, using the two-dimensional potential of mean force, are extracted. Radial distribution functions, free energy profiles, radii of gyration, and the root-mean-square displacement computed from ab initio path integral molecular dynamics simulations reveal that quantum effects do significantly extend the size of the protonic defect and increase the frequency of proton transfer events by nearly 15%. The calculated IR spectra confirm that the dominant protonic defect mostly exists as an Eigen cation but contains some Zundel ion characteristics. Chain lengths and ring sizes determined from the

  5. Molecular glass positive i-line photoresist materials containing 2,1,4-DNQ and acid labile group

    Science.gov (United States)

    Wang, Liyuan; Yu, Jinxing; Xu, Na

    2010-04-01

    Recent years increasing attention has been given to molecular glass resist materials. In this paper, maleopimaric acid, cycloaddition reaction product of rosin with maleic anhydride, was reacted with hydroxylamine and then further esterified with 2-diazo-1-naphthoquinone-4-sulfonyl chloride to give N-hydroxy maleopimarimide sulfonate. The carboxylic acid group of the compound was then protected by the reaction of this compound with vinyl ethyl ether or dihydropyran. Thus obtained compounds were amorphous. When irradiated with i-line light, the 2,1,4-DNQ group undergo photolysis not only to give off nitrogen gas but also generate sulfonic acid which can result in the decomposition of the acid labile group. So, a novel chemically amplified positive i-line molecular glass photoresists can be formed by the compound and other acidolytic molecular glass compounds. The lithographic performance of the resist materials is evaluated.

  6. Molecular Characterization and Enhancement of Anticancer Activity of Caffeic Acid Phenethyl Ester by γ Cyclodextrin

    Science.gov (United States)

    Wadhwa, Renu; Nigam, Nupur; Bhargava, Priyanshu; Dhanjal, Jaspreet Kaur; Goyal, Sukriti; Grover, Abhinav; Sundar, Durai; Ishida, Yoshiyuki; Terao, Keiji; Kaul, Sunil C

    2016-01-01

    Caffeic Acid Phenethyl Ester (CAPE) is a key component in New Zealand propolis, known for a variety of health promoting and therapeutic potentials. We investigated the molecular mechanism of anticancer and anti-metastasis activities of CAPE. cDNA array performed on the control and CAPE-treated breast cancer cells revealed activation of DNA damage signaling involving upregulation of GADD45α and p53 tumor suppressor proteins. Molecular docking analysis revealed that CAPE is capable of disrupting mortalin-p53 complexes. We provide experimental evidence and demonstrate that CAPE induced disruption of mortalin-p53 complexes led to nuclear translocation and activation of p53 resulting in growth arrest in cancer cells. Furthermore, CAPE-treated cells exhibited downregulation of mortalin and several other key regulators of cell migration accountable for its anti-metastasis activity. Of note, we found that whereas CAPE was unstable in the culture medium (as it gets degraded into caffeic acid by secreted esterases), its complex with gamma cyclodextrin (γCD) showed high efficacy in anti-tumor and anti-metastasis assays in vitro and in vivo (when administered through either intraperitoneal or oral route). The data proposes that CAPE-γCD complex is a potent anti-cancer and anti-metastasis reagent. PMID:27698914

  7. The 2015 Nucleic Acids Research Database Issue and molecular biology database collection.

    Science.gov (United States)

    Galperin, Michael Y; Rigden, Daniel J; Fernández-Suárez, Xosé M

    2015-01-01

    The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNAcentral, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of 'moonlighting' proteins, and two new databases of protein-protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  8. Characterization of Gallic Acid Interaction with Human Serum Albumin by Spectral and Molecular Modeling Methods

    Institute of Scientific and Technical Information of China (English)

    LIU Zuo-jia; LI Dan; NIU Feng-lan

    2012-01-01

    The binding of drugs with human serum albumin(HSA)is a crucial factor influencing the distribution and bioactivity of drugs in the body.To understand the action mechanisms between gallic acid(GA,3,4,5-trihydroxybenzoic acid)and HSA,the binding of GA with HSA was investigated by a combined experimental and computational approach.The fluorescence properties of HSA and the binding parameters of GA collectively indicate that the binding is characterized by static quenching mechanism at one high affinity binding site.According to the estimated molecular distance between the donor(HSA)and the acceptor(GA),the binding is related to the fluorescence resonance energy transfer.As indicated by the thermodynamic parameters,hydrophobic interaction plays a major role in the GA-HSA complex.Further,the experimental results reveal that GA is bound in the large hydrophobic cavity of subdomain ⅡA in the site Ⅰ of HSA,which is well approved by molecular docking.

  9. Molecular classification based on apomorphic amino acids (Arthropoda, Hexapoda): Integrative taxonomy in the era of phylogenomics.

    Science.gov (United States)

    Wu, Hao-Yang; Wang, Yan-Hui; Xie, Qiang; Ke, Yun-Ling; Bu, Wen-Jun

    2016-06-17

    With the great development of sequencing technologies and systematic methods, our understanding of evolutionary relationships at deeper levels within the tree of life has greatly improved over the last decade. However, the current taxonomic methodology is insufficient to describe the growing levels of diversity in both a standardised and general way due to the limitations of using only morphological traits to describe clades. Herein, we propose the idea of a molecular classification based on hierarchical and discrete amino acid characters. Clades are classified based on the results of phylogenetic analyses and described using amino acids with group specificity in phylograms. Practices based on the recently published phylogenomic datasets of insects together with 15 de novo sequenced transcriptomes in this study demonstrate that such a methodology can accommodate various higher ranks of taxonomy. Such an approach has the advantage of describing organisms in a standard and discrete way within a phylogenetic framework, thereby facilitating the recognition of clades from the view of the whole lineage, as indicated by PhyloCode. By combining identification keys and phylogenies, the molecular classification based on hierarchical and discrete characters may greatly boost the progress of integrative taxonomy.

  10. The 2013 Nucleic Acids Research Database Issue and the online molecular biology database collection.

    Science.gov (United States)

    Fernández-Suárez, Xosé M; Galperin, Michael Y

    2013-01-01

    The 20th annual Database Issue of Nucleic Acids Research includes 176 articles, half of which describe new online molecular biology databases and the other half provide updates on the databases previously featured in NAR and other journals. This year's highlights include two databases of DNA repeat elements; several databases of transcriptional factors and transcriptional factor-binding sites; databases on various aspects of protein structure and protein-protein interactions; databases for metagenomic and rRNA sequence analysis; and four databases specifically dedicated to Escherichia coli. The increased emphasis on using the genome data to improve human health is reflected in the development of the databases of genomic structural variation (NCBI's dbVar and EBI's DGVa), the NIH Genetic Testing Registry and several other databases centered on the genetic basis of human disease, potential drugs, their targets and the mechanisms of protein-ligand binding. Two new databases present genomic and RNAseq data for monkeys, providing wealth of data on our closest relatives for comparative genomics purposes. The NAR online Molecular Biology Database Collection, available at http://www.oxfordjournals.org/nar/database/a/, has been updated and currently lists 1512 online databases. The full content of the Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/).

  11. The 2012 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection.

    Science.gov (United States)

    Galperin, Michael Y; Fernández-Suárez, Xosé M

    2012-01-01

    The 19th annual Database Issue of Nucleic Acids Research features descriptions of 92 new online databases covering various areas of molecular biology and 100 papers describing recent updates to the databases previously described in NAR and other journals. The highlights of this issue include, among others, a description of neXtProt, a knowledgebase on human proteins; a detailed explanation of the principles behind the NCBI Taxonomy Database; NCBI and EBI papers on the recently launched BioSample databases that store sample information for a variety of database resources; descriptions of the recent developments in the Gene Ontology and UniProt Gene Ontology Annotation projects; updates on Pfam, SMART and InterPro domain databases; update papers on KEGG and TAIR, two universally acclaimed databases that face an uncertain future; and a separate section with 10 wiki-based databases, introduced in an accompanying editorial. The NAR online Molecular Biology Database Collection, available at http://www.oxfordjournals.org/nar/database/a/, has been updated and now lists 1380 databases. Brief machine-readable descriptions of the databases featured in this issue, according to the BioDBcore standards, will be provided at the http://biosharing.org/biodbcore web site. The full content of the Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  12. Revised molecular basis of the promiscuous carboxylic acid perhydrolase activity in serine hydrolases.

    Science.gov (United States)

    Yin, DeLu Tyler; Kazlauskas, Romas J

    2012-06-25

    Several serine hydrolases catalyze a promiscuous reaction: perhydrolysis of carboxylic acids to form peroxycarboxylic acids. The working hypothesis is that perhydrolases are more selective than esterases for hydrogen peroxide over water. In this study, we tested this hypothesis, and focused on L29P-PFE (Pseudomonas fluorescens esterase), which catalyzes perhydrolysis of acetic acid 43-fold faster than wild-type PFE. This hypothesis predicts that L29P-PFE should be approximately 43-fold more selective for hydrogen peroxide than wild-type PFE, but experiments show that L29P-PFE is less selective. The ratio of hydrolysis to perhydrolysis of methyl acetate at different concentrations of hydrogen peroxide fit a kinetic model for nucleophile selectivity. L29P-PFE (β(0)=170  M(-1)) is approximately half as selective for hydrogen peroxide over water than wild-type PFE (β(0)=330  M(-1)), which contradicts the working hypothesis. An alternative hypothesis is that carboxylic acid perhydrolases increase perhydrolysis by forming the acyl-enzyme intermediate faster. Consistent with this hypothesis, the rate of acetyl-enzyme formation, measured by (18)O-water exchange into acetic acid, was 25-fold faster with L29P-PFE than with wild-type PFE, which is similar to the 43-fold faster perhydrolysis with L29P-PFE. Molecular modeling of the first tetrahedral intermediate (T(d)1) suggests that a closer carbonyl group found in perhydrolases accepts a hydrogen bond from the leaving group water. This revised understanding can help design more efficient enzymes for perhydrolysis and shows how subtle changes can create new, unnatural functions in enzymes.

  13. Thermodynamic properties of multifunctional oxygenates in atmospheric aerosols from quantum mechanics and molecular dynamics: dicarboxylic acids.

    Science.gov (United States)

    Tong, Chinghang; Blanco, Mario; Goddard, William A; Seinfeld, John H

    2004-07-15

    Ambient particulate matter contains polar multifunctional oxygenates that partition between the vapor and aerosol phases. Vapor pressure predictions are required to determine the gas-particle partitioning of such organic compounds. We present here a method based on atomistic simulations combined with the Clausius-Clapeyron equation to predict the liquid vapor pressure, enthalpies of vaporization, and heats of sublimation of atmospheric organic compounds. The resulting temperature-dependent vapor pressure equation is a function of the heat of vaporization at the normal boiling point [deltaHvap(Tb)], normal boiling point (Tb), and the change in heat capacity (liquid to gas) of the compound upon phase change [deltaCp(Tb)]. We show that heats of vaporization can be estimated from calculated cohesive energy densities (CED) of the pure compound obtained from multiple sampling molecular dynamics. The simulation method (CED) uses a generic force field (Dreiding) and molecular models with atomic charges determined from quantum mechanics. The heats of vaporization of five dicarboxylic acids [malonic (C3), succinic (C4), glutaric (C5), adipic (C6), and pimelic (C7)] are calculated at 500 K. Results are in agreement with experimental values with an averaged error of about 4%. The corresponding heats of sublimation at 298 K are also predicted using molecular simulations. Vapor pressures of the five dicarboxylic acids are also predicted using the derived Clausius-Clapeyron equation. Predicted liquid vapor pressures agree well with available literature data with an averaged error of 29%, while the predicted solid vapor pressures at ambient temperature differ considerably from a recent study by Bilde et al. (Environ. Sci. Technol. 2003, 37, 1371-1378) (an average of 70%). The difference is attributed to the linear dependence assumption thatwe used in the derived Clausius-Clapeyron equation.

  14. Rapid Molecular Detection of Multidrug-Resistant Tuberculosis by PCR-Nucleic Acid Lateral Flow Immunoassay.

    Directory of Open Access Journals (Sweden)

    Hatairat Kamphee

    Full Text Available Several existing molecular tests for multidrug-resistant tuberculosis (MDR-TB are limited by complexity and cost, hindering their widespread application. The objective of this proof of concept study was to develop a simple Nucleic Acid Lateral Flow (NALF immunoassay as a potential diagnostic alternative, to complement conventional PCR, for the rapid molecular detection of MDR-TB. The NALF device was designed using antibodies for the indirect detection of labeled PCR amplification products. Multiplex PCR was optimized to permit the simultaneous detection of the drug resistant determining mutations in the 81-bp hot spot region of the rpoB gene (rifampicin resistance, while semi-nested PCR was optimized for the S315T mutation detection in the katG gene (isoniazid resistance. The amplification process additionally targeted a conserved region of the genes as Mycobacterium tuberculosis (Mtb DNA control. The optimized conditions were validated with the H37Rv wild-type (WT Mtb isolate and Mtb isolates with known mutations (MT within the rpoB and katG genes. Results indicate the correct identification of WT (drug susceptible and MT (drug resistant Mtb isolates, with the least limit of detection (LOD being 104 genomic copies per PCR reaction. NALF is a simple, rapid and low-cost device suitable for low resource settings where conventional PCR is already employed on a regular basis. Moreover, the use of antibody-based NALF to target primer-labels, without the requirement for DNA hybridization, renders the device generic, which could easily be adapted for the molecular diagnosis of other infectious and non-infectious diseases requiring nucleic acid detection.

  15. Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms

    Science.gov (United States)

    Monroig, Óscar; Tocher, Douglas R.; Navarro, Juan C.

    2013-01-01

    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs. PMID:24152561

  16. New Diethyl Ammonium Salt of Thiobarbituric Acid Derivative: Synthesis, Molecular Structure Investigations and Docking Studies

    Directory of Open Access Journals (Sweden)

    Assem Barakat

    2015-11-01

    Full Text Available The synthesis of the new diethyl ammonium salt of diethylammonium(E-5-(1,5-bis(4-fluorophenyl-3-oxopent-4-en-1-yl-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity value of 0.229.

  17. Synthesis and Evaluation of Molecularly Imprinted Silica Gel for 2-Hydroxybenzoic Acid in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Mhd Radzi Abas

    2013-03-01

    Full Text Available A molecularly imprinted silica gel sorbent for selective removal of 2-Hydroxybenzoic acid (2-HA was prepared by a surface imprinting technique with a sol-gel process. The 2-HA molecularly imprinted silica gel (2-HA-MISG sorbent was evaluated by various parameters, including the influence of pH, static, kinetic adsorption and selectivity experiments. The optimum adsorption capacity to the 2-HA appeared to be around pH 2 by the polymer. Morevoer, the imprinted sorbent displayed fast uptake kinetics, obtained within 20 min. The adsorption capacity of the 2-HA-MISG (76.2 mg g−1 was higher than that of the non-imprinted silica gel (NISG (42.58 mg g−1. This indicates that the 2-HA-MISG offers a higher affinity for 2-HA than the NISG. The polymer displays good selectivity and exhibits good reusability. Experimental results show the potential of molecularly imprinted silica sorbent for selective removal of 2-HA.

  18. Synthesis and evaluation of molecularly imprinted silica gel for 2-hydroxybenzoic Acid in aqueous solution.

    Science.gov (United States)

    Raof, Siti Farhana Abdul; Mohamad, Sharifah; Abas, Mhd Radzi

    2013-03-14

    A molecularly imprinted silica gel sorbent for selective removal of 2-Hydroxybenzoic acid (2-HA) was prepared by a surface imprinting technique with a sol-gel process. The 2-HA molecularly imprinted silica gel (2-HA-MISG) sorbent was evaluated by various parameters, including the influence of pH, static, kinetic adsorption and selectivity experiments. The optimum adsorption capacity to the 2-HA appeared to be around pH 2 by the polymer. Morevoer, the imprinted sorbent displayed fast uptake kinetics, obtained within 20 min. The adsorption capacity of the 2-HA-MISG (76.2 mg g-1) was higher than that of the non-imprinted silica gel (NISG) (42.58 mg g-1). This indicates that the 2-HA-MISG offers a higher affinity for 2-HA than the NISG. The polymer displays good selectivity and exhibits good reusability. Experimental results show the potential of molecularly imprinted silica sorbent for selective removal of 2-HA.

  19. Synthesis and Molecular Recognition of Novel Cyclic Pseudopeptides Containing L-Glutamic Acid or L-Aspartic Acid Backbones

    Institute of Scientific and Technical Information of China (English)

    WANG Tao王涛; HUANG Xiao-Yi黄小毅; XIA Chuan-Qin夏传琴; YU Xiao-Qi余孝其; XIE Ru-Gang谢如刚

    2004-01-01

    Novel cyclic pseudopeptides containing L-glutamic acid or L-aspartic acid backbone structures were efficiently synthesized and characterized. Their chiral recognition properties for L- and D-amino acid methyl ester hydrochloride were discussed also.

  20. The 2014 Nucleic Acids Research Database Issue and an updated NAR online Molecular Biology Database Collection.

    Science.gov (United States)

    Fernández-Suárez, Xosé M; Rigden, Daniel J; Galperin, Michael Y

    2014-01-01

    The 2014 Nucleic Acids Research Database Issue includes descriptions of 58 new molecular biology databases and recent updates to 123 databases previously featured in NAR or other journals. For convenience, the issue is now divided into eight sections that reflect major subject categories. Among the highlights of this issue are six databases of the transcription factor binding sites in various organisms and updates on such popular databases as CAZy, Database of Genomic Variants (DGV), dbGaP, DrugBank, KEGG, miRBase, Pfam, Reactome, SEED, TCDB and UniProt. There is a strong block of structural databases, which includes, among others, the new RNA Bricks database, updates on PDBe, PDBsum, ArchDB, Gene3D, ModBase, Nucleic Acid Database and the recently revived iPfam database. An update on the NCBI's MMDB describes VAST+, an improved tool for protein structure comparison. Two articles highlight the development of the Structural Classification of Proteins (SCOP) database: one describes SCOPe, which automates assignment of new structures to the existing SCOP hierarchy; the other one describes the first version of SCOP2, with its more flexible approach to classifying protein structures. This issue also includes a collection of articles on bacterial taxonomy and metagenomics, which includes updates on the List of Prokaryotic Names with Standing in Nomenclature (LPSN), Ribosomal Database Project (RDP), the Silva/LTP project and several new metagenomics resources. The NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/c/, has been expanded to 1552 databases. The entire Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/).

  1. The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection.

    Science.gov (United States)

    Galperin, Michael Y; Cochrane, Guy R

    2011-01-01

    The current 18th Database Issue of Nucleic Acids Research features descriptions of 96 new and 83 updated online databases covering various areas of molecular biology. It includes two editorials, one that discusses COMBREX, a new exciting project aimed at figuring out the functions of the 'conserved hypothetical' proteins, and one concerning BioDBcore, a proposed description of the 'minimal information about a biological database'. Papers from the members of the International Nucleotide Sequence Database collaboration (INSDC) describe each of the participating databases, DDBJ, ENA and GenBank, principles of data exchange within the collaboration, and the recently established Sequence Read Archive. A testament to the longevity of databases, this issue includes updates on the RNA modification database, Definition of Secondary Structure of Proteins (DSSP) and Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not been featured here in >12 years. There is also a block of papers describing recent progress in protein structure databases, such as Protein DataBank (PDB), PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on protein structure modeling, protein-protein interactions and the organization of inter-protein contact sites. Other highlights include updates of the popular gene expression databases, GEO and ArrayExpress, several cancer gene databases and a detailed description of the UK PubMed Central project. The Nucleic Acids Research online Database Collection, available at: http://www.oxfordjournals.org/nar/database/a/, now lists 1330 carefully selected molecular biology databases. The full content of the Database Issue is freely available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  2. Proton transport in triflic acid hydrates studied via path integral car-parrinello molecular dynamics.

    Science.gov (United States)

    Hayes, Robin L; Paddison, Stephen J; Tuckerman, Mark E

    2009-12-31

    The mono-, di-, and tetrahydrates of trifluoromethanesulfonic acid, which contain characteristic H(3)O(+), H(5)O(2)(+), and H(9)O(4)(+) structures, provide model systems for understanding proton transport in materials with high perfluorosulfonic acid density such as perfluorosulfonic acid membranes commonly employed in hydrogen fuel cells. Ab initio molecular dynamics simulations indicate that protons in these solids are predisposed to transfer to the water most strongly bound to sulfonate groups via a Grotthuss-type mechanism, but quickly return to the most solvated defect structure either due to the lack of a nearby species to stabilize the new defect or a preference for the proton to be maximally hydrated. Path integral molecular dynamics of the mono- and dihydrate reveal significant quantum effects that facilitate proton transfer to the "presolvated" water or SO(3)(-) in the first solvation shell and increase the Zundel character of all the defects. These trends are quantified in free energy profiles for each bonding environment. Hydrogen bonding criteria for HOH-OH(2) and HOH-O(3)S are extracted from the two-dimensional potential of mean force. The quantum radial distribution function, radius of gyration, and root-mean-square displacement position correlation function show that the protonic charge is distributed over two or more water molecules. Metastable structural defects with one excess proton shared between two sulfonate groups and another Zundel or Eigen type cation defect are found for the mono- and dihydrate but not for the tetrahydrate crystal. Results for the tetrahydrate native crystal exhibit minor differences at 210 and 250 K. IR spectra are calculated for all native and stable defect structures. Graph theory techniques are used to characterize the chain lengths and ring sizes in the hydrogen bond network. Low conductivities when limited water is present may be attributable to trapping of protons between SO(3)(-) groups and the increased

  3. Effect of molecular structure of aniline-formaldehyde copolymers on corrosion inhibition of mild steel in hydrochloric acid solution.

    Science.gov (United States)

    Zhang, Yan; Nie, Mengyan; Wang, Xiutong; Zhu, Yukun; Shi, Fuhua; Yu, Jianqiang; Hou, Baorong

    2015-05-30

    Aniline-formaldehyde copolymers with different molecular structures have been prepared and investigated for the purpose of corrosion control of mild steel in hydrochloric acid. The copolymers were synthesized by a condensation polymerization process with different ratios of aniline to formaldehyde in acidic precursor solutions. The corrosion inhibition efficiency of as-synthesized copolymers for Q235 mild steel was investigated in 1.0 mol L(-1) hydrochloric acid solution by weight loss measurement, potentiodynamic polarization, and electrochemical impedance spectroscopy, respectively. All the results demonstrate that as-prepared aniline-formaldehyde copolymers are efficient mixed-type corrosion inhibitors for mild steels in hydrochloric acid. The corrosion inhibition mechanism is discussed in terms of the role of molecular structure on adsorption of the copolymers onto the steel surface in acid solution.

  4. Molecular Analysis of the Polymeric Glutenins with Gliadin-Like Characteristics That Were Produced by Acid Dispersion of Wheat Gluten.

    Science.gov (United States)

    Murakami, Tetsuya; Nishimura, Takahisa; Kitabatake, Naofumi; Tani, Fumito

    2016-03-01

    We had earlier shown that the dispersion of wheat gluten in acetic acid solution conferred gliadin-like characteristics to the polymeric glutenins. To elucidate the molecular behavior of its polymeric glutenins, the characteristics of gluten powder prepared from dispersions with various types of acid were investigated in this study. Mixograph measurements showed that the acid-treated gluten powders, regardless of the type of acid, had dough properties markedly weakened in both resistance and elasticity properties, as though gliadin was supplemented. The polymeric glutenins extracted with 70% ethanol increased greatly in all acid-treated gluten powders. Size exclusion HPLC and SDS-PAGE indicated that the behavior of polymeric glutenins due to acid treatment was attributed to their subunit composition rich in high molecular weight glutenin subunit (HMW-GS) and not their molecular size. The gluten prepared with the addition of NaCl in acid dispersion had properties similar to those of the control gluten. The results suggest that ionic repulsion induced by acid dispersion made the polymeric glutenins rich in HMW-GS disaggregate, and therefore, act like gliadins.

  5. Molecular dynamic simulation of asphaltene co-aggregation with humic acid during oil spill.

    Science.gov (United States)

    Zhu, Xinzhe; Chen, Daoyi; Wu, Guozhong

    2015-11-01

    Humic acid in water and sediment plays a key role in the fate and transport of the spilled oil, but little is known about its influence on the aggregation of heavy oil asphaltenes which is adverse for remediation. Molecular dynamic simulation was performed to characterize the co-aggregation of asphaltenes (continental model and Violanthrone-79 model) with Leonardite humic acid (LHA) at the toluene-water interface and in bulk water, respectively, to simulate the transport of asphaltenes from oil to water. At the toluene-water interface, a LHA layer tended to form and bind to the water by hydrogen bonding which provided a surface for the accumulation of asphaltenes by parallel or T-shape stacking. After entering the bulk water, asphaltene aggregates stacked in parallel were tightly sequestrated inside the inner cavity of LHA aggregates following surface adsorption and structure deformation. Asphaltene aggregation in water was 2-fold higher than at the toluene-water interface. The presence of LHA increased the intensity of asphaltene aggregation by up to 83% in bulk water while relatively less influence was observed at the toluene-water interface. Overall results suggested that the co-aggregation of asphaltene with humic acid should be incorporated to the current oil spill models for better interpreting the overall environmental risks of oil spill.

  6. The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120)*

    Science.gov (United States)

    Hudson, Brian D.; Shimpukade, Bharat; Milligan, Graeme; Ulven, Trond

    2014-01-01

    The long-chain fatty acid receptor FFA4 (previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. This study examines for the first time the detailed mode of binding of both long-chain fatty acid and synthetic agonist ligands at FFA4 by integrating molecular modeling, receptor mutagenesis, and ligand structure-activity relationship approaches in an iterative format. In doing so, residues required for binding of fatty acid and synthetic agonists to FFA4 have been identified. This has allowed for the refinement of a well validated model of the mode of ligand-FFA4 interaction that will be invaluable in the identification of novel ligands and the future development of this receptor as a therapeutic target. The model reliably predicted the effects of substituent variations on agonist potency, and it was also able to predict the qualitative effect of binding site mutations in the majority of cases. PMID:24860101

  7. Molecular Dynamics Simulations Capture the Misfolding of the Bovine Prion Protein at Acidic pH

    Directory of Open Access Journals (Sweden)

    Chin Jung Cheng

    2014-02-01

    Full Text Available Bovine spongiform encephalopathy (BSE, or mad cow disease, is a fatal neurodegenerative disease that is transmissible to humans and that is currently incurable. BSE is caused by the prion protein (PrP, which adopts two conformers; PrPC is the native innocuous form, which is α-helix rich; and PrPSc is the β-sheet rich misfolded form, which is infectious and forms neurotoxic species. Acidic pH induces the conversion of PrPC to PrPSc. We have performed molecular dynamics simulations of bovine PrP at various pH regimes. An acidic pH environment induced conformational changes that were not observed in neutral pH simulations. Putative misfolded structures, with nonnative β-strands formed in the flexible N-terminal domain, were found in acidic pH simulations. Two distinct pathways were observed for the formation of nonnative β-strands: at low pH, hydrophobic contacts with M129 nucleated the nonnative β-strand; at mid-pH, polar contacts involving Q168 and D178 facilitated the formation of a hairpin at the flexible N-terminus. These mid- and low pH simulations capture the process of nonnative β-strand formation, thereby improving our understanding of how PrPC misfolds into the β-sheet rich PrPSc and how pH factors into the process.

  8. Molecularly imprinted polymer for chlorogenic acid by modified precipitation polymerization and its application to extraction of chlorogenic acid from Eucommia ulmodies leaves.

    Science.gov (United States)

    Miura, Chitose; Li, Hui; Matsunaga, Hisami; Haginaka, Jun

    2015-10-10

    Molecularly imprinted polymers (MIPs) for chlorogenic acid (CGA) were prepared by modified precipitation polymerization using methacrylic acid as a functional monomer, divinylbenzene as a crosslinker and methanol or dimethylsulfoxide as a co-solvent. The prepared MIPs were microspheres with a narrow particle size distribution. Binding experiments and Scatchard analyses revealed that two classes of binding sites, high and low affinity sites, were formed on the MIP. The retention and molecular-recognition properties of the prepared MIP were evaluated using a mixture of water and acetonitrile as a mobile phase in hydrophilic interaction chromatography. With an increase of acetonitrile content, the retention factor of CGA was increased on the MIP. In addition to shape recognition, hydrophilic interactions seem to work for the recognition of CGA on the MIP. The MIP had a specific molecular-recognition ability for CGA, while other related compounds, such as caffeic acid, gallic acid, protocatechuic acid and vanillic acid, could not be recognized by the MIP. Furthermore, the MIP for CGA was successfully applied for extraction of CGA in the leaves of Eucommia ulmodies.

  9. Marsh plant response to metals: Exudation of aliphatic low molecular weight organic acids (ALMWOAs)

    Science.gov (United States)

    Rocha, A. Cristina S.; Almeida, C. Marisa R.; Basto, M. Clara P.; Vasconcelos, M. Teresa S. D.

    2016-03-01

    Metal exposure is known to induce the production and secretion of substances, such as aliphatic low molecular weight organic acids (ALMWOAs), into the rhizosphere by plant roots. Knowledge on this matter is extensive for soil plants but still considerably scarce regarding marsh plants roots adapted to high salinity media. Phragmites australis and Halimione portulacoides, two marsh plants commonly distributed in European estuarine salt marshes, were used to assess the response of roots of both species, in terms of ALMWOAs exudation, to Cu, Ni and Cd exposure (isolated and in mixture since in natural environment, they are exposed to mixture of metals). As previous studies were carried out in unrealistic and synthetic media, here a more natural medium was selected. Therefore, in vitro experiments were carried out, with specimens of both marsh plants, and in freshwater contaminated with two different Cu, Ni and Cd concentrations (individual metal and in mixture). Both marsh plants were capable of liberating ALMWOAs into the surrounding medium. Oxalic, citric and maleic acids were found in P. australis root exudate solutions and oxalic and maleic acids in H. portulacoides root exudate solutions. ALMWOA liberation by both plants was plant species and metal-dependent. For instance, Cu affected the exudation of oxalic acid by H. portulacoides and of oxalic and citric acids by P. australis roots. In contrast, Ni and Cd did not stimulate any specific response. Regarding the combination of all metals, H. portulacoides showed a similar response to that observed for Cu individually. However, in the P. australis case, at high metal concentration mixture, a synergetic effect led to the increase of oxalic acid levels in root exudate solution and to a decrease of citric acid liberation. A correlation between ALMWOAs exudation and metal accumulation could not be established. P. australis and H. portulacoides are considered suitable metal phytoremediators of estuarine impacted areas

  10. Proton transport properties of poly(aspartic acid) with different average molecular weights

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Yuki, E-mail: ynagao@kuchem.kyoto-u.ac.j [Department of Mechanical Systems and Design, Graduate School of Engineering, Tohoku University, 6-6-01 Aoba Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Imai, Yuzuru [Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-cho, Aoba-ku, Sendai 980-8575 (Japan); Matsui, Jun [Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 2-1-1 Katahira, Sendai 980-8577 (Japan); Ogawa, Tomoyuki [Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, 6-6-05 Aoba Aramaki, Aoba-ku, Sendai 980-8579 (Japan); Miyashita, Tokuji [Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 2-1-1 Katahira, Sendai 980-8577 (Japan)

    2011-04-15

    Research highlights: Seven polymers with different average molecular weights were synthesized. The proton conductivity depended on the number-average degree of polymerization. The difference of the proton conductivities was more than one order of magnitude. The number-average molecular weight contributed to the stability of the polymer. - Abstract: We synthesized seven partially protonated poly(aspartic acids)/sodium polyaspartates (P-Asp) with different average molecular weights to study their proton transport properties. The number-average degree of polymerization (DP) for each P-Asp was 30 (P-Asp30), 115 (P-Asp115), 140 (P-Asp140), 160 (P-Asp160), 185 (P-Asp185), 205 (P-Asp205), and 250 (P-Asp250). The proton conductivity depended on the number-average DP. The maximum and minimum proton conductivities under a relative humidity of 70% and 298 K were 1.7 . 10{sup -3} S cm{sup -1} (P-Asp140) and 4.6 . 10{sup -4} S cm{sup -1} (P-Asp250), respectively. Differential thermogravimetric analysis (TG-DTA) was carried out for each P-Asp. The results were classified into two categories. One exhibited two endothermic peaks between t = (270 and 300) {sup o}C, the other exhibited only one peak. The P-Asp group with two endothermic peaks exhibited high proton conductivity. The high proton conductivity is related to the stability of the polymer. The number-average molecular weight also contributed to the stability of the polymer.

  11. Effects of molecular weight and ratio of guluronic acid to mannuronic acid on the antioxidant properties of sodium alginate fractions prepared by radiation-induced degradation

    Energy Technology Data Exchange (ETDEWEB)

    Sen, Murat, E-mail: msen@hacettepe.edu.t [Hacettepe University, Department of Chemistry, Polymer Chemistry Division, Beytepe, 06800 Ankara (Turkey)

    2011-01-15

    In this study, the effects of the molecular weight and ratio of guluronic acid (G) to mannuronic acid (M), G/M, of some sodium alginate (NaAlg) fractions on their antioxidative properties were investigated. Low-molecular-weight-fractions with various G/M were prepared by gamma radiation-induced degradation of NaAlg. Change in their molecular weight was monitored. Antioxidant properties of the fractions with various molecular weight and G/M were evaluated by determining the scavenging ability of 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH{sup {center_dot}}). 50% inhibition concentrations of the 50 kGy-irradiated NaAlgs having molecular weights of 20.5, 17.7, and 16.0 kDa were found to be 11.0, 18.0, and 24.0 mg/ml, respectively, whereas the fractions of the same molecular weight with a lower G/M exhibited a better DPPH{sup {center_dot}}scavenging activity. The results demonstrated that its molecular weight and G/M were important factors in controlling the antioxidant properties of NaAlg.

  12. Branched chain amino acids maintain the molecular weight of poly(γ-glutamic acid) of Bacillus licheniformis ATCC 9945 during the fermentation.

    Science.gov (United States)

    Mitsunaga, Hitoshi; Meissner, Lena; Büchs, Jochen; Fukusaki, Eiichiro

    2016-10-01

    Poly(γ-glutamic acid) mainly produced by Bacillus spp. is an industrially important compound due to several useful features. Among them, molecular weight is an important characteristic affecting on the physical properties such as viscosities and negative charge densities. However, it is difficult to control the molecular size of PGA since it decreases during fermentation. Previous study reported that PGA produced in the media containing different carbon sources such as glucose and glycerol showed differences in molecular weight. Therefore in this study, the effect of carbon source on the PGA molecular weight was examined; with the aim of developing a strategy to maintain the high molecular weight of PGA during fermentation. Our result showed that the weight average molecular weight (Mw) of PGA of Bacillus licheniformis ATCC 9945 cultivated in the media containing PTS-sugars were higher than the medium containing glycerol (non-PTS). The result of metabolome analysis indicated the possibility of CodY (a global regulator protein) activation in the cells cultivated in the media containing PTS-sugars. To mimic this effect, branched-chain amino acids (BCAAs), which are activators of CodY, were added to a medium containing glycerol. As the result, the Mw of PGA in the BCAAs-supplemented media were maintained and high during the early production phase compared to the non BCAAs-supplemented medium. These results indicate that BCAAs can repress the PGA molecular weight reduction during fermentation in B. licheniformis ATCC 9945.

  13. Conformational choreography of a molecular switch region in myelin basic protein--molecular dynamics shows induced folding and secondary structure type conversion upon threonyl phosphorylation in both aqueous and membrane-associated environments.

    Science.gov (United States)

    Polverini, Eugenia; Coll, Eoin P; Tieleman, D Peter; Harauz, George

    2011-03-01

    The 18.5 kDa isoform of myelin basic protein is essential to maintaining the close apposition of myelin membranes in central nervous system myelin, but its intrinsic disorder (conformational dependence on environment), a variety of post-translational modifications, and a diversity of protein ligands (e.g., actin and tubulin) all indicate it to be multifunctional. We have performed molecular dynamics simulations of a conserved central segment of 18.5 kDa myelin basic protein (residues Glu80-Gly103, murine sequence numbering) in aqueous and membrane-associated environments to ascertain the stability of constituent secondary structure elements (α-helix from Glu80-Val91 and extended poly-proline type II from Thr92-Gly103) and the effects of phosphorylation of residues Thr92 and Thr95, individually and together. In aqueous solution, all four forms of the peptide bent in the middle to form a hydrophobic cluster. The phosphorylated variants were stabilized further by electrostatic interactions and formation of β-structures, in agreement with previous spectroscopic data. In simulations performed with the peptide in association with a dimyristoylphosphatidylcholine bilayer, the amphipathic α-helical segment remained stable and membrane-associated, although the degree of penetration was less in the phosphorylated variants, and the tilt of the α-helix with respect to the plane of the membrane also changed significantly with the modifications. The extended segment adjacent to this α-helix represents a putative SH3-ligand and remained exposed to the cytoplasm (and thus accessible to binding partners). The results of these simulations demonstrate how this segment of the protein can act as a molecular switch: an amphipathic α-helical segment of the protein is membrane-associated and presents a subsequent proline-rich segment to the cytoplasm for interaction with other proteins. Phosphorylation of threonyl residues alters the degree of membrane penetration of the

  14. Formation and growth of molecular clusters containing sulfuric acid, water, ammonia, and dimethylamine.

    Science.gov (United States)

    DePalma, Joseph W; Doren, Douglas J; Johnston, Murray V

    2014-07-24

    The structures and thermochemistry of molecular clusters containing sulfuric acid, water, ammonia, and/or dimethylamine ((CH3)2NH or DMA) are explored using a combination of Monte Carlo configuration sampling, semiempirical calculations, and density functional theory (DFT) calculations. Clusters are of the general form [(BH(+))n(HSO4(-))n(H2O)y], where B = NH3 or DMA, 2 ≤ n ≤ 8, and 0 ≤ y ≤ 10. Cluster formulas are written based on the computed structures, which uniformly show proton transfer from each sulfuric acid molecule to a base molecule while the water molecules remain un-ionized. Cluster formation is energetically favorable, owing to strong electrostatic attraction among the ions. Water has a minor effect on the energetics of cluster formation, lowering the free energy of formation by ∼ 10% depending on the cluster size and number of water molecules. Cluster growth (addition of one base molecule and one sulfuric acid molecule to a pre-existing cluster) and base substitution (substituting DMA for ammonia) are also energetically favorable processes for both anhydrous and hydrated clusters. However, the effect of water is different for different bases. Hydrated ammonium bisulfate clusters have a more favorable free energy for growth (i.e., incrementing n with fixed y) than anhydrous clusters, while the reverse is observed for dimethylammonium bisulfate clusters, where the free energy for growth is more favorable for anhydrous clusters. The substitution of DMA for ammonia in bisulfate clusters is favorable but exhibits a complex water dependence. Base substitution in smaller bisulfate clusters is enhanced by the presence of water, while base substitution in larger bisulfate clusters is less favorable for hydrated clusters than that for anhydrous clusters. While DMA substitution can stabilize small clusters containing one or a few sulfuric acid molecules, the free energy advantage of forming amine clusters relative to ammonia clusters becomes less

  15. Voltammetric sensor for vanillylmandelic acid based on molecularly imprinted polymer-modified electrodes.

    Science.gov (United States)

    Blanco-López, M C; Lobo-Castañón, M J; Miranda-Ordieres, A J; Tuñón-Blanco, P

    2003-04-01

    Despite the increasing number of applications of molecularly imprinted polymers (MIPs) in analytical chemistry, the construction of a biomimetic voltammetric sensor remains still challenging. This work investigates the development of a voltammetric sensor for vanillylmandelic acid (VMA) based on acrylic MIP-modified electrodes. Thin layers of MIPs for VMA have been prepared by spin coating the surface of a glassy carbon electrode with the monomers mixture (template, methacrylic acid, a cross-linking agent and solvent), followed by in situ photopolymerisation. After extraction of the template molecule, the peak current recorded with the imprinted sensor after rebinding was linear with VMA concentration in the range 19-350 microg ml(-1), whereas the response of the control electrode is independent of incubation concentration, and was about one-tenth of the value recorded with the imprinted sensor at the maximum concentration tested. Under the conditions used, the sensor is able to differentiate between VMA and other closely structural-related compounds, such as 3-methoxy-4-hydroxyphenylethylene glycol (not detected), or 3,4- and 2,5-dihydroxyphenilacetic acids, which are adsorbed on the bare electrode surface but not at the polymer layer. Homovanillic acid was detected with the imprinted sensors after incubation, indicating that the presence of both methoxy and carboxylic groups in the same position as in VMA is necessary for effective binding in the imprinted sites. Nevertheless, both species can be differentiated by the oxidation potential. It can be concluded that MIP-based voltammetric electrodes are very promising analytical tool for the development of highly selective analytical sensors.

  16. Effect of low molecular weight organic acids on phosphorus adsorption by ferric-alum water treatment residuals.

    Science.gov (United States)

    Wang, Changhui; Wang, Ziyuan; Lin, Lu; Tian, Binghui; Pei, Yuansheng

    2012-02-15

    Effects of low molecular weight organic acids (LMWOAs; citric acid, oxalic acid and tartaric acid) on phosphorus (P) adsorption by ferric-alum water treatment residuals (FARs) were studied. Both batch and column experiments indicated that the effects of LMWOAs on P adsorption were closely related to adsorption time. Initially, all acids presented inhibitory function on P adsorption. The inhibition became weaker with time, eventually promoting P adsorption for citric acid and tartaric acid. In the column experiment with a 61-day duration, high P adsorption rates (>55%) were observed for the test groups containing citric acid and tartaric acid. Interestingly, higher pH likely enhanced P adsorption with the effects of LMWOAs and a distinct relationship between LMWOAs' effects on P adsorption and their concentrations was not observed. Moreover, fractionation of the adsorbed P from the FARs demonstrated that oxalic acid reduced P adsorption capacity, while citric acid and tartaric acid increased. Based on the forms of Fe and Al existing in the FARs and Fourier transform infrared spectroscopy analyses, LMWOAs can promote P adsorption through activating crystalline Fe/Al and preventing crystallization of amorphous Fe/Al to increase P adsorption sites, and can also inhibit P adsorption by competition with adsorption sites.

  17. Carbohydrate-based switch-on molecular sensor for Cu(II) in buffer: absorption and fluorescence study of the selective recognition of Cu(II) ions by galactosyl derivatives in HEPES buffer.

    Science.gov (United States)

    Singhal, Nitin Kumar; Ramanujam, Balaji; Mariappanadar, Vairamani; Rao, Chebrolu Pulla

    2006-08-03

    [graph: see text] 1-(Beta-D-galactopyranosyl-1'-deoxy-1'-iminomethyl)-2-hydroxynaphthalene (L1), possessing an ONO binding core, was found to be selective for Cu2+ ions in N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] buffer, at concentrations < or = 580 ppb, at physiological pH by eliciting switch-on behavior, whereas the other ions, viz., Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Zn2+, and Cd2+, caused no significant change in the fluorescence. Whereas the binding characteristics were ascertained by absorption spectroscopy, the species formed were shown by Q-TOF ES MS.

  18. Molecular dynamics study of solvation effects on acid dissociation in aprotic media

    CERN Document Server

    Laria, D; Estrin, D A; Ciccotti, G; Laria, Daniel; Kapral, Raymond; Estrin, Dario; Ciccotti, Giovanni

    1996-01-01

    Acid ionization in aprotic media is studied using Molecular Dynamics techniques. In particular, models for HCl ionization in acetonitrile and dimethylsulfoxide are investigated. The proton is treated quantum mechanically using Feynman path integral methods and the remaining molecules are treated classically. Quantum effects are shown to be essential for the proper treatment of the ionization. The potential of mean force is computed as a function of the ion pair separation and the local solvent structure is examined. The computed dissociation constants in both solvents differ by several orders of magnitude which are in reasonable agreement with experimental results. Solvent separated ion pairs are found to exist in dimethylsulfoxide but not in acetonitrile. Dissociation mechanisms in small clusters are also investigated. Solvent separated ion pairs persist even in aggregates composed of rather few molecules, for instance, as few as thirty molecules. For smaller clusters or for large ion pair separations cluste...

  19. Extreme genetic code optimality from a molecular dynamics calculation of amino acid polar requirement.

    Science.gov (United States)

    Butler, Thomas; Goldenfeld, Nigel; Mathew, Damien; Luthey-Schulten, Zaida

    2009-06-01

    A molecular dynamics calculation of the amino acid polar requirement is used to score the canonical genetic code. Monte Carlo simulation shows that this computational polar requirement has been optimized by the canonical genetic code, an order of magnitude more than any previously known measure, effectively ruling out a vertical evolution dynamics. The sensitivity of the optimization to the precise metric used in code scoring is consistent with code evolution having proceeded through the communal dynamics of statistical proteins using horizontal gene transfer, as recently proposed. The extreme optimization of the genetic code therefore strongly supports the idea that the genetic code evolved from a communal state of life prior to the last universal common ancestor.

  20. Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids.

    Science.gov (United States)

    Déprez, S; Brezillon, C; Rabot, S; Philippe, C; Mila, I; Lapierre, C; Scalbert, A

    2000-11-01

    Polymeric proanthocyanidins are common constituents of many foods and beverages. Their fate in the human body remains largely unknown. Their metabolism by human colonic microflora incubated in vitro in anoxic conditions has been investigated using nonlabeled and (14)C-labeled purified proanthocyanidin polymers. Polymers were almost totally degraded after 48 h of incubation. Phenylacetic, phenylpropionic and phenylvaleric acids, monohydroxylated mainly in the meta or para position, were identified as metabolites by gas chromatography coupled to mass spectrometry (GC-MS). Yields were similar to those previously reported for flavonoid monomers. These results provide the first evidence of degradation of dietary phenolic polymers into low-molecular-weight aromatic compounds. To understand the nutritional properties of proanthocyanidins, it is therefore essential to consider the biological properties of these metabolites.

  1. Development and characterisation of molecularly imprinted polymers based on methacrylic acid for selective recognition of drugs.

    Science.gov (United States)

    Shi, Xizhi; Wu, Aibo; Qu, Guorun; Li, Rongxiu; Zhang, Dabing

    2007-09-01

    Specific molecularly imprinted polymers (MIPs) for the drug reserpine (RES) using methacrylic acid (MAA) as the functional monomer were developed and characterised for the first time in this study. Evaluation of the various polymers by binding assays indicated that the optimum ratio of functional monomer to template was 4:1. Furthermore, the imprinting effect of the MIPs was assessed by the chromatographic method, which demonstrated that the MIPs had better chromatographic behavior and selectivity than those of the corresponding NIPs. A combination of BET, NMR, UV spectroscopy, and MISPE analyses for investigation of the imprinting and recognition properties revealed that strong specific interactions between the functional monomer and RES in the prepolymerization solutions and the aqueous solutions were probably responsible for RES recognition. The preparation of RES MIPs and elucidation of imprinting and recognition mechanisms may serve as useful references for other drug MIPs.

  2. Comparative Molecular Mechanics and Quantum Mechanics Study of Microhydration of Nucleic Acid Bases

    CERN Document Server

    Lino, J; Deriabina, A; Velasco, M; Poltev, V

    2013-01-01

    DNA is the most important biological molecule, and its hydration contributes essentially to the structure and functions of the double helix. We analyze the microhydration of the individual bases of nucleic acids and their methyl derivatives using methods of molecular mechanics (MM) with the Poltev-Malenkov (PM), AMBER and OPLS force fields, as well as ab initio Quantum Mechanics (QM) calculations at MP2/6-31G(d,p) level of theory. A comparison is made between the calculated interaction energies and the experimental enthalpies of microhydration of bases, obtained from mass spectrometry at low temperatures. Each local water-base interaction energy minimum obtained with MM corresponds to the minimum obtained with QM. General qualitative agreement was observed in the geometrical characteristics of the local minima obtained via the two groups of methods. MM minima correspond to slightly more coplanar structures than those obtained via QM methods, and the absolute MM energy values overestimate corresponding values ...

  3. Way toward "dietary pesticides": molecular investigation of insecticidal action of caffeic acid against Helicoverpa armigera.

    Science.gov (United States)

    Joshi, R S; Wagh, T P; Sharma, N; Mulani, F A; Sonavane, U; Thulasiram, H V; Joshi, R; Gupta, V S; Giri, A P

    2014-11-12

    Bioprospecting of natural molecules is essential to overcome serious environmental issues and pesticide resistance in insects. Here we are reporting insights into insecticidal activity of a plant natural phenol. In silico and in vitro screening of multiple molecules supported by in vivo validations suggested that caffeic acid (CA) is a potent inhibitor of Helicoverpa armigera gut proteases. Protease activity and gene expression were altered in CA-fed larvae. The structure-activity relationship of CA highlighted that all the functional groups are crucial for inhibition of protease activity. Biophysical studies and molecular dynamic simulations revealed that sequential binding of multiple CA molecules induces conformational changes in the protease(s) and thus lead to a significant decline in their activity. CA treatment significantly inhibits the insect's detoxification enzymes, thus intensifying the insecticidal effect. Our findings suggest that CA can be implicated as a potent insecticidal molecule and explored for the development of effective dietary pesticides.

  4. Molecular dynamics simulations of Palmitic acid adsorbed on NaCl

    Science.gov (United States)

    Lovrić, Josip; Brizquez, Stéphane; Duflot, Denis; Monnerville, Maurice; Pouilly, Brigitte; Toubin, Céline

    2015-04-01

    The aerosol and gases effects in the atmosphere play an important role on health, air quality and climate, affecting both political decisions and economic activities around the world [1]. Among the several approaches of studying the origin of these effects, computational modeling is of fundamental importance, providing insights on the elementary chemical processes. Sea salts are the most important aerosol in the troposphere (109T/year) [2]. Our theoretical work consists in modeling a (100) NaCl surface coated with palmitic acid (PA) molecules. Molecular dynamics simulations are carried out with the GROMACS package [3], in the NPT ensemble at different temperatures, different PA coverages and various humidity. We focus on two aspects of the PA organization at the salt surface: the first one is related to transition in molecular orientation of the adsorbate as a function of PA coverage. The second one implies the effect of humidity, by adding water molecules, on the organization of the fatty acid at the salt surface, and especially on the occurrence of PA isolated islands as observed in the experiments [4]. For high humidity conditions, PA are removed from the salt surface and form islands on top of the water. This effect is enhanced when temperature increases. Acknowledgments: this research has been supported by the CaPPA project (Chemical and Physical Properties of the Atmosphere), funded by the French National Research Agency (ANR) through the PIA (Programme d'Investissement d'Avenir) under contract ANR-10-LABX-005. [1] O. Boucher et al, 5th Assessment Report IPCC, (2013) [2] B. J. Finlayson-Pitts, Chem. Rev.103, 4801-4822 (2003) [3] http://www.gromacs.org/ [4] S. Sobanska et al, private communication

  5. A Portable, Pressure Driven, Room Temperature Nucleic Acid Extraction and Storage System for Point of Care Molecular Diagnostics

    OpenAIRE

    Byrnes, Samantha; Fan, Andy; Trueb, Jacob; Jareczek, Francis; Mazzochette, Mark; Sharon, Andre; Sauer-Budge, Alexis F.; Klapperich, Catherine M.

    2013-01-01

    Many new and exciting portable HIV viral load testing technologies are emerging for use in global medicine. While the potential to provide fast, isothermal, and quantitative molecular diagnostic information to clinicians in the field will soon be a reality, many of these technologies lack a robust front end for sample clean up and nucleic acid preparation. Such a technology would enable many different downstream molecular assays. Here, we present a portable system for centrifuge-free room tem...

  6. Nucleotide binding switches the information flow in ras GTPases.

    Science.gov (United States)

    Raimondi, Francesco; Portella, Guillem; Orozco, Modesto; Fanelli, Francesca

    2011-03-01

    The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP) and S(GTP), respectively). For all the considered systems, the intrinsic flexibility of S(GDP) was higher than that of S(GTP), suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP) of Gα(t), is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP.

  7. Nucleotide binding switches the information flow in ras GTPases.

    Directory of Open Access Journals (Sweden)

    Francesco Raimondi

    2011-03-01

    Full Text Available The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP and S(GTP, respectively. For all the considered systems, the intrinsic flexibility of S(GDP was higher than that of S(GTP, suggesting that Guanine Exchange Factor (GEF recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP of Gα(t, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins, compared to GTP.

  8. Molecular recognition of amino acids with some fluorescent ditopic pyrylium- and pyridinium-based crown ether receptors

    Science.gov (United States)

    Moghimi, A.; Maddah, B.; Yari, A.; Shamsipur, M.; Boostani, M.; Fall Rastegar, M.; Ghaderi, A. R.

    2005-10-01

    The molecular recognition of L-amino acids such as asparagine, glutamine, lysine and arginine with some crownpyryliums, CP's, and a crownpyridinium compound, as receptors, were examined in methanol. 1H NMR spectroscopy was used to examine the structural stability of the receptors in the presence of the amino acids. The fluorimetric titration of the receptors by specified amino acids, other than arginine, was followed within a few minutes and the stoichiometry and stability of the resulting amino acid complexes were evaluated. The data analysis clearly demonstrated the critical role of the terminal amino group to carboxylic acid distance of amino acids for their proper fixation on the receptor molecules. Ion pairing for the two oppositely charged carboxylate anion and pyrylium (or pyridinium) cation, as well as the hydrogen bonding between crown ethers' oxygens and ammonium hydrogens are expected as the main interaction sources in the host-guest complexations.

  9. 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.

  10. Gate-controlled conductance switching in DNA

    Science.gov (United States)

    Xiang, Limin; Palma, Julio L.; Li, Yueqi; Mujica, Vladimiro; Ratner, Mark A.; Tao, Nongjian

    2017-02-01

    Extensive evidence has shown that long-range charge transport can occur along double helical DNA, but active control (switching) of single-DNA conductance with an external field has not yet been demonstrated. Here we demonstrate conductance switching in DNA by replacing a DNA base with a redox group. By applying an electrochemical (EC) gate voltage to the molecule, we switch the redox group between the oxidized and reduced states, leading to reversible switching of the DNA conductance between two discrete levels. We further show that monitoring the individual conductance switching allows the study of redox reaction kinetics and thermodynamics at single molecular level using DNA as a probe. Our theoretical calculations suggest that the switch is due to the change in the energy level alignment of the redox states relative to the Fermi level of the electrodes.

  11. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events.

    Science.gov (United States)

    Mozaffarian, Dariush; Wu, Jason H Y

    2011-11-08

    We reviewed available evidence for cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) consumption, focusing on long chain (seafood) n-3 PUFA, including their principal dietary sources, effects on physiological risk factors, potential molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and existing dietary guidelines. Major dietary sources include fatty fish and other seafood. n-3 PUFA consumption lowers plasma triglycerides, resting heart rate, and blood pressure and might also improve myocardial filling and efficiency, lower inflammation, and improve vascular function. Experimental studies demonstrate direct anti-arrhythmic effects, which have been challenging to document in humans. n-3 PUFA affect a myriad of molecular pathways, including alteration of physical and chemical properties of cellular membranes, direct interaction with and modulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in eicosanoid profiles, and conversion of n-3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n-3 PUFA seem most consistent for coronary heart disease mortality and sudden cardiac death. Potential effects on other cardiovascular outcomes are less-well-established, including conflicting evidence from observational studies and/or randomized trials for effects on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, recurrent ventricular arrhythmias, and heart failure. Research gaps include the relative importance of different physiological and molecular mechanisms, precise dose-responses of physiological and clinical effects, whether fish oil provides all the benefits of fish consumption, and clinical effects of plant-derived n-3 PUFA. Overall, current data provide strong concordant evidence that n-3 PUFA are bioactive compounds that reduce risk of cardiac

  12. Molecular composition of dicarboxylic acids, ketocarboxylic acids, α-dicarbonyls and fatty acids in atmospheric aerosols from Tanzania, East Africa during wet and dry seasons

    Directory of Open Access Journals (Sweden)

    S. L. Mkoma

    2013-02-01

    Full Text Available Atmospheric aerosol samples of PM2.5 and PM10 were collected during the wet and dry seasons in 2011 from a rural site in Tanzania and analysed for water-soluble dicarboxylic acids, ketocarboxylic acids, α-dicarbonyls, and fatty acids using a gas chromatography/flame ionization detector (GC/FID and GC/mass spectrometry. Here we report the molecular composition and sources of diacids and related compounds for wet and dry seasons. Oxalic acid (C2 was found as the most abundant diacid species followed by succinic and/or malonic acids whereas glyoxylic acid and glyoxal were the dominant ketoacid and α-dicarbonyl, respectively in both seasons in PM2.5 and PM10. Mean concentration of C2 in PM2.5 (121 ± 47 ng m−3 was lower in wet season than dry season (258 ± 69 ng m−3. Similarly, PM10 samples showed lower concentration of C2 (169 ± 42 ng m−3 in wet season than dry season (292 ± 165 ng m−3. Relative abundances of C2 in total diacids were 65% and 67% in PM2.5 and 65% and 64% in PM10 in the wet and dry seasons, respectively. Total concentrations of diacids (289–362 ng m−3, ketoacids (37.8–53.7 ng m−3, and α-dicarbonyls (5.7–7.8 ng m−3 in Tanzania are higher than those reported at a rural background site in Nylsvley (South Africa but comparable or lower than those reported from sites in Asia and Europe. Diacids and ketoacids were found to be present mainly in PM2.5 in both seasons (total α-dicarbonyls in the dry season, suggesting a production of organic acids from pyrogenic sources and photochemical oxidations. Averaged contributions of total diacids to aerosol total carbon were 1.4% in PM2.5 and 2.1% in PM10 during wet season and 3.3% in PM2.5 and 3.9% in PM10 during

  13. The Interaction between an Acidic Transcriptional Activator and Its Inhibitor: The Molecular Basis of Ga14p Recognition by Ga180p

    Energy Technology Data Exchange (ETDEWEB)

    Thoden, James B.; Ryan, Louise A.; Reece, Richard J.; Holden, Hazel M. (Manchester); (UW)

    2009-02-16

    The GAL genes, which encode the enzymes required for normal galactose metabolism in yeast, are transcriptionally regulated by three proteins: Gal4p, an activator; Gal80p, an inhibitor; and Gal3p, a galactose sensor. These proteins control the switch between inert and active gene expression. The transcriptional activation function of Gal4p is rendered inactive in the presence of Gal80p. Here we present the three-dimensional structure of a complex between the acidic activation domain of Gal4p and Gal80p. The transactivation domain initiates with an extended region of polypeptide chain followed by two turns of an amphipathic alpha-helix. It fits into and across a deep cleft within the Gal80p dimer with the protein-protein interface defined primarily by hydrophobic interactions. A disordered loop in the apo-Gal80p structure (Asp-309 to Ser-316) becomes well-defined upon binding of the transactivation domain. This investigation provides a new molecular scaffold for understanding previous biochemical and genetic studies.

  14. Molecular assembly, interfacial rheology and foaming properties of oligofructose fatty acid esters.

    Science.gov (United States)

    van Kempen, Silvia E H J; Schols, Henk A; van der Linden, Erik; Sagis, Leonard M C

    2014-01-01

    Two major types of food-grade surfactants used to stabilize foams are proteins and low molecular weight (LMW) surfactants. Proteins lower the surface tension of interfaces and tend to unfold and stabilize the interface by the formation of a visco-elastic network, which leads to high surface moduli. In contrast, LMW surfactants lower the surface tension more than proteins, but do not form interfaces with a high modulus. Instead, they stabilize the interface through the Gibbs-Marangoni mechanism that relies on rapid diffusion of surfactants, when surface tension gradients develop as a result of deformations of the interface. A molecule than can lower the surface tension considerably, like a LMW surfactant, but also provide the interface with a high modulus, like a protein, would be an excellent foam stabilizer. In this article we will discuss molecules with those properties: oligofructose fatty acid esters, both in pure and mixed systems. First, we will address the synthesis and structural characterization of the esters. Next, we will address self-assembly and rheological properties of air/water interfaces stabilized by the esters. Subsequently, this paper will deal with mixed systems of mono-esters with either di-esters and lauric acid, or proteins. Then, the foaming functionality of the esters is discussed.

  15. Folic acid: nutritional biochemistry, molecular biology, and role in disease processes.

    Science.gov (United States)

    Lucock, M

    2000-01-01

    This paper reviews the chemistry, metabolism, and molecular biology of folic acid, with a particular emphasis on how it is, or may be, involved in many disease processes. Folic acid prevents neural tube defects like spina bifida, while its ability to lower homocysteine suggests it might have a positive influence on cardiovascular disease. A role for this B vitamin in maintaining good health may, in fact, extend beyond these clinical conditions to encompass other birth defects, several types of cancer, dementia, affective disorders, Down's syndrome, and serious conditions affecting pregnancy outcome. The effect of folate in these conditions can be explained largely within the context of folate-dependent pathways leading to methionine and nucleotide biosynthesis, and genetic variability resulting from a number of common polymorphisms of folate-dependent enzymes involved in the homocysteine remethylation cycle. Allelic variants of folate genes that have a high frequency in the population, and that may play a role in disease formation include 677C --> T-MTHFR, 1298A --> C-MTHFR, 2756A --> G-MetSyn, and 66A --> G-MSR. Future work will probably uncover further polymorphisms of folate metabolism, and lead to a wider understanding of the interaction between this essential nutrient and the many genes which underpin its enzymatic utilization in a plethora of critical biosynthetic reactions, and which, under adverse nutritional conditions, may promote disease.

  16. Revealing the Molecular Structural Transformation of Hardwood and Softwood in Dilute Acid Flowthrough Pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Libing; Pu, Yunqiao; Cort, John R.; Ragauskas, Arthur J.; Yang, Bin

    2016-12-05

    To better understand the intrinsic recalcitrance of lignocellulosic biomass, the main hurdle to its efficient deconstruction, the effects of dilute acid flowthrough pretreatment on the dissolution chemistry of hemicellulose, cellulose, and lignin for both hardwood (e.g. poplar wood) and softwood (e.g. lodgepole pine wood) were investigated at temperatures of 200 °C to 270 °C and a flow rate of 25 mL/minute with 0.05% (w/w) H2SO4. Results suggested that the softwood cellulose was more readily to be degraded into monomeric sugars than that of hardwood under same pretreatment conditions. However, while the hardwood lignin was completely removed into hydrolysate, ~30% of the softwood lignin remained as solid residues under identical conditions, which was plausibly caused by vigorous C5-active recondensation reactions (C-C5). Unique molecular structural features that pronounced the specific recalcitrance of hardwood and softwood to dilute acid pretreatment were identified for the first time in this study, providing important insights to establish the effective biomass pretreatment.

  17. Impact of low molecular weight organic acids (LMWOAs) on biochar micropores and sorption properties for sulfamethoxazole.

    Science.gov (United States)

    Sun, Binbin; Lian, Fei; Bao, Qiongli; Liu, Zhongqi; Song, Zhengguo; Zhu, Lingyan

    2016-07-01

    The interaction between biochar (BC) and antibiotics with the presence of low molecular weight organic acids (LMWOAs) is largely unknown, although it is crucial for understanding the role of BC in reducing the bioavailability of antibiotics in rhizosphere. The impacts of two typical LMWOAs (citric and malic acids) on sorption of sulfamethoxazole (SMX) by crop-straw BCs produced at 300 °C (BCs300) and 600 °C (BCs600), respectively, were examined. The sorption of SMX on BCs increased more than 5 times with the concentration of LMWOAs increasing from 0 to 100 mmol/L, which was mainly attributed to the elevated microporosity of BCs (measured by CO2) after treated by LMWOAs. The pore development of BCs was mainly derived from the release of dissolved organic residues from BC by LMWOA washing. For H2O2-oxidized BCs, however, LMWOAs had little effect on SMX sorption by BCs300 but greatly increased that by BCs600, which can be explained by the distinct sorption mechanisms of SMX on BCs300 and BCs600. These results indicate that the impact of LMWOAs on SMX sorption is highly dependent on the properties of BCs and LMWOAs, as well as their interaction mechanisms.

  18. 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.

  19. Isolation, enumeration, molecular identification and probiotic potential evaluation of lactic acid bacteria isolated from sheep milk

    Directory of Open Access Journals (Sweden)

    L.B. Acurcio

    2014-06-01

    Full Text Available Lactic acid bacteria species were molecularly identified in milk from Lacaune, Santa Inês and crossbred sheep breeds and their in vitro probiotic potential was evaluated. The species identified were Enterococcus faecium (56.25%, E. durans (31.25% and E. casseliflavus (12.5%. No other lactic acid bacteria species, such as lactobacilli, was identified. Most of the isolated enterococci were resistant to gastric pH (2.0 and to 0.3% oxgall. All tested enterococci were resistant to ceftazidime, oxacillin and streptomycin and sensible to clindamycin, erythromycin and penicillin. The resistance to ciprofloxacin, gentamicin, tetracycline and vancomycin varied among tested species. All tested enterococci strongly inhibited (P<0.05 Escherichia coli and Listeria monocytogenes, moderately inhibited E. faecalis and Staphylococcus aureus and did not inhibit Pseudomonas aeruginosa, Salmonella enterica var. Typhimurium and also one E. durans sample isolated from sheep milk. Four samples of E. faecium, one of E. durans and one of E. casseliflavus presented the best probiotic potential.

  20. Molecular mechanisms of the coordination between astaxanthin and fatty acid biosynthesis in Haematococcus pluvialis (Chlorophyceae).

    Science.gov (United States)

    Chen, Guanqun; Wang, Baobei; Han, Danxiang; Sommerfeld, Milton; Lu, Yinghua; Chen, Feng; Hu, Qiang

    2015-01-01

    Astaxanthin, a red ketocarotenoid with strong antioxidant activity and high commercial value, possesses important physiological functions in astaxanthin-producing microalgae. The green microalga Haematococcus pluvialis accumulates up to 4% fatty acid-esterified astaxanthin (by dry weight), and is used as a model species for exploring astaxanthin biosynthesis in unicellular photosynthetic organisms. Although coordination of astaxanthin and fatty acid biosynthesis in a stoichiometric fashion was observed in H. pluvialis, the interaction mechanism is unclear. Here we dissected the molecular mechanism underlying coordination between the two pathways in H. pluvialis. Our results eliminated possible coordination of this inter-dependence at the transcriptional level, and showed that this interaction was feedback-coordinated at the metabolite level. In vivo and in vitro experiments indicated that astaxanthin esterification drove the formation and accumulation of astaxanthin. We further showed that both free astaxanthin biosynthesis and esterification occurred in the endoplasmic reticulum, and that certain diacylglycerol acyltransferases may be the candidate enzymes catalyzing astaxanthin esterification. A model of astaxanthin biosynthesis in H. pluvialis was subsequently proposed. These findings provide further insights into astaxanthin biosynthesis in H. pluvialis.

  1. A classical reactive potential for molecular clusters of sulphuric acid and water

    Energy Technology Data Exchange (ETDEWEB)

    Stinson, Jake L.; Kathmann, Shawn M.; Ford, Ian J.

    2015-10-12

    We present a two state empirical valence bond (EVB) potential describing interactions between sulphuric acid and water molecules and designed to model proton transfer between them within a classical dynamical framework. The potential has been developed in order to study the properties of molecular clusters of these species, which are thought to be relevant to atmospheric aerosol nucleation. The particle swarm optimisation method has been used to fit the parameters of the EVB model to density functional theory (DFT) calculations. Features of the parametrised model and DFT data are compared and found to be in satisfactory agreement. In particular, it is found that a single sulphuric acid molecule will donate a proton when clustered with four water molecules at 300 K and that this threshold is temperature dependent. SMK was supported in part by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences; JLS and IJF were supported by the IMPACT scheme at University College London (UCL). We acknowledge the UCL Legion High Performance Computing Facility, and associated support services together with the resources of the National Energy Research Scientific Computing Center (NERSC), which is supported by the U.S. Department of Energy under Contract No. DE-AC02- 05CH11231. JLS thanks Dr. Gregory Schenter, Dr. Theo Kurtén and Prof. Hanna Vehkamäki for important guidance and discussions.

  2. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis.

    Science.gov (United States)

    Borow, Kenneth M; Nelson, John R; Mason, R Preston

    2015-09-01

    Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk.

  3. Enhanced conformational sampling of nucleic acids by a new Hamiltonian replica exchange molecular dynamics approach.

    Science.gov (United States)

    Curuksu, Jeremy; Zacharias, Martin

    2009-03-14

    Although molecular dynamics (MD) simulations have been applied frequently to study flexible molecules, the sampling of conformational states separated by barriers is limited due to currently possible simulation time scales. Replica-exchange (Rex)MD simulations that allow for exchanges between simulations performed at different temperatures (T-RexMD) can achieve improved conformational sampling. However, in the case of T-RexMD the computational demand grows rapidly with system size. A Hamiltonian RexMD method that specifically enhances coupled dihedral angle transitions has been developed. The method employs added biasing potentials as replica parameters that destabilize available dihedral substates and was applied to study coupled dihedral transitions in nucleic acid molecules. The biasing potentials can be either fixed at the beginning of the simulation or optimized during an equilibration phase. The method was extensively tested and compared to conventional MD simulations and T-RexMD simulations on an adenine dinucleotide system and on a DNA abasic site. The biasing potential RexMD method showed improved sampling of conformational substates compared to conventional MD simulations similar to T-RexMD simulations but at a fraction of the computational demand. It is well suited to study systematically the fine structure and dynamics of large nucleic acids under realistic conditions including explicit solvent and ions and can be easily extended to other types of molecules.

  4. Molecular evolution of the nicotinic acid requirement within the Shigella/EIEC pathotype.

    Science.gov (United States)

    Di Martino, Maria Letizia; Fioravanti, Rosa; Barbabella, Giada; Prosseda, Gianni; Colonna, Bianca; Casalino, Mariassunta

    2013-12-01

    Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor in several anabolic and catabolic reactions. NAD derives from quinolinic acid (QUIN) which in Escherichia coli is obtained through a pyridine salvage pathway or a de novo synthesis pathway. In the latter case, two enzymes, L-aspartate oxidase (NadB) and quinolinate synthase (NadA), are required for the synthesis of QUIN. In contrast to its E. coli ancestor, Shigella spp., the causative agent of bacillary dissentery, lacks the de novo pathway and strictly requires nicotinic acid for growth (Nic⁻ phenotype). This phenotype depends on the silencing of the nadB and nadA genes and its pathoadaptive nature is suggested by the observation that QUIN attenuates the Shigella invasive process. Shigella shares the pathogenicity mechanism with enteronvasive E. coli (EIEC), a group of pathogenic E. coli. On the basis of this similarity EIEC and Shigella have been grouped into a single E. coli pathotype. However EIEC strains do not constitute a homogeneous group and do not possess the complete set of characters that define Shigella strains. In this work we have analysed thirteen EIEC strains belonging to different serotypes and originating from different geographic areas. We show that, in contrast to Shigella, only some EIEC strains require nicotinic acid for growth in minimal medium. Moreover, by studying the emergence of the Nic⁻ phenotype in all serotypes of S. flexneri, as well as in S. sonnei and S. dysenteriae, we describe which molecular rearrangements occurred and which mutations are responsible for the inactivation of the nadA and nadB genes. Our data confirm that the genome of Shigella is extremely dynamic and support the hypothesis that EIEC might reflect an earlier stage of the pathoadaptation process undergone by Shigella.

  5. Enhanced anion electroadsorption into carbon molecular sieve electrodes in acidic media.

    Science.gov (United States)

    Eliad, Linoam; Salitra, Gregory; Pollak, Elad; Soffer, Abraham; Aurbach, Doron

    2005-11-08

    We previously showed that, for neutral electrolytes of small cations and relatively larger anions, it is possible to design certain pore sizes in active carbons that are large enough to electroadsorb cations but too small to allow anion electroadsorption. This situation leads to an electrical double-layer (EDL) capacitance that is significant only at potentials that are negative to the potential of zero charge (PZC); hence, much smaller capacitance is measured at potentials positive to the PZC. It was found that when the electrolyte is a strong acid (e.g., H(2)SO(4), HCl), a considerable capacitance is observed at positive potentials, even when the average pore size is too small to allow the insertion of large anions in neutral electrolyte solutions. This effect disappears when the pore size becomes considerably larger than the size of the ions. In this case, the EDL capacitance at positive potentials for both neutral and acidic solutions is comparable. The following four-step mechanism was found to comply best with the experimental data: (1) By acid catalysis, the protons form carbonium species within the conjugated carbon network. (2) The anions react with the carbonium ions, providing uncharged species in an activated state, which are chemibound as surface groups to the walls of the pores. (3) Because these surface groups are effectively much smaller in size than are the charged ions, they can migrate by chemical bond exchange within the carbon skeleton via constrictions (known to exist in microporous and molecular sieving carbons), which are too narrow to accommodate hydrated charged species. (4) Upon reaching wider spaces, the uncharged species are reionized and solvated by water molecules, which can fill small pores. The justification for the above mechanism is thoroughly discussed and demonstrated by the experimental results.

  6. Estimating successive pKa values of polyprotic acids from ab initio molecular dynamics using metadynamics: the dissociation of phthalic acid and its isomers.

    Science.gov (United States)

    Tummanapelli, Anil Kumar; Vasudevan, Sukumaran

    2015-03-01

    Estimation of the dissociation constant, or pKa, of weak acids continues to be a central goal in theoretical chemistry. Here we show that ab initio Car-Parrinello molecular dynamics simulations in conjunction with metadynamics calculations of the free energy profile of the dissociation reaction can provide reasonable estimates of the successive pKa values of polyprotic acids. We use the distance-dependent coordination number of the protons bound to the hydroxyl oxygen of the carboxylic group as the collective variable to explore the free energy profile of the dissociation process. Water molecules, sufficient to complete three hydration shells surrounding the acid molecule, were included explicitly in the computation procedure. Two distinct minima corresponding to the dissociated and un-dissociated states of the acid are observed and the difference in their free energy values provides the estimate for pKa, the acid dissociation constant. We show that the method predicts the pKa value of benzoic acid in good agreement with experiment and then show using phthalic acid (benzene dicarboxylic acid) as a test system that both the first and second pKa values as well, as the subtle difference in their values for different isomers can be predicted in reasonable agreement with experimental data.

  7. Molecular characterization of the level of sialic acids N-acetylneuraminic acid, N-glycolylneuraminic acid, and ketodeoxynonulosonic acid in porcine milk during lactation.

    Science.gov (United States)

    Jahan, M; Wynn, P C; Wang, B

    2016-10-01

    Sialic acids (Sia) are key monosaccharide constituents of sialylated glycoproteins (Sia-GP), human sialylated milk oligosaccharide (Sia-MOS), and gangliosides. Human milk sialylated glycoconjugates (Sia-GC) are bioactive compounds known to act as prebiotics and promote neurodevelopment, immune function, and gut maturation in newborns. Only limited data are available on the Sia content of porcine milk. The objective of this study was to quantitatively determine the total level of Sia N-acetylneuraminic acid (Neu5Ac), N-glycolylneuraminic acid (Neu5Gc), and ketodeoxynonulosonic acid (KDN) in porcine milk and to compare these levels in gilt and sow milk during lactation. Milk from 8 gilts and 22 sows was collected at 3 stages of lactation (colostrum, transition, and mature milk). Standard and experimental samples were derivatized using 1,2-diamino-4,5-methylenedioxy-benzene and analyzed by ultra-high-performance liquid chromatography using a fluorescence detector. The following new findings are reported: (1) Gilt and sow milk contained significant levels of total Sia, with the highest concentration in colostrum (1,238.5 mg/L), followed by transition milk (778.3 mg/L) and mature milk (347.2 mg/L); (2) during lactation, the majority of Sia was conjugated to Sia-GP (41-46%), followed by Sia-MOS (31-42%) and a smaller proportion in gangliosides (12-28%); (3) Neu5Ac was the major form of Sia (93-96%), followed by Neu5Gc (3-6%) and then KDN (1-2%), irrespective of milk fraction or stage of lactation; (4) the concentration of Sia in Sia-GP and Sia-MOS showed a significant decline during lactation, but the level of ganglioside Sia remained relatively constant; (5) mature gilt milk contained a significantly higher concentration of Sia-GP than sow milk. The high concentration of total Sia in porcine milk suggests that Sia-GC are important nutrients that contribute to the optimization of neurodevelopment, immune function, and growth and development in piglets. These findings

  8. Effects of cross-linking molecular weights in a hyaluronic acid-poly(ethylene oxide) hydrogel network on its properties

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Insup [Department of Chemical Engineering, Seoul National University of Technology, 172 Gongnung-dong, Nowon-gu, Seoul 139-743 (Korea, Republic of); Kim, Gun-Woo [Department of Chemical Engineering, Seoul National University of Technology, 172 Gongnung-dong, Nowon-gu, Seoul 139-743 (Korea, Republic of); Choi, Yoon-Jeong [Department of Chemical Engineering, Seoul National University of Technology, 172 Gongnung-dong, Nowon-gu, Seoul 139-743 (Korea, Republic of); Kim, Mi-Sook [Department of Chemical Engineering, Seoul National University of Technology, 172 Gongnung-dong, Nowon-gu, Seoul 139-743 (Korea, Republic of); Park, Yongdoo [Korea Artificial Organ Center, Korea University, Seoul 136-705 (Korea, Republic of); Lee, Kyu-Back [Korea Artificial Organ Center, Korea University, Seoul 136-705 (Korea, Republic of); Kim, In-Sook [Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Hwang, Soon-Jung [Dental Research Institute, Seoul National University, Seoul 110-749 (Korea, Republic of); Tae, Giyoong [Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

    2006-09-15

    We examined the effects of cross-linking molecular weights on the properties of a hyaluronic acid (HA)-poly(ethylene oxide) (PEO) hydrogel. Swelling behaviors, mechanical strength and rheological behaviors of the HA-PEO hydrogel were evaluated by employing different cross-linking molecular weights (100 kDa and 1.63 mDa) of the HAs in the hydrogel networks. The low molecular weight of HA was obtained in advance by treating high molecular weight HA with a hydrogen chloride solution. Methacrylation of HA was obtained by grafting aminopropylmethacrylate to its caroboxylic acid functional groups. While reduction of the HA molecular weights was confirmed by gel permeation chromatography, the degree of methacrylate grafting to the HA was measured by {sup 1}H-nuclear magnetic resonance. Synthesis of the HA-PEO hydrogel was successfully achieved via the Michael-type addition reaction between the methacrylate arm groups in the HA and the six thiol groups in PEO. The hydrogel formation was not dependent upon the HA molecular weights and its gelation behaviors were markedly different. Compared to the properties of the high molecular weight HA-based PEO one, the low molecular weight HA-based hydrogel induced quicker hydrogelation, as observed from the behaviors of the elastic and viscous modulus. Furthermore, the low molecular weight HA-based hydrogel demonstrated stronger mechanical properties as measured with a texture analyzer, lower water absorption as measured with a microbalance and smaller pore sizes on its surface and cross section as observed with scanning electron microscopy. The information about the effects of the cross-linking molecular weights of the gel network on the properties of the HA-based PEO hydrogel may lead to better design of hydrogels, especially in tissue engineering applications.

  9. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    OpenAIRE

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-01-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-bindin...

  10. Switched on!

    CERN Multimedia

    2008-01-01

    Like a star arriving on stage, impatiently followed by each member of CERN personnel and by millions of eyes around the world, the first beam of protons has circulated in the LHC. After years in the making and months of increasing anticipation, today the work of hundreds of people has borne fruit. WELL DONE to all! Successfully steered around the 27 kilometres of the world’s most powerful particle accelerator at 10:28 this morning, this first beam of protons circulating in the ring marks a key moment in the transition from over two decades of preparation to a new era of scientific discovery. "It’s a fantastic moment," said the LHC project leader Lyn Evans, "we can now look forward to a new era of understanding about the origins and evolution of the universe". Starting up a major new particle accelerator takes much more than flipping a switch. Thousands of individual elements have to work in harmony, timings have to be synchronize...

  11. A rapid method for the determination of perfluoroalkyl substances including structural isomers of perfluorooctane sulfonic acid in human serum using 96-well plates and column-switching ultra-high performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Salihovic, Samira; Kärrman, Anna; Lindström, Gunilla; Lind, P Monica; Lind, Lars; van Bavel, Bert

    2013-08-30

    To facilitate high-throughput analysis suitable for large epidemiological studies we developed an automated column-switching ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for determination of perfluorocarboxylic acids (PFCAs; C5, C6, C7, C8, C9, C10, C11, C12, and C13), perfluoroalkyl sulfonic acids (PFSAs; C4, C6, C8, and C10), perfluorooctane sulfonamide (PFOSA), and five groups of structural perfluorooctane sulfonic acid (PFOS) isomers in human serum or plasma. The analytical procedure involves rapid protein precipitation using 96-well plates followed by an automated sample clean-up using an on-line trap column removing many potentially interfering sample components while through the mobile phase gradient the target analytes are eluted onto the analytical column for further separation and subsequent mass detection. The method was linear (R(2)method detection limits ranging between 0.01 and 0.17ngmL(-1) depending on the analyte. The developed method was precise, with repeatability (n=7) and reproducibility (n=103) coefficients of variation between 2% and 20% for most compounds including PFOS (2% and 8%) and its structural isomers (2-6% and 4-8%). The method was in conformity with a standard reference material. The column-switching HPLC-MS/MS method has been successfully applied for the determination of perfluoroalkyl substances including structural PFOS isomers in human plasma from an epidemiological study.

  12. Molecular analysis of benthic biofilms from acidic coal mine drainage, Pennsylvania, USA

    Science.gov (United States)

    Mills, D. B.; Jones, D. S.; Burgos, W. D.; Macalady, J. L.

    2010-12-01

    Acid mine drainage (AMD) is a common environmental problem in Pennsylvania that results from the oxidation of sulfide minerals exposed at abandoned coal mines. In these systems, acidophilic microorganisms catalyze the oxidation of ferrous (Fe2+) to ferric iron (Fe3+), which precipitates as iron-hydroxide minerals. To develop and improve low-pH bioremediation strategies, characterization of the microbiology of AMD systems is essential. An acidic (pH 2-4) AMD spring known as ‘Lower Red Eyes’ in Gallitzan State Forest, PA, is fed by anoxic groundwater with ferrous iron concentrations above 550 mg/L. More than half of the total iron is removed after the springwater flows downstream over 80 m of stagnant pools and iron-oxide terraces. We used fluorescence in situ hybridization (FISH) and 16S rDNA cloning to characterize the microbial communities from orange sediments and green benthic biofilms. 16S rDNA sequences were extracted from a green biofilm found in a pH 3.5 pool 10 m downstream of the emergence. Based on chloroplast 16S rDNA sequences and morphological characteristics, we found that Euglena mutabilis was the dominant eukaryotic organism from this location. Euglena mutabilis is a photosynthetic protozoan common in acidic and heavy metal affected environments, and likely contributes to the precipitation of iron oxides through the production of molecular oxygen. Bacterial 16S rDNA sequences were cloned from iron-oxide sediments with orange cauliflower morphology 27 m downstream from the spring emergence. More than 60% of bacterial sequences retrieved from the orange sediment sample are related to the iron-oxidizing Betaproteobacterium Ferrovum myxofaciens. Other bacterial sequences include relatives of iron-oxidizing genera in the Gammaproteobacteria, Betaproteobacteria, and Actinobacteria. FISH analyses show that Betaproteobacteria-dominated communities are associated with Euglena in multiple upstream locations where pH is above 3.0. Using light microscopy

  13. High yield stress associated with capillary attraction between alumina surfaces in the presence of low molecular weight dicarboxylic acids.

    Science.gov (United States)

    Teh, E-Jen; Leong, Yee-Kwong; Liu, Yinong; Craig, Vincent S J; Walsh, Rick B; Howard, Shaun C

    2010-03-02

    Adsorbed low molecular weight charged molecules are known to give rise to a range of surface forces that affect the rheological behavior of oxide dispersions. The behavior of dicarboxylic acid bolaform compounds in alumina slurry was investigated to determine the influence of the molecular structure on the nanoscale interactions between alumina surfaces and on the macroscopic properties of the slurry. The surface forces in dispersions and between a single particle and a flat surface were characterized by yield stress and atomic force microscopy (AFM) respectively. Absorbed muconic acid increased the yield stress of the alumina system, which indicates an additional attractive interaction between the particles. Adsorbed trans,trans (TT) muconic acid resulted in a much higher yield stress than cis,cis (CC) muconic acid. Force-distance data obtained via AFM displayed features indicating the presence of a capillary force attraction at low pH between the alumina surfaces when TT and CC muconic acids were adsorbed at high surface coverage. This force appeared to explain the high yield stress at low pH (pH 3.6), but the absence of a net attractive force at higher pH (pH 5) did not correlate with the yield stress results. At low pH, the muconic acids become less soluble in the confined space between the interacting surfaces resulting in the formation of an "oily" muconic acid phase located between the interacting surfaces. The nanosized "oil" phase is the source of the capillary force.

  14. Styrene oligomerization as a molecular probe reaction for zeolite acidity: a UV-Vis spectroscopy and DFT study

    NARCIS (Netherlands)

    Buurmans, I.L.C.; Pidko, E.A.; de Groot, J.M.; Stavitski, I.; van Santen, R.A.; Weckhuysen, B.M.

    2013-01-01

    A series of H-ZSM-5 crystallites with different framework Si/Al ratios was studied by analyzing the kinetics and reaction mechanism of the oligomerization of 4-fluorostyrene as molecular probe reaction for Brønsted acidity. The formation of carbocationic species was followed by UV-Vis spectroscopy.

  15. Effect of CMC Molecular Weight on Acid-Induced Gelation of Heated WPI-CMC Soluble Complex.

    Science.gov (United States)

    Huan, Yan; Zhang, Sha; Vardhanabhuti, Bongkosh

    2016-02-01

    Acid-induced gelation properties of heated whey protein isolate (WPI) and carboxymethylcellulose (CMC) soluble complex were investigated as a function of CMC molecular weight (270, 680, and 750 kDa) and concentrations (0% to 0.125%). Heated WPI-CMC soluble complex with 6% protein was made by heating biopolymers together at pH 7.0 and 85 °C for 30 min and diluted to 5% protein before acid-induced gelation. Acid-induced gel formed from heated WPI-CMC complexes exhibited increased hardness and decreased water holding capacity with increasing CMC concentrations but gel strength decreased at higher CMC content. The highest gel strength was observed with CMC 750 k at 0.05%. Gels with low CMC concentration showed homogenous microstructure which was independent of CMC molecular weight, while increasing CMC concentration led to microphase separation with higher CMC molecular weight showing more extensive phase separation. When heated WPI-CMC complexes were prepared at 9% protein the acid gels showed improved gel hardness and water holding capacity, which was supported by the more interconnected protein network with less porosity when compared to complexes heated at 6% protein. It is concluded that protein concentration and biopolymer ratio during complex formation are the major factors affecting gel properties while the effect of CMC molecular weight was less significant.

  16. Structural, electrochemical, and photophysical properties of a molecular shuttle attached to an acid-terminated self-assembled monolayer

    NARCIS (Netherlands)

    Cecchet, F; Rudolf, P; Rapino, S; Margotti, M; Paolucci, F; Baggerman, J; Kay, ER; Wong, JKY; Leigh, DA; Kay, Euan R.; Wong, Jenny K.Y.; Brouwer, A.M.

    2004-01-01

    A benzylic amide macrocycle containing a pyridine moiety (macrocycle 2) and a related benzylic amide macrocycle-based molecular shuttle (naphthalimide rotaxane) with two pyridine moieties on the macrocyclic unit were grafted onto a self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid (11-MUA

  17. Phenylalanine-containing cyclic dipeptides--the lowest molecular weight hydrogelators based on unmodified proteinogenic amino acids.

    Science.gov (United States)

    Kleinsmann, Alexander J; Nachtsheim, Boris J

    2013-09-14

    Cyclic dipeptides (diketopiperazines - DKPs) that are based on the proteinogenic amino acid phenylalanine in combination with serine, cysteine, glutamate, histidine and lysine are described as simple and remarkable low molecular weight hydrogelators. Blends of selected DKPs show remarkable pH-dependent properties and can be applied as easy to tune materials in drug delivery.

  18. Quantum Chemical Calculations and Molecular Docking Studies of Some NSAID Drugs (Aceclofenac, Salicylic Acid, and Piroxicam as 1PGE Inhibitors

    Directory of Open Access Journals (Sweden)

    S. Suresh

    2016-01-01

    Full Text Available The molecular structure of the three compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III has been determined using Gaussian 03W program with B3LYP method using 6-311++G (d,p basis set calculations. The molecular structures were fully optimized with atomic numbering scheme adopted in the study. To understand the mode of binding and molecular interaction, the docking studies of compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III have been carried out with prostaglandin H2 synthase-1 (1PGE as target using induced fit docking. The molecular docking results show that the interactions and energy for Aceclofenac, Salicylic Acid, and Piroxicam show the best results when docked with prostaglandin H2 synthase-1 (1PGE. The hydrogen bonding interactions of compound I (Aceclofenac are prominent with Arginine moiety, those of compound II (Salicylic Acid are prominent with Tyrosine and Serine moieties, and compound III (Piroxicam shows such interaction with Tyrosine and Arginine moieties. These interactions of prostaglandin H2 synthase-1 (1PGE with substrates are responsible for governing COX-1 inhibitor potency which in turn is a direct measure of the potency of the drug.

  19. Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides

    NARCIS (Netherlands)

    Zhang, Ruiyan; Loers, Gabriele; Schachner, Melitta; Boelens, Rolf; Wienk, Hans; Siebert, Simone; Eckert, Thomas; Kraan, Stefan; Rojas-Macias, Miguel A.; Lütteke, Thomas; Galuska, Sebastian P.; Scheidig, Axel; Petridis, Athanasios K.; Liang, Songping; Billeter, Martin; Schauer, Roland; Steinmeyer, Jürgen; Schröder, Jens Michael; Siebert, Hans Christian

    2016-01-01

    Polysialic acid (polySia) and polySia glycomimetic molecules support nerve cell regeneration, differentiation, and neuronal plasticity. With a combination of biophysical and biochemical methods, as well as data mining and molecular modeling techniques, it is possible to correlate specific ligand-rec

  20. Changes in the molecular composition of ester-bound aliphatics with depth in an acid andic forest soil

    NARCIS (Netherlands)

    Naafs, Derck Ferdinand Werner; Nierop, K.G.J.; Bergen, P.F. van; Leeuw, J.W. de

    2005-01-01

    Changes in the molecular composition of ester-linked aliphatic compounds with depth in an acid andic forest soil are studied. Thermally assisted hydrolysis and methylation (THM) using tetramethylammonium hydroxide in combination with gas chromatography/mass spectrometry revealed a dominance of cutin

  1. Lipid Classes, Fatty Acid Composition, and Glycerolipid Molecular Species of the Red Alga Gracilaria vermiculophylla, a Prostaglandin-Producing Seaweed.

    Science.gov (United States)

    Honda, Masaki; Ishimaru, Takashi; Itabashi, Yutaka

    2016-01-01

    The red alga Gracilaria vermiculophylla is a well-known producer of prostaglandins, such as PGE2 and PGF2α. In this study, the characteristics of glycerolipids as substrates of prostaglandin production were clarified, and the lipid classes, fatty acid composition, and glycerolipid molecular species were investigated in detail. The major lipid classes were monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and sulfoquinovosyldiacylglycerol (SQDG), as well as phosphatidylcholine (PC), which accounted for 43.0% of the total lipid profile. Arachidonic acid (20:4n-6), a prostaglandin precursor, and palmitic acid (16:0) were the predominant fatty acids in the total lipid profile. The 20:4n-6 content was significantly high in MGDG and PC (more than 60%), and the 16:0 content was significantly high in DGDG and SQDG (more than 50%). Chiral-phase high-performance liquid chromatography determined that fatty acids were esterified at the sn-1 and sn-2 positions of those lipids. The main glycerolipid molecular species were 20:4n-6/20:4n-6 (sn-1/sn-2) for MGDG (56.5%) and PC (40.0%), and 20:4n-6/16:0 for DGDG (75.4%) and SQDG (58.4%). Thus, it was considered that the glycerolipid molecular species containing one or two 20:4n-6 were the major substrates for prostaglandin production in G. vermiculophylla.

  2. Electrochemical Preparation of a Molecularly Imprinted Polypyrrole-modified Pencil Graphite Electrode for Determination of Ascorbic Acid

    Directory of Open Access Journals (Sweden)

    Yücel Sahin

    2008-09-01

    Full Text Available A molecularly imprinted polymer (MIP polypyrrole (PPy-based film was fabricated for the determination of ascorbic acid. The film was prepared by incorporation of a template molecule (ascorbic acid during the electropolymerization of pyrrole onto a pencil graphite electrode (PGE in aqueous solution using a cyclic voltammetry method. The performance of the imprinted and non-imprinted (NIP films was evaluated by differential pulse voltammetry (DPV. The effect of pH, monomer and template concentrations, electropolymerization cycles and interferents on the performance of the MIP electrode was investigated and optimized. The molecularly imprinted film exhibited a high selectivity and sensitivity toward ascorbic acid. The DPV peak current showed a linear dependence on the ascorbic acid concentration and a linear calibration curve was obtained in the range of 0.25 to 7.0 mM of ascorbic acid with a correlation coefficient of 0.9946. The detection limit (3σ was determined as 7.4x10-5 M (S/N=3. The molecularly-imprinted polypyrrole-modified pencil graphite electrode showed a stable and reproducible response, without any influence of interferents commonly existing in pharmaceutical samples. The proposed method is simple and quick. The PPy electrodes have a low response time, good mechanical stability and are disposable simple to construct.

  3. Mineral Dissolution and Metal Mobility From Rhizosphere and Non-rhizosphere Soils by Low Molecular Weight Organic Acids

    Science.gov (United States)

    Little, D. A.; Field, J. B.; Welch, S. A.

    2005-12-01

    This research is part of an ongoing investigation of micro-biogeochemistry in the rhizosphere of co-occurring Eucalyptus mannifera and Acacia falciformis on the Southern Tablelands of New South Wales, Australia. While there is still considerable controversy in the literature regarding the roles of low molecular weight organic acids in soil processes there is growing evidence suggesting low molecular weight compounds, especially di-carboxylic acids, have large impacts on mineral dissolution and metal mobility in the rhizosphere. Rhizosphere and non-rhizosphere samples from adjacent E. mannifera and A. falciformis trees were subjected to four separate treatments in sets of 3 replicates; +oxalic acid, +malic acid, +citric acid or +NaCl control solution. These three acids were chosen because they are produced by rhizosphere species and they form stable complexes with nutrient elements such as Phosphorus (P), Iron (Fe), and Calcium (Ca). Solution samples were collected at day 1, day 8 and day 15 for pH measurement and analysed for major and trace elements by ICP-AES and ICP-MS. The results of the preliminary dissolution experiments show that milli-molar concentrations of individual organic acids, malate and oxalate, and in particular citrate, greatly increase the release of major and trace metals to solution compared to inorganic controls. Concentrations of Al and Fe in organic acid solutions were up to 10 times greater than in the inorganic controls. Si concentrations were a factor of 2-5 greater in the organic acid solutions, suggesting preferential weathering of Fe and Al oxyhydroxide phases rather than primary silicate minerals. Dissolution of elements such as Si, Al and Fe from rhizosphere soils were about twice that observed from non-rhizosphere soils, further supporting this. Interestingly Ti and Zr, which are usually considered to be immobile during chemical weathering and are not usually taken up by plants, were also mobilised from the rhizosphere soils

  4. Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.

    Science.gov (United States)

    Youn, Kumju; Yun, Eun-Young; Lee, Jinhyuk; Kim, Ji-Young; Hwang, Jae-Sam; Jeong, Woo-Sik; Jun, Mira

    2014-02-01

    In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.

  5. Influence of polymer molecular weight and concentration on coexistence curve of isobutyric acid + water.

    Science.gov (United States)

    Reddy, P Madhusudhana; Venkatesu, P; Bohidar, H B

    2011-10-27

    We report the influence of variation of molecular weights (MWs = 2, 4, 6, and 9 × 10(5) g mol(-1)) and concentration (C) of a long-chain polymer (polyethylene oxide, PEO) on an upper critical solution temperature (UCST) of isobutyric acid (I) + water (W) using density (ρ) measurements as a function of temperature. The ρ values in each coexisting phase of IW have been measured at three different PEO concentrations (C = 0.395, 0.796, and 1.605 mg/cm(3)) in the near critical composition of IW at temperatures below the system's upper critical point for each molecular weight (MW) of PEO. Further, to ascertain the PEO behavior in IW we have measured the polydispersity values for both coexisting liquid phases by using dynamic light scattering (DLS). The data show that the polymer was significantly affected in the critical region of IW and these various MWs and concentrations of PEO show significant modulation on the critical exponents (β), the critical temperatures (T(c)), and critical composition (ϕ(c)), which are depicting the shape of the coexistence curve. The values of β and T(c) increase with increasing PEO MW and concentrations. Besides, the ϕ(c) values slightly decrease with increasing the C values in the mixture of IW. However, the rate of decrease in ϕ(c) is insignificant. Our experimental results explicitly elucidate that most of polymer chain entangles in water rich phase, thereby the polymer monomers strongly interact with neighbor solvent particles and also intra chain interaction between polymer monomers.

  6. 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.

  7. Recurrent disruption of the Imu splice donor site in t(14;18) positive lymphomas: a potential molecular basis for aberrant downstream class switch recombination.

    Science.gov (United States)

    Ruminy, Philippe; Jardin, Fabrice; Penther, Dominique; Picquenot, Jean-Michel; Parmentier, Françoise; Buchonnet, Gérard; Bertrand, Philippe; Tilly, Hervé; Bastard, Christian

    2007-08-01

    t(14;18) positive lymphomas are mature germinal center B-cell neoplasms. In agreement with this cellular origin, most have somatically mutated immunoglobulin variable genes and the IGH@ locus has almost always been reorganized by class switch recombination (CSR). However, contrasting with normal B-cells, a majority of cases still express an IgM while the constant genes are normally rearranged only on the non-productive allele. Concurrently, aberrant intra-allelic junctions involving downstream switch regions, with a lack of engagement of the switch mu (Smu), often accumulate on the functional alleles, suggesting some recurrent CSR perturbation during the onset of the disease. To clarify these surprising observations, we addressed the accessibility of the Smu to the CSR machinery in a large series of patients by characterizing the mutations that are expected to accumulate at this place upon CSR activation. Our data indicate that the Smu is mutated in a large majority of cases, often on both alleles, indicating that these cells usually reach a differentiation stage where CSR is activated and where this region remains accessible. Interestingly, we also identified a significant cluster of mutations at the splicing donor site of the first exon of the Smu germline transcripts, on the functional allele. This location suggests a possible relation with CSR perturbations in lymphoma and the clustering points to a probable mechanism of selection. In conclusion, our data suggest that an acquired mutation at the splicing donor site of the Smu transcripts may participate in the selection of lymphoma cells and play a significant role during the onset of the disease.

  8. Grafting molecularly imprinted poly(2-acrylamido-2-methylpropanesulfonic acid) onto the surface of carbon microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Yang Yongzhen [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); Research Center on Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Zhang Yan; Li Sha [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024 (China); Liu Xuguang, E-mail: liuxuguang@tyut.edu.cn [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan 030024 (China); Xu Bingshe [Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan 030024 (China); Research Center on Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China)

    2012-06-15

    Poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) was grafted on the surface of carbon microspheres (CMSs), which were modified in prior by a mixed acid (HNO{sub 3} and H{sub 2}SO{sub 4}) oxidation and 3-methacryloxypropyl trimethoxysilane silanization. Then, the molecularly imprinting polymerization was carried out towards the macromolecule PAMPS grafted on the surface of CMSs using dibenzothiophene (DBT) as template, ethylene dimethacrylate as cross-linking agent and (NH{sub 4}){sub 2}S{sub 2}O{sub 8} (APS) as initiator to prepare surface molecularly imprinted polymer (MIP-PAMPS/CMSs) for adsorbing DBT. The optimized conditions of grafting PAMPS, including AMPS dosage, APS content, reaction temperature and reaction time, were emphasized in this paper. The morphology of the samples was characterized by field emission scanning electron microscopy. The functional groups were analyzed qualitatively by Fourier transform infrared spectrometry. The grafting degree of PAMPS was investigated by thermogravimetry. The results show that the preferable AMPS dosage, APS content, reaction temperature and time were 5 g, 0.15 g, 70 Degree-Sign C and 12 h, respectively, for preparing PAMPS/CMSs composite on the basis of 1.0 g of silanized-CMSs. The absorbing characteristic of MIP-PAMPS/CMSs toward DBT was studied preliminarily with dynamic adsorption. In the experiment of dynamic adsorption, MIP-PAMPS/CMSs and non-imprinted polymer (NIP-PAMPS/CMSs) were compared with respect to their rapid adsorption in 1 mmol/L of DBT solution in n-hexane. When the first 1 mL of 1 mmol/L DBT solution was injected and flowed through a column packed with 0.1 g of MIP-PAMPS/CMSs, the content of DBT reduced to 0.265 mmol/L, that is, decreased significantly from 279 to 74 ppm. When 3 mL of DBT solution was flowed through the packed column, the adsorption of MIP-PAMPS/CMSs toward DBT reached saturation with the maximum adsorption amount of 1.38 Multiplication-Sign 10{sup -2} mmol/g and the

  9. Grafting molecularly imprinted poly(2-acrylamido-2-methylpropanesulfonic acid) onto the surface of carbon microspheres

    Science.gov (United States)

    Yang, Yongzhen; Zhang, Yan; Li, Sha; Liu, Xuguang; Xu, Bingshe

    2012-06-01

    Poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) was grafted on the surface of carbon microspheres (CMSs), which were modified in prior by a mixed acid (HNO3 and H2SO4) oxidation and 3-methacryloxypropyl trimethoxysilane silanization. Then, the molecularly imprinting polymerization was carried out towards the macromolecule PAMPS grafted on the surface of CMSs using dibenzothiophene (DBT) as template, ethylene dimethacrylate as cross-linking agent and (NH4)2S2O8 (APS) as initiator to prepare surface molecularly imprinted polymer (MIP-PAMPS/CMSs) for adsorbing DBT. The optimized conditions of grafting PAMPS, including AMPS dosage, APS content, reaction temperature and reaction time, were emphasized in this paper. The morphology of the samples was characterized by field emission scanning electron microscopy. The functional groups were analyzed qualitatively by Fourier transform infrared spectrometry. The grafting degree of PAMPS was investigated by thermogravimetry. The results show that the preferable AMPS dosage, APS content, reaction temperature and time were 5 g, 0.15 g, 70 °C and 12 h, respectively, for preparing PAMPS/CMSs composite on the basis of 1.0 g of silanized-CMSs. The absorbing characteristic of MIP-PAMPS/CMSs toward DBT was studied preliminarily with dynamic adsorption. In the experiment of dynamic adsorption, MIP-PAMPS/CMSs and non-imprinted polymer (NIP-PAMPS/CMSs) were compared with respect to their rapid adsorption in 1 mmol/L of DBT solution in n-hexane. When the first 1 mL of 1 mmol/L DBT solution was injected and flowed through a column packed with 0.1 g of MIP-PAMPS/CMSs, the content of DBT reduced to 0.265 mmol/L, that is, decreased significantly from 279 to 74 ppm. When 3 mL of DBT solution was flowed through the packed column, the adsorption of MIP-PAMPS/CMSs toward DBT reached saturation with the maximum adsorption amount of 1.38 × 10-2 mmol/g and the overall adsorption efficiency of 46%, while NIP-PAMPS/CMSs adsorbed only 1.66

  10. Molecular Modeling of Acidic Treated PSTM-3T Polymer for Removal of Heavy Metal Ions by Experimental and Computational Studies

    Directory of Open Access Journals (Sweden)

    Natsagdorj Narantsogt

    2014-01-01

    Full Text Available The synthesized poly[N,N′-bis(3-silsesquioxanilpropyl-thiocarbamide] (PSTM-3T was used and the surface morphology and microstructure of it were analyzed by scanning electron microscopy with energy dispersive spectrometer (SEM/EDS. The molecular structure change of the PSTM-3T polymer of the PSTM-3T after treatment by acidic solution with different pHs was revealed using FT-IR experiments and ab initio calculations with density functional theory method. The sorption efficiency of the heavy metal ions depends on the molecular structure change of PSTM-3T after treatment of different pH aqueous solutions. After the treatment of acidic solution (pH = 2 of PSTM-3T, the polymer formed the tautomer state to increase the sorption efficiency for chromate ion. For the increment of pH value for acidic solution, the PSTM-3T polymer was dissociated to increase the sorption efficiency for copper ion.

  11. Molecular mechanisms in the activation of abscisic acid receptor PYR1.

    Science.gov (United States)

    Dorosh, Lyudmyla; Kharenko, Olesya A; Rajagopalan, Nandhakishore; Loewen, Michele C; Stepanova, Maria

    2013-01-01

    The pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory component of abscisic acid (ABA) response (RCAR) proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodimers (PYR1 and PYLs 1-3) or mediate basal inhibition of downstream target type 2C protein phosphatases (PP2Cs; PYLs 4-10) respectively in vitro. Addition of ABA has been shown to release the apo-homodimers yielding ABA-bound monomeric holo-receptors that can interact with PP2Cs; highlighting a competitive-interaction process. Interaction selectivity has been shown to be mediated by subtle structural variations of primary sequence and ligand binding effects. Now, the dynamical contributions of ligand binding on interaction selectivity are investigated through extensive molecular dynamics (MD) simulations of apo and holo-PYR1 in monomeric and dimeric form as well as in complex with a PP2C, homology to ABA insensitive 1 (HAB1). Robust comparative interpretations were enabled by a novel essential collective dynamics approach. In agreement with recent experimental findings, our analysis indicates that ABA-bound PYR1 should efficiently bind to HAB1. However, both ABA-bound and ABA-extracted PYR1-HAB1 constructs have demonstrated notable similarities in their dynamics, suggesting that apo-PYR1 should also be able to make a substantial interaction with PP2Cs, albeit likely with slower complex formation kinetics. Further analysis indicates that both ABA-bound and ABA-free PYR1 in complex with HAB1 exhibit a higher intra-molecular structural stability and stronger inter-molecular dynamic correlations, in comparison with either holo- or apo-PYR1 dimers, supporting a model that includes apo-PYR1 in complex with HAB1. This possibility of a conditional functional apo-PYR1-PP2C complex was validated in vitro. These findings are generally consistent with the competitive-interaction model

  12. Molecular mechanisms in the activation of abscisic acid receptor PYR1.

    Directory of Open Access Journals (Sweden)

    Lyudmyla Dorosh

    Full Text Available The pyrabactin resistance 1 (PYR1/PYR1-like (PYL/regulatory component of abscisic acid (ABA response (RCAR proteins comprise a well characterized family of ABA receptors. Recent investigations have revealed two subsets of these receptors that, in the absence of ABA, either form inactive homodimers (PYR1 and PYLs 1-3 or mediate basal inhibition of downstream target type 2C protein phosphatases (PP2Cs; PYLs 4-10 respectively in vitro. Addition of ABA has been shown to release the apo-homodimers yielding ABA-bound monomeric holo-receptors that can interact with PP2Cs; highlighting a competitive-interaction process. Interaction selectivity has been shown to be mediated by subtle structural variations of primary sequence and ligand binding effects. Now, the dynamical contributions of ligand binding on interaction selectivity are investigated through extensive molecular dynamics (MD simulations of apo and holo-PYR1 in monomeric and dimeric form as well as in complex with a PP2C, homology to ABA insensitive 1 (HAB1. Robust comparative interpretations were enabled by a novel essential collective dynamics approach. In agreement with recent experimental findings, our analysis indicates that ABA-bound PYR1 should efficiently bind to HAB1. However, both ABA-bound and ABA-extracted PYR1-HAB1 constructs have demonstrated notable similarities in their dynamics, suggesting that apo-PYR1 should also be able to make a substantial interaction with PP2Cs, albeit likely with slower complex formation kinetics. Further analysis indicates that both ABA-bound and ABA-free PYR1 in complex with HAB1 exhibit a higher intra-molecular structural stability and stronger inter-molecular dynamic correlations, in comparison with either holo- or apo-PYR1 dimers, supporting a model that includes apo-PYR1 in complex with HAB1. This possibility of a conditional functional apo-PYR1-PP2C complex was validated in vitro. These findings are generally consistent with the competitive

  13. Application of molecularly imprinted polymers to selective removal of clofibric acid from water.

    Directory of Open Access Journals (Sweden)

    Chaomeng Dai

    Full Text Available A new molecularly imprinted polymer (MIP adsorbent for clofibric acid (CA was prepared by a non-covalent protocol. Characterization of the obtained MIP was achieved by scanning electron microscopy (SEM and nitrogen sorption. Sorption experimental results showed that the MIP had excellent binding affinity for CA and the adsorption of CA by MIP was well described by pseudo-second-order model. Scatchard plot analysis revealed that two classes of binding sites were formed in the MIP with dissociation constants of 7.52 ± 0.46 mg L(-1 and 114 ± 4.2 mg L(-1, respectively. The selectivity of MIP demonstrated higher affinity for CA over competitive compound than that of non-imprinted polymers (NIP. The MIP synthesized was used to remove CA from spiked surface water and exhibited significant binding affinity towards CA in the presence of total dissolved solids (TDS. In addition, MIP reusability was demonstrated for at least 12 repeated cycles without significant loss in performance.

  14. Effect of preparation parameters on ultra low molecular weight chitosan/hyaluronic acid nanoparticles.

    Science.gov (United States)

    Nazeri, Niloofar; Avadi, Mohammad Reza; Faramarzi, Mohammad Ali; Safarian, Shahrokh; Tavoosidana, Gholamreza; Khoshayand, Mohammad Reza; Amani, Amir

    2013-11-01

    Nanoparticles of ultra low molecular weight chitosan (ULMWCS)/hyaluronic acid (HA) were prepared by ion gelation. Three independent variables, namely, ratio of concentration of ULMWCS to HA (CS/HA), pH of solution and stirring time were studied to identify their effects on size, polydispersity and zeta potential of prepared nanoparticles using a Box-Behnken design. Results showed that pH and CS/HA have a direct effect on size, while increase of stirring time decreases the size of nanoparticles. Additionally, it was shown that all the independent parameters have direct effects on zeta potential. Also, the minimum polydispersity index was observed at lowest values of CS/HA. The model also predicted that the optimum values are 4.15, 4.14 and 180 (min) for the CS/HA, solution pH and stirring time, respectively. The obtained preparation had a size of 200 nm, polydispersity index of 0.37, and zeta potential of 13.0 mV.

  15. Molecular Simulation of Oxygen Sorption and Diffusion in the Poly (lactic acid)

    Institute of Scientific and Technical Information of China (English)

    SUN Delin; ZHOU Jian

    2013-01-01

    Grand canonical Monte Carlo and molecular dynamics simulation methods are used to simulate oxygen sorption and diffusion in amorphous poly(lactic acid) (PLA).The simulated solubility coefficient of oxygen is close to experimental data obtained from the quartz crystal microbalance but much higher than those from the time-lag method.This discrepancy is explained by using the dual-mode sorption model.It is found that oxygen sorption in PLA is predominantly Langmuir type controlled,i.e.,through the process of filling holes.The time-lag method only takes into account oxygen molecules that participate the diffusion process whereas a large proportion of oxygen molecules trapped in the void have little chance to execute hopping due to the glassy nature of PLA at room temperature.The simulated diffusion coefficient of oxygen is reasonably close to the data obtained from the time-lag method.The solubility coefficient of oxygen decreases linearly with increasing relative humidity while its diffusion coefficient firstly decreases and then increases as a function of relative humidity.

  16. Fluorescent properties of low-molecular-weight fractions from chernozem humic acids

    Science.gov (United States)

    Trubetskoi, O. A.; Demin, D. V.; Trubetskaya, O. E.

    2013-10-01

    The polyacrylamide gel electrophoresis of chernozem humic acids (HAs) followed by ultraviolet detection (λ = 312 nm) has revealed a new highly fluorescent fraction that has the highest electrophoretic mobility and the lowest nominal molecular weight (NMW). The preparative isolation of the fraction has been performed using the multiple microfiltration of the same HA sample in a 7 M carbamide solution on a membrane with a nominal pore size of 5 kDa. Thirty ultrafiltrates with NMW 5 kDa. Fluorescence maximums at and below 490 nm have been noted only in the first four ultrafiltrates. All the ultrafiltrates have been combined into the fraction with NMW membranes of 3 and 1 kDa. Solutions of subfractions F 3-5 kDa, F 1-3 kDa, and F < 1 kDa with fluorescence maximums at 505, 488, and 465 nm, respectively, have been prepared. The F < 1 kDa subfraction with the lowest NMW had the highest fluorescence intensity. The distribution of the fluorescence maximums in the ultrafiltrates has indicated the presence of at least two groups of fluorophores and has confirmed the supramolecular organization of the extracted soil HAs.

  17. Molecular structure of hydrazoic acid with hydrogen-bonded tetramers in nearly planar layers.

    Science.gov (United States)

    Evers, Jürgen; Göbel, Michael; Krumm, Burkhard; Martin, Franz; Medvedyev, Sergey; Oehlinger, Gilbert; Steemann, Franz Xaver; Troyan, Ivan; Klapötke, Thomas M; Eremets, Mikhail I

    2011-08-10

    Hydrazoic acid (HN(3))--potentially explosive, highly toxic, and very hygroscopic--is the simplest covalent azide and contains 97.7 wt % nitrogen. Although its molecular structure was established decades ago, its crystal structure has now been solved by X-ray diffraction for the first time. Molecules of HN(3) are connected to each other by hydrogen bonds in nearly planar layers parallel to (001) with stacking sequence A, B, ... The layer distance, at 2.950(1) Å, is shorter than that in 2H-graphite [3.355(2) Å]. The hydrogen bonds N-H···N are of great interest, since the azido group consists of three homonuclear atoms with identical electronegativity, but different formal charges. These hydrogen bonds are bifurcated into moderate ones with ≈2.0 Å and into weak ones with ≈2.6 Å. The moderate ones build up tetramers (HN(3))(4) in a nearly planar net of eight-membered rings. To the best of our knowledge, such a network of tetramers of a simple molecule is unique.

  18. Molecularly imprinted polymer for 2, 4-dichlorophenoxyacetic acid prepared by a sol-gel method

    Indian Academy of Sciences (India)

    Yanli Sun

    2014-07-01

    Based on a sol-gel procedure, a molecularly imprinted polymer (MIP) for 2, 4-dichlorophenoxyacetic acid (2, 4-D) was synthesized, using phenyltrimethoxysilane (PTMOS), aminopropyltriethoxysilane (APTES) as monomers and tetraethoxysilane (TEOS) as cross-linking agent. In addition to the amount of the template, some factors in the sol-gel process: TEOS/APTES/PTMOS molar ratio, H2O/Si molar ratio, CH3CH2OH/Si molar ratio, etc. were investigated in detail. Results show that the optimum conditions for the preparation of the MIPs were 20:1.5:1 (TEOS: APTES: PTMOS), ca. 4 (H2O/Si), ca. 4 (CH3CH2OH/Si), respectively. Effects of various parameters involved in the adsorption process of 2, 4-D on MIP such as incubation time, pH, etc. were also evaluated. It is found that the adsorption attained equilibrium within 3 h, the optimum pH for adsorption was about 7 and the adsorption obeyed Langmuir model. Test results also demonstrated that the present MIP for 2, 4-D had large adsorption capacity (the maximum adsorption concluded from Langmuir model reached 243.3 mg/g) and good selectivity.

  19. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

    Directory of Open Access Journals (Sweden)

    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  20. Ancient low–molecular-weight organic acids in permafrost fuel rapid carbon dioxide production upon thaw

    Science.gov (United States)

    Drake, Travis W.; Wickland, Kimberly P.; Spencer, Robert G. M.; McKnight, Diane M.; Striegl, Robert G.

    2015-01-01

    Northern permafrost soils store a vast reservoir of carbon, nearly twice that of the present atmosphere. Current and projected climate warming threatens widespread thaw of these frozen, organic carbon (OC)-rich soils. Upon thaw, mobilized permafrost OC in dissolved and particulate forms can enter streams and rivers, which are important processors of OC and conduits for carbon dioxide (CO2) to the atmosphere. Here, we demonstrate that ancient dissolved organic carbon (DOC) leached from 35,800 y B.P. permafrost soils is rapidly mineralized to CO2. During 200-h experiments in a novel high–temporal-resolution bioreactor, DOC concentration decreased by an average of 53%, fueling a more than sevenfold increase in dissolved inorganic carbon (DIC) concentration. Eighty-seven percent of the DOC loss to microbial uptake was derived from the low–molecular-weight (LMW) organic acids acetate and butyrate. To our knowledge, our study is the first to directly quantify high CO2 production rates from permafrost-derived LMW DOC mineralization. The observed DOC loss rates are among the highest reported for permafrost carbon and demonstrate the potential importance of LMW DOC in driving the rapid metabolism of Pleistocene-age permafrost carbon upon thaw and the outgassing of CO2 to the atmosphere by soils and nearby inland waters.

  1. Deep Eutectic Solvents Modified Molecular Imprinted Polymers for Optimized Purification of Chlorogenic Acid from Honeysuckle.

    Science.gov (United States)

    Li, Guizhen; Wang, Wei; Wang, Qian; Zhu, Tao

    2016-02-01

    Deep eutectic solvents (DES) were synthesized with choline chloride (ChCl), and DES modified molecular imprinted polymers (DES-MIPs), DES modified non-imprinted polymers (DES-NIPs, without template), MIPs and NIPs were prepared in an identical procedure. Fourier transform infrared spectrometer (FT-IR) and field emission scanning electron microscopy (FE-SEM) were used to characterize the obtained polymers. Rebinding experiment and solid-phase extraction (SPE) were used to prove the high selectivity adsorption properties of the polymers. Box-Behnken design (BBD) with three factors was used to optimize the extraction condition of chlorogenic acid (CA) from honeysuckles. The optimum extraction conditions were found to be ultrasonic time optimized (20 min), the volume fraction of ethanol (60%) and ratio of liquid to material (15 mL g(-1)). Under these conditions, the mean extraction yield of CA was 12.57 mg g(-1), which was in good agreement with the predicted BBD model value. Purification of hawthorn extract was achieved by SPE process, and SPE recoveries of CA were 72.56, 64.79, 69.34 and 60.08% by DES-MIPs, DES-NIPs, MIPs and NIPs, respectively. The results showed DES-MIPs had potential for promising functional adsorption material for the purification of bioactive compounds.

  2. Direct ab initio molecular dynamics study of the two photodissociation channels of formic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Yuzuru; Yokoyama, Keiichi; Teranishi, Yoshiaki

    2005-01-31

    A total of {approx}1200 trajectories have been integrated for the two photodissociation channels of formic acid, HCOOH {yields} H{sub 2}O + CO (1) and HCOOH {yields} CO{sub 2} + H{sub 2} (2), which occur with 248 and 193 nm photons, using the direct ab initio molecular dynamics method at the RMP2(full)/cc-pVDZ level of theory. It was found that the percentage of the energy distributed to a relative translational mode in reaction is much larger than that in reaction . This is mainly due to the difference in the geometry of transition state (TS); the H{sub 2}O geometry in the TS of reaction was predicted to significantly deviate from the equilibrium one, whereas the CO{sub 2} and H{sub 2} geometries in the TS of reaction were found to be more similar to their equilibrium ones. It was also found that the product diatomic molecules, CO and H{sub 2}, are both vibrationally and rotationally excited. The calculated relative population of the vibrationally excited CO for the 248 nm photodissociation was consistent with experiment.

  3. Molecular interactions of α-amino acids insight into aqueous β-cyclodextrin systems.

    Science.gov (United States)

    Ekka, Deepak; Roy, Mahendra Nath

    2013-10-01

    Qualitative and quantitative analysis of molecular interaction prevailing in glycine, L-alanine, L-valine and aqueous solution of β-cyclodextrin (β-CD) have been probed by thermophysical properties. Density (ρ), viscosity (η), and ultrasonic speed (u) measurements have been reported at different temperatures. The extent of interaction (solute-solvent interaction) is expressed in terms of the limiting apparent molar volume ([Formula: see text]), viscosity B-coefficient and limiting apparent molar adiabatic compressibility ([Formula: see text]). The changes on the enthalpy ([Formula: see text]) and entropy ([Formula: see text]) of the encapsulation analysis give information about the driving forces governing the inclusion. The temperature dependence behaviour of partial molar quantities and group contributions to partial molar volumes has been determined for the amino acids. The trends in transfer volumes, [Formula: see text], have been interpreted in terms of solute-cosolute interactions based on a cosphere overlap model. The role of the solvent (aqueous solution of β-CD) and the contribution of solute-solute and solute-solvent interactions to the solution complexes have also been analyzed through the derived properties.

  4. Influences of Bronsted Acidic Sites in H[Al] ZSM-5 on Polarization and Electronegativity of Ethene Studied by Molecular Dynamics

    Institute of Scientific and Technical Information of China (English)

    FAN,Jian-Fen(樊建芬); XIAO,He-Ming(肖鹤鸣); van de GRAAF,B; WANG,Qiu-Xia(王秋霞); NJO,S.L; XIA,Qi-Ying(夏其英)

    2002-01-01

    Molecular dynamics simulation has been performed for studying the polarization and electronegativity of ethene molecules near Bronsted acidic sites in H[Al]ZSM-5. The result shows that the molecules are polarized most at the edges of intersections and least at the segments of channels. On the contrary, the highest global molecular electronegativity is fotund at the centers of channel segments. Al substitution slightly increases the molecular dipole moment, but hardly affects the molecular electronegativity. Bronsted acidic proton decreases the dipole moment of guest molecule, but increases the molecular electronegativity.

  5. Density functional theory fragment descriptors to quantify the reactivity of a molecular family: application to amino acids.

    Science.gov (United States)

    Senet, P; Aparicio, F

    2007-04-14

    By using the exact density functional theory, one demonstrates that the value of the local electronic softness of a molecular fragment is directly related to the polarization charge (Coulomb hole) induced by a test electron removed (or added) from (at) the fragment. Our finding generalizes to a chemical group a formal relation between these molecular descriptors recently obtained for an atom in a molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem. Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of the Coulomb hole and related local descriptors of reactivity of a molecular family having in common a similar fragment is presented. As a blind test, the method is applied to the lateral chains of the 20 isolated amino acids. One demonstrates that the local softness of the lateral chain is a quantitative measure of the similarity of the amino acids. It predicts the separation of amino acids in different biochemical groups (aliphatic, basic, acidic, sulfur contained, and aromatic). The present approach may find applications in quantitative structure activity relationship methodology.

  6. Stereocomplexation of low molecular weight poly(L-lactic acid) and high molecular weight poly(D-lactic acid), radiation crosslinking PLLA/PDLA stereocomplexes and their characterization

    Science.gov (United States)

    Quynh, Tran Minh; Mai, Hoang Hoa; Lan, Pham Ngoc

    2013-02-01

    Poly(L-lactic acid)s (PLLAx) were synthesized from L-lactic acid by polycondensation. Different stereocomplexes were also obtained with equimolar mixtures of synthesized PLLAx and a commercial PDLA. The stereocomplexes were crosslinked with triallyl isocyanurate (TAIC) by gamma irradiation. Crosslinking density increased with radiation doses, the heavier the crosslinking network, the lower its swelling degree. The crosslinking structures were introduced in the stereocomplexes inhibiting the mobility for crystallization of PLLA molecules. Thermal and mechanical properties of PLA stereocomplexes were remarkably enhanced by radiation induced crosslinking. PLA stereocomplex does not seem to be degraded by PLLA degrading microorganisms existing in compost at room temperature, but the synthesized PLLA was significantly degraded.

  7. Preparation of magnetic dummy molecularly imprinted polymers for selective extraction and analysis of salicylic acid in Actinidia chinensis.

    Science.gov (United States)

    You, Qing-Ping; Peng, Mi-Jun; Zhang, Yu-Ping; Guo, Jun-Fang; Shi, Shu-Yun

    2014-01-01

    Compounds with strong intramolecular hydrogen bonds (e.g., salicylic acid) have weak intermolecular hydrogen bonding interactions between them and functional monomers in the imprinting process. Consequently, the corresponding molecularly imprinted polymers (MIPs) have no specific adsorption ability. Here, the first magnetic dummy MIPs (MDMIPs) based on benzonic acid as dummy template are successfully developed and evaluated with respect to the applications in selective enrichment and analysis of salicylic acid from complex mixtures. Various parameters affecting absorption/desorption were evaluated for achieving optimal recovery and reducing nonspecific interactions. The prepared MDMIPs showed high adsorption capacity, good selectivity, rapid kinetic binding (40 min) and magnetic separation (5 s), high reproducibility (RSDsalicylic acid was quantified (0.2 μg/g of fresh mass) in Actinidia chinensis by high-performance liquid chromatography.

  8. Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

    Science.gov (United States)

    Hariono, Maywan; Abdullah, Nurshariza; Damodaran, K.V.; Kamarulzaman, Ezatul E.; Mohamed, Nornisah; Hassan, Sharifah Syed; Shamsuddin, Shaharum; Wahab, Habibah A.

    2016-01-01

    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors. PMID:27995961

  9. Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

    Science.gov (United States)

    Hariono, Maywan; Abdullah, Nurshariza; Damodaran, K. V.; Kamarulzaman, Ezatul E.; Mohamed, Nornisah; Hassan, Sharifah Syed; Shamsuddin, Shaharum; Wahab, Habibah A.

    2016-12-01

    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

  10. Genetic variation assessment of acid lime accessions collected from south of Iran using SSR and ISSR molecular markers.

    Science.gov (United States)

    Sharafi, Ata Allah; Abkenar, Asad Asadi; Sharafi, Ali; Masaeli, Mohammad

    2016-01-01

    Iran has a long history of acid lime cultivation and propagation. In this study, genetic variation in 28 acid lime accessions from five regions of south of Iran, and their relatedness with other 19 citrus cultivars were analyzed using Simple Sequence Repeat (SSR) and Inter-Simple Sequence Repeat (ISSR) molecular markers. Nine primers for SSR and nine ISSR primers were used for allele scoring. In total, 49 SSR and 131 ISSR polymorphic alleles were detected. Cluster analysis of SSR and ISSR data showed that most of the acid lime accessions (19 genotypes) have hybrid origin and genetically distance with nucellar of Mexican lime (9 genotypes). As nucellar of Mexican lime are susceptible to phytoplasma, these acid lime genotypes can be used to evaluate their tolerance against biotic constricts like lime "witches' broom disease".

  11. Acetic acid in aged vinegar affects molecular targets for thrombus disease management.

    Science.gov (United States)

    Jing, Li; Yanyan, Zhang; Junfeng, Fan

    2015-08-01

    To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.

  12. Molecular docking and molecular dynamics simulation studies on Thermus thermophilus leucyl-tRNA synthetase complexed with different amino acids and pre-transfer editing substrates

    Directory of Open Access Journals (Sweden)

    Rayevsky A. V.

    2016-02-01

    Full Text Available Aim. To investigate the structural bases for the amino acid selectivity of the Thermus thermophilus leucyl-tRNA synthetase (LeuRSTT aminoacylation site and to disclose the binding pattern of pre-transfer editing substrates. Methods. Eight amino acids proposed as semi-cognate substrates for aminoacylation and eight aminoacyl-adenylates (formed from AMP and eight amino acids were prepared in zwitterions form. The protein structure with a co-crystallized substrate in the aminoacylation site [PDBID: 1OBH] was taken from RCSB. Docking settings and evaluation of substrate efficiency were followed by twofold docking function analysis for each conformation with Gold CCDC. The molecular dynamics simulation was performed using Gromacs. The procedures of relaxation and binding study were separated in two different subsequent simulations for 50ns and 5ns. Results. The evaluation of substrate efficiency for 8 amino acids by twofold docking function analysis, based on score values,has shown that the ligands of LeuRSTT can be positioned in the following order: Leu>Nva>Hcy>Nle>Met>Cys>Ile >Val. MD simulation has revealed lower electrostatic interactions of isoleucine with the active site of the enzyme compared with those for norvaline and leucine. In the case of aminoacyl-adenylates no significant differences were found based on score values for both GoldScore and Asp functions. Molecular dynamics of leucyl-, isoleucyl- and norvalyl-adenylates showed that the most stable and conformationally favorable is leucine, then follow norvaline and isoleucine. It has been also found that the TYR43 of the active site covers carboxyl group of leucine and norvaline like a shield and deflected towards isoleucine, allowing water molecules to come closer. Conclusions. In this study we revealed some structural basis for screening unfavorable substrates by shape, size and flexibility of a radical. The results obtained for different amino acids by molecular docking and MD studies

  13. Molecular Imprinting Fibrous Membranes of Poly(acrylonitrile-co-acrylic acid) Prepared by Electrospinning

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Introduction Over the past few decades, molecular imprinting has been described as a technology for preparing "molecular doors" which can be matched to "template keys". It has been found to be a simple and effective approach to introduce specific recognition sites into synthetic polymers, namely, to create molecular imprinting polymers[1-4]. Remarkable features such as stability,ease of preparation and low cost, have made molecular imprinting polymers particularly attractive in chemical sensors, catalysis, drug delivery, and dedicated separations.

  14. Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

    Science.gov (United States)

    Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

    2016-11-01

    In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an AL type curve with a stability constant K1:1=821M(-1). (1)H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅DA-MS=5.23±1.65μm and ∅DA:HP-β-CD-MS=4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζDA-MS=-7.85±0.32mV and ζDA:HP-β-CD-MS=-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k2=0.042±0.001; r(2)=0.996) when compared with DA-MS (k2=0.183±0.005; r(2)=0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC50=43.29μM) against Vero cells (IC50 of DA-MS=108.48μM and IC50 of DA:HP-β-CD-MS=142.63μM).

  15. Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG

    Directory of Open Access Journals (Sweden)

    Claes Ingmar JJ

    2012-12-01

    Full Text Available Abstract Background Probiotic bacteria are increasingly used as immunomodulatory agents. Yet detailed molecular knowledge on the immunomodulatory molecules of these bacteria is lagging behind. Lipoteichoic acid (LTA is considered a major microbe-associated molecular pattern (MAMP of Gram-positive bacteria. However, many details and quantitative data on its immune signalling capacity are still unknown, especially in beneficial bacteria. Recently, we have demonstrated that a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG, having modified LTA molecules, has an enhanced probiotic efficacy in a DSS-induced colitis model as compared to wild-type. Results In this study, the importance of D-alanylated and acylated LTA for the pro-inflammatory activity of LGG was studied in vitro. Purified native LTA of LGG wild-type exhibited a concentration-dependent activation of NF-κB signalling in HEK293T cells after interaction with TLR2/6, but not with TLR2 alone. Chemical deacylation of LTA interfered with the TLR2/6 interaction, while a moderate effect was observed with chemical dealanylation. Similarly, the dltD mutant of LGG exhibited a significantly reduced capacity to activate TLR2/6-dependent NF-κB signalling in a HEK293T reporter cell line compared to wild-type. In addition, the dltD mutant of LGG showed a reduced induction of mRNA of the chemokine IL-8 in the Caco-2 epithelial cell line compared to wild-type. Experiments with highly purified LTA of LGG confirmed that LTA is a crucial factor for IL-8 mRNA induction in Caco-2 epithelial cells. Chemical dealanylation and deacylation reduced IL-8 mRNA expression. Conclusions Taken together, our results indicate that LTA of LGG is a crucial MAMP with pro-inflammatory activities such as IL-8 induction in intestinal epithelial cells and NF-κB induction in HEK293T cells via TLR2/6 interaction. The lipid chains of LGG LTA are needed for these activities, while also the D-alanine substituents

  16. Latching micro optical switch

    Science.gov (United States)

    Garcia, Ernest J; Polosky, Marc A

    2013-05-21

    An optical switch reliably maintains its on or off state even when subjected to environments where the switch is bumped or otherwise moved. In addition, the optical switch maintains its on or off state indefinitely without requiring external power. External power is used only to transition the switch from one state to the other. The optical switch is configured with a fixed optical fiber and a movable optical fiber. The movable optical fiber is guided by various actuators in conjunction with a latching mechanism that configure the switch in one position that corresponds to the on state and in another position that corresponds to the off state.

  17. Stable carbon isotopic compositions of low-molecular-weight dicarboxylic acids, oxocarboxylic acids, α-dicarbonyls, and fatty acids: Implications for atmospheric processing of organic aerosols

    Science.gov (United States)

    Zhang, Yan-Lin; Kawamura, Kimitaka; Cao, Fang; Lee, Meehye

    2016-04-01

    Stable carbon isotopic compositions (δ13C) were measured for 23 individual organic species including 9 dicarboxylic acids, 7 oxocarboxylic acids, 1 tricarboxylic acid, 2 α-dicarbonyls, and 4 fatty acids in the aerosols from Gosan background site in East Asia. δ13C values of particle phase glyoxal and methylglyoxal are significantly larger than those previously reported for isoprene and other precursors. The values are consistently less negative in oxalic acid (C2, average -14.1‰), glyoxylic acid (-13.8‰), pyruvic acid (-19.4‰), glyoxal (-13.5‰), and methylglyoxal (-18.6‰) compared to other organic species (e.g., palmitic acid, -26.3‰), which can be explained by the kinetic isotope effects during atmospheric oxidation of pre-aged precursors (e.g., isoprene) and the subsequent gas-particle partitioning after the evaporation of clouds or wet aerosols. The δ13C values of C2 is positively correlated with C2 to organic carbon ratio, indicating that photochemical production of C2 is more pronounced than its degradation during long-range atmospheric transport. The isotopic results also suggest that aqueous phase oxidation of glyoxal and methylglyoxal is a major formation process of oxalic acid via the intermediates such as glyoxylic acid and pyruvic acid. This study provides evidence that organic aerosols are intensively photochemically aged in the western North Pacific rim.

  18. Different low-molecular-mass organic acids specifically control leaching of arsenic and lead from contaminated soil

    Science.gov (United States)

    Ash, Christopher; Tejnecký, Václav; Borůvka, Luboš; Drábek, Ondřej

    2016-04-01

    Low-molecular-mass organic acids (LMMOA) are of key importance for mobilisation and fate of metals in soil, by functioning as ligands that increase the amount of dissolved metal in solution or by dissociation of metal binding minerals. Column leaching experiments were performed on soil polluted with As and Pb, in order to determine the specificity of LMMOA related release for individual elements, at varying organic acid concentrations. Acetic, citric and oxalic acids were applied in 12 h leaching experiments over a concentration range (0.5-25 mM) to soil samples that represent organic and mineral horizons. The leaching of As followed the order: oxalic > citric > acetic acid in both soils. Arsenic leaching was attributed primarily to ligand-enhanced dissolution of mineral oxides followed by As released into solution, as shown by significant correlation between oxalic and citric acids and content of Al and Fe in leaching solutions. Results suggest that subsurface mineral soil layers are more vulnerable to As toxicity. Leaching of Pb from both soils followed the order: citric > oxalic > acetic acid. Mineral soil samples were shown to be more susceptible to leaching of Pb than samples characterised by a high content of organic matter. The leaching efficiency of citric acid was attributed to formation of stable complexes with Pb ions, which other acids are not capable of. Results obtained in the study are evidence that the extent of As and Pb leaching in contaminated surface and subsurface soil depends significantly on the types of carboxylic acid involved. The implications of the type of acid and the specific element that can be mobilised become increasingly significant where LMMOA concentrations are highest, such as in rhizosphere soil.

  19. Complex Formation of Selected Radionuclides with Ligands Commonly Found in Ground Water: Low Molecular Organic Acids

    DEFF Research Database (Denmark)

    Jensen, Bror Skytte; Jensen, H.

    1985-01-01

    A general approach to the analysis of potentiometric data on complex formation between cations and polybasic amphoteric acids is described. The method is used for the characterisation of complex formation between Cs+, Sr2+, Co2+, La 3+, and Eu3+ with a α-hydroxy acids, tartaric acid and citric ac......, and with the α-amino acids, aspartic acid and L-cysteine. The cations have been chosen as typical components of reactor waste, and the acids because they are often found as products of microbial activity in pits or wherever organic material decays...

  20. High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury

    Science.gov (United States)

    Khaing, Zin Z.; Milman, Brian D.; Vanscoy, Jennifer E.; Seidlits, Stephanie K.; Grill, Raymond J.; Schmidt, Christine E.

    2011-08-01

    A major hurdle for regeneration after spinal cord injury (SCI) is the ability of axons to penetrate and grow through the scar tissue. After SCI, inflammatory cells, astrocytes and meningeal cells all play a role in developing the glial scar. In addition, degradation of native high molecular weight (MW) hyaluronic acid (HA), a component of the extracellular matrix, has been shown to induce activation and proliferation of astrocytes. However, it is not known if the degradation of native HA actually enhances glial scar formation. We hypothesize that the presence of high MW HA (HA with limited degradation) after SCI will decrease glial scarring. Here, we demonstrate that high MW HA decreases cell proliferation and reduces chondroitin sulfate proteoglycan (CSPG) production in cultured neonatal and adult astrocytes. In addition, stiffness-matched high MW HA hydrogels crosslinked to resist degradation were implanted in a rat model of spinal dorsal hemisection injury. The numbers of immune cells (macrophages and microglia) detected at the lesion site in animals with HA hydrogel implants were significantly reduced at acute time points (one, three and ten days post-injury). Lesioned animals with HA implants also exhibited significantly lower CSPG expression at ten days post-injury. At nine weeks post-injury, animals with HA hydrogel implants exhibited a significantly decreased astrocytic response, but did not have significantly altered CSPG expression. Combined, these data suggest that high MW HA, when stabilized against degradation, mitigates astrocyte activation in vitro and in vivo. The presence of HA implants was also associated with a significant decrease in CSPG deposition at ten days after SCI. Therefore, HA-based hydrogel systems hold great potential for minimizing undesired scarring as part of future repair strategies after SCI.

  1. The Physiological and Molecular Responses of Arabidopsis thaliana to the Stress of Oxalic Acid

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-ting; LIN Jie; SHAO Xue-feng; OU Xiao-ming; WANG Zong-hua; LU Guo-dong

    2009-01-01

    Many fungal phytopathogens can secrete oxalic acid (OA), which is the crucial pathogenic determinant and plays important roles in pathogenicity and virulence of pathogen during infection process. However, how plants respond to OA stress still needs further characterization. In this study, we observed the physiological and molecular responses of Arabidopsis thaliana to OA stress. The leaves of 6-wk-old A. thaliana were sprayed with OA and distilled water respectively, and 0, 2, 4, 8, 12, and 24 h later, the leaves were collected and the contents of MDA, H2O2, and GSH, and the activities of CAT, SOD, and POD were determined and the expressions of PR1 and PDF1.2 were also studied. Under the stress of 30 mmol L-1 OA, SOD activity was first enhanced to reduce the accumulation of O2-. But immediately, POD, CAT, and GSH all decreased extremely resulting in the accumulation of H2O2, and the MDA content increased 24 h later. GSH activity was enhanced significantly at 24 h after OA used. However, H2O2 wasn't eliminated at the same time, suggesting that the activity inhibitions of POD and CAT might be the reasons that caused Arabidopsis cells' impairment under OA stress. RT-PCR results indicated that PDF1.2, a marker gene of the JA/ET signaling was significantly induced; PR1, an indicator gene in SA signaling, was slighlty induced from 8 to 12 h after OA stress. In conclusion, Arabidopsis may recruit metabolism of reactive oxygen, both JA/ET and SA signaling pathways to respond to OA stress. These results will facilitate our further understanding the mechanisms of plant response to OA and OA-dependent fungal infection.

  2. Preparation of molecularly imprinted polymers using anacardic acid monomers derived from cashew nut shell liquid.

    Science.gov (United States)

    Philip, Joseph Y N; Buchweishaija, Joseph; Mkayula, Lupituko L; Ye, Lei

    2007-10-31

    The objective of this work was to use monomers from cashew ( Anacardium occidentale L.) nut shells to develop molecularly imprinted polymers. Cashew nut shell liquid (CNSL) is a cheap and renewable agro byproduct consisting of versatile monomers. Solvent-extracted CNSL contains over 80% anacardic acid (AnAc) with more than 90% degree of unsaturation in its C 15 side chain. From AnAc monomer, anacardanyl acrylate (AnAcr) and anacardanyl methacrylate (AnMcr) monomers were synthesized and their chemical structures were characterized by Fourier transform IR and NMR. Different imprinted bulk polymers based on AnAc, AnAcr, and AnMcr functional monomers have been prepared. In the present study, each functional monomer was separately copolymerized in toluene with ethylene glycol dimethacrylate and divinylbenzene as cross-linkers, using racemic propranolol as a model template. While the AnAc based polymer revealed a meager rebinding ability, the imprinted polymers made from AnAcr and AnMcr displayed highly specific propranolol binding. At a polymer concentration of 2 mg/mL, AnAcr and AnMcr based imprinted polymers were able to bind over 50% of trace propranolol (initial concentration 1.2 nM). Under the same condition propranolol uptake by the two nonimprinted control polymers was less than 20%. Chiral recognition properties of these polymers were further confirmed using tritium-labeled (S)-propranolol as a tracer in displacement experiments, suggesting that the apparent affinity of the imprinted chiral sites for the correct enantiomer is at least 10 times that of the mismatched (R)-propranolol. Moreover, cross reactivity studies of these polymers showed that the (S)-imprinted sites have higher cross-reactivity toward (R, S)-metoprolol than (R)-propranolol and (R)-timolol.

  3. Born Oppenheimer Molecular Dynamics calculation of the νO-H IR spectra for acetic acid cyclic dimers

    Science.gov (United States)

    El Amine Benmalti, Mohamed; Krallafa, Abdelghani; Gaigeot, Marie-Pierre

    2015-01-01

    Both ab initio molecular dynamics simulations based on the Born-Oppenheimer approach calculations and a quantum theoretical model are used in order to study the IR spectrum of the acetic acid dimer in the gas phase. The theoretical model is taking into account the strong anharmonic coupling, Davydov coupling, multiple Fermi resonances between the first harmonics of some bending modes and the first excited state of the symmetric combination of the two vO-H modes and the quantum direct and indirect relaxation. The IR spectra obtained from DFT-based molecular dynamics is compared with our theoretical lineshape and with experiment. Note that in a previous work we have shown that our approach reproduces satisfactorily the main futures of the IR experimental lineshapes of the acetic acid dimer [Mohamed el Amine Benmalti, Paul Blaise, H. T. Flakus, Olivier Henri-Rousseau, Chem Phys, 320(2006) 267-274.].

  4. Molecular identification and physiological characterization of yeasts, lactic acid bacteria and acetic acid bacteria isolated from heap and box cocoa bean fermentations in West Africa.

    Science.gov (United States)

    Visintin, Simonetta; Alessandria, Valentina; Valente, Antonio; Dolci, Paola; Cocolin, Luca

    2016-01-04

    Yeast, lactic acid bacteria (LAB) and acetic acid bacteria (AAB) populations, isolated from cocoa bean heap and box fermentations in West Africa, have been investigated. The fermentation dynamicswere determined by viable counts, and 106 yeasts, 105 LAB and 82 AAB isolateswere identified by means of rep-PCR grouping and sequencing of the rRNA genes. During the box fermentations, the most abundant species were Saccharomyces cerevisiae, Candida ethanolica, Lactobacillus fermentum, Lactobacillus plantarum, Acetobacter pasteurianus and Acetobacter syzygii, while S. cerevisiae, Schizosaccharomyces pombe, Hanseniaspora guilliermondii, Pichia manshurica, C. ethanolica, Hanseniaspora uvarum, Lb. fermentum, Lb. plantarum, A. pasteurianus and Acetobacter lovaniensis were identified in the heap fermentations. Furthermore, the most abundant species were molecularly characterized by analyzing the rep-PCR profiles. Strains grouped according to the type of fermentations and their progression during the transformation process were also highlighted. The yeast, LAB and AAB isolates were physiologically characterized to determine their ability to grow at different temperatures, as well as at different pH, and ethanol concentrations, tolerance to osmotic stress, and lactic acid and acetic acid inhibition. Temperatures of 45 °C, a pH of 2.5 to 3.5, 12% (v/v) ethanol and high concentrations of lactic and acetic acid have a significant influence on the growth of yeasts, LAB and AAB. Finally, the yeastswere screened for enzymatic activity, and the S. cerevisiae, H. guilliermondii, H. uvarumand C. ethanolica species were shown to possess several enzymes that may impact the quality of the final product.

  5. Electrospun Scaffolds from Low Molecular Weight Poly(ester amides Based on Glycolic Acid, Adipic Acid and Odd or Even Diamines

    Directory of Open Access Journals (Sweden)

    Sara Keiko Murase

    2015-05-01

    Full Text Available Electrospinning of regular poly(ester amides (PEAs constituted by glycolic acid, adipic acid and diamines with five and six carbon atoms has been carried out. Selected PEAs were constituted by natural origin products and could be easily prepared by a polycondensation method that avoids tedious protection and deprotection steps usually required for obtaining polymers with a regular sequence. Nevertheless, the synthesis had some limitations that mainly concerned the final low/moderate molecular weight that could be attained. Therefore, it was considered interesting to evaluate if electrospun scaffolds could still be prepared taking also advantage of the capability of PEAs to establish intermolecular hydrogen bonds. Results indicated that the crucial factor was the control of polymer concentration in the electrospun solution, being necessary that this concentration was higher than 40% (w/v. The PEA with the lowest molecular weight (Mw close to 8000 g/mol was the most appropriate to obtain electrospun samples with a circular cross-section since higher molecular sized polymers show solvent retention problems derived from the high viscosity of the electrospun solution that rendered ribbon-like morphologies after the impact of fibers into the collector. The studied PEAs were semicrystalline and biodegradable, as demonstrated by calorimetric and degradation studies. Furthermore, the new scaffolds were able to encapsulate drugs with anti-inflammatory and bacteriostatic activities like ketoprofen. The corresponding release and bactericide activity was evaluated in different media and against different bacteria. Finally, biocompatibility was demonstrated using both fibroblast and epithelial cell lines.

  6. Molecular Imprinted Polymer of Methacrylic Acid Functionalised β-Cyclodextrin for Selective Removal of 2,4-Dichlorophenol

    OpenAIRE

    Hemavathy Surikumaran; Sharifah Mohamad; Norazilawati Muhamad Sarih

    2014-01-01

    This work describes methacrylic acid functionalized β-cyclodextrin (MAA-βCD) as a novel functional monomer in the preparation of molecular imprinted polymer (MIP MAA-βCD) for the selective removal of 2,4-dichlorophenol (2,4-DCP). The polymer was characterized using Fourier Transform Infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) and Field Emission Scanning Electron Microscopy (FESEM) techniques. The influence of parameters such as solution pH, contact time, temperature and initia...

  7. Photo- and electro-chromic organometallics with dithienylethene (DTE) linker, L2CpM-DTE-MCpL2: dually stimuli-responsive molecular switch.

    Science.gov (United States)

    Motoyama, Keiko; Li, Huifang; Koike, Takashi; Hatakeyama, Makoto; Yokojima, Satoshi; Nakamura, Shinichiro; Akita, Munetaka

    2011-10-28

    Photochromic dithienylethene (DTE) derivatives, M-DTE-M (M: M(η(5)-C(5)R(5))L(2); M = Fe, Ru; R = H, Me; L = CO, phosphine), with direct σ-bonded, redox-active organometallic attachments are prepared and their response to photo- and electro-chemical stimuli as well as wire-like and switching performance has been investigated. These properties turn out to be dependent on the metal and the auxiliary ligands. The DTE complexes with the MCp(CO)(2) and RuCp(CO)(PPh(3)) fragments undergo reversible photochemical ring-closing and -opening of the DTE moiety upon UV and visible-light irradiation, respectively, whereas the other FeCp(CO)(PPh(3)) and Fe(η(5)-C(5)R(5))(dppe) derivatives are virtually inert with respect to the photochemical ring closing process. Electrochemical analysis of the DTE complexes reveals that 2e-oxidation of the open isomer O also brings about the ring closure of the DTE moiety to afford the Fischer-carbene-type, dicationic closed derivatives C(2+) with the π-conjugated system different from that in the neutral ones C obtained photochemically. Subsequent reduction of C(2+) furnishes the neutral closed species C. Thus the ring closure is mediated not only by the conventional photochemical process but also by the sequential oxidation-reduction process, i.e. the organometallic DTE complexes are found to be dually photo- and electro-chromic. It is notable that the oxidative procedures are viable for the photochemically inert derivatives. Wire-like and switching performance has been evaluated on the basis of the comproportionation constant K(C) for the 1e-oxidized mixed valence monocationic species obtained by the electrochemical analysis and the switching factor SF (K(C)(C)/K(C)(O)), respectively. The K(C)(C) (7.5 × 10(4)) and SF values (5.4 × 10(3)) for phosphine-substituted derivatives are significantly large, as a result of the distinct π-conjugated systems of the DTE moieties involved in the O- (with cross-conjugation) and C-forms (fully

  8. Molecular distributions and isotopic compositions of marine aerosols over the western North Atlantic: Dicarboxylic acids, ketoacids, α-dicarbonyls (glyoxal and methylglyoxal), fatty acids, sugars, and SOA tracers

    Science.gov (United States)

    Kawamura, K.; Ono, K.; Tachibana, E.; Quinn, P.; Bates, T. S.

    2013-12-01

    Marine aerosols were collected over the western North Atlantic from off the coast of Boston to Bermuda during the WACS (Western Atlantic Climate Study) cruise of R/V Ronald H. Brown in August 2012 using a high volume air sampler and pre-combusted quartz fiber filters. Aerosol filter samples (n=5) were analyzed for OC/EC, major inorganic ions, low molecular weight dicarboxylic acids and various secondary organic aerosol (SOA) tracers using carbon analyzer, ion chromatograph, GC/FID and GC/MS, respectively. Homologous series (C2-C12) of dicarboxylic acids (31-335 ng m-3) were detected with a predominance of oxalic acid. Total carbon and nitrogen and their stable isotope ratios were determined as well as stable carbon isotopic compositions of individual diacids using IRMS. Diacids were found to be the most abundant compound class followed by monoterpene-SOA tracers > isoprene-SOA tracers > sugar compounds > ketoacids > fatty alcohols > fatty acids > α-dicarbonyls > aromatic acids > n-alkanes. The concentrations of these compounds were higher in the coastal site and decreased in the open ocean. However, diacids stayed relatively high even in the remote ocean. Interestingly, contributions of oxalic acid to total aerosol carbon increased from the coast (2.3%) to the remote ocean (5.6%) during long-range atmospheric transport. Stable carbon isotopic composition of oxalic acid increased from the coast (-17.5‰) to open ocean (-12.4‰), suggesting that photochemical aging of organic aerosols occurred during the atmospheric transport over the ocean. Stable carbon isotope ratios of bulk aerosol carbon also increased from the coast near Boston to the open ocean near Bermuda.

  9. Hybrid molecularly imprinted poly(methacrylic acid-TRIM)-silica chemically modified with (3-glycidyloxypropyl)trimethoxysilane for the extraction of folic acid in aqueous medium.

    Science.gov (United States)

    de Oliveira, Fernanda Midori; Segatelli, Mariana Gava; Tarley, César Ricardo Teixeira

    2016-02-01

    In the present study a hybrid molecularly imprinted poly(methacrylic acid-trimethylolpropane trimethacrylate)-silica (MIP) was synthesized and modified with (3-glycidyloxypropyl)trimethoxysilane (GPTMS) with posterior opening of epoxy ring to provide hydrophilic properties of material in the extraction of folic acid from aqueous medium. The chemical and structural aggregates of hybrid material were characterized by means of Fourier Transform Infrared (FT-IR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Thermogravimetric analysis (TGA) and textural data. Selectivity data of MIP were compared to non-imprinted polymer (NIP) through competitive sorption studies in the presence of caffeine, paracetamol or 4-aminobenzamide yielding relative selectivity coefficients (k′) higher than one unit, thus confirming the selective character of MIP even in the presence of structurally smaller compounds than the folic acid. The lower hydrophobic sorption by bovine serum albumin (BSA) in the MIP as compared to unmodified MIP proves the hydrophilicity of polymer surface by using GPTMS with opening ring. Under acid medium(pH 1.5) the sorption of folic acid onto MIP from batch experiments was higher than the one achieved for NIP. Equilibrium sorption of folic acid was reached at 120 min for MIP, NIP and MIP without GPTMS and kinetic sorption data were well described by pseudo-second-order, Elovich and intraparticle diffusion models. Thus, these results indicate the existence of different binding energy sites in the polymers and a complex mechanism consisting of both surface sorption and intraparticle transport of folic acid within the pores of polymers.

  10. Theoretical and experimental research on the self-assembled system of molecularly imprinted polymers formed by salbutamol and methacrylic acid.

    Science.gov (United States)

    Jun-Bo, Liu; Yang, Shi; Shan-Shan, Tang; Rui-Fa, Jin

    2015-03-01

    The quantum chemical method was applied for screening functional monomers in the rational design of salbutamol-imprinted polymers. Salbutamol was the template molecule, and methacrylic acid was the single functional monomer. The LC-WPBE/6-31G(d,p) method was used to investigate the geometry optimization, active sites, natural bond orbital charges, binding energies of the imprinted molecule, and solvation energy. The mechanism of action between salbutamol and methacrylic acid was also discussed. The theoretical results show that salbutamol interacts with functional monomers by hydrogen bonds, and the salbutamol-imprinted polymers with a ratio of 1:4 (salbutamol/methacrylic acid) in acetonitrile had the highest stability. The salbutamol-imprinted polymers were prepared by precipitation polymerization. The experimental results indicated that the maximum adsorption capacity for salbutamol toward molecularly imprinted polymers was 7.33 mg/g, and the molecularly imprinted polymers had a higher selectivity for salbutamol than for norepinephrine and terbutaline sulfate. Herein, the studies can provide theoretical and experimental references for the salbutamol molecular imprinted system.

  11. Optical packet switched networks

    DEFF Research Database (Denmark)

    Hansen, Peter Bukhave

    1999-01-01

    Optical packet switched networks are investigated with emphasis on the performance of the packet switch blocks. Initially, the network context of the optical packet switched network is described showing that a packet network will provide transparency, flexibility and bridge the granularity gap...... between the electrical switched layer and the WDM transport layer. Analytical models are implemented to determine the signal quality ghrough the switch blocks in terms of power penalty and to assess the traffic performance of different switch block architectures. Further, a computer simulation model...... is used to investigate the influence on the traffic performance of asynchronous operation of the switch blocks. The signal quality investigation illustrates some of the component requirements in respect to gain saturation in SOA gates and crosstalk in order to obtain high cascadability of the switch...

  12. Crude palm oil from interspecific hybrid Elaeis oleifera×Elaeis guineensis: fatty acid regiodistribution and molecular species of glycerides.

    Science.gov (United States)

    Mozzon, Massimo; Pacetti, Deborah; Lucci, Paolo; Balzano, Michele; Frega, Natale Giuseppe

    2013-11-01

    The composition and structure of triacylglycerols (TAGs) and partial glycerides of crude palm oil obtained from interspecific hybrid Elaeis oleifera×Elaeis guineensis, grown in Colombia, were fully characterised and compared to data obtained by analysing crude African palm oil. Hybridisation appears to substantially modify the biosynthesis of fatty acids (FAs) rather than their assembly in TAGs. In fact, total FAs analysis showed significant differences between these two types of oil, with hybrid palm oil having a higher percentage of oleic acid (54.6 ± 1.0 vs 41.4 ± 0.3), together with a lower saturated fatty acid content (33.5 ± 0.5 vs 47.3 ± 0.1), while the percentage of essential fatty acid, linoleic acid, does not undergo significant changes. Furthermore, 34 TAG types were identified, with no qualitative differences between African and E. guineensis×E. oleifera hybrid palm oil samples. Short and medium chain FAs (8:0, 10:0, 12:0, 14:0) were utilised, together, to build a restricted number of TAG molecular species. Oil samples from the E. guineensis×E. oleifera hybrid showed higher contents of monosaturated TAGs (47.5-51.0% vs 36.7-37.1%) and triunsaturated TAGs (15.5-15.6% vs 5.2-5.4%). The sn-2 position of TAGs in hybrid palm oil was shown to be predominantly esterified with oleic acid (64.7-66.0 mol% vs 55.1-58.2 mol% in African palm oil) with only 10-15% of total palmitic acid and 6-20% of stearic acid acylated in the secondary position. The total amount of diacylglycerols (DAGs) was in agreement with the values of free acidity; DAG types found were in agreement with the representativeness of different TAG species.

  13. Remote switch actuator

    Science.gov (United States)

    Haas, Edwin Gerard; Beauman, Ronald; Palo, Jr., Stefan

    2013-01-29

    The invention provides a device and method for actuating electrical switches remotely. The device is removably attached to the switch and is actuated through the transfer of a user's force. The user is able to remain physically removed from the switch site obviating need for protective equipment. The device and method allow rapid, safe actuation of high-voltage or high-current carrying electrical switches or circuit breakers.

  14. Perancangan Switch Matrik Besar Menggunakan Array Switch Analog Zarlink

    OpenAIRE

    2009-01-01

    Secara tradisional, perancangan sebuah switch matrik yang besar dilakukan dengan menggunakan switch-switch elektromekanik. Dengan demikian, banyak bagian yang bergerak yang digunakan untuk membangun switch matrik ini. Dengan kemajuan bidang elektronik, switch elektromekanik saat ini dapat digantikan dengan switch-switch semikonduktor yang ekivalen yang menawarkan solusi yang lebih ekonomis dan memiliki keandalan yang lebih baik. Rumpun switch crosspoint analog Zarlink dapat disusun dengan mud...

  15. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    Science.gov (United States)

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  16. In Silico Phylogenetic Analysis and Molecular Modelling Study of 2-Haloalkanoic Acid Dehalogenase Enzymes from Bacterial and Fungal Origin

    Directory of Open Access Journals (Sweden)

    Raghunath Satpathy

    2016-01-01

    Full Text Available 2-Haloalkanoic acid dehalogenase enzymes have broad range of applications, starting from bioremediation to chemical synthesis of useful compounds that are widely distributed in fungi and bacteria. In the present study, a total of 81 full-length protein sequences of 2-haloalkanoic acid dehalogenase from bacteria and fungi were retrieved from NCBI database. Sequence analysis such as multiple sequence alignment (MSA, conserved motif identification, computation of amino acid composition, and phylogenetic tree construction were performed on these primary sequences. From MSA analysis, it was observed that the sequences share conserved lysine (K and aspartate (D residues in them. Also, phylogenetic tree indicated a subcluster comprised of both fungal and bacterial species. Due to nonavailability of experimental 3D structure for fungal 2-haloalkanoic acid dehalogenase in the PDB, molecular modelling study was performed for both fungal and bacterial sources of enzymes present in the subcluster. Further structural analysis revealed a common evolutionary topology shared between both fungal and bacterial enzymes. Studies on the buried amino acids showed highly conserved Leu and Ser in the core, despite variation in their amino acid percentage. Additionally, a surface exposed tryptophan was conserved in all of these selected models.

  17. Preparation and application of zirconium sulfate supported on SAPO-34 molecular sieve as solid acid catalyst for esterification

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Dongyan, E-mail: xdy0156@sina.com; Ma, Hong; Cheng, Fei

    2014-05-01

    Graphical abstract: - Highlights: • SAPO-34 supported zirconium sulfate solid acid catalyst was prepared. • Esterification of acetic acid with ethanol can be catalyzed by ZS/SAPO-34. • The hydration of ZS is vital to the acidic property and catalytic performance. • The ZS/SAPO-34 catalyst treated at 200 °C shows good reusability. - Abstract: Zirconium sulfate (ZS) was supported on SAPO-34 molecular sieve by using an incipient wetness impregnation method with zirconium sulfate as the precursor. The as-prepared catalysts were used as solid acid catalyst for esterification reaction of acetic acid with ethanol. The influence of calcination temperature on the acidic property, catalytic activity, and reusability of ZS/SAPO-34 catalysts were mainly investigated. FT-IR, SEM, EDS and TG analysis have been carried out to demonstrate the characteristics of ZS/SAPO-34 catalysts. It was found that the 30 wt%ZS/SAPO-34 catalysts display the property of superacid irrespective of calcination temperature. The ZS/SAPO-34 catalyst treated at 200 °C can enhance the interaction between the supported ZS and SAPO-34 and keep the catalyst remaining substantially active after several reaction cycles. However, further increasing calcination temperature will cause the transfer of ZS from hydrate to anhydrous phase, and thus the decrease of activity.

  18. Multi-Functional Molecular Switches Based on Photochromic Dithienylethenes%多功能二噻吩乙烯光致变色光分子开关材料

    Institute of Scientific and Technical Information of China (English)

    邹祺; 张隽佶; 田禾

    2012-01-01

    光致变色材料是一类在不同波长的光交替照射下,产生两种可进行可逆转换的光致异构体并伴随明显的光物理和光化学性能变化的材料。基于其特殊的光致异构性质,人们已开发出多种光致变色功能材料并将其广泛应用于超高密度光信息存储、分子开关、分子逻辑门、分子导线、光电材料、多光子器件、表面/纳米器件、液晶材料、化学传感、生物成像、自组装、聚集诱导发光、光控生物体系等诸多领域。其中,二噻吩乙烯类化合物因其出色的热稳定性、优良的耐疲劳性、快的响应速率、高的转化率和量子产率以及出色的固相反应活性而成为理想的光致变色材料之一。本文主要围绕近期本研究组研究成果着重介绍近几年二噻吩乙烯类化合物从溶液体系到功能化表面体系的研究进展,探讨当前该领域存在的问题并对其前景和发展方向进行展望。%Photochromic materials are those which can undergo reversible photo-switches between two different states or isomers upon alternative irradiation with different wavelengths of light accompanied by distinct photophysieal and photochemical properties. Inspired by their special photo-switchable characteristics, a variety of light-driven functional materials have been exploited, such as ultrahigh-density optical data storage, molecular switches, logic gates, molecular wires, optic/electronic devices, multi-photon devices, surfaee/nanopartiele devices, liquid crystals, bio-imaging and so on. Apart from these, further creation of optoelectronic and photo- optical devices based on photochromic molecular switches which operate at both molecular and supramoleeular levels have recently attracted many attentions. Thus photo-switchable compounds also have played an important role in sensing, self-assembly, aggregation-induced enhanced emission and photo-controlled biological systems. In particular

  19. Synthesis, molecular docking and kinetic properties of β-hydroxy-β-phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors.

    Science.gov (United States)

    Xiao, Zhu-Ping; Peng, Zhi-Yun; Dong, Jing-Jun; Deng, Rui-Cheng; Wang, Xu-Dong; Ouyang, Hui; Yang, Pan; He, Juan; Wang, Yuan-Feng; Zhu, Man; Peng, Xiao-Chun; Peng, Wan-Xi; Zhu, Hai-Liang

    2013-10-01

    Inhibition of urease results in Helicobacter pylori growth arrest in the stomach, promoting urease as promising targets for gastrointestinal ulcer therapy. Twenty hybrid derivatives of flavonoid scaffold and hydroxamic acid, β-hydroxy-β-phenylpropionylhydroxamic acids, were therefore synthesized and evaluated against H. pylori urease. Biological evaluation of these compounds showed improved urease inhibition exhibiting micromolar to mid-nanomolar IC50 values. Most importantly, 3-(3-chlorophenyl)-3-hydroxypropionyl-hydroxamic acid (6g) exhibited high potency with IC50 of 0.083±0.004 μM and Ki of 0.014±0.003 μM, indicating that 6g is an excellent candidate to develop novel antiulcer agent. A mixture of competitive and uncompetitive mechanism was putatively proposed to understand the inconsistency between the crystallographic and kinetic studies for the first time, which is supported by our molecular docking studies.

  20. Five-State Molecular Shuttling of a Pair of [2]Rotaxanes: Distinct Outputs in Response to Acid and Base Stimuli.

    Science.gov (United States)

    Ueda, Masahiro; Terazawa, Shoya; Deguchi, Yasuaki; Kimura, Masaki; Matsubara, Naoki; Miyagawa, Shinobu; Kawasaki, Tsuneomi; Tokunaga, Yuji

    2016-08-19

    In this study we synthesized two acid-/base-controllable [2]rotaxanes featuring aminodiazobenzene and aminocoumarin units, respectively, as chromophores and dibenzo[24]crown-8 and dibenzo[25]crown-8 units, respectively, as their macrocyclic components. Each [2]rotaxane contained N-alkylarylamine (ammonium) and N,N-dialkylamine (ammonium) centers as binding sites for their crown ether components. The absorption patterns of the chromophores were dependent on the position of the encircling macrocyclic component and the degree of protonation, with three distinct states (under acidic, neutral, and basic conditions) evident for each [2]rotaxane. The mixed [2]rotaxane system displayed stepwise and independent molecular shuttling behavior based on the degree of protonation of the amino groups in response to both the amount and strength of added acids or bases; as such, the system provided five different absorption signals as outputs that could be read using UV/Vis spectroscopy.

  1. Molecular Structure, NMR, HOMO, LUMO, and Vibrational Analysis of O-Anisic Acid and Anisic Acid Based on DFT Calculations

    Directory of Open Access Journals (Sweden)

    R. Mathammal

    2013-01-01

    Full Text Available This work deals with the vibrational spectroscopy of O-Anisic acid (OAA and Anisic acid (AA. The fundamental vibrational frequencies and intensity of vibrational bands were evaluated using density functional theory (DFT with standard B3LYP/6-31G** method and basis set combinations. The vibrational spectra were interpreted, with the aid of normal coordinate analysis based on a scaled quantum mechanical force field. The infrared and Raman spectra were also predicted from the calculated intensities. The effects of carbonyl and methyl substitutions on the structure and vibrational frequencies have been investigated. Comparison of simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes. The 13C and 1H NMR chemical shifts of the DFA and CA molecules were calculated using the gauge-invariant-atomic orbital (GIAO method in DMSO solution using IEF-PCM model and compared with experimental data.

  2. In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid

    Directory of Open Access Journals (Sweden)

    Blasi Elisabetta

    2011-03-01

    Full Text Available Abstract Background hyaluronic acid (HA, a non-sulphated glycosaminoglycan, is present in synovial fluid, vitreous humour serum and many connective tissues. Pharmaceutical preparations of HA are used in clinical practice for wound healing, joint pain, kerato-conjunctivitis, asthma, mouth care, oesophageal-reflux, and gastritis. Moreover, it is used as a filler to counteract ageing and facial lipoatrophy. Our study aims at investigating the in vitro antiviral activity of a high molecular weight HA. Methods the MTT test was used to rule out the potential toxic effects of HA on the different cell lines used in the antiviral assays. The antiviral activity of HA against Coxsackievirus B5, Herpes Simplex Virus-1, Mumps Virus, Adenovirus-5, Influenza Virus A/H1N1, Human Herpesvirus-6, Porcine Parvovirus, Porcine Reproductive and Respiratory Syndrome Virus was assessed by virus yield assays. Results the most effective inhibition was observed against Coxsackievirus B5, with 3Log reduction of the virus yield at 4 mg/ml, and a reduction of 3.5Log and 2Log, at 2 mg/ml and 1 mg/ml, respectively: the selectivity index was 16. Mumps virus was highly inhibited too showing a reduction of 1.7Log at 1 mg/ml and 1Log at 4 mg/ml and 2 mg/ml (selectivity index = 12. The selectivity index for Influenza Virus was 12 with the highest inhibition (1Log observed at 4 mg/ml. Herpes Simplex Virus-1 and Porcine Parvovirus were mildly inhibited, whereas no antiviral activity was observed with respect to Adenovirus-5, Human Herpesvirus-6, Porcine Reproductive and Respiratory Syndrome Virus. No HA virucidal activity was ever observed against any of the viruses tested. Kinetic experiments showed that both Coxsackievirus B5 and Herpes simplex virus-1 replication were consistently inhibited, not influenced by the time of HA addition, during the virus replication cycle. Conclusions the spectrum of the antiviral activity exhibited by HA against both RNA and DNA viruses, known to have

  3. Circuit switched optical networks

    DEFF Research Database (Denmark)

    Kloch, Allan

    2003-01-01

    Some of the most important components required for enabling optical networking are investigated through both experiments and modelling. These all-optical components are the wavelength converter, the regenerator and the space switch. When these devices become "off-the-shelf" products, optical cross...... are often considered as a part of the optical cross-connect, where also optical space switching is performed. Therefore, space switching based on both optical gates and interferometric switches is investigated. Moreover, an experiment including both space switching and wavelength conversion is carried out...

  4. Identification of Aspartic Acid Enantiomers Based on Molecularly Imprinted Polyaniline%Identification of Aspartic Acid Enantiomers Based on Molecularly Imprinted Polyaniline

    Institute of Scientific and Technical Information of China (English)

    孔泳; 姚超; 倪珺华; 周永生; 陈智栋

    2011-01-01

    Affinity sites for L-aspartic acid (L-Asp) in polyaniline (PAn) were created by two successive processes: first, L-Asp was simply added as template molecules during the polymerization of aniline; second, L-Asp incorporated in PAn backbone was extracted by solvent. PAn with cavities complementary to L-Asp template molecules has been utilized for enantioselective recognition of L- and D-Asp. Enantioselectivity of the imprinted PAn could be attributed to the cavities in the imprinted PAn which was complementary to L-Asp templates both in shape and in positioning of groups. Also in this paper, the structural changes before and after extraction of L-Asp templates were revealed by Fourier-transform infrared (FTIR) spectrum.

  5. Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

    OpenAIRE

    YAN, JING; Gong, Yuewen; She, Yi-Min; Wang, Guqi; Roberts, Michael S; Burczynski, Frank J.

    2009-01-01

    Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrup...

  6. Design of two-layer switching rule for stabilization of switched linear systems with mismatched switching

    Institute of Scientific and Technical Information of China (English)

    Dan MA

    2014-01-01

    A two-layer switching architecture and a two-layer switching rule for stabilization of switched linear control systems are proposed, under which the mismatched switching between switched systems and their candidate hybrid controllers can be allowed. In the low layer, a state-dependent switching rule with a dwell time constraint to exponentially stabilize switched linear systems is given;in the high layer, supervisory conditions on the mismatched switching frequency and the mismatched switching ratio are presented, under which the closed-loop switched system is still exponentially stable in case of the candidate controller switches delay with respect to the subsystems. Different from the traditional switching rule, the two-layer switching architecture and switching rule have robustness, which in some extend permit mismatched switching between switched subsystems and their candidate controllers.

  7. Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches.

    Directory of Open Access Journals (Sweden)

    Tobias Sikosek

    2016-06-01

    Full Text Available Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein's folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-α and GB α+β folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic π-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches.

  8. The influence of poly(acrylic) acid number average molecular weight and concentration in solution on the compressive fracture strength and modulus of a glass-ionomer restorative.

    LENUS (Irish Health Repository)

    Dowling, Adam H

    2011-06-01

    The aim was to investigate the influence of number average molecular weight and concentration of the poly(acrylic) acid (PAA) liquid constituent of a GI restorative on the compressive fracture strength (σ) and modulus (E).

  9. ESTIMATION OF HYDROLYSIS RATE CONSTANTS OF CARBOXYLIC ACID ESTER AND PHOSPHATE ESTER COMPOUNDS IN AQUEOUS SYSTEMS FROM MOLECULAR STRUCTURE BY SPARC

    Science.gov (United States)

    SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate hydrolysis rate constants for carboxylic acid ester and phosphate ester compounds in aqueous non- aqueous and systems strictly from molecular structure. The energy diffe...

  10. Orbital order switching in molecular calculations using GGA functionals: Qualitative errors in materials modeling for electrochemical power sources and how to fix them

    Science.gov (United States)

    Sk, Mahasin Alam; Chen, Yingqian; Manzhos, Sergei

    2016-08-01

    We report a qualitative difference in molecular band structures and frontier orbital nodal structures in DFT calculations using GGA vs. hybrid functionals and Hartree Fock in molecules used in electrochemical power sources. This can have a significant effect in applications sensitive to redox potentials and to orbital overlaps (excitations, electron transfer rates) but for which the use of hybrid functionals is impractical, such as solids or interfaces used in electrochemical energy conversion and storage technologies. We show that correct band structures and nodal structures (ordering) of frontier orbitals can be obtained by applying a Hubbard correction to selected atomic states.

  11. Blue to near-IR energy transfer cascade within a dye-doped polymer matrix, mediated by a photochromic molecular switch.

    Science.gov (United States)

    Dryza, Viktoras; Smith, Trevor A; Bieske, Evan J

    2016-02-21

    The spectroscopic properties of a poly(methyl methacrylate) matrix doped with a coumarin dye, a cyanine dye, and a photochromic spiropyran dye have been investigated. Before UV irradiation of the matrix, excitation of the coumarin dye results in minimal energy transfer to the cyanine dye. The energy transfer is substantially enhanced following UV irradiation of the matrix, which converts the colourless spiropyran isomer to the coloured merocyanine isomer, which then acts as an intermediate bridge by accepting energy from the coumarin dye and then donating energy to the cyanine dye. This demonstration of a switchable energy transfer cascade should help initiate new research directions in molecular photonics.

  12. Molecularly imprinted polymer-matrix nanocomposite for enantioselective electrochemical sensing of D- and L-aspartic acid.

    Science.gov (United States)

    Prasad, Bhim Bali; Srivastava, Amrita; Tiwari, Mahavir Prasad

    2013-10-01

    A new molecularly imprinted polymer-matrix (titanium dioxide nanoparticle/multiwalled carbon nanotubes) nanocomposite was developed for the modification of pencil graphite electrode as an enantioselective sensing probe for aspartic acid isomers, prevalent at ultra trace level in aqueous and real samples. The nanocomposite having many shape complementary cavities was synthesized adopting surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. The proposed sensor has high stability, nanocomposite uniformity, good reproducibility, and enhanced electrocatalytic activity to respond oxidative peak current of L-aspartic acid quantitatively by differential pulse anodic stripping voltammetry, without any cross-reactivity in real samples. Under the optimized operating conditions, the L-aspartic acid imprinted modified electrode showed a wide linear response for L-aspartic acid within the concentration range 9.98-532.72 ng mL(-1), with the minimum detection limit of 1.73-1.79 ng mL(-1) (S/N=3) in aqueous and real samples. Almost similar stringent limit (1.79 ng mL(-1)) was obtained with cerebrospinal fluid which is typical for the primitive diagnosis of neurological disorders, caused by an acute depletion of L-aspartic acid biomarker, in clinical settings.

  13. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein.

    Science.gov (United States)

    Shubeita, H E; Sambrook, J F; McCormick, A M

    1987-08-01

    A recombinant cDNA clone, pCRABP-HS1, encoding cellular retinoic acid-binding protein was isolated from a bovine adrenal cDNA library. COS-7 cells transfected with pCRABP-HS1 produced a biologically active retinoic acid-binding protein molecule of the expected molecular mass (15.5 kDa). RNA blot hybridization analysis using pCRABP-HS1 as a probe revealed a single 1050-nucleotide mRNA species in bovine adrenal, uterus, and testis, tissues that contain the highest levels of retinoic acid-binding activity. No hybridization was detected in RNA extracted from ovary, spleen, kidney, or liver, which contain relatively low levels of cellular retinoic acid-binding protein activity. Analysis of genomic clones isolated from an EcoRI bovine genomic library demonstrated that the bovine cellular retinoic acid-binding protein gene is composed of four exons and three introns. Two putative promoter sequences were identified in the cloned 5' sequence of the gene.

  14. Molecular Cloning and Characterization of a Novel Gene Involved in Fatty Acid Synthesis in Brassica napus L.

    Institute of Scientific and Technical Information of China (English)

    XIAO Gang; ZHANG Zhen-qian; LIU Rui-yang; YIN Chang-fa; WU Xian-meng; TAN Tai-long; GUAN Chun-yun

    2013-01-01

    Based on the sequence of a novel expressed sequence tag (EST), the full-length cDNA of 1 017 nucleotides was cloned from Brassica napus cv. Xiangyou 15 through rapid amplification of cDNA ends (RACE). The gene was designated as Bnhol34 (HQ585980), encoding a protein of 338 amino acids. BLAST analysis showed no high degree of sequence identity to any known gene. The calculated molecular weight of the Bnhol34 protein was 36.23 kDa, and the theoretical isoelectric point was 8.74. The Bnhol34 was also cloned from a high oleic acid mutant 854-1 through homologous cloning. There was no difference between the two Bnhol34 genes. Bnhol34 was localized in a tissue-specific manner in B. napus, and its expression level was about eight-fold greater in Xiangyou 15 seeds than in 854-1. The promoter region sequences of Bnhol34 were then isolated from Xiangyou 15 and 854-1, and a 93-bp deletion was found to occur in the Bnhol34 promoter region of 854-1. Three abscisic acid-responsive cis-elements (ABRE) were identified in the promoter region of Xiangyou 15. Real-time PCR analyses revealed that exogenous abscisic acid increased Bnhol34 expression by about four-fold in Xiangyou 15 seeds, yet did not change Bnhol34 expression in 854-1. It appeared that Bnhol34 might be abscisic acid insensitive in 854-1.

  15. Effect of backbone chemistry on hybridization thermodynamics of oligonucleic acids: a coarse-grained molecular dynamics simulation study.

    Science.gov (United States)

    Ghobadi, Ahmadreza F; Jayaraman, Arthi

    2016-02-28

    In this paper we study how varying oligonucleic acid backbone chemistry affects the hybridization/melting thermodynamics of oligonucleic acids. We first describe the coarse-grained (CG) model with tunable parameters that we developed to enable the study of both naturally occurring oligonucleic acids, such as DNA, and their chemically-modified analogues, such as peptide nucleic acids (PNAs) and locked nucleic acids (LNAs). The DNA melting curves obtained using such a CG model and molecular dynamics simulations in an implicit solvent and with explicit ions match with the melting curves obtained using the empirical nearest-neighbor models. We use these CG simulations to then elucidate the effect of backbone flexibility, charge, and nucleobase spacing along the backbone on the melting curves, potential energy and conformational entropy change upon hybridization and base-pair hydrogen bond residence time. We find that increasing backbone flexibility decreases duplex thermal stability and melting temperature mainly due to increased conformational entropy loss upon hybridization. Removing charges from the backbone enhances duplex thermal stability due to the elimination of electrostatic repulsion and as a result a larger energetic gain upon hybridization. Lastly, increasing nucleobase spacing decreases duplex thermal stability due to decreasing stacking interactions that are important for duplex stability.

  16. Quantum chemical density functional theory studies on the molecular structure and vibrational spectra of Gallic acid imprinted polymers

    Science.gov (United States)

    Pardeshi, Sushma; Dhodapkar, Rita; Kumar, Anupama

    2013-12-01

    Gallic acid (GA) is known by its antioxidant, anticarcinogenic properties and scavenger activity against several types of harmful free radicals. Molecularly imprinted polymers (MIPs) are used in separation of a pure compound from complex matrices. A stable template-monomer complex generates the MIPs with the highest affinity and selectivity for the template. The quantum chemical computations based on density functional theory (DFT) was used on the template Gallic acid (GA), monomer acrylic acid (AA) and GA-AA complex to study the nature of interactions involved in the GA-AA complex. B3LYP/6-31+G(2d,2p) model chemistry was used to optimize their structures and frequency calculations. The effect of porogen acetonitrile (ACN) on complex formation was included by using polarizable continuum model (PCM). The results demonstrated the formation of a stable GA-AA complex through the intermolecular hydrogen bonding between carboxylic acid groups of GA and AA. The Mulliken atomic charge analysis and simulated vibrational spectra also supported the stable hydrogen bonding interaction between the carboxylic acid groups of GA and AA with minimal interference of porogen ACN. Further, simulations on GA-AA mole ratio revealed that 1:4 GA-AA was optimum for synthesis of MIP for GA.

  17. Molecular features of the L-type amino acid transporter 2 determine different import and export profiles for thyroid hormones and amino acids.

    Science.gov (United States)

    Hinz, Katrin M; Neef, Dominik; Rutz, Claudia; Furkert, Jens; Köhrle, Josef; Schülein, Ralf; Krause, Gerd

    2017-03-05

    The L-type amino acid transporter 2 (LAT2) imports amino acids (AA) and also certain thyroid hormones (TH), e.g. 3,3'-T2 and T3, but not rT3 and T4. We utilized LAT2 mutations (Y130A, N133S, F242W) that increase 3,3'-T2 import and focus here on import and export capacity for AA, T4, T3, BCH and derivatives thereof to delineate molecular features. Transport studies and analysis of competitive inhibition of import by radiolabelled TH and AA were performed in Xenopus laevis oocytes. Only Y130A, a pocket widening mutation, enabled import for T4 and increased it for T3. Mutant F242W showed increased 3,3'-T2 import but no import rates for other TH derivatives. No export was detected for any TH by LAT2-wild type (WT). Mutations Y130A and N133S enabled only the export of 3,3'-T2, while N133S also increased AA export. Thus, distinct molecular LAT2-features determine bidirectional AA transport but only an unidirectional 3,3'-T2 and T3 import.

  18. Amino acid composition, molecular weight distribution and gel electrophoresis of walnut (Juglans regia L.) proteins and protein fractionations.

    Science.gov (United States)

    Mao, Xiaoying; Hua, Yufei; Chen, Guogang

    2014-01-01

    As a by-product of oil production, walnut proteins are considered as an additional source of plant protein for human food. To make full use of the protein resource, a comprehensive understanding of composition and characteristics of walnut proteins are required. Walnut proteins have been fractionated and characterized in this study. Amino acid composition, molecular weight distribution and gel electrophoresis of walnut proteins and protein fractionations were analyzed. The proteins were sequentially separated into four fractions according to their solubility. Glutelin was the main component of the protein extract. The content of glutelin, albumin, globulin and prolamin was about 72.06%, 7.54%, 15.67% and 4.73% respectively. Glutelin, albumin and globulin have a balanced content of essential amino acids, except for methionine, with respect to the FAO pattern recommended for adults. SDS-PAGE patterns of albumin, globulin and glutelin showed several polypeptides with molecular weights 14.4 to 66.2 kDa. The pattern of walnut proteins in two-dimension electrophoresis (2-DE) showed that the isoelectric point was mainly in the range of 4.8-6.8. The results of size exclusion chromatogram indicated molecular weight of the major components of walnut proteins were between 3.54 and 81.76 kDa.

  19. Amino Acid Composition, Molecular Weight Distribution and Gel Electrophoresis of Walnut (Juglans regia L. Proteins and Protein Fractionations

    Directory of Open Access Journals (Sweden)

    Xiaoying Mao

    2014-01-01

    Full Text Available As a by-product of oil production, walnut proteins are considered as an additional source of plant protein for human food. To make full use of the protein resource, a comprehensive understanding of composition and characteristics of walnut proteins are required. Walnut proteins have been fractionated and characterized in this study. Amino acid composition, molecular weight distribution and gel electrophoresis of walnut proteins and protein fractionations were analyzed. The proteins were sequentially separated into four fractions according to their solubility. Glutelin was the main component of the protein extract. The content of glutelin, albumin, globulin and prolamin was about 72.06%, 7.54%, 15.67% and 4.73% respectively. Glutelin, albumin and globulin have a balanced content of essential amino acids, except for methionine, with respect to the FAO pattern recommended for adults. SDS-PAGE patterns of albumin, globulin and glutelin showed several polypeptides with molecular weights 14.4 to 66.2 kDa. The pattern of walnut proteins in two-dimension electrophoresis (2-DE showed that the isoelectric point was mainly in the range of 4.8–6.8. The results of size exclusion chromatogram indicated molecular weight of the major components of walnut proteins were between 3.54 and 81.76 kDa.

  20. Stearic acid and high molecular weight PEO as matrix for the highly water soluble metoprolol tartrate in continuous twin-screw melt granulation

    OpenAIRE

    Monteyne, Tinne; Adriaensens, Peter; Brouckaert, Davinia; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-01-01

    Granules with release-sustaining properties were developed by twin screw hot melt granulation (HMG) using a combination of stearic acid (SA) and high molecular weight polyethylene oxide (PEO) as matrix for a highly water soluble model drug, metoprolol tartrate (MPT). Earlier studies demonstrated that mixing molten SA and PEO resulted in hydrogen bond formation between hydroxyl groups of fatty acid molecules and ether groups in PEO chains. These molecular interactions might be beneficial in or...

  1. The Correlation of Binary Acid Strengths with Molecular Properties in First-Year Chemistry

    Science.gov (United States)

    Fridgen, Travis D.

    2008-01-01

    This article deals with the rather complicated if not incorrect way that the strengths of binary acids are rationalized to students in many classrooms owing to the way it is presented in first-year chemistry textbooks. The common explanations, which use the homolytic bond dissociation energy as a rationalization of the trend in acid strengths when…

  2. The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120)

    DEFF Research Database (Denmark)

    Hudson, Brian D; Shimpukade, Bharat; Milligan, Graeme

    2014-01-01

    The long-chain fatty acid receptor FFA4 (previously GPR120) is receiving substantial interest as a novel target for the treatment of metabolic and inflammatory disease. This study examines for the first time the detailed mode of binding of both long-chain fatty acid and synthetic agonist ligands ...

  3. The Farnesoid X receptor - A molecular link between bile acid and lipid and glucose metabolism

    NARCIS (Netherlands)

    Claudel, T; Staels, B; Kuipers, F

    2005-01-01

    Bile acids are the end products of cholesterol metabolism. They are synthesized in the liver and secreted via bile into the intestine, where they aid in the absorption of fat-soluble vitamins and dietary fat. Subsequently, bile acids return to the liver to complete their enterohepatic circulation. T

  4. Q开关1064 nm激光联合氨甲环酸治疗黄褐斑临床观察%Combined Q-Switched Nd: YAG Laser and oral tranexamic acid for the treatment of melasma

    Institute of Scientific and Technical Information of China (English)

    邓永辉; 苑凯华; 李勤; 蔡金辉

    2013-01-01

    目的 探讨Q开关1064 nm激光联合氨甲环酸治疗黄褐斑的临床疗效和安全性.方法 100例黄褐斑患者随机分为两组,每组50例.A组接受Q开关1064 nm激光治疗,同时口服氨甲环酸;B组单纯接受Q开关1064 nm激光治疗.经过3个疗程治疗后观察疗效及不良反应.结果 A组基本治愈率46%,有效率74%;B组基本治愈率18%,有效率30.2%,两组疗效差异有统计学意义(P<0.05).口服氨甲环酸8个月未见严重不良反应.结论 口服氨甲环酸可提高Q开关1064 nm激光治疗黄褐斑的临床疗效,且不良反应小.%Objective To explore the clinical effect and safety of treating melasma with the combination of Q-Switched Nd:YAG Laser and oral tranexamic acid. Methods One hundred patients were randomly divided into group A and B. Group A was treated by Q-Switched Nd:YAG Laser combinated with oral tranexamic acid. Group B was only treated by Q-Switched Nd:YAG Laser. The clinical effect and side effects were observed after three courses of treatment. Results In group A, the basic cure rates was 46%, total effective rate was 74%. In group B, the basic cure rates was 18%, total effective rate was 30.2%. The results had significant difference between the two groups (P<0.05). Conclusion Combination therapy can promote the efficacy of melasma and without severe side-effects.

  5. Q开关激光辅助氨甲环酸治疗黄褐斑疗效观察%Clinical efficacy of using Q-Switched Nd:YAG Laser combined with tranexamic acid for the treatment of melasma

    Institute of Scientific and Technical Information of China (English)

    陈晓莉; 蒋艳; 皮超; 王鸿健; 高鹃

    2015-01-01

    目的:观察Q开关1064nm激光辅助氨甲环酸治疗黄褐斑的疗效与不良反应。方法:入组女性黄褐斑患者共280例,随机分两组,每组140例。治疗组:采用Q开关1064nm激光辅助口服氨甲环酸治疗;对照组:单独使用Q开关1064nm激光治疗。治疗6个周期后对比分析两组患者疗效与不良反应情况。结果:治疗组基本治愈率46.43%,有效率75.00%;对照组基本治愈率17.86%,有效率32.14%,两组间差异有统计学意义(P<0.05)。治疗组无严重不良反应发生。结论:Q开关1064nm激光辅助口服氨甲环酸可以提高黄褐斑的疗效。%Objective To explore the clinical efficacy of using Q-Switched Nd:YAG Laser combined with tranexamic acid for the treatment of melasma. Methods Two hundred and eighty patients were randomized into treatment group and control group. The treatment group was treated by Q-Switched Nd:YAG Laser combinated with oral tranexamic acid. The control group was only treated by Q-Switched Nd:YAG Laser. The clinical effect and side effects were observed after six courses of treatment. Results In the treatment group, the basic cure rates was 46.43%, total effective rate was 75.00%. In the control group, the basic cure rates was 17.86%, total effective rate was 32.14%. The results had significant difference between the two groups (P<0.05). Conclusion Combination therapy can promote the efficacy of melasma and without severe side effects.

  6. Molecular docking study investigating the possible mode of binding of C.I. Acid Red 73 with DNA.

    Science.gov (United States)

    Guo, Yumei; Yue, Qinyan; Gao, Baoyu

    2011-07-01

    C.I. Acid Red 73 is a reactive azo dye with a variable potential carcinogenicity. The mechanism mediating interactions that occur between the dye and DNA have not been completely understood thus far. In this study, molecular docking techniques were applied to describe the most probable mode of DNA binding as well as the sequence selectivity of the C.I. Acid Red 73 dye. These docking experiments revealed that the dye is capable of interacting with the minor groove of the DNA on the basis of its curved shape, which fits well with the topology of double-stranded DNA. In addition, the dye can bind selectively to the minor groove of the DNA by applying CGT sequence selectivity. Further, the minor groove can be recognized although DNA targets present intercalation gaps. However, intercalative binding can also occur when the DNA target possesses an appropriate intercalation gap. Compared with the other eight DNA sequences that were studied, the DNA dodecamer d(CGCGATATCGCG)(2) (PDB ID: 1DNE) presents a very favorable target for the binding of C.I. Acid Red 73 to the minor groove, with the lowest binding free energy -9.19 kcal/mol. Results reported from this study are expected to provide useful information for research involving further simulations of molecular dynamics and toxicology investigations of the dye.

  7. Molecular dynamics simulations of triflic acid and triflate ion/water mixtures: a proton conducting electrolytic component in fuel cells.

    Science.gov (United States)

    Sunda, Anurag Prakash; Venkatnathan, Arun

    2011-11-30

    Triflic acid is a functional group of perflourosulfonated polymer electrolyte membranes where the sulfonate group is responsible for proton conduction. However, even at extremely low hydration, triflic acid exists as a triflate ion. In this work, we have developed a force-field for triflic acid and triflate ion by deriving force-field parameters using ab initio calculations and incorporated these parameters with the Optimized Potentials for Liquid Simulations - All Atom (OPLS-AA) force-field. We have employed classical molecular dynamics (MD) simulations with the developed force field to characterize structural and dynamical properties of triflic acid (270-450 K) and triflate ion/water mixtures (300 K). The radial distribution functions (RDFs) show the hydrophobic nature of CF(3) group and presence of strong hydrogen bonding in triflic acid and temperature has an insignificant effect. Results from our MD simulations show that the diffusion of triflic acid increases with temperature. The RDFs from triflate ion/water mixtures shows that increasing hydration causes water molecules to orient around the SO(3)(-) group of triflate ions, solvate the hydronium ions, and other water molecules. The diffusion of triflate ions, hydronium ion, and water molecules shows an increase with hydration. At λ = 1, the diffusion of triflate ion is 30 times lower than the diffusion of triflic acid due to the formation of stable triflate ion-hydronium ion complex. With increasing hydration, water molecules break the stability of triflate ion-hydronium ion complex leading to enhanced diffusion. The RDFs and diffusion coefficients of triflate ions, hydronium ions and water molecules resemble qualitatively the previous findings using per-fluorosulfonated membranes.

  8. Phragmites australis response to Cu in terms of low molecular weight organic acids (LMWOAs) exudation: Influence of the physiological cycle

    Science.gov (United States)

    Rocha, A. Cristina S.; Almeida, C. Marisa R.; Basto, M. Clara P.; Vasconcelos, M. Teresa S. D.

    2014-06-01

    Plant roots have the ability to produce and secrete substances, such as aliphatic low molecular weight organic acids (ALMWOAs), into the rhizosphere for several purposes, including in response to metal contamination. Despite this, little is yet known about the exudation of such substances from marsh plants roots in response to metal exposure. This work aimed at assessing the influence of the physiological cycle of marsh plants on the exudation of ALMWOAs in response to Cu contamination. In vitro experiments were carried out with Phragmites australis specimens, collected in different seasons. Plant roots were exposed to freshwater contaminated with two different Cu concentrations (67 μg/L and 6.9 mg/L), being the ALMWOAs released by the roots measured. Significant differences (both qualitative and quantitative) were observed during the Phragmites australis life cycle. At growing stage, Cu stimulated the exudation of oxalic and formic acids but no significant stimulation was observed for citric acid. At developing stage, exposure to Cu caused inhibition of oxalic acid exudation whereas citric acid liberation was stimulated but only in the media spiked with the lowest Cu concentration tested. At the decaying stage, no significant variation on oxalic acid was observed, whereas the citric and formic acids release increased as a consequence of the plant exposure to Cu. The physiological cycle of Phragmites australis, and probably also of other marsh plants, is therefore an important feature conditioning plants response to Cu contamination, in terms of ALMWOAs exudation. Hence this aspect should be considered when conducting studies on rhizodeposition involving marsh plants exposed to metals and in the event of using marsh plants for phytoremediation purposes in contaminated estuarine areas.

  9. Charting molecular composition of phosphatidylcholines by fatty acid scanning and ion trap MS3 fragmentation

    DEFF Research Database (Denmark)

    Ekroos, Kim; Ejsing, Christer S.; Bahr, Ute

    2003-01-01

    The molecular composition of phosphatidylcholines (PCs) in total lipid extracts was characterized by a combination of multiple precursor ion scanning on a hybrid quadrupole time-of-flight mass spectrometer and MS3 fragmentation on an ion trap mass spectrometer. Precursor ion spectra for 50 acyl...... spectrometer quantified the relative amount of their positional isomers, thus providing the most detailed and comprehensive characterization of the molecular composition of the pool of PCs at the low-picomole level. The method is vastly simplified, compared with conventional approaches, and does not require...... preliminary separation of lipid classes or of individual molecular species, enzymatic digestion, or chemical derivatization. The approach was validated by the comparative analysis of the molecular composition of PCs from human red blood cells. In the total lipid extract of Madin-Darby canine kidney II cells...

  10. Resonance Energy Transfer-Based Molecular Switch Designed Using a Systematic Design Process Based on Monte Carlo Methods and Markov Chains

    Science.gov (United States)

    Rallapalli, Arjun

    A RET network consists of a network of photo-active molecules called chromophores that can participate in inter-molecular energy transfer called resonance energy transfer (RET). RET networks are used in a variety of applications including cryptographic devices, storage systems, light harvesting complexes, biological sensors, and molecular rulers. In this dissertation, we focus on creating a RET device called closed-diffusive exciton valve (C-DEV) in which the input to output transfer function is controlled by an external energy source, similar to a semiconductor transistor like the MOSFET. Due to their biocompatibility, molecular devices like the C-DEVs can be used to introduce computing power in biological, organic, and aqueous environments such as living cells. Furthermore, the underlying physics in RET devices are stochastic in nature, making them suitable for stochastic computing in which true random distribution generation is critical. In order to determine a valid configuration of chromophores for the C-DEV, we developed a systematic process based on user-guided design space pruning techniques and built-in simulation tools. We show that our C-DEV is 15x better than C-DEVs designed using ad hoc methods that rely on limited data from prior experiments. We also show ways in which the C-DEV can be improved further and how different varieties of C-DEVs can be combined to form more complex logic circuits. Moreover, the systematic design process can be used to search for valid chromophore network configurations for a variety of RET applications. We also describe a feasibility study for a technique used to control the orientation of chromophores attached to DNA. Being able to control the orientation can expand the design space for RET networks because it provides another parameter to tune their collective behavior. While results showed limited control over orientation, the analysis required the development of a mathematical model that can be used to determine the

  11. The nucleic acid revolution continues - will forensic biology become forensic molecular biology?

    Science.gov (United States)

    Gunn, Peter; Walsh, Simon; Roux, Claude

    2014-01-01

    Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to "forensic molecular biology." Aside from DNA's established role in identifying the "who" in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about "when" a crime took place and "what" took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

  12. The nucleic acid revolution continues – will forensic biology become forensic molecular biology ?

    Directory of Open Access Journals (Sweden)

    Peter eGunn

    2014-03-01

    Full Text Available Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to forensic molecular biology.Aside from DNA’s established role in identifying the who in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about when a crime took place and what took place.However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

  13. Molecular cloning and functional characterization of a Δ6-fatty acid desaturase gene from Rhizopus oryzae.

    Science.gov (United States)

    Zhu, Yu; Zhang, Bi-Bo

    2013-09-01

    The objective was to screen for and isolate a novel enzyme with the specific activity of a Δ6-fatty acid desaturase from Rhizopus oryzae. In this study, R. oryzae was identified as a novel fungal species that produces large amounts of γ-linolenic acid. A full-length cDNA, designated here as RoD6D, with high homology to fungal Δ6-fatty acid desaturase genes was isolated from R. oryzae by using the rapid amplification of cDNA ends method. It had an open reading frame of 1176 bp encoding a deduced polypeptide of 391 amino acids. Bioinformatics analysis characterized the putative RoD6D protein as a typical membrane-bound desaturase, including three conserved histidine-rich motifs, a hydropathy profile, and a cytochrome b5 -like domain in the N terminus. When the coding sequence was expressed in the Saccharomyces cerevisiae strain INVScl, the encoded product of RoD6D exhibited Δ6-fatty acid desaturase activity that led to the accumulation of γ-linolenic acid. The corresponding genomic sequence of RoD6D was 1565 bp in length, with five introns. This is the first report on the characterization and gene cloning of a Δ6-fatty acid desaturase of R. oryzae from Douchi.

  14. Molecular sled is an eleven-amino acid vehicle facilitating biochemical interactions via sliding components along DNA.

    Science.gov (United States)

    Mangel, Walter F; McGrath, William J; Xiong, Kan; Graziano, Vito; Blainey, Paul C

    2016-02-02

    Recently, we showed the adenovirus proteinase interacts productively with its protein substrates in vitro and in vivo in nascent virus particles via one-dimensional diffusion along the viral DNA. The mechanism by which this occurs has heretofore been unknown. We show sliding of these proteins along DNA occurs on a new vehicle in molecular biology, a 'molecular sled' named pVIc. This 11-amino acid viral peptide binds to DNA independent of sequence. pVIc slides on DNA, exhibiting the fastest one-dimensional diffusion constant, 26±1.8 × 10(6) (bp)(2) s(-1). pVIc is a 'molecular sled,' because it can slide heterologous cargos along DNA, for example, a streptavidin tetramer. Similar peptides, for example, from the C terminus of β-actin or NLSIII of the p53 protein, slide along DNA. Characteristics of the 'molecular sled' in its milieu (virion, nucleus) have implications for how proteins in the nucleus of cells interact and imply a new form of biochemistry, one-dimensional biochemistry.

  15. Analytical strategy for the molecular weight determination of random copolymers of poly(methyl methacrylate) and poly(methacrylic acid).

    Science.gov (United States)

    Giordanengo, Rémi; Viel, Stéphane; Hidalgo, Manuel; Allard-Breton, Béatrice; Thévand, André; Charles, Laurence

    2010-06-01

    Molecular weight characterization of random amphiphilic copolymers currently represents an analytical challenge. In particular, molecules composed of methacrylic acid (MAA) and methyl methacrylate (MMA) as the repeat units raise issues in commonly used techniques. The present study shows that when random copolymers cannot be properly ionized by MALDI, and hence detected and measured in MS, one possible analytical strategy is to transform them into homopolymers, which are more amenable to this ionization technique. Then, by combining the molecular weight of the so-obtained homopolymers, as measured by MS, with the relative molar proportion of the MMA and MMA units, as given by (1)H NMR spectrum, one can straightforwardly estimate the molecular weight of the initial copolymer. A methylation reaction was performed to transform MAA-MMA copolymer samples into PMMA homopolymers, using trimethylsilyldiazomethane as a derivatization agent. Weight average molecular weight (M(w)) parameters of the MAA-MMA copolymers could then be derived from M(w) values obtained for the methylated MAA-MMA molecules by MALDI, which were also validated by pulsed gradient spin echo (PGSE) NMR. An alkene function in one of the studied copolymer end-groups was also shown to react with the methylation agent, giving rise to MMA-like polymeric by-products characterized by tandem mass spectrometry and which could be avoided by adjusting the amount of the trimethylsilyldiazomethane in the reaction medium.

  16. Acid Hydrolysis and Molecular Density of Phytoglycogen and Liver Glycogen Helps Understand the Bonding in Glycogen α (Composite) Particles

    Science.gov (United States)

    Powell, Prudence O.; Sullivan, Mitchell A.; Sheehy, Joshua J.; Schulz, Benjamin L.; Warren, Frederick J.; Gilbert, Robert G.

    2015-01-01

    Phytoglycogen (from certain mutant plants) and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired. PMID:25799321

  17. Acid hydrolysis and molecular density of phytoglycogen and liver glycogen helps understand the bonding in glycogen α (composite particles.

    Directory of Open Access Journals (Sweden)

    Prudence O Powell

    Full Text Available Phytoglycogen (from certain mutant plants and animal glycogen are highly branched glucose polymers with similarities in structural features and molecular size range. Both appear to form composite α particles from smaller β particles. The molecular size distribution of liver glycogen is bimodal, with distinct α and β components, while that of phytoglycogen is monomodal. This study aims to enhance our understanding of the nature of the link between liver-glycogen β particles resulting in the formation of large α particles. It examines the time evolution of the size distribution of these molecules during acid hydrolysis, and the size dependence of the molecular density of both glucans. The monomodal distribution of phytoglycogen decreases uniformly in time with hydrolysis, while with glycogen, the large particles degrade significantly more quickly. The size dependence of the molecular density shows qualitatively different shapes for these two types of molecules. The data, combined with a quantitative model for the evolution of the distribution during degradation, suggest that the bonding between β into α particles is different between phytoglycogen and liver glycogen, with the formation of a glycosidic linkage for phytoglycogen and a covalent or strong non-covalent linkage, most probably involving a protein, for glycogen as most likely. This finding is of importance for diabetes, where α-particle structure is impaired.

  18. Car-Parrinello and path integral molecular dynamics study of the hydrogen bond in the chloroacetic acid dimer system

    Science.gov (United States)

    Durlak, Piotr; Morrison, Carole A.; Middlemiss, Derek S.; Latajka, Zdzislaw

    2007-08-01

    We have studied the double proton transfer (DPT) reaction in the cyclic dimer of chloroacetic acid using both classical and path integral Car-Parrinello molecular dynamics. We also attempt to quantify the errors in the potential energy surface that arise from the use of a pure density functional. In the classical dynamics a clear reaction mechanism can be identified, where asynchronized DPT arises due to coupling between the O-H stretching oscillator and several low energy intermolecular vibrational modes. This mechanism is considerably altered when quantum tunneling is permitted in the simulation. The introduction of path integrals leads to considerable changes in the thermally averaged molecular geometry, leading to shorter and more centered hydrogen bond linkages.

  19. Topology and parameter data of thirteen non-natural amino acids for molecular simulations with CHARMM22

    Directory of Open Access Journals (Sweden)

    Olujide O. Olubiyi

    2016-12-01

    Full Text Available In this article we provide a data package containing the topology files and parameters compatible with the CHARMM22 force field for thirteen non-natural amino acids. The force field parameters were derived based on quantum mechanical (QM calculations involving geometry optimization and potential energy surface scanning at the HF 6-31G(d and HF 6-311G(d,p levels of theory. The resulting energy data points were fitted to mathematical functions representing each component of the CHARMM22 force field. Further fine-tuning of the parameters utilized molecular mechanics energies, which were iteratively calculated and compared to the corresponding QM values until the latter were satisfactorily reproduced. The final force field data were validated with molecular dynamics simulations in explicit solvent conditions.

  20. Surface grafted chitosan gels. Part I. Molecular insight into the formation of chitosan and poly(acrylic acid) multilayers

    DEFF Research Database (Denmark)

    Liu, Chao; Thormann, Esben; Claesson, Per M.

    2014-01-01

    Composite polyelectrolyte multilayers of chitosan and low molecular weight poly(acrylic acid) (PAA) have been assembled by sequential adsorption as a first step toward building a surface anchored chitosan gel. Silane chemistry was used to graft the first chitosan layer to prevent film detachment...... and decomposition. The assembly process is characterized by nonlinear growth behavior, with different adsorption kinetics for chitosan and PAA. In situ analysis of the multilayer by means of surface sensitive total internal reflection Raman (TIRR) spectroscopy, combined with target factor analysis of the spectra...... molecular weight chitosan shows a similar behavior, although to a much lower extent. Our data demonstrate that the charged monomeric units of chitosan are mainly compensated by carboxylate ions from PAA. Furthermore, the morphology and mechanical properties of the multilayers were investigated in situ using...

  1. Formation of molecular complexes of salicylic acid, acetylsalicylic acid, and methyl salicylate in a mixture of supercritical carbon dioxide with a polar cosolvent

    Science.gov (United States)

    Petrenko, V. E.; Antipova, M. L.; Gurina, D. L.; Odintsova, E. G.

    2015-08-01

    The solvate structures formed by salicylic acid, acetylsalicylic acid, and methyl salicylate in supercritical (SC) carbon dioxide with a polar cosolvent (methanol, 0.03 mole fractions) at a density of 0.7 g/cm3 and a temperature of 318 K were studied by the molecular dynamics method. Salicylic and acetylsalicylic acids were found to form highly stable hydrogen-bonded complexes with methanol via the hydrogen atom of the carboxyl group. For methyl salicylate in which the carboxyl hydrogen is substituted by a methyl radical, the formation of stable hydrogen bonds with methanol was not revealed. The contribution of other functional groups of the solute to the interactions with the cosolvent was much smaller. An analysis of correlations between the obtained data and the literature data on the cosolvent effect on the solubility of the compounds in SC CO2 showed that the dissolving ability of SC CO2 with respect to a polar organic substance in the presence of a cosolvent increased only when stable hydrogen-bonded complexes are formed between this substance and the cosolvent.

  2. Phenotypic, genetic and molecular characterization of a maize low phytic acid mutant (lpa241)

    DEFF Research Database (Denmark)

    Pilu, R.; Panzeri, D.; Gavazzi, G.

    2003-01-01

    Phytic acid, myo-inositol 1,2,3,4,5,6-hexakisphosphate, is the major storage compound of phosphorous (P) in plants, predominantly accumulating in seeds (up to 4-5% of dry weight) and pollen. In cereals, phytic acid is deposited in embryo and aleurone grain tissues as a mixed 'phytate' salt...... of potassium and magnesium, although phytates contain other mineral cations such as iron and zinc. During germination, phytates are broken down by the action of phytases, releasing their P, minerals and myo-inositol which become available to the growing seedling. Phytic acid represents an anti...

  3. From amino acids to nature-inspired molecular scaffolds: incorporation of medium-sized bridged heterocycles into a peptide backbone.

    Science.gov (United States)

    La-Venia, Agustina; Ventosa-Andrés, Pilar; Hradilová, Ludmila; Krchňák, Viktor

    2014-11-07

    Novel molecular scaffolds comprising two to four bridged and fused heterocycles were synthesized from amino acids using seven-membered endocyclic N-acyliminium ions as key intermediates in acid-mediated tandem reactions with internal nucleophiles. This complexity-generating synthesis proceeds with high efficiency and with full stereocontrol of the newly generated stereogenic center. These results have extended the scope of medium-sized cyclic iminium ion chemistry, making it applicable as a regio- and stereoselective synthetic strategy for the generation of complex polycyclic structures. Furthermore, its compatibility with the traditional Merrifield synthesis of peptides on solid supports allowed the incorporation of the previously unexplored conformationally restricted cyclic systems into peptides without a need to independently synthesize the scaffold.

  4. Molecularly imprinted poly(N-vinyl imidazole) based polymers grafted onto nonwoven fabrics for recognition/removal of phloretic acid

    Science.gov (United States)

    Llorina Rañada, Ma.; Akbulut, Meshude; Abad, Lucille; Güven, Olgun

    2014-01-01

    A solution of N-vinyl imidazole (VIm), ethylene glycol dimethylacrylate (EGDMA), and phloretic acid (p-hydroxyphenylpropionic acid, HPPA) as functional monomer, crosslinker and template, respectively, were used to graft molecularly imprinted polymer (MIP) onto polyethylene/polypropylene (PE/PP) nonwoven fabric via gamma radiation at room temperature. Control grafted films were also synthesized using the same procedure in the absence of HPPA. Binding performance of the MIP grafts was investigated for different template molecule concentrations and contact time. An imprinting factor for the sample prepared at 5 kGy dose was determined as 2.41 for 50 ppm HPPA solution for 3-h incubation. MIP graft layers were investigated by positron annihilation lifetime spectroscopy (PALS) as well as SEM.

  5. Experimental and Molecular Dynamics Simulations for Investigating the Effect of Fatty Acid and Its Derivatives on Low Sulfur Diesel Lubricity

    Institute of Scientific and Technical Information of China (English)

    Luo Hui; Fan Weiyu; Li Yang; Zhao Pinhui; Nan Guozhi

    2013-01-01

    In this work, fatty acid and its derivatives were adopted as lubricity additives for low sulfur diesel. Tribological evaluation obtained from the High-Frequency Reciprocating Rig (HFRR) apparatus showed that the lubricating performance of the additives increased in the following order:stearic acid>glycol monopalmitate>stearyl alcohol>ethyl palmitate>cetyl ethyl ether. The adsorption behavior of the additives on Fe (110) surface and Fe2O3 (001) surface was investigated by mo-lecular dynamics (MD) simulations to verify their lubricity performance. The results suggested that adsorption energies of the additives on Fe (110) surface are determined by the van der Waals forces, while adsorptions on Fe2O3 (001) surface are signiifcantly attributed to the electrostatic attractive forces. Higher values of adsorption energy of the additives on Fe2O3 (001) surface indicate that the additive has more efifcient lubricity enhancing properties.

  6. Molecular characteristics of humic acids isolated from vermicomposts and their relationship to bioactivity.

    Science.gov (United States)

    Martinez-Balmori, Dariellys; Spaccini, Riccardo; Aguiar, Natália Oliveira; Novotny, Etelvino Henrique; Olivares, Fábio Lopes; Canellas, Luciano Pasqualoto

    2014-11-26

    Vermitechnology is an effective composting method, which transforms biomass into nutrient-rich organic fertilizer. Mature vermicompost is a renewable organic product containing humic substances with high biological activity. The aim of this study was to assess the chemical characteristics and the bioactivity of humic acids isolated from different vermicomposts produced with either cattle manure, sugar cane bagasse, sunflower cake from seed oil extraction, or filter cake from a sugar cane factory. More than 200 different molecules were found, and it was possible to identify chemical markers on humic acids according to the nature of the organic source. The large hydrophobic character of humic extracts and the preservation of altered lignin derivatives confer to humic acids the ability to induce lateral root emergence in maize seedlings. Humic acid-like substances extracted from plant biomass residues represent an additional valuable product of vermicomposting that can be used as a plant growth promoter.

  7. Molecular Characterization of Intrinsic and Acquired antibiotic resistance in lactic Acid bacteria and Bifidobacteria

    NARCIS (Netherlands)

    Ammor, M.S.; Flórez, A.B.; Hoek, van A.H.A.M.; Reyes-Gavilan, de los C.G.; Aarts, H.J.M.; Margolles, A.; Mayo, B.

    2008-01-01

    The minimum inhibitory concentrations (MICs) of 6 different antibiotics (chloramphenicol, clindamycin, erythromycin, streptomycin, tetracycline and vancomycin) were determined for 143 strains of lactic acid bacteria and bifidobacteria using the Etest. Different MICs were found for different species

  8. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah

    2012-01-01

    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  9. Tetrazolyl isoxazole amino acids as ionotropic glutamate receptor antagonists: synthesis, modelling and molecular pharmacology.

    Science.gov (United States)

    Frølund, Bente; Greenwood, Jeremy R; Holm, Mai M; Egebjerg, Jan; Madsen, Ulf; Nielsen, Birgitte; Bräuner-Osborne, Hans; Stensbøl, Tine B; Krogsgaard-Larsen, Povl

    2005-09-15

    Two 3-(5-tetrazolylmethoxy) analogues, 1a and 1b, of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA), a selective AMPA receptor agonist, and (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA), a GluR5-preferring agonist, were synthesized. Compounds 1a and 1b were pharmacologically characterized in receptor binding assays, and electrophysiologically on homomeric AMPA receptors (GluR1-4), homomeric (GluR5 and GluR6) and heteromeric (GluR6/KA2) kainic acid receptors, using two-electrode voltage-clamped Xenopus laevis oocytes expressing these receptors. Both analogues proved to be antagonists at all AMPA receptor subtypes, showing potencies (Kb=38-161 microM) similar to that of the AMPA receptor antagonist (RS)-2-amino-3-[3-(carboxymethoxy)-5-methyl-4-isoxazolyl]propionic acid (AMOA) (Kb=43-76 microM). Furthermore, the AMOA analogue, 1a, blocked two kainic acid receptor subtypes (GluR5 and GluR6/KA2), showing sevenfold preference for GluR6/KA2 (Kb=19 microM). Unlike the iGluR antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid [(S)-ATPO], the corresponding tetrazolyl analogue, 1b, lacks kainic acid receptor effects. On the basis of docking to a crystal structure of the isolated extracellular ligand-binding core of the AMPA receptor subunit GluR2 and a homology model of the kainic acid receptor subunit GluR5, we were able to rationalize the observed structure-activity relationships.

  10. Chemical modification of chitosan film via surface grafting of citric acid molecular to promote the biomineralization

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yang, E-mail: liuyang@cczu.edu.cn [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Engineering Research Center of Nano-Geo Materials of Ministry of Education, China University of Geosciences, Wuhan 430074 (China); School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); Shen, Xin; Zhou, Huan [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China); Wang, Yingjun [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); Deng, Linhong, E-mail: dlh@cczu.edu.cn [Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164 (China)

    2016-05-01

    Graphical abstract: - Highlights: • Chitosan film was modified by surface grafting of citric acid. • The modified film has good hydrophilicity and moisture-retaining capacity. • The citric acid grafting treatment significantly promote the biomineralization. • MC3T3-E1 osteoblasts research confirms the biocompatibility of the film. - Abstract: We develop a novel chitosan–citric acid film (abbreviated as CS–CA) suitable for biomedical applications in this study. In this CS–CA film, the citric acid, which is a harmless organic acid has been extensively investigated as a modifying agent on carbohydrate polymers, was cross-linked by 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) onto the surface of chitosan (CS) film. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) confirms the graft copolymerization of the modified chitosan film (CS–CA). Surface wettability, moisturizing performance, the capacity of mineralization in vitro and biocompatibility of the films were characterized. After modification, this CS–CA film has good hydrophilicity. It is very evident that the citric acid grafting treatment significantly promotes the biomineralization of the chitosan based substrates. Cell experiments show that the MC3T3-E1 osteoblasts can adhere and proliferate well on the surface of CS–CA film. This CS–CA film, which can be prepared in large quantities and at low cost, should have potential application in bone tissue engineering.

  11. Factors affecting the interactions between beta-lactoglobulin and fatty acids as revealed in molecular dynamics simulations

    Science.gov (United States)

    Yi, Changhong; Wambo, Thierry O.

    2015-01-01

    Beta-lactoglobulin (BLG), a bovine dairy protein, is a promiscuously interacting protein that can bind multiple hydrophobic ligands. Fatty acids (FAs), common hydrophobic molecules bound to BLG, are important sources of fuel for life because they yield large quantities of ATP when metabolized. The binding affinity increases with the length of the ligands, indicating the importance of the van der Waals (vdW) interactions between the hydrocarbon tail and the hydrophobic calyx of BLG. An exception to this rule is caprylic acid (OCA) which is two-carbon shorter but has a stronger binding affinity than capric acid. Theoretical calculations in the current literature are not accurate enough to shed light on the underlying physics of this exception. The computed affinity values are greater for longer fatty acids without respect for the caprylic exception and those values are generally several orders of magnitude away from the experimental data. In this work, we used hybrid steered molecular dynamics to accurately compute the binding free energies between BLG and the five saturated FAs of 8 to 16 carbon atoms. The computed binding free energies agree well with experimental data not only in rank but also in absolute values. We gained insights into the exceptional behavior of caprylic acid in the computed values of entropy and electrostatic interactions. We found that the electrostatic interaction between the carboxyl group of caprylic acid and the two amino groups of K60/69 in BLG is much stronger than the vdW force between OCA’s hydrophobic tail and the BLG calyx. This pulls OCA to the top of the beta barrel where it is easier to fluctuate, giving rise to greater entropy of OCA at the binding site. PMID:26272099

  12. Molecularly imprinted polymer-matrix nanocomposite for enantioselective electrochemical sensing of D- and L-aspartic acid

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Bhim Bali, E-mail: prof.bbpd@yahoo.com; Srivastava, Amrita; Tiwari, Mahavir Prasad

    2013-10-15

    A new molecularly imprinted polymer-matrix (titanium dioxide nanoparticle/multiwalled carbon nanotubes) nanocomposite was developed for the modification of pencil graphite electrode as an enantioselective sensing probe for aspartic acid isomers, prevalent at ultra trace level in aqueous and real samples. The nanocomposite having many shape complementary cavities was synthesized adopting surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. The proposed sensor has high stability, nanocomposite uniformity, good reproducibility, and enhanced electrocatalytic activity to respond oxidative peak current of L-aspartic acid quantitatively by differential pulse anodic stripping voltammetry, without any cross-reactivity in real samples. Under the optimized operating conditions, the L-aspartic acid imprinted modified electrode showed a wide linear response for L-aspartic acid within the concentration range 9.98–532.72 ng mL{sup −1}, with the minimum detection limit of 1.73–1.79 ng mL{sup −1} (S/N = 3) in aqueous and real samples. Almost similar stringent limit (1.79 ng mL{sup −1}) was obtained with cerebrospinal fluid which is typical for the primitive diagnosis of neurological disorders, caused by an acute depletion of L-aspartic acid biomarker, in clinical settings. Highlights: • We have adopted surface initiated-activators regenerated by electron transfer for atom transfer radical polymerization. • This approach takes advantage of the nanostructured ultrathin imprinted film. • Successful enantioselective sensing and ultratrace analysis of D- and L-aspartic acid. • Stringent detection limit without any non-specific false-positive contribution.

  13. Combined effects of low-molecular-weight organic acids on mobilization of arsenic and lead from multi-contaminated soils.

    Science.gov (United States)

    Onireti, Olaronke O; Lin, Chuxia; Qin, Junhao

    2017-03-01

    A batch experiment was conducted to examine the combined effects of three common low-molecular-weight organic acids (LMWOAs) on the mobilization of arsenic and lead in different types of multi-contaminated soils. The capacity of individual LMWOAs (at a same molar concentration) to mobilize soil-borne As and Pb varied significantly. The combination of the organic acids did not make a marked "additive" effect on the mobilization of the investigated three elements. An "antagonistic" effect on element mobilization was clear in the treatments involving oxalic acid for some soils. The acid strength of a LMWOA did not play an important role in controlling the mobilization of elements. While the mobilization of As and Pb was closely associated with the dissolution of soil-borne Fe, soil properties such as original soil pH, organic matter contents and the total amount of the element relative to the total Fe markedly complicated the mobility of that element. Aging led to continual consumption of proton introduced from addition of LMWOAs and consequently caused dramatic changes in solution-borne Fe, which in turn resulted in change in As and Pb in the soil solution though different elements behaved differently.

  14. A comparison of the Maillard reactivity of proline to other amino acids using pyrolysis-molecular beam mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Luc Moens; Robert J. Evans; Michael J. Looker; Mark R. Nimlos [National Bioenergy Center, Golden, CO (United States). National Renewable Energy Laboratory

    2004-08-01

    Maillard chemistry, or the low temperature condensation of amino acids and carbohydrates, is shown to be relevant to the practical regime of biomass pyrolysis and leads to dramatic changes in low-temperature volatile products and residual solid structure. Mixtures of amino acids and glucose were subjected to a two-temperature heating sequence (5 min each at 170 and 325{sup o}C) and the volatile products analyzed by molecular beam mass spectrometry. Significant volatile yield was observed from the mixtures at 170{sup o}C where neither amino acids nor glucose generated volatile material in the time frame studied. Proline was the most active of the amino acids studied. Volatile products at low temperature included the diketopiperazine, which were generated in higher yields than from proline alone. Also generated were Maillard condensation such as 1-(1{prime}-pyrrolidinyl)-2-propanone. These products were also generated at 325{sup o}C, but in addition, the mass spectra included evidence for the direct formation of nitrogen-containing aromatics. These observations are discussed in relation to known Maillard chemistry. 37 refs., 8 figs., 1 tab.

  15. FreeSWITCH Cookbook

    CERN Document Server

    Minessale, Anthony

    2012-01-01

    This is a problem-solution approach to take your FreeSWITCH skills to the next level, where everything is explained in a practical way. If you are a system administrator, hobbyist, or someone who uses FreeSWITCH on a regular basis, this book is for you. Whether you are a FreeSWITCH expert or just getting started, this book will take your skills to the next level.

  16. Single Atom Plasmonic Switch

    OpenAIRE

    Emboras, Alexandros; Niegemann, Jens; Ma, Ping; Haffner, Christian; Luisier, Mathieu; Hafner, Christian; Schimmel, Thomas; Leuthold, Juerg

    2015-01-01

    The atom sets an ultimate scaling limit to Moores law in the electronics industry. And while electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling-similar to electronics-is only limited by the atom. More precisely, we introduce an electrically controlled single atom plasmonic switch. The switch allows for fast and reproducible switching by means of the relocation of an individ...

  17. Atomic Scale Plasmonic Switch

    OpenAIRE

    Emboras, A.; Niegemann, J.; Ma, P.; Haffner, C; Pedersen, A.; Luisier, M.; Hafner, C.; Schimmel, T.; Leuthold, J.

    2016-01-01

    The atom sets an ultimate scaling limit to Moore’s law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocat...

  18. Production of nanocrystalline cellulose from an empty fruit bunches using sulfuric acid hydrolysis: Effect of reaction time on the molecular characteristics

    Science.gov (United States)

    Al-Dulaimi, Ahmed A.; R, Rohaizu; D, Wanrosli W.

    2015-06-01

    Nanocrystalline cellulose (NCC) was isolated from OPEFB pulp via sulfuric acid hydrolysis. The influence of reaction time to the molecular weight and surface charge of the NCC was investigated. Characterization of the product was carried out using zeta potential measurement and gel permeation chromatography test. Zeta potential measurement showed that the surface negative charge significantly increases with increasing reaction time. Gel permeation chromatography test indicates that molecular weight of NCC change variably with increasing of hydrolysis time. (Keywords: Nanocrystalline cellulose; acid hydrolysis; sulfate content; molecular weight)

  19. Switching to nilotinib in patients with chronic myeloid leukemia in chronic phase with molecular suboptimal response to frontline imatinib: SENSOR final results and BIM polymorphism substudy.

    Science.gov (United States)

    Miyamura, Koichi; Miyamoto, Toshihiro; Tanimoto, Mitsune; Yamamoto, Kazuhito; Kimura, Shinya; Kawaguchi, Tatsuya; Matsumura, Itaru; Hata, Tomoko; Tsurumi, Hisashi; Saito, Shigeki; Hino, Masayuki; Tadokoro, Seiji; Meguro, Kuniaki; Hyodo, Hideo; Yamamoto, Masahide; Kubo, Kohmei; Tsukada, Junichi; Kondo, Midori; Aoki, Makoto; Okada, Hikaru; Yanada, Masamitsu; Ohyashiki, Kazuma; Taniwaki, Masafumi

    2016-12-01

    Optimal management of patients with chronic myeloid leukemia in chronic phase with suboptimal molecular response (MR) to frontline imatinib is undefined. We report final results from SENSOR, which evaluated efficacy/safety of nilotinib in this setting. A substudy assessed whether BIM polymorphisms impacted response to nilotinib. In this single-arm, multicenter study, Japanese patients with suboptimal MR per European LeukemiaNet 2009 criteria (complete cytogenetic response, but not major MR [MMR]) after ≥18 months of frontline imatinib received nilotinib 400mg twice daily for 24 months. MR, BCR-ABL1 mutations/variants, and BIM polymorphisms were evaluated in a central laboratory. Primary endpoint was the MMR rate at 12 months (null hypothesis of 40%). Of 45 patients (median exposure, 22.08 months), 39 completed the study and six discontinued. At 12 and 24 months, 51.1% (95% CI, 35.8%-66.3%) and 66.7% (95% CI, 51.0%-80.0%) achieved MMR, respectively. Cumulative MMR incidence by 24 months was 75.6%. Of 40 patients analyzed, 10 of 12 (83.3%) with and 17 of 28 (60.7%) without BIM polymorphisms achieved MMR at 24 months. The safety profile was manageable with dose reductions and interruptions. Nilotinib provided clinical benefit for patients with suboptimal response to imatinib, and BIM polymorphisms did not influence MMR achievement. ClinicalTrials.gov: NCT01043874.

  20. Platform switching and bone platform switching.

    Science.gov (United States)

    Carinci, Francesco; Brunelli, Giorgio; Danza, Matteo

    2009-01-01

    Bone platform switching involves an inward bone ring in the coronal part of the implant that is in continuity with the alveolar bone crest. Bone platform switching is obtained by using a dental fixture with a reverse conical neck. A retrospective study was performed to evaluate the effectiveness of conventional vs reverse conical neck implants. In the period between May 2004 and November 2007, 86 patients (55 females and 31 males; median age, 53 years) were operated and 234 implants were inserted: 40 and 194 were conventional vs reverse conical neck implants, respectively. Kaplan-Meier algorithm and Cox regression were used to detect those variables associated with the clinical outcome. No differences in survival and success rates were detected between conventional vs reverse conical neck implants alone or in combination with any of the studied variables. Although bone platform switching leads to several advantages, no statistical difference in alveolar crest resorption is detected in comparison with reverse conical neck implants. We suppose that the proximity of the implant abutment junction to the alveolar crestal bone gives no protection against the microflora contained in the micrograph. Additional studies on larger series and a combination of platform switching and bone platform switching could lead to improved clinical outcomes.