Sample records for biologically inactive molecule

  1. Diversity in Biological Molecules (United States)

    Newbury, H. John


    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  2. Geochemical Origin of Biological Molecules (United States)

    Bassez, Marie-Paule


    A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article: 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the

  3. Carotenoids as signaling molecules in cardiovascular biology

    Directory of Open Access Journals (Sweden)

    Abolfazl Barzegari


    Full Text Available Oxidative stress and inflammation play important roles in the etiology of cardiovascular disease (CVD. Thus, natural antioxidant carotenoids existing in fruits and vegetables could have a significant role in the prevention of CVD. Nevertheless,clinical data are conflicting about the positive effect of some antioxidant carotenoids in reducing cardiovascular morbidity and mortality. Many biological actions of carotenoids have been attributed to their antioxidant effect; however, the precise mechanism by which carotenoids produce their beneficial effects is still under discussion. They might modulate molecular pathways involved in cell proliferation, acting at Akt, tyrosine kinases, mitogen activated protein kinase (MAP kinase and growth factor signaling cascades. Screening for a promising cardiovascular protective carotenoids therefore might be performed in vitro and in vivo with caution in cross-interaction with other molecules involved in signaling pathways especially those affecting microRNAs, performing a role in molecular modulation of cardiovascular cells.

  4. Gold Nanoparticle-Biological Molecule Interactions and Catalysis

    Directory of Open Access Journals (Sweden)

    Jonathan G. Heddle


    Full Text Available This review gives a brief summary of the field of gold nanoparticle interactions with biological molecules, particularly those with possible catalytic relevance. Gold nanoparticles are well known as catalysts in organic chemistry but much is unknown regarding their potential as catalysts of reactions involving biological molecules such as protein and nucleic acids. Biological molecules may be the substrate for catalysis or, if they are the ligand coating the gold particle, may be the catalyst itself. In other cases biological molecules may form a template upon which gold nanoparticles can be precisely arrayed. As relatively little is currently known about the catalytic capabilities of gold nanoparticles in this area, this review will consider templating in general (including, but not restricted to, those which result in structures having potential as catalysts before going on to consider firstly catalysis by the gold nanoparticle itself followed by catalysis by ligands attached to gold nanoparticles, all considered with a focus on biological molecules.

  5. Origins of the handedness of biological molecules. (United States)

    Mason, S F


    Pasteur (1860) showed that many organic molecules form enantiomeric pairs with non-superposable mirror-image shapes, characterized by their oppositely signed optical rotation but otherwise apparently identical. Equal numbers of left-handed and right-handed molecules resulted from laboratory synthesis, whereas biosynthetic processes afforded only one of the two enantiomers, leading Pasteur to conclude that biosynthesis involves a chiral force. Fischer demonstrated (1890-1919) that functional biomolecules are composed specifically of the D-sugars and the L-amino acids and that the laboratory synthetic reactions of such molecules propagate with chiral stereoselectivity. Given a primordial enantiomer, biomolecular homochirality follows without the intervention of a chiral natural force, except prebiotically. Chiral forces known at the time were found to be even handed on a time and space average, exemplifying parity conservation (1927). The weak nuclear force, shown to violate parity (1956), was unified with electro-magnetism in the electroweak force (1970). Ab initio estimations including the chiral electroweak force indicate that the L-amino acids and the D-sugars are more stable than the corresponding enantiomers. The small energy difference between these enantiomeric pairs, with Darwinian reaction kinetics in a flow reactor, account for the choice of biomolecular handedness made when life began.

  6. First molecules, biological chirality, origin(s) of life. (United States)

    Caglioti, Luciano; Micskei, Károly; Pályi, Gyula


    Origin(s) of biological chirality appear(s) to be intimately connected to origin(s) of life. Prebiotic evolution toward these important turning points can be traced back to single chiral molecules. These can be small (monomeric) units as amino acids or monosaccharides or oligomers as oligo-RNA type molecules. Earlier speculations about these two kinds of entries to biological chirality are critically reviewed.

  7. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server


    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  8. Photoactive molecules for applications in molecular imaging and cell biology. (United States)

    Shao, Qing; Xing, Bengang


    Photoactive technology has proven successful for non-invasive regulation of biological activities and processes in living cells. With the light-directed generation of biomaterials or signals, mechanisms in cell biology can be investigated at the molecular level with spatial and temporal resolution. In this tutorial review, we aim to introduce the important applications of photoactive molecules for elucidating cell biology on aspects of protein engineering, fluorescence labelling, gene regulation and cell physiological functions.

  9. Perspective: Mechanochemistry of biological and synthetic molecules

    Energy Technology Data Exchange (ETDEWEB)

    Makarov, Dmitrii E., E-mail: [Department of Chemistry and Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas 78712 (United States)


    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field.

  10. Caenorhabditis elegans chemical biology: lessons from small molecules (United States)

    How can we complement Caenorhabditis elegans genomics and proteomics with a comprehensive structural and functional annotation of its metabolome? Several lines of evidence indicate that small molecules of largely undetermined structure play important roles in C. elegans biology, including key pathw...

  11. Evidence of disorder in biological molecules from single molecule pulling experiments

    CERN Document Server

    Hyeon, Changbong; Thirumalai, D


    Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an exactly solvable model in which the unfolding rate due to mechanical force depends parametrically on an auxiliary variable representing an entropy barrier arising from fluctuations in internal dynamics. When the rate of fluctuations, a measure of dynamical disorder, is comparable to or smaller than the rate of force-induced unbinding, we show that there are two experimentally observable consequences: non-exponential survival probability at constant force, and a heavy-tailed rupture force distribution at constant loading rate. By fitting our analytical expressions to data from single molecule pulling experiments on proteins and DNA, we quantify the extent of disorder. We show that only by analyzing data over a wide range of forces and loading rates can the role of disorder due...

  12. Functionalization of hydroxyl terminated polybutadiene with biologically active fluorescent molecule

    Indian Academy of Sciences (India)

    R Murali Sankar; Subhadeep Saha; K Seeni Meera; Tushar Jana


    A biologically active molecule, 2-chloro-4,6-bis(dimethylamino)-1,3,5-triazine (CBDT), has been covalently attached at the terminal carbon atoms of the hydroxyl terminated polybutadiene (HTPB) backbone. The modification of HTPB backbone by CBDT molecule does not affect the unique physico-chemical properties such as fluidity, hydroxyl value and microstructure of the parent HTPB. The formation of hydrogen bonding between the terminal hydroxyl groups and the nitrogen atoms of triazine moiety is the driving force for the terminal attachment chemistry. The functionalized HTPB (HTPB–CBDT) shows a strong fluorescence emission at 385 nm.

  13. Study of complex molecules of biological interest with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Prince, K.C. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Istituto Officina dei Materiali, Consiglio Nazionale delle Ricerche, in Area Science Park, I-34149 Trieste (Italy); Molecular Model Discovery Laboratory, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Victoria, 3122 (Australia); Bolognesi, P., E-mail: [CNR-ISM, Area della Ricerca di Roma 1, Via Salaria Km. 29,300, Monterotondo (Roma) (Italy); Feyer, V. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Research Center Jülich, Peter Grünberg Institute (PGI-6), 52425 Jülich (Germany); Plekan, O. [Elettra-Sincrotrone Trieste, Strada Statale 14–km 163,5 in AREA Science Park, I-34149 Trieste (Italy); Avaldi, L. [CNR-ISM, Area della Ricerca di Roma 1, Via Salaria Km. 29,300, Monterotondo (Roma) (Italy)


    Synchrotron radiation and synchrotron based spectroscopic techniques have found important applications in the study of isolated molecular species of biological interest. In this paper, some examples of spectroscopic and dynamic studies of amino acids and small peptides, nucleobases and pharmaceuticals are reviewed. Opportunities offered by the advent of new radiation sources combined with novel methods for the production of beams of these molecules are also discussed.

  14. Tracking Electrons in Biological Macromolecules: From Ensemble to Single Molecule

    Directory of Open Access Journals (Sweden)

    Leandro C. Tabares


    Full Text Available Nature utilizes oxido-reductases to cater to the energy demands of most biochemical processes in respiratory species. Oxido-reductases are capable of meeting this challenge by utilizing redox active sites, often containing transition metal ions, which facilitate movement and relocation of electrons/protons to create a potential gradient that is used to energize redox reactions. There has been a consistent struggle by researchers to estimate the electron transfer rate constants in physiologically relevant processes. This review provides a brief background on the measurements of electron transfer rates in biological molecules, in particular Cu-containing enzymes, and highlights the recent advances in monitoring these electron transfer events at the single molecule level or better to say, at the individual event level.

  15. Novel nuclear magnetic resonance techniques for studying biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    Laws, David D.


    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone ({phi}/{psi}) dihedral angles by comparing experimentally determined {sup 13}C{sub a}, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of {alpha}-helical and {beta}-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly {beta}-sheet.

  16. Small molecule screening at Helmholtz Zentrum München - from biology to molecules. (United States)

    Schorpp, Kenji; Hadian, Kamyar


    Within the last few years the Helmholtz Zentrum München has established several initiatives enabling the translation of basic research results into discovery of novel small molecules that affect pathomechanisms of chronic and complex diseases. Here, one of the main operations is the Assay Development and Screening Platform (ADSP) that has state-of-the-art equipment for compound screening and provides knowledge in a variety of biochemical or cell-based phenotypic assays. In particular, ADSP has a strong focus on complex assays such as high-content screening in stem cells that are likely to provide an innovative approach complementary to biochemical assays for the discovery of novel small molecules modulating key biological processes.

  17. Single-molecule experiments in biological physics: methods and applications. (United States)

    Ritort, F


    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  18. Novel nuclear magnetic resonance techniques for studying biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    Laws, David Douglas [Univ. of California, Berkeley, CA (United States)


    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (Φ/Ψ) dihedral angles by comparing experimentally determined 13Ca, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.

  19. Voltammetric detection of biological molecules using chopped carbon fiber. (United States)

    Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira


    Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

  20. Single-molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update. (United States)

    Widom, Julia R; Dhakal, Soma; Heinicke, Laurie A; Walter, Nils G


    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy.

  1. Single Molecule Spectroscopy in Chemistry, Physics and Biology Nobel Symposium

    CERN Document Server

    Gräslund, Astrid; Widengren, Jerker


    Written by the leading experts in the field, this book describes the development and current state-of-the-art in single molecule spectroscopy. The application of this technique, which started 1989, in physics, chemistry and biosciences is displayed.

  2. Semiconductor Quantum Rods as Single Molecule FluorescentBiological Labels

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Aihua; Gu, Weiwei; Boussert, Benjamine; Koski, Kristie; Gerion, Daniele; Manna, Liberato; Le Gros, Mark; Larabell, Carolyn; Alivisatos, A. Paul


    In recent years, semiconductor quantum dots have beenapplied with great advantage in a wide range of biological imagingapplications. The continuing developments in the synthesis of nanoscalematerials and specifically in the area of colloidal semiconductornanocrystals have created an opportunity to generate a next generation ofbiological labels with complementary or in some cases enhanced propertiescompared to colloidal quantum dots. In this paper, we report thedevelopment of rod shaped semiconductor nanocrystals (quantum rods) asnew fluorescent biological labels. We have engineered biocompatiblequantum rods by surface silanization and have applied them fornon-specific cell tracking as well as specific cellular targeting. Theproperties of quantum rods as demonstrated here are enhanced sensitivityand greater resistance for degradation as compared to quantum dots.Quantum rods have many potential applications as biological labels insituations where their properties offer advantages over quantumdots.

  3. The altered expression of inflammation-related molecules and secretion of IL-6 and IL-8 by HUVEC from newborns with maternal inactive systemic lupus erythematosus is modified by estrogens. (United States)

    Rodriguez, E; Guevara, J; Paez, A; Zapata, E; Collados, M T; Fortoul, T I; Lopez-Marure, R; Masso, F; Montaño, L F


    Systemic lupus erythematosus (SLE) predominantly affects women, especially those in reproductive age. Genetic contributions to disease susceptibility as well as immune dysregulation, particularly persistent inflammatory responses, are considered essential features. Our aim was to determine whether human umbilical vein endothelial cells (HUVEC) isolated from healthy newborns to women with inactive SLE show inflammation-related abnormalities that might lead to an early development of SLE in the offsprings. HUVEC isolated from six women with inactive SLE were stimulated with 2.5 ng/mL of TNF-alpha and/or physiological and pharmacological doses of 17-I(2) estradiol (E2). Then the expression of VCAM-1, ICAM-1, E-selectin, toll-like receptor-9 (TLR-9), heat shock protein 70 (HSP70) and HSP90 were measured. The concentrations of IL-6, IL-8, and IL-10 were also determined in maternal serum and in TNF-alpha stimulated and non-stimulated HUVEC culture supernatant. HUVEC from children with no family history of autoimmune disease served as controls. Our results showed that in HUVEC from SLE+ mothers, a constitutively low expression of adhesion molecules was enhanced by TNF-alpha treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF-alpha-treated cells. IL-6 was constitutively higher in SLE+ HUVEC, whereas IL-8 was lower; E2 treatment diminished the latter. The E2 had no effect upon IL-6 and IL-8 secretions in TNF-alpha-treated cells. SLE+ HUVEC showed a disordered cytoskeleton and overexpressed HSP70, HSP90, and TLR-9. Our results indicate that endothelial cells of newborns to SLE+ mothers are in a proinflammatory condition which can be upregulated by estrogens.

  4. Rapid searches for complex patterns in biological molecules.


    Abarbanel, R M; Wieneke, P R; Mansfield, E; Jaffe, D A; Brutlag, D L


    The intrinsic redundancy of genetic information makes searching for patterns in biological sequences a difficult task. We have designed an interactive self-documenting computer program called QUEST that allows rapid searching of large DNA and protein data banks for highly redundant consensus sequences or character patterns. QUEST uses a concise language for specifying character patterns containing several levels of ambiguity and pattern arrangement. Examples of the use of this program for seq...


    Energy Technology Data Exchange (ETDEWEB)

    Professor William Moerner


    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in


    Directory of Open Access Journals (Sweden)



    Full Text Available The marine environment is a tremendous source of natural products. Marine microorganisms have become an important source of pharmacologically active metabolites Fungi are well known for their vast diversity of secondary metabolites that include many life-saving drugs and highly toxic mycotoxins. In general, fungal cultures producing such metabolites are immune to their toxic effects. However, some are known to produce self-toxic compounds that can pose production optimization challenges if the metabolites are needed in large amounts for chemical modification. Objective: The main objective of the present study was the isolation of new and preferably biologically active secondary metabolites from marine microorganisms, especially marine-derived fungi. Method: Marine fungi had isolated from marine soil by serial dilution method from Rose Bengal medium. Single colony was isolated by microscopic and macroscopic observation. Secondary metabolites are produced by marine fungi. Biological evaluation was performed by microbial studies. TLC is performed to identify the number of sub compounds in the crude extract. Further species level identification and structure elucidation of the compound are to be done. Results: The isolated marine fungi Aspergillus sp, showed maximum activity against the Candida rugosa with a zone diameter of 16mm at a concentration of 200μg and for bacterial strains it showed maximum activity against the E.coli with a diameter of 24mm at a concentration of 200μg. From the thin layer chromatography it has nearly 2-3 compounds to be purified. Conclusion: The selected organism which produces the compounds contains the biological activities which include anti-bacterial and anti fungal activities.

  7. Nano- and micro-fabrication for single-molecule biological studies

    NARCIS (Netherlands)

    Huang, Z.


    Heterogeneity is a general feature in biological system. In order to avoid possible misleading effects of ensemble averaging, and to ensure a correct understanding of the biological system, it is very important to look into individuals, such as a single bio-molecule or a single cell, for details. Th

  8. Uncovering the basis for nonideal behavior of biological molecules. (United States)

    Rösgen, Jörg; Pettitt, Bernard Montgomery; Bolen, David Wayne


    The molecular origin of the nonideal behavior for concentrated binary solutions of biochemical compounds is examined. The difference between activities expressed in the molar and molal conventions can be large. Considering the range from dilute to concentrated, we show that molar activity coefficients can be represented by simple but rigorous equations involving between one and three parameters only. We derive a universal relationship interconverting the scales of molarity and molality without requiring the density of the solution. The equations are developed from first principles using a statistical thermodynamic theory of molar activity coefficients. It is shown how to express activity coefficients in different concentration scales, and the advantages and disadvantages of using certain scales are discussed and compared with the experimental data. Several classes of biochemically relevant compounds, many of which are naturally occurring osmolytes, are discussed: six saccharides (glucose, xylose, maltose, mannose, raffinose, and sucrose), four polyols (glycerol, mannitol, erythritol, and sorbitol), five amino acids (glycine, alanine, sarcosine, glycine betaine, and proline), and urea. Of the 16 solutes, 10 could be described in terms of a single parameter that is due to pure first-order effects (packing, hydration, or space limitation). The remaining six exhibit significant second-order effects (solute-solute interactions) and require two additional parameters, one typically identified with the volume occupied per solute molecule in the pure solute (crystal or liquid) and the other with a self-association constant. The activity coefficients of the osmolytes roughly display the rank order found with respect to their ability to stabilize proteins. These findings are discussed in terms of the physical principles that give rise to the activity coefficients.

  9. Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule (United States)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica


    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

  10. Connecting synthetic chemistry decisions to cell and genome biology using small-molecule phenotypic profiling. (United States)

    Wagner, Bridget K; Clemons, Paul A


    Discovering small-molecule modulators for thousands of gene products requires multiple stages of biological testing, specificity evaluation, and chemical optimization. Many cellular profiling methods, including cellular sensitivity, gene expression, and cellular imaging, have emerged as methods to assess the functional consequences of biological perturbations. Cellular profiling methods applied to small-molecule science provide opportunities to use complex phenotypic information to prioritize and optimize small-molecule structures simultaneously against multiple biological endpoints. As throughput increases and cost decreases for such technologies, we see an emerging paradigm of using more information earlier in probe-discovery and drug-discovery efforts. Moreover, increasing access to public datasets makes possible the construction of 'virtual' profiles of small-molecule performance, even when multiplexed measurements were not performed or when multidimensional profiling was not the original intent. We review some key conceptual advances in small-molecule phenotypic profiling, emphasizing connections to other information, such as protein-binding measurements, genetic perturbations, and cell states. We argue that to maximally leverage these measurements in probe-discovery and drug-discovery requires a fundamental connection to synthetic chemistry, allowing the consequences of synthetic decisions to be described in terms of changes in small-molecule profiles. Mining such data in the context of chemical structure and synthesis strategies can inform decisions about chemistry procurement and library development, leading to optimal small-molecule screening collections.

  11. Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

    Directory of Open Access Journals (Sweden)

    Sungsoo Na


    Full Text Available Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins.

  12. Suppression and enhancement of non-native molecules within biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Jones, E.A. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)]. E-mail:; Lockyer, N.P. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom); Vickerman, J.C. [Surface Analysis Research Centre, CEAS, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)


    With the aim of evaluating the potential of SIMS to provide molecular information from small molecules within biological systems, here we investigate the effect of different biological compounds as they act as matrices. The results highlight the fact that the chemical environment of a molecule can have a significant effect on its limit of detection. This has implications for the imaging of drugs and xenobiotics in tissue sections and other biological matrices. A 1:1 mixture of the organic acid 2,4,6-trihydroxyacetophenone and the dipeptide valine-valine demonstrates that almost complete suppression of the [M + H]{sup +} ion of one compound can be caused by the presence of a compound of higher proton affinity. The significance of this is highlighted when two similar drug molecules, atropine (a neutral molecule) and ipratropium bromide (a quaternary nitrogen containing salt) are mixed with brain homogenate. The atropine [M + H]{sup +} ion shows significant suppression whilst the [M - Br]{sup +} of ipratopium bromide is detected at an intensity that can be rationalised by its decreased surface concentration. By investigating the effect of two abundant tissue lipids, cholesterol and dipalmitoylphosphatidyl choline (DPPC), on the atropine [M + H]{sup +} signal detected in mixtures with these lipids we see that the DPPC has a strong suppressing effect, which may be attributed to gas phase proton transfer.

  13. Pragmatic turn in biology: From biological molecules to genetic content operators

    Institute of Scientific and Technical Information of China (English)

    Guenther; Witzany


    Erwin Schrdinger‘s question "What is life?" received the answer for decades of "physics + chemistry". The concepts of Alain Turing and John von Neumann introduced a third term: "information". This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings "sequence space". Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract "sequence space" concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.

  14. The corrosion inhibition of iron and aluminum by various naturally occurring biological molecules

    Energy Technology Data Exchange (ETDEWEB)

    McCafferty, E.; Hansen, D.C. [Naval Research Lab., Washington, DC (United States)


    Biological polymers that exhibit a strong affinity for metal surfaces are increasingly becoming the focus of research toward the development of environmentally friendly corrosion inhibitors. This paper deals with the use of various naturally occurring organic molecules as corrosion inhibitors for iron or aluminum. Among the organic molecules considered are catecholate and hydroxamate siderophores isolated from bacteria, the adhesive protein from the blue mussel Mytilus edulis L, and caffeic acid and chlorogenic acid. FTIR analysis, anodic polarization curves, and AC impedance measurements were used to determine the adsorption and effectiveness of the various organic molecules as corrosion inhibitors. Parabactin, a catecholate siderophore, was effective in inhibiting both the corrosion of iron in hydrochloric acid and the pitting of aluminum in 0.1 M sodium chloride. The adhesive protein from the blue mussel was also effective in inhibiting the pitting of aluminum.

  15. Gold nanoparticle wire and integrated wire array for electronic detection of chemical and biological molecules

    Directory of Open Access Journals (Sweden)

    J. J. Diao


    Full Text Available Nanoparticle wire and integrated nanoparticle wire array have been prepared through a green technique: discontinuous vertical evaporation-driven colloidal deposition. The conducting gold nanoparticle wire made by this technique shows ability for the sensitive electronic detection of chemical and biological molecules due to its high surface to volume ratio. Furthermore, we also demonstrate a potential usage of integrated gold nanoparticle wire array for the localized detection.

  16. Structure-property relationship of quinuclidinium surfactants--Towards multifunctional biologically active molecules. (United States)

    Skočibušić, Mirjana; Odžak, Renata; Štefanić, Zoran; Križić, Ivana; Krišto, Lucija; Jović, Ozren; Hrenar, Tomica; Primožič, Ines; Jurašin, Darija


    Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical

  17. Surface-enhanced and tip-enhanced Raman spectroscopy of biological molecules on nanostructured metallic surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Hennemann, Laura E.; Mihaljevic, Josip; Braun, Kai; Meixner, Alfred J.; Zhang, Dai [Institute of Physical and Theoretical Chemistry, University of Tuebingen, Tuebingen (Germany); Kolloch, Andreas [Department of Physics, University of Konstanz, Universitaetsstrasse 10, 78457 Konstanz (Germany)


    We use a custom built apertureless scanning near-field optical microscope (SNOM) to investigate several kinds of biological molecules. The setup is an extended parabolic mirror based confocal microscope working with higher order laser modes in order to tune the polarization of the light in its focus. We detected the presence of a (sub)monolayer of biological molecules ranging from DNA bases to double stranded DNA by collecting their unique Raman fingerprint spectrum. In order to detect such small amounts of molecules, we performed surface-enhanced Raman scattering (SERS) or tip-enhanced Raman scattering (TERS). For SERS, either the irregular rough edges of evaporated noble metal grids or regular arrays of gold nano triangles served as enhancing substrates. We compared the plasmonic properties of gold triangles of different aspect ratios and on different substrates to optimize the electromagnetic enhancement for the 632.8 nm laser excitation. The obtained optical patterns were compared to those computed in simulations. In the case of TERS, an electrochemically etched sharp gold tip (approx. 20 nm tip apex diameter) was approached to the surface, thus acting simultaneously as a scanning probe microscopy tip for topographic measurements and as a near-field antenna collecting optical information. We collected TERS spectra of single calf thymus DNA molecules immobilized on smooth Au(111) surfaces. Strongly enhanced spectra were obtained both in the SERS and in the TERS measurements.

  18. Application of terahertz spectroscopy for characterization of biologically active organic molecules in natural environment (United States)

    Karaliūnas, Mindaugas; Jakštas, Vytautas; Nasser, Kinan E.; Venckevičius, Rimvydas; Urbanowicz, Andrzej; Kašalynas, Irmantas; Valušis, Gintaras


    In this work, a comparative research of biologically active organic molecules in its natural environment using the terahertz (THz) time domain spectroscopy (TDS) and Fourier transform spectroscopy (FTS) systems is carried out. Absorption coefficient and refractive index of Nicotiana tabacum L. leaves containing nicotine, Cannabis sativa L. leaves containing tetrahydrocannabinol, and Humulu lupulus L. leaves containing α-acids, active organic molecules that obtain in natural environment, were measured in broad frequency range from 0.1 to 13 THz at room temperature. In the spectra of absorption coefficient the features were found to be unique for N. tabacum, C. sativa and H. lupulus. Moreover, those features can be exploited for identification of C. sativa sex and N. tabacum origin. The refractive index can be also used to characterize different species.

  19. The universality and biological significance of signal molecules with intracellular-extracellular compatible functions

    Institute of Scientific and Technical Information of China (English)


    Generally,cell signal molecules are classified into the extracellular signal molecules (the first messengers) and the intracellular signal ones (the second messengers).Cyclic adenosine monophosphate (cAMP),calcium ions and calmodulin (CaM) are the traditional intracellular messengers,but they are also present in extracellular matrix (ECM).Some of them have been discovered to act as the first messengers through cell surface receptors.Other second messengers,such as cyclic guanosine monophosphate (cGMP),cyclic adenosine diphosphate ribose (cADPR) and annexin,are also found existing outside animal and plant cells.The existence of these messengers with intracellular-extracellular compatible functions in cells may be a regular biological phenomenon.These compatible messengers might be the communication factors between intracellular and extracellular regions or among the cell populations,and are also important in regulating cell development procedure.

  20. Concepts of neuroendocrine cardiology and neuroendocrine immunology, chemistry and biology of signal molecules. (United States)

    Galoyan, Armen


    Discovery of neurosecretion of cardioactive neurohormones produced by hypothalamic nuclei (NSO and NPV), as well as the biosynthesis of several immunomodulators (signal molecules of the neuroendocrine immune system of brain), deciphering of their chemical structure and study of their biological properties led to the foundation of two important trends of neurobiology: neuroendocrine immunology and cardiology. Hormone formation by atrium ganglionary nerve cells and auriculum establishment of neurohumoral interactions between hypothalamic and atrium neurosecretion indicated the existence of the system neuroendocrine hypothalamus--endocrine heart. Study of their biological properties promoted creation of powerful neurohormonal preparations for the treatment of immune, cardio-vascular, neurodegenerative, infectious and tumor diseases. Concepts suggested by us on neuroendocrine cardiology and immunology, create large perspectives for development of the theory and its implementation in medicine.

  1. Single Fluorescent Molecules as Nano-Illuminators for Biological Structure and Function (United States)

    Moerner, W. E.


    Since the first optical detection and spectroscopy of a single molecule in a solid (Phys. Rev. Lett. {62}, 2535 (1989)), much has been learned about the ability of single molecules to probe local nanoenvironments and individual behavior in biological and nonbiological materials in the absence of ensemble averaging that can obscure heterogeneity. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic imaging of individual fluorophores leads naturally to superlocalization, or determination of the position of the molecule with precision beyond the optical diffraction limit, simply by digitization of the point-spread function from the single emitter. For example, the shape of single filaments in a living cell can be extracted simply by allowing a single molecule to move through the filament (PNAS {103}, 10929 (2006)). The addition of photoinduced control of single-molecule emission allows imaging beyond the diffraction limit (super-resolution) and a new array of acronyms (PALM, STORM, F-PALM etc.) and advances have appeared. We have used the native blinking and switching of a common yellow-emitting variant of green fluorescent protein (EYFP) reported more than a decade ago (Nature {388}, 355 (1997)) to achieve sub-40 nm super-resolution imaging of several protein structures in the bacterium Caulobacter crescentus: the quasi-helix of the actin-like protein MreB (Nat. Meth. {5}, 947 (2008)), the cellular distribution of the DNA binding protein HU (submitted), and the recently discovered division spindle composed of ParA filaments (Nat. Cell Biol. {12}, 791 (2010)). Even with these advances, better emitters would provide more photons and improved resolution, and a new photoactivatable small-molecule emitter has recently been synthesized and targeted to specific structures in living cells to provide super-resolution images (JACS {132}, 15099 (2010)). Finally, a new optical method for extracting three-dimensional position information based on

  2. Incorporation and characterization of biological molecules in droplet-interface bilayer networks for novel active systems (United States)

    Sarles, Stephen A.; Ghanbari Bavarsad, Pegah; Leo, Donald J.


    Biological molecules including phospholipids and proteins offer scientists and engineers a diverse selection of materials to develop new types of active materials and smart systems based on ion conduction. The inherent energy-coupling abilities of these components create novel kinds of transduction elements. Networks formed from droplet-interface bilayers (DIB) are a promising construct for creating cell mimics that allow for the assembly and study of these active biological molecules. The current-voltage relationship of symmetric, "lipid-in" dropletinterface bilayers are characterized using electrical impedance spectroscopy (EIS) and cyclic voltammetry (CV). "Lipid-in" diphytanoyl phosphatidylcholine (DPhPC) droplet-interface bilayers have specific resistances of nearly 10MΩ•cm2 and rupture at applied potentials greater than 300mV, indicating the "lipid-in" approach produces higher quality interfacial membranes than created using the original "lipid-out" method. The incorporation of phospholipids into the droplet interior allows for faster monolayer formation but does not inhibit the selfinsertion of transmembrane proteins into bilayer interfaces that separate adjacent droplets. Alamethicin proteins inserted into single and multi-DIB networks produce a voltage-dependent membrane conductance and current measurements on bilayers containing this type of protein exhibit a reversible, 3-4 order-of-magnitude conductance increase upon application of voltage.

  3. Franck-Condon-like Progressions in Infrared Spectra of Biological Molecules. (United States)

    Zabuga, Aleksandra V; Kamrath, Michael Z; Rizzo, Thomas R


    Infrared spectra in the NH stretch region are often used for structure determination of gas-phase biological molecules. Vibrational couplings complicate the structure determination process by giving rise to additional vibrational bands along with the expected fundamental transitions. We present an example of a strong anharmonic coupling in a biological molecule, Ac-Phe-Ala-LysH(+), which causes the appearance of long vibrational progressions in the infrared spectrum. By analyzing the spectra of the ground and the electronically excited state, we determined that the coupling occurs between the NH stretch (ωNH) and a low-frequency torsion of the phenyl ring (ωτ). We describe the vibrational progressions using a Born-Oppenheimer-like separation of the high-frequency stretch and low-frequency torsion with a quartic Taylor expansion for the potential energy surface that accounts for the equilibrium distance and frequency change of the torsional vibration upon the NH stretch excitation. We also demonstrate that small conformational changes in the peptide are sufficient to break this coupling.

  4. High Throughput Extraction of Plant, Marine and Fungal Specimens for Preservation of Biologically Active Molecules

    Directory of Open Access Journals (Sweden)

    Thomas G. McCloud


    Full Text Available The Developmental Therapeutics Program (DTP of the U.S. National Cancer Institute (NCI, at its NCI-Frederick facility, has built perhaps the largest and most diverse natural products screening library in the world for drug discovery. Composed of plant, marine organism and microbial extracts, it currently contains in excess of 230,000 unique materials. From the inception of this program to identify new anticancer chemotherapeutics from natural products sources in 1987, two extracts have been sequentially prepared from each specimen: one produced by organic solvent extraction, which yields a complex material that contains non- to moderately polar small molecules, and a water-soluble extract, a milieu largely unexplored for useful drugs in earlier years, which contains polar small to medium-sized molecules. Plant specimens and microbial ferments are extracted by modified traditional methods, while the method developed to produce extracts from marine organisms is unique and very different from that used by marine natural products chemists previously, but again yields both an organic solvent soluble and a water soluble material for inclusion into the screening library. Details of high throughput extract production for preservation of biologically active molecules are presented.

  5. Electron transfer behaviour of biological macromolecules towards the single-molecule level

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jingdong [Department of Chemistry, Building 207, Technical University of Denmark, DK-2800 Lyngby (Denmark); Grubb, Mikala [Department of Chemistry, Building 207, Technical University of Denmark, DK-2800 Lyngby (Denmark); Hansen, Allan G [Department of Chemistry, Building 207, Technical University of Denmark, DK-2800 Lyngby (Denmark); Kuznetsov, Alexander M [A N Frumkin Institute of Electrochemistry of the Russian Academy of Sciences, Leninskij Prospect 31, 117071 Moscow (Russian Federation); Boisen, Anja [Microelectronics Centre, Building 345, Technical University of Denmark, DK-2800 Lyngby (Denmark); Wackerbarth, Hainer [Department of Chemistry, Building 207, Technical University of Denmark, DK-2800 Lyngby (Denmark); Ulstrup, Jens [Department of Chemistry, Building 207, Technical University of Denmark, DK-2800 Lyngby (Denmark)


    Redox metalloproteins immobilized on metallic surfaces in contact with aqueous biological media are important in many areas of pure and applied sciences. Redox metalloprotein films are currently being addressed by new approaches where biotechnology including modified and synthetic proteins is combined with state-of-the-art physical electrochemistry with emphasis on single-crystal, atomically planar electrode surfaces, in situ scanning tunnelling microscopy (STM) and other surface techniques. These approaches have brought bioelectrochemistry important steps forward towards the nanoscale and single-molecule levels. We discuss here these advances with reference to two specific redox metalloproteins, the blue single-copper protein Pseudomonas aeruginosa azurin and the single-haem protein Saccharomyces cerevisiae yeast cytochrome c, and a short oligonucleotide. Both proteins can be immobilized on Au(111) by chemisorption via exposed sulfur-containing residues. Voltammetric, interfacial capacitance, x-ray photoelectron spectroscopy and microcantilever sensor data, together with in situ STM with single-molecule resolution, all point to a coherent view of monolayer organization with protein electron transfer (ET) function retained. In situ STM can also address the microscopic mechanisms for electron tunnelling through the biomolecules and offers novel notions such as coherent multi-ET between the substrate and tip via the molecular redox levels. This differs in important respects from electrochemical ET at a single metal/electrolyte interface. Similar data for a short oligonucleotide immobilized on Au(111) show that oligonucleotides can be characterized with comparable detail, with novel perspectives for addressing DNA electronic conduction mechanisms and for biological screening towards the single-molecule level.

  6. The pandemic of physical inactivity

    DEFF Research Database (Denmark)

    Kohl, Harold W; Craig, Cora Lynn; Lambert, Estelle Victoria


    Physical inactivity is the fourth leading cause of death worldwide. We summarise present global efforts to counteract this problem and point the way forward to address the pandemic of physical inactivity. Although evidence for the benefits of physical activity for health has been available since ...

  7. TOPICAL REVIEW: Single-molecule experiments in biological physics: methods and applications (United States)

    Ritort, F.


    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  8. Challenges of biological sample preparation for SIMS imaging of elements and molecules at subcellular resolution

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Subhash [Cornell SIMS Laboratory, Department of Earth and Atmospheric Sciences, Snee Hall, Cornell University, Ithaca, NY 14853 (United States)], E-mail:


    Secondary ion mass spectrometry (SIMS) based imaging techniques capable of subcellular resolution characterization of elements and molecules are becoming valuable tools in many areas of biology and medicine. Due to high vacuum requirements of SIMS, the live cells cannot be analyzed directly in the instrument. The sample preparation, therefore, plays a critical role in preserving the native chemical composition for SIMS analysis. This work focuses on the evaluation of frozen-hydrated and frozen freeze-dried sample preparations for SIMS studies of cultured cells with a CAMECA IMS-3f dynamic SIMS ion microscope instrument capable of producing SIMS images with a spatial resolution of 500 nm. The sandwich freeze-fracture method was used for fracturing the cells. The complimentary fracture planes in the plasma membrane were characterized by field-emission secondary electron microscopy (FESEM) in the frozen-hydrated state. The cells fractured at the dorsal surface were used for SIMS analysis. The frozen-hydrated SIMS analysis of individual cells under dynamic primary ion beam (O{sub 2}{sup +}) revealed local secondary ion signal enhancements correlated with the water image signals of {sup 19}(H{sub 3}O){sup +}. A preferential removal of water from the frozen cell matrix in the Z-axis was also observed. These complications render the frozen-hydrated sample type less desirable for subcellular dynamic SIMS studies. The freeze-drying of frozen-hydrated cells, either inside the instrument or externally in a freeze-drier, allowed SIMS imaging of subcellular chemical composition. Morphological evaluations of fractured freeze-dried cells with SEM and confocal laser scanning microscopy (CLSM) revealed well-preserved mitochondria, Golgi apparatus, and stress fibers. SIMS analysis of fractured freeze-dried cells revealed well-preserved chemical composition of even the most highly diffusible ions like K{sup +} and Na{sup +} in physiologically relevant concentrations. The high K

  9. Surface-enhanced Raman spectroscopy at single-molecule scale and its implications in biology. (United States)

    Wang, Yuling; Irudayaraj, Joseph


    Single-molecule (SM) spectroscopy has been an exciting area of research offering significant promise and hope in the field of sensor development to detect targets at ultra-low levels down to SM resolution. To the experts and developers in the field of surface-enhanced Raman spectroscopy (SERS), this has often been a challenge and a significant opportunity for exploration. Needless to say, the opportunities and excitement of this multidisciplinary area impacts span the fields of physics, chemistry and engineering, along with a significant thrust in applications constituting areas in medicine, biology, environment and agriculture among others. In this review, we will attempt to provide a quick snapshot of the basics of SM-SERS, nanostructures and devices that can enable SM Raman measurement. We will conclude with a discussion on SERS implications in biomedical sciences.

  10. Small molecules unravel complex interplay between auxin biology and endomembrane trafficking. (United States)

    Doyle, Siamsa M; Vain, Thomas; Robert, Stéphanie


    The establishment and maintenance of controlled auxin gradients within plant tissues are essential for a multitude of developmental processes. Auxin gradient formation is co-ordinated via local biosynthesis and transport. Cell to cell auxin transport is facilitated and precisely regulated by complex endomembrane trafficking mechanisms that target auxin carrier proteins to their final destinations. In turn, auxin and cross-talk with other phytohormones regulate the endomembrane trafficking of auxin carriers. Dissecting such rapid and complicated processes is challenging for classical genetic experiments due to trafficking pathway diversity, gene functional redundancy, and lethality in loss-of-function mutants. Many of these difficulties can be bypassed via the use of small molecules to modify or disrupt the function or localization of proteins. Here, we will review examples of the knowledge acquired by the use of such chemical tools in this field, outlining the advantages afforded by chemical biology approaches.

  11. Biophysics of DNA-Protein Interactions From Single Molecules to Biological Systems

    CERN Document Server

    Williams, Mark C


    This book presents a concise overview of current research on the biophysics of DNA-protein interactions. A wide range of new and classical methods are presented by authors investigating physical mechanisms by which proteins interact with DNA. For example, several chapters address the mechanisms by which proteins search for and recognize specific binding sites on DNA, a process critical for cellular function. Single molecule methods such as force spectroscopy as well as fluorescence imaging and tracking are described in these chapters as well as other parts of the book that address the dynamics of protein-DNA interactions. Other important topics include the mechanisms by which proteins engage DNA sequences and/or alter DNA structure. These simple but important model interactions are then placed in the broader biological context with discussion of larger protein-DNA complexes . Topics include replication forks, recombination complexes, DNA repair interactions, and ultimately, methods to understand the chromatin...

  12. Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

    Institute of Scientific and Technical Information of China (English)

    Judith Su; Alexander FG Goldberg; Brian M Stoltz


    Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being studied.Analyte size plays an important role in determining detectability.Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell.Our results,covering several orders of magnitude of particle radius (100 nm to 2 nm),agree with the 'reactive' model prediction for the frequency shift of the resonator upon particle binding.This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle.We anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor-ligand and protein-protein interactions in real time.

  13. Aqueous phase separation as a possible route to compartmentalization of biological molecules. (United States)

    Keating, Christine D


    How could the incredible complexity of modern cells evolve from something simple enough to have appeared in a primordial soup? This enduring question has sparked the interest of researchers since Darwin first considered his theory of natural selection. Organic molecules, even potentially functional molecules including peptides and nucleotides, can be produced abiotically. Amphiphiles such as surfactants and lipids display remarkable self-assembly processes including the spontaneous formation of vesicles resembling the membranes of living cells. Nonetheless, numerous questions remain. Given the presumably dilute concentrations of macromolecules in the prebiotic pools where the earliest cells are thought to have appeared, how could the necessary components become concentrated and encapsulated within a semipermeable membrane? What would drive the further structural complexity that is a hallmark of modern living systems? The interior of modern cells is subdivided into microcompartments such as the nucleoid of bacteria or the organelles of eukaryotic cells. Even within what at first appears to be a single compartment, for example, the cytoplasm or nucleus, chemical composition is often nonuniform, containing gradients, macromolecular assemblies, and/or liquid droplets. What might the internal structure of intermediate evolutionary forms have looked like? The nonideal aqueous solution chemistry of macromolecules offers an attractive possible answer to these questions. Aqueous polymer solutions will form multiple coexisting thermodynamic phases under a variety of readily accessible conditions. In this Account, we describe aqueous phase separation as a model system for biological compartmentalization in both early and modern cells, with an emphasis on systems that have been encapsulated within a lipid bilayer. We begin with an introduction to aqueous phase separation and discuss how this phenomenon can lead to microcompartmentalization and could facilitate biopolymer

  14. Force per cross-sectional area from molecules to muscles: a general property of biological motors. (United States)

    Rospars, Jean-Pierre; Meyer-Vernet, Nicole


    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

  15. MicroRNA: a small molecule with a big biological impact. (United States)

    Zhou, Xiaofeng; Yang, Pan-Chyr


    One of the most significant achievements in biological science in the last decade is the discovery of RNA interference (RNAi), a process within living cells that regulates gene expression at post-transcriptional levels. Historically, this process was described by other more generic names, such as co-suppression and post transcriptional gene silencing. Only after the molecular mechanism underlying these apparently unrelated processes was fully understood did it become apparent that they all described the RNAi phenomenon. In 2006, Dr. Andrew Fire and Dr. Craig C. Mello were awarded the Nobel Prize in Physiology or Medicine for their work on RNAi interference. RNAi is an RNA-dependent gene silencing process that is controlled by the RNA-induced silencing complex (RISC) and is initiated by two types of small RNA molecules - microRNA (miRNA) and small interfering RNA (siRNA). However, the function of microRNA appears to be far beyond RNAi alone, including direct interaction with the gene promoter and epigenetic regulation of the DNA methylation and histone modification. By regulating gene expression, miRNAs are likely to be involved in diverse biological activities, such as tumorigenesis, immune response, insulin secretion, neurotransmitter synthesis, and circadian rhythm, to name a few. MicroRNAs are 21-23 nucleotide single stranded RNA molecules found in eukaryotic cells. The first miRNA, lin-4, was characterized in C. elegans in the early 1990s [1]. In the early years, the progress on microRNA research was slow and experienced substantial growing pains. The short length and uniqueness of each microRNA rendered many conventional hybridization based methods ineffective; very small RNAs are difficult to reliably amplify or label without introducing bias. In addition, hybridization-based methods for microRNA profiling relied on probes designed to detect known microRNAs or known microRNA species previously identified by sequencing or homology search. Recent evidence of

  16. Detection, Characterization, and Biological Effect of Quorum-Sensing Signaling Molecules in Peanut-Nodulating Bradyrhizobia

    Directory of Open Access Journals (Sweden)

    Walter Giordano


    Full Text Available Bacteria of the genus Bradyrhizobium are able to establish a symbiotic relationship with peanut (Arachis hypogaea root cells and to fix atmospheric nitrogen by converting it to nitrogenous compounds. Quorum sensing (QS is a cell-cell communication mechanism employed by a variety of bacterial species to coordinate behavior at a community level through regulation of gene expression. The QS process depends on bacterial production of various signaling molecules, among which the N-acylhomoserine lactones (AHLs are most commonly used by Gram-negative bacteria. Some previous reports have shown the production of QS signaling molecules by various rhizobia, but little is known regarding mechanisms of communication among peanut-nodulating strains. The aims of this study were to identify and characterize QS signals produced by peanut-nodulating bradyrhizobial strains and to evaluate their effects on processes related to cell interaction. Detection of AHLs in 53 rhizobial strains was performed using the biosensor strains Agrobacterium tumefaciens NTL4 (pZLR4 and Chromobacterium violaceum CV026 for AHLs with long and short acyl chains, respectively. None of the strains screened were found to produce AHLs with short acyl chains, but 14 strains produced AHLs with long acyl chains. These 14 AHL-producing strains were further studied by quantification of β-galactosidase activity levels (AHL-like inducer activity in NTL4 (pZLR4. Strains displaying moderate to high levels of AHL-like inducer activity were subjected to chemical identification of signaling molecules by high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS. For each AHL-producing strain, we found at least four different AHLs, corresponding to N-hexanoyl-DL-homoserine lactone (C6, N-(3-oxodecanoyl-L-homoserine lactone (3OC10, N-(3-oxododecanoyl-L-homoserine lactone (3OC12, and N-(3-oxotetradecanoyl-L-homoserine lactone (3OC14. Biological roles of 3OC10, 3OC12, and 3OC14 AHLs


    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Julio [Columbia University


    Single molecule techniques are rapidly occupying a central role in biological research at all levels. This transition was made possible by the availability and dissemination of robust techniques that use fluorescence and force probes to track the conformation of molecules one at a time, in vitro as well as in live cells. Single-molecule approaches have changed the way many biological problems are studied. These novel techniques provide previously unobtainable data on fundamental biochemical processes that are essential for all forms of life. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of the molecular systems that underpin the functioning of living cells. Hence, our conference seeks to disseminate the implementation and use of single molecule techniques in the pursuit of new biological knowledge. Topics covered include: Molecular Motors on the Move; Origin And Fate Of Proteins; Physical Principles Of Life; Molecules and Super-resolution Microscopy; Nanoswitches In Action; Active Motion Or Random Diffusion?; Building Blocks Of Living Cells; From Molecular Mechanics To Physiology; Tug-of-war: Force Spectroscopy Of Single Proteins.

  18. Single-molecule conformational dynamics of a biologically functional hydroxocobalamin riboswitch. (United States)

    Holmstrom, Erik D; Polaski, Jacob T; Batey, Robert T; Nesbitt, David J


    Riboswitches represent a family of highly structured regulatory elements found primarily in the leader sequences of bacterial mRNAs. They function as molecular switches capable of altering gene expression; commonly, this occurs via a conformational change in a regulatory element of a riboswitch that results from ligand binding in the aptamer domain. Numerous studies have investigated the ligand binding process, but little is known about the structural changes in the regulatory element. A mechanistic description of both processes is essential for deeply understanding how riboswitches modulate gene expression. This task is greatly facilitated by studying all aspects of riboswitch structure/dynamics/function in the same model system. To this end, single-molecule fluorescence resonance energy transfer (smFRET) techniques have been used to directly observe the conformational dynamics of a hydroxocobalamin (HyCbl) binding riboswitch (env8HyCbl) with a known crystallographic structure.1 The single-molecule RNA construct studied in this work is unique in that it contains all of the structural elements both necessary and sufficient for regulation of gene expression in a biological context. The results of this investigation reveal that the undocking rate constant associated with the disruption of a long-range kissing-loop (KL) interaction is substantially decreased when the ligand is bound to the RNA, resulting in a preferential stabilization of the docked conformation. Notably, the formation of this tertiary KL interaction directly sequesters the Shine-Dalgarno sequence (i.e., the ribosome binding site) via base-pairing, thus preventing translation initiation. These results reveal that the conformational dynamics of this regulatory switch are quantitatively described by a four-state kinetic model, whereby ligand binding promotes formation of the KL interaction. The results of complementary cell-based gene expression experiments conducted in Escherichia coli are highly

  19. Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies. (United States)

    Elyoussfi, Sarah; Thomas, Benjamin J; Ciurtin, Coziana


    The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I-IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are

  20. A small molecule (pluripotin as a tool for studying cancer stem cell biology: proof of concept.

    Directory of Open Access Journals (Sweden)

    Susan D Mertins

    Full Text Available BACKGROUND: Cancer stem cells (CSC are thought to be responsible for tumor maintenance and heterogeneity. Bona fide CSC purified from tumor biopsies are limited in supply and this hampers study of CSC biology. Furthermore, purified stem-like CSC subpopulations from existing tumor lines are unstable in culture. Finding a means to overcome these technical challenges would be a useful goal. In a first effort towards this, we examined whether a chemical probe that promotes survival of murine embryonic stem cells without added exogenous factors can alter functional characteristics in extant tumor lines in a fashion consistent with a CSC phenotype. METHODOLOGY/PRINCIPAL FINDINGS: The seven tumor lines of the NCI60 colon subpanel were exposed to SC-1 (pluripotin, a dual kinase and GTPase inhibitor that promotes self-renewal, and then examined for tumorigenicity under limiting dilution conditions and clonogenic activity in soft agar. A statistically significant increase in tumor formation following SC-1 treatment was observed (p<0.04. Cloning efficiencies and expression of putative CSC surface antigens (CD133 and CD44 were also increased. SC-1 treatment led to sphere formation in some colon tumor lines. Finally, SC-1 inhibited in vitro kinase activity of RSK2, and another RSK2 inhibitor increased colony formation implicating a role for this kinase in eliciting a CSC phenotype. CONCLUSIONS/SIGNIFICANCE: These findings validate a proof of concept study exposure of extant tumor lines to a small molecule may provide a tractable in vitro model for understanding CSC biology.

  1. Current and Future Perspectives on the Structural Identification of Small Molecules in Biological Systems

    Directory of Open Access Journals (Sweden)

    Daniel A. Dias


    Full Text Available Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as “statistically significant” in the study. Such metabolic “dark matter” means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function.

  2. Zeolite H-BEA catalysed multicomponent reaction: One-pot synthesis of amidoalkyl naphthols - Biologically active drug-like molecules

    Indian Academy of Sciences (India)

    Sunil R Mistry; Rikesh S Joshi; Kalpana C Maheria


    Zeolite has been used as an efficient and a novel heterogeneous catalyst for one-pot synthesis of biologically active drug-like molecules, amidoalkyl naphthols. This green route involves multicomponent reaction of 2-naphthol, aromatic aldehydes and amide in the presence of a catalytic amount of zeolite H-Beta (H-BEA) under solvent reflux as well as solvent-free conditions.

  3. From Molecules to Living Organisms : an Interplay between Biology and Physics : Lecture Notes of the Les Houches School of Physics

    CERN Document Server

    Nury, Hughes; Parcy, François; Ruigrok, Rob W H; Ziegler, Christine; Cugliandolo, Leticia F; Session CII


    The aim of this book is to provide new ideas for studying living matter by a simultaneous understanding of behavior from molecules to the cell, to the whole organism in the light of physical concepts. Indeed, forces guide most biological phenomena. In some cases these forces can be well-described and thus used to model a particular biological phenomenon. This is exemplified here by the study of membranes, where their shapes and curvatures can be modeled using a limited number of parameters that are measured experimentally. The growth of plants is another example where the combination of physics, biology and mathematics leads to a predictive model. The laws of thermodynamics are essential, as they dictate the behavior of proteins, or more generally biological molecules, in an aqueous environment. Integrated studies from the molecule to a larger scale need a combination of cutting-edge approaches, such as the use of new X-ray sources, in-cell NMR, cryo-electron microscopy or single-molecule microscopy. Some are...

  4. Introducing Bond-Line Organic Structures in High School Biology: An Activity that Incorporates Pleasant-Smelling Molecules (United States)

    Rios, Andro C.; French, Gerald


    Chemical education occurs in settings other than just the chemistry classroom. High school biology courses are frequently where students are introduced to organic molecules and their importance to cellular chemistry. However, structural representations are often intimidating because students have not been introduced to the language. As part of a…

  5. Physical inactivity in Parkinson's disease

    NARCIS (Netherlands)

    Nimwegen, M.L. van; Speelman, A.D.; Hofman-van Rossum, E.J.; Overeem, S.; Deeg, D.J.G.; Borm, G.F.; Horst, M.H. van der; Bloem, B.R.; Munneke, M.


    Patients with Parkinson's disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD

  6. Laser desorption/ionization mass spectrometry for direct profiling and imaging of small molecules from raw biological materials

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Sangwon [Iowa State Univ., Ames, IA (United States)


    Matrix-assisted laser desorption/ionization(MALDI) mass spectrometry(MS) has been widely used for analysis of biological molecules, especially macromolecules such as proteins. However, MALDI MS has a problem in small molecule (less than 1 kDa) analysis because of the signal saturation by organic matrixes in the low mass region. In imaging MS (IMS), inhomogeneous surface formation due to the co-crystallization process by organic MALDI matrixes limits the spatial resolution of the mass spectral image. Therefore, to make laser desorption/ionization (LDI) MS more suitable for mass spectral profiling and imaging of small molecules directly from raw biological tissues, LDI MS protocols with various alternative assisting materials were developed and applied to many biological systems of interest. Colloidal graphite was used as a matrix for IMS of small molecules for the first time and methodologies for analyses of small metabolites in rat brain tissues, fruits, and plant tissues were developed. With rat brain tissues, the signal enhancement for cerebroside species by colloidal graphite was observed and images of cerebrosides were successfully generated by IMS. In addition, separation of isobaric lipid ions was performed by imaging tandem MS. Directly from Arabidopsis flowers, flavonoids were successfully profiled and heterogeneous distribution of flavonoids in petals was observed for the first time by graphite-assisted LDI(GALDI) IMS.

  7. Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research

    Directory of Open Access Journals (Sweden)

    Toshitsugu Fujita


    Full Text Available Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE proteins and the clustered regularly interspaced short palindromic repeats (CRISPR and CRISPR-associated proteins (Cas (CRISPR/Cas system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing.

  8. Conformational, spectroscopic and nonlinear optical properties of biologically active N,N-dimethyltryptamine molecule: A theoretical study (United States)

    Öner, Nazmiye; Tamer, Ömer; Avcı, Davut; Atalay, Yusuf


    The effective psychoactive properties of N,N-dimethyltryptamine (DMT) known as the near-death molecule have encouraged the imagination of many research disciplines for several decades. Although there is no theoretical study, a number of paper composed by experimental techniques have been reported for DMT molecule. In this study, the molecular modeling of DMT was carried out using B3LYP and HSEh1PBE levels of density functional theory (DFT). Our calculations showed that the energy gap between HOMO and LUMO is low, demonstrating that DMT is a biologically active molecule. Large hyperconjugation interaction energies imply that molecular charge transfer occurs in DMT. Moreover, NLO analysis indicates that DMT can be used an effective NLO material.

  9. In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine. (United States)

    Pi, Jiang; Jin, Hua; Yang, Fen; Chen, Zheng W; Cai, Jiye


    The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In

  10. Case studies in quantitative biology: Biochemistry on a leash and a single-molecule Hershey-Chase experiment (United States)

    Van Valen, David


    The last 50 years of biological research has seen a marked increase in the amount of quantitative data that describes living systems. This wealth of data provides a unique opportunity to recast the pictorial level descriptions of biological processes in the language of mathematics, with the hope that such an undertaking will lead to deeper insights into the behavior of living systems. To achieve this end, we have undertaken three case studies in physical biology. In the first case study, we used statistical mechanics and polymer physics to construct a simple model that describes how flexible chains of amino acids, referred to as tethers, influence the information processing properties of signaling proteins. In the second case study, we studied the DNA ejection process of phage lambda in vitro. In particular, we used bulk and single-molecule methods to study the control parameters that govern the force and kinematics of the ejection process in vitro. In the last case study, we studied the DNA ejection process of phage lambda in vivo. We developed an assay that allows real-time monitoring of DNA ejection in vivo at the single-molecule level. We also developed a parallel system that allows the simultaneous visualization of both phage capsids and phage DNA at the single-cell level, constituting a true single-molecule Hershey-Chase experiment. The work described in this thesis outlines new tools, both in theory and experiment, that can be used to study biological systems as well as a paradigm that can be employed to mathematicize the cartoons of biology.

  11. Inactive ingredient Search for Approved Drug Products (United States)

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  12. A simple method of determination of partition coefficient for biologically active molecules. (United States)

    Sersen, F


    A simple method is presented for the determination of partition coefficient of an effector between water environment and biological material, based on concentration-dependent effects. The method allows the determination of partition coefficients for biological objects such as algae, bacteria and other microorganisms.

  13. SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints (United States)

    Curtis, Joseph E.; Raghunandan, Sindhu; Nanda, Hirsh; Krueger, Susan


    A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summaryProgram title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL: Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input

  14. Transfer of noncovalent chiral information along an optically inactive helical peptide chain: allosteric control of asymmetry of the C-terminal site by external molecule that binds to the N-terminal site. (United States)

    Ousaka, Naoki; Inai, Yoshihito


    This study aims at demonstrating end-to-end transfer of noncovalent chiral information along a peptide chain. The domino-type induction of helical sense is proven by using achiral peptides 1-m of bis-chromophoric sequence with different chain lengths: H-(Aib-Delta(Z)Phe)(m)-(Aib-Delta(Z)Bip)(2)-Aib-OCH(3) [m = 2, 4, and 6; Aib = alpha-aminoisobutyric acid; Delta(Z)Phe = (Z)-alpha,beta-didehydrophenylalanine; Delta(Z)Bip = (Z)-beta-(4,4'-biphenyl)-alpha,beta-didehydroalanine]. They all showed the tendency to adopt a 3(10)-helix. Whereas peptide 1-m originally shows no circular dichroism (CD) signals, marked CD signals were induced at around 270-320 nm based on both the beta-aryl didehydroresidues by chiral Boc-proline (Boc = tert-butoxycarbonyl). The observed CD spectra were interpreted on the basis of the exciton chirality method and theoretical CD simulation of several helical conformations that were energy-minimized. The experimental and theoretical CD analysis reveals that Boc-l-proline induces the preference for a right-handed helicity in the whole chain of 1-m. Such noncovalent chiral induction was not observed in the corresponding N-terminally protected 1-m. Obviously, helicity induction in 1-m originates from the binding of Boc-proline to the N-terminal site. In the 17-mer (1-6), the information of helix sense reaches the 16th residue from the N-terminus. We have monitored precise transfer of noncovalent chiral stimulus along a helical peptide chain. The present study also proposes a primitive allosteric model of a single protein-mimicking backbone. Here chiral molecule binding the N-terminal site of 1-6 controls the chiroptical signals and helical sense of the C-terminal site about 30 A away.

  15. Chemical biology--identification of small molecule modulators of cellular activity by natural product inspired synthesis. (United States)

    Hübel, Katja; Lessmann, Torben; Waldmann, Herbert


    The aim of this tutorial review is to introduce the reader to the concept, synthesis and application of natural product-inspired compound collections as an important field in chemical biology. This review will discuss how potentially interesting scaffolds can be identified (structural classification of natural products), synthesized in an appropriate manner (including stereoselective transformations for solid phase-bound compounds) and tested in biological assays (cell-based screening as well as biochemical in vitro assays). These approaches will provide the opportunity to identify new and interesting compounds as well as new targets for chemical biology and medicinal chemistry research.

  16. Current parallel chemistry principles and practice: application to the discovery of biologically active molecules. (United States)

    Edwards, Paul J


    This article describes the use of parallel chemistry techniques for drug discovery, based on publications from January 2006 to December 2008. Chemical libraries that yielded active compounds across a range of biological targets are presented, together with synthetic details when appropriate. Background information for the biological targets involved and any SAR that could be discerned within members of a library series also is discussed. New technological developments, as applied to library design and synthesis and, more generally, in the discovery of biologically active entities, are highlighted. In addition, the likely future directions for parallel chemistry in its ability to impact upon drug discovery are also presented.

  17. Monte Carlo simulation of several biologically relevant molecules and zwitterions in water (United States)

    Patuwo, Michael Y.; Bettens, Ryan P. A.


    In this work, we study the hydration free energies of butane, zwitterionic alanine, valine, serine, threonine, and asparagine, and two neuraminidase inhibitors by means of Monte Carlo (MC) simulation. The solute molecule, represented in the form of distributed multipoles and modified 6-12 potential, was varied from a non-interacting 'ghost' molecule to its full potential functions in TIP4P water. Intermediate systems with soft-core solute-solvent interaction potentials are simulated separately and then subjected to Bennett's Acceptance ratio (BAR) for the free energy calculation. Hydration shells surrounding the solute particles were used to assess the quality of potential functions.

  18. Single molecule optical measurements of orientation and rotations of biological macromolecules (United States)

    Shroder, Deborah Y.; Lippert, Lisa G.; Goldman, Yale E.


    Subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measurement of their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, review the relevant types of probes and labeling techniques, and highlight the advantages and disadvantages of these technologies for addressing specific inquiries.

  19. Electron transfer behaviour of biological macromolecules towards the single-molecule level

    DEFF Research Database (Denmark)

    Zhang, Jingdong; Grubb, Mikala; Hansen, Allan Glargaard


    on Au(111) by chemisorption via exposed sulfur-containing residues. Voltammetric, interfacial capacitance, x-ray photoelectron spectroscopy and microcantilever sensor data, together with in situ STM with single-molecule resolution, all point to a coherent view of monolayer organization with protein...

  20. Integration of biological ion channels onto optically addressable micro-fluidic electrode arrays for single molecule characterization.

    Energy Technology Data Exchange (ETDEWEB)

    Brozik, Susan Marie; Frink, Laura J. Douglas; Bachand, George David; Keller, David J. (University of New Mexico, Albuquerque, NM); Patrick, Elizabeth L.; Marshall, Jason A. (University of New Mexico, Albuquerque, NM); Ortiz, Theodore P. (University of New Mexico, Albuquerque, NM); Meyer, Lauren A. (University of New Mexico, Albuquerque, NM); Davis, Ryan W. (University of New Mexico, Albuquerque, NM); Brozik, James A. (University of New Mexico, Albuquerque, NM); Flemming, Jeb Hunter


    The challenge of modeling the organization and function of biological membranes on a solid support has received considerable attention in recent years, primarily driven by potential applications in biosensor design. Affinity-based biosensors show great promise for extremely sensitive detection of BW agents and toxins. Receptor molecules have been successfully incorporated into phospholipid bilayers supported on sensing platforms. However, a collective body of data detailing a mechanistic understanding of membrane processes involved in receptor-substrate interactions and the competition between localized perturbations and delocalized responses resulting in reorganization of transmembrane protein structure, has yet to be produced. This report describes a systematic procedure to develop detailed correlation between (recognition-induced) protein restructuring and function of a ligand gated ion channel by combining single molecule fluorescence spectroscopy and single channel current recordings. This document is divided into three sections: (1) reported are the thermodynamics and diffusion properties of gramicidin using single molecule fluorescence imaging and (2) preliminary work on the 5HT{sub 3} serotonin receptor. Thirdly, we describe the design and fabrication of a miniaturized platform using the concepts of these two technologies (spectroscopic and single channel electrochemical techniques) for single molecule analysis, with a longer term goal of using the physical and electronic changes caused by a specific molecular recognition event as a transduction pathway in affinity based biosensors for biotoxin detection.

  1. Effect of Co-Existing Biologically Relevant Molecules and Ions on DNA Photocleavage Caused by Pyrene and its Derivatives

    Directory of Open Access Journals (Sweden)

    Hongtao Yu


    Full Text Available Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs, in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I-, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD, glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP, and 1-aminopyrene (1-AP, is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered.

  2. Surface-enhanced Raman spectroscopy at single-molecule scale and its implications in biology


    Wang, Yuling; Irudayaraj, Joseph


    Single-molecule (SM) spectroscopy has been an exciting area of research offering significant promise and hope in the field of sensor development to detect targets at ultra-low levels down to SM resolution. To the experts and developers in the field of surface-enhanced Raman spectroscopy (SERS), this has often been a challenge and a significant opportunity for exploration. Needless to say, the opportunities and excitement of this multidisciplinary area impacts span the fields of physics, chemi...

  3. Prion-like nanofibrils of small molecules (PriSM): A new frontier at the intersection of supramolecular chemistry and cell biology


    Zhou, Jie; Du, Xuewen; Xu, Bing


    Formed by non-covalent interactions and not defined at genetic level, the assemblies of small molecules in biology are complicated and less explored. A common morphology of the supramolecular assemblies of small molecules is nanofibrils, which coincidentally resembles the nanofibrils formed by proteins such as prions. So these supramolecular assemblies are termed as prion-like nanofibrils of small molecules (PriSM). Emerging evidence from several unrelated fields over the past decade implies ...

  4. Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase: dynamics in nucleotides, amino acids and beyond


    Staniforth, Michael; Stavros, Vasilios G.


    In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radia...

  5. The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.

    Directory of Open Access Journals (Sweden)

    David S Goodsell


    Full Text Available The Research Collaboratory for Structural Bioinformatics (RCSB Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at

  6. Social background, bullying, and physical inactivity

    DEFF Research Database (Denmark)

    Henriksen, P W; Rayce, S B; Melkevik, O;


    More children from lower social backgrounds are physically inactive than those from higher ones. We studied whether bullying was a mediating factor between lower social background and physical inactivity. We also examined the combined effect of low social class and exposure to bullying on physical...... inactivity. The Danish sample of the Health Behaviour in School-aged Children (HBSC) study 2006 included 6269 schoolchildren in three age groups: 11-, 13-, and 15-year-olds from a random sample of 80 schools. The students answered the internationally standardized HBSC questionnaire. The applied definition...... leaves 4.0% in the category physically inactive. The sex and age-adjusted OR (95% CI) for physical inactivity was 2.10 (1.39-3.18) among students with low social class and unclassifiable 3.53 (2.26-5.53). Exposure to bullying was associated with physical inactivity, sex and age-adjusted OR = 2.39 (1...

  7. Inactive sites and the evolution of cooperation (United States)

    da Silva Júnior, E. J.; Wardil, L. L.; da Silva, J. K. L.


    Cooperation is often conditioned on environmental factors. Behaviors may be inactive due to external factors, and yet the trait itself may not change. We study the evolution of cooperation with active and inactive sites. In inactive sites cooperators behave as defectors, receiving but not providing benefits. This unintentional mimicry provides local advantage to cooperation, but also prevents the mutual reinforcement provided by clusters of active cooperators. In general, we found that cooperation is enhanced by inactivity. In particular, if most sites are inactive, cooperation survives even if the temptation to defect is very large. Interestingly, in the square lattice with pairwise comparison rule we found that cooperation is enforced by inactive sites only up to a certain limit.

  8. Holography and coherent diffraction with low-energy electrons: A route towards structural biology at the single molecule level

    Energy Technology Data Exchange (ETDEWEB)

    Latychevskaia, Tatiana; Longchamp, Jean-Nicolas; Escher, Conrad; Fink, Hans-Werner, E-mail:


    The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2 Å has been achieved revealing the 660.000 unit cells of the graphene sheet from a single data set. Once applied to individual biomolecules the method shall ultimately allow for non-destructive imaging and imports the potential to distinguish between different conformations of proteins with atomic resolution. - Highlights: • Structural biology of single proteins. • Radiation damage-free imaging of individual biomolecules. • Holography. • Low-energy electrons. • Coherent diffraction and phase retrieval.

  9. Max Delbruck Prize in Biological Physics Lecture: Single-molecule protein folding and transition paths (United States)

    Eaton, William


    The transition path is the tiny fraction of an equilibrium molecular trajectory when a transition occurs by crossing the free energy barrier between two states. It is a uniquely single-molecule property, and has not yet been observed experimentally for any system in the condensed phase. The importance of the transition path in protein folding is that it contains all of the mechanistic information on how a protein folds. As a major step toward observing transition paths, we have determined the average transition-path time for a fast and a slow-folding protein from a photon-by-photon analysis of fluorescence trajectories in single-molecule FRET experiments. While the folding rate coefficients differ by 10,000-fold, surprisingly, the transition-path times differ by less than 5-fold, showing that a successful barrier crossing event takes almost the same time for a fast- and a slow-folding protein, i.e. almost the same time to fold when it actually happens.

  10. Topology simplification: Important biological phenomenon or evolutionary relic?. Comment on "Disentangling DNA molecules" by Alexander Vologodskii (United States)

    Bates, Andrew D.; Maxwell, Anthony


    The review, Disentangling DNA molecules[1], gives an excellent technical description of the phenomenon of topology simplification (TS) by type IIA DNA topoisomerases (topos). In the 20 years since its discovery [2], this effect has attracted a good deal of attention, probably because of its apparently magical nature, and because it seemed to offer a solution to the conundrum that all type II topos rely on ATP hydrolysis, but only bacterial DNA gyrases were known to transduce the free energy of hydrolysis into torsion (supercoiling) in the DNA. It made good sense to think that the other enzymes are using the energy to reduce the level of supercoiling, knotting, and particularly decatenation (unlinking), below equilibrium, since the key activity of the non-supercoiling topos is the removal of links between daughter chromosomes [3]. As Vologodskii discusses [1], there have been a number of theoretical models developed to explain how the local effect of a type II topo can influence the global level of knotting and catenation in large DNA molecules, and he explains how features of two of the most successful models (bent G segment and hooked juxtapositions) may be combined to explain the magnitude of the effect and overcome a kinetic problem with the hooked juxtaposition model.

  11. Animal lectins as self/non-self recognition molecules. Biochemical and genetic approaches to understanding their biological roles and evolution. (United States)

    Vasta, G R; Ahmed, H; Fink, N E; Elola, M T; Marsh, A G; Snowden, A; Odom, E W


    In recent years, the significant contributions from molecular research studies on animal lectins have elucidated structural aspects and provided clues not only to their evolution but also to their multiple biological functions. The experimental evidence has suggested that distinct, and probably unrelated, groups of molecules are included under the term "lectin." Within the invertebrate taxa, major groups of lectins can be identified: One group would include lectins that show significant homology to membrane-integrated or soluble vertebrate C-type lectins. The second would include those beta-galactosyl-specific lectins homologous to the S-type vertebrate lectins. The third group would be constituted by lectins that show homology to vertebrate pentraxins that exhibit lectin-like properties, such as C-reactive protein and serum amyloid P. Finally, there are examples that do not exhibit similarities to any of the aforementioned categories. Moreover, the vast majority of invertebrate lectins described so far cannot yet be placed in one or another group because of the lack of information regarding their primary structure. (See Table 1.) Animal lectins do not express a recombinatorial diversity like that of antibodies, but a limited diversity in recognition capabilities would be accomplished by the occurrence of multiple lectins with distinct specificities, the presence of more than one binding site, specific for different carbohydrates in a single molecule, and by certain "flexibility" of the binding sites that would allow the recognition of a range of structurally related carbohydrates. In order to identify the lectins' "natural" ligands, we have investigated the interactions between those proteins and the putative endogenous or exogenous glycosylated substances or cells that may be relevant to their biological function. Results from these studies, together with information on the biochemical properties of invertebrate and vertebrate lectins, including their structural

  12. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects (United States)

    Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi


    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells.

  13. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects. (United States)

    Kojima, Shuji; Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi


    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells.

  14. Use of biological molecules in the treatment of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Seidelin, J B; Munck, Lena;


    The introduction of biological agents (i.e. antitumour necrosis factor-α and anti-integrin treatments) for the treatment of inflammatory bowel disease (IBD) [i.e. Crohn's disease (CD) and ulcerative colitis] has led to a substantial change in the treatment algorithms and guidelines, especially...... might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity...

  15. Use of biological molecules in the treatment of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Seidelin, J B; Munck, Lars Kristian;


    The introduction of biological agents (i.e. antitumour necrosis factor-a and anti-integrin treatments) for the treatment of inflammatory bowel disease (IBD) [i.e. Crohn's disease (CD) and ulcerative colitis] has led to a substantial change in the treatment algorithms and guidelines, especially...... might maximize the clinical benefit for those in most need of an effective therapy to avoid disabling disease whilst also minimizing the complications associated with therapy. Further, the 'trough-level strategy' may help clinicians to optimize therapy and to avoid loss of response and/or immunogenicity...

  16. Analyzing free zinc(II) ion concentrations in cell biology with fluorescent chelating molecules. (United States)

    Maret, Wolfgang


    Essential metal ions are tightly controlled in biological systems. An understanding of metal metabolism and homeostasis is being developed from quantitative information of the sizes, concentrations, and dynamics of cellular and subcellular metal ion pools. In the case of human zinc metabolism, minimally 24 proteins of two zinc transporter families and a dozen metallothioneins participate in cellular uptake, extrusion, and re-distribution among cellular compartments. Significantly, zinc(ii) ions are now considered signaling ions in intra- and intercellular communication. Such functions require transients of free zinc ions. It is experimentally quite challenging to distinguish zinc that is protein-bound from zinc that is not bound to proteins. Measurement of total zinc is relatively straightforward with analytical techniques such as atomic absorption/emission spectroscopy or inductively coupled plasma mass spectrometry. Total zinc concentrations of human cells are 200-300 μM. In contrast, the pool of non-protein bound zinc is mostly examined with fluorescence microscopy/spectroscopy. There are two widely applied fluorescence approaches, one employing low molecular weight chelating agents ("probes") and the other metal-binding proteins ("sensors"). The protein sensors, such as the CALWY, Zap/ZifCY, and carbonic anhydrase-based sensors, can be genetically encoded and have certain advantages in terms of controlling intracellular concentration, localization, and calibration. When employed correctly, both probes and sensors can establish qualitative differences in free zinc ion concentrations. However, when quantitative information is sought, the assumptions underlying the applications of probes and sensors must be carefully examined and even then measured pools of free zinc ions remain methodologically defined. A consensus is building that the steady-state free zinc ion concentrations in the cytosol are in the picomolar range but there is no consensus on their

  17. Absorption into fluorescence. A method to sense biologically relevant gas molecules. (United States)

    Strianese, Maria; Varriale, Antonio; Staiano, Maria; Pellecchia, Claudio; D'Auria, Sabato


    In this work we present an innovative optical sensing methodology based on the use of biomolecules as molecular gating nano-systems. Here, as an example, we report on the detection of analytes related to climate change. In particular, we focused our attention on the detection of nitric oxide (NO) and oxygen (O2). Our methodology builds on the possibility of modulating the excitation intensity of a fluorescent probe used as a transducer and a sensor molecule whose absorption is strongly affected by the binding of an analyte of interest used as a filter. The two simple conditions that have to be fulfilled for the method to work are: (a) the absorption spectrum of the sensor placed inside the cuvette, and acting as the recognition element for the analyte of interest, should strongly change upon the binding of the analyte and (b) the fluorescence dye transducer should exhibit an excitation band which overlaps with one or more absorption bands of the sensor. The absorption band of the sensor affected by the binding of the specific analyte should overlap with the excitation band of the transducer. The high sensitivity of fluorescence detection combined with the use of proteins as highly selective sensors makes this method a powerful basis for the development of a new generation of analytical assays. Proof-of-principle results showing that cytochrome c peroxidase (CcP) for NO detection and myoglobin (Mb) for O2 detection can be successfully used by exploiting our new methodology are reported. The proposed technology can be easily expanded to the determination of different target analytes.

  18. Phytohormones as Important Biologically Active Molecules – Their Simple Simultaneous Detection

    Directory of Open Access Journals (Sweden)

    Ladislav Havel


    Full Text Available Phytohormones, their functions, synthesis and effects, are of great interest. To study them in plant tissues accurate and sensitive methods are required. In the present study we aimed at optimizing experimental conditions to separate and determine not only plant hormones but also their metabolites, by liquid chromatography coupled with a UV-VIS detector. The mixture we analyzed was composed of benzyladenine, kinetin, trans-zeatin, cis-zeatin, dihydrozeatin, meta-topolin, ortho-topolin, α-naphthalene acetic acid, indole-3-acetic acid, trans-zeatin-7-glucoside, trans-zeatin-O-glucoside, trans-zeatin-9-riboside, meta-topolin-9-riboside and ortho-topolin-9-riboside. We measured the calibration dependences and estimated limits of detection and quantification under the optimal chromatographic conditions (column: Polaris C18; mobile phase: gradient starting at 2:98 (methanol:0.001% TFA and was increasing to 55:45 during twenty minutes, and then decreasing for 10 min to 35:65, flow rate: 200 µL·min-1, temperature: 50 °C, wavelength: 210 nm. The detection limits for the target molecules were estimated as tens of ng per mL. We also studied the effect of flax extracts on the phytohormones’ signals. Recovery of aliphatic and aromatic cytokinins, metabolites of cytokinins and auxinswere within the range from 87 to 105 %. The experimental conditions were tested on a mass selective detector. In addition we analysed a commercial product used for stimulation of roots formation in cuttings of poorly rooting plants. The determined content of α-naphthalene acetic acid was in good agreement with that declared by the manufacturer.

  19. Biological functions of hCG and hCG-related molecules

    Directory of Open Access Journals (Sweden)

    Cole Laurence A


    Full Text Available Abstract Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

  20. Characterization of the electronic states of the biological relevant SSNO molecule (United States)

    Ayari, Tarek; Hochlaf, Majdi; Mogren Al-Mogren, Muneerah; Francisco, Joseph S.


    Using configuration interaction ab initio methods, we investigate the lowest electronic states of doublet and quartet spin multiplicities of SSNO where the one-dimensional cuts of the six-dimensional potential energy surfaces of these electronic states along the stretching and bending coordinates are computed. Mainly, these electronic states are found to be repulsive along the central SN distance. A high density of electronic states is computed even at low excitation energies that may favor their couplings. Therefore, the dynamics of the SSNO electronic states is expected to be very complex. We also characterized the bound electronic states spectroscopically where we derived their equilibrium structures and vibrational frequencies. Our calculations show the importance of taking into account of dynamical correlation, in addition to static correlation, for the accurate description of SSNO electronic excited states and more generally for those of R-NO molecular species. Finally, we highlighted the potential role of SSNO in light-induced NO delivery from SSNO related species in biological media.

  1. Life at extreme conditions: Neutron scattering studies of biological molecules suggest that evolution selected dynamics

    Indian Academy of Sciences (India)

    Joseph (Giuseppe) Zaccai


    The short review concentrates on recent work performed at the neutrons in biology laboratories of the Institut Laue Langevin and Institut de Biologie Structurale in Grenoble. Extremophile organisms have been discovered that require extreme conditions of temperature, pressure or solvent environment for survival. The existence of such organisms poses a significant challenge in understanding the physical chemistry of their proteins, in view of the great sensitivity of protein structure and stability to the aqueous environment and to external conditions in general. Results of neutron scattering measurements on the dynamics of proteins from extremophile organisms, in vitro as well as in vivo, indicated remarkably how adaptation to extreme conditions involves forces and fluctuation amplitudes that have been selected specifically, suggesting that evolutionary macromolecular selection proceeded via dynamics. The experiments were performed on a halophilic protein, and membrane adapted to high salt, a thermophilic enzyme adapted to high temperature and its mesophilic (adapted to 37°C) homologue; and in vivo for psychrophilic, mesophilic, thermophilic and hyperthermophilic bacteria, adapted respectively to temperatures of 4°C, 37°C, 75°C and 85°C. Further work demonstrated the existence of a water component of exceptionally low mobility in an extreme halophile from the Dead Sea, which is not present in mesophile bacterial cells.

  2. How carbo-benzenes fit molecules in their inner core as do biologic ion carriers?

    KAUST Repository

    Turias, Francesc


    The present computational study complements experimental efforts to describe and characterize carbo-benzene derivatives as paradigms of aromatic carbo-mers. A long-lasting issue has been the possibility of the π-electron crown of the C18 carbo-benzene ring to fit metals or any chemical agents in its core. A systematic screening of candidate inclusion complexes was carried out by density functional theory calculations. Mayer bond order, aromaticity indices, and energy decomposition analyses complete the understanding of the strength of the host-guest interaction. The change in steric and electronic properties induced by the guest agent is investigated by means of steric maps. Substitution of H atoms at the carbo-benzene periphery by electron-withdrawing or electron-donating groups is shown to have a determining influence on the stability of the inclusion complex ions: while electronegative substituents enhance the recognition of cations, electropositive substituents do the same for anions. The results confirm the experimental failure hitherto to evidence a carbo-benzene complex. Nevertheless, the affinity of carbo-benzene for the potassium cation appears promising for the design of planar hydrocarbon analogues of biologic ion carriers. © 2015 Springer Science+Business Media New York.

  3. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

    Directory of Open Access Journals (Sweden)

    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  4. A ligation-triggered DNAzyme cascade for amplified fluorescence detection of biological small molecules with zero-background signal. (United States)

    Lu, Li-Min; Zhang, Xiao-Bing; Kong, Rong-Mei; Yang, Bin; Tan, Weihong


    Many types of fluorescent sensing systems have been reported for biological small molecules. Particularly, several methods have been developed for the recognition of ATP or NAD(+), but they only show moderate sensitivity, and they cannot discriminate either ATP or NAD(+) from their respective analogues. We have addressed these limitations and report here a dual strategy which combines split DNAzyme-based background reduction with catalytic and molecular beacon (CAMB)-based amplified detection to develop a ligation-triggered DNAzyme cascade, resulting in ultrahigh sensitivity. First, the 8-17 DNAzyme is split into two separate oligonucleotide fragments as the building blocks for the DNA ligation reaction, thereby providing a zero-background signal to improve overall sensitivity. Next, a CAMB strategy is further employed for amplified signal detection achieved through cycling and regenerating the DNAzyme to realize the true enzymatic multiple turnover (one enzyme catalyzes the cleavage of several substrates) of catalytic beacons. This combination of zero-background signal and signal amplification significantly improves the sensitivity of the sensing systems, resulting in detection limits of 100 and 50 pM for ATP and NAD(+), respectively, much lower than those of previously reported biosensors. Moreover, by taking advantage of the highly specific biomolecule-dependence of the DNA ligation reaction, the developed DNAzyme cascades show significantly high selectivity toward the target cofactor (ATP or NAD(+)), and the target biological small molecule can be distinguished from its analogues. Therefore, as a new and universal platform for the design of DNA ligation reaction-based sensing systems, this novel ligation-triggered DNAzyme cascade method may find a broad spectrum of applications in both environmental and biomedical fields.

  5. Holography and coherent diffraction with low-energy electrons: A route towards structural biology at the single molecule level. (United States)

    Latychevskaia, Tatiana; Longchamp, Jean-Nicolas; Escher, Conrad; Fink, Hans-Werner


    The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2Å has been achieved revealing the 660.000 unit cells of the graphene sheet from a single data set. Once applied to individual biomolecules the method shall ultimately allow for non-destructive imaging and imports the potential to distinguish between different conformations of proteins with atomic resolution.

  6. Holography and Coherent Diffraction with Low-Energy Electrons: A Route towards Structural Biology at the Single Molecule Level

    CERN Document Server

    Latychevskaia, Tatiana; Escher, Conrad; Fink, Hans-Werner


    The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2 Angstrom has been achieved revealing the 660.000 unit cells of the graphene sheet from one data set at once. Applied to individual biomolecules the method allows for non-destructive imaging and imports the potential to distinguish between di...

  7. The inaction approach to gauge theories

    CERN Document Server

    Pivovarov, Grigorii


    The inaction approach introduced previously for phi^4 is generalized to gauge theories. It combines the advantages of the effective field theory and causal approaches to quantum fields. Also, it suggests ways to generalizing gauge theories.

  8. Leaf-specific pathogenesis-related 10 homolog, PgPR-10.3, shows in silico binding affinity with several biologically important molecules

    Directory of Open Access Journals (Sweden)

    Jin Haeng Han


    Conclusion: Although ginseng PR-10.3 gene is expressed in all organs of 3-wk-old plantlets, its expression is restricted to leaves in mature 2-yr-old ginseng plants. The putative binding property of PgPR-10.3 with Re is intriguing. Further verification of binding affinity with other biologically important molecules in the large hydrophobic cavity of PgPR-10.3 may provide an insight into the biological features of PR-10 proteins.

  9. Prospect of detection and recognition of single biological molecules using ultrafast coherent dynamics in quantum dot-metallic nanoparticle systems (United States)

    Sadeghi, S. M.


    Conventional plasmonic sensors are based on the intrinsic resonances of metallic nanoparticles. In such sensors wavelength shift of such resonances are used to detect biological molecules. Recently we introduced ultra-sensitive timedomain nanosensors based on the way variations in the environmental conditions influence coherent dynamics of hybrid systems consisting of metallic nanoparticles and quantum dots. Such dynamics are generated via interaction of these systems with a laser field, generating quantum coherence and coherent exciton-plasmon coupling. These sensors are based on impact of variations of the refractive index of the environment on such dynamics, generating time-dependent changes in the emission of the QDs. In this paper we study the impact of material properties of the metallic nanoparticles on this process and demonstrate the key role played by the design of the quantum dots. We show that Ag nanoparticles, even in a simple spherical shape, may allow these sensors to operate at room temperature, owing to the special properties of quantum dot-metallic nanoparticle systems that may allow coherent effects utilized in such sensors happen in the presence of the ultrafast polarization dephasing of quantum dots.

  10. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Falko Lange


    Full Text Available Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC patients, to evaluate effects of the small molecule kinase inhibitors (SMI vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.

  11. Prion-like nanofibrils of small molecules (PriSM): A new frontier at the intersection of supramolecular chemistry and cell biology. (United States)

    Zhou, Jie; Du, Xuewen; Xu, Bing


    Formed by non-covalent interactions and not defined at genetic level, the assemblies of small molecules in biology are complicated and less explored. A common morphology of the supramolecular assemblies of small molecules is nanofibrils, which coincidentally resembles the nanofibrils formed by proteins such as prions. So these supramolecular assemblies are termed as prion-like nanofibrils of small molecules (PriSM). Emerging evidence from several unrelated fields over the past decade implies the significance of PriSM in biology and medicine. This perspective aims to highlight some recent advances of the research on PriSM. This paper starts with description of the intriguing similarities between PriSM and prions, discusses the paradoxical features of PriSM, introduces the methods for elucidating the biological functions of PriSM, illustrates several examples of beneficial aspects of PriSM, and finishes with the promises and current challenges in the research of PriSM. We anticipate that the research of PriSM will contribute to the fundamental understanding at the intersection of supramolecular chemistry and cell biology and ultimately lead to a new paradigm of molecular (or supramolecular) therapeutics for biomedicine.

  12. Properties of inactive Photosystem II centers. (United States)

    Lavergne, J; Leci, E


    A fraction (usually in the range of 10-25%) of PS II centers is unable to transfer electrons from the primary quinone acceptor QA to the secondary acceptor QB. These centers are inactive with respect to O2 evolution since their reopening after photochemical charge separation to the S2OA (-) state involves predominantly a back reaction to S1QA in the few seconds time range (slower phases are also occurring). Several properties of these centers are analyzed by fluorescence and absorption change experiments. The initial rise phase Fo-Fpl of fluorescence induction under weak illumination reflects both the closure of inactive centers and the modulation of the fluorescence yield by the S-states of the oxygen-evolving system: We estimate typical relative amplitudes of these contributions as, respectively, 65 and 35% of the Fo-Fpl amplitude. The half-rise time of this phase is significantly shorter than for the fluorescence induction in the presence of DCMU (in which all centers are involved). This finding is shown to be consistent with inactive centers sharing the same light-harvesting antenna as normal centers, a view which is also supported by comparing the dependence of the fluorescence yield on the amount of closed active or inactive centers estimated through absorption changes. It is argued that the exponential kinetics of the Fo-Fpl phase does not indicate absence of excitation energy transfer between the antennas of inactive and active centers. We show that the acceptor dichlorobenzoquinone does not restore electron transfer in inactive centers, in disagreement with previous suggestions. We confirm, however, the enhancement of steady-state electron flow caused by this quinone and suggest that it acts by relieving a blocking step involved in the reoxidation of a fraction of the plastoquinone pool. Part of the discrepancies between the present results and those from previous literature may arise from the confusion of inactive centers characterized on a single

  13. Light saturation response of inactive photosystem II reaction centers in spinach. (United States)

    Chylla, R A; Whitmarsh, J


    The effective absorption cross section of inactive photosystem II (PS II) centers, which is the product of the effective antenna size and the quantum yield for photochemistry, was investigated by comparing the light saturation curves of inactive PS II and active reaction centers in intact chloroplasts and thylakoid membranes of spinach (Spinacia oleracea). Inactive PS II centers are defined as the impaired PS II reaction centers that require greater than 50 ms for the reoxidation of QA (-) subsequent to a single turnover flash. Active reaction centers are defined as the rapidly turning over PS II centers (recovery time less than 50 ms) and all of the PS I centers. The electrochromic shift, measured by the flash-induced absorbance increase at 518 nm, was used to probe the activity of the reaction centers. Light saturation curves were generated for inactive PS II centers and active reaction centers by measuring the extent of the absorbance increase at 518 nm induced by red actinic flashes of variable energy. The light saturation curves show that inactive PS II centers required over twice as many photons as active reaction centers to achieve the same yield. The ratio of the flash energy required for 50% saturation for active reaction centers (PS II active + PS I) compared to inactive PS II centers was 0.45±0.04 in intact chloroplasts, and 0.54±0.11 in thylakoid membranes. Analysis of the light saturation curves using a Poisson statistical model in which the ratio of the antenna size of active PS II centers to that of PS I is considered to range from 1 to 1.5, indicates that the effective absorption cross section of inactive PS II centers was 0.54-0.37 times that of active PS II centers. If the quantum yield for photochemistry is assumed to be one, we estimate that the antenna system serving the inactive PS II centers contains approx. 110 chlorophyll molecules.

  14. Detrimental effects of physical inactivity on neurogenesis

    Directory of Open Access Journals (Sweden)

    Trenton Lippert


    Full Text Available Patients diagnosed with neurological disorders exhibit a variety of physical and psychiatric symptoms, including muscle atrophy, general immobility, and depression. Patients who participate in physical rehabilitation at times show unexpected clinical improvement, which includes diminished depression and other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for central nervous system (CNS disorders, transplantation of exogenous stem cells, and enhancing the endogenous neurogenesis. The latter therapy utilizes a natural method of re-innervating the injured brain, which may mend neurological impairments. In this study, we examine how inactivity-induced atrophy, using the hindlimb suspension model, alters neurogenesis in rats. The hypothesis is that inactivity inhibits neurogenesis by decreasing circulation growth or trophic factors, such as vascular endothelial growth or neurotrophic factors. The restriction modifies neurogenesis and stem cell differentiation in the CNS, the stem cell microenvironment is examined by the trophic and growth factors, including stress-related proteins. Despite growing evidence revealing the benefits of "increased" exercise on neurogenesis, the opposing theory involving "physical inactivity," which simulates pathological states, continues to be neglected. This novel theory will allow us to explore the effects on neurogenesis by an intransigent stem cell microenvironment likely generated by inactivity. 5-bromo-2-deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid, and brain levels of trophic factors, growth factors, and stress-related proteins are suggested identifiers of neurogenesis, while evaluation of spontaneous movements will give insight into the psychomotor effects of inactivity. Investigations devised to show how in vivo stimulation, or lack thereof, affects the stem cell microenvironment are necessary to establish


    Institute of Scientific and Technical Information of China (English)

    杨章民; 司履生; 王一理; 来宝长


    Objective To design and construct the eukaryotic expression vector which expresses Anti-CD3 ScFv-B7.1 fusion molecules and predict the biological characteristics, the rationality and feasibility of the spacer. Methods To analyze the flexibility, Hoop & Woods hydrophilicity and the epitope of Anti-CD3 ScFv-B7.1 fusion molecule at secondary structure level by computer simulation utilizing the GoldKey software. Results By comparing with Anti-CD3 ScFv and B7.1 respectively, it shows that Anti-CD3 ScFv-B7.1 fusion molecules can form correct secondary structure with the linking of the spacer, the fusion does not change the original hydrophilicity and epitopes of both Anti-CD3 ScFv and B7.1, no new epitopes emerge; The spacer is flexible and shows low antigenicity. Conclusion The design of Anti-CD3 ScFv-B7.1 fusion molecule are rational and feasible, the expressed fusion protein could retain the maximum biological activity and the function of both Anti-CD3 ScFv and B7.1.

  16. Inactive DNMT3B Splice Variants Modulate De Novo DNA Methylation


    Gordon, Catherine A.; Hartono, Stella R; Frédéric Chédin


    Inactive DNA methyltransferase (DNMT) 3B splice isoforms are associated with changes in DNA methylation, yet the mechanisms by which they act remain largely unknown. Using biochemical and cell culture assays, we show here that the inactive DNMT3B3 and DNMT3B4 isoforms bind to and regulate the activity of catalytically competent DNMT3A or DNMT3B molecules. DNMT3B3 modestly stimulated the de novo methylation activity of DNMT3A and also counteracted the stimulatory effects of DNMT3L, therefore l...

  17. Study of radionuclides speciation with biological molecules of interest by spectrometric techniques; Etude de la speciation des radionucleides avec les molecules d'interet biologique par approche spectrometrique

    Energy Technology Data Exchange (ETDEWEB)

    Lourenco, V


    Mechanisms of complexation and accumulation of the radionuclides at the cellular and molecular level are complex and poorly known because the studies on these subjects are scarce. Within the framework of this thesis, we studied the interactions of these cations with biological molecules of interest. We chose to focus on an actinide: uranium (VI) as well as europium as an analogue of trivalent actinides. The selected biological molecules are the phyto-chelatins: their role is to protect cells against intrusions from nonessential heavy metals (thus toxic). These proteins are likely to be implied in the mechanisms of sequestration of radionuclides in living organisms. However, their structure is complex, this is why, in order to better include/understand their reactivity, we extended our studies to lower entities which constitute them (amino acid: glycine, glutamic acid and cysteine; polypeptides: glutathione reduced and oxidized forms). In particular, we determined solution speciation (stoichiometry, structure) as well as the complexing constants associated with the formation with these species. These studies were undertaken by Time Resolved Laser induced Fluorescence (TRLIF), Electro-Spray-Mass Spectrometry (ES-MS), Nuclear Magnetic Resonance (NMR), Fourier Transform Infra-Rouge spectroscopy (FTIR) and Extended X-ray Absorption Fine Structure Spectroscopy (EXAFS).The determination of the complexation constants enabled us to conclude that the complexing capacity of these molecules with respect to radionuclides was moderate (log{sub 10}K{sub 1} {<=} 3, pH 3 or 6), the formed species are mononuclear with only one ligand molecule (1:1). The interaction is performed via oxygenated (hard) groups. The direct complexation of europium with phyto-chelatins at acidic pH was studied jointly by TRLIF and ES-MS. The complexing capacity of these molecules is much higher than that of GSH from which they result. The interaction of europium with metallothioneins is, on the contrary

  18. The bottom-up approach to defining life : deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    Directory of Open Access Journals (Sweden)

    Sathish ePeriyasamy


    Full Text Available In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell’s multi-objective topology formed by spatially and temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organise in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly evolving, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organised into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organisation, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modelling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterises the properties and constraints that are consequential to the organisational and adaptive dynamics in biological cells.

  19. Exploring human inactivity in computer power consumption (United States)

    Candrawati, Ria; Hashim, Nor Laily Binti


    Managing computer power consumption has become an important challenge in computer society and this is consistent with a trend where a computer system is more important to modern life together with a request for increased computing power and functions continuously. Unfortunately, previous approaches are still inadequately designed to handle the power consumption problem due to unpredictable workload of a system caused by unpredictable human behaviors. This is happens due to lack of knowledge in a software system and the software self-adaptation is one approach in dealing with this source of uncertainty. Human inactivity is handled by adapting the behavioral changes of the users. This paper observes human inactivity in the computer usage and finds that computer power usage can be reduced if the idle period can be intelligently sensed from the user activities. This study introduces Control, Learn and Knowledge model that adapts the Monitor, Analyze, Planning, Execute control loop integrates with Q Learning algorithm to learn human inactivity period to minimize the computer power consumption. An experiment to evaluate this model was conducted using three case studies with same activities. The result show that the proposed model obtained those 5 out of 12 activities shows the power decreasing compared to others.

  20. Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy. (United States)

    Sun, Shiyu; Zhao, Guangxu; Huang, Yibing; Cai, Mingjun; Shan, Yuping; Wang, Hongda; Chen, Yuxin


    In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers.

  1. 40 CFR 256.25 - Recommendation for inactive facilities. (United States)


    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommendation for inactive facilities. 256.25 Section 256.25 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID... Disposal Programs § 256.25 Recommendation for inactive facilities. Inactive facilities that continue...

  2. Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules. (United States)

    Toshima, Kazunobu


    Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

  3. Max Delbruck Biological Physics Prize Talk: The Biophysics of Gene Regulation, Studied One Molecule at a Time (United States)

    Block, Steven


    Advances have led to a new field, dubbed single molecule biophysics. Prominent among the new technologies is the optical trap, or `optical tweezers.' Sensitive systems for measuring force and displacement in optical traps permit the nanomechanical properties of individual macromolecules to be explored with unprecedented precision, revealing behaviors heretofore obscured by ensemble-based approaches. This talk will focus on some of our current work with single-molecule systems, including transcription by RNA polymerase and structural transitions in nucleic acids. We developed high-resolution instrumentation that has broken the nanometer barrier and is thereby able to detect displacements down to the atomic level, in aqueous buffer at room temperature. Consequently, we can monitor the motions of RNA polymerase molecules in real time as these step from base to base along DNA. On the practical side, base-pair resolution makes it possible to sequence DNA in a new way, based on enzyme motions, and points to new directions in nanoscience. The improved stability afforded by the current generation of optical trapping apparatus has allowed us to reconstruct the complete energy landscapes for folding transitions in nucleic-acid hairpins. Recently, we have turned our attention to the problem of co-transcriptional folding, aptamers, and riboswitches formed in nascent mRNAs, and to the DNA or RNA sequence elements that regulate expression.

  4. The AstroBiology Explorer (ABE) MIDEX Mission: Using Infrared Spectroscopy to Identify Organic Molecules in Space (United States)

    Sandford, S. A.


    The AstroBiology Explorer (ABE) mission is one of four selected for Phase A Concept Study in NASA's current call for MIDEX class missions. ABE is a cooled space telescope equipped with spectrographs covering the 2.5-20 micron spectral range. The ABE mission is devoted to the detection and identification of organic and related molecular species in space. ABE is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace.

  5. Identification of inactivity behavior in smart home. (United States)

    Poujaud, J; Noury, N; Lundy, J-E


    To help elderly people live independently at home, the TIMC-IMAG laboratory developed Health Smart Homes called 'HIS'. These smart Homes are composed of several sensors to monitor the activities of daily living of the patients. Volunteers have accepted to be monitored during 2 years in their own flats. During one year, we carried out our survey on one elderly patient. Thanks to this experimentation, we will access to relevant information like physiological, environmental and activity. This paper focuses on daily living activity. We will introduce an original data splitting method based on the relationship between the frame of time and the location in the flat. Moreover we will present two different methods to determine a threshold of critical inactivity and eventually we will discuss their possible utilities.

  6. Catalytic enantioselective construction of quaternary stereocenters: assembly of key building blocks for the synthesis of biologically active molecules. (United States)

    Liu, Yiyang; Han, Seo-Jung; Liu, Wen-Bo; Stoltz, Brian M


    The ever-present demand for drugs with better efficacy and fewer side effects continually motivates scientists to explore the vast chemical space. Traditionally, medicinal chemists have focused much attention on achiral or so-called "flat" molecules. More recently, attention has shifted toward molecules with stereogenic centers since their three-dimensional structures represent a much larger fraction of the chemical space and have a number of superior properties compared with flat aromatic compounds. Quaternary stereocenters, in particular, add greatly to the three-dimensionality and novelty of the molecule. Nevertheless, synthetic challenges in building quaternary stereocenters have largely prevented their implementation in drug discovery. The lack of effective and broadly general methods for enantioselective formation of quaternary stereocenters in simple molecular scaffolds has prompted us to investigate new chemistry and develop innovative tools and solutions. In this Account, we describe three approaches to constructing quaternary stereocenters: nucleophilic substitution of 3-halooxindoles, conjugate addition of boronic acids to cyclic enones, and allylic alkylation of enolates. In the first approach, malonic ester nucleophiles attack electrophilic 3-halooxindoles, mediated by a copper(II)-bisoxazoline catalyst. A variety of oxindoles containing a benzylic quaternary stereocenter can be accessed through this method. However, it is only applicable to the specialized 3,3-disubstituted oxindole system. To access benzylic quaternary stereocenters in a more general context, we turned our attention to the enantioselective conjugate addition of carbon nucleophiles to α,β-unsaturated carbonyl acceptors. We discovered that in the presence of catalytic palladium-pyridinooxazoline complex, arylboronic acids add smoothly to β-substituted cyclic enones to furnish ketones with a β-benzylic quaternary stereocenter in high yields and enantioselectivities. The reaction is

  7. Differential membrane fluidization by active and inactive cannabinoid analogues. (United States)

    Mavromoustakos, T; Papahatjis, D; Laggner, P


    The effects of the two cannabinomimetic drugs (-)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethyl-1-hydroxy-6H-dibenzo[b,d]pyranyl-2-(hexyl)-1,3-dithiolane (AMG-3) and its pharmacologically less active 1-methoxy analogue (AMG-18) on the thermotropic and structural properties of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) liposomes have been studied by X-ray diffraction and differential scanning calorimetry (DSC). DSC data revealed that the incorporation of the drugs affect differently the thermotropic properties of DPPC. The presence of the more active drug distinctly broadened and attenuated both the pretransition and main phase transition of DPPC bilayers, while the inactive analogue had only minor effects. Small and wide angle X-ray diffraction data showed that the two cannabinoids have different effects on the lipid phase structures and on the hydrocarbon chain packing. The pharmacologically active analogue, AMG-3, was found to efficiently fluidize domains of the lipids in the L(beta)' gel phase, and to perturb the regular multibilayer lattice. In the liquid crystalline L(alpha) phase, AMG-3 was also found to cause irregularities in packing, suggesting that the drug induces local curvature. At the same concentration, the inactive AMG-18 had only minor structural effects on the lipids. At about 10-fold or higher concentrations, AMG-18 was found to produce similar but still less pronounced effects in comparison to those observed by AMG-3. The dose-dependent, different thermotropic and structural effects by the two cannabinoid analogues suggest that these may be related to their biological activity.

  8. Biologic

    CERN Document Server

    Kauffman, L H


    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  9. Surface functionalization of bioactive glasses with natural molecules of biological significance, part II: Grafting of polyphenols extracted from grape skin (United States)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica


    Polyphenols, as one of the most important family of phytochemicals protective substances from grape fruit, possess various biological activities and health-promoting benefits, for example: inhibition of some degenerative diseases, cardiovascular diseases and certain types of cancers, reduction of plasma oxidative stress and slowing aging. The combination of polyphenols and biomaterials may have good potential to reach good bioavailability and controlled release, as well as to give biological signaling properties to the biomaterial surfaces. In this research, conventional solvent extraction was developed for obtaining polyphenols from dry grape skins. The Folin&Ciocalteu method was used to determine the amount of total polyphenols in the extracts. Surface functionalization of two bioactive glasses (SCNA and CEL2) was performed by grafting the extracted polyphenols on their surfaces. The effectiveness of the functionalization was tested by UV spectroscopy, which analyzes the amount of polyphenols in the uptake solution (before and after functionalization) and on solid samples, and XPS, which analyzes the presence of phenols on the material surface.

  10. Biology-oriented synthesis of a natural-product inspired oxepane collection yields a small-molecule activator of the Wnt-pathway. (United States)

    Basu, Sudipta; Ellinger, Bernhard; Rizzo, Stefano; Deraeve, Céline; Schürmann, Markus; Preut, Hans; Arndt, Hans-Dieter; Waldmann, Herbert


    In Biology Oriented Synthesis the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is met by the structurally complex scaffolds of natural products (NPs) selected in evolution. The synthesis of NP-inspired compound collections approaching the complexity of NPs calls for the development of efficient synthetic methods. We have developed a one pot 4-7 step synthesis of mono-, bi-, and tricyclic oxepanes that resemble the core scaffolds of numerous NPs with diverse bioactivities. This sequence entails a ring-closing ene-yne metathesis reaction as key step and makes productive use of polymer-immobilized scavenger reagents. Biological profiling of a corresponding focused compound collection in a reporter gene assay monitoring for Wnt-signaling modulation revealed active Wntepanes. This unique class of small-molecule activators of the Wnt pathway modulates the van-Gogh-like receptor proteins (Vangl), which were previously identified in noncanonical Wnt signaling, and acts in synergy with the canonical activator protein (Wnt-3a).

  11. A mechanistic approach to link biological effects of radioactive substances from molecules to populations in wildlife species - A mechanistic approach to link biological effects of radionuclides from molecules to populations in wildlife species

    Energy Technology Data Exchange (ETDEWEB)

    Alonzo, Frederic; Parisot, Florian; Plaire, Delphine; Adam-Guillermin, Christelle; Garnier- Laplace, Jacqueline [Institut de Radioprotection et de Surete Nucleaire (IRSN), PRP-ENV, SERIS, LECO, Cadarache, Saint-Paul- Lez-Durance, 13115 (France)


    Understanding how toxic contaminants affect wildlife species at various levels of biological organisation (sub-cellular, histological, physiological, organism, population levels) is a major research goal in both ecotoxicology and radioecology. A mechanistic understanding of the links between the different observed perturbations is necessary to predict consequences for survival, growth and reproduction which are critical for population dynamics. However, time scales at which such links are established in the laboratory are rarely relevant for natural populations. With a small size and short life cycle, the cladoceran micro-crustacean Daphnia magna is a particularly suitable biological model for studying effects of radioactive contaminants over several generations. Multi-generational exposures are much more representative of the environmental context of field populations for which contaminations can last for durations which largely exceed individual longevity and involve exposure of many successive generations. Over the last decade, multi-generational investigations of toxic effects were conducted under controlled conditions in D. magna exposed to various radionuclides including depleted uranium, americium-241 and cesium-137, representing respectively a dominantly chemo-toxic metal, an alpha internal contamination and a gamma external radiation. Results showed in all cases that toxic effects on physiology and life history (survival, body size, fecundity) increased in severity across generations. These observations demonstrated that measured effects in one generation might not be representative of toxicity in the following offspring generations, and ultimately of the population response. Reduction in somatic growth and reproduction induced by uranium were analysed using the mechanistic modelling approach known as DEBtox (model of dynamic energy budget applied to toxicology). Modelling results suggested that uranium primarily affects assimilation. This metabolic mode

  12. Investigating how the attributes of self-associated drug complexes influence the passive transport of molecules through biological membranes. (United States)

    Inacio, R; Barlow, D; Kong, X; Keeble, J; Jones, S A


    Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (ptransport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96±0.31μgcm(-2)min(-1) and 1.59±0.26μgcm(-2)min(-1) respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (ptransport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration.

  13. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites (United States)

    Kevin, Dion A; Meujo, Damaris AF; Hamann, Mark T


    Background As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics. PMID:23480512

  14. Adsorption of small biological molecules on silica from diluted aqueous solutions: Quantitative characterization and implications to the Bernal's hypothesis (United States)

    Basiuk, Vladimir A.; Gromovoy, Taras Yu.; Khil'Chevskaya, Elena G.


    To describe quantitatively the adsorption of prebiotically important compounds of low molecular weight (amino acids, short linear peptides, cyclic dipeptides, the Krebs's cycle and other carboxylic acids, nucleosides and related phosphates) on silica surface from diluted neutral aqueous solutions, equilibrium constants (K) and free energies (-ΔG) of adsorption were determined from the retention values measured by means of high-performance liquid chromatography on a silica gel column and from the isotherms measured under static conditions. For most carboxylic acids (including amino acids and linear peptides) -ΔG values were negative and K0 and K>1 were found for most of them. Influence of the structure of α-substituent on the adsorbability is analyzed. A linear dependence of -ΔG on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the row from glycine to triglycyl glycine. The adsorption of nucleosides and their phosphates is characterized by much higherK and -ΔG values (of the order of 102 and 104, respectively). The adsorption data available from our work and literature are summarized and discussed with implications to the Bernal's hypothesis on the roles of solid surfaces in the prebiotic formation of biopolymers from monomeric ‘building blocks’.

  15. Predictive models for anti-tubercular molecules using machine learning on high-throughput biological screening datasets

    Directory of Open Access Journals (Sweden)

    Periwal Vinita


    Full Text Available Abstract Background Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis (Mtb, affecting more than two billion people around the globe and is one of the major causes of morbidity and mortality in the developing world. Recent reports suggest that Mtb has been developing resistance to the widely used anti-tubercular drugs resulting in the emergence and spread of multi drug-resistant (MDR and extensively drug-resistant (XDR strains throughout the world. In view of this global epidemic, there is an urgent need to facilitate fast and efficient lead identification methodologies. Target based screening of large compound libraries has been widely used as a fast and efficient approach for lead identification, but is restricted by the knowledge about the target structure. Whole organism screens on the other hand are target-agnostic and have been now widely employed as an alternative for lead identification but they are limited by the time and cost involved in running the screens for large compound libraries. This could be possibly be circumvented by using computational approaches to prioritize molecules for screening programmes. Results We utilized physicochemical properties of compounds to train four supervised classifiers (Naïve Bayes, Random Forest, J48 and SMO on three publicly available bioassay screens of Mtb inhibitors and validated the robustness of the predictive models using various statistical measures. Conclusions This study is a comprehensive analysis of high-throughput bioassay data for anti-tubercular activity and the application of machine learning approaches to create target-agnostic predictive models for anti-tubercular agents.

  16. Ion-pairing HPLC methods to determine EDTA and DTPA in small molecule and biological pharmaceutical formulations$

    Institute of Scientific and Technical Information of China (English)

    George Wang; Frank P. Tomasella


    Ion-pairing high-performance liquid chromatography–ultraviolet (HPLC–UV) methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid (EDTA) in Abilifys (a small molecule drug with aripiprazole as the active pharmaceutical ingredient) oral solution and die-thylenetriaminepentaacetic acid (DTPA) in Yervoys (a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient) intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions (Cu2 þ , Fe3 þ ) which generate highly stable metallocom-plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in-volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de-termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids (APCAs) including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.

  17. Preface - From molecules to molecular materials, biological molecular systems and nanostructures: A collection of contributions presented at the XIIIth International Conference on Molecular Spectroscopy (United States)

    Ratajczak, Henryk; Drozd, Marek; Fausto, Rui


    This volume contains a series of selected contributions presented at the XIIIth International Conference on Molecular Spectroscopy (ICMS): "From Molecules to Molecular Materials, Biological Molecular Systems and Nanostructures" held in Wrocław, Poland, 9-12 September 2015, under the auspices of the Mayor of Wrocław and the European Academy of Sciences, Arts and Humanities. Wrocław was chosen not accidentally as venue for the conference. With more than a thousand years of history, Wrocław is the location of one of the oldest universities in Central Europe. Being a place where education and science play major roles in the daily life of its inhabitants, Wrocław is also a privileged center for spectroscopy in Poland.

  18. Characterization of inactive renin from human kidney and plasma. Evidence of a renal source of circulating inactive renin.


    Hsueh, W A; Carlson, E J; Dzau, V J


    An inactive form of renin has been isolated from human plasma. It has been suggested that this may represent renin precursor secreted from the kidney. However, early studies failed to isolate inactive renin from human renal tissue. In this investigation, rapid processing of human kidney cortex at temperatures below 4 degrees C in the presence of protease inhibitors followed by cibacron-blue affinity chromatography allowed us to extract a totally inactive form of renal renin. Furthermore, we f...

  19. Design, synthesis and biological evaluation of novel 1,2,3-triazolyl [Formula: see text]-hydroxy alkyl/carbazole hybrid molecules. (United States)

    Rad, Mohammad Navid Soltani; Behrouz, Somayeh; Behrouz, Marzieh; Sami, Akram; Mardkhoshnood, Mehdi; Zarenezhad, Ali; Zarenezhad, Elham


    The design, synthesis and biological study of several novel 1,2,3-triazolyl [Formula: see text]-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9H-carbazole. The 'Click' Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H-carbazole with diverse [Formula: see text]-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between [Formula: see text]-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a-10n as potential lead antifungal agents for future investigations.

  20. Effects of Physical (Inactivity on Platelet Function

    Directory of Open Access Journals (Sweden)

    Stefan Heber


    Full Text Available As platelet activation is closely related to the liberation of growth factors and inflammatory mediators, platelets play a central role in the development of CVD. Virtually all cardiovascular risk factors favor platelet hyperreactivity and, accordingly, also physical (inactivity affects platelet function. Within this paper, we will summarize and discuss the current knowledge on the impact of acute and habitual exercise on platelet function. Although there are apparent discrepancies regarding the reported effects of acute, strenuous exercise on platelet activation, a deeper analysis of the available literature reveals that the applied exercise intensity and the subjects’ cardiorespiratory fitness represent critical determinants for the observed effects. Consideration of these factors leads to the summary that (i acute, strenuous exercise can lead to platelet activation, (ii regular physical activity and/or physical fitness diminish or prevent platelet activation in response to acute exercise, and (iii habitual physical activity and/or physical fitness also favorably modulate platelet function at physical rest. Notably, these effects of exercise on platelet function show obvious similarities to the well-recognized relation between exercise and the risk for cardiovascular events where vigorous exercise transiently increases the risk for myocardial infarction and a physically active lifestyle dramatically reduces cardiovascular mortality.

  1. FOB-SH: Fragment orbital-based surface hopping for charge carrier transport in organic and biological molecules and materials (United States)

    Spencer, J.; Gajdos, F.; Blumberger, J.


    We introduce a fragment orbital-based fewest switches surface hopping method, FOB-SH, designed to efficiently simulate charge carrier transport in strongly fluctuating condensed phase systems such as organic semiconductors and biomolecules. The charge carrier wavefunction is expanded and the electronic Hamiltonian constructed in a set of singly occupied molecular orbitals of the molecular sites that mediate the charge transfer. Diagonal elements of the electronic Hamiltonian (site energies) are obtained from a force field, whereas the off-diagonal or electronic coupling matrix elements are obtained using our recently developed analytic overlap method. We derive a general expression for the exact forces on the adiabatic ground and excited electronic state surfaces from the nuclear gradients of the charge localized electronic states. Applications to electron hole transfer in a model ethylene dimer and through a chain of ten model ethylenes validate our implementation and demonstrate its computational efficiency. On the larger system, we calculate the qualitative behaviour of charge mobility with change in temperature T for different regimes of the intermolecular electronic coupling. For small couplings, FOB-SH predicts a crossover from a thermally activated regime at low temperatures to a band-like transport regime at higher temperatures. For higher electronic couplings, the thermally activated regime disappears and the mobility decreases according to a power law. This is interpreted by a gradual loss in probability for resonance between the sites as the temperature increases. The polaron hopping model solved for the same system gives a qualitatively different result and underestimates the mobility decay at higher temperatures. Taken together, the FOB-SH methodology introduced here shows promise for a realistic investigation of charge carrier transport in complex organic, aqueous, and biological systems.

  2. Inactive DNMT3B splice variants modulate de novo DNA methylation. (United States)

    Gordon, Catherine A; Hartono, Stella R; Chédin, Frédéric


    Inactive DNA methyltransferase (DNMT) 3B splice isoforms are associated with changes in DNA methylation, yet the mechanisms by which they act remain largely unknown. Using biochemical and cell culture assays, we show here that the inactive DNMT3B3 and DNMT3B4 isoforms bind to and regulate the activity of catalytically competent DNMT3A or DNMT3B molecules. DNMT3B3 modestly stimulated the de novo methylation activity of DNMT3A and also counteracted the stimulatory effects of DNMT3L, therefore leading to subtle and contrasting effects on activity. DNMT3B4, by contrast, significantly inhibited de novo DNA methylation by active DNMT3 molecules, most likely due to its ability to reduce the DNA binding affinity of co-complexes, thereby sequestering them away from their substrate. Immunocytochemistry experiments revealed that in addition to their effects on the intrinsic catalytic function of active DNMT3 enzymes, DNMT3B3 and DNMT34 drive distinct types of chromatin compaction and patterns of histone 3 lysine 9 tri-methylation (H3K9me3) deposition. Our findings suggest that regulation of active DNMT3 members through the formation of co-complexes with inactive DNMT3 variants is a general mechanism by which DNMT3 variants function. This may account for some of the changes in DNA methylation patterns observed during development and disease.

  3. Inactive DNMT3B splice variants modulate de novo DNA methylation.

    Directory of Open Access Journals (Sweden)

    Catherine A Gordon

    Full Text Available Inactive DNA methyltransferase (DNMT 3B splice isoforms are associated with changes in DNA methylation, yet the mechanisms by which they act remain largely unknown. Using biochemical and cell culture assays, we show here that the inactive DNMT3B3 and DNMT3B4 isoforms bind to and regulate the activity of catalytically competent DNMT3A or DNMT3B molecules. DNMT3B3 modestly stimulated the de novo methylation activity of DNMT3A and also counteracted the stimulatory effects of DNMT3L, therefore leading to subtle and contrasting effects on activity. DNMT3B4, by contrast, significantly inhibited de novo DNA methylation by active DNMT3 molecules, most likely due to its ability to reduce the DNA binding affinity of co-complexes, thereby sequestering them away from their substrate. Immunocytochemistry experiments revealed that in addition to their effects on the intrinsic catalytic function of active DNMT3 enzymes, DNMT3B3 and DNMT34 drive distinct types of chromatin compaction and patterns of histone 3 lysine 9 tri-methylation (H3K9me3 deposition. Our findings suggest that regulation of active DNMT3 members through the formation of co-complexes with inactive DNMT3 variants is a general mechanism by which DNMT3 variants function. This may account for some of the changes in DNA methylation patterns observed during development and disease.

  4. Physical inactivity, depression, and risk of cardiovascular mortality

    NARCIS (Netherlands)

    Kamphuis, M.H.; Geerlings, M.I.; Tijhuis, M.A.R.; Giampaoli, S.; Nissinen, A.; Grobbee, D.E.; Kromhout, D.


    Purpose: Studies indicate that depression may increase risk of cardiovascular disease (CVD) in addition to classical risk factors. One of the hypotheses to explain this relation is that depressed subjects become physically inactive. We set out to determine the role of physical inactivity in the rela

  5. How dependent are molecular and atomic properties on the electronic structure method? Comparison of Hartree-Fock, DFT, and MP2 on a biologically relevant set of molecules. (United States)

    Matta, Chérif F


    This article compares molecular properties and atomic properties defined by the quantum theory of atoms in molecules (QTAIM) obtained from three underlying levels of theory: MP2(full), density functional theory (DFT) (B3LYP), and Hartree-Fock (H-F). The same basis set (6-311++G(d,p)) has been used throughout the study. The calculations and comparisons were applied to a set of 30 small molecules representing common fragments of biological molecules. The molecular properties investigated are the energies and the electrostatic moments (up to and including the quadrupoles), and the atomic properties include electron populations (and atomic charge), atomic dipolar and quadrupolar polarizations, atomic volumes, and corrected and raw atomic energies. The Cartesian distance between dipole vectors and the Frobenius distance between the quadrupole tensors calculated at the three levels of theory provide a measure of their correlation (or lack thereof). With the exception of energies (atomic and molecular), it is found that both DFT and H-F are in excellent agreement with MP2, especially with regards to the electrostatic mutipoles up to the quadrupoles, but DFT and MP2 agree better in almost all studied properties (with the exception of molecular geometries). QTAIM properties whether obtained from H-F, DFT(B3LYP), or MP2 calculations when used in the construction of empirical correlations with experiment such as quantitative structure-activity-(or property)-relationships (QSAR/QSPR) are equivalent (because the properties calculated at the three levels are very highly correlated among themselves with r(2) typically >0.95, and therefore preserving trends). These results suggest that the massive volume of results that were published in the older literature at the H-F level is valid especially when used to study trends or in QSAR or QSPR studies, and, as long as our test set of molecules is representative, there is no pressing need to re-evaluate them at other levels of theory

  6. Transport dynamics of molecular motors that switch between an active and inactive state. (United States)

    Pinkoviezky, I; Gov, N S


    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.

  7. Physical inactivity and arterial stiffness in COPD

    Directory of Open Access Journals (Sweden)

    Sievi NA


    Full Text Available Noriane A Sievi,1 Daniel Franzen,1 Malcolm Kohler,1,2 Christian F Clarenbach1 1Division of Pulmonology, University Hospital of Zurich, 2Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland Background: Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors. Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness. Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness. Methods: In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted, arterial stiffness was assessed by augmentation index (AI. Daily physical activity level (PAL was measured by an activity monitor (SenseWear Pro™ >1 week. The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities. Results: Patients suffered from moderate (35%, severe (32%, and very severe (33% COPD, and 22% were active smokers. Median (quartile PAL was 1.4 (1.3/1.5 and mean (standard deviation AI 26% (9.2%. PAL showed a negative association with AI (B=-9.32, P=0.017 independent of age, sex, blood pressure, and airflow limitation. Conclusion: In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk. Clinical Trial Registration:, NCT01527773 Keywords: activity monitor, airflow limitation, COPD, physical activity level

  8. Total cross sections for ionizing processes induced by proton impact on molecules of biological interest: A classical trajectory Monte Carlo approach

    Energy Technology Data Exchange (ETDEWEB)

    Lekadir, H.; Abbas, I.; Champion, C. [Universite Paul Verlaine Metz, Laboratoire de Physique Moleculaire et des Collisions, Institut J. Barriol FR CNRS 2843, 1 Bd Arago, 57078 Metz Cedex3 (France); Hanssen, J. [Universite Paul Verlaine Metz, Laboratoire de Physique Moleculaire et des Collisions, Institut J. Barriol FR CNRS 2843, 1 Bd Arago, 57078 Metz Cedex3 (France)], E-mail:


    In the current work, we present a study of ionizing interactions between protons and molecular targets of biological interest like water vapour and DNA bases. Total cross sections for single and multiple ionizing processes are calculated in the independent electron model and compared to existing theoretical and experimental results for impact energies ranging from 10 keV/amu to 10 MeV/amu. The theoretical approach combines some characteristics of the classical trajectory Monte Carlo method with the classical over-barrier framework. In this 'mixed' approach, all the particles are described in a classical way by assuming that the target electrons are involved in the collision only when their binding energy is greater than the maximum of the potential energy of the system projectile-target. We test our theoretical approach on the water molecule and the obtained results are compared to a large set of data and a reasonable agreement is generally observed specially for impact energies greater than 100 keV, except for the double ionization process for which large discrepancies are reported. Considering the DNA bases, the obtained results are given without any comparison since the literature is till now very poor in terms of cross section measurements.

  9. Chronic Recreational Physical Inactivity and Epithelial Ovarian Cancer Risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J; Risch, Harvey A


    BACKGROUND: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC ri...

  10. Prevalence of physical inactivity in Iran: a systematic review (United States)

    Fakhrzadeh, Hossein; Djalalinia, Shirin; Mirarefin, Mojdeh; Arefirad, Tahereh; Asayesh, Hamid; Safiri, Saeid; Samami, Elham; Mansourian, Morteza; Shamsizadeh, Morteza; Qorbani, Mostafa


    Introduction: Physical inactivity is one of the most important risk factors for chronic diseases, including cardiovascular disease, cancer, and stroke. We aim to conduct a systematic review of the prevalence of physical inactivity in Iran. Methods: We searched international databases; ISI, PubMed/Medline, Scopus, and national databases Irandoc, Barakat knowledge network system, and Scientific Information Database (SID). We collected data for outcome measures of prevalence of physical inactivity by sex, age, province, and year. Quality assessment and data extraction has been conducted independently by two independent research experts. There were no limitations for time and language. Results: We analyzed data for prevalence of physical inactivity in Iranian population. According to our search strategy we found 254 records; of them 185 were from international databases and the remaining 69 were obtained from national databases after refining the data, 34 articles that met eligible criteria remained for data extraction. From them respectively; 9, 20, 2 and 3 studies were at national, provincial, regional and local levels. The estimates for inactivity ranged from approximately 30% to almost 70% and had considerable variation between sexes and studied sub-groups. Conclusion: In Iran, most of studies reported high prevalence of physical inactivity. Our findings reveal a heterogeneity of reported values, often from differences in study design, measurement tools and methods, different target groups and sub-population sampling. These data do not provide the possibility of aggregation of data for a comprehensive inference. PMID:27777692

  11. Plasma miR-182 expression in non-small cell lung cancer and its relationship with tumor CT findings and malignant biological molecule expression

    Institute of Scientific and Technical Information of China (English)

    Xue-Ping Zeng; Li Lu; Ting Huang; Qi-Cong Zhu


    Objective:To study the plasma miR-182 expression in non-small cell lung cancer and its relationship with tumor CT findings and malignant biological molecule expression.Methods:A total of 60 patients who were diagnosed with non-small cell lung cancer in our hospital from May 2012 to October 2015 were included in NSCLC group of the study, and 80 cases of healthy volunteers who received physical examination in our hospital during the same period and whose general data matched with that of NSCLC patients were included in control group of the study. Contrast-enhanced CT was conducted and the major diameter and minor diameter of lesions were measured, plasma was collected to determine miR-182 expression as well as CEA, CYFRA21-1, SCC-Ag and TSGF levels, and tumor tissue was collected to determine the content of RECK, MTSS1, PDCD4 and DNMT3a.Results: Relative plasma miR-182 expression of NSCLC group was significantly higher than that of control group; axial maximum major diameter, maximum minor diameter perpendicular to it and coronary maximum vertical major diameter in non-small cell lung cancer patients with high plasma miR-182 expression were significantly higher than those in non-small cell lung cancer patients with low plasma miR-182 expression, plasma CEA, CYFRA21-1, SCC-Ag and TSGF levels were significantly higher than those in non-small cell lung cancer patients with low plasma miR-182 expression, RECK, MTSS1, PDCD4 and DNMT3a levels in tumor tissue were significantly lower than those in non-small cell lung cancer patients with low plasma miR-182 expression, and differences in above indexes between two groups were statistically significant (P<0.05).Conclusions: Plasma miR-182 expression is abnormally high in non-small cell lung cancer and is closely related to the CT findings of tumor, the content of serum tumor markers and the expression of malignant molecules in tumor tissue.

  12. Prevalence and factors associated with physical inactivity among Malaysian adults. (United States)

    Ying, Chanying; Kuay, Lim Kuang; Huey, Teh Chien; Hock, Lim Kuang; Hamid, Hamizatul Akmal Abd; Omar, Mohd Azahadi; Ahmad, Noor Ani; Cheong, Kee Chee


    Using data from the Third National Health and Morbidity Survey (NHMS III) in 2006, this study examined the association between socio-demographic factors and physical inactivity in a sample of 33,949 adults aged 18 years and above by gender. Physical activity levels were measured using the Global Physical Activity Questionnaire (GPAQ vers 1). Physical inactivity was defined as having a total physical activity level of less than 600 metabolic equivalents-minutes per week (METs-minutes/week) contributed by all three different life domains.Logistic regression analyses were conducted.The prevalence of overall physical inactivity was 43.7% (95% CI: 42.9-44.5). The mean total physical activity level was 894.2 METs-minutes/ week. The means METs-minutes/week for the domain of work, travelling, and leisure time were 518.4, 288.1, and 134.8, respectively. Multivariable logistic regression analyses indicated that females were more likely to be physically inactive than males were (aOR=1.62; 95% CI: 1.53-1.72). Among women, being a housewife (aOR = 1.78; 95% CI: 1.56-2.03), widow/divorcee (aOR = 1.23; 95% CI: 1.05-1.43), and those with no formal education (aOR = 1.20; 95% CI: 1.01-1.43) were found to be significantly associated with physical inactivity.Urban residents, older adults aged 65 years and above, private employees, nonworking group, and those with a monthly household income level of MYR5,000 and above appeared to be consistently associated with physical inactivity across men, women, and combined group (both). Specific health intervention strategies to promote physical activity should be targeted on population subgroups who are inactive.

  13. Redox potential tuning by redox-inactive cations in nature's water oxidizing catalyst and synthetic analogues. (United States)

    Krewald, Vera; Neese, Frank; Pantazis, Dimitrios A


    The redox potential of synthetic oligonuclear transition metal complexes has been shown to correlate with the Lewis acidity of a redox-inactive cation connected to the redox-active transition metals of the cluster via oxo or hydroxo bridges. Such heterometallic clusters are important cofactors in many metalloenzymes, where it is speculated that the redox-inactive constituent ion of the cluster serves to optimize its redox potential for electron transfer or catalysis. A principal example is the oxygen-evolving complex in photosystem II of natural photosynthesis, a Mn4CaO5 cofactor that oxidizes water into dioxygen, protons and electrons. Calcium is critical for catalytic function, but its precise role is not yet established. In analogy to synthetic complexes it has been suggested that Ca(2+) fine-tunes the redox potential of the manganese cluster. Here we evaluate this hypothesis by computing the relative redox potentials of substituted derivatives of the oxygen-evolving complex with the cations Sr(2+), Gd(3+), Cd(2+), Zn(2+), Mg(2+), Sc(3+), Na(+) and Y(3+) for two sequential transitions of its catalytic cycle. The theoretical approach is validated with a series of experimentally well-characterized Mn3AO4 cubane complexes that are structural mimics of the enzymatic cluster. Our results reproduce perfectly the experimentally observed correlation between the redox potential and the Lewis acidities of redox-inactive cations for the synthetic complexes. However, it is conclusively demonstrated that this correlation does not hold for the oxygen evolving complex. In the enzyme the redox potential of the cluster only responds to the charge of the redox-inactive cations and remains otherwise insensitive to their precise identity, precluding redox-tuning of the metal cluster as a primary role for Ca(2+) in biological water oxidation.

  14. (pro)renin receptor: A stable molecule


    Wiwanitkit, Viroj


    Background: Basically, (pro)renin acts via a specific receptor, (pro)renin receptor (PRR) binding between renin and prorenin, its inactive proenzyme form. The study on the molecular level of PRR can give useful knowledge to help understand many renal disorders. Method: Here, the author focuses on the stability of the PRR molecule. The mutation prone positions within the PRR molecule was assessed using standard reference technique. Result: The study showed there is no identified mutation prone...

  15. Isolation of Specific Genomic Regions and Identification of Their Associated Molecules by Engineered DNA-Binding Molecule-Mediated Chromatin Immunoprecipitation (enChIP) Using the CRISPR System and TAL Proteins. (United States)

    Fujii, Hodaka; Fujita, Toshitsugu


    Comprehensive understanding of genome functions requires identification of molecules (proteins, RNAs, genomic regions, etc.) bound to specific genomic regions of interest in vivo. To perform biochemical and molecular biological analysis of specific genomic regions, we developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) to purify genomic regions of interest. In enChIP, specific genomic regions are tagged for biochemical purification using engineered DNA-binding molecules, such as transcription activator-like (TAL) proteins and a catalytically inactive form of the clustered regularly interspaced short palindromic repeats (CRISPR) system. enChIP is a comprehensive approach that emphasizes non-biased search using next-generation sequencing (NGS), microarrays, mass spectrometry (MS), and other methods. Moreover, this approach is not restricted to cultured cell lines and can be easily extended to organisms. In this review, we discuss applications of enChIP to elucidating the molecular mechanisms underlying genome functions.

  16. Assessing compliance: Active versus inactive trainees in a memory intervention

    Directory of Open Access Journals (Sweden)

    Dana K Bagwell


    Full Text Available Dana K Bagwell, Robin L WestDepartment of Psychology, University of Florida, Gainesville, FL, USAAbstract: Extensive research on memory interventions has confirmed their success with older adults, but the individual difference factors that predict successful training outcomes remain relatively unexplored. In the current intervention, trainees were identified as active (compliant with training regimens or inactive using trainer ratings based on attendance, homework completion, and class participation. The active group showed significantly greater training-related gains than the inactive group and the control group on most measures. Compliance was predicted by health, education, and self-efficacy. Specifically, active trainees were more likely to have advanced degrees and somewhat higher self-efficacy, and to have higher vitality and fewer functional limitations than the inactive trainees. This research may assist future investigators to target interventions to those who will show the most benefit.Keywords: compliance, memory training, aging, intervention

  17. The economic benefits of reducing physical inactivity: an Australian example

    Directory of Open Access Journals (Sweden)

    Cumming Toby B


    Full Text Available Abstract Background Physical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as 'opportunity cost savings', which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities. Methods Simulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%. Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions. Results A 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000, days of home-based production (180,000 while conferring a AUD96 million reduction in health sector costs

  18. Single molecules and nanotechnology

    CERN Document Server

    Vogel, Horst


    This book focuses on recent advances in the rapidly evolving field of single molecule research. These advances are of importance for the investigation of biopolymers and cellular biochemical reactions, and are essential to the development of quantitative biology. Written by leading experts in the field, the articles cover a broad range of topics, including: quantum photonics of organic dyes and inorganic nanoparticles their use in detecting properties of single molecules the monitoring of single molecule (enzymatic) reactions single protein (un)folding in nanometer-sized confined volumes the dynamics of molecular interactions in biological cells The book is written for advanced students and scientists who wish to survey the concepts, techniques and results of single molecule research and assess them for their own scientific activities.

  19. Inaction inertia, regret, and valuation : A closer look

    NARCIS (Netherlands)

    Zeelenberg, Marcel; Nijstad, Bernard A.; van Putten, Marijke; van Dijk, Eric


    Inaction inertia is the phenomenon that one is not likely to act on an attractive opportunity after having bypassed an even more attractive opportunity. So far, all published work has assumed a causal role for the emotion regret in this effect. In a series of 5 experiments we found no support for th

  20. Home Delivery Medicament Program: access, inactivity and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Roque da Silva Araújo

    Full Text Available ABSTRACT Objective: to verify causes of inactivity in the Home Delivery Medicament Program, as referred by users from a Primary Health Care Service in São Paulo, comparing them to the causes registered in the program and analyzing them in the theoretical model Concept of Access to Health. Methods: cross-sectional study, interviewing 111 inactive users; and documentary study in the program records. Results: half of the users did not know the condition of inactivity. Discrepancies were found between the user's and the program's information, observing different levels of agreement: Absence of physician and administrative staff member 0%; Transfer to other service 25%; Death 50%; Option to quit 50%; Address change 57% and Change in therapeutic schedule 80%. The users' feeling of accepting the program was observed. In the health access concept, inactivity can be explained in the information dimension, in the degree of asymmetry between the patient's and the health professional's knowledge, identified through the indicators: education, knowledge and information sources. Conclusions: due to the low education level, the user does not assimilate the information on the steps of the program flowchart, does not return for the assessment that guarantees its continuity. Consequently, (she stops receiving the medication and spends a long time without treatment, increasing the cardiovascular risk of hypertensive (92% of the sample, diabetic (44% and dyslipidemic patients (31%.

  1. Automatic Detection of Inactive Solar Cell Cracks in Electroluminescence Images

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso


    We propose an algorithm for automatic determination of the electroluminescence (EL) signal threshold level corresponding to inactive solar cell cracks, resulting from their disconnection from the electrical circuit of the cell. The method enables automatic quantification of the cell crack size...

  2. Physical inactivity and muscle oxidative capacity in humans

    DEFF Research Database (Denmark)

    Gram, Martin; Dahl, Rannvá; Dela, Flemming


    of proteins related to oxidative phosphorylation. With such a substantial down-regulation, it is likely that a range of adenosine triphosphate (ATP)-dependent pathways such as calcium signalling, respiratory capacity and apoptosis are affected by physical inactivity. However, this has not been investigated...

  3. Muscle activity and inactivity periods during normal daily life. (United States)

    Tikkanen, Olli; Haakana, Piia; Pesola, Arto J; Häkkinen, Keijo; Rantalainen, Timo; Havu, Marko; Pullinen, Teemu; Finni, Taija


    Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg) were measured during normal daily life using shorts measuring muscle electromyographic (EMG) activity (recording time 11.3±2.0 hours). EMG was normalized to isometric MVC (EMG(MVC)) during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC)). During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC) (mean duration of 1.4±1.4 s) which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC)). Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min). Women had more activity bursts and spent more time at intensities above 40% EMG(MVC) than men (p<0.05). In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

  4. Muscle activity and inactivity periods during normal daily life.

    Directory of Open Access Journals (Sweden)

    Olli Tikkanen

    Full Text Available Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg were measured during normal daily life using shorts measuring muscle electromyographic (EMG activity (recording time 11.3±2.0 hours. EMG was normalized to isometric MVC (EMG(MVC during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC. During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC (mean duration of 1.4±1.4 s which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC. Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min. Women had more activity bursts and spent more time at intensities above 40% EMG(MVC than men (p<0.05. In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

  5. Molecule nanoweaver (United States)

    Gerald, II; Rex E.; Klingler, Robert J.; Rathke, Jerome W.; Diaz, Rocio; Vukovic, Lela


    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  6. Revegetation/rock cover for stabilization of inactive uranium mill tailings disposal sites

    Energy Technology Data Exchange (ETDEWEB)

    Beedlow, P.A.; McShane, M.C.; Cadwell, L.L.


    Pacific Northwest Laboratory is developing design and performance guidelines for surface stabilization of inactive uranium mill tailings. In this work, vegetation and rock covers are being evaluated for maintaining long-term integrity of impoundment systems. Methods are being developed to estimate erosion rates associated with rock and/or vegetation covers, and to determine the effects of surface treatments on soil moisture. Interactions between surface treatments and barriers (radon and biological) are being studied as well. The product will be a set of guidelines to aid in designing surface covers. This report presents the status of this program and a discussion of considerations pertinent to the application of surface covers to tailings. Test plots located in Grand Junction, Colorado and Waterflow, New Mexico are being used to study: (1) the interactions between vegetation and radon and biological barriers, (2) the effects of surface covers on soil moisture, and (3) the effects of rock covers on vegetation.

  7. Different design of enzyme-triggered CO-releasing molecules (ET-CORMs reveals quantitative differences in biological activities in terms of toxicity and inflammation

    Directory of Open Access Journals (Sweden)

    E. Stamellou


    This study further provides a rational framework for designing acyloxydiene–Fe(CO3 complexes as ET-CORMs with differential CO release and biological activities. We also provide a better understanding of how these complexes affect cell-biology in mechanistic terms.

  8. Multimotor transport in a system of active and inactive kinesin-1 motors. (United States)

    Scharrel, Lara; Ma, Rui; Schneider, René; Jülicher, Frank; Diez, Stefan


    Long-range directional transport in cells is facilitated by microtubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multimotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multimotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.

  9. Do Running and Strength Exercises Reduce Daily Muscle Inactivity Time?

    Directory of Open Access Journals (Sweden)

    Taija Finni


    Full Text Available Understanding how a specific exercise changes daily activity patterns is important when designing physical activity interventions. We examined the effects of strength and interval running exercise sessions on daily activity patterns using recordings of quadriceps and hamstring muscle electromyographic (EMG activity and inactivity. Five male and five female subjects taking part in a 10-week training programme containing both strength and interval running training sessions were measured for daily muscle EMG activities during three days: on a strength day, an interval running day, and a day without exercise. EMG was measured using textile electrodes embedded into sport shorts that were worn 9.1 ± 1.4 hours/day and results are given as % of recording time. During the total measurement time the muscles were inactive 55 ± 26%, 53 ± 30% and 71 ± 12% during strength training day, interval running day, and day without exercise (n.s.. When compared to the day without exercise, the change in muscle inactivity correlated negatively with change in light muscle activity in strength (r = -0.971,p< 0.001 and interval running days (r = -0.965,p< 0.001. While interval running exercise bout induced a more systematic decrease in muscle inactivity time (from 62 ± 15% to 6 ± 6%,p< 0.001, reductions in muscle inactivity in response to strength exercise were highly individual (range 5–70 pp despite the same training programme. Strength, but not running exercise bout, increased muscle activity levels occurring above 50% MVC (p< 0.05 when compared to a similar period without exercise. The effect of strength exercise bout on totaldaily recording time increased the EMG amplitudes across the entire intensity spectrum. While strength and interval running exercise are effective in increasing muscle moderate-to-vigorous activity when compared to a similar period without exercise, it comprises only a small part of the day and does not seem to have a systematic effect

  10. Synthesis beyond the molecule

    NARCIS (Netherlands)

    Reinhoudt, D.N.; Crego-Calama, M.


    Weak, noncovalent interactions between molecules control many biological functions. In chemistry, noncovalent interactions are now exploited for the synthesis in solution of large supramolecular aggregates. The aim of these syntheses is not only the creation of a particular structure, but also the i

  11. 基于原子力显微镜的单分子力谱在生物研究中的应用%Application of Atomic Force Microscopy Based Single Molecule Force Spectroscopy in Biological Research

    Institute of Scientific and Technical Information of China (English)

    黎虹颖; 古宁宇; 唐纪琳


    Atomic force microscopy(AFM) is widely used in biological research,AFM based single molecule force spectroscopy can be applied to study the intramolecular and intermolecular interactions of biomolecules at the single-molecule and single-cell levels.In this paper,we present the latest progress of AFM based single molecule force spectroscopy in biomolecular interaction,protein unfolding,cell surface biomolecules,cell mechanical properties and single molecule force spectroscopy imaging.%原子力显微镜被广泛应用于生物研究领域,基于原子力显微镜的单分子力谱可以在单分子、单细胞水平上研究生物分子内和分子间的相互作用.本文介绍了原子力显微镜单分子力谱在生物分子间相互作用、蛋白质去折叠、细胞表面生物分子、细胞力学性质和基于单分子力谱成像等研究中的最新进展.

  12. ERICA: leisure-time physical inactivity in Brazilian adolescents (United States)

    Cureau, Felipe Vogt; da Silva, Thiago Luiz Nogueira; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; de Carvalho, Kênia Mara Baiocchi; de Leon, Elisa Brosina; de Vasconcellos, Mauricio Teixeira Leite; Ekelund, Ulf; Schaan, Beatriz D


    ABSTRACT OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (< 300; 0 min). The prevalences were estimated for the total sample and by sex. Poisson regression models were used to assess associated factors. RESULTS The prevalence of leisure-time physical inactivity was 54.3% (95%CI 53.4-55.2), and higher for the female sex (70.7%, 95%CI 69.5-71.9) compared to the male (38.0%, 95%CI 36.7-39.4). More than a quarter of adolescents (26.5%, 95%CI 25.8-27.3) reported not practicing physical activity in the leisure time, a condition more prevalent for girls (39.8%, 95%CI 38.8-40.9) than boys (13.4%, 95%CI 12.4-14.4). For girls, the variables that were associated with physical inactivity were: reside in the Northeast (RP = 1.13, 95%CI 1.08-1.19), Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p < 0.001) and declaring to be indigenous (RP = 0.37, 95%CI 0.19-0.73) were also associated with not practicing physical activities in the leisure time. CONCLUSIONS The prevalence of leisure-time physical inactivity in Brazilian adolescents is high. It presents regional variations and is associated with age and low

  13. Synthesis and in Vivo Biological Evaluation of (68)Ga-Labeled Carbonic Anhydrase IX Targeting Small Molecules for Positron Emission Tomography. (United States)

    Sneddon, Deborah; Niemans, Raymon; Bauwens, Matthias; Yaromina, Ala; van Kuijk, Simon J A; Lieuwes, Natasja G; Biemans, Rianne; Pooters, Ivo; Pellegrini, Paul A; Lengkeek, Nigel A; Greguric, Ivan; Tonissen, Kathryn F; Supuran, Claudiu T; Lambin, Philippe; Dubois, Ludwig; Poulsen, Sally-Ann


    Tumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [(68)Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing (68)Ga for preclinical CA IX imaging are scarce, and this is one of the first effective (68)Ga compounds reported for PET imaging of CA IX.

  14. Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method.

    Directory of Open Access Journals (Sweden)

    Chao-Yie Yang

    Full Text Available The interleukin-1 receptor (IL-1R is the founding member of the interleukin 1 receptor family which activates innate immune response by its binding to cytokines. Reports showed dysregulation of cytokine production leads to aberrant immune cells activation which contributes to auto-inflammatory disorders and diseases. Current therapeutic strategies focus on utilizing antibodies or chimeric cytokine biologics. The large protein-protein interaction interface between cytokine receptor and cytokine poses a challenge in identifying binding sites for small molecule inhibitor development. Based on the significant conformational change of IL-1R type 1 (IL-1R1 ectodomain upon binding to different ligands observed in crystal structures, we hypothesized that transient small molecule binding sites may exist when IL-1R1 undergoes conformational transition and thus suitable for inhibitor development. Here, we employed accelerated molecular dynamics (MD simulation to efficiently sample conformational space of IL-1R1 ectodomain. Representative IL-1R1 ectodomain conformations determined from the hierarchy cluster analysis were analyzed by the SiteMap program which leads to identify small molecule binding sites at the protein-protein interaction interface and allosteric modulator locations. The cosolvent mapping analysis using phenol as the probe molecule further confirms the allosteric modulator site as a binding hotspot. Eight highest ranked fragment molecules identified from in silico screening at the modulator site were evaluated by MD simulations. Four of them restricted the IL-1R1 dynamical motion to inactive conformational space. The strategy from this study, subject to in vitro experimental validation, can be useful to identify small molecule compounds targeting the allosteric modulator sites of IL-1R and prevent IL-1R from binding to cytokine by trapping IL-1R in inactive conformations.

  15. System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells

    Directory of Open Access Journals (Sweden)

    Malina Halina Z


    Full Text Available Abstract Background The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Results Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]. Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. Conclusions The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites. The formation of these polymers (aggregates leads to an unregulated and, consequently, pathological protein network. The results

  16. Enumerating molecules.

    Energy Technology Data Exchange (ETDEWEB)

    Visco, Donald Patrick, Jr. (, . Tennessee Technological University, Cookeville, TN); Faulon, Jean-Loup Michel; Roe, Diana C.


    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  17. A Selective Assay to Detect Chitin and Biologically Active Nano-Machineries for Chitin-Biosynthesis with Their Intrinsic Chitin-Synthase Molecules

    Directory of Open Access Journals (Sweden)

    Hildgund Schrempf


    Full Text Available A new assay system for chitin has been developed. It comprises the chitin-binding protein ChbB in fusion with a His-tag as well as with a Strep-tag, the latter of which was chemically coupled to horseradish peroxidase. With the resulting complex, minimal quantities of chitin are photometrically detectable. In addition, the assay allows rapid scoring of the activity of chitin-synthases. As a result, a refined procedure for the rapid purification of yeast chitosomes (nano-machineries for chitin biosynthesis has been established. Immuno-electronmicroscopical studies of purified chitosomes, gained from a yeast strain carrying a chitin-synthase gene fused to that for GFP (green-fluorescence protein, has led to the in situ localization of chitin-synthase-GFP molecules within chitosomes.

  18. Feasibility study of home telerehabilitation for physically inactive veterans

    Directory of Open Access Journals (Sweden)

    Nancy D. Harada, PhD


    Full Text Available The aim of this study was to develop a system for and determine the feasibility of monitoring home exercise for physically inactive older adults using a Health Buddy (HB text messaging device (Robert Bosch Healthcare; Palo Alto, California. Questions and messages related to exercise adherence are displayed on the HB screen and participants choose a response by pressing the corresponding button on the device. Responses are transmitted through a landline connection and high-risk responses are highlighted by the system for follow-up. We developed the questions and messages based on input from patient and clinician focus groups. We evaluated feasibility by administering the intervention to inpatient and outpatient adults aged 60 or older. We gave participants a choice of exercise monitoring by HB (n = 20 or telephone (n = 18. The results showed that home exercise monitoring by HB and telephone is safe, as evidenced by low adverse event rates. We saw a decline in exercise adherence rates to both the HB and telephone after 8 weeks, although adherence was better for HB than telephone. Taken together, the results demonstrate the feasibility of using text messaging to monitor home exercise adherence in physically inactive older adults.

  19. Kepler Flares I. Active and Inactive M dwarfs

    CERN Document Server

    Hawley, Suzanne L; Kowalski, Adam F; Wisniewski, John P; Hebb, Leslie; Deitrick, Russell; Hilton, Eric J


    We analyzed Kepler short-cadence M dwarf observations. Spectra from the ARC 3.5m telescope identify magnetically active (H$\\alpha$ in emission) stars. The active stars are of mid-M spectral type, have numerous flares, and well-defined rotational modulation due to starspots. The inactive stars are of early-M type, exhibit less starspot signature, and have fewer flares. A Kepler to U-band energy scaling allows comparison of the Kepler flare frequency distributions with previous ground-based data. M dwarfs span a large range of flare frequency and energy, blurring the distinction between active and inactive stars designated solely by the presence of H$\\alpha$. We analyzed classical and complex (multiple peak) flares on GJ 1243, finding strong correlations between flare energy, amplitude, duration and decay time, with only a weak dependence on rise time. Complex flares last longer and have higher energy at the same amplitude, and higher energy flares are more likely to be complex. A power law fits the energy dist...

  20. Inactivity amplifies the catabolic response of skeletal muscle to cortisol (United States)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.


    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  1. Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer. (United States)

    Choe, Cholho; Yang, Ling; Lv, Zhanao; Mo, Wanling; Chen, Zhuqi; Li, Guangxin; Yin, Guochuan


    Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate.

  2. Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

    Energy Technology Data Exchange (ETDEWEB)

    J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari


    The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

  3. Social background, bullying, and physical inactivity: National study of 11- to 15-year-olds. (United States)

    Henriksen, P W; Rayce, S B; Melkevik, O; Due, P; Holstein, B E


    More children from lower social backgrounds are physically inactive than those from higher ones. We studied whether bullying was a mediating factor between lower social background and physical inactivity. We also examined the combined effect of low social class and exposure to bullying on physical inactivity. The Danish sample of the Health Behaviour in School-aged Children (HBSC) study 2006 included 6269 schoolchildren in three age groups: 11-, 13-, and 15-year-olds from a random sample of 80 schools. The students answered the internationally standardized HBSC questionnaire. The applied definition leaves 4.0% in the category physically inactive. The sex and age-adjusted OR (95% CI) for physical inactivity was 2.10 (1.39-3.18) among students with low social class and unclassifiable 3.53 (2.26-5.53). Exposure to bullying was associated with physical inactivity, sex and age-adjusted OR = 2.39 (1.67-3.41). Exposure to bullying did not explain the association between social class and physical inactivity. The association between social class and physical inactivity was more pronounced among participants also exposed to bullying. In conclusion, there was a significantly increased odds ratio for physical inactivity among students from lower social classes and for students exposed to bullying. There was a combined effect of low social class and bullying on physical inactivity.

  4. Small Molecules Target Carcinogenic Proteins (United States)

    Gradinaru, Claudiu


    An ingenious cellular mechanism of effecting protein localization is prenylation: the covalent attachment of a hydrophobic prenyl group to a protein that facilitates protein association with cell membranes. Fluorescence microscopy was used to investigate whether the oncogenic Stat3 protein can undergo artificial prenylation via high-affinity prenylated small-molecule binding agents and thus be rendered inactive by localization at the plasma membrane instead of nucleus. The measurements were performed on a home-built instrument capable of recording simultaneously several optical parameters (lifetime, polarization, color, etc) and with single-molecule sensitivity. A pH-invariant fluorescein derivative with double moiety was designed to bridge a prenyl group and a small peptide that binds Stat3 with high affinity. Confocal fluorescence images show effective localization of the ligand to the membrane of liposomes. Stat3 predominantly localizes at the membrane only in the presence of the prenylated ligand. Single-molecule FRET (fluorescence resonance energy transfer) between donor-labeled prenylated agents and acceptor-labeled, surface tethered Stat3 protein is used to determine the dynamic heterogeneity of the protein-ligand interaction and follow individual binding-unbinding events in real time. The data indicates that molecules can effect protein localization, validating a therapeutic design that influences protein activity via induced localization.

  5. Modeling the Relationship Between Social Network Activity, Inactivity, and Growth

    CERN Document Server

    Ribeiro, Bruno


    Online Social Networks (OSNs) are multi-billion dollar enterprises. Surprisingly, little is known about the mechanisms that drive them to growth, stability, or death. This study sheds light on these mechanisms. We are particularly interested in OSNs where current subscribers can invite new users to join the network (e.g., Facebook, LinkedIn). Measuring the relationship between subscriber activity and network growth of a large OSN over five years, we formulate three hypotheses that together describe the observed OSN subscriber behavior. We then provide a model (and extensions) that simultaneously satisfies all three hypotheses. Our model provides deep insights into the dynamics of subscriber activity, inactivity, and network growth rates, even predicting four types of OSNs with respect to subscriber activity evolution. Finally, we present activity data of nearly thirty OSN websites, measured over five years, and show that the observed activity is well described by one of the four activity time series predicted...

  6. TALE proteins bind to both active and inactive chromatin. (United States)

    Scott, James N F; Kupinski, Adam P; Kirkham, Christopher M; Tuma, Roman; Boyes, Joan


    TALE (transcription activator-like effector) proteins can be tailored to bind to any DNA sequence of choice and thus are of immense utility for genome editing and the specific delivery of transcription activators. However, to perform these functions, they need to occupy their sites in chromatin. In the present study, we have systematically assessed TALE binding to chromatin substrates and find that in vitro TALEs bind to their target site on nucleosomes at the more accessible entry/exit sites, but not at the nucleosome dyad. We show further that in vivo TALEs bind to transcriptionally repressed chromatin and that transcription increases binding by only 2-fold. These data therefore imply that TALEs are likely to bind to their target in vivo even at inactive loci.

  7. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule

    Directory of Open Access Journals (Sweden)

    Gurunathan S


    Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Eun Su Kim, Jung Hyun Park, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea Objective: Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells.Methods: The successful reduction of graphene oxide (GO to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO. Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells.Results: The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3.Conclusion: Our data demonstrate a single, simple green

  8. Spacer conformation in biologically active molecules. Part 2. Structure and conformation of 4-[2-(diphenylmethylamino)ethyl]-1-(2-methoxyphenyl) piperazine and its diphenylmethoxy analog—potential 5-HT 1A receptor ligands (United States)

    Karolak-Wojciechowska, J.; Fruziński, A.; Czylkowski, R.; Paluchowska, M. H.; Mokrosz, M. J.


    As a part of studies on biologically active molecule structures with aliphatic linking chain, the structures of 4-[2-diphenylmethylamino)ethyl]-1-(2-methoxyphenyl)piperazine dihydrochloride ( 1) and 4-[2-diphenylmethoxy)ethyl]-1-(2-methoxyphenyl)piperazine fumarate ( 2) have been reported. In both compounds, four atomic non-all-carbons linking chains (N)C-C-X-C are present. The conformation of that linking spacer depends on the nature of the X-atom. The preferred conformation for chain with XNH has been found to be fully extended while for that with XO—the bend one. It was confirmed by conformational calculations (strain energy distribution and random search) and crystallographic data, including statistics from CCDC.

  9. Energy dependence of effective atomic numbers for photon energy absorption and photon interaction: Studies of some biological molecules in the energy range 1 keV-20 MeV

    DEFF Research Database (Denmark)

    Manohara, S.R.; Hanagodimath, S.M.; Gerward, Leif


    Effective atomic numbers for photon energy absorption, Z(PEA,eff), and for photon interaction, Z(PI,eff), have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for biological molecules, such as fatty acids (lauric, myristic, palmitic, stearic, oleic, linoleic...... dependence of the mass attenuation coefficient, Z(PEA, eff), and the mass energy-absorption coefficient, Z(PI, eff), is shown graphically and in tabular form. Significant differences of 17%-38% between Z(PI, eff) and Z(PEA, eff) occur in the energy region 5-100 keV. The reasons for these differences...

  10. Feasibility study for the rapid screening of target molecules using translational diffusion coefficients: diffusion-ordered NMR spectroscopy of biological toxins. (United States)

    Henderson, Terry J


    A panel of 15 biological toxins ranging between approximately 60-28,000 g/mol was used to evaluate the feasibility of screening aqueous samples for toxin analytes based on their translational diffusion coefficients, D(t). Toxin D(t) values were measured by pulsed-field gradient (1)H NMR spectroscopy using a bipolar pulse pair, longitudinal eddy current delay pulse sequence incorporating water suppression to achieve the maximum dynamic range for toxin signals. To collect data for an effective screening protocol, reference D(t) values were determined from five independent measurements at both 25 and 37 degrees C for all toxins in the panel. In the protocol, D(t) values are measured at both temperatures for a suspected toxin target in a sample, and for assignment as a potential toxin analyte, the measurements are required to fall within +/-0.25 x 10(-6) cm(2)/s of both reference D(t) values for at least one toxin in the panel. Only solution viscosity was found to influence sample D(t) measurements appreciably; however, the measurements are easily corrected for viscosity effects by calculating the D(t) value of the suspected toxin at infinite dilution. In conclusion, the protocol provides a rapid and effective means for screening aqueous samples for all toxins in the panel, narrowing toxin identification to < or = 2 possibilities in virtually all cases.

  11. Photo fragmentation dynamics of small argon clusters and biological molecular: new tools by trapping and vectorial correlation; Dynamique de photofragmentation de petits agregats d'argon et de molecules biologiques: nouvel outil par piegeage et correlation vectorielle

    Energy Technology Data Exchange (ETDEWEB)

    Lepere, V


    The present work concerns the building up of a complex set-up whose aim being the investigation of the photo fragmentation of ionised clusters and biological molecules. This new tool is based on the association of several techniques. Two ion sources are available: clusters produced in a supersonic beam are ionised by 70 eV electrons while ions of biological interest are produced in an 'electro-spray'. Ro-vibrational cooling is achieved in a 'Zajfman' electrostatic ion trap. The lifetime of ions can also be measured using the trap. Two types of lasers are used to excite the ionised species: the femtosecond laser available at the ELYSE facilities and a nanosecond laser. Both lasers have a repetition rate of 1 kHz. The neutral and ionised fragments are detected in coincidence using a sophisticated detection system allowing time and localisation of the various fragments to be determined. With such a tool, I was able to investigate in details the fragmentation dynamics of ionised clusters and bio-molecules. The first experiments deal with the measurement of the lifetime of the Ar{sup 2+} dimer II(1/2)u metastable state. The relative population of this state was also determined. The Ar{sup 2+} and Ar{sup 3+} photo-fragmentation was then studied and electronic transitions responsible for their dissociation identified. The detailed analysis of our data allowed to distinguish the various fragmentation mechanisms. Finally, a preliminary investigation of the protonated tryptamine fragmentation is presented. (author)

  12. Effect of physical inactivity on major non-communicable diseases worldwide

    DEFF Research Database (Denmark)

    Lee, I-Min; Shiroma, Eric J; Lobelo, Felipe;


    Strong evidence shows that physical inactivity increases the risk of many adverse health conditions, including major non-communicable diseases such as coronary heart disease, type 2 diabetes, and breast and colon cancers, and shortens life expectancy. Because much of the world's population...... is inactive, this link presents a major public health issue. We aimed to quantify the eff ect of physical inactivity on these major non-communicable diseases by estimating how much disease could be averted if inactive people were to become active and to estimate gain in life expectancy at the population level....

  13. Structural organization of the inactive X chromosome in the mouse. (United States)

    Giorgetti, Luca; Lajoie, Bryan R; Carter, Ava C; Attia, Mikael; Zhan, Ye; Xu, Jin; Chen, Chong Jian; Kaplan, Noam; Chang, Howard Y; Heard, Edith; Dekker, Job


    X-chromosome inactivation (XCI) involves major reorganization of the X chromosome as it becomes silent and heterochromatic. During female mammalian development, XCI is triggered by upregulation of the non-coding Xist RNA from one of the two X chromosomes. Xist coats the chromosome in cis and induces silencing of almost all genes via its A-repeat region, although some genes (constitutive escapees) avoid silencing in most cell types, and others (facultative escapees) escape XCI only in specific contexts. A role for Xist in organizing the inactive X (Xi) chromosome has been proposed. Recent chromosome conformation capture approaches have revealed global loss of local structure on the Xi chromosome and formation of large mega-domains, separated by a region containing the DXZ4 macrosatellite. However, the molecular architecture of the Xi chromosome, in both the silent and expressed regions,remains unclear. Here we investigate the structure, chromatin accessibility and expression status of the mouse Xi chromosome in highly polymorphic clonal neural progenitors (NPCs) and embryonic stem cells. We demonstrate a crucial role for Xist and the DXZ4-containing boundary in shaping Xi chromosome structure using allele-specific genome-wide chromosome conformation capture (Hi-C) analysis, an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) and RNA sequencing. Deletion of the boundary disrupts mega-domain formation, and induction of Xist RNA initiates formation of the boundary and the loss of DNA accessibility. We also show that in NPCs, the Xi chromosome lacks active/inactive compartments and topologically associating domains (TADs), except around genes that escape XCI. Escapee gene clusters display TAD-like structures and retain DNA accessibility at promoter-proximal and CTCF-binding sites. Furthermore, altered patterns of facultative escape genes indifferent neural progenitor clones are associated with the presence of different TAD

  14. Computational Systems Chemical Biology


    Oprea, Tudor I.; Elebeoba E. May; Leitão, Andrei; Tropsha, Alexander


    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  15. Catalytic inactive heme oxygenase-1 protein regulates its own expression in oxidative stress. (United States)

    Lin, Qing S; Weis, Sebastian; Yang, Guang; Zhuang, Tiangang; Abate, Aida; Dennery, Phyllis A


    Heme oxygenase-1 (HO-1) catalyzes the degradation of heme and forms antioxidant bile pigments as well as the signaling molecule carbon monoxide. HO-1 is inducible in response to a variety of chemical and physical stress conditions to function as a cytoprotective molecule. Therefore, it is important to maintain the basal level of HO-1 expression even when substrate availability is limited. We hypothesized that the HO-1 protein itself could regulate its own expression in a positive feedback manner, and that this positive feedback was important in the HO-1 gene induction in response to oxidative stress. In cultured NIH 3T3 cells, transfection of HO-1 cDNA or intracellular delivery of pure HO-1 protein resulted in activation of a 15-kb HO-1 promoter upstream of luciferase as visualized by bioluminescent technology and increased HO-1 mRNA and protein levels. These effects were independent of HO activity because an enzymatically inactive mutant form of HO-1 similarly activated the HO-1 promoter and incubation with HO inhibitor metalloporphyrin SnPP did not affect the promoter activation. In addition, HO-1-specific siRNA significantly reduced hemin and cadmium chloride-mediated HO-1 induction. Furthermore, deletion analyses demonstrated that the E1 and E2 distal enhancers of the HO-1 promoter are required for this HO-1 autoregulation. These experiments document feed-forward autoregulation of HO-1 in oxidative stress and suggest that HO-1 protein has a role in the induction process. We speculate that this mechanism may be useful for maintaining HO-1 expression when substrate is limited and may also serve to up-regulate other genes to promote cytoprotection and to modulate cell proliferation.

  16. Network social capital, social participation, and physical inactivity in an urban adult population. (United States)

    Legh-Jones, Hannah; Moore, Spencer


    Research on individual social capital and physical activity has tended to focus on the association among physical activity, generalized trust, and social participation. Less is known about the association between network social capital, i.e., the resources accessed through one's social connections, and physical inactivity. Using formal network measures of social capital, this study examined which specific dimension of network capital (i.e. diversity, reach and range) was associated with physical inactivity, and whether network social capital mediated the association between physical inactivity and social participation. Data came from the 2008 Montreal (Canada) Neighbourhood Networks and Healthy Aging survey, in which 2707 adults 25 years and older in 300 Montreal neighbourhoods were surveyed. Physical activity was self-reported using the International Physical Activity Questionnaire (IPAQ). IPAQ guidelines provided the basis for the physical inactivity cutoff. Network social capital was measured with a position generator instrument. Multilevel logistic methods were used to examine the association between physical inactivity and individual social capital dimensions, while adjusting for socio-demographic and -economic factors. Higher network diversity was associated with a decreased likelihood of physical inactivity. Consistent with previous findings, individuals who did not participate in any formal associations were more likely to be physically inactive compared to those with high levels of participation. Network diversity mediated the association between physical inactivity and participation. Generalized trust and the network components of reach and range were not shown associated with physical inactivity. Findings highlight the importance of social participation and network social capital and the added value of network measures in the study of social capital and physical inactivity. Population-based programs targeting physical inactivity among adults might

  17. Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark

    DEFF Research Database (Denmark)

    Christensen, Birgitte S; Grønbaek, Morten; Pedersen, Bo V;


    Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting.......Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting....

  18. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis. (United States)


    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now...

  19. Murine Extracellular Superoxide Dismutase Is Converted into the Inactive Fold by the Ser195Cys Mutation

    DEFF Research Database (Denmark)

    Scavenius, Carsten; Petersen, Jane Savskov; Thomsen, Line Rold


    We have previously shown that human extracellular superoxide dismutase (EC-SOD) exists as two variants with differences in their disulfide bridge patterns: one form is the active enzyme (aEC-SOD), and the other is inactive (iEC-SOD). The availability of both active and inactive folding variants...

  20. Hadron Molecules

    CERN Document Server

    Gutsche, Thomas; Faessler, Amand; Lee, Ian Woo; Lyubovitskij, Valery E


    We discuss a possible interpretation of the open charm mesons $D_{s0}^*(2317)$, $D_{s1}(2460)$ and the hidden charm mesons X(3872), Y(3940) and Y(4140) as hadron molecules. Using a phenomenological Lagrangian approach we review the strong and radiative decays of the $D_{s0}^* (2317)$ and $D_{s1}(2460)$ states. The X(3872) is assumed to consist dominantly of molecular hadronic components with an additional small admixture of a charmonium configuration. Determing the radiative ($\\gamma J/\\psi$ and $\\gamma \\psi(2s)$) and strong ($J/\\psi 2\\pi $ and $ J/\\psi 3\\pi$) decay modes we show that present experimental observation is consistent with the molecular structure assumption of the X(3872). Finally we give evidence for molecular interpretations of the Y(3940) and Y(4140) related to the observed strong decay modes $J/\\psi + \\omega$ or $J/\\psi + \\phi$, respectively.

  1. Inference problems in structural biology

    DEFF Research Database (Denmark)

    Olsson, Simon

    The structure and dynamics of biological molecules are essential for their function. Consequently, a wealth of experimental techniques have been developed to study these features. However, while experiments yield detailed information about geometrical features of molecules, this information is of...

  2. Emergent ultra-long-range interactions between active particles in hybrid active-inactive systems (United States)

    Steimel, Joshua P.; Aragones, Juan L.; Hu, Helen; Qureshi, Naser


    Particle-particle interactions determine the state of a system. Control over the range of such interactions as well as their magnitude has been an active area of research for decades due to the fundamental challenges it poses in science and technology. Very recently, effective interactions between active particles have gathered much attention as they can lead to out-of-equilibrium cooperative states such as flocking. Inspired by nature, where active living cells coexist with lifeless objects and structures, here we study the effective interactions that appear in systems composed of active and passive mixtures of colloids. Our systems are 2D colloidal monolayers composed primarily of passive (inactive) colloids, and a very small fraction of active (spinning) ferromagnetic colloids. We find an emergent ultra-long-range attractive interaction induced by the activity of the spinning particles and mediated by the elasticity of the passive medium. Interestingly, the appearance of such interaction depends on the spinning protocol and has a minimum actuation timescale below which no attraction is observed. Overall, these results clearly show that, in the presence of elastic components, active particles can interact across very long distances without any chemical modification of the environment. Such a mechanism might potentially be important for some biological systems and can be harnessed for newer developments in synthetic active soft materials.

  3. Vasoconstrictor eicosanoids and impaired microvascular function in inactive and insulin-resistant primates. (United States)

    Chadderdon, S M; Belcik, J T; Bader, L; Kievit, P; Grove, K L; Lindner, J R


    The inability to augment capillary blood volume (CBV) in response to insulin or glucose is thought to contribute to insulin resistance (IR) by limiting glucose uptake in key storage sites. Understanding the mechanisms that contribute to impaired CBV augmentation early in the onset of IR may lead to new future therapies. We hypothesized that inactivity alters the balance of vasoactive eicosanoids and contributes to microvascular IR. In ten activity-restricted (AR) and six normal activity adult male rhesus macaques, contrast-enhanced ultrasound of skeletal muscle blood flow and CBV was performed at baseline and during intravenous glucose tolerance test (IVGTT). Plasma was analyzed for vasoconstrictor hydroxyeicosatetraenoic acids (HETEs) and the ratio of vasodilatory epoxyeicosatrienoic acids (EETs) to their less biologically active dihydroxyeicosatrienoic acids (DHETs) as an indirect measure of soluble epoxide hydrolase activity. AR primates were IR during IVGTT and had a 45% lower glucose-stimulated CBV response. Vasoconstrictor 18-HETE and 19-HETE and the DHET/EET ratio were markedly elevated in the AR group and correlated inversely with the CBV response. In addition, levels of 18-HETE and 19-HETE correlated directly with microvascular IR. We conclude that a shift toward increased eicosanoid vasoconstrictor tone correlates with abnormal skeletal muscle vascular recruitment and may contribute to IR.

  4. Enhanced Raman scattering of biological molecules (United States)

    Montoya, Joseph R.

    The results presented in this thesis, originate from the aspiration to develop an identification algorithm for Salmonella enterica Serovar Enteritidis (S. enterica), Escherichia coli (E. coli), Bacillus globigii ( B. globigii), and Bacillus megaterium ( B. megaterium) using "enhanced" Raman scattering. We realized our goal, with a method utilizing an immunoassay process in a spectroscopic technique, and the direct use of the enhanced spectral response due to bacterial surface elements. The enhanced Raman signal originates from Surface Enhanced Raman Scattering (SERS) and/or Morphological Dependent Resonances (MDR's). We utilized a modified Lee-Meisel colloidal production method to produce a SERS active substrate, which was applied to a SERS application for the amino acid Glycine. The comparison indicates that the SERS/FRACTAL/MDR process can produce an increase of 107 times more signal than the bulk Raman signal from Glycine. In the extension of the Glycine results, we studied the use of SERS related to S. enterica, where we have shown that the aromatic amino acid contribution from Phenylalanine, Tyrosine, and Tryptophan produces a SERS response that can be used to identify the associated SERS vibrational modes of a S. enterica one or two antibody complexes. The "fingerprint" associated with the spectral signature in conjunction with an enhanced Raman signal allows conclusions to be made: (1) about the orientation of the secondary structure on the metal; (2) whether bound/unbound antibody can be neglected; (3) whether we can lower the detection limit. We have lowered the detection limit of S. enterica to 106 bacteria/ml. We also show a profound difference between S. enterica and E. coli SERS spectra even when there exists non-specific binding on E. coli indicating a protein conformation change induced by the addition of the antigen S. enterica. We confirm TEM imagery data, indicating that the source of the aromatic amino acid SERS response is originating from fractal structures on the surface of the bacteria with appropriate associated absorption spectra. In addition, we show that SERS may be used by directly detecting cell surface chemistry, with a report of a SERS response from gram-positive bacteria, B. globigii and B. megaterium combined, with silver fractal aggregates.

  5. Computational systems chemical biology. (United States)

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander


    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  6. Physical inactivity and obesity: relation to asthma and chronic obstructive pulmonary disease? (United States)

    ten Hacken, Nick H T


    Physical inactivity and obesity are modifiable risk factors for many chronic diseases, including cardiovascular disease, diabetes mellitus, osteoporosis, osteoarthritis, and depression. Both physical inactivity and obesity are associated with low-grade systemic inflammation that may contribute to the inflammatory processes present in many chronic diseases. In asthma, almost no studies are available in which physical inactivity has been studied using performance-based instruments. In contrast, the association between obesity and a higher prevalence of asthma has often been suggested in a large number of studies. In chronic obstructive pulmonary disease (COPD) physical inactivity has been demonstrated in a few studies that used performance-based instruments; this was associated with the higher COPD Global Initiative on Obstructive Lung Disease (GOLD) stages and a higher degree of systemic inflammation, independent of body mass index. In contrast to physical inactivity, obesity in COPD is associated with the lower GOLD stages. Additionally, obesity is associated with the chronic obstructive phenotype and features of the metabolic syndrome. To elucidate the independent relation of physical inactivity and obesity with systemic inflammation, performance-based studies of physical inactivity in asthma and COPD are highly needed.

  7. Novel Catalytically-Inactive PII Metalloproteinases from a Viperid Snake Venom with Substitutions in the Canonical Zinc-Binding Motif (United States)

    Camacho, Erika; Sanz, Libia; Escalante, Teresa; Pérez, Alicia; Villalta, Fabián; Lomonte, Bruno; Neves-Ferreira, Ana Gisele C.; Feoli, Andrés; Calvete, Juan J.; Gutiérrez, José María; Rucavado, Alexandra


    Snake venom metalloproteinases (SVMPs) play key biological roles in prey immobilization and digestion. The majority of these activities depend on the hydrolysis of relevant protein substrates in the tissues. Hereby, we describe several isoforms and a cDNA clone sequence, corresponding to PII SVMP homologues from the venom of the Central American pit viper Bothriechis lateralis, which have modifications in the residues of the canonical sequence of the zinc-binding motif HEXXHXXGXXH. As a consequence, the proteolytic activity of the isolated proteins was undetectable when tested on azocasein and gelatin. These PII isoforms comprise metalloproteinase and disintegrin domains in the mature protein, thus belonging to the subclass PIIb of SVMPs. PII SVMP homologues were devoid of hemorrhagic and in vitro coagulant activities, effects attributed to the enzymatic activity of SVMPs, but induced a mild edema. One of the isoforms presents the characteristic RGD sequence in the disintegrin domain and inhibits ADP- and collagen-induced platelet aggregation. Catalytically-inactive SVMP homologues may have been hitherto missed in the characterization of snake venoms. The presence of such enzymatically-inactive homologues in snake venoms and their possible toxic and adaptive roles deserve further investigation. PMID:27754342

  8. Prevalence of Irritable Bowel Syndrome–like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease (United States)

    Tomita, Toshihiko; Kato, Yu; Takimoto, Mayu; Yamasaki, Takahisa; Kondo, Takashi; Kono, Tomoaki; Tozawa, Katsuyuki; Yokoyama, Yoko; Ikehara, Hisatomo; Ohda, Yoshio; Oshima, Tadayuki; Fukui, Hirokazu; Tanaka, Shigemi; Shima, Masayuki; Watari, Jiro; Miwa, Hiroto


    Background/Aims Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients. PMID:27193973

  9. Chemical space and biology. (United States)

    Dobson, Christopher M


    Chemical space--which encompasses all possible small organic molecules, including those present in biological systems--is vast. So vast, in fact, that so far only a tiny fraction of it has been explored. Nevertheless, these explorations have greatly enhanced our understanding of biology, and have led to the development of many of today's drugs. The discovery of new bioactive molecules, facilitated by a deeper understanding of the nature of the regions of chemical space that are relevant to biology, will advance our knowledge of biological processes and lead to new strategies to treat disease.

  10. Logical impossibilities in biological networks

    Directory of Open Access Journals (Sweden)

    Monendra Grover


    Full Text Available Biological networks are complex and involve several kinds of molecules. For proper biological function it is important for these biomolecules to act at an individual level and act at the level of interaction of these molecules. In this paper some of the logical impossibilities that may arise in the biological networks and their possible solutions are discussed. It may be important to understand these paradoxes and their possible solutions in order to develop a holistic view of biological function.

  11. Fostering synergy between cell biology and systems biology



    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules; predicting mechanisms and identifying generalizable themes; generating hypotheses...

  12. A new light on DNA replication from the inactive X chromosome. (United States)

    Aladjem, Mirit I; Fu, Haiqing


    While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, "silent" chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular.

  13. 2014 consensus statement from the first Economics of Physical Inactivity Consensus (EPIC) conference (Vancouver). (United States)

    Davis, Jennifer C; Verhagen, Evert; Bryan, Stirling; Liu-Ambrose, Teresa; Borland, Jeff; Buchner, David; Hendriks, Marike R C; Weiler, Richard; Morrow, James R; van Mechelen, Willem; Blair, Steven N; Pratt, Mike; Windt, Johann; al-Tunaiji, Hashel; Macri, Erin; Khan, Karim M


    This article describes major topics discussed from the 'Economics of Physical Inactivity Consensus Workshop' (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence.

  14. Single Molecule Study of the Weak Biological Interactions Between P53 and DNA%纳米通道单分子检测P53蛋白与DNA的弱相互作用

    Institute of Scientific and Technical Information of China (English)

    应佚伦; 张星; 刘钰; 薛梦竹; 李洪林; 龙亿涛


    Many important cellular events, including protein-DNA interactions, are attributed to weak interactions. Almost all of the known biological functions of P53 depend critically upon its DNA-binding properties via numerous weak interactions. At the single-molecule level, information about the weak interactions between each residue of the P53 DNA binding domain (P53 DBD) and DNA is essential for understanding the biological function of P53 and for anti-cancer drug design. Here, we used the a-hemolysin (α-HL) pore to detect the weak interaction between a peptide of the P53 DBD (P53-P) and a 40-bp double-stranded DNA (B40) that includes the p21 wafl/cipl DNA response element. The weak interactions in the complex of p53-P and B40 (p53-P:B40) produce a unique current trace through an a-HL nanopore with diagnostic ionic current blockages. Each current trace at a particular potential is related to the characterized behavior of captured p53-P:B40. Nanopore analysis indicates that the conformation of B40 might be changed by binding to p53-P, this change is confirmed by the molecule docking simulation. In the presence of the weak interactions between p53-P and B40, the analyte exhibits an increase in the rate constant of association with the nanopore vestibule. This reveals that the analyte-pore interactions could be enhanced by the weak interactions between p53-P and B40. The distorted B40 might be prone to translocate through the narrow constriction in the nanopore at the higher potential (> +120 mV). Moreover, our findings demonstrate that the structure of distorted B40 in p53-P:B40 could be broken by the electric force. Our results support the possibility of identifying the weak interaction between two biomolecules. In addition, the analyte-pore association rate constant could be used to estimate the weak binding energy between different parts of the p53 binding domain and the target sequence. The signatures of the current trace may assist in the prediction of the

  15. Metabolic rates and biochemical compositions of Apostichopus japonicus (Selenka) tissue during periods of inactivity

    Institute of Scientific and Technical Information of China (English)

    包杰; 董双林; 田相利; 王芳; 高勤峰; 董云伟


    Estivation, hibernation, and starvation are indispensable inactive states of sea cucumbers Apostichopus japonicus in nature and in culture ponds. Generally, temperature is the principal factor that induces estivation or hibernation in the sea cucumber. The present study provided insight into the physiological adaptations of A. japonicus during the three types of inactivity (hibernation, estivation, and starvation) by measuring the oxygen consumption rates (Vo2) and biochemical compositions under laboratory ...

  16. Single-molecule dynamics at variable temperatures

    NARCIS (Netherlands)

    Zondervan, Rob


    Single-molecule optics has evolved from a specialized variety of optical spectroscopy at low temperatures into a versatile tool to address questions in physics, chemistry, biology, and materials science. In this thesis, the potential of single-molecule (and ensemble) optical microscopy at variable t

  17. A Src-like inactive conformation in the abl tyrosine kinase domain.

    Directory of Open Access Journals (Sweden)

    Nicholas M Levinson


    Full Text Available The improper activation of the Abl tyrosine kinase results in chronic myeloid leukemia (CML. The recognition of an inactive conformation of Abl, in which a catalytically important Asp-Phe-Gly (DFG motif is flipped by approximately 180 degrees with respect to the active conformation, underlies the specificity of the cancer drug imatinib, which is used to treat CML. The DFG motif is not flipped in crystal structures of inactive forms of the closely related Src kinases, and imatinib does not inhibit c-Src. We present a structure of the kinase domain of Abl, determined in complex with an ATP-peptide conjugate, in which the protein adopts an inactive conformation that resembles closely that of the Src kinases. An interesting aspect of the Src-like inactive structure, suggested by molecular dynamics simulations and additional crystal structures, is the presence of features that might facilitate the flip of the DFG motif by providing room for the phenylalanine to move and by coordinating the aspartate side chain as it leaves the active site. One class of mutations in BCR-Abl that confers resistance to imatinib appears more likely to destabilize the inactive Src-like conformation than the active or imatinib-bound conformations. Our results suggest that interconversion between distinctly different inactive conformations is a characteristic feature of the Abl kinase domain.

  18. Structural basis for morpheein-type allosteric regulation of Escherichia coli glucosamine-6-phosphate synthase: equilibrium between inactive hexamer and active dimer. (United States)

    Mouilleron, Stéphane; Badet-Denisot, Marie-Ange; Pecqueur, Ludovic; Madiona, Karine; Assrir, Nadine; Badet, Bernard; Golinelli-Pimpaneau, Béatrice


    The amino-terminal cysteine of glucosamine-6-phosphate synthase (GlmS) acts as a nucleophile to release and transfer ammonia from glutamine to fructose 6-phosphate through a channel. The crystal structure of the C1A mutant of Escherichia coli GlmS, solved at 2.5 Å resolution, is organized as a hexamer, where the glutaminase domains adopt an inactive conformation. Although the wild-type enzyme is active as a dimer, size exclusion chromatography, dynamic and quasi-elastic light scattering, native polyacrylamide gel electrophoresis, and ultracentrifugation data show that the dimer is in equilibrium with a hexameric state, in vitro and in cellulo. The previously determined structures of the wild-type enzyme, alone or in complex with glucosamine 6-phosphate, are also consistent with a hexameric assembly that is catalytically inactive because the ammonia channel is not formed. The shift of the equilibrium toward the hexameric form in the presence of cyclic glucosamine 6-phosphate, together with the decrease of the specific activity with increasing enzyme concentration, strongly supports product inhibition through hexamer stabilization. Altogether, our data allow us to propose a morpheein model, in which the active dimer can rearrange into a transiently stable form, which has the propensity to form an inactive hexamer. This would account for a physiologically relevant allosteric regulation of E. coli GlmS. Finally, in addition to cyclic glucose 6-phosphate bound at the active site, the hexameric organization of E. coli GlmS enables the binding of another linear sugar molecule. Targeting this sugar-binding site to stabilize the inactive hexameric state is therefore suggested for the development of specific antibacterial inhibitors.

  19. Correction: El Azab, I.H., et al. Microwave-Assisted Synthesis of Novel 2H-Chromene Derivatives Bearing Phenylthiazolidinones and Their Biological Activity Assessment. Molecules 2014, 19, 19648-19664. (United States)

    El Azab, Islam H; Youssef, Mohamed M; Amin, Amin M


    The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution's generous financial support[...].

  20. Exploring the Linkage between Activity-Friendly Zoning, Inactivity, and Cancer Incidence in the United States. (United States)

    Nicholson, Lisa M; Leider, Julien; Chriqui, Jamie F


    Background: Physical activity (PA) protects against cancer and enhances cancer survivorship. Given high inactivity rates nationwide, population-level physical activity facilitators are needed. Several authoritative bodies have recognized that zoning and planning helps create activity-friendly environments. This study examined the association between activity-friendly zoning, inactivity, and cancer in 478 of the most populous U.S. counties.Methods: County geocodes linked county-level data: cancer incidence and smoking (State Cancer Profiles), inactivity (Behavioral Risk Factor Surveillance System), 11 zoning measures (compiled by the study team), and covariates (from the American Community Survey and NAVTEQ). For each zoning measure, single mediation regression models and Sobel tests examined whether activity-friendly zoning was associated with reduced cancer incidence, and whether inactivity mediated those associations. All models were clustered on state with robust SEs and significance at the P Zoning for crosswalks, bike-pedestrian connectivity, and bike-pedestrian trails/paths were associated with reduced cancer incidence (β between -0.71 and -1.27, P zoning. Except for crosswalks, each association was mediated by inactivity. However, county smoking attenuated these results, with only crosswalks remaining significant. Results were similar for males (with zoning for bike-pedestrian connectivity, street connectivity, and bike-pedestrian trails/paths), but not females, alone.Conclusions: Zoning can help to create activity-friendly environments that support decreased inactivity, and possibly reduced cancer incidence.Impact: Given low physical activity levels nationwide, cross-sectoral collaborations with urban planning can inform cancer prevention and public health efforts to decrease inactivity and cancer. Cancer Epidemiol Biomarkers Prev; 1-9. ©2017 AACR.See all the articles in this CEBP Focus section, "Geospatial Approaches to Cancer Control and Population

  1. High prevalence of inactivity among young patients with type 1 diabetes in south Spain

    Directory of Open Access Journals (Sweden)

    José Vicente Gutiérrez Manzanedo


    Full Text Available Objectives: To describe usual physical activity level and analyze its association with metabolic control and presence of microvascular complications in a cohort of patients with type 1 diabetes (DM-1 in south Spain. Methods: Observational, cross-sectional study that included one hundred thirty patients, aged 33.9 ± 11.5 years-old with disease duration of 16.5 ± 9.5 years that consecutively were recruited among patients attending the Endocrinology Service of Puerta del Mar University Hospital (Cádiz, Spain. Usual physical activity level was assessed using the "General Practice Physical Activity Questionnaire" (GPPAQ together with clinical, anthropometric, metabolic parameters and microvascular complications. Results: DM-1 patients were grouped in four categories of physical activity level: inactive (n = 33; 25.3%, moderately inactive (n = 31; 23.8%, moderately active (n = 26; 20.0% and active (n = 40; 30.9%. We observed no significant differences in glycated haemoglobin (HbA1c level between the different physical activity groups analyzed. Patients classified as moderately active and active were more often men, significantly younger and presented lower plasmatic levels of triglycerides than patients classified as inactive or moderately inactive, with no differences in other clinical or anthropometric variables. In addition, active and moderately active patients had a lower prevalence of diabetic retinopathy and microvascular complications in general compared to inactive or moderately inactive patients. Conclusions: Half of patients with type 1 diabetes evaluated were classified as inactive and these patients had a higher prevalence of diabetic retinopathy than active patients. No difference in HbA1c levels was documented among different groups of physical activity.

  2. Mesoscopic biology

    Indian Academy of Sciences (India)

    G V Shivashankar


    In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in biological systems. In recent years advances in technology have led to the study of some of the design principles of these machines; in particular at the level of an individual molecule. For example, the forces that operate in molecular interactions, the stochasticity involved in these interactions and their spatio-temporal dynamics are beginning to be explored. Understanding such design principles is opening new possibilities in mesoscopic physics with potential applications.

  3. Single-Molecule Studies in Live Cells (United States)

    Yu, Ji


    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies.

  4. Computer Simulation Studies on Apatite Crystal and Its Interaction with Biologic Molecules%磷灰石晶体构型及其与生物分子相互作用的计算模拟研究

    Institute of Scientific and Technical Information of China (English)

    沈娟; 金波; 蒋琪英; 钟国清; 霍冀川


    生物磷灰石是动物和人体骨骼及牙釉质的主要无机矿物成分,磷灰石矿物晶体的组成和结构影响了骨及牙釉质的机械强度和生理功能。羟基磷灰石空间群的确定一直存在争议,其中羟基存在两种不同排列方式,使得其具有六方和单斜两种晶相。另外,磷灰石晶体结构中的类质同象替换,影响了其结构、物理和化学特性。本文综述了计算机模拟方法在原子及分子水平上对磷灰石晶体的空间群确定、磷灰石替代机制、小分子及生物大分子相互作用的研究,对磷灰石晶体化学、界面化学及开发生物材料的深入研究具有一定的科学意义和较强的应用价值。%Biological apatite is the main inorganic mineral component of animal and human bone and tooth enamel,moreover apatite mineral composition and structure affect on the bone and tooth enamel mechanical strength and physiological behavior.The structure of hydroxyapatite(HAP) has proved more difficult to resolve,two different hydroxyl arrangements may occur in HAP resulting in hexagonal and monoclinic structures.Extensive isomorphic substitutions may greatly affect the properties of this mineral.In the paper,computational methods are well placed to calculate at the atomic level the geometry and relative energies of the various possible hydroxy groups in apatite,and they have been employed to study the uptake and distribution of small molecule or biomacromolecule in the hydroxyapatite.Application of computer simulation at the atomic level to investigate apatites,especially HAP,is anticipated to provide a deeper understanding of crystal chemistry and interaction with biomacromolecules.These results offer a more comprehensive investigation of bio-apatite and perspective applications.

  5. Juvenile idiopathic arthritis in adulthood: fulfilment of classification criteria for adult rheumatic diseases, long-term outcomes and predictors of inactive disease, functional status and damage (United States)

    Oliveira-Ramos, Filipa; Eusébio, Mónica; M Martins, Fernando; Mourão, Ana Filipa; Furtado, Carolina; Campanilho-Marques, Raquel; Cordeiro, Inês; Ferreira, Joana; Cerqueira, Marcos; Figueira, Ricardo; Brito, Iva; Santos, Maria José; Melo-Gomes, José A; Fonseca, João Eurico


    Objectives To determine how adult juvenile idiopathic arthritis (JIA) patients fulfil classification criteria for adult rheumatic diseases, evaluate their outcomes and determine clinical predictors of inactive disease, functional status and damage. Methods Patients with JIA registered on the Rheumatic Diseases Portuguese Register ( older than 18 years and with more than 5 years of disease duration were included. Data regarding sociodemographic features, fulfilment of adult classification criteria, Health Assessment Questionnaire, Juvenile Arthritis Damage Index—articular (JADI-A) and Juvenile Arthritis Damage Index—extra-articular (JADI-E) damage index and disease activity were analysed. Results 426 patients were included. Most of patients with systemic JIA fulfilled criteria for Adult Still's disease. 95.6% of the patients with rheumatoid factor (RF)-positive polyarthritis and 57.1% of the patients with RF-negative polyarthritis matched criteria for rheumatoid arthritis (RA). 38.9% of the patients with extended oligoarthritis were classified as RA while 34.8% of the patients with persistent oligoarthritis were classified as spondyloarthritis. Patients with enthesitis-related arthritis fulfilled criteria for spondyloarthritis in 94.7%. Patients with psoriatic arthritis maintained this classification. Patients with inactive disease had lower disease duration, lower diagnosis delay and corticosteroids exposure. Longer disease duration was associated with higher HAQ, JADI-A and JADI-E. Higher JADI-A was also associated with biological treatment and retirement due to JIA disability and higher JADI-E with corticosteroids exposure. Younger age at disease onset was predictive of higher HAQ, JADI-A and JADI-E and decreased the chance of inactive disease. Conclusions Most of the included patients fulfilled classification criteria for adult rheumatic diseases, maintain active disease and have functional impairment. Younger age at disease onset was predictive

  6. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules (United States)

    Almutairi, Maha S.; Xavier, S.; Sathish, M.; Ghabbour, Hazem A.; Sebastian, S.; Periandy, S.; Al-Wabli, Reem I.; Attia, Mohamed I.


    Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000-500 and 4000-50 cm-1, respectively. The fundamental modes of the vibrations were assigned and the UV-visible spectrum of the MMIC molecule was recorded in the range of 200-400 nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.

  7. Boolean network model for GPR142 against Type 2 diabetes and relative dynamic change ratio analysis using systems and biological circuits approach. (United States)

    Kaushik, Aman Chandra; Sahi, Shakti


    Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature and kinetic simulation of GPR142 was carried out in order to determine the dynamic interactions. The major objective of this work was to design a GPR142 biochemical pathway using both systems biology as well as biological circuits synthetically. The term 'synthetically' refers to building biological circuits for cell signaling pathway especially for hormonal pathway disease. The focus of the paper is on logical components and logical circuits whereby using these applications users can create complex virtual circuits. Logic gates process represents only true or false and investigates whether biological regulatory circuits are active or inactive. The basic gates used are AND, NAND, OR, XOR and NOT gates and Integrated circuit composition of many such basic gates and some derived gates. Biological circuits may have a futuristic application in biomedical sciences which may involve placing a micro chip in human cells to modulate the down or up regulation of hormonal disease.

  8. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States

    Directory of Open Access Journals (Sweden)

    Yan Jiang


    Full Text Available Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA, using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA’s influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence—influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.

  9. Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States. (United States)

    Jiang, Yan; Yuan, Yongping; Neale, Anne; Jackson, Laura; Mehaffey, Megan


    Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.

  10. Establishment of X chromosome inactivation and epigenomic features of the inactive X depend on cellular contexts. (United States)

    Vallot, Céline; Ouimette, Jean-François; Rougeulle, Claire


    X chromosome inactivation (XCI) is an essential epigenetic process that ensures X-linked gene dosage equilibrium between sexes in mammals. XCI is dynamically regulated during development in a manner that is intimately linked to differentiation. Numerous studies, which we review here, have explored the dynamics of X inactivation and reactivation in the context of development, differentiation and diseases, and the phenotypic and molecular link between the inactive status, and the cellular context. Here, we also assess whether XCI is a uniform mechanism in mammals by analyzing epigenetic signatures of the inactive X (Xi) in different species and cellular contexts. It appears that the timing of XCI and the epigenetic signature of the inactive X greatly vary between species. Surprisingly, even within a given species, various Xi configurations are found across cellular states. We discuss possible mechanisms underlying these variations, and how they might influence the fate of the Xi.

  11. A novel PWM scheme to eliminate the diode freewheeling In the Inactive phase in BLDC motor

    Institute of Scientific and Technical Information of China (English)

    WEI Kun; HU Chang-sheng; ZHANG Zhong-chao


    The brushless DC motor (BLDCM) with trapezoidal electromotive force (back-EMF) waveform is used widely.In principle,when the motor runs in the 120°conduction mode,two of the three phases are active while the other phase is inactive at all times.However,a ripple current occurs in the inactive phase due to the diode freewheeling during the non-commutation period in the traditional pulse width modulation (PWM) methods,which aggravates the torque ripples.A new PWM method is proposed in this paper to eliminate the diode freewheeling during the non-commutation period in the inactive phase.As a result,the torque ripple is suppressed using the proposed method.The simulation and experimental results are demonstrated to verify the validity of the proposed PWM method.

  12. Aerobic exercise and cold pressor test induce hypoalgesia in active and inactive men and women

    DEFF Research Database (Denmark)

    Vaegter, Henrik Bjarke; Handberg, Gitte; Jørgensen, Maria N.;


    and after exercise, PPTs increased to the same degree in active and inactive subjects, and the CPM and EIH responses were correlated (P aerobic exercise caused......). Conditioned pain modulation (CPM) was assessed by cold pressor testing. Exercise-induced hypoalgesia (EIH) was assessed after 15 minutes bicycling at a heart rate corresponding to 75% VO2max. A control session of 15 minutes quiet rest was also included. Pressure pain thresholds (PPTs) were recorded...... at the dominant arm and leg before, immediately after, and 15 minutes after conditioning and exercise as well as before and after rest. PPTs were also recorded during conditioning. RESULTS: At baseline, PPTs in inactive men were increased compared with inactive women (P 

  13. Dual-wavelength polymer laser based on an active/inactive/active sandwich-like structure (United States)

    Zhai, Tianrui; Wu, Xiaofeng; Wang, Meng; Tong, Fei; Li, Songtao; Ma, Yanbin; Deng, Jinxiang; Zhang, Xinping


    Dual-wavelength laser emission is achieved by using an active/inactive/active sandwich-like structure, which can be conveniently fabricated using spin coating technique. Poly [(9, 9-dioctylfluorenyl-2, 7-diyl)-alt-co-(1, 4-benzo-(2, 1', 3) -thiadiazole)] and polyvinyl alcohol are employed as the active and the inactive materials, respectively. Two laser wavelengths are simultaneously observed, which are attributed to the difference of the surrounding refractive index of two active waveguides in the sandwich-like structure. Each wavelength is controlled by the respective waveguide structure, meaning that multi-wavelength laser can be designed by stacking the active/inactive layer pair. These results provide more flexibility to design compact laser sources.

  14. Remarks Regarding the Activity of Taxpayers Declared Inactive and Subsequent Economical Consequences

    Directory of Open Access Journals (Sweden)

    Despina-Martha ILUCA


    Full Text Available Declaring a taxpayer as inactive is a procedure founded on expressly stipulated law conditions and it has both individual effects and effects on the relation established between an inactive taxpayer and an active one. The primary effect, which is the cause for all of the others, is the ex officio cancellation of the VAT registration. This marks the loss of the taxpayer’s right to deduct the VAT using the “downstream VAT – upstream VAT” mechanism, becoming just a final consumer. The active taxpayer engaging in commercial transactions with an inactive taxpayer cannot deduct expenses, nor the VAT, as these operations are based on a document that is not issued in accordance with the legal provisions.

  15. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012 (United States)

    Kirtland, Karen; Lin, Ji; Shrestha, Sundar; Thompson, Ted; Albright, Ann; Gregg, Edward W.


    Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004–2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008–2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity. PMID

  16. Light saturation curves show competence of the water splitting complex in inactive Photosystem II reaction centers. (United States)

    Nedbal, L; Gibas, C; Whitmarsh, J


    Photosystem II complexes of higher plants are structurally and functionally heterogeneous. While the only clearly defined structural difference is that Photosystem II reaction centers are served by two distinct antenna sizes, several types of functional heterogeneity have been demonstrated. Among these is the observation that in dark-adapted leaves of spinach and pea, over 30% of the Photosystem II reaction centers are unable to reduce plastoquinone to plastoquinol at physiologically meaningful rates. Several lines of evidence show that the impaired reaction centers are effectively inactive, because the rate of oxidation of the primary quinone acceptor, QA, is 1000 times slower than in normally active reaction centers. However, there are conflicting opinions and data over whether inactive Photosystem II complexes are capable of oxidizing water in the presence of certain artificial electron acceptors. In the present study we investigated whether inactive Photosystem II complexes have a functional water oxidizing system in spinach thylakoid membranes by measuring the flash yield of water oxidation products as a function of flash intensity. At low flash energies (less that 10% saturation), selected to minimize double turnovers of reaction centers, we found that in the presence of the artificial quinone acceptor, dichlorobenzoquinone (DCBQ), the yield of proton release was enhanced 20±2% over that observed in the presence of dimethylbenzoquinone (DMBQ). We argue that the extra proton release is from the normally inactive Photosystem II reaction centers that have been activated in the presence of DCBQ, demonstrating their capacity to oxidize water in repetitive flashes, as concluded by Graan and Ort (Biochim Biophys Acta (1986) 852: 320-330). The light saturation curves indicate that the effective antenna size of inactive reaction centers is 55±12% the size of active Photosystem II centers. Comparison of the light saturation dependence of steady state oxygen evolution

  17. The association of ambient air pollution and physical inactivity in the United States.

    Directory of Open Access Journals (Sweden)

    Jennifer D Roberts

    Full Text Available BACKGROUND: Physical inactivity, ambient air pollution and obesity are modifiable risk factors for non-communicable diseases, with the first accounting for 10% of premature deaths worldwide. Although community level interventions may target each simultaneously, research on the relationship between these risk factors is lacking. OBJECTIVES: After comparing spatial interpolation methods to determine the best predictor for particulate matter (PM2.5; PM10 and ozone (O3 exposures throughout the U.S., we evaluated the cross-sectional association of ambient air pollution with leisure-time physical inactivity among adults. METHODS: In this cross-sectional study, we assessed leisure-time physical inactivity using individual self-reported survey data from the Centers for Disease Control and Prevention's 2011 Behavioral Risk Factor Surveillance System. These data were combined with county-level U.S. Environmental Protection Agency air pollution exposure estimates using two interpolation methods (Inverse Distance Weighting and Empirical Bayesian Kriging. Finally, we evaluated whether those exposed to higher levels of air pollution were less active by performing logistic regression, adjusting for demographic and behavioral risk factors, and after stratifying by body weight category. RESULTS: With Empirical Bayesian Kriging air pollution values, we estimated a statistically significant 16-35% relative increase in the odds of leisure-time physical inactivity per exposure class increase of PM2.5 in the fully adjusted model across the normal weight respondents (p-value<0.0001. Evidence suggested a relationship between the increasing dose of PM2.5 exposure and the increasing odds of physical inactivity. CONCLUSIONS: In a nationally representative, cross-sectional sample, increased community level air pollution is associated with reduced leisure-time physical activity particularly among the normal weight. Although our design precludes a causal inference, these

  18. Linking geology and microbiology: inactive pockmarks affect sediment microbial community structure.

    Directory of Open Access Journals (Sweden)

    Thomas H A Haverkamp

    Full Text Available Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslofjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmarks and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial communities at the sediment surface are affected by the water column, while the deeper (40 cm sediment communities are affected by local conditions within the sediment.

  19. Linking geology and microbiology: inactive pockmarks affect sediment microbial community structure. (United States)

    Haverkamp, Thomas H A; Hammer, Øyvind; Jakobsen, Kjetill S


    Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined what the microbial composition of inactive pockmarks is and if it shows a similar pattern as the macrofauna. The Norwegian Oslofjord contains many inactive pockmarks and they are well suited to study the influence of these geological features on the microbial community in the sediment. Here we present a detailed analysis of the microbial communities found in three inactive pockmarks and two control samples at two core depth intervals. The communities were analyzed using high-throughput amplicon sequencing of the 16S rRNA V3 region. Microbial communities of surface pockmark sediments were indistinguishable from communities found in the surrounding seabed. In contrast, pockmark communities at 40 cm sediment depth had a significantly different community structure from normal sediments at the same depth. Statistical analysis of chemical variables indicated significant differences in the concentrations of total carbon and non-particulate organic carbon between 40 cm pockmarks and reference sample sediments. We discuss these results in comparison with the taxonomic classification of the OTUs identified in our samples. Our results indicate that microbial communities at the sediment surface are affected by the water column, while the deeper (40 cm) sediment communities are affected by local conditions within the sediment.

  20. Unemployment, Employment and Inactivity in Denmark: An Analysis of Event History Data

    DEFF Research Database (Denmark)

    Lauzadyté, Agné

    and inactivity. The less educated and unskilled workers are found to be another risk group to face the marginalisation from the labour market. Being previously employed reduces the risk of OLF, and increases the re-entry to employment probability, while living in the biggest Danish cities makes persons......In this paper I estimate a discrete time hazard model for the exits from the different labour market states - unemployment, employment and inactivity (or OLF) - in the Danish labour market. I find that women and individuals over fifty are more likely to experience the long-term unemployment...

  1. A recombinant fusion toxin based on enzymatic inactive C3bot1 selectively targets macrophages.

    Directory of Open Access Journals (Sweden)

    Lydia Dmochewitz

    Full Text Available BACKGROUND: The C3bot1 protein (~23 kDa from Clostridium botulinum ADP-ribosylates and thereby inactivates Rho. C3bot1 is selectively taken up into the cytosol of monocytes/macrophages but not of other cell types such as epithelial cells or fibroblasts. Most likely, the internalization occurs by a specific endocytotic pathway via acidified endosomes. METHODOLOGY/PRINCIPAL FINDINGS: Here, we tested whether enzymatic inactive C3bot1E174Q serves as a macrophage-selective transport system for delivery of enzymatic active proteins into the cytosol of such cells. Having confirmed that C3bot1E174Q does not induce macrophage activation, we used the actin ADP-ribosylating C2I (∼50 kDa from Clostridium botulinum as a reporter enzyme for C3bot1E174Q-mediated delivery into macrophages. The recombinant C3bot1E174Q-C2I fusion toxin was cloned and expressed as GST-protein in Escherichia coli. Purified C3bot1E174Q-C2I was recognized by antibodies against C2I and C3bot and showed C2I-specific enzyme activity in vitro. When applied to cultured cells C3bot1E174Q-C2I ADP-ribosylated actin in the cytosol of macrophages including J774A.1 and RAW264.7 cell lines as well as primary cultured human macrophages but not of epithelial cells. Together with confocal fluorescence microscopy experiments, the biochemical data indicate the selective uptake of a recombinant C3-fusion toxin into the cytosol of macrophages. CONCLUSIONS/SIGNIFICANCE: In summary, we demonstrated that C3bot1E174Q can be used as a delivery system for fast, selective and specific transport of enzymes into the cytosol of living macrophages. Therefore, C3-based fusion toxins can represent valuable molecular tools in experimental macrophage pharmacology and cell biology as well as attractive candidates to develop new therapeutic approaches against macrophage-associated diseases.

  2. The Molecule Cloud - compact visualization of large collections of molecules

    Directory of Open Access Journals (Sweden)

    Ertl Peter


    Full Text Available Abstract Background Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. Summary A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach “Molecule Cloud”. The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Conclusions Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large

  3. Teacher Educators' In-Action Mental Models in Different Teaching Situations (United States)

    Mevorach, Miriam; Strauss, Sidney


    In previous studies on teachers' cognition, we discovered that teachers' teaching can be described via a general in-action mental model (IAMM) concerning the structure of the mind and the roles of teaching in fostering children's learning. The purpose of our study was to examine teacher educators' IAMM regarding student teachers' minds and…

  4. Physical inactivity and obesity: Using a novel environmental quality measure to control confounding (United States)

    Physical inactivity is well-established as a contributor to obesity prevalence in the US. Many aspects of the ambient environment (e.g., air pollution, food deserts, neighborhood socioeconomics) have also been associated with obesity. Yet, controlling for the overall ambient envi...

  5. A conceptualisation of help-avoidance as motivated inaction: implications for theory, research, and society

    NARCIS (Netherlands)

    Täuber, Susanne; Zagefka, Hanna; van Leeuwen, Esther


    This chapter zooms in on the strategic motives of help-avoidance, an intriguing yet under-researched phenomenon. Conceptualising this phenomenon as a particular form of inaction, I propose that help-avoidance is a strategic response to disadvantage that is motivated by identity concerns. I provide t

  6. Job strain as a risk factor for leisure-time physical inactivity

    DEFF Research Database (Denmark)

    Fransson, Eleonor I; Heikkilä, Katriina; Nyberg, Solja T


    Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 Europ...

  7. Comparison of fractions of inactive modules between Run1 and Run2

    CERN Document Server

    Motohashi, Kazuki; The ATLAS collaboration


    Fraction of inactive modules for each component of the ATLAS pixel detector at the end of Run 1 and the beginning of Run 2. A similar plot which uses a result of functionality tests during LS1 can be found in ATL-INDET-SLIDE-2014-388.

  8. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis. (United States)

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail


    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  9. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis (United States)

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.


    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  10. Peripheral aneurysm rupture in a patient with inactive systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Engelke, Christoph; Sabharwal, Tarun; Reidy, John F. [Department of Radiology, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom); Mohan, Aarthi R. [Department of Chest Medicine, Guy' s and St. Thomas' Hospital Trust, St. Thomas' Street, London SE1 9RT (United Kingdom)


    We describe a patient with inactive systemic lupus erythematosus (SLE) presenting with sudden haemothorax, due to a ruptured internal mammary artery (IMA) aneurysm 7 years after the corticosteroid treatment was terminated. The unusual imaging findings and the treatment with embolization are discussed with a view to the role of a regular vascular screening in this patient group. (orig.)

  11. Sauna-induced body mass loss in physically inactive young women and men

    Directory of Open Access Journals (Sweden)

    Podstawski Robert


    Full Text Available Study aim: The aim of this study was to evaluate the relationship between basic somatic features (body mass and height and body mass loss in physically inactive young women and men exposed to thermal stress in a dry sauna.

  12. 38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis. (United States)


    ... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence...

  13. Reactivation of inactive X chromosome in buccal smear of carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Natekar Prashant


    Full Text Available Buccal mucosal smears of 100 female patients of carcinoma of breast were compared with 100 controls matched accordingly. The frequency of Barr bodies was significantly lower in carcinoma of breast patients (menstruating and menopausal women P < 0.001 when compared with controls indicating reactivation of the inactive X chromosome.

  14. Obesity, smoking, and physical inactivity as risk factors for CKD: Are men more vulnerable?

    NARCIS (Netherlands)

    S. Hallan; R. de Mutsert; S. Carlsen; F.W. Dekker; K. Aasarod; J. Holmen


    Background: The incidence of end-stage renal disease is especially high in men, and some studies indicated that smoking is a risk factor for men only. We investigated associations between obesity, smoking, and physical inactivity and chronic kidney disease (CKD) in the general population and whether

  15. Cosmopolitan Utilitarianism and the Problem of Local Inaction in a Globalized World

    Directory of Open Access Journals (Sweden)

    Fausto Corvino


    Full Text Available This article explores the problem of the public acceptability of political inaction as an extreme consequence of cosmopolitan utilitarianism. The case of political inaction as the utility-maximizing public policy option emerges more clearly in the globalized world, because of a misalignment between the electoral body and the persons that the government ought to consider while evaluating the consequences of a given policy. In this context, a situation can easily occur in which the only way to maximize utility in a global context is by renouncing action at the national or local level. However, the problem of inaction should not be interpreted simply as a by-product of globalization. Its origins can be traced to the basic structure of utilitarianism as a normative consequentialist theory. This drawback can even present itself at the local level in a less visible form. One example is that in which the performance of a supererogatory act in the exercise of public office leads to a reduction in overall utility. The aim of the article is to demonstrate that cosmopolitan utilitarianism can bind the decision maker to a series of inactions at the global and local levels that contradict his own mandate, generating a dangerous moral confusion in the implementation of public policies. This can seriously threaten the universal applicability of cosmopolitan utilitarianism as a normative political theory, especially in the age of globalization.

  16. Comparing Levels of Depression in Healthy Active and Inactive Elders versus Those with Knee Osteoarthritis Disease

    Directory of Open Access Journals (Sweden)

    Amir Shams


    Full Text Available Knee osteoarthritis can have negative effects on the physical and mental conditions, social and family relations, general health and positive feelings of elders. For example, severe limitation of motion and increased depression, which are results of this disease, can have negative impacts on elders. The purpose of this study was to compare the levels of depression in healthy active and inactive elders versus those with knee osteoarthritis disease. Two hundred and twenty (220 elders with knee osteoarthritis disease (110 active and 110 inactive patients and 220 healthy elders (110 active and 110 inactive were voluntarily selected, and they filled the questionnaire about elders’ personal characteristics, physical activity and depression levels. Four groups had differences with respect to education, age and gender. The results of chi-square test revealed that women with knee osteoarthritis disease had increased levels of depression compared to men with the same condition (p<0.05. Older patients had increased levels of depression and educated elders reported lower levels of depression. The results of the one way analysis of variance (ANOVA revealed that there exist a significant difference in depression scores of healthy active and healthy inactive elders and those with knee osteoarthritis disease. The results of Tukey’s test revealed that healthy active elder had lower depression scores compared to inactive elders with knee osteoarthritis disease. Carrying out exercises and physical activities can help improve the health state of patients with knee osteoarthritis problem and can also improve the elders’ mental condition and thus decrease their pain and depression.

  17. A national survey of 'inactive' physicians in the United States of America: enticements to reentry

    Directory of Open Access Journals (Sweden)

    Brotherton Sarah E


    Full Text Available Abstract Background Physicians leaving and reentering clinical practice can have significant medical workforce implications. We surveyed inactive physicians younger than typical retirement age to determine their reasons for clinical inactivity and what barriers, real or perceived, there were to reentry into the medical workforce. Methods A random sample of 4975 inactive physicians aged under 65 years was drawn from the Physician Masterfile of the American Medical Association in 2008. Physicians were mailed a survey about activity in medicine and perceived barriers to reentry. Chi-square statistics were used for significance tests of the association between categorical variables and t-tests were used to test differences between means. Results Our adjusted response rate was 36.1%. Respondents were fully retired (37.5%, not currently active in medicine (43.0% or now active (reentered, 19.4%. Nearly half (49.5% were in or had practiced primary care. Personal health was the top reason for leaving for fully retired physicians (37.8% or those not currently active in medicine (37.8% and the second highest reason for physicians who had reentered (28.8%. For reentered (47.8% and inactive (51.5% physicians, the primary reason for returning or considering returning to practice was the availability of part-time work or flexible scheduling. Retired and currently inactive physicians used similar strategies to explore reentry, and 83% of both groups thought it would be difficult; among those who had reentered practice, 35.9% reported it was difficult to reenter. Retraining was uncommon for this group (37.5%. Conclusion Availability of part-time work and flexible scheduling have a strong influence on decisions to leave or reenter clinical practice. Lack of retraining before reentry raises questions about patient safety and the clinical competence of reentered physicians.

  18. Single Molecule Studies on Dynamics in Liquid Crystals

    Directory of Open Access Journals (Sweden)

    Daniela Täuber


    Full Text Available Single molecule (SM methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC. Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion caused by the guest molecules. The anisotropic structure of LC materials is used to retrieve specific conformation related properties of larger guest molecules like conjugated polymers. This in particular sheds light on organization mechanisms within biological cells, where large molecules are found in nematic LC surroundings. This review gives a short overview related to the application of highly sensitive SM detection schemes in LC.

  19. Single Molecule Biophysics Experiments and Theory

    CERN Document Server

    Komatsuzaki, Tamiki; Takahashi, Satoshi; Yang, Haw; Silbey, Robert J; Rice, Stuart A; Dinner, Aaron R


    Discover the experimental and theoretical developments in optical single-molecule spectroscopy that are changing the ways we think about molecules and atoms The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. This latest volume explores the advent of optical single-molecule spectroscopy, and how atomic force microscopy has empowered novel experiments on individual biomolecules, opening up new frontiers in molecular and cell biology and leading to new theoretical approaches

  20. Redox-inactive metal ions modulate the reactivity and oxygen release of mononuclear non-haem iron(III)-peroxo complexes. (United States)

    Bang, Suhee; Lee, Yong-Min; Hong, Seungwoo; Cho, Kyung-Bin; Nishida, Yusuke; Seo, Mi Sook; Sarangi, Ritimukta; Fukuzumi, Shunichi; Nam, Wonwoo


    Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating the reactivity of oxygen-containing metal complexes and metalloenzymes, such as the oxygen-evolving complex in photosystem II and its small-molecule mimics. Here we report the synthesis and characterization of non-haem iron(III)-peroxo complexes that bind redox-inactive metal ions, (TMC)Fe(III)-(μ,η(2):η(2)-O2)-M(n+) (M(n+) = Sr(2+), Ca(2+), Zn(2+), Lu(3+), Y(3+) and Sc(3+); TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). We demonstrate that the Ca(2+) and Sr(2+) complexes showed similar electrochemical properties and reactivities in one-electron oxidation or reduction reactions. However, the properties and reactivities of complexes formed with stronger Lewis acidities were found to be markedly different. Complexes that contain Ca(2+) or Sr(2+) ions were oxidized by an electron acceptor to release O2, whereas the release of O2 did not occur for complexes that bind stronger Lewis acids. We discuss these results in the light of the functional role of the Ca(2+) ion in the oxidation of water to dioxygen by the oxygen-evolving complex.

  1. Low-volume high-intensity swim training is superior to high-volume low-intensity training in relation to insulin sensitivity and glucose control in inactive middle-aged women

    DEFF Research Database (Denmark)

    Connolly, Luke J; Nordsborg, Nikolai Baastrup; Nyberg, Michael Permin


    to an inactive control (n = 20; CON), a high-intensity low-volume (n = 21; HIT) or a low-intensity high-volume (n = 21; LIT) training group. During the 15-week intervention period, HIT performed 3 weekly 6-10 × 30-s all-out swimming intervals (average heart rate (HR) = 86 ± 3 % HRmax) interspersed by 2-min...... adhesion molecule 1 had decreased (P swimming is an effective and time-efficient training strategy for improving insulin sensitivity, glucose control and biomarkers of vascular function......PURPOSE: We tested the hypothesis that low-volume high-intensity swimming has a larger impact on insulin sensitivity and glucose control than high-volume low-intensity swimming in inactive premenopausal women with mild hypertension. METHODS: Sixty-two untrained premenopausal women were randomised...

  2. Small-molecule control of protein function through Staudinger reduction (United States)

    Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander


    Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

  3. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.


    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  4. Synthetic biology: insights into biological computation. (United States)

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc


    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  5. 3D Studies of Neutral and Ionised Gas and Stars in Seyfert and Inactive Galaxies

    CERN Document Server

    Mundell, C G; Schinnerer, E; Nagar, N; Haan, S; Wilcots, E; Wilson, A S; Emsellem, E; Ferruit, P; Peletier, R F; De Zeeuw, P T


    We are conducting the first systematic 3D spectroscopic imaging survey to quantify the properties of the atomic gas (HI) in a distance-limited sample of 28 Seyfert galaxies and a sample of 28 inactive control galaxies with well-matched optical properties (the VHIKINGS survey). This study aims to address the role of the host galaxy in nuclear activity and confront outstanding controversies in optical/IR imaging surveys. Early results show possible relationships between Seyfert activity and HI extent, content and the prevalence of small, nearby gas-rich dwarf galaxies (M(HI)~10^7 Msun); results will be tested via rigorous comparison with control galaxies. Initial results from our optical followup study of 15 of our galaxies using the SAURON integral field unit on the WHT suggest a possible difference between Seyfert and inactive stellar and gaseous kinematics that support the conclusion that internal kinematics of galaxies are the key to nuclear activity.

  6. Revegetation and rock cover for stabilization of inactive uranium mill tailings disposal sites. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Beedlow, P.A.


    Guidelines for using vegetation and rock to protect inactive uranium mill tailings from erosion were developed by Pacific Northwest Laboratory as part of the Department of Energy's Uranium Mill Tailings Remedial Action Project (UMTRAP) Technology Development program. Information on soils, climate, and vegetation were collected for 20 inactive tailings sites in the western United States. Sites were grouped according to similarities in climate and vegetation. Soil loss for those sites was characterized using the Universal Soil Loss Equation. Test plots were used to evaluate (1) the interaction between vegetation and sealant barrier systems and (2) the effects of surface rock on soil water and vegetation. Lysimeter and simulation studies were used to direct and support field experiments. 49 references, 17 figures, 16 tables.

  7. Heterogeneous reallocation of presynaptic efficacy in recurrent excitatory circuits adapting to inactivity. (United States)

    Mitra, Ananya; Mitra, Siddhartha S; Tsien, Richard W


    Recurrent excitatory circuits face extreme challenges in balancing efficacy and stability. We recorded from CA3 pyramidal neuron pairs in rat hippocampal slice cultures to characterize synaptic and circuit-level changes in recurrent synapses resulting from long-term inactivity. Chronic tetrodotoxin treatment greatly reduced the percentage of connected CA3-CA3 neurons, but enhanced the strength of the remaining connections; presynaptic release probability sharply increased, whereas quantal size was unaltered. Connectivity was decreased in activity-deprived circuits by functional silencing of synapses, whereas three-dimensional anatomical analysis revealed no change in spine or bouton density or aggregate dendrite length. The silencing arose from enhanced Cdk5 activity and could be reverted by acute Cdk5 inhibition with roscovitine. Our results suggest that recurrent circuits adapt to chronic inactivity by reallocating presynaptic weights heterogeneously, strengthening certain connections while silencing others. This restricts synaptic output and input, preserving signaling efficacy among a subset of neuronal ensembles while protecting network stability.

  8. A new algorithm for inactive orbital optimization in valence bond theory

    Institute of Scientific and Technical Information of China (English)

    CHEN ZhenHua; ZHANG QianEr; WU Wei


    This paper presents an efficient algorithm for energy gradients in valence bond self-consistent field (VBSCF) method with non-orthogonal orbitals.The frozen core approximation method is extended to the case of non-orthogonal orbitals.The expressions for the total energy and its gradients are presented by introducing auxiliary orbitals,where inactive orbitals are orthogonal,while active orbitals are non-orthogonal themselves but orthogonal to inactive orbitsls.It is shown that our new algorithm has a low scaling of (N_a+ 1)m~4,where N_a and m are the numbers of the active orbitals and basis functions,respectively,and is more efficient than the existing VBSCF algorithms.

  9. A new algorithm for inactive orbital optimization in valence bond theory

    Institute of Scientific and Technical Information of China (English)


    This paper presents an efficient algorithm for energy gradients in valence bond self-consistent field(VBSCF) method with non-orthogonal orbitals.The frozen core approximation method is extended to the case of non-orthogonal orbitals.The expressions for the total energy and its gradients are presented by introducing auxiliary orbitals,where inactive orbitals are orthogonal,while active orbitals are non-orthogonal themselves but orthogonal to inactive orbitals.It is shown that our new algorithm has a low scaling of(Na+1)m4,where Na and m are the numbers of the active orbitals and basis functions,respectively,and is more efficient than the existing VBSCF algorithms.

  10. The effects of exergaming on physical activity among inactive children in a physical education classroom. (United States)

    Fogel, Victoria A; Miltenberger, Raymond G; Graves, Rachel; Koehler, Shannon


    Childhood obesity, which is due in part to lack of physical activity, is a serious concern that requires the attention of the behavioral community. Although excessive video game play has been noted in the literature as a contributor to childhood obesity, newer video gaming technology, called exergaming, has been designed to capitalize on the reinforcing effects of video games to increase physical activity in children. This study evaluated the effects of exergaming on physical activity among 4 inactive children in a physical education (PE) classroom. Results showed that exergaming produced substantially more minutes of physical activity and more minutes of opportunity to engage in physical activity than did the standard PE program. In addition, exergaming was socially acceptable to both the students and the PE teacher. Exergaming appears to hold promise as a method for increasing physical activity among inactive children and might be a possible intervention for childhood obesity.

  11. Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Cannioto, Rikki A; LaMonte, Michael J; Kelemen, Linda E


    and mortality. METHODS: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models......BACKGROUND: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity.......12-1.33) further adjustment for residual disease, respectively. CONCLUSION: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC....

  12. Influence of radiative processes on the ignition of deuterium-tritium plasma containing inactive impurities (United States)

    Gus'kov, S. Yu.; Sherman, V. E.


    The degree of influence of radiative processes on the ignition of deuterium-tritium (DT) plasma has been theoretically studied as dependent on the content of inactive impurities in plasma. The analytic criterion of plasma ignition in inertial confinement fusion (ICF) targets is modified taking into account the absorption of intrinsic radiation from plasma in the ignition region. The influence of radiative processes on the DT plasma ignition has been analytically and numerically studied for plasma that contains a significant fraction of inactive impurities either as a result of DT fuel mixing with ICF target ablator material or as a result of using light metal DT-hydrides as solid noncryogenic fuel. It has been shown that the effect of the absorption of intrinsic radiation leads to lower impurity-induced increase in the ignition energy as compared to that calculated in the approximation of optically transparent ignition region.

  13. The burden of abdominal obesity with physical inactivity on health expenditure in Brazil

    Directory of Open Access Journals (Sweden)

    Jamile S. Codogno


    Full Text Available The purpose of this study was to analyze the association between the clustering of physical inactivity with abdominal obesity and public health care expenditure in Brazilian adults. The sample was composed of 963 patients of both genders, randomly selected in the Brazilian Public Health care System during 2010. Entire health care expenditures during the last year were computed and stratified into: medical consultations, medication dispensing, laboratory tests and overall expenditure. Waist circumference was used to diagnose abdominal obesity and physical activity was assessed by previously validated questionnaire. Sedentary and abdominally obese patients (OR= 3.01 [OR95%CI= 1.81-4.99] had higher likelihood be inserted in the group of higher expenditures than only abdominally obese patients (OR= 1.66 [OR95%CI= 1.07-2.59]. There is a synergic effect between abdominal obesity and physical inactivity on overall health care expenditures.

  14. Food reward in active compared to inactive men: Roles for gastric emptying and body fat. (United States)

    Horner, Katy M; Finlayson, Graham; Byrne, Nuala M; King, Neil A


    Habitual exercise could contribute to weight management by altering processes of food reward via the gut-brain axis. We investigated hedonic processes of food reward in active and inactive men and characterised relationships with gastric emptying and body fat. Forty-four men (active: n=22; inactive: n=22, BMI range 21-36kg/m(2); percent fat mass range 9-42%) were studied. Participants were provided with a standardised fixed breakfast and an ad libitum lunch meal 5h later. Explicit liking, implicit wanting and preference among high-fat, low-fat, sweet and savoury food items were assessed immediately post-breakfast (fed state) and again pre-lunch (hungry state) using the Leeds Food Preference Questionnaire. Gastric emptying was assessed by (13)C-octanoic acid breath test. Active individuals exhibited a lower liking for foods overall and a greater implicit wanting for low-fat savoury foods in the fed state, compared to inactive men. Differences in the fed state remained significant after adjusting for percent fat mass. Active men also had a greater increase in liking for savoury foods in the interval between breakfast and lunch. Faster gastric emptying was associated with liking for savoury foods and with an increase in liking for savoury foods in the postprandial interval. In contrast, greater implicit wanting for high-fat foods was associated with slower gastric emptying. These associations were independent of each other, activity status and body fat. In conclusion, active and inactive men differ in processes of food reward. The rate of gastric emptying may play a role in the association between physical activity status and food reward, via the gut-brain axis.

  15. Differences in some physical characteristics and motor abilities at dance active and dance inactive children


    Petrič, Anja


    In Degree dissertation titled “Differences in some physical characteristics and motor abilities at dance active and dance inactive children” we compared some physical characteristics and motor abilities in the two groups of children: the ones that are taking the interests in dance and the ones that are not interested in dance. In theoretical part of dissertation we presented the offer of dance schools in Slovenia, projects School dance festival, recognition of dance in elementary schools, in...

  16. Pyridinediimine Iron Complexes with Pendant Redox-Inactive Metals Located in the Secondary Coordination Sphere. (United States)

    Delgado, Mayra; Ziegler, Joshua M; Seda, Takele; Zakharov, Lev N; Gilbertson, John D


    A series of pyridinediimine (PDI) iron complexes that contain a pendant 15-crown-5 located in the secondary coordination sphere were synthesized and characterized. The complex Fe((15c5)PDI)(CO)2 (2) was shown in both the solid state and solution to encapsulate redox-inactive metal ions. Modest shifts in the reduction potential of the metal-ligand scaffold were observed upon encapsulation of either Na(+) or Li(+).

  17. Formation of Ultracold Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cote, Robin [Univ. of Connecticut, Storrs, CT (United States)


    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  18. Inactive vaccine derived from velogenic strain of local Newcastle disease virus .

    Directory of Open Access Journals (Sweden)



    Full Text Available The objective of this research is to evaluate an application of an inactive Newcastle disease (ND vaccine derived from velogenic strain of local Newcastle disease virus (NDV. In this research . the Ira strain of velogenic ND virus was grown in specific pathogen free (SPF eggs and then was inactivated by formalin at a final concentration of 1 :1,000 at 4°C. The inactive antigen was then emulsified with an oil adjuvant or aluminium hydroxide gel before being administered for vaccination in layers and compared to a commercial inactive ND vaccine . Results indicated that application of these inactivated ND vaccines for booster vaccination following vaccination with an active lentogenic ND virus in pullets nearly producing eggs, resulted in high antibody titre which persisted for considerable long period of time and capable of protecting layers from sick of ND and from reducing egg production . Hence, it could be concluded that the inactivated vaccine emulsified in either oil-adjuvant (lanolin-paraffin or aluminium hydroxide gel were considered to be highly immunogenic and capable of protecting layers from sick of ND and from reducing egg production

  19. Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Charlotte Proudhon


    Full Text Available V(DJ recombination relies on the presence of proximal enhancers that activate the antigen receptor (AgR loci in a lineage- and stage-specific manner. Unexpectedly, we find that both active and inactive AgR enhancers cooperate to disseminate their effects in a localized and long-range manner. Here, we demonstrate the importance of short-range contacts between active enhancers that constitute an Igk super-enhancer in B cells. Deletion of one element reduces the interaction frequency between other enhancers in the hub, which compromises the transcriptional output of each component. Furthermore, we establish that, in T cells, long-range contact and cooperation between the inactive Igk enhancer MiEκ and the active Tcrb enhancer Eβ alters enrichment of CBFβ binding in a manner that impacts Tcrb recombination. These findings underline the complexities of enhancer regulation and point to a role for localized and long-range enhancer-sharing between active and inactive elements in lineage- and stage-specific control.

  20. A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

    Directory of Open Access Journals (Sweden)

    Florbela Pereira


    Full Text Available The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.

  1. New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: design, synthesis, structure-activity relationships and biological evaluation. (United States)

    Fortin, Sébastien; Brasseur, Kevin; Morin, Nathalie; Asselin, Éric; Bérubé, Gervais


    Prostate cancer is a major public health problem worldwide and, more specifically, new treatments for hormone-refractory cancers are highly sought by several research groups. Although platinum(II)-based chemotherapy and other strategies grow in interest to treat castration-resistant prostate cancer (CRPC), they still exhibit modest activity on CRPC and overall patient survival. In this study, we designed and prepared new combi-molecules using 17β-acetyl-testosterone and amino acid platinum(II) complexes linked at the position 7α to target and to improve the antiproliferative activity of platinum(II)-based chemotherapy on prostate cancer cells. Twelve chemical intermediates and six new combi-molecules were prepared and characterized. Structure-activity relationships studies show that the platinum complex moiety is essential for an optimal cytocidal activity. Moreover, stereochemistry of the amino acid involved in the platinum complexes had only minor effects on the antiproliferative activity whereas pyridinyl (10a and b) and thiazolyl (10f) complexes exhibited the highest cytocidal activities that are significantly superior to that of cisplatin used as control on human prostate adenocarcinoma LNCaP (AR+), PC3 (AR-) and DU145 (AR-). Compounds 10a, b and f arrested the cell cycle progression in S-phase and induced double strand breaks as confirmed by the phosphorylation of histone H2AX into γH2AX. Compounds 10a and f showed 33 and 30% inhibition, respectively of the growth of HT-1080 tumors grafted onto chick chorioallantoic membranes. Finally, compounds 10a and 10f exhibited low toxicity on the chick embryos (18 and 21% of death, respectively), indicating that these new combi-molecules might be a promising new class of anticancer agents for prostate cancer.

  2. Evidence for the importance of openness to experience on performance of a fluid intelligence task by physically active and inactive participants. (United States)

    Lochbaum, Marc R; Karoly, Paul; Landers, Daniel M


    The cross-sectional relationship between exercise training history and performance on a fluid intelligence test was examined. In addition, openness to experience was included as a potential trait-based contributor to predicting cognitive performance. Results supported past literature demonstrating that aerobically trained or active participants performed significantly better on the fluid intelligence task than aerobically untrained or inactive participants. Hierarchical regression analysis results revealed, as predicted, that openness to experience was a significant predictor of fluid intellectual performance. When entered into the hierarchical regression equation, openness to experience accounted for 16.0% of unique variance in Culture Fair Intelligence Test performance. By contrast, participants' exercise training history, which initially and significantly (p performance, accounted for 5.0% (p > .05) after openness was entered. Participants were, on average, more open than inactive participants. Results are discussed in terms of the possible mechanisms aerobic exercise training and openness to experience share in regard to brain functioning and performance of fluid intelligence tasks. Future research is suggested that examines biological factors known to influence cognitive performance in exercise settings.

  3. Spectroscopic capture and reactivity of a low-spin cobalt(IV)-oxo complex stabilized by binding redox-inactive metal ions. (United States)

    Hong, Seungwoo; Pfaff, Florian F; Kwon, Eunji; Wang, Yong; Seo, Mi-Sook; Bill, Eckhard; Ray, Kallol; Nam, Wonwoo


    High-valent cobalt-oxo intermediates are proposed as reactive intermediates in a number of cobalt-complex-mediated oxidation reactions. Herein we report the spectroscopic capture of low-spin (S=1/2) Co(IV)-oxo species in the presence of redox-inactive metal ions, such as Sc(3+), Ce(3+), Y(3+), and Zn(2+), and the investigation of their reactivity in C-H bond activation and sulfoxidation reactions. Theoretical calculations predict that the binding of Lewis acidic metal ions to the cobalt-oxo core increases the electrophilicity of the oxygen atom, resulting in the redox tautomerism of a highly unstable [(TAML)Co(III)(O˙)](2-) species to a more stable [(TAML)Co(IV)(O)(M(n+))] core. The present report supports the proposed role of the redox-inactive metal ions in facilitating the formation of high-valent metal-oxo cores as a necessary step for oxygen evolution in chemistry and biology.

  4. Evidence of water molecules--a statistical evaluation of water molecules based on electron density. (United States)

    Nittinger, Eva; Schneider, Nadine; Lange, Gudrun; Rarey, Matthias


    Water molecules play important roles in many biological processes, especially when mediating protein-ligand interactions. Dehydration and the hydrophobic effect are of central importance for estimating binding affinities. Due to the specific geometric characteristics of hydrogen bond functions of water molecules, meaning two acceptor and two donor functions in a tetrahedral arrangement, they have to be modeled accurately. Despite many attempts in the past years, accurate prediction of water molecules-structurally as well as energetically-remains a grand challenge. One reason is certainly the lack of experimental data, since energetic contributions of water molecules can only be measured indirectly. However, on the structural side, the electron density clearly shows the positions of stable water molecules. This information has the potential to improve models on water structure and energy in proteins and protein interfaces. On the basis of a high-resolution subset of the Protein Data Bank, we have conducted an extensive statistical analysis of 2.3 million water molecules, discriminating those water molecules that are well resolved and those without much evidence of electron density. In order to perform this classification, we introduce a new measurement of electron density around an individual atom enabling the automatic quantification of experimental support. On the basis of this measurement, we present an analysis of water molecules with a detailed profile of geometric and structural features. This data, which is freely available, can be applied to not only modeling and validation of new water models in structural biology but also in molecular design.

  5. Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Klein-Seetharaman Judith


    Full Text Available Abstract Metabotropic glutamate receptors (mGluRs are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is experimentally known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. We find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%, the negative modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%, the positive modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86% and 8/9 (89% for ArgusLab and 10/14 (71% and 7/9 (78% for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by


    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko


    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposi-tion of human activity and inactivity that may lead to a profound understanding of the essence, causes and existen-tial aspects of human activity and inactivity. The implementation of the objective assumes the solution of the follow-ing tasks: analysis of philosophical interpretation of fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inac-tivity through the opposition of fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of hu-man activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authen-tic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific nov-elty. For the first time the analysis of the fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the fundamental existential character of the fear and courage opposition and its es-sential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being. If classical philosophy placed emphasis on courage and associated fear with human mind and conscious decision, non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental mean

  7. The prevalence and correlates of physical inactivity among adults in Ho Chi Minh City

    Directory of Open Access Journals (Sweden)

    Phongsavan Philayrath


    Full Text Available Abstract Background Socioeconomic changes have led to profound changes in individuals' lifestyles, including the adoption of unhealthy food consumption patterns, prevalent tobacco use, alcohol abuse and physical inactivity, especially in large cities like Ho Chi Minh City (HCMC. The Stepwise Approach to Surveillance of Non-communicable Disease Risk Factors survey was conducted to identify physical activity patterns and factors associated with 'insufficient' levels of physical activity for health in adults in HCMC. Methods A cross-sectional survey was conducted in 2005 among 1906 adults aged 25–64 years using a probability proportional to size cluster sampling method to estimate the prevalence of non-communicable disease risk factors including physical inactivity. Data on socioeconomic status, health behaviours, and time spent in physical activity during work, commuting and leisure time were collected. Physical activity was measured using the validated Global Physical Activity Questionnaire (GPAQ. Responders were classified as 'sufficiently active' or 'insufficiently active' using the GPAQ protocol. Correlates of insufficient physical activity were identified using multivariable logistic regression. Results A high proportion of adults were physically inactive, with only 56.2% (95% CI = 52.1–60.4 aged 25–64 years in HCMC achieving the minimum recommendation of 'doing 30 minutes moderate-intensity physical activity for at least 5 days per week'. The main contributors to total physical activity among adults were from working and active commuting. Leisure-time physical activity represented a very small proportion (9.4% of individuals' total activity level. Some differences in the pattern of physical activity between men and women were noted, with insufficient activity levels decreasing with age among women, but not among men. Physical inactivity was positively associated with high income (OR = 1.77, 95% CI = 1.05–2.97 and high household

  8. Trapping molecules on chips

    CERN Document Server

    Santambrogio, Gabriele


    In the last years, it was demonstrated that neutral molecules can be loaded on a microchip directly from a supersonic beam. The molecules are confined in microscopic traps that can be moved smoothly over the surface of the chip. Once the molecules are trapped, they can be decelerated to a standstill, for instance, or pumped into selected quantum states by laser light or microwaves. Molecules are detected on the chip by time-resolved spatial imaging, which allows for the study of the distribution in the phase space of the molecular ensemble.

  9. [Endothelial cell adhesion molecules]. (United States)

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu


    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  10. Diamond based single molecule magnetic resonance spectroscopy

    CERN Document Server

    Cai, J -M; Plenio, M B; Retzker, A


    The detection of a nuclear spin in an individual molecule represents a key challenge in physics and biology whose solution has been pursued for many years. The small magnetic moment of a single nucleus and the unavoidable environmental noise present the key obstacles for its realization. Here, we theoretically demonstrate that a single nitrogen-vacancy (NV) center in diamond can be used to construct a nano-scale single molecule spectrometer that is capable of detecting the position and spin state of a single nucleus and can determine the distance and alignment of a nuclear or electron spin pair. In combination with organic spin labels, this device will find applications in single molecule spectroscopy in chemistry and biology, such as in determining protein structure or monitoring macromolecular motions and can thus provide a tool to help unravelling the microscopic mechanisms underlying bio-molecular function.

  11. Inducible removal of UV-induced pyrimidine dimers from transcriptionally active and inactive genes of Saccharomyces cerevisiae. (United States)

    Waters, R; Zhang, R; Jones, N J


    The prior UV irradiation of alpha haploid Saccharomyces cerevisiae with a UV dose of 25 J/m2 substantially increases the repairability of damage subsequently induced by a UV dose of 70 J/m2 given 1 h after the first irradiation. This enhancement of repair is seen at both the MAT alpha and HML alpha loci, which are, respectively, transcriptionally active and inactive in alpha haploid cells. The presence in the medium of the protein synthesis inhibitor, cycloheximide in the period between the two irradiations eliminated this effect. Enhanced repair still occurred if cycloheximide was present only after the final UV irradiation. This indicated that the first result is not due to cycloheximide merely blocking the synthesis of repair enzymes associated with a hypothetical rapid turnover of such molecules. The enhanced repairability is not the result of changes in chromatin accessibility without protein synthesis, merely caused by the repair of the damage induced by the prior irradiation. The data clearly show that a UV-inducible removal of pyrimidine dimers has occurred which involves the synthesis of new proteins. The genes known to possess inducible promoters, and which are involved in excision are RAD2, RAD7, RAD16 and RAD23. Studies with the rad7 and rad16 mutants which are defective in the ability to repair HML alpha and proficient in the repair of MAT alpha showed that in rad7, preirradiation enhanced the repair at MAT alpha, whereas in rad16 this increased repair of MAT alpha was absent. The preirradiation did not modify the inability to repair HML alpha in either strain. Thus RAD16 has a role in this inducible repair.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Effect of the Mn Oxidation State on Single-Molecule-Magnet Properties: Mn(III) vs Mn(IV) in Biologically Inspired DyMn3O4 Cubanes. (United States)

    Lin, Po-Heng; Tsui, Emily Y; Habib, Fatemah; Murugesu, Muralee; Agapie, Theodor


    Inspired by the ferromagnetic coupling in the cubane model CaMn(IV)3O4 of the oxygen-evolving complex of photosystem II, 3d-4f mixed-metal DyMn3O4 clusters were prepared for investigation of the magnetic properties. For comparison, YMn(IV)3O4 and YMn(IV)2Mn(III)O4 clusters were investigated as well and showed ferromagnetic interactions, like the calcium analogue. DyMn(IV)3O4 displays single-molecule-magnet properties, while the one-electron-reduced species (DyMn(IV)2Mn(III)O4) does not, despite the presence of a Mn(III) center with higher spin and single-ion anisotropy.


    NARCIS (Netherlands)


    In this paper, some results obtained on the formation of isolated molecules of composition SnOx in silver and SnFx in copper-are reviewed. Hyperfine interaction and ion beam interaction techniques were used for the identification of these molecules.

  14. Algebraic theory of molecules

    CERN Document Server

    Iachello, F


    1. The Wave Mechanics of Diatomic Molecules. 2. Summary of Elements of Algebraic Theory. 3. Mechanics of Molecules. 4. Three-Body Algebraic Theory. 5. Four-Body Algebraic Theory. 6. Classical Limit and Coordinate Representation. 8. Prologue to the Future. Appendices. Properties of Lie Algebras; Coupling of Algebras; Hamiltonian Parameters

  15. Basic Principle of Molecular Dynamics and Application in The Filed of Biologic Molecules Simulation%分子动力学模拟及在生物大分子模拟领域的应用

    Institute of Scientific and Technical Information of China (English)



    简要介绍了分子动力学的发展历史、基本理论、基本步骤以及其作为基本研究手段来进行生物大分子模拟领域的应用。%This article briefly describes the molecular dynamics of development history,basic theory,basic steps and basic research as a means to carry out simulation in the field of application of biological macromolecules.

  16. Molecules in galaxies

    CERN Document Server

    Omont, Alain


    The main achievements, current developments and prospects of molecular studies in external galaxies are reviewed. They are put in the context of the results of several decades of studies of molecules in local interstellar medium, their chemistry and their importance for star formation. CO observations have revealed the gross structure of molecular gas in galaxies. Together with other molecules, they are among the best tracers of star formation at galactic scales. Our knowledge about molecular abundances in various local galactic environments is progressing. They trace physical conditions and metallicity, and they are closely related to dust processes and large aromatic molecules. Major recent developments include mega-masers, and molecules in Active Galactic Nuclei; millimetre emission of molecules at very high redshift; and infrared H2 emission as tracer of warm molecular gas, shocks and photodissociation regions. The advent of sensitive giant interferometers from the centimetre to sub-millimetre range, espe...

  17. Depressive symptoms are associated with physical inactivity in patients with type 2 diabetes. The DIAZOB Primary Care Diabetes study

    DEFF Research Database (Denmark)

    Koopmans, Berber; Pouwer, Francois; de Bie, Robert A


    BACKGROUND: Depression is a common complication of type 2 diabetes, associated with poor disease outcomes such as impaired glycaemic control, cardiovascular disease and increased mortality. The mechanisms behind these associations are unclear. Depression might contribute to poor disease outcomes...... through decreased physical activity. OBJECTIVE: To test whether type 2 diabetes patients with elevated depression scores are more often physically inactive. METHODS: Demographic features, clinical factors, level of physical inactivity and depressive symptoms were assessed in 2646 primary care patients...... with type 2 diabetes. Sequential multiple logistic regression analyses [odds ratio, 95% confidence interval (CI)] were performed to test the association between depressive symptoms and physical inactivity. RESULTS: About 48% of the respondents were physically inactive. Elevated depressive symptoms were...

  18. Effect of inactive yeast cell wall on growth performance, survival rate and immune parameters in Pacific White Shrimp (Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    Rutchanee Chotikachinda


    Full Text Available Effects of dietary inactive yeast cell wall on growth performance, survival rate, and immune parameters in pacific white shrimp (Litopenaeus vannamei was investigated. Three dosages of inactive yeast cell wall (0, 1, and 2 g kg-1 were tested in three replicate groups of juvenile shrimps with an average initial weight of 7.15±0.05 g for four weeks. There was no significant difference in final weight, survival rate, specific growth rate, feed conversion ratio, feed intake, protein efficiency ratio, and apparent net protein utilization of each treatments. However, different levels of inactive yeast cell wall showed an effect on certain immune parameters (p<0.05. Total hemocyte counts, granular hemocyte count, and bacterial clearance were better in shrimp fed diets supplemented with 1 and 2 g kg-1 inactive yeast cell wall as compared with thecontrol group.

  19. Administration of additional inactive iodide during radioiodine therapy for Graves' disease. Who might benefit?

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Moka, D.; Reinholz, U.; Schmidt, M.; Schomaecker, K.; Schicha, H.; Wellner, U. [Koeln Univ. (Germany). Dept. of Nuclear Medicine


    Aim: Graves' hyperthyroidism and antithyroid drugs empty the intrathyroid stores of hormones and iodine. The consequence is rapid {sup 131}I turnover and impending failure of radioiodine therapy. Can administration of additional inactive iodide improve 131I kinetics? Patients, methods: Fifteen consecutive patients, in whom the 48 h post-therapeutically calculated thyroid dose was between 150 and 249 Gy due to an unexpectedly short half-life, received 3 x 200 {mu}g inactive potassium-iodide ({sup 127}I) daily for 3 days (Group A), while 17 consecutive patients with a thyroid dose of = 250 Gy (Group B) served as the non-iodide group. 48 hours after {sup 131}I administration (M1) and 4 or 5 days later (M2) the following parameters were compared: effective {sup 131}I half-life, thyroid dose, total T3, total T4, {sup 131}I-activity in the T3- and T4-RIAs. Results: In Group A, the effective {sup 131}I half-life M1 before iodine (3.81 {+-} 0.93 days) was significantly (p <0.01) shorter than the effective {sup 131}I half-life M2 (4.65 {+-} 0.79 days). Effective {sup 131}I half-life M1 correlated with the benefit from inactive {sup 127}I (r = -0.79): Administration of {sup 127}I was beneficial in patients with an effective {sup 131}I half-life M1 of <3 or 4 days. Patients from Group A with high initial specific {sup 131}I activity of T3 and T4 showed lower specific {sup 131}I activity after addition of inactive iodine compared with patients from the same group with a lower initial specific {sup 131}I activity of T3 and T4 and compared with the patient group B who was given no additional inactive iodide. This correlation was mathematically described and reflected in the flatter gradient in Group A (y = 0.5195x + 0.8727 for {sup 131}I T3 and y = 1.0827x - 0.4444 for {sup 131}I T4) and steeper gradient for Group B (y = 0.6998x + 0.5417 for {sup 131}I T3 and y = 1.3191x - 0.2901 for {sup 131}I T4). Radioiodine therapy was successful in all 15 patients from Group A

  20. Physical inactivity prevalence and trends among Mexican adults: results from the National Health and Nutrition Survey (ENSANUT) 2006 and 2012



    Background Lifestyles such as unhealthy diets and the lack of physical activity have been contributed to the increased prevalence of obesity. In 2012, the world health organization published the first global recommendation for physical activity and health. People who do not meet at least 150 minutes of moderate-to-vigorous physical activity are considered to be physically inactive. The prevalence of physical inactivity worldwide is 31%, however there is insufficient data from prevalence and t...

  1. Anthropometric measurements of students athletes in relation to physically inactive students

    Directory of Open Access Journals (Sweden)

    Namik Trtak


    Full Text Available Introduction: Anthropometry is a method of anthropology that refers to the measuring and testing the human body and to the relationship between the size of its individual parts.The task of anthropometry is as accurately as possible quantitatively characterize the morphological features of the human body.Measurements are made due to the anthropometric points which can be: fixed (standard on the site of prominence and virtual (change due to the bodyposition. Goals of research: To evaluate the impact of basketball on the growth and development of seventeen years old adolescents and prevention of deformities of the spinal column and chest.Methods: The study included 40 respondents. Criteria for inclusion: male respondents aged 17 years who played basketball for more than one year, male respondents aged 17 years who are physically inactive. Criteria for exclusion: female respondents, respondents who played basketball for less than one year, respondents who are engaged in some other sport professionally or recreationally, respondents younger and olderthan 17 years. In the study,there were made measurements of thorax scope in the axillary and mamilar level, measurements of body weight and height and measurements of Body mass index.Results of research: Out of 40 respondents 20 are basketball players and 20 physically inactive. Compared to the average value between the two groups of respondents certain differences were observed, which aremost noticeable in body weight (basketball players had more weigh about, 5 kg on average and height (basketball players are taller, about 7 cm on average. During the anthropometric measurements of thoraxdeformities of the spinal column have been observed which affect the deformation of the thorax. Of the 20 players one has a deformity of the spinal column, and out of the same number of physically inactive studentseven 12 have deformed spine.Conclusion: Basketball has a positive effect on the proper growth and development

  2. Dynamics of Activated Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Mullin, Amy S. [Univ. of Maryland, College Park, MD (United States)


    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  3. Therapy of ovarian inactivity in postpartum Bulgarian Murrah buffaloes by PRID and Ovsynch estrus synchronization protocols

    Institute of Scientific and Technical Information of China (English)

    Stanimir Yotov; Anatoli Atanasov; Yordanka Ilieva


    Objective:The aim of the present study was to assess therapeutical effect of modified Ovsynch and PRID estrus synchronization protocols in Bulgarian Murrah buffalo with inactive ovaries during the low-breeding season. Methods:The study was carried out in 46 Bulgarian Murrah buffaloes with small inactive ovaries established by two consecutive transrectal ultrasonographies on Day 40 and 50 postpartum. At the start of the therapy the buffaloes were randomly divided into three groups. Group I (n=18) was treated by PRID-based protocol;Group II (n=18) was treated by Ovsynch based protocol and Group III (control;n=10) was injected intramuscular with saline at the same days as in the first two groups and fertile bull was introduced after that. The animals in the different groups were submitted to ultrasound examination at day of artificial insemination or bull introduction. Ovulation was determined 7 days post insemination by ultrasound. The pregnancy diagnosis was done 30 days after insemination. Mean diameter of the largest follicles at the start of therapy and the day of AI was registered. In the hormonal treated buffaloes estrus clinical sings, ovulation rate and pregnancy rate after AI were determined. In the control group pregnancy rate after spontaneous estrus was established. The mean diameter of the largest follicles determined on Days 40 and 50 after calving was not over 9 mm for all buffaloes. Results:At day of AI the average diameters of the preo-vulatory follicles in PRID and Ovsynch treated buffaloes were significantly (P<0.01) greater than these on Day 0. The cases of a clear uterine mucus discharge during the induced estrus were significant more (P<0.05) for Group I (94.4%) than Group II (66.7%). The pregnancy rate after AI (56.6%and 38.8%) in PRID and Ovsynch program was significant higher (P<0.05) than pregnancy rate after spontaneous estrus (10%) in the control group. Conclusions:the treatment of buffalo ovarian inactivity could start on Day 50

  4. The black hole - bulge mass relation in active and inactive galaxies


    McLure, R. J.; Dunlop, J. S.


    New virial black-hole mass estimates are presented for a sample of 72 AGN covering three decades in optical luminosity. Using a model in which the AGN broad-line region (BLR) has a flattened geometry, we investigate the M_{bh)-L_{bulge} relation for a combined 90-object sample, consisting of the AGN plus a sample of 18 nearby inactive elliptical galaxies with dynamical black-hole mass measurements. It is found that, for all reasonable mass-to-light ratios, the M_{bh}-L_{bulge} relation is equ...

  5. Assessment of the Radiological Impact of the Inactive Uranium-Mill Tailings at Mexican Hat, Utah


    Haywood, F. F.; Goldsmith, W. A.; Ellis, B. S.; Hubbard Jr., H. M.; Fox, W. F.; Shinpaugh, W. H.; Oak Ridge National Laboratory


    High surface soil concentrations of 226Ra and high above-ground measurements of gamma-ray intensity in the vicinity of the inactive uranium-mill tailings at Mexican Hat show both wind and water erosion of the tailings. The former mill area, occupied by a trade school at the time of this survey, shows a comparatively high level of contamination, probably from unprocessed ore on the surface of the ore storage area near the location of the former mill buildings. However, the estimated health e...

  6. Chronic fatigue syndrome in an ethnically diverse population: the influence of psychosocial adversity and physical inactivity

    Directory of Open Access Journals (Sweden)

    Wessely Simon


    Full Text Available Abstract Background Chronic fatigue syndrome (CFS is a complex multifactorial disorder. This paper reports the prevalence of chronic fatigue (CF and CFS in an ethnically diverse population sample and tests whether prevalence varies by social adversity, social support, physical inactivity, anxiety and depression. Methods Analysis of survey data linking the Health Survey for England (1998 and 1999 and the Ethnic Minority Psychiatric Illness Rates in the Community (EMPIRIC study undertaken in 2000. The study population comprised a national population sample of 4,281 people ages 16 to 74 years. CF and CFS were operationally defined on the basis of an interview in the EMPIRIC study, alongside questions about psychosocial risk factors. Previous illnesses were reported in the Health Survey for England during 1998 and 1999, as was physical inactivity. Results All ethnic minority groups had a higher prevalence of CFS than the White group. The lowest prevalence was 0.8% in the White group, and it was highest at 3.5% in the Pakistani group (odds ratio (OR, 4.1; 95% confidence interval (95% CI, 1.6 to 10.4. Anxiety (OR, 1.8; 95% CI, 1.4 to 2.2, depression (OR, 1.4; 95% CI, 1.1 to 1.8, physical inactivity (OR, 2.0; 95% CI, 1.1 to 3.8, social strain (OR, 1.24; 95% CI, 1.04 to 1.48 and negative aspects of social support (OR, 2.12; 95% CI, 1.4 to 3.3 were independent risk factors for CFS in the overall sample. Together these risk factors explained ethnic differences in the prevalence of CFS, but no single risk factor could explain a higher prevalence in all ethnic groups. Conclusions The prevalence of CFS, but not CF, varies by ethnic group. Anxiety, depression, physical inactivity, social strain and negative aspects of social support together accounted for prevalence differences of CFS in the overall sample.

  7. Physical inactivity affects skeletal muscle insulin signaling in a birth weight-dependent manner

    DEFF Research Database (Denmark)

    Mortensen, Brynjulf; Friedrichsen, Martin; Andersen, Nicoline Resen;


    AIMS: We investigated whether physical inactivity could unmask defects in insulin and AMPK signaling in low birth weight (LBW) subjects. METHODS: Twenty LBW and 20 normal birth weight (NBW) subjects were investigated using the euglycemic-hyperinsulinemic clamp with excision of skeletal muscle...... is not explained by impaired muscle insulin or AMPK signaling in subjects with or without LBW. Lower muscle insulin signaling in LBW subjects post bed rest despite similar degree of insulin resistance as seen in controls may to some extent support the idea that LBW subjects are at higher risk of developing type 2...

  8. An Internet-Based Physical Activity Intervention to Improve Quality of Life of Inactive Older Adults

    DEFF Research Database (Denmark)

    Broekhuizen, Karen; de Gelder, Jelle; Wijsman, Carolien A


    BACKGROUND: Increasing physical activity is a viable strategy for improving both the health and quality of life of older adults. OBJECTIVE: The aim of this study was to assess if an Internet-based intervention aimed to increase physical activity was effective in improving quality of life of inact......-based physical activity program was effective in improving quality of life in 60-70-year-olds after 3 months, particularly in participants that reached their individually targeted increase in daily physical activity. TRIAL REGISTRATION: Nederlands Trial Register: NTR 3045; http...

  9. Remedial action plan for stabilization of the inactive uranium mill tailings site at Monument Valley, Arizona

    Energy Technology Data Exchange (ETDEWEB)



    This Remedial Action Plan (RAP) has been developed to serve a two-fold purpose. It presents the series of activities which are proposed by the U.S. Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site located near Monument Valley, Arizona It also serves to document the concurrence of both the Navajo Nation and the U.S. Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by DOE and the Navajo Nation and concurrence by NRC, becomes Appendix B of the Cooperative Agreement.

  10. Dynamic gadolinium-enhanced MR imaging in active and inactive immunoinflammatory gonarthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Lorenzen, I; Henriksen, O


    examined 16 clinically active (CAG), 7 clinically inactive (CIG) and 4 healthy knees. The synovium of a preselected slice was outlined. Its area and relative signal intensity increase after gadopentetate dimeglumine on T1-SE and FLASH (at each time t) were calculated. The CAG knees showed a mean signal...... intensity increase on early dynamic FLASH images higher by far than the CIG knees, while no significant difference was found on spin-echo images obtained 5 to 15 min after contrast injection. The early signal enhancement probably reflects the perfusion and capillary permeability of the synovium. The area...

  11. Electron correlation in molecules

    CERN Document Server

    Wilson, S


    Electron correlation effects are of vital significance to the calculation of potential energy curves and surfaces, the study of molecular excitation processes, and in the theory of electron-molecule scattering. This text describes methods for addressing one of theoretical chemistry's central problems, the study of electron correlation effects in molecules.Although the energy associated with electron correlation is a small fraction of the total energy of an atom or molecule, it is of the same order of magnitude as most energies of chemical interest. If the solution of quantum mechanical equatio

  12. Heavy Exotic Molecules

    CERN Document Server

    Liu, Yizhuang


    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general strictures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with $J^{PC}=1^{++}$ binds, which we identify as the reported neutral $X(3872)$. The bottom isotriplet exotic with $J^{PC}=1^{+-}$ binds, and is identified as a mixed state of the reported charged exotics $Z^+_b(10610)$ and $Z^+_b(10650)$. The bound bottom isosinglet molecule with $J^{PC}=1^{++}$ is a possible neutral $X_b(10532)$ to be observed.

  13. All biology is computational biology (United States)


    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science. PMID:28278152

  14. Electron-molecule collisions

    CERN Document Server

    Takayanagi, Kazuo


    Scattering phenomena play an important role in modern physics. Many significant discoveries have been made through collision experiments. Amongst diverse kinds of collision systems, this book sheds light on the collision of an electron with a molecule. The electron-molecule collision provides a basic scattering problem. It is scattering by a nonspherical, multicentered composite particle with its centers having degrees of freedom of motion. The molecule can even disintegrate, Le., dissociate or ionize into fragments, some or all of which may also be molecules. Although it is a difficult problem, the recent theoretical, experimental, and computational progress has been so significant as to warrant publication of a book that specializes in this field. The progress owes partly to technical develop­ ments in measurements and computations. No less important has been the great and continuing stimulus from such fields of application as astrophysics, the physics of the earth's upper atmosphere, laser physics, radiat...

  15. Inactive corrinoid-compound significantly decreases in Spirulina platensis grown in a cobalt-deficient medium. (United States)

    Watanabe, F; Miyamoto, E; Nakano, Y


    Spirulina platensis NIES-39 was grown under open culture system in the presence or absence of CoSO(4) (12 microg/L) and/or vitamin B(12) (10 microg/L) to confirm whether CoSO(4) and/or vitamin B(12) stimulate or are essential for growth of the algal cells and for accumulation of vitamin B(12). The addition of CoSO(4) and/or vitamin B(12) could not affect both cell growth and cell yield of the alga. The amount of corrinoid-compound was increased significantly by the addition of CoSO(4) but not by vitamin B(12). A C18 reversed-phase HPLC pattern of the Spirulina corrinoid-compound increased by the addition of CoSO(4) was identical to that of authentic pseudovitamin B(12), which is inactive for human. These results indicate that the algal cells grown in the absence of CoSO(4) are suitable for use of human health foods because the inactive corrinoid-compound can be reduced significantly.

  16. Epigenome changes in active and inactive Polycomb-group-controlled regions (United States)

    Breiling, Achim; O'Neill, Laura P; D'Eliseo, Donatella; Turner, Bryan M; Orlando, Valerio


    The Polycomb group (PcG) of proteins conveys epigenetic inheritance of repressed transcriptional states. In Drosophila, the Polycomb repressive complex 1 (PRC1) maintains the silent state by inhibiting the transcription machinery and chromatin remodelling at core promoters. Using immunoprecipitation of in vivo formaldehyde-fixed chromatin in phenotypically diverse cultured cell lines, we have mapped PRC1 components, the histone methyl transferase (HMT) Enhancer of zeste (E(z)) and histone H3 modifications in active and inactive PcG-controlled regions. We show that PRC1 components are present in both cases, but at different levels. In particular, active target promoters are nearly devoid of E(z) and Polycomb. Moreover, repressed regions are trimethylated at lysines 9 and 27, suggesting that these histone modifications represent a mark for inactive PcG-controlled regions. These PcG-specific repressive marks are maintained by the action of the E(z) HMT, an enzyme that has an important role not only in establishing but also in maintaining PcG repression. PMID:15448640

  17. "Spatial Energetics": Integrating Data From GPS, Accelerometry, and GIS to Address Obesity and Inactivity. (United States)

    James, Peter; Jankowska, Marta; Marx, Christine; Hart, Jaime E; Berrigan, David; Kerr, Jacqueline; Hurvitz, Philip M; Hipp, J Aaron; Laden, Francine


    To address the current obesity and inactivity epidemics, public health researchers have attempted to identify spatial factors that influence physical inactivity and obesity. Technologic and methodologic developments have led to a revolutionary ability to examine dynamic, high-resolution measures of temporally matched location and behavior data through GPS, accelerometry, and GIS. These advances allow the investigation of spatial energetics, high-spatiotemporal resolution data on location and time-matched energetics, to examine how environmental characteristics, space, and time are linked to activity-related health behaviors with far more robust and detailed data than in previous work. Although the transdisciplinary field of spatial energetics demonstrates promise to provide novel insights on how individuals and populations interact with their environment, there remain significant conceptual, technical, analytical, and ethical challenges stemming from the complex data streams that spatial energetics research generates. First, it is essential to better understand what spatial energetics data represent, the relevant spatial context of analysis for these data, and if spatial energetics can establish causality for development of spatially relevant interventions. Second, there are significant technical problems for analysis of voluminous and complex data that may require development of spatially aware scalable computational infrastructures. Third, the field must come to agreement on appropriate statistical methodologies to account for multiple observations per person. Finally, these challenges must be considered within the context of maintaining participant privacy and security. This article describes gaps in current practice and understanding and suggests solutions to move this promising area of research forward.

  18. Any link between sexual inactivity and treadle pump performance characteristics: The Malawi case (United States)

    Joseph, Chidanti-Malunga; Yamikani, Malunga

    In mitigating the effects of climate change in Malawi, government promotes the use of low cost irrigation technologies to small-scale farmers, especially in wetlands where water is available. The treadle pump is one such technology. The pump is a manual water lifting device operated by feet. Although the technology has been widely accepted by small-scale farmers, there are documented reports that some farmers abandon the technology, preferring other technologies such as river diversion. One theory for the abandonment is that female farmers claim that the technology makes their male counterparts sexually inactive. This research seeks to find an explanation to the misconception. The study analyzed the physical characteristics of the treadle pump and its users. The results show that the technology is male-dominated (30% were females out of a sample of 40). The results also show that the technology is labor-intensive with very small discharge rates (an average of 0.78 l/s) achieved regardless of the BMI of the operator. With such small discharge rates, in order to fulfill irrigation requirements of a crop, the operator has to pump for long hours. This exercise makes men naturally tired, perhaps making them sexually inactive as well.

  19. Intestinal pseudo-obstruction in inactive systemic lupus erythematosus: An unusual finding

    Institute of Scientific and Technical Information of China (English)

    Giulia; Leonardi; Nicola; de; Bortoli; Massimo; Bellini; Maria; Gloria; Mumolo; Francesco; Costa; Angelo; Ricchiuti; Stefano; Bombardieri; Santino; Marchi


    Chronic intestinal pseudo-obstruction (CIP) is an infre-quent complication of an active systemic lupus erythema-tosus (SLE). We illustrate a case of SLE inactive-related CIP. A 51-year old female with inactive SLE (ECLAM score 2) was hospitalized with postprandial fullness, vomiting, abdominal bloating and abdominal pain. She had had no bowel movements for five days. Plain abdominal X-ray revealed multiple fluid levels and dilated small and large bowel loops with air-fluid levels. Intestinal contrast radiology detected dilated loops. CIP was diagnosed. The patient was treated with prokinetics, octreotide, claritromycin, rifaximin, azathioprine and tegaserod without any clinical improvement. Then methylprednisolone (500 mg iv daily) was started. After the first administration, the patient showed peristaltic movements. A bowel movement was reported after the second administration. A plain abdominal X-ray revealed no air-fluid levels. Steroid therapy was slowly reduced with complete resolution of the symptoms. The patient is still in a good clinical condition. SLE-related CIP is generally reported as a complication of an active disease. In our case, CIP was the only clinical demonstration of the SLE.

  20. Influence of obesity, physical inactivity, and weight cycling on chronic inflammation. (United States)

    Strohacker, K; McFarlin, Brian K


    Obesity prevalence continues to rise due to excessive caloric intake and sedentary behavior. Weight loss can be achieved through diet and/or exercise, but maintenance of a reduced weight is rare and relapse is prevalent. Repeated periods of weight loss and regain have been termed "weight cycling." It has been speculated that weight cycling may further increase the elevated disease risk common with weight gain, obesity, and physical inactivity. Alterations in adipose tissue with weight cycling may create a more hypoxic environment; hypoxic adipose tissue secretes leptin, a stimulus for macrophage activation and accumulation within adipose tissue. Hypoxic adipocytes and macrophages release pro-inflammatory cytokines into circulation. Elevated body weight and adiposity are linked to cardiovascular disease and type 2 diabetes via an inflammatory mechanism. Thus, it is reasonable to speculate that weight cycling causes a more profound change in chronic inflammation than sustained weight gain. The purpose of this review is to explore inflammatory consequences associated with weight cycling as they are related to sustained weight gain, obesity, physical inactivity as well as relative disease risk.

  1. Detection of (Inactivity Periods in Human Body Motion Using Inertial Sensors: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Miguel Damas


    Full Text Available Determination of (inactivity periods when monitoring human body motion is a mandatory preprocessing step in all human inertial navigation and position analysis applications. Distinction of (inactivity needs to be established in order to allow the system to recompute the calibration parameters of the inertial sensors as well as the Zero Velocity Updates (ZUPT of inertial navigation. The periodical recomputation of these parameters allows the application to maintain a constant degree of precision. This work presents a comparative study among different well known inertial magnitude-based detectors and proposes a new approach by applying spectrum-based detectors and memory-based detectors. A robust statistical comparison is carried out by the use of an accelerometer and angular rate signal synthesizer that mimics the output of accelerometers and gyroscopes when subjects are performing basic activities of daily life. Theoretical results are verified by testing the algorithms over signals gathered using an Inertial Measurement Unit (IMU. Detection accuracy rates of up to 97% are achieved.

  2. Why are Jupiter-family comets active and asteroids in cometary-like orbits inactive?

    CERN Document Server

    Gundlach, B


    Surveys in the visible and near-infrared spectral range have revealed the presence of low-albedo asteroids in cometary like orbits (ACOs). In contrast to Jupiter family comets (JFCs), ACOs are inactive, but possess similar orbital parameters. In this work, we discuss why ACOs are inactive, whereas JFCs show gas-driven dust activity, although both belong to the same class of primitive solar system bodies. We hypothesize that ACOs and JFCs have formed under the same physical conditions, namely by the gravitational collapse of ensembles of ice and dust aggregates. We use the memory effect of dust-aggregate layers under gravitational compression to discuss under which conditions the gas-driven dust activity of these bodies is possible. Owing to their smaller sizes, JFCs can sustain gas-driven dust activity much longer than the bigger ACOs, whose sub-surface regions possess an increased tensile strength, due to gravitational compression of the material. The increased tensile strength leads to the passivation again...

  3. Special Issue: "Molecules against Alzheimer". (United States)

    Decker, Michael; Muñoz-Torrero, Diego


    This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor. The development of novel AD diagnostic agents based on tau protein imaging and the use of lithium or intranasal insulin for the prevention or the symptomatic treatment of AD is also covered in some articles of the Special Issue.

  4. Research Progress on Electrochemical Behavior of Drugs and Biological Molecules on Nickel (Composite)Modified Electrode%药物与生物分子在镍(复合)修饰电极上的电化学行为研究进展

    Institute of Scientific and Technical Information of China (English)

    崔闻宇; 权茂华; 樊宇; 张乔; 贾琦


    The electrochemical behavior of drugs and biological molecules can be detected by electrochemical biosensor and the interaction between them can be studied.The sensitivity and the recognition specificity can be improved greatly by electrode surface modification technology.In this paper,the electrochemical behavior of drugs and biological molecules on nickel modified electrodes and nickel composite modified electrodes were re-viewed.The preparation of nickel (composite)modified electrodes by ionic liquid electrodeposition was intro-duced,and its application in electrochemical biosensor was prospected.%电化学生物传感器可以检测药物与生物分子的电化学行为,从而研究二者之间的相互作用,而电极的表面修饰技术不仅可极大地提高电化学生物传感器的灵敏度,且具有很高的识别专一性。综述了金属镍及其复合材料修饰电极上药物与生物分子的电化学行为研究进展,并介绍了离子液体电沉积制备金属镍(复合)修饰电极研究概况,对该电极在电化学生物传感器方面的应用前景进行了展望。

  5. High throughput screens yield small molecule inhibitors of Leishmania CRK3:CYC6 cyclin-dependent kinase.

    Directory of Open Access Journals (Sweden)

    Roderick G Walker

    Full Text Available BACKGROUND: Leishmania species are parasitic protozoa that have a tightly controlled cell cycle, regulated by cyclin-dependent kinases (CDKs. Cdc2-related kinase 3 (CRK3, an essential CDK in Leishmania and functional orthologue of human CDK1, can form an active protein kinase complex with Leishmania cyclins CYCA and CYC6. Here we describe the identification and synthesis of specific small molecule inhibitors of bacterially expressed Leishmania CRK3:CYC6 using a high throughput screening assay and iterative chemistry. We also describe the biological activity of the molecules against Leishmania parasites. METHODOLOGY/PRINCIPAL FINDINGS: In order to obtain an active Leishmania CRK3:CYC6 protein kinase complex, we developed a co-expression and co-purification system for Leishmania CRK3 and CYC6 proteins. This active enzyme was used in a high throughput screening (HTS platform, utilising an IMAP fluorescence polarisation assay. We carried out two chemical library screens and identified specific inhibitors of CRK3:CYC6 that were inactive against the human cyclin-dependent kinase CDK2:CycA. Subsequently, the best inhibitors were tested against 11 other mammalian protein kinases. Twelve of the most potent hits had an azapurine core with structure activity relationship (SAR analysis identifying the functional groups on the 2 and 9 positions as essential for CRK3:CYC6 inhibition and specificity against CDK2:CycA. Iterative chemistry allowed synthesis of a number of azapurine derivatives with one, compound 17, demonstrating anti-parasitic activity against both promastigote and amastigote forms of L. major. Following the second HTS, 11 compounds with a thiazole core (active towards CRK3:CYC6 and inactive against CDK2:CycA were tested. Ten of these hits demonstrated anti-parasitic activity against promastigote L. major. CONCLUSIONS/SIGNIFICANCE: The pharmacophores identified from the high throughput screens, and the derivatives synthesised, selectively

  6. Long-range effects in electron scattering by polar molecules (United States)

    Fabrikant, Ilya I.


    We review long-range effects in electron collisions with polar molecules, starting with elastic scattering. We then go to rotationally and vibrationally inelastic processes and dissociative electron attachment. The last two are strongly affected by vibrational Feshbach resonances which have been observed and described theoretically in many systems from simple diatomic molecules to more complex polyatomics, biologically relevant molecules, and van der Waals clusters. We then review environmental effects which include electron interaction with molecules adsorbed on surfaces and molecules in cluster environments. We concentrate on physics rather than on listing results of ab initio calculations. With increasing complexity of targets and processes model approaches become more relevant. We demonstrate their success in the theoretical description of electron attachment to polyatomic molecules and to molecules in complex environments.

  7. Combining supramolecular chemistry with biology. (United States)

    Uhlenheuer, Dana A; Petkau, Katja; Brunsveld, Luc


    Supramolecular chemistry has primarily found its inspiration in biological molecules, such as proteins and lipids, and their interactions. Currently the supramolecular assembly of designed compounds can be controlled to great extent. This provides the opportunity to combine these synthetic supramolecular elements with biomolecules for the study of biological phenomena. This tutorial review focuses on the possibilities of the marriage of synthetic supramolecular architectures and biological systems. It highlights that synthetic supramolecular elements are for example ideal platforms for the recognition and modulation of proteins and cells. The unique features of synthetic supramolecular systems with control over size, shape, valency, and interaction strength allow the generation of structures fitting the demands to approach the biological problems at hand. Supramolecular chemistry has come full circle, studying the biology and its molecules which initially inspired its conception.

  8. Handbook of Single-Molecule Biophysics

    CERN Document Server

    Hinterdorfer, Peter


    The last decade has seen the development of a number of novel biophysical methods that allow the manipulation and study of individual biomolecules. The ability to monitor biological processes at this fundamental level of sensitivity has given rise to an improved understanding of the underlying molecular mechanisms. Through the removal of ensemble averaging, distributions and fluctuations of molecular properties can be characterized, transient intermediates identified, and catalytic mechanisms elucidated. By applying forces on biomolecules while monitoring their activity, important information can be obtained on how proteins couple function to structure. The Handbook of Single-Molecule Biophysics provides an introduction to these techniques and presents an extensive discussion of the new biological insights obtained from them. Coverage includes: Experimental techniques to monitor and manipulate individual biomolecules The use of single-molecule techniques in super-resolution and functional imaging Single-molec...

  9. Factors increasing the risk of inactivity among administrative, technical, and manual workers in Warszawa public institutions

    Directory of Open Access Journals (Sweden)

    Elżbieta Biernat


    Full Text Available Objectives: The research aims to assess the level of physical activity among administrative, technical, and manual workers employed in Warszawa public institutions and to analyze the factors that increase the risk of failing to meet World Health Organization (WHO recommendations. Material and Methods: The study comprised 373 employees of randomly selected institutions. A short version of International Physical Activity Questionnaire (IPAQ was applied. The correlation between the mean values of duration, days, MET-min/week of efforts, gender, and type of work was analyzed using the Tukey’s honest significant difference (HSD test, while the correlation between the level of physical activity and the socio-demographic characteristics was assessed with the Chi2 test. The strength of the relationship between socio-demographic characteristics and fulfilment of WHO standards was expressed by the odds ratio (OR and 95% confidence interval (95% CI. The significance level was p = 0.05. Results: High levels of physical activity were declared by 41.8% of the manual workers, 14.7% of the administration staff, and 7.3% of the technicians; 19%, 31.5% and 54.5%, respectively, reported low levels of physical activity. Factors determining the fulfilment of the WHO recommendations include: the nature of work (p = 0.003, education (p = 0.004, and income (p = 0.003. The risk of being inactive nearly doubles in the case of administration staff (31.5% and increases more than 4 times in the case of technicians (54.5%. Respondents with secondary school education (31.6% are exposed to a 3-fold higher risk of inactivity, while in respondents with higher education (37.2%, the level of the risk is 4-fold higher. Compared to those in the highest income group (23.4%, people who earn less (34.1% are inactive almost twice as often. Conclusions: Urgent intervention is necessary in all studied groups: increased energy expenditure for recreation and locomotion, educational offers

  10. Population-attributable causes of cancer in Korea: obesity and physical inactivity.

    Directory of Open Access Journals (Sweden)

    Sohee Park

    Full Text Available BACKGROUND: Changes in lifestyle including obesity epidemic and reduced physical activity influenced greatly to increase the cancer burden in Korea. The purpose of the current study was to perform a systematic assessment of cancers attributable to obesity and physical inactivity in Korea. METHODOLOGY/PRINCIPAL FINDINGS: Gender- and cancer site-specific population-attributable fractions (PAF were estimated using the prevalence of overweight and obesity in 1992-1995 from a large-scale prospective cohort study, the prevalence of low physical activity in 1989 from a Korean National Health Examination Survey, and pooled relative risk estimates from Korean epidemiological studies. The overall PAF was then estimated using 2009 national cancer incidence data from the Korea Central Cancer Registry. Excess body weight was responsible for 1,444 (1.5% and 2,004 (2.2% cancer cases among men and women, respectively, in 2009 in Korea. Among men, 6.8% of colorectal, 2.9% of pancreatic, and 16.0% of kidney cancer was attributable to excess body weight. In women, 6.6% of colorectal, 3.9% of pancreatic, 18.7% of kidney, 8.2% of postmenopausal breast, and 32.7% of endometrial cancer was attributable to excess body weight. Low leisure-time physical activity accounted for 8.8% of breast cancer, whereas the PAF for overall cancer was low (0.1% in men, 1.4% in women. Projections suggest that cancers attributable to obesity will increase by 40% in men and 16% in women by 2020. CONCLUSIONS/SIGNIFICANCE: With a significantly increasing overweight and physically inactive population, and increasing incidence of breast and colorectal cancers, Korea faces a large cancer burden attributable to these risk factors. Had the obese population of Korea remained stable, a large portion of obesity-related cancers could have been avoided. Efficient cancer prevention programs that aim to reduce obesity- and physical inactivity-related health problems are essential in Korea.

  11. Prevalence of physical inactivity and associated factors among adolescents from public schools in Uruguaiana, Rio Grande do Sul State, Brazil

    Directory of Open Access Journals (Sweden)

    Gabriel Gustavo Bergmann


    Full Text Available This study aimed to identify the prevalence of physical inactivity and associated factors in adolescents, using a cross-sectional design with a sample of 1,455 adolescents (741 females. Data were collected using a questionnaire consisting of socio-demographic, perceptual, and behavioral variables. Physical activity was estimated with the Physical Activity Questionnaire for Older Children and Adolescents. Prevalence of physical inactivity was 68% (95%CI: 65.6%-70.4%. The following variables remained associated with physical inactivity in the adjusted analysis (p < 0.05: living in an apartment, female gender, older adolescents, lower self-rated physical activity compared to peers, low perception of maternal physical activity, passive commuting to school, non-participation in physical education at school, non-enjoyment of physical education classes, and limited involvement in other types of physical exercise besides physical education at school. There were a high proportion of inactive adolescents. Strategies to prevent physical inactivity in adolescents should be elaborated with a central role for the school and family.

  12. Meta-analysis of three diabetes population studies: association of inactive ALDH2 genotype with maternal inheritance of diabetes. (United States)

    Murata, C; Taniyama, M; Kuriyama, S; Muramatsu, T; Atsumi, Y; Matsuoka, K; Suzuki, Y


    To date, there have been three population studies that examined the association of mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype with inheritance of diabetes. Here, we summarize the results by meta-analysis. The study 1 consisted of 212 type 2 diabetics who did not have renal failure. The study 2 consisted of 73 type 2 diabetics who had renal failure. The study 3 consisted of 230 type 1 diabetics. In total, 515 subjects were examined for the association of ALDH2 genotype with inheritance of diabetes. Out of 515 subjects, 307 (60%) had active ALDH2 (ALDH2*1/ALDH2*1) and 208 (40%) had inactive ALDH2 (175 had ALDH2*1/ALDH2*2 and 33 had ALDH2*2/ALDH2*2). As for family history, 25 subjects (8.1%) in the active ALDH2 group had a diabetic mother, compared with 43 (20.6%) in the inactive ALDH2 group. Twenty-nine subjects (9.4%) in the active ALDH2 group had a diabetic father, compared with 14 (6.7%) in the inactive ALDH2 group. The percentage of diabetic mother was higher in the inactive ALDH2 group, the differences were statistically significant (P maternal trait of diabetes inheritance. In conclusion, meta-analysis using three diabetes population studies strongly confirmed the association between ALDH2 inactivity and maternal inheritance.

  13. Molecules in supernova ejecta

    CERN Document Server

    Cherchneff, Isabelle


    The first molecules detected at infrared wavelengths in the ejecta of a Type II supernova, namely SN1987A, consisted of CO and SiO. Since then, confirmation of the formation of these two species in several other supernovae a few hundred days after explosion has been obtained. However, supernova environments appear to hamper the synthesis of large, complex species due to the lack of microscopically-mixed hydrogen deep in supernova cores. Because these environments also form carbon and silicate dust, it is of importance to understand the role played by molecules in the depletion of elements and how chemical species get incorporated into dust grains. In the present paper, we review our current knowledge of the molecular component of supernova ejecta, and present new trends and results on the synthesis of molecules in these harsh, explosive events.


    Energy Technology Data Exchange (ETDEWEB)

    Loinard, Laurent; Menten, Karl M.; Guesten, Rolf [Max-Planck Institut fuer Radioastronomie, Auf dem Huegel 69, 53121 Bonn (Germany); Zapata, Luis A.; Rodriguez, Luis F. [Centro de Radioastronomia y Astrofisica, Universidad Nacional Autonoma de Mexico, Apartado Postal 3-72, 58090 Morelia, Michoacan (Mexico)


    We report the detection toward {eta} Carinae of six new molecules, CO, CN, HCO{sup +}, HCN, HNC, and N{sub 2}H{sup +}, and of two of their less abundant isotopic counterparts, {sup 13}CO and H{sup 13}CN. The line profiles are moderately broad ({approx}100 km s{sup -1}), indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO{sup +} do not appear to be underabundant in {eta} Carinae. On the other hand, molecules containing nitrogen or the {sup 13}C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of {eta} Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  15. Molecules in \\eta\\ Carinae

    CERN Document Server

    Loinard, Laurent; Guesten, Rolf; Zapata, Luis A; Rodriguez, Luis F


    We report the detection toward \\eta\\ Carinae of six new molecules, CO, CN, HCO+, HCN, HNC, and N2H+, and of two of their less abundant isotopic counterparts, 13CO and H13CN. The line profiles are moderately broad (about 100 km /s) indicating that the emission originates in the dense, possibly clumpy, central arcsecond of the Homunculus Nebula. Contrary to previous claims, CO and HCO+ do not appear to be under-abundant in \\eta\\ Carinae. On the other hand, molecules containing nitrogen or the 13C isotope of carbon are overabundant by about one order of magnitude. This demonstrates that, together with the dust responsible for the dimming of eta Carinae following the Great Eruption, the molecules detected here must have formed in situ out of CNO-processed stellar material.

  16. Bioinspired assembly of small molecules in cell milieu. (United States)

    Wang, Huaimin; Feng, Zhaoqianqi; Xu, Bing


    Self-assembly, the autonomous organization of components to form patterns or structures, is a prevalent process in nature at all scales. Particularly, biological systems offer remarkable examples of diverse structures (as well as building blocks) and processes resulting from self-assembly. The exploration of bioinspired assemblies not only allows for mimicking the structures of living systems, but it also leads to functions for applications in different fields that benefit humans. In the last several decades, efforts on understanding and controlling self-assembly of small molecules have produced a large library of candidates for developing the biomedical applications of assemblies of small molecules. Moreover, recent findings in biology have provided new insights on the assemblies of small molecules to modulate essential cellular processes (such as apoptosis). These observations indicate that the self-assembly of small molecules, as multifaceted entities and processes to interact with multiple proteins, can have profound biological impacts on cells. In this review, we illustrate that the generation of assemblies of small molecules in cell milieu with their interactions with multiple cellular proteins for regulating cellular processes can result in primary phenotypes, thus providing a fundamentally new molecular approach for controlling cell behavior. By discussing the correlation between molecular assemblies in nature and the assemblies of small molecules in cell milieu, illustrating the functions of the assemblies of small molecules, and summarizing some guiding principles, we hope this review will stimulate more molecular scientists to explore the bioinspired self-assembly of small molecules in cell milieu.

  17. Clinical review: Oxygen as a signaling molecule



    Molecular oxygen is obviously essential for conserving energy in a form useable for aerobic life; however, its utilization comes at a cost - the production of reactive oxygen species (ROS). ROS can be highly damaging to a range of biological macromolecules, and in the past the overproduction of these short-lived molecules in a variety of disease states was thought to be exclusively toxic to cells and tissues such as the lung. Recent basic research, however, has indicated that ROS production -...

  18. Isatin, a versatile molecule: studies in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Barbara, E-mail: [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)


    Isatin is a small, versatile and widely applicable pharmacological molecule. These characteristics make isatin and its derivatives attractive to many research groups as resources for chemical and pharmacological studies. Although it has a relatively simple structure, isatin is a useful chemical scaffold for a variety of chemical transformations. This article discusses several studies performed by Brazilian groups, including investigations of its structural changes, biological assay designs and new methods for the synthesis of isatin. (author)

  19. Gated container molecules

    Institute of Scientific and Technical Information of China (English)

    LIU Fang; WANG Hao; HOUK K. N.


    Donald J.Cram,the great UCLA chemist,received the Nobel Prize for his discoveries about host-guest complexes [1].Both theoretical and experimental studies have been conducted about the nature and strength of interactions between the host and guest molecules.The concepts of constrictive binding (the activation energy of the binding process) and intrinsic binding (the free energy difference between the complex and the free host and guest molecules) were introduced to characterize different binding properties (Figure 1)[2].

  20. Enzyme molecules as nanomotors. (United States)

    Sengupta, Samudra; Dey, Krishna K; Muddana, Hari S; Tabouillot, Tristan; Ibele, Michael E; Butler, Peter J; Sen, Ayusman


    Using fluorescence correlation spectroscopy, we show that the diffusive movements of catalase enzyme molecules increase in the presence of the substrate, hydrogen peroxide, in a concentration-dependent manner. Employing a microfluidic device to generate a substrate concentration gradient, we show that both catalase and urease enzyme molecules spread toward areas of higher substrate concentration, a form of chemotaxis at the molecular scale. Using glucose oxidase and glucose to generate a hydrogen peroxide gradient, we induce the migration of catalase toward glucose oxidase, thereby showing that chemically interconnected enzymes can be drawn together.

  1. Novel approaches for single molecule activation and detection

    CERN Document Server

    Benfenati, Fabio; Torre, Vincent


    How can we obtain tools able to process and exchange information at the molecular scale In order to do this, it is necessary to activate and detect single molecules under controlled conditions. This book focuses on the generation of biologically-inspired molecular devices. These devices are based on the developments of new photonic tools able to activate and stimulate single molecule machines. Additionally, new light sensitive molecules can be selectively activated by photonic tools. These technological innovations will provide a way to control activation of single light-sensitive molecules, a

  2. Plant antimutagenic agents, 4. Isolation and structure elucidation of maesol, an inactive constituent of Maesa spp. (United States)

    Wall, M E; Wani, M C; Gaetano, K; Manikumar, G; Taylor, H; McGivney, R


    Maesol, a novel dimeric phenol, was isolated from seeds of Maesa montana and Maesa indica. Maesol was shown to have the formula C28H42O4 with structure 1, a dimeric, symmetrical 1,12-bis(3,3'-dihydroxy-4,4'-dimethyl-5,5'-dimethoxyphenyl)dodecane. It is the first compound with such structure to be isolated from plant material. Structure elucidation was based largely on 1H- and 13C-nmr techniques and comparison with a known synthetic isomeric dimer 3. Although crude extracts showed strong inhibition of 2-aminoanthracene activity against Salmonella typhimurium (T-98), the pure compound was inactive when tested for inhibition of the mutagenic activity of several mutagens.

  3. Inactive experiments for advanced separation processes prior to high activity trials in ATALANTE

    Energy Technology Data Exchange (ETDEWEB)

    Duhamet, Jean; Lanoe, Jean-Yves; Rivalier, Patrick; Borda, Gilles [Commissariat a l' Energie Atomique (CEA), CEA/DEN/VRH/DTEC/SGCS, Centre de Marcoule - BP 17171, 302007 Bagnols-sur-Ceze cedex (France)


    Many trials have been performed in ATALANTE's shielded cells to demonstrate the technical feasibility of processes involving minor actinide separation. They required developments of new extractors as well as a step by step procedure have been used to lower the risks of malfunction during high active operation. The design of the extractors developed by Cea has included shielded cells restrictions, miniaturization to lower the quantity of high active material and wastes and the care for being representative of industrial equipment. After individual shake down inactive tests, with actual phases, each process experiment scheduled in ATALANTE has been tested at G1 Facility in Marcoule. The objective was to reproduce as much as possible all the equipment chosen for active tests. This procedure has demonstrated its efficiency to detect many problems that would have heavy impact if they have been discovered during active trials. It was also used for operators'training. (authors)

  4. Physical inactivity as a risk factor for diabetic retinopathy? A review. (United States)

    Dirani, Mohamed; Crowston, Jonathan G; van Wijngaarden, Peter


    Physical inactivity and sedentary behaviour have been identified as modifiable risk factors for diabetes. However, little is known of the associations between physical activity, sedentary behaviour and diabetic retinopathy. The development of diabetic retinopathy is associated with longer duration of diabetes, elevated blood pressure and poor glycaemic control. However these factors only explain a proportion of the risk of retinopathy in individuals with diabetes. Several studies have suggested a protective role for physical activity in diabetic retinopathy. Other work has shown that the time spent watching television is independently associated with abnormal retinal vascular signs. Limitations of the existing studies, such as the absence of objective measures of physical activity, a lack of sedentary behaviour measures, the inclusion of only those with type 1 diabetes and a lack of longitudinal data, make it difficult to draw firm conclusions about the strength of these associations.

  5. Groundwater contamination from an inactive uranium mill tailings pile: 1. Application of a chemical mixing model (United States)

    White, A. F.; Delany, J. M.; Narasimhan, T. N.; Smith, A.


    Low-pH process waters contained in a number of inactive and abandoned uranium mill tailings in the United States represent potential sources of radionuclide and trace metal contamination of groundwater. Detailed investigations at a typical site at Riverton, Wyoming, indicate that chemical transport occurs from initial dewatering of the tailings, downward infiltration due to precipitation, and groundwater intrusion into the base of the tailings pile. Except for elevated uranium and molybdenum concentrations, current radionuclide and trace metal transport is limited by the near-neutral pH conditions of the groundwater. Significant reactions include the dissolution of calcite, production of CO2, and precipitation of gypsum and the hydroxides of iron and aluminum. A geochemical mixing model employing the PHREEQE computer code is used to estimate current rates of the groundwater contamination by tailings water. A maximum mixing of 1.7% of pore water is a factor of 2 less than steady state estimates based on hydraulic parameters.

  6. Efficient production of transgenic chickens using self-inactive HIV-based lentiviral vectors

    Institute of Scientific and Technical Information of China (English)

    Shiyong XU; Yan SUN; Hongmei DING; Meng WANG; Yafei CAI; Jie CHEN; Honglin LIU


    We demonstrated the simple and effective production of transgenic chickens, in which the enhanced green fluorescence protein (EGFP) was expressed by using third-generation self-inactive HIV-based lentiviral vectors. In our experiments, lentiviruses were injected into 204 fertilized eggs, from which 30 ( 15% ) chickens were hatched. The exogenous gene was detected in the genomes of 16 out of 30 (53%) chickens. The green fluorescence signal was observed directly in various body parts, and was particularly significant in the testes. The transgenes were also found in the offspring of these chickens. The results indicate that HIV-based lentivirul vectors can be used to generate transgenic birds economically and effectively [Current Zoology 55 (5): 383 - 387,2009].

  7. Inactive dry yeast application on grapes modify Sauvignon Blanc wine aroma. (United States)

    Šuklje, Katja; Antalick, Guillaume; Buica, Astrid; Coetzee, Zelmari A; Brand, Jeanne; Schmidtke, Leigh M; Vivier, Melané A


    This study investigated the potential to improve wine aroma by applying two inactive dry yeast products (IDYs) at the onset of ripening on Sauvignon Blanc grapes. Both products led to increased reduced glutathione concentrations in the grape juice and corresponding wines, as well as differences in individual higher alcohol acetates (HAAs) and ethyl esters of straight chain fatty acids (EEFAs) at the end of fermentation. After two months of storage, a significantly slower decrease of EEFAs and to a lesser extent of HAAs was found for wines made from grapes with IDY applications. These wines also resulted in significantly slower synthesis of ethyl esters of branched acids, whereas varietal thiols were altered in a product-specific manner. The modifications in the wine chemical composition were also sensorially corroborated. This study showed that vineyard additions of IDY products directly on the grapes at the onset of ripening have a subsequent benefit to the production and preservation of aroma in wines.

  8. First inactive conformation of CK2 alpha, the catalytic subunit of protein kinase CK2

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Issinger, Olaf-Georg; Niefind, Karsten


    (EPKs). To function as regulatory key components, EPKs normally exist in inactive ground states and are activated only upon specific signals. Typically, this activation is accompanied by large conformational changes in helix alpha C and in the activation segment, leading to a characteristic arrangement......The Ser/Thr kinase casein kinase 2 (CK2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha, catalytic subunit of CK2) attached to a dimer of two noncatalytic subunits (CK2beta, noncatalytic subunit of CK2). CK2alpha belongs to the superfamily of eukaryotic protein kinases...... of catalytic key elements. For CK2alpha, however, no strict physiological control of activity is known. Accordingly, CK2alpha was found so far exclusively in the characteristic conformation of active EPKs, which is, in this case, additionally stabilized by a unique intramolecular contact between the N...

  9. LOXL2 catalytically inactive mutants mediate epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Eva P. Cuevas


    Lysyl-oxidase-like 2 (LOXL2 is a member of the lysyl oxidase family that catalyzes the cross-linking of collagens or elastins in the extracellular matrix, thus regulating the tensile strength of tissues. However, many reports have suggested different intracellular roles for LOXL2, including the ability to regulate gene transcription and tumor progression. We previously reported that LOXL2 mediates epithelial-to-mesenchymal transition (EMT by Snail1-dependent and independent mechanisms, related to E-cadherin silencing and downregulation of epidermal differentiation and cell polarity components, respectively. Whether or not the catalytic activity of LOXL2 is required to induce/sustain EMT is actually unknown. Here we show that LOXL2 catalytic inactive mutants collaborate with Snail1 in E-cadherin gene repression to trigger EMT and, in addition, promote FAK/Src pathway activation to support EMT. These findings reveal a non-conventional role of LOXL2 on regulating epithelial cell plasticity.

  10. Short term aerobic exercise alters the reinforcing value of food in inactive adults. (United States)

    Panek, Leah M; Jones, Kelly R; Temple, Jennifer L


    Motivation to eat, or the reinforcing value of food, may be influenced by a number of factors, including physical activity. The purpose of these studies was to test the hypothesis that short-term moderate-vigorous intensity aerobic exercise would alter the reinforcing value of high (HED) and low (LED) energy density foods in inactive adults. The reinforcing value of LED and HED food was measured at baseline and again after two weeks of aerobic exercise. In Experiment 1, 41 participants were randomized to a no exercise condition or aerobic exercise for 3 days per week for two weeks. In Experiment 2, 76 participants were randomized to one of four aerobic exercise frequencies, 0, 1, 3, or 5 days per week for two weeks. In both experiments, exercise reduced the reinforcing value of HED food compared to baseline and to non-exercise controls. In Experiment 2, the 5 day group also showed a significant increase in the reinforcing value of LED food compared to baseline and other exercise frequencies. Liking of HED and LED foods and consumption of HED food were not affected by exercise treatment. Finally, in Experiment 2, the 5 day group reported consuming more energy outside of the laboratory than the other groups. Taken together, these data suggest, in inactive individuals, motivation to obtain HED and LED foods can be altered with a short-term moderate-vigorous intensity exercise intervention. Further research is needed to understand the cognitive and physiological processes involved in food choices paired with exercise.

  11. Maternal inflammation during late pregnancy is lower in physically active compared with inactive obese women. (United States)

    Tinius, Rachel A; Cahill, Alison G; Strand, Eric A; Cade, W Todd


    The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and lipid metabolism and maternal and neonatal metabolic health in these women. A cross-sectional, observational study design was performed in 16 obese-inactive (OBI; means ± SD; age, 25.0 ± 4.8 years; prepregnancy body mass index (BMI), 36.3 ± 4.3 kg/m(2); body fat percentage in late gestation, 37.7% ± 3.5%) and 16 obese-active (OBA; age, 28.9 ± 4.8 years; prepregnancy BMI, 34.0 ± 3.7 kg/m(2); body fat in late gestation, 36.6% ± 3.8%) women during the third trimester of pregnancy. Maternal plasma inflammation (C -reactive protein (CRP)) and insulin resistance (Homeostatic Model Assessment-Insulin Resistance) were measured at rest. Plasma lipid concentration and metabolism (lipid oxidation and lipolysis) were measured at rest, during a 30-min bout of low-intensity (40% peak oxygen uptake) exercise, and during a resting recovery period using indirect calorimetry. Umbilical cord blood was collected for measurement of neonatal plasma insulin resistance, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Maternal plasma CRP concentration was significantly higher in OBI compared with OBA women (9.1 ± 4.0 mg/L vs. 6.3 ± 2.5 mg/L, p = 0.02). Maternal plasma CRP concentration was significantly associated with maternal lipolysis (r = 0.43, p = 0.02), baseline lipid oxidation rate (r = 0.39, p = 0.03), and baseline plasma free fatty acid concentration (r = 0.36, p = 0.04). In conclusion, maternal physical activity may reduce inflammation during pregnancy in obese women. Maternal lipid metabolism is related to systemic inflammation.

  12. Survey of active and inactive mines for possible use as in situ test facilities

    Energy Technology Data Exchange (ETDEWEB)


    A survey of active and inactive mines which might be useful for radioactive waste storage in situ test experiments was conducted. It was performed for Union Carbide Corporation, Nuclear Division, Office of Waste Isolation. The report covers available information gathered from literature, U.S. Bureau of Mines, the Mining Enforcement and Safety Agency, and a limited number of personal contacts with constructors or operators of facilities. This survey is preliminary in nature and the objective is to develop potential candidate facilities for in situ experiments which warrant further investigation. Included are descriptions of 244 facilities, with all the data about each one which was available within the time restraint of the study. These facility descriptions are additionally indexed by depth of mine, nature of the country rock, mineral mined, and type of entry. A total of 14 inactive mines and 34 active mines has been selected as those most worthy of further investigation for possible service as nuclear waste isolation test facilities. This investigation, being preliminary and having been performed in a very short time period, must be qualified, and the description of the qualification is presented in the body of this report. Qualifications deal primarily with the hazard of having omitted facilities and having incomplete data in some instances. Results indicate sedimentary rock mines of minerals of evaporite origin as a first ranking of preference for in situ testing, followed by other sedimentary rocks and then by mines producing minerals from any type rock where the mine is above the local water table. These are general rules and of course there can be exceptions to them.

  13. A method of active conformation search based on active and inactive analogues, and its application to allylamine antimycotics

    Institute of Scientific and Technical Information of China (English)

    张万年; 季海涛; 周有骏; 朱杰; 朱驹; 吕加国


    A new program ACSBAIA (Active Conformation Search Based on Active and Inactive Analogues) for determination of the active conformations was developed based on the rationales that specific functional groups of active analogues could reach and interact with the active site of target receptor by means of the change of conformations, but that of inactive analogues could not interact with the active site owing to conformational restriction. The program consisted of 4 sub-programs: conformation sampling system, active conformation constraint system, inactive conformation exclusion system, and activity prediction system. Pharmacophoric conformation of allylamine antimycotics was studied by this method. Activities of 2 analogues were predicted and tested. The results suggested that the method was scientific and practical. The application of this method was not restricted by the three-dimensional structural knowledge of target receptor. In the absence of structural information about the receptor, the method was

  14. Functional ability at age 75: is there an impact of physical inactivity from middle age to early old age?

    DEFF Research Database (Denmark)

    Christensen, Ulla; Støvring, N; Schultz-Larsen, K


    The aim of this study is to analyze the impact of physical inactivity from middle age to early old age on functional ability at age 75. Physical activity is measured both as cumulated activity from age 50 to 60 to 70 and at three separate points in time. Three hundred eighty-seven men and women......) and smoking, sex, school education, household composition, chronic disease at baseline and functional ability at age 70 as possible confounders. There was a strong association between physical inactivity at age 70 and disability at age 75. However, the analyses showed no effect of cumulated physical...... born in 1914 and living in seven municipalities in the western part of the County of Copenhagen were followed for 25 years with examinations in 1964, 1974, 1984 and 1989. Analyses were conducted with physical inactivity as an independent variable (accumulated and separately for each point in time...

  15. Disentangling DNA molecules (United States)

    Vologodskii, Alexander


    The widespread circular form of DNA molecules inside cells creates very serious topological problems during replication. Due to the helical structure of the double helix the parental strands of circular DNA form a link of very high order, and yet they have to be unlinked before the cell division. DNA topoisomerases, the enzymes that catalyze passing of one DNA segment through another, solve this problem in principle. However, it is very difficult to remove all entanglements between the replicated DNA molecules due to huge length of DNA comparing to the cell size. One strategy that nature uses to overcome this problem is to create the topoisomerases that can dramatically reduce the fraction of linked circular DNA molecules relative to the corresponding fraction at thermodynamic equilibrium. This striking property of the enzymes means that the enzymes that interact with DNA only locally can access their topology, a global property of circular DNA molecules. This review considers the experimental studies of the phenomenon and analyzes the theoretical models that have been suggested in attempts to explain it. We describe here how various models of enzyme action can be investigated computationally. There is no doubt at the moment that we understand basic principles governing enzyme action. Still, there are essential quantitative discrepancies between the experimental data and the theoretical predictions. We consider how these discrepancies can be overcome.

  16. Properties of entanglement molecules

    Energy Technology Data Exchange (ETDEWEB)

    Huang Yanxia [Department of Physics, Hubei Normal University, Huangshi 435002 (China); Zhan Mingsheng [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China)


    We propose a scheme to prepare a certain kind of N-atom entangled state that allows us to construct some possible types of entanglement molecules via cavity QED. The entanglement properties of entanglement molecules vertical bar {psi}{sub N}){sub {alpha}} are studied with respect to bipartite entanglement that is robust against the disposal of particles and are compared with entanglement molecules {rho}{sub I} introduced in Dur (2001 Phys. Rev. A 63 020303). We also give the maximal amount of entanglement achievable for two particular situations in two possible configurations. Meanwhile, we investigate the entanglement properties of entanglement molecules vertical bar {psi}{sub N}){sub {alpha}} in terms of local measurement using the maximum connectedness and persistency and compare them with other kinds of N-atom entangled states such as |GHZ), vertical bar W{sub N}) and vertical bar {phi}{sub N}). We show that the maximal value N - 1 of the persistency of the state vertical bar {psi}{sub N}){sub {alpha}} corresponds to the case that all atoms are pairwise entangled. If any pair of atoms {rho}{sub ij} is disentangled, the entanglement of the state vertical bar {psi}{sub N}){sub {alpha}} is very easy to destroy by a single local measurement.

  17. Properties of entanglement molecules (United States)

    Huang, Yan-Xia; Zhan, Ming-Sheng


    We propose a scheme to prepare a certain kind of N-atom entangled state that allows us to construct some possible types of entanglement molecules via cavity QED. The entanglement properties of entanglement molecules |psgrNrangagr are studied with respect to bipartite entanglement that is robust against the disposal of particles and are compared with entanglement molecules rgrI introduced in Dur (2001 Phys. Rev. A 63 020303). We also give the maximal amount of entanglement achievable for two particular situations in two possible configurations. Meanwhile, we investigate the entanglement properties of entanglement molecules |psgrNrangagr in terms of local measurement using the maximum connectedness and persistency and compare them with other kinds of N-atom entangled states such as |GHZrang, |WNrang and |phgrNrang. We show that the maximal value N - 1 of the persistency of the state |psgrNrangagr corresponds to the case that all atoms are pairwise entangled. If any pair of atoms rgrij is disentangled, the entanglement of the state |psgrNrangagr is very easy to destroy by a single local measurement.

  18. Atoms, Molecules, and Compounds

    CERN Document Server

    Manning, Phillip


    Explores the atoms that govern chemical processes. This book shows how the interactions between simple substances such as salt and water are crucial to life on Earth and how those interactions are predestined by the atoms that make up the molecules.

  19. Disentangling DNA molecules. (United States)

    Vologodskii, Alexander


    The widespread circular form of DNA molecules inside cells creates very serious topological problems during replication. Due to the helical structure of the double helix the parental strands of circular DNA form a link of very high order, and yet they have to be unlinked before the cell division. DNA topoisomerases, the enzymes that catalyze passing of one DNA segment through another, solve this problem in principle. However, it is very difficult to remove all entanglements between the replicated DNA molecules due to huge length of DNA comparing to the cell size. One strategy that nature uses to overcome this problem is to create the topoisomerases that can dramatically reduce the fraction of linked circular DNA molecules relative to the corresponding fraction at thermodynamic equilibrium. This striking property of the enzymes means that the enzymes that interact with DNA only locally can access their topology, a global property of circular DNA molecules. This review considers the experimental studies of the phenomenon and analyzes the theoretical models that have been suggested in attempts to explain it. We describe here how various models of enzyme action can be investigated computationally. There is no doubt at the moment that we understand basic principles governing enzyme action. Still, there are essential quantitative discrepancies between the experimental data and the theoretical predictions. We consider how these discrepancies can be overcome.

  20. Sex differences in the physical inactivity and health-related quality of life relationship among rural adults (United States)

    Hart, Peter D


    Background: The purpose of this study was to investigate the relationship between physical inactivity (PIA) and health-related quality of life (HRQOL) in rural adults and examine the extent to which sex differences exist in this relationship. Methods: A total of 5617 adults 18 years of age and older who indicated residing in a rural county was included in this analysis. PIA status was assessed by questions regarding recreational physical activity during the previous month. Five HRQOL measures (physical health, mental health, inactivity health, general health, & unhealthy days) were used as primary outcome variables. PIA and HRQOL prevalence estimates were computed with 95% CIs. Multiple logistic regression was used to obtain odds ratios (ORs) and 95% CIs adjusted for age, ethnicity, and income. Results: Physically inactive rural adults were significantly more likely to report poor HRQOL in all overall crude models with ORs ranging from 1.59 to 2.16. Additionally, sex-by-PIA interactions were significant across all crude HRQOL models with ORs ranging from 2.27 to 3.08 and 1.56 to 2.42 for women and men, respectively. Sex differences were maintained in fully adjusted models, except for mental health and inactivity health with ORs ranging from 1.80 to 2.58 and 1.41 to 1.79 for women and men, respectively. Conclusion: Results from this study show that PIA is a strong predictor of poor HRQOL even after controlling for confounding variables. Furthermore, physically inactive rural women appear more likely to report poor levels of HRQOL than physically inactive rural men.

  1. Metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy in postpartum dairy cows with ovarian inactivity. (United States)

    Xu, Chuchu; Xia, Cheng; Sun, Yuhang; Xiao, Xinhuan; Wang, Gang; Fan, Ziling; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Yang, Wei


    To understand the differences in metabolic changes between cows with ovarian inactivity and estrus cows, we selected cows at 60-90 days postpartum from an intensive dairy farm. According to clinical manifestations, B-ultrasound scan, rectal examination, 10 cows were assigned to the estrus group (A) and 10 to the ovarian inactivity group (B). All plasma samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy to compare plasma metabolomic profiles between the groups. We used multivariate pattern recognition to screen for different metabolites in plasma of anestrus cows. Compared with normal estrous cows, there were abnormalities in 12 kinds of metabolites in postpartum cows with ovarian inactivity (|r|> 0.602), including an increase in acetic acid (r = -0.817), citric acid (r = -0.767), and tyrosine (r = -0.714), and a decrease in low-density lipoprotein (r = 0.820), very low-density lipoprotein (r = 0.828), lipids (r = 0.769), alanine (r = 0.816), pyruvate (r = 0.721), creatine (r = 0.801), choline (r = 0.639), phosphorylcholine (r = 0.741), and glycerophosphorylcholine (r = 0.881). These metabolites were closely related to abnormality of glucose, amino acid, lipoprotein and choline metabolism, which may disturb the normal estrus. The decrease in plasma creatine and the increase in tyrosine were new changes for ovarian inactivity of postpartum cows. The decrease in plasma creatine and choline and the increase in tyrosine and p-hydroxyphenylalanine in cows with ovarian inactivity provide new directions for research on the mechanism of ovarian inactivity in cows.

  2. Sex differences in the physical inactivity and health-related quality of life relationship among rural adults

    Directory of Open Access Journals (Sweden)

    Peter D Hart


    Full Text Available Background: The purpose of this study was to investigate the relationship between physical inactivity (PIA and health-related quality of life (HRQOL in rural adults and examine the extent to which sex differences exist in this relationship. Methods: A total of 5617 adults 18 years of age and older who indicated residing in a rural county was included in this analysis. PIA status was assessed by questions regarding recreational physical activity during the previous month. Five HRQOL measures (physical health, mental health, inactivity health, general health, & unhealthy days were used as primary outcome variables. PIA and HRQOL prevalence estimates were computed with 95% CIs. Multiple logistic regression was used to obtain odds ratios (ORs and 95% CIs adjusted for age, ethnicity, and income. Results: Physically inactive rural adults were significantly more likely to report poor HRQOL in all overall crude models with ORs ranging from 1.59 to 2.16. Additionally, sex-by-PIA interactions were significant across all crude HRQOL models with ORs ranging from 2.27 to 3.08 and 1.56 to 2.42 for women and men, respectively. Sex differences were maintained in fully adjusted models, except for mental health and inactivity health with ORs ranging from 1.80 to 2.58 and 1.41 to 1.79 for women and men, respectively. Conclusion: Results from this study show that PIA is a strong predictor of poor HRQOL even after controlling for confounding variables. Furthermore, physically inactive rural women appear more likely to report poor levels of HRQOL than physically inactive rural men.

  3. Biological computation

    CERN Document Server

    Lamm, Ehud


    Introduction and Biological BackgroundBiological ComputationThe Influence of Biology on Mathematics-Historical ExamplesBiological IntroductionModels and Simulations Cellular Automata Biological BackgroundThe Game of Life General Definition of Cellular Automata One-Dimensional AutomataExamples of Cellular AutomataComparison with a Continuous Mathematical Model Computational UniversalitySelf-Replication Pseudo Code Evolutionary ComputationEvolutionary Biology and Evolutionary ComputationGenetic AlgorithmsExample ApplicationsAnalysis of the Behavior of Genetic AlgorithmsLamarckian Evolution Genet

  4. The diseasome of physical inactivity--and the role of myokines in muscle--fat cross talk

    DEFF Research Database (Denmark)

    Pedersen, Bente K


    Type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, dementia and depression constitute a cluster of diseases, which defines 'a diseasome of physical inactivity'. Both physical inactivity and abdominal adiposity, reflecting accumulation of visceral fat mass, are associated...... of exercise. The finding that muscles produce and release myokines provides a conceptual basis to understand the mechanisms whereby exercise influences metabolism and exerts anti-inflammatory effects. According to our theory, contracting skeletal muscles release myokines, which work in a hormone-like fashion......, exerting specific endocrine effects on visceral fat. Other myokines work locally within the muscle via paracrine mechanisms, exerting their effects on signalling pathways involved in fat oxidation....

  5. Bacterial invasion reconstructed molecule by molecule

    Energy Technology Data Exchange (ETDEWEB)

    Werner, James H [Los Alamos National Laboratory


    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the

  6. Marine molecular biology: An emerging field of biological sciences

    Digital Repository Service at National Institute of Oceanography (India)

    Thakur, N.L.; Jain, R.; Natalio, F.; Hamer, B.; Thakur, A.N.; Muller, W.E.G.

    to tackle problems associated with global climate changes, bio- diversity, environmental quality and use of marine living re- sources (Molecular biology in marine science, 1994). Marine biologists study oceanic life in relation to marine environment... that often range from small to global scale, whereas, molecular biologist study biological events in terms of the physiochemical properties of molecules. The immediate benefits of the collab- orative research between these two disciplines could include...

  7. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    sites of diet on the disease pathway. We propose a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. The fifth chapter of the thesis is on discovering of novel anti...... number of thoroughly selected targets. Our need for fundamental understanding of the building blocks of the complex biological systems had been the main reason for the reductionist approach that was mainly applied in the past to elucidate these systems. Nowadays, it is widely recognized that systems...... components with biological systems and their connection to health and disease. The database will be enriched with predicted interactions between food components and protein targets, based on their structural and pharmacophore similarity with known small molecule ligands. Further to this, the associations...

  8. Molecules in Magnetic Fields (United States)

    Berdyugina, Svetlana


    Molecules probe cool matter in the Universe and various astrophysical objects. Their ability to sense magnetic fields provides new insights into magnetic properties of these objects. During the past fifteen years we have carried out a theoretical study of molecular magnetic effects such as the Zeeman, Paschen-Back and Hanle effects and their applications for inferring magnetic structures and spatial inhomogeneities on the Sun, cool stars, brown dwarfs, and exoplanets from molecular spectro-polarimetry (e.g., Berdyugina 2011). Here, we present an overview of this study and compare our theoretical predictions with recent laboratory measurements of magnetic properties of some molecules. We present also a new web-based tool to compute molecular magnetic effects and polarized spectra which is supported by the ERC Advanced Grant HotMol.

  9. Atoms, molecules & elements

    CERN Document Server

    Graybill, George


    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  10. The aesthetics of chemical biology. (United States)

    Parsons, Glenn


    Scientists and philosophers have long reflected on the place of aesthetics in science. In this essay, I review these discussions, identifying work of relevance to chemistry and, in particular, to the field of chemical biology. Topics discussed include the role of aesthetics in scientific theory choice, the aesthetics of molecular images, the beauty-making features of molecules, and the relation between the aesthetics of chemical biology and the aesthetics of industrial design.

  11. Model molecules mimicking asphaltenes. (United States)

    Sjöblom, Johan; Simon, Sébastien; Xu, Zhenghe


    Asphalthenes are typically defined as the fraction of petroleum insoluble in n-alkanes (typically heptane, but also hexane or pentane) but soluble in toluene. This fraction causes problems of emulsion formation and deposition/precipitation during crude oil production, processing and transport. From the definition it follows that asphaltenes are not a homogeneous fraction but is composed of molecules polydisperse in molecular weight, structure and functionalities. Their complexity makes the understanding of their properties difficult. Proper model molecules with well-defined structures which can resemble the properties of real asphaltenes can help to improve this understanding. Over the last ten years different research groups have proposed different asphaltene model molecules and studied them to determine how well they can mimic the properties of asphaltenes and determine the mechanisms behind the properties of asphaltenes. This article reviews the properties of the different classes of model compounds proposed and present their properties by comparison with fractionated asphaltenes. After presenting the interest of developing model asphaltenes, the composition and properties of asphaltenes are presented, followed by the presentation of approaches and accomplishments of different schools working on asphaltene model compounds. The presentation of bulk and interfacial properties of perylene-based model asphaltene compounds developed by Sjöblom et al. is the subject of the next part. Finally the emulsion-stabilization properties of fractionated asphaltenes and model asphaltene compounds is presented and discussed.

  12. Photonic Molecule Lasers Revisited (United States)

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.


    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

  13. Hydrogen molecules in semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Joerg [Technische Universitaet Dresden, 01062 Dresden (Germany)], E-mail:; Hiller, Martin; Lavrov, Edward V. [Technische Universitaet Dresden, 01062 Dresden (Germany)


    Molecular hydrogen, the simplest of all molecules, allows a direct insight into the fundamental properties of quantum mechanics. In the case of H{sub 2}, the Pauli principle leads to two different species, para-H{sub 2} and ortho-H{sub 2}. A conversion between these species is prohibited. Vibrational mode spectra reflect the fundamental properties and allow an unambiguous identification of the H{sub 2} molecules. Today, we have experimental evidence for the trapping of hydrogen molecules in the semiconductors Si, Ge and GaAs at the interstitial sites, within hydrogen-induced platelets, in voids and at impurities (interstitial oxygen in Si). Interstitial H{sub 2} is a nearly free rotor with a surprisingly simple behavior. We review on interstitial H{sub 2} in semiconductors and report on the unexpected preferential disappearance of the para-H{sub 2} or ortho-D{sub 2} species. The origin of the detected ortho-para conversion will be discussed.

  14. Radium-226 in vegetation and substrates at inactive uranium mill sites

    Energy Technology Data Exchange (ETDEWEB)

    Marple, M.L.


    Results of a study of the content of radium-226 in plants growing on inactive uranium mill tailings sites in the Four Corners Region of the southwestern United States and in plants grown under greenhouse conditions with minimal surficial contamination are reported. Field plant samples and associated substrates were analyzed from two carbonate tailings sites in the Grants Mineral Belt of New Mexico. Radium activities in air-cleaned samples ranged from 5 to 368 pCi/g (dry weight) depending on species and location: activities in plants growing on local soils averaged 1.0 pCi/g. The talings and local soils contain 140 to 1400 pCi/g and 2.1 pCi/g, respectively. An evaluation of cleaning methods on selected samples showed that from 17 to 79% of the radium activity measured in air-cleaned samples was due to surficial contamination, which varied with species and location. A survey of 18 inactive uranium mill sites in the Four Corners Region was performed. Radium activity in plant tissues from nine species ranged from 2 to 210 pCi/g on bare tailings and from 0.3 to 30 pCi/g on covered tailings The radium content in most of the soil overburdens on the covered tailings piles was 10 to 17 pCi/g. An experiment was performed to measure radium-226 uptake by two species grown on tailings covered with a shallow (5 cm) soil layer. A grass, Sporobolus airoides (alkali sacaton) and a shrub, Atriplex canescens (four-wing saltbush), were studied. The tailings were a mixture of sands and slimes from a carbonate pile. The tailings treatments were plants grown in a soil cover over tailings; the controls were plants grown only in soil. Three soil types, dune sand, clay loam, and loam, were used. The radium activity of the plant tissue from the tailings treatment compared to that of the appropriate control was 1 to 19 times greater for the grass and 4 to 27 times greater for the shrub.

  15. Bacterial and archaeal communities in the deep-sea sediments of inactive hydrothermal vents in the Southwest India Ridge (United States)

    Zhang, Likui; Kang, Manyu; Xu, Jiajun; Xu, Jian; Shuai, Yinjie; Zhou, Xiaojian; Yang, Zhihui; Ma, Kesen


    Active deep-sea hydrothermal vents harbor abundant thermophilic and hyperthermophilic microorganisms. However, microbial communities in inactive hydrothermal vents have not been well documented. Here, we investigated bacterial and archaeal communities in the two deep-sea sediments (named as TVG4 and TVG11) collected from inactive hydrothermal vents in the Southwest India Ridge using the high-throughput sequencing technology of Illumina MiSeq2500 platform. Based on the V4 region of 16S rRNA gene, sequence analysis showed that bacterial communities in the two samples were dominated by Proteobacteria, followed by Bacteroidetes, Actinobacteria and Firmicutes. Furthermore, archaeal communities in the two samples were dominated by Thaumarchaeota and Euryarchaeota. Comparative analysis showed that (i) TVG4 displayed the higher bacterial richness and lower archaeal richness than TVG11; (ii) the two samples had more divergence in archaeal communities than bacterial communities. Bacteria and archaea that are potentially associated with nitrogen, sulfur metal and methane cycling were detected in the two samples. Overall, we first provided a comparative picture of bacterial and archaeal communities and revealed their potentially ecological roles in the deep-sea environments of inactive hydrothermal vents in the Southwest Indian Ridge, augmenting microbial communities in inactive hydrothermal vents.

  16. Norm theory and the action-effect: The role of social norms in regret following action and inaction

    NARCIS (Netherlands)

    Feldman, Gilad; Albarracín, Dolores


    The action-effect (Kahneman & Tversky, 1982) is one of the most widely cited and replicated effects in the regret literature, showing that negative outcomes are regretted more when they are a result of action compared to inaction. Building on theoretical arguments by norm theory (Kahneman & Miller,

  17. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome

    DEFF Research Database (Denmark)

    da Rocha, Simão Teixeira; Boeva, Valentina; Escamilla-Del-Arenal, Martin;


    During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2) is thought to participate in the early maintenance of the inactive state. Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate th...

  18. [Biological weapons]. (United States)

    Kerwat, K; Becker, S; Wulf, H; Densow, D


    Biological weapons are weapons of mass destruction that use pathogens (bacteria, viruses) or the toxins produced by them to target living organisms or to contaminate non-living substances. In the past, biological warfare has been repeatedly used. Anthrax, plague and smallpox are regarded as the most dangerous biological weapons by various institutions. Nowadays it seems quite unlikely that biological warfare will be employed in any military campaigns. However, the possibility remains that biological weapons may be used in acts of bioterrorism. In addition all diseases caused by biological weapons may also occur naturally or as a result of a laboratory accident. Risk assessment with regard to biological danger often proves to be difficult. In this context, an early identification of a potentially dangerous situation through experts is essential to limit the degree of damage.

  19. A Comparing of Body Composition Components in Physically Active and Inactive Male Students of Sharoud University of Technology

    Directory of Open Access Journals (Sweden)

    Hassan Bahrololoum


    Full Text Available Introduction: Obesity is a serious health problem that reduces life expectancy by increasing one's risk of developing coronary artery disease, hypertension, type 2 diabetes, obstructive pulmonary disease, osteoarthritis and certain types of cancer. Moreover, body composition is divided into fat and fat free mass components. Research shows that physical activity is an important factor that affects body composition. This research aimed at estimating and comparing the body composition components of physically active and inactive male student of Shahroud University of technologyMethods: Participants of this study were 70 inactive male students with average age of (20.86±1.72 years and 65 physically active male students with average age of (20.86±1.72 years. The participants were randomly selected through stratified sampling procedure from various faculties and different admission years. Body composition was estimated with Body composition analyzer system that measured body composition components using bioelectrical impedance method.Results: Data analysis with SPSS-15 software revealed that: average of BF% in physically active sample was (13.43±3.15 and average of inactive samples was (16.73±6.16 which statistically showed significant difference (P<0.001 ; the LBM in physically active samples was (60.27±8.05 Kg and average of inactive samples was (56.43±7.6 Kg which statistically showed significant difference (P<0.005; the average of BMI in physically active sample was (22.62±2.8 kgm and average of inactive samples was (22.25±3.84 kgm which statistically did not show significant difference (P=0.519; the WHR average of physically active samples was (0.798±.03m and average of inactive samples was (0.81±.06m and there was not a significant difference between the two groups. Conclusion: These results revealed that body composition of physically active students were better than that of the inactive ones, so it can be concluded that there is a

  20. Recent progress in histochemistry and cell biology. (United States)

    Hübner, Stefan; Efthymiadis, Athina


    Studies published in Histochemistry and Cell Biology in the year 2011 represent once more a manifest of established and newly sophisticated techniques being exploited to put tissue- and cell type-specific molecules into a functional context. The review is therefore the Histochemistry and Cell Biology's yearly intention to provide interested readers appropriate summaries of investigations touching the areas of tissue biology, developmental biology, the biology of the immune system, stem cell research, the biology of subcellular compartments, in order to put the message of such studies into natural scientific-/human- and also pathological-relevant correlations.

  1. Cooperativity in noncovalent interactions of biologically relevant molecules. (United States)

    Antony, Jens; Brüske, Björn; Grimme, Stefan


    Using a recently published benchmark MP2 database of nucleic acid base trimers, the three-body contribution to the interaction energy (TBE, also termed (non)cooperativity) as a function of base composition and complex geometry is studied. In 28 out of 141 cases (or 20%), the counterpoise-corrected MP2/TZV(2df,2pd) TBE exceeds 1 kcal mol(-1). The TBE is below 1 kcal mol(-1) for all trimers in the benchmark set consisting of U, T, and A, irrespective of the geometrical arrangement in the database. The largest MP2/TZV(2df,2pd) cooperativity of -9 kcal mol(-1) is obtained for a hydrogen-bonded guanine trimer. The largest anti-cooperativity occurs for a protonated cytosine-guanine-cytosine trimer (6 kcal mol(-1)). Generally, the many-body non-additivity term is an order of magnitude smaller than the interaction energies (on average -33 kcal mol(-1)). Employing various density functionals (GGA, meta-GGA, and hybrid) and wave function methods up to third order perturbation theory, and using atomic-orbital basis sets of double-, triple-, and quadruple-zeta quality, we find that the non-additivity effects are almost independent of one particle basis set and method. To enable an interpretation of the TBE, the intermolecular interaction energy is subjected to an energy decomposition analysis (EDA) with a similar definition of the energy terms as the Morokuma decomposition scheme. We find that nonadditive effects are mainly due to the induction, while exchange repulsion, electrostatic, and dispersion contributions are essentially additive, the latter also beyond second order at the MP3/SV(d,p) level. The performance of dispersion-corrected density functional theory for the prediction of structures and binding energies is assessed. While an accurate reproduction of the MP2-optimized reference structures of the trimers can already be accomplished with modern density functionals, only the inclusion of the long-range (London) dispersion interaction provides a consistent picture for both structures and binding energies.

  2. Dynamical model for biological functions of DNA molecules

    Institute of Scientific and Technical Information of China (English)

    PANGXiao-fengI; YANGYao


    We proposed a dynamic model of DNA to study its nonlinear excitation and duplication and transcription in the basis of molecular structure and changes of conformation of DNA under influence of bioenergy.

  3. The importance of correct tautomeric structures for biological molecules

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Mortensen, John; Kamounah, Fadhil S.


    The structures of usnic acid and tetracycline are determined using deuterium isotope effects on 13C chemical shifts in a water environment. In case of usnic acid this is achieved by synthesizing a more water soluble usnic acid with a PEG linker. In the usnic acid case an enolic b-triketone (C-1, C......-14 and C-3) tautomeric equilibrium is at hand below pH 5. At pH 7.4 it exists as a mono anion. In case of tetracycline equilibrium between a zwitter ion and a neutral form is found together with an amide functional group and a hydrogen bonded enolic b-diketone system shifted strongly towards one...

  4. On the accurate molecular dynamics analysis of biological molecules (United States)

    Yamashita, Takefumi


    As the evolution of computational technology has now enabled long molecular dynamics (MD) simulation, the evaluation of many physical properties shows improved convergence. Therefore, we can examine the detailed conditions of MD simulations and perform quantitative MD analyses. In this study, we address the quantitative and accuracy aspects of MD simulations using two example systems. First, it is found that several conditions of the MD simulations influence the area/lipid of the lipid bilayer. Second, we successfully detect the small but important differences in antibody motion between the antigen-bound and unbound states.

  5. Nestedness across biological scales (United States)

    Marquitti, Flavia M. D.; Raimundo, Rafael L. G.; Sebastián-González, Esther; Coltri, Patricia P.; Perez, S. Ivan; Brandt, Débora Y. C.; Nunes, Kelly; Daura-Jorge, Fábio G.; Floeter, Sergio R.; Guimarães, Paulo R.


    Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions that shape ecosystem dynamics. The network thinking revealed recurrent organizational patterns in complex biological systems, such as the formation of semi-independent groups of connected elements (modularity) and non-random distributions of interactions among elements. Other structural patterns, such as nestedness, have been primarily assessed in ecological networks formed by two non-overlapping sets of elements; information on its occurrence on other levels of organization is lacking. Nestedness occurs when interactions of less connected elements form proper subsets of the interactions of more connected elements. Only recently these properties began to be appreciated in one-mode networks (where all elements can interact) which describe a much wider variety of biological phenomena. Here, we compute nestedness in a diverse collection of one-mode networked systems from six different levels of biological organization depicting gene and protein interactions, complex phenotypes, animal societies, metapopulations, food webs and vertebrate metacommunities. Our findings suggest that nestedness emerge independently of interaction type or biological scale and reveal that disparate systems can share nested organization features characterized by inclusive subsets of interacting elements with decreasing connectedness. We primarily explore the implications of a nested structure for each of these studied systems, then theorize on how nested networks are assembled. We hypothesize that nestedness emerges across scales due to processes that, although system-dependent, may share a general compromise between two features: specificity (the number of interactions the elements of the system can have) and affinity (how these elements can be connected to each other). Our findings suggesting occurrence of nestedness

  6. Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles. (United States)

    Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki


    This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis.

  7. Exercise Modality Choices One Year After Intervention in Previously Inactive Older Men and Women. (United States)

    Stathokostas, Liza; Jones, Gareth R


    A convenience sample of 176 healthy, community-dwelling, inactive older adults (mean age 70 ± 5 years; 62 males, 114 females) were tracked for one year. The purpose was to describe the exercise modality choices older adults make one year following participation in an exercise and education intervention. Telephone follow-up contacted 137 participants (78%, men = 50, women = 87) and 62% of the men and 69% of the women reported to be "currently exercising." Exercising independently was the most common type of exercise reported by 81% and 64% of men and women, respectively. Walking was the most commonly reported modality by both genders. The setting of exercise was most often reported to be at home or outside for both men and women. The main reason for continued participation at 12 months was for overall health (50% of men and 40% of women). Little variation was observed for exercise modality choice. Future interventions should consider a variety of exercise and physical activity opportunities for older adults.

  8. Selected indicators of physical activities and inactivities of persons with visual impairments

    Directory of Open Access Journals (Sweden)

    Ladislav Bláha


    Full Text Available BACKGROUND: For persons with visual impairments it is more difficult in many ways to carry out physical activities. They usually have a lower level of locomotive faculties and the negative trends of contemporary lifestyle related to the imbalance in energy intake and expenditure may affect them in larger measure. AIM: The objective of this research was to find out the volume of everyday physical activities compared to the passive relaxation. METHODS: Using the questionnaire IPAQ-short, we investigated the indicators characterizing the applied physical activity and inactivity during the week of citizens with visual impairment in the Usti Region (n = 152. The acquired data was converted to values MET and MET- min. . week-1. RESULTS: We recorded low values in intense physical activities and moderate activities. In the total volume of reported activities during the week (2967 METmin. . week-1 there is an increased share of walking (2222 MET-min. . week-1. CONCLUSIONS: Only a small part of the persons with visual impairments meets more of the health recommended criteria. Their lifestyle may suffer from an excess of sedentary activities that may have an unfavorable influence on health. These manifestations appear most in the persons with the highest degree of impairment. We recommend supporting their activity by the presence of tracers, improvements in navigation and preparation of specific programs. We see the possible measures also in the municipal politics.

  9. Engineering study of 50 miscellaneous inactive underground radioactive waste tanks located at the Hanford Site, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Freeman-Pollard, J.R.


    This engineering study addresses 50 inactive underground radioactive waste tanks. The tanks were formerly used for the following functions associated with plutonium and uranium separations and waste management activities in the 200 East and 200 West Areas of the Hanford Site: settling solids prior to disposal of supernatant in cribs and a reverse well; neutralizing acidic process wastes prior to crib disposal; receipt and processing of single-shell tank (SST) waste for uranium recovery operations; catch tanks to collect water that intruded into diversion boxes and transfer pipeline encasements and any leakage that occurred during waste transfer operations; and waste handling and process experimentation. Most of these tanks have not been in use for many years. Several projects have, been planned and implemented since the 1970`s and through 1985 to remove waste and interim isolate or interim stabilize many of the tanks. Some tanks have been filled with grout within the past several years. Responsibility for final closure and/or remediation of these tanks is currently assigned to several programs including Tank Waste Remediation Systems (TWRS), Environmental Restoration and Remedial Action (ERRA), and Decommissioning and Resource Conservation and Recovery Act (RCRA) Closure (D&RCP). Some are under facility landlord responsibility for maintenance and surveillance (i.e. Plutonium Uranium Extraction [PUREX]). However, most of the tanks are not currently included in any active monitoring or surveillance program.

  10. A novel large filamentous deltaproteobacterium on hydrothermally inactive sulfide chimneys of the Southern Mariana Trough (United States)

    Kato, Shingo; Yamagishi, Akihiko


    Unusual large filamentous bacteria (LFB) have been found on the deep seafloor environments. They play a significant role in geochemical cycling in the dark environments. However, our knowledge of the spatial distribution and phylogenetic diversity of the LFB on the deep seafloor are still limited due to the inaccessibility to these environments. Here, we report the discovery of a novel LFB on a hydrothermally inactive sulfide chimney in a deep-sea hydrothermal field of the Southern Mariana Trough. Light and electron microscopic observation showed that the width and total length of the LFB were >8 μm and >100 μm, respectively, of which morphology was similar to that of other known LFB such as "cable bacteria" of the Desulfobulbaceae. Analyses of a 16S rRNA gene clone library and fluorescence in situ hybridization revealed that this LFB belongs to the Desulfobulbaceae. The 16S rRNA gene of the LFB showed 94% similarity to those of the reported cable bacteria and cultured deltaproteobacterial species, suggesting that the LFB is a novel cable bacterium of the Desulfobulbaceae. The novel LFB potentially play a role in sulfur cycling on sulfide chimneys at the hydrothermally ceasing or even ceased deep-sea hydrothermal fields.

  11. Inhibition of ERBB2-overexpressing Tumors by Recombinant Human Prolidase and Its Enzymatically Inactive Mutant

    Directory of Open Access Journals (Sweden)

    Lu Yang


    Full Text Available ERBB2 is an oncogenic receptor tyrosine kinase overexpressed in a subset of human breast cancer and other cancers. We recently found that human prolidase (PEPD, a dipeptidase, is a high affinity ERBB2 ligand and cross-links two ERBB2 monomers. Here, we show that recombinant human PEPD (rhPEPD strongly inhibits ERBB2-overexpressing tumors in mice, whereas it does not impact tumors without ERBB2 overexpression. rhPEPD causes ERBB2 depletion, disrupts oncogenic signaling orchestrated by ERBB2 homodimers and heterodimers, and induces apoptosis. The impact of enzymatically-inactive mutant rhPEPDG278D on ERBB2 is indistinguishable from that of rhPEPD, but rhPEPDG278D is superior to rhPEPD for tumor inhibition. The enzymatic function of rhPEPD stimulates HIF-1α and other pro-survival factors in tumors, which likely attenuates its antitumor activity. rhPEPDG278D is also attractive in that it may not interfere with the physiologic function of endogenous PEPD in normal cells. Collectively, we have identified a human protein as an inhibitory ERBB2 ligand that inhibits ERBB2-overexpressing tumors in vivo. Several anti-ERBB2 agents are on the market but are hampered by drug resistance and high drug cost. rhPEPDG278D may synergize with these agents and may also be highly cost-effective, since it targets ERBB2 with a different mechanism and can be produced in bacteria.

  12. Phospholipase C-related catalytically inactive protein (PRIP controls KIF5B-mediated insulin secretion

    Directory of Open Access Journals (Sweden)

    Satoshi Asano


    Full Text Available We previously reported that phospholipase C-related catalytically inactive protein (PRIP-knockout mice exhibited hyperinsulinemia. Here, we investigated the role of PRIP in insulin granule exocytosis using Prip-knockdown mouse insulinoma (MIN6 cells. Insulin release from Prip-knockdown MIN6 cells was higher than that from control cells, and Prip knockdown facilitated movement of GFP-phogrin-labeled insulin secretory vesicles. Double-immunofluorescent staining and density step-gradient analyses showed that the KIF5B motor protein co-localized with insulin vesicles in Prip-knockdown MIN6 cells. Knockdown of GABAA-receptor-associated protein (GABARAP, a microtubule-associated PRIP-binding partner, by Gabarap silencing in MIN6 cells reduced the co-localization of insulin vesicles with KIF5B and the movement of vesicles, resulting in decreased insulin secretion. However, the co-localization of KIF5B with microtubules was not altered in Prip- and Gabarap-knockdown cells. The presence of unbound GABARAP, freed either by an interference peptide or by Prip silencing, in MIN6 cells enhanced the co-localization of insulin vesicles with microtubules and promoted vesicle mobility. Taken together, these data demonstrate that PRIP and GABARAP function in a complex to regulate KIF5B-mediated insulin secretion, providing new insights into insulin exocytic mechanisms.

  13. Growth, Metabolism and Physiological Response of the Sea Cucumber, Apostichopus japonicus Selenka During Periods of Inactivity

    Institute of Scientific and Technical Information of China (English)

    DU Rongbin; ZANG Yuanqi; TIAN Xiangli; DONG Shuanglin


    The growth,metabolism and physiological response of the sea cucumber,Apostichopus japonicus,were investigated during periods of inactivity.The body weight,oxygen consumption rate (OCR),activities of acidic phosphatase (ACP),alkaline phosphatase (AKP),catalase (CAT) and superoxide dismutase (SOD),and content of heat shock protein 70 (Hsp70) in the body wall and coelomic fluid of A.japonicus were measured during starvation,experimental aestivation and aestivation.The results showed that the body weight of sea cucumber in the three treatments decreased significantly during the experimental period (P<0.05).The OCR of sea cucumber reduced in starvation and experimental aestivation treatments,but increased gradually in natural aestivation treatment.The activities of ACP and AKP of sea cucumber decreased gradually in all treatments,whereas those of SOD and CAT as well as Hsp70 content decreased in the starvation and experimental aestivation treatments and increased in natural aestivation treatment.The sea cucumber entered a state of aestivation at 24℃.To some extent,the animals in experimental aestivation were different from those in natural aestivation in metabolism and physiological response.These findings suggested that the aestivation mechanism ofA.japonicus is complex and may not be attributed to the elevated temperature only.

  14. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture. (United States)

    Darrow, Emily M; Huntley, Miriam H; Dudchenko, Olga; Stamenova, Elena K; Durand, Neva C; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P; Lander, Eric S; Chadwick, Brian P; Aiden, Erez Lieberman


    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging.

  15. Annual status report on the inactive uranium mill tailings sites remedial action program

    Energy Technology Data Exchange (ETDEWEB)


    Assessments of inactive uranium mill tailings sites in the United States led to the designation of 25 processing sites for remedial action under the provisions of Section 102(a) Public Law 95-604. The Department of Energy assessed the potential health effects to the public from the residual radioactive materials on or near the 25 sites; and, with the advice of the Environmental Protection Agency, the Secretary established priorities for performing remedial action. In designating the 25 sites and establishing the priorities for performing remedial action, the Department of Energy consulted with the Environmental Protection Agency, Nuclear Regulatory Commission, Department of the Interior, governors of the affected States, Navajo Nation, and appropriate property owners. Public participation in this process was encouraged. During Fiscal Year 1980, Department of Energy will be conducting surveys to verify the radiological characterization at the designated processing sites; developing cooperative agreements with the affected States; and initiating the appropriate National Environmental Policy Act documentation prior to conducting specific remedial actions.

  16. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Yang


    Full Text Available Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258 completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction.

  17. Neighborhood street scale elements, sedentary time and cardiometabolic risk factors in inactive ethnic minority women.

    Directory of Open Access Journals (Sweden)

    Rebecca E Lee

    Full Text Available BACKGROUND: Cardiometabolic risk factors such as obesity, excess percent body fat, high blood pressure, elevated resting heart rate and sedentary behavior have increased in recent decades due to changes in the environment and lifestyle. Neighborhood micro-environmental, street scale elements may contribute to health above and beyond individual characteristics of residents. PURPOSE: To investigate the relationship between neighborhood street scale elements and cardiometabolic risk factors among inactive ethnic minority women. METHOD: Women (N = 410 completed measures of BMI, percent body fat, blood pressure, resting heart rate, sedentary behavior and demographics. Trained field assessors completed the Pedestrian Environment Data Scan in participants' neighborhoods. Data were collected from 2006-2008. Multiple regression models were conducted in 2011 to estimate the effect of environmental factors on cardiometabolic risk factors. RESULTS: Adjusted regression models found an inverse association between sidewalk buffers and blood pressure, between traffic control devices and resting heart rate, and a positive association between presence of pedestrian crossing aids and BMI (ps<.05. Neighborhood attractiveness and safety for walking and cycling were related to more time spent in a motor vehicle (ps<.05. CONCLUSIONS: Findings suggest complex relationships among micro-environmental, street scale elements that may confer important cardiometabolic benefits and risks for residents. Living in the most attractive and safe neighborhoods for physical activity may be associated with longer times spent sitting in the car.

  18. Outcome of pregnancy in patients with inactive systemic lupus erythromatosus and minimal proteinuria

    Directory of Open Access Journals (Sweden)

    Alshohaib Saad


    Full Text Available Systemic lupus erythematosus (SLE is a multisystem disease. This study was under-taken to assess the outcome of pregnancies in patients with inactive SLE. We prospectively studied 20 female patients with diagnosis of stable class IV Lupus nephritis followed up at King Abdul Aziz University Hospital, in Jeddah, Saudi Arabia between 1998 and 2008. Before each pregnancy all the patients had their blood pressure, serum creatinine, creatinine clearance, serology for SLE and 24-hour urine protein excretion measured and then repeated at monthly intervals during the pregnancy. Statistical analysis was performed using the Wilcoxon signed-rank test. Despite having negative antinuclear antibody (ANA significant complications were observed during pregnancy. The daily proteinuria during 34-36 weeks′ gestation was significantly higher (P< 0.05 than during 32 weeks. Two patients had abortions one stillbirth and 2 required termination of the pregnancy; one due to severe hypertension, and other due to renal impairment. One patient developed HELLP (hemolysis, elevated liver enzymes, low platelets syndrome. 14 patients had a successful preg-nancy, including 4 requiring a cesarian section. In conclusion, although no clinical evidence of lupus disease activity was demonstrated pre-conception proteinuria significantly increased during pregnancy along with maternal and fetal complications. Pregnant females with diagnosis of SLE need a multidisciplinary care during the pregnancy and post-partum period.

  19. Decision tree approach to evaluating inactive uranium processing sites for liner requirements

    Energy Technology Data Exchange (ETDEWEB)

    Relyea, J.F.


    Recently, concern has been expressed about potential toxic effects of both radon emission and release of toxic elements in leachate from inactive uranium mill tailings piles. Remedial action may be required to meet disposal standards set by the states and the US Environmental Protection Agency (EPA). In some cases, a possible disposal option is the exhumation and reburial (either on site or at a new location) of tailings and reliance on engineered barriers to satisfy the objectives established for remedial actions. Liners under disposal pits are the major engineered barrier for preventing contaminant release to ground and surface water. The purpose of this report is to provide a logical sequence of action, in the form of a decision tree, which could be followed to show whether a selected tailings disposal design meets the objectives for subsurface contaminant release without a liner. This information can be used to determine the need and type of liner for sites exhibiting a potential groundwater problem. The decision tree is based on the capability of hydrologic and mass transport models to predict the movement of water and contaminants with time. The types of modeling capabilities and data needed for those models are described, and the steps required to predict water and contaminant movement are discussed. A demonstration of the decision tree procedure is given to aid the reader in evaluating the need for the adequacy of a liner.

  20. AGN feedback at z~2 and the mutual evolution of active and inactive galaxies

    CERN Document Server

    Cimatti, A; Talia, M; Mignoli, M; Rodighiero, G; Kurk, J; Cassata, P; Halliday, C; Renzini, A; Daddi, E


    The relationships between galaxies of intermediate stellar mass and moderate luminosity active galactic nuclei (AGNs) at 110^42.3 erg s^-1 disappear from the blue cloud/green valley where they were hosted predominantly by star-forming systems with disk and irregular morphologies. These results are even clearer when the rest-frame colors are corrected for dust reddening. At z~2.2, the ultraviolet spectra of active galaxies (including two Type 1 AGNs) show possible gas outflows with velocities up to about -500 km s^-1 that are not observed neither in inactive systems at the same redshift, nor at lower redshifts. Such outflows indicate the presence of gas that can move faster than the escape velocities of active galaxies. These results suggest that feedback from moderately luminous AGNs (logL_X~2 by contributing to outflows capable of ejecting part of the interstellar medium and leading to a rapid decrease in the star formation in host galaxies with stellar masses 10

  1. Stereoselective Modulation of P-Glycoprotein by Chiral Small Molecules. (United States)

    Carocci, Alessia; Catalano, Alessia; Turi, Francesco; Lovece, Angelo; Cavalluzzi, Maria M; Bruno, Claudio; Colabufo, Nicola A; Contino, Marialessandra; Perrone, Maria G; Franchini, Carlo; Lentini, Giovanni


    Inhibition of drug efflux pumps such as P-glycoprotein (P-gp) is an approach toward combating multidrug resistance, which is a significant hurdle in current cancer treatments. To address this, N-substituted aryloxymethyl pyrrolidines were designed and synthesized in their homochiral forms in order to investigate the stereochemical requirements for the binding site of P-gp. Our study provides evidence that the chiral property of molecules could be a strategy for improving the capacity for interacting with P-gp, as the most active compounds of the series stereoselectively modulated this efflux pump. The naphthalene-1-yl analogue (R)-2-[(2,3-dichlorophenoxy)methyl]-1-(naphthalen-1-ylmethyl)pyrrolidine) [(R)-7 a] emerged foremost for its potency and stereoselectivity toward P-gp, with the S enantiomer being nearly inactive. The modulation of P-gp by (R)-7 a involved consumption of ATP, thus demonstrating that the compound behaves as a P-gp substrate.

  2. Identification of hydrogen molecules in ZnO. (United States)

    Lavrov, E V; Herklotz, F; Weber, J


    Hydrogen molecules in ZnO are identified by their local vibrational modes. In a Raman study, interstitial H2, HD, and D2 species were found to exhibit local vibrational modes at frequencies 4145, 3628, and 2985 cm-1, respectively. After thermal treatment of vapor phase grown ZnO samples in hydrogen atmosphere, most hydrogen forms shallow donors at the bond-centered site (HBC). Subsequently, HBC migrates through the crystal and forms electrically inactive H2. These results imply that the "hidden" hydrogen in ZnO [G. A. Shi et al., Appl. Phys. Lett. 85, 5601 (2004)10.1063/1.1832736] occurs in the form of interstitial H2.

  3. Molecules in crystals (United States)

    Spackman, Mark A.


    Hirshfeld surface analysis has developed from the serendipitous discovery of a novel partitioning of the crystal electron density into discrete molecular fragments, to a suite of computational tools used widely for the identification, analysis and discussion of intermolecular interactions in molecular crystals. The relationship between the Hirshfeld surface and very early ideas on the internal structure of crystals is outlined, and applications of Hirshfeld surface analysis are presented for three molecules of historical importance in the development of modern x-ray crystallography: hexamethylbenzene, hexamethylenetetramine and diketopiperazine.

  4. Recognition of Nucleic Acid Junctions Using Triptycene-Based Molecules


    Barros, Stephanie A.; Chenoweth, David M.


    Nucleic acid modulation by small molecules is an essential process across the kingdoms of life. Targeting nucleic acids with small molecules represents a significant challenge at the forefront of chemical biology. Nucleic acid junctions are ubiquitous structural motifs in nature and in designed materials. Herein, we describe a new class of structure specific nucleic acid junction stabilizers based on a triptycene scaffold. Triptycenes provide significant stabilization of DNA and RNA three-way...

  5. Laser electrospray mass spectrometry of adsorbed molecules at atmospheric pressure (United States)

    Brady, John J.; Judge, Elizabeth J.; Simon, Kuriakose; Levis, Robert J.


    Atmospheric pressure mass analysis of solid phase biomolecules is performed using laser electrospray mass spectrometry (LEMS). A non-resonant femtosecond duration laser pulse vaporizes native samples at atmospheric pressure for subsequent electrospray ionization and transfer into a mass spectrometer. LEMS was used to detect a complex molecule (irinotecan HCl), a complex mixture (cold medicine formulation with active ingredients: acetaminophen, dextromethorphan HBr and doxylamine succinate), and a biological building block (deoxyguanosine) deposited on steel surfaces without a matrix molecule.

  6. Low-intensity wheelchair training in inactive people with long-term spinal cord injury : A randomized controlled trial on fitness, wheelchair skill performance and physical activity levels

    NARCIS (Netherlands)

    van der Scheer, Jan W; de Groot, Sonja; Tepper, Marga; Faber, Willemijn; Group, Allrisc; Veeger, DirkJan H; van der Woude, Lucas H V


    OBJECTIVE: To investigate the effects of low-intensity wheelchair training on wheelchair-specific fitness, wheelchair skill performance and physical activity levels in inactive people with long-term spinal cord injury. DESIGN: Randomized controlled trial. PARTICIPANTS: Inactive manual wheelchair use

  7. Small molecule screening identifies targetable zebrafish pigmentation pathways

    DEFF Research Database (Denmark)

    Colanesi, Sarah; Taylor, Kerrie L; Temperley, Nicholas D


    Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish and investig......Small molecules complement genetic mutants and can be used to probe pigment cell biology by inhibiting specific proteins or pathways. Here, we present the results of a screen of active compounds for those that affect the processes of melanocyte and iridophore development in zebrafish...

  8. Modelling proton transfer in water molecule chains

    CERN Document Server

    Korzhimanov, Artem; Shutova, Tatiana; Samuelsson, Goran


    The process of protons transport in molecular water chains is of fundamental interest for many biological systems. Although many features of such systems can be analyzed using large-scale computational modeling, other features are better understood in terms of simplified model problems. Here we have tested, analytically and numerically, a model describing the classical proton hopping process in molecular water chains. In order to capture the main features of the proton hopping process in such molecular chains, we use a simplified model for our analysis. In particular, our discrete model describes a 1D chain of water molecules situated in an external protein channel structure, and each water molecule is allowed to oscillate around its equilibrium point in this system, while the protons are allowed to move along the line of neighboring oxygen atoms. The occurrence and properties of nonlinear solitary transport structures, allowing for much faster proton transport, are discussed, and the possible implications of...

  9. Interstellar molecules - Formation in solar nebulae (United States)

    Anders, E.


    Herbig's (1970) hypothesis that solar nebulae might be the principal source of interstellar grains and molecules is investigated. The investigation includes the determination of physical and chemical conditions in the early solar system. The production of organic compounds in the solar nebula is studied, and the compounds in meteorites are compared with those obtained in Miller-Urey and Fischer-Tropsch-type (FTT) reactions, taking into consideration aliphatic hydrocarbons, aromatic hydrocarbons, purines, pyrimidines, amino acids, porphyrins, and aspects of carbon-isotope fractionation. It is found that FTT reactions account reasonably well for all well-established features of organic matter in meteorites investigated. The distribution of compounds produced by FTT reactions is compared with the distribution of interstellar molecules. Biological implications of the results are considered.

  10. Molecules Best Paper Award 2013. (United States)

    McPhee, Derek J


    Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013.

  11. Passing Current through Touching Molecules

    DEFF Research Database (Denmark)

    Schull, G.; Frederiksen, Thomas; Brandbyge, Mads


    The charge flow from a single C-60 molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two...

  12. Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery. (United States)

    Hu, Jianping; Feng, Zhiwei; Ma, Shifan; Zhang, Yu; Tong, Qin; Alqarni, Mohammed Hamed; Gou, Xiaojun; Xie, Xiang-Qun


    Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse. The lack of an experimental three-dimensional CB2 structure has hindered not only the development of studies of conformational differences between the inactive and active CB2 but also the rational discovery of novel functional compounds targeting CB2. In this work, we constructed models of both inactive and active CB2 by homology modeling. Then we conducted two comparative 100 ns molecular dynamics (MD) simulations on the two systems-the active CB2 bound with both the agonist and G protein and the inactive CB2 bound with inverse agonist-to analyze the conformational difference of CB2 proteins and the key residues involved in molecular recognition. Our results showed that the inactive CB2 and the inverse agonist remained stable during the MD simulation. However, during the MD simulations, we observed dynamical details about the breakdown of the "ionic lock" between R131(3.50) and D240(6.30) as well as the outward/inward movements of transmembrane domains of the active CB2 that bind with G proteins and agonist (TM5, TM6, and TM7). All of these results are congruent with the experimental data and recent reports. Moreover, our results indicate that W258(6.48) in TM6 and residues in TM4 (V164(4.56)-L169(4.61)) contribute greatly to the binding of the agonist on the basis of the binding energy decomposition, while residues S180-F183 in extracellular loop 2 (ECL2) may be of importance in recognition of the inverse agonist. Furthermore, pharmacophore modeling and virtual screening were carried out for the inactive and active CB2 models in parallel. Among all 10 hits, two compounds exhibited novel scaffolds and can be used as novel chemical probes for future studies of CB2. Importantly, our studies show that the hits obtained from the inactive CB2 model mainly act as inverse agonist(s) or neutral

  13. Recent progress in molecule modification with heavy ion beam irradiation

    Institute of Scientific and Technical Information of China (English)


    The research into heavy ion beam biology started in the 1960s, and so far it has become an important interdisciplinary study. Heavy ion beam is more suitable for molecule modification than other sorts of radiation, for it has many superiorities such as the energy transfer effect and the mass deposition effect. Molecule modification with heavy ion beam irradiation can be applied to developing new medicines and their precursors, genetic engineering, protein engi neering, outer space radiobiology, etc. Retrospect and prospect of the research and development of molecule modifica tion with heavy ion beam irradiation are given.

  14. Electron Scattering From Atoms, Molecules, Nuclei, and Bulk Matter

    CERN Document Server

    Whelan, Colm T


    Topics that are covered include electron scattering in the scanning TEM; basic theory of inelastic electron imaging; study of confined atoms by electron excitation; helium bubbles created in extreme pressure with application to nuclear safety; lithium ion implantation; electron and positron scattering from clusters; electron scattering from physi- and chemi-absorbed molecules on surfaces; coincidence studies; electron scattering from biological molecules; electron spectroscopy as a tool for environmental science; electron scattering in the presence of intense fields; electron scattering from astrophysical molecules; electon interatctions an detection of x-ray radiation.

  15. Multifunctional and biologically active matrices from multicomponent polymeric solutions (United States)

    Kiick, Kristi L. (Inventor); Yamaguchi, Nori (Inventor); Rabolt, John (Inventor); Casper, Cheryl (Inventor)


    A functionalized electrospun matrix for the controlled-release of biologically active agents, such as growth factors, is presented. The functionalized matrix comprises a matrix polymer, a compatibilizing polymer and a biomolecule or other small functioning molecule. In certain aspects the electrospun polymer fibers comprise at least one biologically active molecule functionalized with low molecular weight heparin.

  16. Modelo hierárquico multivariado da inatividade física em crianças de escolas públicas Multivariate hierarchical model for physical inactivity among public school children

    Directory of Open Access Journals (Sweden)

    Mario M. Bracco


    Full Text Available OBJETIVO: Identificar fatores biológicos e sociodemográficos atribuíveis à inatividade física em crianças de escolas públicas. MÉTODOS: Foram estudadas, através de questionário auto-relatado pelos pais, 2.519 crianças (49,3% meninas, de 7 a 10 anos (média = 7,6±0,9 anos, de oito escolas públicas da cidade de São Paulo. Aplicamos a análise de correspondência múltipla para identificar grupos de respostas relacionadas com padrões de atividade e inatividade física e a geração de uma escala ótima. A análise de agrupamento identificou os grupos de crianças ativas e inativas. A análise de curva ROC (receiver operator characteristic, para o estudo das propriedades diagnósticas de uma escala simplificada de inatividade física derivada da escala ótima, mostrou o ponto de corte = 3 como o de melhor sensibilidade e especificidade, sendo utilizado como a variável de resposta no modelo de regressão. Um modelo hierárquico multivariado foi construído, assumindo variáveis categóricas como distais e proximais, adotando-se p OBJECTIVE: To identify biological and sociodemographic factors associated with physical inactivity in public school children. METHODS: Parents of 2,519 children (49.3% of whom were girls, aged 7 to 10 years (mean = 7.6±0.9 years, from eight public schools in São Paulo, Brazil, completed a self-administered questionnaire. We used multiple correspondence analysis to identify groups of responses related to levels of physical activity and inactivity and to obtain an optimal scale. The cluster analysis identified groups of active and inactive children. The analysis of the receiver operator characteristic (ROC curve, for the study of diagnostic properties of a simplified scale for physical inactivity derived from the optimal scale, revealed that a cutoff point of 3 had the best sensitivity and specificity, being therefore used as outcome variable in the regression model. A multivariate hierarchical model was

  17. Massively parallel single-molecule manipulation using centrifugal force

    CERN Document Server

    Halvorsen, Ken


    Precise manipulation of single molecules has already led to remarkable insights in physics, chemistry, biology and medicine. However, widespread adoption of single-molecule techniques has been impeded by equipment cost and the laborious nature of making measurements one molecule at a time. We have solved these issues with a new approach: massively parallel single-molecule force measurements using centrifugal force. This approach is realized in a novel instrument that we call the Centrifuge Force Microscope (CFM), in which objects in an orbiting sample are subjected to a calibration-free, macroscopically uniform force-field while their micro-to-nanoscopic motions are observed. We demonstrate high-throughput single-molecule force spectroscopy with this technique by performing thousands of rupture experiments in parallel, characterizing force-dependent unbinding kinetics of an antibody-antigen pair in minutes rather than days. Additionally, we verify the force accuracy of the instrument by measuring the well-est...

  18. Is synthetic biology mechanical biology? (United States)

    Holm, Sune


    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  19. Personalised Prescription of Scalable High Intensity Interval Training to Inactive Female Adults of Different Ages.

    Directory of Open Access Journals (Sweden)

    Jacqueline L Mair

    Full Text Available Stepping is a convenient form of scalable high-intensity interval training (HIIT that may lead to health benefits. However, the accurate personalised prescription of stepping is hampered by a lack of evidence on optimal stepping cadences and step heights for various populations. This study examined the acute physiological responses to stepping exercise at various heights and cadences in young (n = 14 and middle-aged (n = 14 females in order to develop an equation that facilitates prescription of stepping at targeted intensities. Participants completed a step test protocol consisting of randomised three-minute bouts at different step cadences (80, 90, 100, 110 steps·min-1 and step heights (17, 25, 30, 34 cm. Aerobic demand and heart rate values were measured throughout. Resting metabolic rate was measured in order to develop female specific metabolic equivalents (METs for stepping. Results revealed significant differences between age groups for METs and heart rate reserve, and within-group differences for METs, heart rate, and metabolic cost, at different step heights and cadences. At a given step height and cadence, middle-aged females were required to work at an intensity on average 1.9 ± 0.26 METs greater than the younger females. A prescriptive equation was developed to assess energy cost in METs using multilevel regression analysis with factors of step height, step cadence and age. Considering recent evidence supporting accumulated bouts of HIIT exercise for health benefits, this equation, which allows HIIT to be personally prescribed to inactive and sedentary women, has potential impact as a public health exercise prescription tool.

  20. Mercury Methylation and Environmental Effects of Inactive Mercury Mines in the Circum-Pacific Region (United States)

    Gray, J. E.


    Mercury mines worldwide contain of some the highest concentrations of mercury on earth, and as a result of local mercury contamination, these mines represent areas of environmental concern when mine-drainage enters downstream aquatic systems. The most problematic aspect of mine site mercury contamination is the conversion of inorganic mercury to highly toxic organic mercury compounds, such as methylmercury, and their subsequent uptake by aquatic organisms in surrounding ecosystems. Mercury and methylmercury concentrations were measured in sediment and water samples collected from several inactive mercury mines in Nevada, Alaska, and the Philippines, which are part of the circum-Pacific mineral belt. The mines studied represent different mercury deposit types and sizes, and climatic settings. Geochemical data collected from these mines indicate that areas surrounding hot-springs type mercury deposits generally have lower methylmercury concentrations than silica-carbonate mercury deposits. In hot-springs mercury deposits in Nevada and Alaska, ore is dominantly cinnabar with few acid-water generating minerals such as pyrite, and as a result, mine-water drainage has near neutral pH in which there is low solubility of mercury. Conversely, silica-carbonate deposits, such as Palawan, Philippines, contain abundant cinnabar and pyrite, and the resultant acidic-mine drainage generally has higher concentrations of mercury and methylmercury. Additional factors such as the proximity of mercury mines to wetlands, climatic effects, or mine wastes containing highly soluble mercury compounds potentially enhance mercury methylation. The Palawan mercury mine may be a unique example where several adverse environmental factors produced local mercury contamination, high mercury methylation, fish contamination, and mercury poisoning of humans that consumed these contaminated fish.

  1. Employment status and health: understanding the health of the economically inactive population in Scotland

    Directory of Open Access Journals (Sweden)

    Brown Judith


    Full Text Available Abstract Background Although the association between health and unemployment has been well examined, less attention has been paid to the health of the economically inactive (EI population. Scotland has one of the worst health records compared to any Western European country and the EI population account for 23% of the working age population. The aim of this study is to investigate and compare the health outcomes and behaviours of the employed, unemployed and the EI populations (further subdivided into the permanently sick, looking after home and family [LAHF] and others in Scotland. Methods Using data from the 2003 Scottish Health Survey, the differences in health and health behaviours among the employed, unemployed and the subgroups of the EI population were examined. Results Both low educational attainment and residence in a deprived community were more likely in the permanently sick group. The LAHF and the unemployed showed worse self-reported health and limiting longstanding illness compared to the employed but no significant differences were observed between these groups. The permanently sick group had significantly poorer health outcomes than all the other economic groups. Similar to the unemployed and LAHF they are more likely to smoke than the employed but less likely (along with LAHF and ‘others’ to exhibit heavy alcohol consumption. Interestingly, the LAHF showed better mental health than the rest of the EI group, but a similar mental health status to the unemployed. On the physical health element of lung function, the LAHF were no worse than the employed. Conclusion While on-going health promotion and vocational rehabilitation efforts need to be directed towards all, our data suggests that the EI group is at higher risk and policies and strategies directed at this group may need particular attention.

  2. Physical activity and inactivity in primary and secondary school boys' and girls' daily program

    Directory of Open Access Journals (Sweden)

    Romana Hubáčková


    Full Text Available Background: Children's and youth education is becoming more and more demanding. In conjunction with development of information technology, this fact negatively affects lifestyle of children and youth. Apart from families, schools should play a crucial role in healthy lifestyle promotion in children and youth. Objective: The present study aimed to assess differences in physical activity (PA and physical inactivity (PI among primary and secondary school boys and girls in specific segments of a school day. Methods: The research was conducted between 2010 and 2014 at 15 secondary schools (SS and 9 primary schools (PS in the Silesia-Katowice region in Poland. In total, 86 boys and 71 girls at PS and 125 boys and 113 girls at SS took part in the research. We recorded 587 school days, in total. The ActiTrainer accelerometer was used for PA and PI monitoring. Results: PS boys and girls were more physically active than SS boys and girls. Before school, we observed SS boys to have higher energy expenditure than PS boys (p < .001 and also than SS girls (p < .001. During the school time, 73% of PS boys (40% at SS and 58% of PS girls (42% at SS met the recommendation of 500 steps/hour. Within the entire school day monitoring, 44% of PS boys (29% at SS and 41% of PS girls (34% at SS met the recommended 11,000 steps/day. Conclusions: The results of our study confirmed the facts that PS boys and girls are more physically active than SS boys and girls and, furthermore, that boys are more physically active than girls at both types of schools.

  3. Protection of inactive intranasal ántrax vaccine to Bacillus anthracis infection

    Directory of Open Access Journals (Sweden)

    Adin Priadi


    Full Text Available Ánthrax is an endemic zoonotic disease distributed in many parts of Indonesia. Although vaccination program has been implemented in many areas, cases are still frequently reported. Farmers are reluctant to vaccinate their livestock since spore vaccine used in the field often cause side effects and death of the animals. To overcome this problem, an inactive vaccine composes of Bacillus anthracis toxins, cell wall and capsule subunits was developed. B. anthracis Sterne strain (34F2 was selected to produce toxins and cell walls. Local Bacillus anthracis isolated from Citaringgul was used to produce capsule as the Polymerase Chain Reaction (PCR revealed that this isolate poses cap gene encoding for capsule. Two vaccines compose of 15 μg toxoid, 30 μg of capsule, 15 μg of cell wall and 30 μg toxoid, 60 μg of capsule, 15 μg of cell walls were designated as vaccine I and vaccine II respectively. For each experiment, 10 mice were nasally immunized by placing 5 μl of vaccine into each nare 3 times at 2-week intervals. A group of 10 mice were unvaccinated and used as control. Blood was collected fortnightly to monitor antibody responses. All mice were challenged with 2 x 105 B. anthracis Sterne spores injected subcutaneously two weeks after the last vaccination. Two weeks after vaccination of antibodies to B. anthracis toxin, capsule and cell wall were detected in dot-blot assay. Mice that were immunised intranasally with chitosan adjuvanted vaccine developed high IgG responses in sera as detected by ELISA, and the response was dose dependent. Vaccine II gave better response than vaccine I. Vaccine I and II protected mice from challenge at a rate of 60 and 80% respectively. This results showed that intranasal B. anthracis vaccine composes of toxin, capsule and cell wall with chitosan as an adjuvant gave a good protection against B. anthracis Sterne spores challenge in mice.

  4. The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women

    Directory of Open Access Journals (Sweden)

    I.A. Lesser


    Full Text Available In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55 from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT, visceral adipose tissue (VAT and total abdominal adipose tissue (TAAT between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI. Compared to women in the lowest tertile of VO2 peak (13.8–21.8 mL/kg/min, women in the highest tertile (25.0–27.7 mL/kg/min had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05. We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women.

  5. Nonstationary Stochastic Dynamics Underlie Spontaneous Transitions between Active and Inactive Behavioral States (United States)

    Jun, James J.; Longtin, André


    Abstract The neural basis of spontaneous movement generation is a fascinating open question. Long-term monitoring of fish, swimming freely in a constant sensory environment, has revealed a sequence of behavioral states that alternate randomly and spontaneously between periods of activity and inactivity. We show that key dynamical features of this sequence are captured by a 1-D diffusion process evolving in a nonlinear double well energy landscape, in which a slow variable modulates the relative depth of the wells. This combination of stochasticity, nonlinearity, and nonstationary forcing correctly captures the vastly different timescales of fluctuations observed in the data (∼1 to ∼1000 s), and yields long-tailed residence time distributions (RTDs) also consistent with the data. In fact, our model provides a simple mechanism for the emergence of long-tailed distributions in spontaneous animal behavior. We interpret the stochastic variable of this dynamical model as a decision-like variable that, upon reaching a threshold, triggers the transition between states. Our main finding is thus the identification of a threshold crossing process as the mechanism governing spontaneous movement initiation and termination, and to infer the presence of underlying nonstationary agents. Another important outcome of our work is a dimensionality reduction scheme that allows similar segments of data to be grouped together. This is done by first extracting geometrical features in the dataset and then applying principal component analysis over the feature space. Our study is novel in its ability to model nonstationary behavioral data over a wide range of timescales. PMID:28374017

  6. Dietary and physical activity/inactivity factors associated with obesity in school-aged children. (United States)

    Perez-Rodriguez, Marcela; Melendez, Guillermo; Nieto, Claudia; Aranda, Marisol; Pfeffer, Frania


    Diet and physical activity (PA) are essential components of nutritional status. Adequate nutrition and an active lifestyle are key factors during childhood, because food habits track into adulthood. Children spend more time in school than in any other environment away from home. Studying the diet factors and patterns of PA that affect obesity risk in children during school hours and the complete school day can help identify opportunities to lower this risk. We directly measured the time children spent performing moderate to vigorous PA (MVPA) at school, compared the amount and intensity of PA during school hours with after-school hours, and tried to determine if diet behaviors and PA or inactivity were associated with excess weight and body fat. This cross-sectional study included 143 normal-weight (NLW) and 48 obese children aged 8-10 y. Diet data were obtained from two 24-h recalls. Body composition was measured by bioimpedance. Screen time and sports participation data were self-reported. NLW children drank/ate more dairy servings than the obese children, who consumed more fruit-flavored water than the NLW group. Consumption of soft drinks, sugar-added juices, and fresh juices was low in both groups. Children were less active during school hours than after school. MVPA was lower during school hours in the obese group than in the NLW group. Schools, parents, and authorities should be more involved in promoting strategies to improve the dietary habits and PA levels of school-aged children, because this group is not achieving the recommended level of daily MVPA.

  7. Personalised Prescription of Scalable High Intensity Interval Training to Inactive Female Adults of Different Ages (United States)

    Mair, Jacqueline L.


    Stepping is a convenient form of scalable high-intensity interval training (HIIT) that may lead to health benefits. However, the accurate personalised prescription of stepping is hampered by a lack of evidence on optimal stepping cadences and step heights for various populations. This study examined the acute physiological responses to stepping exercise at various heights and cadences in young (n = 14) and middle-aged (n = 14) females in order to develop an equation that facilitates prescription of stepping at targeted intensities. Participants completed a step test protocol consisting of randomised three-minute bouts at different step cadences (80, 90, 100, 110 steps·min-1) and step heights (17, 25, 30, 34 cm). Aerobic demand and heart rate values were measured throughout. Resting metabolic rate was measured in order to develop female specific metabolic equivalents (METs) for stepping. Results revealed significant differences between age groups for METs and heart rate reserve, and within-group differences for METs, heart rate, and metabolic cost, at different step heights and cadences. At a given step height and cadence, middle-aged females were required to work at an intensity on average 1.9 ± 0.26 METs greater than the younger females. A prescriptive equation was developed to assess energy cost in METs using multilevel regression analysis with factors of step height, step cadence and age. Considering recent evidence supporting accumulated bouts of HIIT exercise for health benefits, this equation, which allows HIIT to be personally prescribed to inactive and sedentary women, has potential impact as a public health exercise prescription tool. PMID:26848956

  8. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers (United States)

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher


    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  9. Engineering life through Synthetic Biology. (United States)

    Chopra, Paras; Kamma, Akhil


    Synthetic Biology is a field involving synthesis of novel biological systems which are not generally found in nature. It has brought a new paradigm in science as it has enabled scientists to create life from the scratch, hence helping better understand the principles of biology. The viability of living organisms that use unnatural molecules is also being explored. Unconventional projects such as DNA playing tic-tac-toe, bacterial photographic film, etc. are taking biology to its extremes. The field holds a promise for mass production of cheap drugs and programming bacteria to seek-and-destroy tumors in the body. However, the complexity of biological systems make the field a challenging one. In addition to this, there are other major technical and ethical challenges which need to be addressed before the field realizes its true potential.

  10. Computational biology

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue


    Computation via biological devices has been the subject of close scrutiny since von Neumann’s early work some 60 years ago. In spite of the many relevant works in this field, the notion of programming biological devices seems to be, at best, ill-defined. While many devices are claimed or proved t...

  11. Lanthanide single molecule magnets

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry


    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

  12. Forces in molecules. (United States)

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W


    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another?

  13. Lanthanide single molecule magnets

    CERN Document Server

    Tang, Jinkui


    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  14. Astrochemistry and Interstellar Molecules (United States)

    Minh, Y. C.


    Astrochemistry provides powerful tools to understand various cosmic phenomena, including those in our solar system to the large-scale structure of the universe. In addition, the chemical property of an astronomical body is a crucial factor which governs the evolution of the system. Recent progress in astrophysical theories, computational modelings, and observational techniques requires a detailed understanding of the interactions between the constituents of an astronomical system, which are atoms and molecules within the system. Especially the far-infrared/sub-millimeter wave range, which is called as the last frontier in astronomical observations, contains numerous molecular lines, which may provide a huge amount of new information. However, we need an astrochemical understanding to use this information fully. Although this review is very limited, I would like to stress the importance of astrochemical approach in this overview for the field, which is getting much more attention than ever before.

  15. News: Synthetic biology leading to specialty chemicals (United States)

    Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate productio...

  16. Biology of Bilirubin Photoisomers. (United States)

    Hansen, Thor Willy Ruud


    Phototherapy is the main treatment for neonatal hyperbilirubinemia. In acute treatment of extreme hyperbilirubinemia, intensive phototherapy may have a role in 'detoxifying' the bilirubin molecule to more polar photoisomers, which should be less prone to crossing the blood-brain barrier, providing a 'brain-sparing' effect. This article reviews the biology of bilirubin isomers. Although there is evidence supporting the lower toxicity of bilirubin photoisomers, there are studies showing the opposite. There are methodologic weaknesses in most studies and better-designed experiments are needed. In an infant acutely threatened by bilirubin-induced brain damage, intensified phototherapy should be used expediently and aggressively.

  17. Evolutionary game theory: molecules as players. (United States)

    Bohl, Katrin; Hummert, Sabine; Werner, Sarah; Basanta, David; Deutsch, Andreas; Schuster, Stefan; Theissen, Günter; Schroeter, Anja


    In this and an accompanying paper we review the use of game theoretical concepts in cell biology and molecular biology. This review focuses on the subcellular level by considering viruses, genes, and molecules as players. We discuss in which way catalytic RNA can be treated by game theory. Moreover, genes can compete for success in replication and can have different strategies in interactions with other genetic elements. Also transposable elements, or "jumping genes", can act as players because they usually bear different traits or strategies. Viruses compete in the case of co-infecting a host cell. Proteins interact in a game theoretical sense when forming heterodimers. Finally, we describe how the Shapley value can be applied to enzymes in metabolic pathways. We show that game theory can be successfully applied to describe and analyse scenarios at the molecular level resulting in counterintuitive conclusions.

  18. Pattern of active and inactive sequences of diabetes self-monitoring in mobile phone and paper diary users. (United States)

    Padhye, Nikhil S; Jing Wang


    In a pilot randomized controlled trial involving overweight or obese participants with type 2 diabetes, we find that smartphone users have sharply higher adherence to self-monitoring of diet, physical activity, blood glucose, and body weight, as compared to paper diary users. By characterizing the pattern of adherence with the probability of continuation of active and inactive sequences of self-monitoring, we find that smartphone users have longer active sequences of self-monitoring of all four behaviors that were being monitored. Smartphone users are also quicker to resume self-monitoring of diet and physical activity after a lapse in self-monitoring, whereas paper diary users have shorter inactive sequences for monitoring blood glucose and body weight. The findings are informative for data collection methodology in this burgeoning area of research.

  19. Oil the possible relationship between the Matsushiro earthquake swarm and the inactivity of Asama-yama Volcano

    Directory of Open Access Journals (Sweden)



    Full Text Available During the famous Matsushiro earthquake swarm more t h a n 700 000 (volcanic earthquakes were observed. At (he same time remarkable contortion of the ground also took place together with other strange geophysical phenomena. In the course of these events, volcano Asama-yama (one of the most active volcanoes of the world showed a perfect inactivity. This volcano is situated at a distance of about 30 km measured from Matsushiro, that is very near the site of the events. In the paper a causal relationship is suggested between the geophysical phenomena at .Matsushiro and the inactivity of Asama-yama. Two alternative possibilites are t r e a t e d briefly. The hypothetical character of these ideas is strongly emphasized by the author, however both possibilities appear to be physically real and can explain all the important geophysical events observed on the spot.

  20. FTIR assay method for UV inactive drug carisoprodol and identification of degradants by RP-HPLC and ESI-MS. (United States)

    Acharya, Pratap Chandra; Vasi, Ruqaiya; Suares, Divya


    A new method of analysis has been developed for UV inactive drug carisoprodol using FTIR spectroscopy. These methods were validated for various parameters according to ICH guidelines. The proposed method has also been successfully applied for the determination of the drug concentration in a tablet formulation. The method proved to be accurate (mean percentage recovery between 95 and 105%), precise and reproducible (relative standard deviation<2%), while being simple, economical and less time consuming than other methods and can be used for routine estimation of carisoprodol in the pharmaceutical industry. The developed method also implicates its utility for other UV inactive substances. The stability of the drug under various stress conditions was studied and the drug was found to be particularly susceptible to alkaline hydrolysis. Degradation products of the alkaline hydrolysis were detected by RP-HPLC and tentatively identified by ESI-MS.

  1. A Smartwatch-Based Assistance System for the Elderly Performing Fall Detection, Unusual Inactivity Recognition and Medication Reminding. (United States)

    Deutsch, Markus; Burgsteiner, Harald


    The growing number of elderly people in our society makes it increasingly important to help them live an independent and self-determined life up until a high age. A smartwatch-based assistance system should be implemented that is capable of automatically detecting emergencies and helping elderly people to adhere to their medical therapy. Using the acceleration data of a widely available smartwatch, we implemented fall detection and inactivity recognition based on a smartphone connected via Bluetooth. The resulting system is capable of performing fall detection, inactivity recognition, issuing medication reminders and alerting relatives upon manual activation. Though some challenges, like the dependence on a smartphone remain, the resulting system is a promising approach to help elderly people as well as their relatives to live independently and with a feeling of safety.

  2. Macrophage migration inhibitory factor (MIF) is rendered enzymatically inactive by myeloperoxidase-derived oxidants but retains its immunomodulatory function. (United States)

    Dickerhof, Nina; Schindler, Lisa; Bernhagen, Jürgen; Kettle, Anthony J; Hampton, Mark B


    Macrophage migration inhibitory factor (MIF) is an important player in the regulation of the inflammatory response. Elevated plasma MIF is found in sepsis, arthritis, cystic fibrosis and atherosclerosis. Immunomodulatory activities of MIF include the ability to promote survival and recruitment of inflammatory cells and to amplify pro-inflammatory cytokine production. MIF has an unusual nucleophilic N-terminal proline with catalytic tautomerase activity. It remains unclear whether tautomerase activity is required for MIF function, but small molecules that inhibit tautomerase activity also inhibit the pro-inflammatory activities of MIF. A prominent feature of the acute inflammatory response is neutrophil activation and production of reactive oxygen species, including myeloperoxidase (MPO)-derived hypochlorous acid and hypothiocyanous acid. We hypothesized that MPO-derived oxidants would oxidize the N-terminal proline of MIF and alter its biological activity. MIF was exposed to hypochlorous acid and hypothiocyanous acid and the oxidative modifications on MIF were examined by LC-MS/MS. Imine formation and carbamylation was observed on the N-terminal proline in response to MPO-dependent generation of hypochlorous and hypothiocyanous acid, respectively. These modifications led to a complete loss of tautomerase activity. However, modified MIF still increased CXCL-8/IL-8 production by peripheral blood mononuclear cells (PBMCs) and blocked neutrophil apoptosis, indicating that tautomerase activity is not essential for these biological functions. Pre-treatment of MIF with hypochlorous acid protected the protein from covalent modification by the MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP). Therefore, oxidant generation at inflammatory sites may protect MIF from inactivation by more disruptive electrophiles, including drugs designed to target the tautomerase activity of MIF.

  3. XML The Impact of High Intensity Interval Training On Lipid Profile, Inflammatory Markers and Anthropometric Parameters in Inactive Women


    Nasrin Zaer Ghodsi (MSc); Mohammad Reza Zolfaghari; Amir Fattah (MSc)


    Background and Objective: High-intensity interval training (HIIT) is a recently proposed exercise protocol, which is time-effective. The aim of this study was to evaluate the effect of HIIT for 8 weeks on the lipid profile, C-reactive protein (CRP), fasting blood sugar (FBS) and anthropometric parameters of young women who do not exercise. Methods: In this study, 20 young physically inactive women performed HIIT workouts for 8 weeks and 3 sessions per week. The training protocol cons...

  4. Climate change adaptation, damages and fossil fuel dependence. An RETD position paper on the costs of inaction

    Energy Technology Data Exchange (ETDEWEB)

    Katofsky, Ryan; Stanberry, Matt; Hagenstad, Marca; Frantzis, Lisa


    The Renewable Energy Technology Deployment (RETD) agreement initiated this project to advance the understanding of the ''Costs of Inaction'', i.e. the costs of climate change adaptation, damages and fossil fuel dependence. A quantitative estimate was developed as well as a better understanding of the knowledge gaps and research needs. The project also included some conceptual work on how to better integrate the analyses of mitigation, adaptation, damages and fossil fuel dependence in energy scenario modelling.

  5. Association Between Living Alone and Physical Inactivity Among People With and Without Disability, Florida Behavioral Risk Factor Surveillance System, 2009


    Escobar-Viera, César G.; Jones, Patrice D.; Schumacher, Jessica R.; Hall, Allyson G


    People with disability may be at risk of developing diseases due to physical inactivity; social support from family and friends is positively related to engaging in regular physical activity. We compared the association between living alone and engagement in physical activity among people with and without disability in Florida. We used multivariate logistical regression to analyze 2009 Florida Behavioral Risk Factor Surveillance System data (n = 10,902) to assess differences in physical activ...

  6. Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

    Energy Technology Data Exchange (ETDEWEB)


    This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

  7. Broad-spectrum health improvements with one year of soccer training in inactive mildly hypertensive middle-aged women

    DEFF Research Database (Denmark)

    Krustrup, P; Skoradal, M-B; Randers, M B


    The study tested the hypothesis that long-term soccer training has positive impact on cardiovascular profile, body composition, bone health, and physical capacity in inactive, pre-menopausal women with mild hypertension. The study applied a randomized controlled design in which physically inactiv...... in broad-spectrum improvements in the health profile of untrained, pre-menopausal women with mild hypertension, including cardiovascular, metabolic, and musculo-skeletal benefits....


    Directory of Open Access Journals (Sweden)



    Full Text Available The biochemical analyses of the blood are largely used for the routine diagnosis and especially for the metabolic survey in farm animals. These facts conduct us to the idea that similar analyses, applied on honeybee hemolymph, could be used IN monitoring the healthy state of honeybee colonies. The present studies represent preliminary researches, which aimed to investigate the variability of the main biochemical parameters in the hemolymph of the healthy honeybees (Apis mellifera in inactive season. The researches were carried out on honeybee samples collected from 5 honeybee colonies belonging to a breeding apiary of the Institute for Beekeeping Research and Development from Bucharest. In order to perform the biochemical analyses, the honeybees samples, consisting in 50 individuals on sample (10 individuals/colony were randomly collected and their haemolimph collected, at different time intervals, in inactive season (fall-winter. Totally, there were collected 250 haemolyph samples in a 2 years interval and the following 21 biochemical parameters were analysed: GLU, HDL-c, ALP, T-cho, Tprot, Alb., BUN, LDH, CPK,, Mg, IP, GGT, GOT, GPT, Ca, Cre,, Amy, T–BIL, TG, UA.. The test was carried out after the collection and processing of the samples using the SPOTCHEM EZSP4430, equipment with dry kits, the slides technique, respectively .During the 2nd part of the inactive season, the values of most biochemical parameters increase in different proportions, their levels being maintained also in the first part of the active seasons (April, May, June.The values obtained for the main studied biochemical parameters in the haemolymph of the healthy honeybees collected from honeybee colonies kept in natural conditions show a highly variable evolution in the two consecutive years of experiments during the inactive season.

  9. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

    DEFF Research Database (Denmark)

    Alibegovic, A C; Sonne, M P; Højbjerre, L


    Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches...... contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity....

  10. Chiral Sensitivity in Electron-Molecule Interactions (United States)

    Dreiling, Joan


    All molecular forms of life possess a chiral asymmetry, with amino acids and sugars found respectively in L- and D-enantiomers only. The primordial origin of this enantiomeric excess is unknown. One possible explanation is given by the Vester- Ulbricht hypothesis, which suggests that left-handed electrons present in beta-radiation, produced by parity-violating weak decays, interacted with biological precursors and preferentially destroyed one of the two enantiomers. Experimental tests of this idea have thus far yielded inconclusive results. We show direct evidence for chirally-dependent bond breaking through a dissociative electron attachment (DEA) reaction when spin-polarized electrons are incident on gas-phase chiral molecules. This provides unambiguous evidence for a well-defined, chirally-sensitive destructive molecular process and, as such, circumstantial evidence for the Vester-Ulbricht hypothesis. I will also present the results of our systematic study of the DEA asymmetry for different chiral halocamphor molecules. Three halocamphor molecules were investigated: 3-bromocamphor (C10H15BrO), 3-iodocamphor(C10H15IO), and 10-iodocamphor. The DEA asymmetries collected for bromocamphor and iodocamphor are qualitatively different, suggesting that the atomic number of the heaviest atom in the molecule plays a crucial role in the asymmetric interactions. The DEA asymmetry data for 3- and 10-iodocamphor have the same qualitative behavior, but the 10-iodocamphor asymmetry is about twice as large at the lowest energies investigated, so the location of the heavy atom in the camphor molecule also affects the asymmetries. This work was performed at the University of Nebraska-Lincoln. This project is funded by NSF Grant PHY-1206067.

  11. Biological Oceanography (United States)

    Dyhrman, Sonya


    The ocean is arguably the largest habitat on the planet, and it houses an astounding array of life, from microbes to whales. As a testament to this diversity and its importance, the discipline of biological oceanography spans studies of all levels of biological organization, from that of single genes, to organisms, to their population dynamics. Biological oceanography also includes studies on how organisms interact with, and contribute to, essential global processes. Students of biological oceanography are often as comfortable looking at satellite images as they are electron micrographs. This diversity of perspective begins the textbook Biological Oceanography, with cover graphics including a Coastal Zone Color Scanner image representing chlorophyll concentration, an electron micrograph of a dinoflagellate, and a photograph of a copepod. These images instantly capture the reader's attention and illustrate some of the different scales on which budding oceanographers are required to think. Having taught a core graduate course in biological oceanography for many years, Charlie Miller has used his lecture notes as the genesis for this book. The text covers the subject of biological oceanography in a manner that is targeted to introductory graduate students, but it would also be appropriate for advanced undergraduates.

  12. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi


    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  13. Histone H3 trimethylation at lysine 9 marks the inactive metaphase X chromosome in the marsupial Monodelphis domestica. (United States)

    Zakharova, Irina S; Shevchenko, Alexander I; Shilov, Alexander G; Nesterova, Tatyana B; Vandeberg, John L; Zakian, Suren M


    In somatic cells of female marsupial and eutherian mammals, X chromosome inactivation (XCI) occurs. XCI results in the transcriptional silencing of one of the two X chromosomes and is accompanied by specific covalent histone modifications attributable to the inactive chromatin state. Because data about repressed chromatin of the inactive X chromosome (Xi) in marsupials are sparse, we examined in more detail the distribution of active and inactive chromatin markers on metaphase X chromosomes of an American marsupial, Monodelphis domestica. Consistent with data reported previously both for eutherian and marsupial mammals, we found that the Xi of M. domestica lacks active histone markers-H3K4 dimethylation and H3K9 acetylation. We did not observe on metaphase spreads enrichment of the Xi with H3K27 trimethylation which is involved in XCI in eutherians and was detected on the Xi in the interphase nuclei of mature female M. domestica in an earlier study. Moreover, we found that the Xi of M. domestica was specifically marked with H3K9 trimethylation, which is known to be a component of the Xi chromatin in eutherians and is involved in both marsupials and eutherians in meiotic sex chromosome inactivation which has been proposed as an ancestral mechanism of XCI.

  14. Role of specific components from commercial inactive dry yeast winemaking preparations on the growth of wine lactic acid bacteria. (United States)

    Andújar-Ortiz, Inmaculada; Pozo-Bayón, Maria Angeles; García-Ruiz, Almudena; Moreno-Arribas, M Victoria


    The role of specific components from inactive dry yeast preparations widely used in winemaking on the growth of three representative wine lactic acid bacteria (Oenococcus oeni, Lactobacillus hilgardii and Pediococcus pentosaceus) has been studied. A pressure liquid extraction technique using solvents of different polarity was employed to obtain extracts with different chemical composition from the inactive dry yeast preparations. Each of the extracts was assayed against the three lactic acid bacteria. Important differences in the effect of the extracts on the growth of the bacteria were observed, which depended on the solvent employed during the extraction, on the type of commercial preparations and on the lactic acid bacteria species. The extracts that exhibited the most different activity were chemically characterized in amino acids, free monosaccharides, monosaccharides from polysaccharides, fatty acids and volatile compounds. In general, specific amino acids and monosaccharides were related to a stimulating effect whereas fatty acid composition and likely some volatile compounds seemed to show an inhibitory effect on the growth of the lactic acid bacteria. These results may provide novel and useful information in trying to obtain better and more specific formulations of winemaking inactive dry yeast preparations.

  15. 不同聚乳酸相对分子质量对其构建复合支架材料生物学功能的影响%Comparative study on the different molecule weight of poly-L-lactic acid in the biological function of composite materials

    Institute of Scientific and Technical Information of China (English)

    张宁; 李昀生


    BACKGROUND: With the development of technology, poly-L-lactic acid/β-tricalcium phosphate composite materials show good characters in the tissue engineering, which can promote osteoblast proliferation, reduce rejection reactions, and improve bone healing in a dose-dependent manner. OBJECTIVE: To test the influence of poly-L-lactic acid with different molecule weights on the structure and function of poly-L-lactic acid/β-tricalcium phosphate composite scaffolds. METHODS: Poly-L-lactic acid with molecule weights of 200 000 and 380 000 were combined with β-tricalcium phosphate to produce composite scaffolds by using freeze-drying method. Porosity and pore size of the samples were measured. The fetal rabbit bone mesenchymal stem cells (BMSCs) were cultured and expanded in vitro. They were harvested and seeded into the prepared poly-L-lactic acid/β-tricalcium phosphate scaffolds. The 3-(4, 5-Dimethylthiazol-2yl)-2, 5 diphenyltetrazolium bromide (MTT) and alkaline phosphatase were examined for comparison between normal cultured BMSCs and those cultured on the different poly-L-lactic acid/β-tricalcium phosphate scaffolds. RESULTS AND CONCLUSION: Images of scanning electron microscope showed that the cells adhered to the scaffolds greatly. The value of MTT and alkaline phosphatase showed no significant difference (P > 0.05). The molecule weight of poly-L-lactic acid has no influence on the biological function of composite materials.%背景:聚乳酸/β-磷酸三钙复合材料作为支架,可以增加成骨细胞的增殖,减少排异反应,提高骨愈合,并具有剂量依赖性.目的:检测不同聚左乳酸相对分子质量对于聚左乳酸-β-磷酸三钙复合支架材料功能及其结构的影响.方法:选用相对分子质量为200 000和 380 000的聚左乳酸通过冻干法与β-磷酸三钙制备成聚左乳酸-β-磷酸三钙复合支架材料,检测样本的孔隙率和孔隙直径,将乳兔的骨髓间充质干细胞与相对分子质量为 200 000

  16. Foldit Biology (United States)


    Report 8/1/2013-7/31/2015 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Foldit Biology NOOO 14-13-C-0221 Sb. GRANT NUMBER N/A Sc. PROGRAM ELEMENT...Include area code) Unclassified Unclassified Unclassified (206) 616-2660 Zoran Popović Foldit Biology (Task 1, 2, 3, 4) Final Report...Period Covered by the Report August 1, 2013 – July 31, 2015 Date of Report: July 31, 2015 Project Title: Foldit Biology Contract Number: N00014-13

  17. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same (United States)

    Croteau, Rodney Bruce; Burke, Charles Cullen


    In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

  18. The time for doing is not the time for change: effects of general action and inaction goals on attitude retrieval and attitude change. (United States)

    Albarracín, Dolores; Handley, Ian M


    Implicit in many informal and formal principles of psychological change is the understudied assumption that change requires either an active approach or an inactive approach. This issue was systematically investigated by comparing the effects of general action goals and general inaction goals on attitude change. As prior attitudes facilitate preparation for an upcoming persuasive message, general action goals were hypothesized to facilitate conscious retrieval of prior attitudes and therefore hinder attitude change to a greater extent than general inaction goals. Experiment 1 demonstrated that action primes (e.g., "go," "energy") yielded faster attitude report than inaction primes (e.g., "rest," "still") among participants who were forewarned of an upcoming persuasive message. Experiment 2 showed that the faster attitude report identified in Experiment 1 was localized on attitudes toward a message topic participants were prepared to receive. Experiments 3, 4, and 5 showed that, compared with inaction primes, action primes produced less attitude change and less argument scrutiny in response to a counterattitudinal message on a previously forewarned topic. Experiment 6 confirmed that the effects of the primes on attitude change were due to differential attitude retrieval. That is, when attitude expression was induced immediately after the primes, action and inaction goals produced similar amounts of attitude change. In contrast, when no attitude expression was induced after the prime, action goals produced less attitude change than inaction goals. Finally, Experiment 7 validated the assumption that these goal effects can be reduced or reversed when the goals have already been satisfied by an intervening task.

  19. Molecule-based magnets

    Indian Academy of Sciences (India)

    J V Yakhmi


    The conventional magnetic materials used in current technology, such as, Fe, Fe2O3, Cr2O3, SmCo5, Nd2Fe14B etc are all atom-based, and their preparation/processing require high temperature routes. Employing self-assembly methods, it is possible to engineer a bulk molecular material with long-range magnetic order, mainly because one can play with the weak intermolecular interactions. Since the first successful synthesis of molecular magnets in 1986, a large variety of them have been synthesized, which can be categorized on the basis of the chemical nature of the magnetic units involved: organic-, metal-based systems, heterobimetallic assemblies, or mixed organic–inorganic systems. The design of molecule-based magnets has also been extended to the design of poly-functional molecular magnets, such as those exhibiting second-order optical nonlinearity, liquid crystallinity, or chirality simultaneously with long-range magnetic order. Solubility, low density and biocompatibility are attractive features of molecular magnets. Being weakly coloured, unlike their opaque classical magnet ‘cousins’ listed above, possibilities of photomagnetic switching exist. Persistent efforts also continue to design the ever-elusive polymer magnets towards applications in industry. While providing a brief overview of the field of molecular magnetism, this article highlights some recent developments in it, with emphasis on a few studies from the author’s own lab.

  20. Strongly interacting ultracold polar molecules

    CERN Document Server

    Gadway, Bryce


    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  1. Alternating-laser excitation : single-molecule FRET and beyond

    NARCIS (Netherlands)

    Hohlbein, Johannes; Craggs, Timothy D.; Cordes, Thorben


    The alternating-laser excitation (ALEX) scheme continues to expand the possibilities of fluorescence-based assays to study biological entities and interactions. Especially the combination of ALEX and single-molecule Forster Resonance Energy Transfer (smFRET) has been very successful as ALEX enables

  2. Single-molecule microscopy using silicone oil immersion objective lenses

    NARCIS (Netherlands)

    M. Hink


    Microscopy techniques capable of detecting individual molecules and providing quantitative data have the potential to offer great biological insight; however, such approaches require the efficient capture of light. Here, Mark Hink explains how the use of new silicone oil immersion objective lenses c

  3. Shift in the equilibrium between on and off states of the allosteric switch in Ras-GppNHp affected by small molecules and bulk solvent composition. (United States)

    Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla


    Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the "on" state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the "ordered off" state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-β. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

  4. Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

    Energy Technology Data Exchange (ETDEWEB)

    Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla (NCSU)


    Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

  5. Fostering synergy between cell biology and systems biology. (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D


    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship.

  6. Domain-based small molecule binding site annotation

    Directory of Open Access Journals (Sweden)

    Dumontier Michel


    Full Text Available Abstract Background Accurate small molecule binding site information for a protein can facilitate studies in drug docking, drug discovery and function prediction, but small molecule binding site protein sequence annotation is sparse. The Small Molecule Interaction Database (SMID, a database of protein domain-small molecule interactions, was created using structural data from the Protein Data Bank (PDB. More importantly it provides a means to predict small molecule binding sites on proteins with a known or unknown structure and unlike prior approaches, removes large numbers of false positive hits arising from transitive alignment errors, non-biologically significant small molecules and crystallographic conditions that overpredict ion binding sites. Description Using a set of co-crystallized protein-small molecule structures as a starting point, SMID interactions were generated by identifying protein domains that bind to small molecules, using NCBI's Reverse Position Specific BLAST (RPS-BLAST algorithm. SMID records are available for viewing at The SMID-BLAST tool provides accurate transitive annotation of small-molecule binding sites for proteins not found in the PDB. Given a protein sequence, SMID-BLAST identifies domains using RPS-BLAST and then lists potential small molecule ligands based on SMID records, as well as their aligned binding sites. A heuristic ligand score is calculated based on E-value, ligand residue identity and domain entropy to assign a level of confidence to hits found. SMID-BLAST predictions were validated against a set of 793 experimental small molecule interactions from the PDB, of which 472 (60% of predicted interactions identically matched the experimental small molecule and of these, 344 had greater than 80% of the binding site residues correctly identified. Further, we estimate that 45% of predictions which were not observed in the PDB validation set may be true positives. Conclusion By

  7. STM investigation of surfactant molecules

    Institute of Scientific and Technical Information of China (English)


    Adsorption and self-organization of sodium alkyl sulfonates (STS and SHS) have been studied on HOPG by using the in situ scanning tunneling microscopy (STM). Both SHS and STS molecules adsorb on the HOPG surface and form long-range well-ordered monolayers. The neighboring molecules in different rows form a "head to head" configuration. In the high-resolution images of STS and SHS molecules, one end of the molecules shows bright spots which are attributed to the SO3- groups.

  8. Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators. (United States)

    Weinmann, Hilmar


    There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators.

  9. Physiological roles of small RNA molecules. (United States)

    Michaux, Charlotte; Verneuil, Nicolas; Hartke, Axel; Giard, Jean-Christophe


    Unlike proteins, RNA molecules have emerged lately as key players in regulation in bacteria. Most reviews hitherto focused on the experimental and/or in silico methods used to identify genes encoding small RNAs (sRNAs) or on the diverse mechanisms of these RNA regulators to modulate expression of their targets. However, less is known about their biological functions and their implications in various physiological responses. This review aims to compile what is known presently about the diverse roles of sRNA transcripts in the regulation of metabolic processes, in different growth conditions, in adaptation to stress and in microbial pathogenesis. Several recent studies revealed that sRNA molecules are implicated in carbon metabolism and transport, amino acid metabolism or metal sensing. Moreover, regulatory RNAs participate in cellular adaptation to environmental changes, e.g. through quorum sensing systems or development of biofilms, and analyses of several sRNAs under various physiological stresses and culture conditions have already been performed. In addition, recent experiments performed with Gram-positive and Gram-negative pathogens showed that regulatory RNAs play important roles in microbial virulence and during infection. The combined results show the diversity of regulation mechanisms and physiological processes in which sRNA molecules are key actors.

  10. Biological preconcentrator (United States)

    Manginell, Ronald P.; Bunker, Bruce C.; Huber, Dale L.


    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  11. Theoretical Investigations Regarding Single Molecules

    DEFF Research Database (Denmark)

    Pedersen, Kim Georg Lind

    Neoclassical Valence Bond Theory, Quantum Transport, Quantum Interference, Kondo Effect, and Electron Pumping. Trap a single organic molecule between two electrodes and apply a bias voltage across this "molecular junction". When electrons pass through the molecule, the different electron paths can...

  12. Micro-Kelvin cold molecules.

    Energy Technology Data Exchange (ETDEWEB)

    Strecker, Kevin E.; Chandler, David W.


    We have developed a novel experimental technique for direct production of cold molecules using a combination of techniques from atomic optical and molecular physics and physical chemistry. The ability to produce samples of cold molecules has application in a broad spectrum of technical fields high-resolution spectroscopy, remote sensing, quantum computing, materials simulation, and understanding fundamental chemical dynamics. Researchers around the world are currently exploring many techniques for producing samples of cold molecules, but to-date these attempts have offered only limited success achieving milli-Kelvin temperatures with low densities. This Laboratory Directed Research and Development project is to develops a new experimental technique for producing micro-Kelvin temperature molecules via collisions with laser cooled samples of trapped atoms. The technique relies on near mass degenerate collisions between the molecule of interest and a laser cooled (micro-Kelvin) atom. A subset of collisions will transfer all (nearly all) of the kinetic energy from the 'hot' molecule, cooling the molecule at the expense of heating the atom. Further collisions with the remaining laser cooled atoms will thermally equilibrate the molecules to the micro-Kelvin temperature of the laser-cooled atoms.

  13. Bioactive molecules: current trends in discovery, synthesis, delivery and testing

    Directory of Open Access Journals (Sweden)

    Yew Beng Kang


    Full Text Available Important bioactive molecules are moleculesthat are pharmacologically active derived from naturalsources and through chemical synthesis. Over the yearsmany of such molecules have been discovered throughbioprospective endeavours. The discovery of taxol fromthe pacific yew tree bark that has the ability in stabilisingcellular microtubules represents one of the hallmarks ofsuccess of such endeavours. In recent years, the discoveryprocess has been aided by the rapid developmentof techniques and technologies in chemistry andbiotechnology. The progress in advanced genetics andcomputational biology has also transformed the wayhypotheses are formulated as well as the strategies for drugdiscovery. Of equal importance is the use of advanceddrug delivery vehicles in enhancing the efficacy andbioavailability of bioactive molecules. The availability ofsuitable animal models for testing and validation is yetanother major determinant in increasing the prospect forclinical trials of bioactive molecules.

  14. Non-destructive Imaging of Individual Bio-Molecules

    CERN Document Server

    Germann, Matthias; Escher, Conrad; Fink, Hans-Werner


    Radiation damage is considered to be the major problem that still prevents imaging an individual biological molecule for structural analysis. So far, all known mapping techniques using sufficient short wave-length radiation, be it X-rays or high energy electrons, circumvent this problem by averaging over many molecules. Averaging, however, leaves conformational details uncovered. Even the anticipated use of ultra-short but extremely bright X-ray bursts of a Free Electron Laser shall afford averaging over 10^6 molecules to arrive at atomic resolution. Here we present direct experimental evidence for non-destructive imaging of individual DNA molecules. In fact, we show that DNA withstands coherent low energy electron radiation with deBroglie wavelength in the Angstrom regime despite a vast dose of 10^8 electrons/nm^2 accumulated over more than one hour.

  15. The Single-Molecule Approach to Membrane Protein Stoichiometry. (United States)

    Nichols, Michael G; Hallworth, Richard


    The advent of techniques for imaging solitary fluorescent molecules has made possible many new kinds of biological experiments. Here, we describe the application of single-molecule imaging to the problem of subunit stoichiometry in membrane proteins. A membrane protein of unknown stoichiometry, prestin, is coupled to the fluorescent enhanced green fluorescent protein (eGFP) and synthesized in the human embryonic kidney (HEK) cell line. We prepare adherent membrane fragments containing prestin-eGFP by osmotic lysis. The molecules are then exposed to continuous low-level excitation until their fluorescence reaches background levels. Their fluorescence decreases in discrete equal-amplitude steps, consistent with the photobleaching of single fluorophores. We count the number of steps required to photobleach each molecule. The molecular stoichiometry is then deduced using a binomial model.

  16. Enzyme Molecules in Solitary Confinement

    Directory of Open Access Journals (Sweden)

    Raphaela B. Liebherr


    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  17. Enzyme molecules in solitary confinement. (United States)

    Liebherr, Raphaela B; Gorris, Hans H


    Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  18. Characterizing Structural Stability of Amyloid Motif Fibrils Mediated by Water Molecules. (United States)

    Choi, Hyunsung; Chang, Hyun Joon; Lee, Myeongsang; Na, Sungsoo


    In biological systems, structural confinements of amyloid fibrils can be mediated by the role of water molecules. However, the underlying effect of the dynamic behavior of water molecules on structural stabilities of amyloid fibrils is still unclear. By performing molecular dynamics simulations, we investigate the dynamic features and the effect of interior water molecules on conformations and mechanical characteristics of various amyloid fibrils. We find that a specific mechanism induced by the dynamic properties of interior water molecules can affect diffusion of water molecules inside amyloid fibrils, inducing their different structural stabilities. The conformation of amyloid fibrils induced by interior water molecules show the fibrils' different mechanical features. We elucidate the role of confined and movable interior water molecules in structural stabilities of various amyloid fibrils. Our results offer insights not only in further understanding of mechanical features of amyloids as mediated by water molecules, but also in the fine-tuning of the functional abilities of amyloid fibrils for applications.

  19. Revised cutoff values of ALT and HBV DNA level can better differentiate HBeAg (- chronic inactive HBV patients from active carriers

    Directory of Open Access Journals (Sweden)

    Gull Sana


    Full Text Available Abstract Background and Aims ELISA is still used as primary test for diagnosis HBV disease. However, ELISA-positive patients were marked as HBV inactive after confirmation with PCR and vice versa. Our aim was to assess the performance of new cut-off value of ALT, HBV DNA load and significance of AST as screening tool for HBeAg (- chronic active or inactive patients in Pakistani population. Materials and methods In a cross-sectional, cohort study, 567 HBeAg (- patients followed for one year were selected. Patients with persistent elevated ALT than normal and HBV DNA ≥ 100,000 copies/mL were taken as active chronic. Diagnostic values for ALT, AST and HBV DNA load in HBV HBeAg (- chronic active and inactive patients compared using receiver operation characteristic (ROC curves. Results Of 567 HBeAg (- patients, 228 were classified as chronic inactive and 339 as active. HBV infection was dominant in male. Serum ALT, AST and HBV DNA levels showed significant and high AUROC to differentiate chronic HBeAg (- inactive patients from active. AUROC for Serum ALT, AST and HBV DNA were observed 0.997, 0.969 and 1.000, respectively. For revised cut off value for ALT (30 IU/L for male and 19 IU/L for female and HBV DNA load ≥100,000 copies/mL, a PPV of 97%, NPV of 94%, a sensitivity of 98%, and a specificity of 92% was observed to discriminate active carriers from inactive carriers. We also observed 93.5% specificity, 83.1% sensitivity, 82% PPV and 89.5% NPV for AST ≤20 IU/L to differentiate inactive carriers from active ones in our study group. Conclusions Revised cut off value of ALT and NIH derived HBV DNA value can better discriminate between HBeAg (- chronic active and inactive patients.

  20. Poor muscle strength and function in physically inactive childhood-onset systemic lupus erythematosus despite very mild disease

    Directory of Open Access Journals (Sweden)

    Ana Jéssica Pinto

    Full Text Available ABSTRACT Objective: To compare muscle strength (i.e. lower- and upper-body strength and function between physically inactive childhood-onset systemic lupus erythematosus patients (C-SLE and healthy controls (CTRL. Methods: This was a cross-sectional study and the sample consisted of 19 C-SLE (age between 9 and 18 years and 15 CTRL matched by age, sex, body mass index (BMI, and physical activity levels (assessed by accelerometry. Lower- and upper-body strength was assessed by the one-repetition-maximum (1-RM test. Isometric strength was assessed through a handgrip dynamometer. Muscle function was evaluated by the timed-stands test (TST and the timed-up-and-go test (TUG. Results: When compared with CTRL, C-SLE showed lower leg-press and bench-press 1-RM (p = 0.026 and p = 0.008, respectively, and a tendency toward lower handgrip strength (p = 0.052. C-SLE showed lower TST scores (p = 0.036 and a tendency toward higher TUG scores (p = 0.070 when compared with CTRL. Conclusion: Physically inactive C-SLE patients with very mild disease showed reduced muscle strength and functionality when compared with healthy controls matched by physical activity levels. These findings suggest C-SLE patients may greatly suffer from a physically inactive lifestyle than healthy controls do. Moreover, some sub-clinical “residual” effect of the disease or its pharmacological treatment seems to affect C-SLE patients even with a well-controlled disease.

  1. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny


    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  2. Controversial issues regarding the roles of IL-10 and IFN-γ in active/inactive chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Hossein; Khorramdelazad; Gholamhossein; Hassanshahi; Mohammad; Kazemi; Arababadi


    According to the important roles played by cytokines in induction of appropriate immune responses against hepatitis B virus(HBV),Dimitropoulou et al have examined the important cytokines in their patients.They showed that the serum levels of interleukin 10(IL-10)and interferon-γ(IFN-γ)were decreased in patients with HBeAg-negative chronic active hepatitis B compared with the inactive hepatitis B virus carriers(Dimitropoulou et al 2013).The controversy can be considered regarding the decreased serum levels of IFN-γin the HBeAg-negative chronic active hepatitis B patients.They concluded that subsequent to decreased expression of IFN-γ,the process of HBV proliferation led to liver diseases.Previous studies stated that HBV is not directly cytopathic for the infected hepatocytes and immune responses are the main reason for destruction of hepatocytes(Chisari et al,2010).Scientists believe that immune responses against HBV are stronger in active forms of chronic HBV infected patients than inactive forms(Zhang et al,2012).Therefore,the findings from Dimitropoulou et al may deserve further attention and discussion.Additionally,downregulation of IL-10 inchronically active hepatitis B infected patients has also confirmed our claim.IL-10 is an anti-inflammatory cytokine and its expression is increased in inactive forms in order to downregulate immune responses(Arababadi et al,2012).Thus,based on the results from Dimitropoulou et al,it can be concluded that increased immune responses in chronically active hepatitis B infected patients are related to declined expression of IL-10 and interestingly IFN-γis not involved in induction of immune responses in these patients.

  3. The Biology of Neisseria Adhesins

    Directory of Open Access Journals (Sweden)

    Miao-Chiu Hung


    Full Text Available Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology.

  4. 试论哲学的无为与有为%On Inaction and Action of Philosophy

    Institute of Scientific and Technical Information of China (English)



    哲学既是有为的又是无为的,说它无为乃是因为这是从功利价值角度分析的,它确实无法为人们带来任何的功利价值,这是由哲学爱智慧的本性决定的.哲学的无为主要表现在:哲学无法解决某一具体经验世界的问题;哲学对于许多问题无法给出一个确定性的答案;哲学无法给人们带来任何现实的功利价值;哲学无法像音乐或艺术作品那样给人以美的享受和艺术鉴赏力.但哲学又是有为的,具体表现在:对经验常识的根据的批判审查,使人获得确定性的知识或真理;对超验世界的终极价值追求,使人获得最高的行为规范和尺度;对人生价值的讯问,是使人过一个好的生活,并力图使灵魂处于卓越状态.哲学正是在这种有所为和有所不为的选择中,来展示自己对智慧的崇高之爱的.%Philosophy is both active and inactive.Analyzed from the perspective of utilitarian value,it is inactive.Its loving-wisdom nature decides that philosophy cannot bring any utilitarian value to people.The inaction of philosophy mainly lies in that philosophy cannot solve the problem of a particular experience of the world;that philosophy cannot give definitive answers to many problems;that philosophy cannot bring any real utilitarian values to people;that philosophy cannot give people aesthetic experience and virtuosity like music or art.But philosophy is active as well which lies in that through critically examining the basis of common sense,people get certain knowledge or truth;that through pursuing the ultimate values of transcendent world,people get the highest norms and standards;that through interrogating the value of life,people live a good life and try to make the soul in excellent condition.It is in the selection of inaction and action that philosophy shows its noble love to wisdom.

  5. Physical inactivity in patients with rheumatoid arthritis: Data from twenty-one countries in a cross-sectional, international study

    DEFF Research Database (Denmark)

    Sokka, T.; Hakkinen, A.; Kautiainen, H.


    exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. Conclusion. In many......Objective. Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease...... countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels Udgivelsesdato: 2008/1/15...

  6. Biology Notes. (United States)

    School Science Review, 1981


    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  7. (Biological dosimetry)

    Energy Technology Data Exchange (ETDEWEB)

    Preston, R.J.


    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  8. Marine Biology (United States)

    Dewees, Christopher M.; Hooper, Jon K.


    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  9. Scaffolded biology. (United States)

    Minelli, Alessandro


    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  10. Biology Notes. (United States)

    School Science Review, 1984


    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  11. Insights into circular RNA biology

    DEFF Research Database (Denmark)

    Ebbesen, Karoline K; Hansen, Thomas B; Kjems, Jørgen


    Circular RNAs (circRNAs) are a novel class of non-coding RNA characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed backsplicing. CircRNAs are emerging as a heterogeneous class of molecules involved in modulating gene expression by regu...... and lastly, an outlook with a focus on unanswered questions regarding circRNA biology will be included....

  12. Overcoming the risk of inaction from emissions uncertainty in smallholder agriculture (United States)

    Berry, N. J.; Ryan, C. M.


    The potential for improving productivity and increasing the resilience of smallholder agriculture, while also contributing to climate change mitigation, has recently received considerable political attention (Beddington et al 2012). Financial support for improving smallholder agriculture could come from performance-based funding including sale of carbon credits or certified commodities, payments for ecosystem services, and nationally appropriate mitigation action (NAMA) budgets, as well as more traditional sources of development and environment finance. Monitoring the greenhouse gas fluxes associated with changes to agricultural practice is needed for performance-based mitigation funding, and efforts are underway to develop tools to quantify mitigation achieved and assess trade-offs and synergies between mitigation and other livelihood and environmental priorities (Olander 2012). High levels of small scale variability in carbon stocks and emissions in smallholder agricultural systems (Ziegler et al 2012) mean that data intensive approaches are needed for precise and unbiased mitigation monitoring. The cost of implementing such monitoring programmes is likely to be high, and this introduces the risk that projects will not be developed in areas where there is the greatest need for agricultural improvements, which are likely to correspond with areas where existing data or research infrastructure are lacking. When improvements to livelihoods and food security are expected as co-benefits of performance-based mitigation finance, the risk of inaction is borne by the rural poor as well as the global climate. In situ measurement of carbon accumulation in smallholders' soils are not usually feasible because of the costs associated with sampling in a heterogeneous landscape, although technological advances could improve the situation (Milori et al 2012). Alternatives to in situ measurement are to estimate greenhouse gas fluxes by extrapolating information from existing

  13. Single Molecule Electronics and Devices

    Directory of Open Access Journals (Sweden)

    Makusu Tsutsui


    Full Text Available The manufacture of integrated circuits with single-molecule building blocks is a goal of molecular electronics. While research in the past has been limited to bulk experiments on self-assembled monolayers, advances in technology have now enabled us to fabricate single-molecule junctions. This has led to significant progress in understanding electron transport in molecular systems at the single-molecule level and the concomitant emergence of new device concepts. Here, we review recent developments in this field. We summarize the methods currently used to form metal-molecule-metal structures and some single-molecule techniques essential for characterizing molecular junctions such as inelastic electron tunnelling spectroscopy. We then highlight several important achievements, including demonstration of single-molecule diodes, transistors, and switches that make use of electrical, photo, and mechanical stimulation to control the electron transport. We also discuss intriguing issues to be addressed further in the future such as heat and thermoelectric transport in an individual molecule.

  14. Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-Calus reporter gene assay

    NARCIS (Netherlands)

    Legler, J.; Jonas, A.; Lahr, J.; Vethaak, A.D.; Brouwer, A.; Murk, A.J.


    Although estrogens are excreted as biologically inactive conjugates, they can be reconverted to an active form, possibly by bacteria. A simple method was developed to deconjugate estrogen metabolites present in human urine and fish bile back to active estrogens by enzymatic hydrolysis with b-glucuro

  15. When water molecules meet air


    Hsie, Cho-Shuen; Campen, R. Kramer; Verde, Ana Vila; Bolhuis, Peter; Nienhuys, Han-Kwang; Bonn, Mischa


    About 70% of our planet is covered in water. Most of that water exists as water in the bulk – the neighbors of water molecules are other water molecules – and only a small fraction of molecules are at the air-water interface. Despite the small relative abundance of interfacial water, it is of the utmost importance: it governs the chemistry involving the surface of oceans and seawater aerosols, or the small water droplets forming clouds. Reactions at the air-water interface are directly releva...

  16. Decoupling Activation of Heme Biosynthesis from Anaerobic Toxicity in a Molecule Active in Staphylococcus aureus


    Dutter, Brendan F.; Mike, Laura A.; Reid, Paul R.; Chong, Katherine M.; Ramos-Hunter, Susan J.; Skaar, Eric P.; Sulikowski, Gary A.


    Small molecules active in the pathogenic bacterium Staphylococcus aureus are valuable tools for the study of its basic biology and pathogenesis, and many molecules may provide leads for novel therapeutics. We have previously reported a small molecule, 1, which activates endogenous heme biosynthesis in S. aureus, leading to an accumulation of intracellular heme. In addition to this novel activity, 1 also exhibits toxicity towards S. aureus growing under fermentative conditions. To determine if...

  17. pyFRET: A Python Library for Single Molecule Fluorescence Data Analysis


    Murphy, Rebecca R.; Jackson, Sophie E.; Klenerman, David


    Single molecule F\\"orster resonance energy transfer (smFRET) is a powerful experimental technique for studying the properties of individual biological molecules in solution. However, as adoption of smFRET techniques becomes more widespread, the lack of available software, whether open source or commercial, for data analysis, is becoming a significant issue. Here, we present pyFRET, an open source Python package for the analysis of data from single-molecule fluorescence experiments from freely...


    Noguchi, H; Bronfenbrenner, J


    The fixing property of a specific precipitate and of syphilitic serum in the presence of certain antigenic lipoids, can be removed by adding certain non-complementary proteins of blood serum or hen's egg. This disappearance of the complementary activity in the syphilis reaction, as well as in the true Bordet-Gengou reaction, is a phenomenon which incidentally accompanies the fixation of certain serum constituents, some of which possess a complementary activity. The presence or absence of the complementary property in these protein components does not influence fixation. Whether the disappearance of the complementary activity during the phenomenon of so-called fixation is due to a mechanical precipitation of the molecules through absorption or whether it is due to a physico-chemical alteration of the active molecules, is unknown. It is more probable that a chemical interaction takes place in the case of the syphilis reaction. Certain sera, for example, those derived from man and goat, show a low fixability. It is interesting to note that the fixability is gradually diminished when these sera and egg-white are heated to a temperature above 56 degrees C., and totally disappears at 85 degrees C. The coagulation of proteins with absolute alcohol or by boiling, destroys their interfering property. The fact that the fixation is not selectively directed towards complement, has a very important meaning for exact serology. The one-sided accuracy as to the complementary unity is no longer sufficient for quantitative work. Both the complementary and the volumetric unity of a serum serving as the source of complement should be taken into consideration. Besides, the fixability of the sera of various species of animals must also be considered. From these facts a formula may be derived for deciding the degree of suitableness of a serum. see PDF for Equation X is the degree of suitableness; K, the species constant for the fixability; P, the complementary activity; and V, the volume

  19. Recursive construction of perfect DNA molecules from imperfect oligonucleotides. (United States)

    Linshiz, Gregory; Yehezkel, Tuval Ben; Kaplan, Shai; Gronau, Ilan; Ravid, Sivan; Adar, Rivka; Shapiro, Ehud


    Making faultless complex objects from potentially faulty building blocks is a fundamental challenge in computer engineering, nanotechnology and synthetic biology. Here, we show for the first time how recursion can be used to address this challenge and demonstrate a recursive procedure that constructs error-free DNA molecules and their libraries from error-prone oligonucleotides. Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed. Our recursive construction procedure surpasses existing methods for de novo DNA synthesis in speed, precision, amenability to automation, ease of combining synthetic and natural DNA fragments, and ability to construct designer DNA libraries. It thus provides a novel and robust foundation for the design and construction of synthetic biological molecules and organisms.

  20. DMSO molecule as ancillary ligand in Ru-based catalysts for ring opening metathesis polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Santana, Sirlane A.A.; Carvalho Junior, Valdemiro P.; Lima-Neto, Benedito S. [Universidade de Sao Paulo, Sao Carlos (USP), SP (Brazil). Inst. de Quimica


    The ring-opening metathesis polymerization (ROMP) of norbornene (NBE) occurs in the presence of the fac-[RuCl{sub 2}(S-DMSO){sub 3}(O-DMSO)] complex and ethyldiazoacetate (5 {mu}L), where DMSO is S- or O-bonded dimethylsulfoxide. The yield is 62% (PDI = 1.64) at room temperature for 5 min and 88% (PDI 1.93) at 50 deg C for 30 min, with [NBE]/[Ru] = 516 in CHCl{sub 3}. The yield is 90% (PDI = 1.64) in the presence of NBu{sub 4}ClO{sub 4} at room temperature for 5 min. The complex is practically inactive when one or two molecules of DMSO are replaced by pyridine, imidazole, 2-methyl-imidazole or benzimidazole. The in situ formation of the catalytic species and the behavior of the DMSO molecules as ancillary ligands in the reactivity of the RuII complexes are discussed. (author)