WorldWideScience

Sample records for biomolecular structures functional

  1. From dynamics to structure and function of model biomolecular systems

    NARCIS (Netherlands)

    Fontaine-Vive-Curtaz, F.

    2007-01-01

    The purpose of this thesis was to extend recent works on structure and dynamics of hydrogen bonded crystals to model biomolecular systems and biological processes. The tools that we have used are neutron scattering (NS) and density functional theory (DFT) and force field (FF) based simulation method

  2. Nanoarchitectonics of biomolecular assemblies for functional applications

    Science.gov (United States)

    Avinash, M. B.; Govindaraju, T.

    2014-10-01

    The stringent processes of natural selection and evolution have enabled extraordinary structure-function properties of biomolecules. Specifically, the archetypal designs of biomolecules, such as amino acids, nucleobases, carbohydrates and lipids amongst others, encode unparalleled information, selectivity and specificity. The integration of biomolecules either with functional molecules or with an embodied functionality ensures an eclectic approach for novel and advanced nanotechnological applications ranging from electronics to biomedicine, besides bright prospects in systems chemistry and synthetic biology. Given this intriguing scenario, our feature article intends to shed light on the emerging field of functional biomolecular engineering.

  3. Retroactivity in the Context of Modularly Structured Biomolecular Systems

    Science.gov (United States)

    Pantoja-Hernández, Libertad; Martínez-García, Juan Carlos

    2015-01-01

    Synthetic biology has intensively promoted the technical implementation of modular strategies in the fabrication of biological devices. Modules are considered as networks of reactions. The behavior displayed by biomolecular systems results from the information processes carried out by the interconnection of the involved modules. However, in natural systems, module wiring is not a free-of-charge process; as a consequence of interconnection, a reactive phenomenon called retroactivity emerges. This phenomenon is characterized by signals that propagate from downstream modules (the modules that receive the incoming signals upon interconnection) to upstream ones (the modules that send the signals upon interconnection). Such retroactivity signals, depending of their strength, may change and sometimes even disrupt the behavior of modular biomolecular systems. Thus, analysis of retroactivity effects in natural biological and biosynthetic systems is crucial to achieve a deeper understanding of how this interconnection between functionally characterized modules takes place and how it impacts the overall behavior of the involved cell. By discussing the modules interconnection in natural and synthetic biomolecular systems, we propose that such systems should be considered as quasi-modular. PMID:26137457

  4. Computational and theoretical aspects of biomolecular structure and dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.E.; Berendzen, J.; Catasti, P., Chen, X. [and others

    1996-09-01

    This is the final report for a project that sought to evaluate and develop theoretical, and computational bases for designing, performing, and analyzing experimental studies in structural biology. Simulations of large biomolecular systems in solution, hydrophobic interactions, and quantum chemical calculations for large systems have been performed. We have developed a code that implements the Fast Multipole Algorithm (FMA) that scales linearly in the number of particles simulated in a large system. New methods have been developed for the analysis of multidimensional NMR data in order to obtain high resolution atomic structures. These methods have been applied to the study of DNA sequences in the human centromere, sequences linked to genetic diseases, and the dynamics and structure of myoglobin.

  5. Structure and Interactions of Isolated Biomolecular Building Blocks.

    Science.gov (United States)

    de Vries, Mattanjah

    2006-03-01

    We investigate biomolecular building blocks and their clusters with each other and with water on a single molecular level. The motivation is the need to distinguish between intrinsic molecular properties and those that result from the biological environment. This is achieved by a combination of laser desorption and jet cooling, applied to aromatic amino acids, small peptides containing those, nucleobases and nucleosides. This approach is coupled with a number of laser spectroscopic techniques, including resonant multi-photon ionization, spectral hole burning and infra-red ion-dip spectroscopy. We will discuss examples illustrating how information can be obtained on spatial structure of individual biomolecules, including peptide conformations and details of DNA base-pairing.

  6. Computer programming and biomolecular structure studies: A step beyond internet bioinformatics.

    Science.gov (United States)

    Likić, Vladimir A

    2006-01-01

    This article describes the experience of teaching structural bioinformatics to third year undergraduate students in a subject titled Biomolecular Structure and Bioinformatics. Students were introduced to computer programming and used this knowledge in a practical application as an alternative to the well established Internet bioinformatics approach that relies on access to the Internet and biological databases. This was an ambitious approach considering that the students mostly had a biological background. There were also time constraints of eight lectures in total and two accompanying practical sessions. The main challenge was that students had to be introduced to computer programming from a beginner level and in a short time provided with enough knowledge to independently solve a simple bioinformatics problem. This was accomplished with a problem directly relevant to the rest of the subject, concerned with the structure-function relationships and experimental techniques for the determination of macromolecular structure.

  7. Computer Programming and Biomolecular Structure Studies: A Step beyond Internet Bioinformatics

    Science.gov (United States)

    Likic, Vladimir A.

    2006-01-01

    This article describes the experience of teaching structural bioinformatics to third year undergraduate students in a subject titled "Biomolecular Structure and Bioinformatics." Students were introduced to computer programming and used this knowledge in a practical application as an alternative to the well established Internet bioinformatics…

  8. Potential-of-mean-force description of ionic interactions and structural hydration in biomolecular systems

    Energy Technology Data Exchange (ETDEWEB)

    Hummer, G.; Garcia, A.E. [Los Alamos National Lab., NM (United States). Theoretical Biology and Biophysics Group; Soumpasis, D.M. [Max-Planck-Inst for Biophysical Chemistry, Goettingen (Germany). Biocomputation Group

    1994-10-01

    To understand the functioning of living organisms on a molecular level, it is crucial to dissect the intricate interplay of the immense number of biological molecules. Most of the biochemical processes in cells occur in a liquid environment formed mainly by water and ions. This solvent environment plays an important role in biological systems. The potential-of-mean-force (PMF) formalism attempts to describe quantitatively the interactions of the solvent with biological macromolecules on the basis of an approximate statistical-mechanical representation. At its current status of development, it deals with ionic effects on the biomolecular structure and with the structural hydration of biomolecules. The underlying idea of the PMF formalism is to identify the dominant sources of interactions and incorporate these interactions into the theoretical formalism using PMF`s (or particle correlation functions) extracted from bulk-liquid systems. In the following, the authors shall briefly outline the statistical-mechanical foundation of the PMF formalism and introduce the PMF expansion formalism, which is intimately linked to superposition approximations for higher-order particle correlation functions. The authors shall then sketch applications, which describe the effects of the ionic environment on nucleic-acid structure. Finally, the authors shall present the more recent extension of the PMF idea to describe quantitatively the structural hydration of biomolecules. Results for the interface of ice and water and for the hydration of deoxyribonucleic acid (DNA) will be discussed.

  9. Conformational thermodynamics guided structural reconstruction of biomolecular fragments.

    Science.gov (United States)

    Sikdar, Samapan; Chakrabarti, J; Ghosh, Mahua

    2016-02-01

    Computational prediction of structure for macromolecular fragments is a formidable challenge. Here we show that the differences in conformational thermodynamics, computed using the equilibrium distribution of dihedral angles from molecular dynamics simulation, can identify the better model for the missing residues in the metal ion free (apo) skeletal muscle Troponin C (TnC). We use the model to understand Troponin I interaction with calcium (Ca(2+)) ion bound TnC. Our method to compare conformational thermodynamics between different models can be easily generalized to any macromolecule to understand the structure and function even if experimental structures are not resolved.

  10. iGNM 2.0: the Gaussian network model database for biomolecular structural dynamics.

    Science.gov (United States)

    Li, Hongchun; Chang, Yuan-Yu; Yang, Lee-Wei; Bahar, Ivet

    2016-01-04

    Gaussian network model (GNM) is a simple yet powerful model for investigating the dynamics of proteins and their complexes. GNM analysis became a broadly used method for assessing the conformational dynamics of biomolecular structures with the development of a user-friendly interface and database, iGNM, in 2005. We present here an updated version, iGNM 2.0 http://gnmdb.csb.pitt.edu/, which covers more than 95% of the structures currently available in the Protein Data Bank (PDB). Advanced search and visualization capabilities, both 2D and 3D, permit users to retrieve information on inter-residue and inter-domain cross-correlations, cooperative modes of motion, the location of hinge sites and energy localization spots. The ability of iGNM 2.0 to provide structural dynamics data on the large majority of PDB structures and, in particular, on their biological assemblies makes it a useful resource for establishing the bridge between structure, dynamics and function.

  11. Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

    Science.gov (United States)

    Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

    2015-12-15

    Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to

  12. Variational Methods for Biomolecular Modeling

    CERN Document Server

    Wei, Guo-Wei

    2016-01-01

    Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrosta...

  13. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E.;

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we intr...

  14. Photochemical functionalization of gallium nitride thin films with molecular and biomolecular layers.

    Science.gov (United States)

    Kim, Heesuk; Colavita, Paula E; Metz, Kevin M; Nichols, Beth M; Sun, Bin; Uhlrich, John; Wang, Xiaoyu; Kuech, Thomas F; Hamers, Robert J

    2006-09-12

    We demonstrate that photochemical functionalization can be used to functionalize and photopattern the surface of gallium nitride crystalline thin films with well-defined molecular and biomolecular layers. GaN(0001) surfaces exposed to a hydrogen plasma will react with organic molecules bearing an alkene (C=C) group when illuminated with 254 nm light. Using a bifunctional molecule with an alkene group at one end and a protected amine group at the other, this process can be used to link the alkene group to the surface, leaving the protected amine exposed. Using a simple contact mask, we demonstrate the ability to directly pattern the spatial distribution of these protected amine groups on the surface with a lateral resolution of <12 mum. After deprotection of the amines, single-stranded DNA oligonucleotides were linked to the surface using a bifunctional cross-linker. Measurements using fluorescently labeled complementary and noncomplementary sequences show that the DNA-modified GaN surfaces exhibit excellent selectivity, while repeated cycles of hybridization and denaturation in urea show good stability. These results demonstrate that photochemical functionalization can be used as an attractive starting point for interfacing molecular and biomolecular systems with GaN and other compound semiconductors.

  15. Biomolecular Deuteration for Neutron Structural Biology and Dynamics.

    Science.gov (United States)

    Haertlein, Michael; Moulin, Martine; Devos, Juliette M; Laux, Valerie; Dunne, Orla; Forsyth, V Trevor

    2016-01-01

    Neutron scattering studies provide important information in structural biology that is not accessible using other approaches. The uniqueness of the technique, and its complementarity with X-ray scattering, is greatest when full use is made of deuterium labeling. The ability to produce tailor-made deuterium-labeled biological macromolecules allows neutron studies involving solution scattering, crystallography, reflection, and dynamics to be optimized in a manner that has major impact on the scope, quality, and throughput of work in these areas. Deuteration facilities have now been developed at many neutron centres throughout the world; these are having a crucial effect on neutron studies in the life sciences and on biologically related studies in soft matter. This chapter describes methods that have been developed for the efficient production of deuterium-labeled samples for a wide range of neutron scattering applications. Examples are given that illustrate the use of these samples for each of the main techniques. Perspectives for biological deuterium labeling are discussed in relation to developments at current facilities and those that are planned in the future.

  16. Stable isotope applications in biomolecular structure and mechanisms. A meeting to bring together producers and users of stable-isotope-labeled compounds to assess current and future needs

    Energy Technology Data Exchange (ETDEWEB)

    Trewhella, J.; Cross, T.A.; Unkefer, C.J. [eds.

    1994-12-01

    Knowledge of biomolecular structure is a prerequisite for understanding biomolecular function, and stable isotopes play an increasingly important role in structure determination of biological molecules. The first Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms was held in Santa Fe, New Mexico, March 27--31, 1994. More than 120 participants from 8 countries and 44 institutions reviewed significant developments, discussed the most promising applications for stable isotopes, and addressed future needs and challenges. Participants focused on applications of stable isotopes for studies of the structure and function of proteins, peptides, RNA, and DNA. Recent advances in NMR techniques neutron scattering, EPR, and vibrational spectroscopy were highlighted in addition to the production and synthesis of labeled compounds. This volume includes invited speaker and poster presentations as well as a set of reports from discussion panels that focused on the needs of the scientific community and the potential roles of private industry, the National Stable Isotope Resource, and the National High Magnetic Field Laboratory in serving those needs. This is the leading abstract. Individual papers are processed separately for the database.

  17. Self-chemisorption of azurin on functionalized oxide surfaces for the implementation of biomolecular devices

    Energy Technology Data Exchange (ETDEWEB)

    Biasco, A.; Maruccio, G.; Visconti, P.; Bramanti, A.; Calogiuri, P.; Cingolani, R.; Rinaldi, R

    2004-06-01

    In this work, we investigate the formation of redox protein Azurin (Az) monolayers on functionalized oxygen exposing surfaces. These metallo-proteins mediate electron transfer in the denitrifying chain of Pseudomonas bacteria and exhibit self-assembly properties, therefore they are good candidates for bio-electronic applications. Azurin monolayers are self-assembled onto silane functionalized surfaces and characterized by atomic force microscopy (AFM). We show also that a biomolecular field effect transistor (FET) in the solid state can be implemented by interconnecting an Azurin monolayer immobilized on SiO{sub 2} with two gold nanoelectrodes. Transport experiments, carried out at room temperature and ambient pressure, show FET behavior with conduction modulated by the gate potential.

  18. Combining vibrational biomolecular spectroscopy with chemometric techniques for the study of response and sensitivity of molecular structures/functional groups mainly related to lipid biopolymer to various processing applications.

    Science.gov (United States)

    Yu, Gloria Qingyu; Yu, Peiqiang

    2015-09-01

    The objectives of this project were to (1) combine vibrational spectroscopy with chemometric multivariate techniques to determine the effect of processing applications on molecular structural changes of lipid biopolymer that mainly related to functional groups in green- and yellow-type Crop Development Centre (CDC) pea varieties [CDC strike (green-type) vs. CDC meadow (yellow-type)] that occurred during various processing applications; (2) relatively quantify the effect of processing applications on the antisymmetric CH3 ("CH3as") and CH2 ("CH2as") (ca. 2960 and 2923 cm(-1), respectively), symmetric CH3 ("CH3s") and CH2 ("CH2s") (ca. 2873 and 2954 cm(-1), respectively) functional groups and carbonyl C=O ester (ca. 1745 cm(-1)) spectral intensities as well as their ratios of antisymmetric CH3 to antisymmetric CH2 (ratio of CH3as to CH2as), ratios of symmetric CH3 to symmetric CH2 (ratio of CH3s to CH2s), and ratios of carbonyl C=O ester peak area to total CH peak area (ratio of C=O ester to CH); and (3) illustrate non-invasive techniques to detect the sensitivity of individual molecular functional group to the various processing applications in the recently developed different types of pea varieties. The hypothesis of this research was that processing applications modified the molecular structure profiles in the processed products as opposed to original unprocessed pea seeds. The results showed that the different processing methods had different impacts on lipid molecular functional groups. Different lipid functional groups had different sensitivity to various heat processing applications. These changes were detected by advanced molecular spectroscopy with chemometric techniques which may be highly related to lipid utilization and availability. The multivariate molecular spectral analyses, cluster analysis, and principal component analysis of original spectra (without spectral parameterization) are unable to fully distinguish the structural differences in the

  19. Biomolecular EPR spectroscopy

    CERN Document Server

    Hagen, Wilfred Raymond

    2008-01-01

    Comprehensive, Up-to-Date Coverage of Spectroscopy Theory and its Applications to Biological SystemsAlthough a multitude of books have been published about spectroscopy, most of them only occasionally refer to biological systems and the specific problems of biomolecular EPR (bioEPR). Biomolecular EPR Spectroscopy provides a practical introduction to bioEPR and demonstrates how this remarkable tool allows researchers to delve into the structural, functional, and analytical analysis of paramagnetic molecules found in the biochemistry of all species on the planet. A Must-Have Reference in an Intrinsically Multidisciplinary FieldThis authoritative reference seamlessly covers all important bioEPR applications, including low-spin and high-spin metalloproteins, spin traps and spin lables, interaction between active sites, and redox systems. It is loaded with practical tricks as well as do's and don'ts that are based on the author's 30 years of experience in the field. The book also comes with an unprecedented set of...

  20. A statistical mechanical description of biomolecular hydration

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    We present an efficient and accurate theoretical description of the structural hydration of biological macromolecules. The hydration of molecules of almost arbitrary size (tRNA, antibody-antigen complexes, photosynthetic reaction centre) can be studied in solution and in the crystal environment. The biomolecular structure obtained from x-ray crystallography, NMR, or modeling is required as input information. The structural arrangement of water molecules near a biomolecular surface is represented by the local water density analogous to the corresponding electron density in an x-ray diffraction experiment. The water-density distribution is approximated in terms of two- and three-particle correlation functions of solute atoms with water using a potentials-of-mean-force expansion.

  1. Computational methods to study the structure and dynamics of biomolecules and biomolecular processes from bioinformatics to molecular quantum mechanics

    CERN Document Server

    2014-01-01

    Since the second half of the 20th century machine computations have played a critical role in science and engineering. Computer-based techniques have become especially important in molecular biology, since they often represent the only viable way to gain insights into the behavior of a biological system as a whole. The complexity of biological systems, which usually needs to be analyzed on different time- and size-scales and with different levels of accuracy, requires the application of different approaches, ranging from comparative analysis of sequences and structural databases, to the analysis of networks of interdependence between cell components and processes, through coarse-grained modeling to atomically detailed simulations, and finally to molecular quantum mechanics. This book provides a comprehensive overview of modern computer-based techniques for computing the structure, properties and dynamics of biomolecules and biomolecular processes. The twenty-two chapters, written by scientists from all over t...

  2. Integrative NMR for biomolecular research.

    Science.gov (United States)

    Lee, Woonghee; Cornilescu, Gabriel; Dashti, Hesam; Eghbalnia, Hamid R; Tonelli, Marco; Westler, William M; Butcher, Samuel E; Henzler-Wildman, Katherine A; Markley, John L

    2016-04-01

    NMR spectroscopy is a powerful technique for determining structural and functional features of biomolecules in physiological solution as well as for observing their intermolecular interactions in real-time. However, complex steps associated with its practice have made the approach daunting for non-specialists. We introduce an NMR platform that makes biomolecular NMR spectroscopy much more accessible by integrating tools, databases, web services, and video tutorials that can be launched by simple installation of NMRFAM software packages or using a cross-platform virtual machine that can be run on any standard laptop or desktop computer. The software package can be downloaded freely from the NMRFAM software download page ( http://pine.nmrfam.wisc.edu/download_packages.html ), and detailed instructions are available from the Integrative NMR Video Tutorial page ( http://pine.nmrfam.wisc.edu/integrative.html ).

  3. Imaging and chemical surface analysis of biomolecular functionalization of monolithically integrated on silicon Mach-Zehnder interferometric immunosensors

    Science.gov (United States)

    Gajos, Katarzyna; Angelopoulou, Michailia; Petrou, Panagiota; Awsiuk, Kamil; Kakabakos, Sotirios; Haasnoot, Willem; Bernasik, Andrzej; Rysz, Jakub; Marzec, Mateusz M.; Misiakos, Konstantinos; Raptis, Ioannis; Budkowski, Andrzej

    2016-11-01

    Time-of-flight secondary ion mass spectrometry (imaging, micro-analysis) has been employed to evaluate biofunctionalization of the sensing arm areas of Mach-Zehnder interferometers monolithically integrated on silicon chips for the immunochemical (competitive) detection of bovine κ-casein in goat milk. Biosensor surfaces are examined after: modification with (3-aminopropyl)triethoxysilane, application of multiple overlapping spots of κ-casein solutions, blocking with 100-times diluted goat milk, and reaction with monoclonal mouse anti-κ-casein antibodies in blocking solution. The areas spotted with κ-casein solutions of different concentrations are examined and optimum concentration providing homogeneous coverage is determined. Coverage of biosensor surfaces with biomolecules after each of the sequential steps employed in immunodetection is also evaluated with TOF-SIMS, supplemented by Atomic force microscopy and X-ray photoelectron spectroscopy. Uniform molecular distributions are observed on the sensing arm areas after spotting with optimum κ-casein concentration, blocking and immunoreaction. The corresponding biomolecular compositions are determined with a Principal Component Analysis that distinguished between protein amino acids and milk glycerides, as well as between amino acids characteristic for Mabs and κ-casein, respectively. Use of the optimum conditions (κ-casein concentration) for functionalization of chips with arrays of ten Mach-Zehnder interferometers provided on-chips assays with dramatically improved both intra-chip response repeatability and assay detection sensitivity.

  4. Grid computing and biomolecular simulation.

    Science.gov (United States)

    Woods, Christopher J; Ng, Muan Hong; Johnston, Steven; Murdock, Stuart E; Wu, Bing; Tai, Kaihsu; Fangohr, Hans; Jeffreys, Paul; Cox, Simon; Frey, Jeremy G; Sansom, Mark S P; Essex, Jonathan W

    2005-08-15

    Biomolecular computer simulations are now widely used not only in an academic setting to understand the fundamental role of molecular dynamics on biological function, but also in the industrial context to assist in drug design. In this paper, two applications of Grid computing to this area will be outlined. The first, involving the coupling of distributed computing resources to dedicated Beowulf clusters, is targeted at simulating protein conformational change using the Replica Exchange methodology. In the second, the rationale and design of a database of biomolecular simulation trajectories is described. Both applications illustrate the increasingly important role modern computational methods are playing in the life sciences.

  5. Stability of Complex Biomolecular Structures: Vander Waals, Hydrogen Bond Cooperativity, and Nuclear Quantum Effects

    CERN Document Server

    Rossi, Mariana; Michaelides, Angelos

    2016-01-01

    Biomolecules are complex systems stabilized by a delicate balance of weak interactions, making it important to assess all energetic contributions in an accurate manner. However, it is a priori unclear which contributions make more of an impact. Here, we examine stacked polyglutamine (polyQ) strands, a peptide repeat often found in amyloid aggregates. We investigate the role of hydrogen bond (HB) cooperativity, van der Waals (vdW) dispersion interactions, and quantum contributions to free energies, including anharmonicities through density functional theory and ab initio path integral simulations. Of these various factors, we find that the largest impact on structural stabilization comes from vdW interactions. HB cooperativity is the second largest contribution as the size of the stacked chain grows. Competing nuclear quantum effects make the net quantum contribution small but very sensitive to anharmonicities, vdW, and the number of HBs. Our results suggest that a reliable treatment of these systems can only ...

  6. Imaging and chemical surface analysis of biomolecular functionalization of monolithically integrated on silicon Mach-Zehnder interferometric immunosensors

    Energy Technology Data Exchange (ETDEWEB)

    Gajos, Katarzyna, E-mail: kasia.fornal@uj.edu.pl [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Angelopoulou, Michailia; Petrou, Panagiota [Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Awsiuk, Kamil [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Kakabakos, Sotirios [Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Haasnoot, Willem [RIKILT Wageningen UR, Akkermaalsbos 2, 6708 WB Wageningen (Netherlands); Bernasik, Andrzej [Faculty of Physics and Applied Computer Science, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Rysz, Jakub [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland); Marzec, Mateusz M. [Academic Centre for Materials and Nanotechnology, AGH University of Science and Technology, Mickiewicza 30, 30-059 Kraków (Poland); Misiakos, Konstantinos; Raptis, Ioannis [Department of Microelectronics, Institute of Nanoscience and Nanotechnology, NCSR Demokritos, P. Grigoriou & Neapoleos St, Aghia Paraksevi 15310, Athens (Greece); Budkowski, Andrzej [M. Smoluchowski Institute of Physics, Jagiellonian University, Łojasiewicza 11, 30-348 Kraków (Poland)

    2016-11-01

    Highlights: • Optimization of probe immobilization with robotic spotter printing overlapping spots. • In-situ inspection of microstructured surfaces of biosensors integrated on silicon. • Imaging and chemical analysis of immobilization, surface blocking and immunoreaction. • Insight with molecular discrimination into step-by-step sensor surface modifications. • Optimized biofunctionalization improves sensor sensitivity and response repeatability. - Abstract: Time-of-flight secondary ion mass spectrometry (imaging, micro-analysis) has been employed to evaluate biofunctionalization of the sensing arm areas of Mach-Zehnder interferometers monolithically integrated on silicon chips for the immunochemical (competitive) detection of bovine κ-casein in goat milk. Biosensor surfaces are examined after: modification with (3-aminopropyl)triethoxysilane, application of multiple overlapping spots of κ-casein solutions, blocking with 100-times diluted goat milk, and reaction with monoclonal mouse anti-κ-casein antibodies in blocking solution. The areas spotted with κ-casein solutions of different concentrations are examined and optimum concentration providing homogeneous coverage is determined. Coverage of biosensor surfaces with biomolecules after each of the sequential steps employed in immunodetection is also evaluated with TOF-SIMS, supplemented by Atomic force microscopy and X-ray photoelectron spectroscopy. Uniform molecular distributions are observed on the sensing arm areas after spotting with optimum κ-casein concentration, blocking and immunoreaction. The corresponding biomolecular compositions are determined with a Principal Component Analysis that distinguished between protein amino acids and milk glycerides, as well as between amino acids characteristic for Mabs and κ-casein, respectively. Use of the optimum conditions (κ-casein concentration) for functionalization of chips with arrays of ten Mach-Zehnder interferometers provided on-chips assays

  7. Programming in biomolecular computation

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2010-01-01

    executable, but are also compilable and interpretable. It is universal: all computable functions can be computed (in natural ways and without arcane encodings of data and algorithm); it is also uniform: new “hardware” is not needed to solve new problems; and (last but not least) it is Turing complete......Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We introduce a model of computation that is evidently programmable......, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only...

  8. Programming in Biomolecular Computation

    DEFF Research Database (Denmark)

    Hartmann, Lars; Jones, Neil; Simonsen, Jakob Grue

    2010-01-01

    Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We introduce a model of computation that is evidently programmable......, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only...... in a strong sense: a universal algorithm exists, that is able to execute any program, and is not asymptotically inefficient. A prototype model has been implemented (for now in silico on a conventional computer). This work opens new perspectives on just how computation may be specified at the biological level....

  9. Proteopedia: Exciting Advances in the 3D Encyclopedia of Biomolecular Structure

    Science.gov (United States)

    Prilusky, Jaime; Hodis, Eran; Sussman, Joel L.

    Proteopedia is a collaborative, 3D web-encyclopedia of protein, nucleic acid and other structures. Proteopedia ( http://www.proteopedia.org ) presents 3D biomolecule structures in a broadly accessible manner to a diverse scientific audience through easy-to-use molecular visualization tools integrated into a wiki environment that anyone with a user account can edit. We describe recent advances in the web resource in the areas of content and software. In terms of content, we describe a large growth in user-added content as well as improvements in automatically-generated content for all PDB entry pages in the resource. In terms of software, we describe new features ranging from the capability to create pages hidden from public view to the capability to export pages for offline viewing. New software features also include an improved file-handling system and availability of biological assemblies of protein structures alongside their asymmetric units.

  10. [Advances in biomolecular machine: methane monooxygenases].

    Science.gov (United States)

    Lu, Jixue; Wang, Shizhen; Fang, Baishan

    2015-07-01

    Methane monooxygenases (MMO), regarded as "an amazing biomolecular machine", catalyze the oxidation of methane to methanol under aerobic conditions. MMO catalyze the oxidation of methane elaborately, which is a novel way to catalyze methane to methanol. Furthermore, MMO can inspire the biomolecular machine design. In this review, we introduced MMO including structure, gene and catalytic mechanism. The history and the taxonomy of MMO were also introduced.

  11. A guide to the visual analysis and communication of biomolecular structural data.

    Science.gov (United States)

    Johnson, Graham T; Hertig, Samuel

    2014-10-01

    Biologists regularly face an increasingly difficult task - to effectively communicate bigger and more complex structural data using an ever-expanding suite of visualization tools. Whether presenting results to peers or educating an outreach audience, a scientist can achieve maximal impact with minimal production time by systematically identifying an audience's needs, planning solutions from a variety of visual communication techniques and then applying the most appropriate software tools. A guide to available resources that range from software tools to professional illustrators can help researchers to generate better figures and presentations tailored to any audience's needs, and enable artistically inclined scientists to create captivating outreach imagery.

  12. H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations.

    Science.gov (United States)

    Anandakrishnan, Ramu; Aguilar, Boris; Onufriev, Alexey V

    2012-07-01

    The accuracy of atomistic biomolecular modeling and simulation studies depend on the accuracy of the input structures. Preparing these structures for an atomistic modeling task, such as molecular dynamics (MD) simulation, can involve the use of a variety of different tools for: correcting errors, adding missing atoms, filling valences with hydrogens, predicting pK values for titratable amino acids, assigning predefined partial charges and radii to all atoms, and generating force field parameter/topology files for MD. Identifying, installing and effectively using the appropriate tools for each of these tasks can be difficult for novice and time-consuming for experienced users. H++ (http://biophysics.cs.vt.edu/) is a free open-source web server that automates the above key steps in the preparation of biomolecular structures for molecular modeling and simulations. H++ also performs extensive error and consistency checking, providing error/warning messages together with the suggested corrections. In addition to numerous minor improvements, the latest version of H++ includes several new capabilities and options: fix erroneous (flipped) side chain conformations for HIS, GLN and ASN, include a ligand in the input structure, process nucleic acid structures and generate a solvent box with specified number of common ions for explicit solvent MD.

  13. Biomolecular rods and tubes in nanotechnology

    Science.gov (United States)

    Bittner, Alexander M.

    2005-02-01

    Biomolecules are vitally important elements in nanoscale science and also in future nanotechnology. Their shape and their chemical and physical functionality can give them a big advantage over inorganic and organic substances. While this becomes most obvious in proteins and peptides, with their complicated, but easily controlled chemistry, other biomolecular substances such as DNA, lipids and carbohydrates can also be important. In this review, the emphasis is on one-dimensional molecules and on molecules that self-assemble into linear structures, and on their potential applications. An important aspect is that biomolecules can act as templates, i.e. their shape and chemical properties can be employed to arrange inorganic substances such as metals or metal compounds on the nanometre scale. In particular, rod- and tube-like nanostructures can show physical properties that are different from those of the bulk material, and thus these structures are likely to be a basis for new technology.

  14. Nonequilibrium phase transitions in biomolecular signal transduction

    Science.gov (United States)

    Smith, Eric; Krishnamurthy, Supriya; Fontana, Walter; Krakauer, David

    2011-11-01

    We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state transitions of any molecule, by means of which the switch is implemented, are highly stochastic. The emergence of switching is a nonequilibrium phase transition in an energetically driven, dissipative system described by a master equation. We use operator and functional integral methods from reaction-diffusion theory to solve for the phase structure, noise spectrum, and escape trajectories and first-passage times of a class of minimal models of switches, showing how all critical properties for switch behavior can be computed within a unified framework.

  15. Programming in biomolecular computation

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We identify a number of common features in programming that seem conspicu...

  16. Conducting polymer based biomolecular electronic devices

    Indian Academy of Sciences (India)

    B D Malhotra; Rahul Singhal

    2003-08-01

    Biomolecular electronics is rapidly evolving from physics, chemistry, biology, electronics and information technology. Organic materials such as proteins, pigments and conducting polymers have been considered as alternatives for carrying out the functions that are presently being performed by semiconductor silicon. Conducting polymers such as polypyrroles, polythiophenes and polyanilines have been projected for applications for a wide range of biomolecular electronic devices such as optical, electronic, drug-delivery, memory and biosensing devices. Our group has been actively working towards the application of conducting polymers to Schottky diodes, metal–insulator–semiconductor (MIS) devices and biosensors for the past 10 years. This paper is a review of some of the results obtained at our laboratory in the area of conducting polymer biomolecular electronics.

  17. Assembly of single wall carbon nanotube-metal nanohybrids using biomolecular components

    Science.gov (United States)

    Kim, Sang Nyon; Slocik, Joseph M.; Naik, Rajesh R.

    2010-08-01

    Biomaterials such as nucleic acids and proteins can be exploited to create higher order structures. The biomolecular components such as DNA and peptides have been used to assemble nanoparticles with high fidelity. Here, we use DNA and peptides, and their preferential interaction with inorganic and carbon nanomaterials to form homogeneous hybrids. The enhanced binding of Pt ions to both DNA and peptide functionalized nanoparticles mediates the assembly of carbon nanotubes functionalized with DNA with peptide coated gold nanoparticles.

  18. Synthesis and biosynthesis of {sup 13}C-, {sup 15}N-labeled deoxynucleosides useful for biomolecular structural determinations

    Energy Technology Data Exchange (ETDEWEB)

    Ashburn, D.A.; Garcia, K.; Hanners, J.L.; Silks, L.A. III; Unkefer, C.J. [Los Alamos National Laboratory, NM (United States)

    1994-12-01

    Currently, there is a great emphasis on elucidating the structure, function, and dynamics of DNA. Much of the research involved in this study uses nuclear magnetic resonance (NMR) spectroscopy. Effective use of NMR spectroscopy for DNA molecules with mw > 10,000 requires stable isotope enrichment. We present strategies for site-specific isotopic labeling of the purine bases adenosine and guanosine and the biosynthesis of (U-{sup 13}C, {sup 15}N) DNA from methylotropic bacteria. With commercially available 6-chloropurine, an effective two-step route leads to 2{prime}-deoxy-(amino-{sup 15}N)adenosine (dA). The resulting d(amino-{sup 15}N)A is used in a series of reactions to synthesize 2{prime}-deoxy-(2-{sup 13}C,1,amino-{sup 15}N{sub 2})guanosine or any combination thereof. An improved biosynthesis of labeled DNA has been accomplished using Methylobacterium extorquens AS1. Each liter of growth medium contains 4 g of methanol to yield 1 g of lyophilized cells. As much as 200 mg of RNA per liter of culture has been obtained. We are currently developing large-scale isolation protocols. General synthetic pathways to oligomeric DNA will be presented.

  19. Application of Nanodiamonds in Biomolecular Mass Spectrometry

    OpenAIRE

    Ping Cheng; Xianglei Kong

    2010-01-01

    The combination of nanodiamond (ND) with biomolecular mass spectrometry (MS) makes rapid, sensitive detection of biopolymers from complex biosamples feasible. Due to its chemical inertness, optical transparency and biocompatibility, the advantage of NDs in MS study is unique. Furthermore, functionalization on the surfaces of NDs expands their application in the fields of proteomics and genomics for specific requirements greatly. This review presents methods of MS analysis based on solid phase...

  20. RASMOL AB - new functionalities in the program for structure analysis.

    Science.gov (United States)

    Pikora, Mateusz; Gieldon, Artur

    2015-01-01

    For many years RasMol was one of the most used programs for molecular visualization. It was an excellent tool due to its simplicity and its low demand of computer power. Today it is replaced by OpenGL programs, which have excellent graphics that new computers can additionally handle. Molecular graphics is one of the best tools for the analysis of biomolecular data. With high efficiency and a low demand of computer power, RasMol can still be used as a quick and handy tool used for the analysis of biomolecular structures with good results. In this paper, we describe modifications to the RasMol program, as implemented on the base of RasMol AB 2. We introduced several new functions, namely: the identification of histidine isomers, and advanced structural selection and macro capabilities (as implemented in the point-click menu), which result in an increase in the speed and accuracy of structural analyses. The program can be downloaded from the project page: http://etoh.chem.univ.gda.pl/rasmol/.

  1. Application of Nanodiamonds in Biomolecular Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Ping Cheng

    2010-03-01

    Full Text Available The combination of nanodiamond (ND with biomolecular mass spectrometry (MS makes rapid, sensitive detection of biopolymers from complex biosamples feasible. Due to its chemical inertness, optical transparency and biocompatibility, the advantage of NDs in MS study is unique. Furthermore, functionalization on the surfaces of NDs expands their application in the fields of proteomics and genomics for specific requirements greatly. This review presents methods of MS analysis based on solid phase extraction and elution on NDs and different application examples including peptide, protein, DNA, glycan and others. Owing to the quick development of nanotechnology, surface chemistry, new MS methods and the intense interest in proteomics and genomics, a huge increase of their applications in biomolecular MS analysis in the near future can be predicted.

  2. Improvements in continuum modeling for biomolecular systems

    CERN Document Server

    Qiao, Yu

    2015-01-01

    Modeling of biomolecular systems plays an essential role in understanding biological processes, such as ionic flow across channels, protein modification or interaction, and cell signaling. The continuum model described by the Poisson-Boltzmann (PB)/Poisson-Nernst-Planck (PNP) equations has made great contributions towards simulation of these processes. However, the model has shortcomings in its commonly used form and cannot capture (or cannot accurately capture) some important physical properties of biological systems. Considerable efforts have been made to improve the continuum model to account for discrete particle interactions and to make progress in numerical methods to provide accurate and efficient simulation. This review will summarize recent main improvements in continuum modeling for biomolecular systems, with focus on the size-modified models, the coupling of the classical density functional theory and PNP equations, the coupling of polar and nonpolar interactions, and numerical progress.

  3. Charge transport through biomolecular wires in a solvent: bridging molecular dynamics and model Hamiltonian approaches.

    Science.gov (United States)

    Gutiérrez, R; Caetano, R A; Woiczikowski, B P; Kubar, T; Elstner, M; Cuniberti, G

    2009-05-22

    We present a hybrid method based on a combination of classical molecular dynamics simulations, quantum-chemical calculations, and a model Hamiltonian approach to describe charge transport through biomolecular wires with variable lengths in presence of a solvent. The core of our approach consists in a mapping of the biomolecular electronic structure, as obtained from density-functional based tight-binding calculations of molecular structures along molecular dynamics trajectories, onto a low-dimensional model Hamiltonian including the coupling to a dissipative bosonic environment. The latter encodes fluctuation effects arising from the solvent and from the molecular conformational dynamics. We apply this approach to the case of pG-pC and pA-pT DNA oligomers as paradigmatic cases and show that the DNA conformational fluctuations are essential in determining and supporting charge transport.

  4. Structure function monitor

    Energy Technology Data Exchange (ETDEWEB)

    McGraw, John T [Placitas, NM; Zimmer, Peter C [Albuquerque, NM; Ackermann, Mark R [Albuquerque, NM

    2012-01-24

    Methods and apparatus for a structure function monitor provide for generation of parameters characterizing a refractive medium. In an embodiment, a structure function monitor acquires images of a pupil plane and an image plane and, from these images, retrieves the phase over an aperture, unwraps the retrieved phase, and analyzes the unwrapped retrieved phase. In an embodiment, analysis yields atmospheric parameters measured at spatial scales from zero to the diameter of a telescope used to collect light from a source.

  5. Purely Functional Structured Programming

    OpenAIRE

    Obua, Steven

    2010-01-01

    The idea of functional programming has played a big role in shaping today's landscape of mainstream programming languages. Another concept that dominates the current programming style is Dijkstra's structured programming. Both concepts have been successfully married, for example in the programming language Scala. This paper proposes how the same can be achieved for structured programming and PURELY functional programming via the notion of LINEAR SCOPE. One advantage of this proposal is that m...

  6. Biomolecular electrostatics and solvation: a computational perspective.

    Science.gov (United States)

    Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

    2012-11-01

    An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

  7. Chromatin Structure and Function

    CERN Document Server

    Wolffe, Alan P

    1999-01-01

    The Third Edition of Chromatin: Structure and Function brings the reader up-to-date with the remarkable progress in chromatin research over the past three years. It has been extensively rewritten to cover new material on chromatin remodeling, histone modification, nuclear compartmentalization, DNA methylation, and transcriptional co-activators and co-repressors. The book is written in a clear and concise fashion, with 60 new illustrations. Chromatin: Structure and Function provides the reader with a concise and coherent account of the nature, structure, and assembly of chromatin and its active

  8. DNA: Structure and function

    DEFF Research Database (Denmark)

    Sinden, Richard R.; E. Pearson, Christopher; N. Potaman, Vladimir

    1998-01-01

    This chapter discusses the structure and function of DNA. DNA occupies a critical role in cells, because it is the source of all intrinsic genetic information. Chemically, DNA is a very stable molecule, a characteristic important for a macromolecule that may have to persist in an intact form...... for a long period of time before its information is accessed by the cell. Although DNA plays a critical role as an informational storage molecule, it is by no means as unexciting as a computer tape or disk drive. The structure of the DNA described by Watson and Crick in 1953 is a right handed helix of two...

  9. The HADDOCK web server for data-driven biomolecular docking

    NARCIS (Netherlands)

    de Vries, S.J.; van Dijk, M.; Bonvin, A.M.J.J.

    2010-01-01

    Computational docking is the prediction or modeling of the three-dimensional structure of a biomolecular complex, starting from the structures of the individual molecules in their free, unbound form. HADDOC K is a popular docking program that takes a datadriven approach to docking, with support for

  10. Azurin for Biomolecular Electronics: a Reliability Study

    Science.gov (United States)

    Bramanti, Alessandro; Pompa, Pier Paolo; Maruccio, Giuseppe; Calabi, Franco; Arima, Valentina; Cingolani, Roberto; Corni, Stefano; Di Felice, Rosa; De Rienzo, Francesca; Rinaldi, Ross

    2005-09-01

    The metalloprotein azurin, used in biomolecular electronics, is investigated with respect to its resilience to high electric fields and ambient conditions, which are crucial reliability issues. Concerning the effect of electric fields, two models of different complexity agree indicating an unexpectedly high robustness. Experiments in device-like conditions confirm that no structural modifications occur, according to fluorescence spectra, even after a 40-min exposure to tens of MV/m. Ageing is then investigated experimentally, at ambient conditions and without field, over several days. Only a small conformational rearrangement is observed in the first tens of hours, followed by an equilibrium state.

  11. Nanotube-Based Chemical and Biomolecular Sensors

    Institute of Scientific and Technical Information of China (English)

    J.Koh; B.Kim; S.Hong; H.Lim; H.C.Choi

    2008-01-01

    We present a brief review about recent results regarding carbon nanotube (CNT)-based chemical and biomolecular sensors. For the fabrication of CNT-based sensors, devices containing CNT channels between two metal electrodes are first fabricated usually via chemical vapor deposition (CVD) process or "surface programmed assembly" method. Then, the CNT surfaces are often functionalized to enhance the selectivity of the sensors. Using this process, highly-sensitive CNT-based sensors can be fabricated for the selective detection of various chemical and biological molecules such as hydrogen, ammonia, carbon monoxide, chlorine gas, DNA, glucose, alcohol, and proteins.

  12. Micro and Nanotechnologies Enhanced Biomolecular Sensing

    Directory of Open Access Journals (Sweden)

    Tza-Huei Wang

    2013-07-01

    Full Text Available This editorial summarizes some of the recent advances of micro and nanotechnology-based tools and devices for biomolecular detection. These include the incorporation of nanomaterials into a sensor surface or directly interfacing with molecular probes to enhance target detection via more rapid and sensitive responses, and the use of self-assembled organic/inorganic nanocomposites that inhibit exceptional spectroscopic properties to enable facile homogenous assays with efficient binding kinetics. Discussions also include some insight into microfluidic principles behind the development of an integrated sample preparation and biosensor platform toward a miniaturized and fully functional system for point of care applications.

  13. Biomolecular Modification of Inorganic Crystal Growth

    Energy Technology Data Exchange (ETDEWEB)

    De Yoreo, J J

    2007-04-27

    The fascinating shapes and hierarchical designs of biomineralized structures are an inspiration to materials scientists because of the potential they suggest for biomolecular control over materials synthesis. Conversely, the failure to prevent or limit tissue mineralization in the vascular, skeletal, and urinary systems is a common source of disease. Understanding the mechanisms by which organisms direct or limit crystallization has long been a central challenge to the biomineralization community. One prevailing view is that mineral-associated macromolecules are responsible for either inhibiting crystallization or initiating and stabilizing non-equilibrium crystal polymorphs and morphologies through interactions between anionic moieties and cations in solution or at mineralizing surfaces. In particular, biomolecules that present carboxyl groups to the growing crystal have been implicated as primary modulators of growth. Here we review the results from a combination of in situ atomic force microscopy (AFM) and molecular modeling (MM) studies to investigate the effect of specific interactions between carboxylate-rich biomolecules and atomic steps on crystal surfaces during the growth of carbonates, oxalates and phosphates of calcium. Specifically, we how the growth kinetics and morphology depend on the concentration of additives that include citrate, simple amino acids, synthetic Asp-rich polypeptides, and naturally occurring Asp-rich proteins found in both functional and pathological mineral tissues. The results reveal a consistent picture of shape modification in which stereochemical matching of modifiers to specific atomic steps drives shape modification. Inhibition and other changes in growth kinetics are shown to be due to a range of mechanisms that depend on chemistry and molecular size. Some effects are well described by classic crystal growth theories, but others, such as step acceleration due to peptide charge and hydrophylicity, were previously unrealized

  14. Accelerated search for biomolecular network models to interpret high-throughput experimental data

    Directory of Open Access Journals (Sweden)

    Sokhansanj Bahrad A

    2007-07-01

    Full Text Available Abstract Background The functions of human cells are carried out by biomolecular networks, which include proteins, genes, and regulatory sites within DNA that encode and control protein expression. Models of biomolecular network structure and dynamics can be inferred from high-throughput measurements of gene and protein expression. We build on our previously developed fuzzy logic method for bridging quantitative and qualitative biological data to address the challenges of noisy, low resolution high-throughput measurements, i.e., from gene expression microarrays. We employ an evolutionary search algorithm to accelerate the search for hypothetical fuzzy biomolecular network models consistent with a biological data set. We also develop a method to estimate the probability of a potential network model fitting a set of data by chance. The resulting metric provides an estimate of both model quality and dataset quality, identifying data that are too noisy to identify meaningful correlations between the measured variables. Results Optimal parameters for the evolutionary search were identified based on artificial data, and the algorithm showed scalable and consistent performance for as many as 150 variables. The method was tested on previously published human cell cycle gene expression microarray data sets. The evolutionary search method was found to converge to the results of exhaustive search. The randomized evolutionary search was able to converge on a set of similar best-fitting network models on different training data sets after 30 generations running 30 models per generation. Consistent results were found regardless of which of the published data sets were used to train or verify the quantitative predictions of the best-fitting models for cell cycle gene dynamics. Conclusion Our results demonstrate the capability of scalable evolutionary search for fuzzy network models to address the problem of inferring models based on complex, noisy biomolecular

  15. Exposing biomolecular properties one molecule at a time

    NARCIS (Netherlands)

    Elmalk, Abdalmohsen

    2012-01-01

    The work described in this thesis was aimed at the study of the functional properties of (isolated and purified) biomolecular systems at the single-molecule level. Two prerequisites are essential for successfully achieving this goal. First of all, single biomolecules should be observable, which mean

  16. Improvements in continuum modeling for biomolecular systems

    Science.gov (United States)

    Yu, Qiao; Ben-Zhuo, Lu

    2016-01-01

    Modeling of biomolecular systems plays an essential role in understanding biological processes, such as ionic flow across channels, protein modification or interaction, and cell signaling. The continuum model described by the Poisson- Boltzmann (PB)/Poisson-Nernst-Planck (PNP) equations has made great contributions towards simulation of these processes. However, the model has shortcomings in its commonly used form and cannot capture (or cannot accurately capture) some important physical properties of the biological systems. Considerable efforts have been made to improve the continuum model to account for discrete particle interactions and to make progress in numerical methods to provide accurate and efficient simulations. This review will summarize recent main improvements in continuum modeling for biomolecular systems, with focus on the size-modified models, the coupling of the classical density functional theory and the PNP equations, the coupling of polar and nonpolar interactions, and numerical progress. Project supported by the National Natural Science Foundation of China (Grant No. 91230106) and the Chinese Academy of Sciences Program for Cross & Cooperative Team of the Science & Technology Innovation.

  17. Smartphones for cell and biomolecular detection.

    Science.gov (United States)

    Liu, Xiyuan; Lin, Tung-Yi; Lillehoj, Peter B

    2014-11-01

    Recent advances in biomedical science and technology have played a significant role in the development of new sensors and assays for cell and biomolecular detection. Generally, these efforts are aimed at reducing the complexity and costs associated with diagnostic testing so that it can be performed outside of a laboratory or hospital setting, requiring minimal equipment and user involvement. In particular, point-of-care (POC) testing offers immense potential for many important applications including medical diagnosis, environmental monitoring, food safety, and biosecurity. When coupled with smartphones, POC systems can offer portability, ease of use and enhanced functionality while maintaining performance. This review article focuses on recent advancements and developments in smartphone-based POC systems within the last 6 years with an emphasis on cell and biomolecular detection. These devices typically comprise multiple components, such as detectors, sample processors, disposable chips, batteries, and software, which are integrated with a commercial smartphone. One of the most important aspects of developing these systems is the integration of these components onto a compact and lightweight platform that requires minimal power. Researchers have demonstrated several promising approaches employing various detection schemes and device configurations, and it is expected that further developments in biosensors, battery technology and miniaturized electronics will enable smartphone-based POC technologies to become more mainstream tools in the scientific and biomedical communities.

  18. Interacting with the biomolecular solvent accessible surface via a haptic feedback device

    Directory of Open Access Journals (Sweden)

    Hayward Steven

    2009-10-01

    Full Text Available Abstract Background From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. Results A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. Conclusion By using the software, named HaptiMol ISAS (available from http://www.haptimol.co.uk, one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water

  19. Global Langevin model of multidimensional biomolecular dynamics

    Science.gov (United States)

    Schaudinnus, Norbert; Lickert, Benjamin; Biswas, Mithun; Stock, Gerhard

    2016-11-01

    Molecular dynamics simulations of biomolecular processes are often discussed in terms of diffusive motion on a low-dimensional free energy landscape F ( 𝒙 ) . To provide a theoretical basis for this interpretation, one may invoke the system-bath ansatz á la Zwanzig. That is, by assuming a time scale separation between the slow motion along the system coordinate x and the fast fluctuations of the bath, a memory-free Langevin equation can be derived that describes the system's motion on the free energy landscape F ( 𝒙 ) , which is damped by a friction field and driven by a stochastic force that is related to the friction via the fluctuation-dissipation theorem. While the theoretical formulation of Zwanzig typically assumes a highly idealized form of the bath Hamiltonian and the system-bath coupling, one would like to extend the approach to realistic data-based biomolecular systems. Here a practical method is proposed to construct an analytically defined global model of structural dynamics. Given a molecular dynamics simulation and adequate collective coordinates, the approach employs an "empirical valence bond"-type model which is suitable to represent multidimensional free energy landscapes as well as an approximate description of the friction field. Adopting alanine dipeptide and a three-dimensional model of heptaalanine as simple examples, the resulting Langevin model is shown to reproduce the results of the underlying all-atom simulations. Because the Langevin equation can also be shown to satisfy the underlying assumptions of the theory (such as a delta-correlated Gaussian-distributed noise), the global model provides a correct, albeit empirical, realization of Zwanzig's formulation. As an application, the model can be used to investigate the dependence of the system on parameter changes and to predict the effect of site-selective mutations on the dynamics.

  20. Quantum dynamics of bio-molecular systems in noisy environments

    OpenAIRE

    Huelga S.F.; Plenio M.B.

    2012-01-01

    We discuss three different aspects of the quantum dynamics of bio-molecular systems and more generally complex networks in the presence of strongly coupled environments. Firstly, we make a case for the systematic study of fundamental structural elements underlying the quantum dynamics of these systems, identify such elements and explore the resulting interplay of quantum dynamics and environmental decoherence. Secondly, we critically examine some existing approaches to the numerical descripti...

  1. RECENT PROGRESS IN BIOMOLECULAR NMR

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Structural genomics and proteomics were born from the understanding that functions of a protein are dictated by its 3D structure and dynamics. To understand protein functions on a genomic scale, we must know protein structures on a genomic scale. High resolution NMR can be used for this purpose. Traditional multidimensional NMR structure determination protocols become ineffective for structural genomics since to obtain a structure of a small protein of 15kD requires many months of painstaking spectral analysis and modeling. Recent advances in magnet and probe technology and in experimental methods have expanded the range of proteins amenable to structure determination and make the large scale structure determination possible. These advances are (1) effective expression systems for protein production, (2) introduction of cryoprobe, (3) structure determination with the use of the minimal amount of structural restraints obtained from the chemical shifts, residual dipolar couplings, NOEs, and computer modeling. In this talk,Iwill briefly outline these developments and related works done in our NMR lab.

  2. Structure functions at large x

    CERN Document Server

    Zhang, Z

    2002-01-01

    Structure function data together with other measurements from fixed-target deep inelastic scattering and hadron-hadron collider experiments which contribute to our knowledge of the parton density functions are reviewed. The inclusive cross-section measurements of neutral and charged current interactions at HERA are presented and their impact on the parton density functions is discussed. Future prospects for an improved knowledge of the parton density functions at large x are briefly mentioned.

  3. Physics at the biomolecular interface fundamentals for molecular targeted therapy

    CERN Document Server

    Fernández, Ariel

    2016-01-01

    This book focuses primarily on the role of interfacial forces in understanding biological phenomena at the molecular scale. By providing a suitable statistical mechanical apparatus to handle the biomolecular interface, the book becomes uniquely positioned to address core problems in molecular biophysics. It highlights the importance of interfacial tension in delineating a solution to the protein folding problem, in unravelling the physico-chemical basis of enzyme catalysis and protein associations, and in rationally designing molecular targeted therapies. Thus grounded in fundamental science, the book develops a powerful technological platform for drug discovery, while it is set to inspire scientists at any level in their careers determined to address the major challenges in molecular biophysics. The acknowledgment of how exquisitely the structure and dynamics of proteins and their aqueous environment are related attests to the overdue recognition that biomolecular phenomena cannot be effectively understood w...

  4. Structural Chemistry of Functional Materials

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ This innovative research group on structural chemistry of functional materials was approved by NSFC in 2005.Headed by Prof.HONG Maochun, the team consists of several young research scientists from the CAS Fujian Institute of Research on the Structures of Matter, including Profs CAO Rong, LU Canzhong, GUO Guocong, CHEN Zhongning, MAO Jianggao Mao and CHEN Ling.

  5. Characterization of a nanoscale S-layer protein based template for biomolecular patterning.

    Science.gov (United States)

    Wong, Wing Sze; Yung, Pun To

    2014-01-01

    Well organized template for biomolecular conjugation is the foundation for biosensing. Most of the current devices are fabricated using lithographic patterning processes and self-assembly monolayer (SAM) methods. However, the research toward developing a sub-10 nm patterned, self-regenerated template on various types of substrates is limited, mainly due to the limited functional groups of the building material. Bacterial surface layer proteins (S-layer proteins) can self-assemble into ordered lattice with regular pore sizes of 2-8 nm on different material supports and interfaces. The ordered structure can regenerate after extreme variations of solvent conditions. In this work, we developed a nanoscale biomolecular template based on S-layer proteins on gold surface for fabrication of sensing layer in biosensors. S-layer proteins were isolated from Bacillus cereus, Lysinibacillus sphaericus and Geobacillus stearothermophilus. Protein concentrations were measured by Bradford assay. The protein purities were verified by SDS-PAGE, showing molecular weights ranging from 97-135 kDa. The hydrophilicity of the substrate surface was measured after surface treatments of protein recrystallization. Atomic force microscopic (AFM) measurement was performed on substrate surface, indicating a successful immobilization of a monolayer of S-layer protein with 8-9 nm height on gold surface. The template can be applied on various material supports and acts as a self-regenerated sensing layer of biosensors in the future.

  6. Structure functions and parton distributions

    Energy Technology Data Exchange (ETDEWEB)

    Martin, A.D.; Stirling, W.J. [Univ. of Durham (United Kingdom); Roberts, R.G. [Rutherford Appleton Lab., Chilton, Didcot (United Kingdom)

    1995-07-01

    The MRS parton distribution analysis is described. The latest sets are shown to give an excellent description of a wide range of deep-inelastic and other hard scattering data. Two important theoretical issues-the behavior of the distributions at small x and the flavor structure of the quark sea-are discussed in detail. A comparison with the new structure function data from HERA is made, and the outlook for the future is discussed.

  7. Proton structure functions at HERA

    Science.gov (United States)

    Stella, Bruno

    2001-10-01

    The electron-proton collider HERA, like an electron-mycroscope, explores the structure of the proton down to 10-16 cm and up to the situation of very high parton densities. The proton energy was upgraded from 820 to 920 GeV in the Fall of '98 and the luminosity has also substantially improved, with another factor of 3 upgrade expected to follow this year. Inclusive proton structure functions have been studied with incident e+ and e- of 27 GeV in the neutral (NC) and charged (CC) current interactions as functions of the squared four-momentum transfer, Q2, and of the fractional proton momentum carried by partons, x. The structure function F2, as well as the γ-Z0 interference term xF3, have been measured in a range of Q2 and 1/x that extends by orders of magnitude that reached by fixed target experiments. The DGLAP evolution equations [1] allow for a perturbative NLO QCD fit of the measured non-perturbative structure functions in the available kinematic range: αS and the gluon density at low x are fitted at the same time with good precision. The longitudinal structure function, FL, can be determined within the DGLAP formalism. With CC, the electroweak unification has been tested; at high x, a first flavor decomposition of the light quarks is achieved. The contribution to F2 of the charm quark has been measured and results to be relevant. Bounds on the radius of quarks and on compositeness are derived from the data at the highest Q2, 100

  8. [Protein phosphatases: structure and function].

    Science.gov (United States)

    Bulanova, E G; Budagian, V M

    1994-01-01

    The process of protein and enzyme systems phosphorylation is necessary for cell growth, differentiation and preparation for division and mitosis. The conformation changes of protein as a result of phosphorylation lead to increased enzyme activity and enhanced affinity to substrates. A large group of enzymes--protein kinases--is responsible for phosphorylation process in cell, which are divided into tyrosine- and serine-threonine-kinases depending on their ability to phosphorylate appropriate amino acid residues. In this review has been considered the functional importance and structure of protein phosphatases--enzymes, which are functional antagonists of protein kinases.

  9. Structure and Function of Glucansucrases

    Science.gov (United States)

    Dijkstra, B. W.; Vujičić-Žagar, A.

    2008-03-01

    Glucansucrases are relatively large (~160 kDa) extracellular enzymes produced by lactic acid bacteria. Using sucrose as a substrate they synthesize high molecular mass glucose polymers, called α-glucans, which allow the bacteria to adhere to surfaces and create a biofilm. The glucan polymers are of importance for the food and dairy industry as thickening and jellying agents. An overview is given of the current insights into the structure and functioning of these and related enzymes.

  10. Mitochondria: isolation, structure and function.

    Science.gov (United States)

    Picard, Martin; Taivassalo, Tanja; Gouspillou, Gilles; Hepple, Russell T

    2011-09-15

    Mitochondria are complex organelles constantly undergoing processes of fusion and fission, processes that not only modulate their morphology, but also their function. Yet the assessment of mitochondrial function in skeletal muscle often involves mechanical isolation of the mitochondria, a process which disrupts their normally heterogeneous branching structure and yields relatively homogeneous spherical organelles. Alternatively, methods have been used where the sarcolemma is permeabilized and mitochondrial morphology is preserved, but both methods face the downside that they remove potential influences of the intracellular milieu on mitochondrial function. Importantly, recent evidence shows that the fragmented mitochondrial morphology resulting from routine mitochondrial isolation procedures used with skeletal muscle alters key indices of function in a manner qualitatively similar to mitochondria undergoing fission in vivo. Although these results warrant caution when interpreting data obtained with mitochondria isolated from skeletal muscle, they also suggest that isolated mitochondrial preparations might present a useful way of interrogating the stress resistance of mitochondria. More importantly, these new findings underscore the empirical value of studying mitochondrial function in minimally disruptive experimental preparations. In this review, we briefly discuss several considerations and hypotheses emerging from this work.

  11. The structure and function of fungal cells

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    The structure and function of fungal cell walls were studied with particular emphasis on dermatophytes. Extraction, isolation, analysis, and observation of the cell wall structure and function were performed. The structure is described microscopically and chemically.

  12. Tissue Factor Structure and Function

    Directory of Open Access Journals (Sweden)

    Saulius Butenas

    2012-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. Many cells, both healthy, and tumor cells, produce detectable amounts of TF, especially when they are stimulated by various agents. Despite the relative simplicity and small size of TF, there are numerous contradictory reports about the synthesis and presentation of TF on blood cells and circulation in normal blood either on microparticles or as a soluble protein. Another subject of controversy is related to the structure/function of TF. It has been almost commonly accepted that cell-surface-associated TF has low (if any activity, that is, is “encrypted” and requires specific conditions/reagents to become active, that is, “decrypted.” However there is a lack of agreement related to the mechanism and processes leading to alterations in TF function. In this paper TF structure, presentation, and function, and controversies concerning these features are discussed.

  13. Supramolecular Structure and Function 9

    CERN Document Server

    Pifat-Mrzljak, Greta

    2007-01-01

    The book is based on International Summer Schools on Biophysics held in Croatia which, contrary to other workshops centered mainly on one topic or technique, has very broad scope providing advanced training in areas related to biophysics. This volume is presenting papers in the field of biophysics for studying biological phenomena by using physical methods (NMR, EPR, FTIR, Mass Spectrometry, etc.) and/or concepts (predictions of protein-protein interactions, virtual ligand screening etc.). The interrelationship of supramolecular structures and there functions is enlightened by applications of principals of these physical methods in the biophysical and molecular biology context.

  14. Origin of organic molecules and biomolecular homochirality.

    Science.gov (United States)

    Podlech, J

    2001-01-01

    Theories about the origin of biomolecular homochirality, which seems to be a prerequisite for the creation of life, are discussed. First, possible terrestrial and extraterrestrial sources of organic molecules are outlined. Then, mechanisms for the formation of enantiomerically enriched compounds and for the amplification of their chirality are described.

  15. Thermodynamic properties of water solvating biomolecular surfaces

    Science.gov (United States)

    Heyden, Matthias

    Changes in the potential energy and entropy of water molecules hydrating biomolecular interfaces play a significant role for biomolecular solubility and association. Free energy perturbation and thermodynamic integration methods allow calculations of free energy differences between two states from simulations. However, these methods are computationally demanding and do not provide insights into individual thermodynamic contributions, i.e. changes in the solvent energy or entropy. Here, we employ methods to spatially resolve distributions of hydration water thermodynamic properties in the vicinity of biomolecular surfaces. This allows direct insights into thermodynamic signatures of the hydration of hydrophobic and hydrophilic solvent accessible sites of proteins and small molecules and comparisons to ideal model surfaces. We correlate dynamic properties of hydration water molecules, i.e. translational and rotational mobility, to their thermodynamics. The latter can be used as a guide to extract thermodynamic information from experimental measurements of site-resolved water dynamics. Further, we study energy-entropy compensations of water at different hydration sites of biomolecular surfaces. This work is supported by the Cluster of Excellence RESOLV (EXC 1069) funded by the Deutsche Forschungsgemeinschaft.

  16. Deciphering fine molecular details of proteins' structure and function with a Protein Surface Topography (PST) method.

    Science.gov (United States)

    Koromyslova, Anna D; Chugunov, Anton O; Efremov, Roman G

    2014-04-28

    Molecular surfaces are the key players in biomolecular recognition and interactions. Nowadays, it is trivial to visualize a molecular surface and surface-distributed properties in three-dimensional space. However, such a representation trends to be biased and ambiguous in case of thorough analysis. We present a new method to create 2D spherical projection maps of entire protein surfaces and manipulate with them--protein surface topography (PST). It permits visualization and thoughtful analysis of surface properties. PST helps to easily portray conformational transitions, analyze proteins' properties and their dynamic behavior, improve docking performance, and reveal common patterns and dissimilarities in molecular surfaces of related bioactive peptides. This paper describes basic usage of PST with an example of small G-proteins conformational transitions, mapping of caspase-1 intersubunit interface, and intrinsic "complementarity" in the conotoxin-acetylcholine binding protein complex. We suggest that PST is a beneficial approach for structure-function studies of bioactive peptides and small proteins.

  17. Recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices.

    Science.gov (United States)

    Sasaki, Naoki

    2012-01-01

    AC electrokinetics is a generic term that refers to an induced motion of particles and fluids under nonuniform AC electric fields. The AC electric fields are formed by application of AC voltages to microelectrodes, which can be easily integrated into microfluidic devices by standard microfabrication techniques. Moreover, the magnitude of the motion is large enough to control the mass transfer on the devices. These advantages are attractive for biomolecular analysis on the microfluidic devices, in which the characteristics of small space and microfluidics have been mainly employed. In this review, I describe recent applications of AC electrokinetics in biomolecular analysis on microfluidic devices. The applications include fluid pumping and mixing by AC electrokinetic flow, and manipulation of biomolecules such as DNA and proteins by various AC electrokinetic techniques. Future prospects for highly functional biomolecular analysis on microfluidic devices with the aid of AC electrokinetics are also discussed.

  18. Mining, modeling, and evaluation of subnetworks from large biomolecular networks and its comparison study.

    Science.gov (United States)

    Hu, Xiaohua; Ng, Michael; Wu, Fang-Xiang; Sokhansanj, Bahrad A

    2009-03-01

    In this paper, we present a novel method to mine, model, and evaluate a regulatory system executing cellular functions that can be represented as a biomolecular network. Our method consists of two steps. First, a novel scale-free network clustering approach is applied to such a biomolecular network to obtain various subnetworks. Second, computational models are generated for the subnetworks and simulated to predict their behavior in the cellular context. We discuss and evaluate some of the advanced computational modeling approaches, in particular, state-space modeling, probabilistic Boolean network modeling, and fuzzy logic modeling. The modeling and simulation results represent hypotheses that are tested against high-throughput biological datasets (microarrays and/or genetic screens) under normal and perturbation conditions. Experimental results on time-series gene expression data for the human cell cycle indicate that our approach is promising for subnetwork mining and simulation from large biomolecular networks.

  19. Structure and function of aggrecan

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Aggrecan is the major proteoglycan in the articular cartilage. This molecule is important in the proper functioning of articular cartilage because it provides a hydrated gel structure (via its interaction with hyaluronan and link protein) that endows the cartilage with load-bearing properties. It is also crucial in chondroskeletal morphogenesis during development. Aggrecan is a multimodular molecule expressed by chondrocytes. Its core protein is composed of three globular domains (Gl, G2, and G3) and a large extended region (CS) between G2 and G3 for glycosaminoglycan chain attachment. G1 comprises the amino terminus of the core protein. This domain has the same structural motif as link protein. Functionally, the G1 domain interacts with hyaluronan acid and link protein, forming stable ternary complexes in the extracellular matrix.G2 is homologous to the tandem repeats of G1 and of link protein and is involved in product processing. G3makes up the carboxyl terminus of the core protein. It enhances glycosaminoglycan modification and product secretion. Aggrecan plays an important role in mediating chondrocyte-chondrocyte and chondrocyte-matrix interactions through its ability to bind hyaluronan.

  20. Programming in Biomolecular Computation: Programs, Self-Interpretation and Visualisation

    Directory of Open Access Journals (Sweden)

    J.G. Simonsen

    2011-01-01

    Full Text Available Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We identify a number of common features in programming that seem conspicuously absent from the literature on biomolecular computing; to partially redress this absence, we introduce a model of computation that is evidently programmable, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only executable, but are also compilable and interpretable. It is universal: all computable functions can be computed (in natural ways and without arcane encodings of data and algorithm; it is also uniform: new ``hardware'' is not needed to solve new problems; and (last but not least it is Turing complete in a strong sense: a universal algorithm exists, that is able to execute any program, and is not asymptotically inefficient.

  1. Structures and Functions of Oligosaccharins

    Energy Technology Data Exchange (ETDEWEB)

    Albersheim, Peter

    1995-12-01

    We have made considerable progress during the 2.5 year funding period just ending in our studies of the structures and functions of oligosaccharide signal molecules (oligosaccharins). We have emphasized studies of the enzymes that solubilize, process, and degrade oligosaccharins and of the proteins that inhibit those enzymes. We have been especially interested in elucidating how oligosaccharins and their processing enzymes participate in determining the outcome of challenges to plants by pathogenic microbes. We have studied, to a lesser extent, the roles of oligosaccharins in plant growth and development. Abstracts of papers describing results acquired with support from this grant that have been published, submitted, or in preparation are presented to summarize the progress made during the last two and one half years. The report highlights the most important contributions made in our oiigosaccharin research during this time period, and the corresponding abstract is referenced. Results of work in progress are described primarily in conjunction with our application for continued support.

  2. Biomolecular Aspects of Mercury Transformations

    Science.gov (United States)

    Johs, A.; Shi, L.; Miller, S. M.; Summers, A. O.; Liang, L.

    2008-12-01

    Bacteria participate significantly in mercury transformation in natural and industrial environments. Previous studies have shown that bacterial mercury resistance is mediated by the mer operon, typically located on transposons or plasmids. It encodes specific genes that facilitate uptake of mercury species, cleavage of organomercurials, and reduction of Hg(II) to Hg(0). Expression of mer operon genes is regulated by MerR, a metal-responsive regulator protein on the level of transcription. In vitro studies have shown that MerR forms a non-transcribing pre-initiation complex with RNA polymerase and the promoter DNA. Binding of Hg(II) induces conformational changes in MerR and other components of the complex resulting in the transcription of mer operon genes. As part of ongoing investigations on allosteric conformational changes induced by Hg(II) in dimeric MerR, and the implications on the binding of RNA polymerase to the promoter of the mer operon, we applied small angle scattering to study the regulatory mechanism of MerR in the presence and absence of Hg(II). Our results show that in the presence of Hg(II) the MerR dimer undergoes a significant reorientation from a compact state to a conformation revealing two distinct domains. Bacterial reduction of Hg(II) can also occur at concentrations too low to induce mer operon functions. Dissimilatory metal reducing bacteria, such as Shewanella and Geobacter are able to reduce Hg(II) in the presence of mineral oxides. This process has been linked to the activity of outer membrane multiheme cytochromes. We isolated and purified a decaheme outer membrane cytochrome OmcA from Shewanella oneidensis MR-1 and characterized its envelope shape in solution by small angle x-ray scattering. Structural features were identified and compared to homology models. These results show that OmcA is an elongated macromolecule consisting of separate modules, which may be connected by flexible linkers.

  3. Structure and functions of fungal cell surfaces

    Science.gov (United States)

    Nozawa, Y.

    1984-01-01

    A review with 24 references on the biochemistry, molecular structure, and function of cell surfaces of fungi, especially dermatophytes: the chemistry and structure of the cell wall, the effect of polyene antibiotics on the morphology and function of cytoplasmic membranes, and the chemical structure and function of pigments produced by various fungi are discussed.

  4. Structure Function Estimated From Histological Tissue Sections.

    Science.gov (United States)

    Han, Aiguo; O'Brien, William D

    2016-09-01

    Ultrasonic scattering is determined by not only the properties of individual scatterers but also the correlation among scatterer positions. The role of scatterer spatial correlation is significant for dense medium, but has not been fully understood. The effect of scatterer spatial correlation may be modeled by the structure function as a frequency-dependent factor in the backscatter coefficient (BSC) expression. The structure function has been previously estimated from the BSC data. The aim of this study is to estimate the structure function from histology to test if the acoustically estimated structure function is indeed caused by the scatterer spatial distribution. Hematoxylin and eosin stained histological sections from dense cell pellet biophantoms were digitized. The scatterer positions were determined manually from the histological images. The structure function was calculated from the extracted scatterer positions. The structure function obtained from histology showed reasonable agreement in the shape but not in the amplitude, compared with the structure function previously estimated from the backscattered data. Fitting a polydisperse structure function model to the histologically estimated structure function yielded relatively accurate cell radius estimates ([Formula: see text]). Furthermore, two types of mouse tumors that have similar cell size and shape but distinct cell spatial distributions were studied, where the backscattered data were shown to be related to the cell spatial distribution through the structure function estimated from histology. In conclusion, the agreement between acoustically estimated and histologically estimated structure functions suggests that the acoustically estimated structure function is related to the scatterer spatial distribution.

  5. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations.

    Science.gov (United States)

    Vergara-Perez, Sandra; Marucho, Marcelo

    2016-01-01

    One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post- analysis of structural and electrical properties of biomolecules.

  6. MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

    Science.gov (United States)

    Vergara-Perez, Sandra; Marucho, Marcelo

    2016-01-01

    One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson-Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post-analysis of structural and electrical properties of biomolecules.

  7. Novel Structure and Function of Typhoid Toxin

    Science.gov (United States)

    ... Matters NIH Research Matters July 29, 2013 Novel Structure and Function of Typhoid Toxin Structure of typhoid toxin, showing the 2 A subunits ( ... to cultured cells. The scientists next determined the structure of the typhoid toxin. The toxin was already ...

  8. Soft nanotechnology: "structure" vs. "function".

    Science.gov (United States)

    Whitesides, George M; Lipomi, Darren J

    2009-01-01

    This paper offers a perspective on "soft nanotechnology"; that is, the branch of nanotechnology concerned with the synthesis and properties of organic and organometallic nanostructures, and with nanofabrication using techniques in which soft components play key roles. It begins with a brief history of soft nanotechnology. This history has followed a path involving a gradual shift from the promise of revolutionary electronics, nanorobotics, and other futuristic concepts, to the realization of evolutionary improvements in the technology for current challenges in information technology, medicine, and sustainability. Soft nanoscience is an area that is occupied principally by chemists, and is in many ways indistinguishable from "nanochemistry". The paper identifies the natural tendency of its practitioners--exemplified by the speakers at this Faraday Discussion--to focus on synthesis and structure, rather than on function and application, of nanostructures. Soft nanotechnology has the potential to apply to a wide variety of large-scale applied (information technology, healthcare cost reduction, sustainability, energy) and fundamental (molecular biochemistry, cell biology, charge transport in organic matter) problems.

  9. Structure and Function of Lipase

    DEFF Research Database (Denmark)

    Skjold-Jørgensen, Jakob

    Lipases are triacylglycerol hydrolases (EC 3.1.1.3) which are able to act on water-insoluble esters, butdisplay very low activity towards water-soluble, monomeric substrates. This is ascribed to theircharacteristic activation mechanism occurring at the boundary between water and lipid, i.e. the w......Lipases are triacylglycerol hydrolases (EC 3.1.1.3) which are able to act on water-insoluble esters, butdisplay very low activity towards water-soluble, monomeric substrates. This is ascribed to theircharacteristic activation mechanism occurring at the boundary between water and lipid, i.......e. the waterlipidinterface. For Thermomyces lanuginosus lipase (TlL) and related lipases, activation of the enzymeinvolves a rearrangement of a structural domain, called the “lid”, which covers the active site inhomogenous aqueous solution. At the water-lipid interface, the lid is displaced from the active site andmoves...... towards an open conformation enabling the substrate to gain access, thus initiating catalysis.Lipases have been studied for decades and their functional features have drawn much attention withinindustrial applications since their first discovery. However, given that their molecular action takes placeat...

  10. Unraveling the biomolecular snapshots of mitosis in healthy and cancer cells using plasmonically-enhanced Raman spectroscopy.

    Science.gov (United States)

    Panikkanvalappil, Sajanlal R; Hira, Steven M; Mahmoud, Mahmoud A; El-Sayed, Mostafa A

    2014-11-12

    Owing to the dynamic and complex nature of mitosis, precise and timely executions of biomolecular events are critical for high fidelity cell division. In this context, visualization of such complex events at the molecular level can provide vital information on the biomolecular processes in abnormal cells. Here, we explored the plasmonically enhanced light scattering properties of functionalized gold nanocubes (AuNCs) together with surface-enhanced Raman spectroscopy (SERS) to unravel the complex and dynamic biological processes involved in mitosis of healthy and cancerous cells from its molecular perspectives. By monitoring various stages of mitosis using SERS, we noticed that relatively high rate of conversion of mitotic proteins from their α-helix structure to β-sheet conformation is likely in the cancer cells during meta-, ana-, and telophases. Unique biochemical modifications to the lipid and amino acid moieties, associated with the observed protein conformational modifications, were also identified. However, in healthy cells, the existence of proteins in their β conformation was momentary and was largely in the α-helix form. The role of abnormal conformational modifications of mitotic proteins on the development of anomalous mitotic activities was further confirmed by looking at plasmonic nanoparticle-induced cytokinesis failure in cancer cells. Our findings illustrate the vast possibilities of SERS in real-time tracking of complex, subtle, and momentary modifications of biomolecules in live cells, which could provide new insights to the role of protein conformation dynamics during mitosis on the development of cancer and many other diseases.

  11. Diffusion Monte Carlo applied to weak interactions - hydrogen bonding and aromatic stacking in (bio-)molecular model systems

    Science.gov (United States)

    Fuchs, M.; Ireta, J.; Scheffler, M.; Filippi, C.

    2006-03-01

    Dispersion (Van der Waals) forces are important in many molecular phenomena such as self-assembly of molecular crystals or peptide folding. Calculating this nonlocal correlation effect requires accurate electronic structure methods. Usual density-functional theory with generalized gradient functionals (GGA-DFT) fails unless empirical corrections are added that still need extensive validation. Quantum chemical methods like MP2 and coupled cluster are more accurate, yet limited to rather small systems by their unfavorable computational scaling. Diffusion Monte Carlo (DMC) can provide accurate molecular total energies and remains feasible also for larger systems. Here we apply the fixed-node DMC method to (bio-)molecular model systems where dispersion forces are significant: (dimethyl-) formamide and benzene dimers, and adenine-thymine DNA base pairs. Our DMC binding energies agree well with data from coupled cluster (CCSD(T)), in particular for stacked geometries where GGA-DFT fails qualitatively and MP2 predicts too strong binding.

  12. 核磁共振、X射线小角散射以及计算机模拟相结合构建生物大分子复合物的结构模型%Determining Structural Models of Biomolecular Complexes Integrating Nuclear Magnetic Resonance, Small-Angle X-ray Scattering and Computational Simulations

    Institute of Scientific and Technical Information of China (English)

    彭俊辉; 赵德彪; 文彬; 张志勇

    2015-01-01

    Structural biology has been paying more attention on biomolecular complexes over the past decades, since they are crucial for many biological processes. Among these techniques for structural determination, nuclear magnetic resonance (NMR) has its advantage when dealing with biomolecules with high flexibility in solution. Small-angle X-ray scattering (SAXS) is a very important complementary technique that provides information on global shape of biomolecules. For biomolecular complexes, it can be much easier to determine atomic structures of individual subunits through NMR. In addition, NMR can also provide other structural information, such as the interface and orientations between subunits, and long range distance and angular restraints. Therefore, to construct structural models of biomolecular complexes, it would be very appropriate to combine experimental restraints obtained through NMR and low-resolution shape information from SAXS by utilizing computational tools, which is the main topic of this review.%近年来,结构生物学研究越来越注重生物大分子复合物的解析,因为许多重要生物学过程都离不开复合物的参与.溶液核磁共振是目前重要的结构解析方法之一.X射线小角散射(SAXS)作为一种新的结构生物学实验手段,近年来发展迅速.SAXS 能提供生物大分子复合物的较低分辨率结构信息,而核磁共振能解析复合物中各个亚基的原子分辨率结构.此外,通过核磁共振还能得到亚基之间的界面、取向以及距离信息.因此近年来通过计算机模拟,整合核磁共振和 SAXS 不同分辨率的结构信息,可以用来搭建生物大分子复合物的结构模型.该综述重点介绍这方面的研究进展.

  13. Systematic evaluation of bundled SPC water for biomolecular simulations.

    Science.gov (United States)

    Gopal, Srinivasa M; Kuhn, Alexander B; Schäfer, Lars V

    2015-04-07

    In bundled SPC water models, the relative motion of groups of four water molecules is restrained by distance-dependent potentials. Bundled SPC models have been used in hybrid all-atom/coarse-grained (AA/CG) multiscale simulations, since they enable to couple atomistic SPC water with supra-molecular CG water models that effectively represent more than a single water molecule. In the present work, we systematically validated and critically tested bundled SPC water models as solvent for biomolecular simulations. To that aim, we investigated both thermodynamic and structural properties of various biomolecular systems through molecular dynamics (MD) simulations. Potentials of mean force of dimerization of pairs of amino acid side chains as well as hydration free energies of single side chains obtained with bundled SPC and standard (unrestrained) SPC water agree closely with each other and with experimental data. Decomposition of the hydration free energies into enthalpic and entropic contributions reveals that in bundled SPC, this favorable agreement of the free energies is due to a larger degree of error compensation between hydration enthalpy and entropy. The Ramachandran maps of Ala3, Ala5, and Ala7 peptides are similar in bundled and unrestrained SPC, whereas for the (GS)2 peptide, bundled water leads to a slight overpopulation of extended conformations. Analysis of the end-to-end distance autocorrelation times of the Ala5 and (GS)2 peptides shows that sampling in more viscous bundled SPC water is about two times slower. Pronounced differences between the water models were found for the structure of a coiled-coil dimer, which is instable in bundled SPC but not in standard SPC. In addition, the hydration of the active site of the serine protease α-chymotrypsin depends on the water model. Bundled SPC leads to an increased hydration of the active site region, more hydrogen bonds between water and catalytic triad residues, and a significantly slower exchange of water

  14. Nuclear effects in the structure functions

    Indian Academy of Sciences (India)

    E Marco; E Oset; S K Singh

    2003-11-01

    By using a relativistic framework and accurate nuclear spectral function the structure functions 2 and 3 of deep inelastic charged lepton and neutrino scattering are calculated in nuclei and results are presented.

  15. The structure and function of cartilage proteoglycans

    Directory of Open Access Journals (Sweden)

    P J Roughley

    2006-11-01

    Full Text Available Cartilage contains a variety of proteoglycans that are essential for its normal function. These include aggrecan, decorin, biglycan, fibromodulin and lumican. Each proteoglycan serves several functions that are determined by both its core protein and its glycosaminoglycan chains. This review discusses the structure/function relationships of the cartilage proteoglycans, and the manner in which perturbations in proteoglycan structure or abundance can adversely affect tissue function.

  16. Insights into cancer severity from biomolecular interaction mechanisms

    Science.gov (United States)

    Raimondi, Francesco; Singh, Gurdeep; Betts, Matthew J.; Apic, Gordana; Vukotic, Ranka; Andreone, Pietro; Stein, Lincoln; Russell, Robert B.

    2016-01-01

    To attain a deeper understanding of diseases like cancer, it is critical to couple genetics with biomolecular mechanisms. High-throughput sequencing has identified thousands of somatic mutations across dozens of cancers, and there is a pressing need to identify the few that are pathologically relevant. Here we use protein structure and interaction data to interrogate nonsynonymous somatic cancer mutations, identifying a set of 213 molecular interfaces (protein-protein, -small molecule or –nucleic acid) most often perturbed in cancer, highlighting several potentially novel cancer genes. Over half of these interfaces involve protein-small-molecule interactions highlighting their overall importance in cancer. We found distinct differences in the predominance of perturbed interfaces between cancers and histological subtypes and presence or absence of certain interfaces appears to correlate with cancer severity. PMID:27698488

  17. Orientation of biomolecular assemblies in a microfluidic jet

    Energy Technology Data Exchange (ETDEWEB)

    Priebe, M; Kalbfleisch, S; Tolkiehn, M; Salditt, T [Institut fuer Roentgenphysik, Universitaet Goettingen, Goettingen (Germany); Koester, S [Courant Research Centre Nano-Spectroscopy and X-Ray Imaging, Universitaet Goettingen, Goettingen (Germany); Abel, B [Institut fuer Physikalische Chemie, Universitaet Goettingen, Goettingen (Germany); Davies, R J, E-mail: tsalditt@gwdg.d [ID13, ESRF, Grenoble (France)

    2010-04-15

    We have investigated multilamellar lipid assemblies in a microfluidic jet, operating at high shear rates of the order of 10{sup 7} s{sup -1}. Compared to classical Couette cells or rheometers, the shear rate was increased by at least 2-3 orders of magnitude, and the sample volume was scaled down correspondingly. At the same time, the jet is characterized by high extensional stress due to elongational flow. A focused synchrotron x-ray beam was used to measure the structure and orientation of the lipid assemblies in the jet. The diffraction patterns indicate conventional multilamellar phases, aligned with the membrane normals oriented along the velocity gradient of the jet. The results indicate that the setup may be well suited for coherent diffractive imaging of oriented biomolecular assemblies and macromolecules at the future x-ray free electron laser (XFEL) sources.

  18. The biomolecular corona of nanoparticles in circulating biological media

    Science.gov (United States)

    Pozzi, D.; Caracciolo, G.; Digiacomo, L.; Colapicchioni, V.; Palchetti, S.; Capriotti, A. L.; Cavaliere, C.; Zenezini Chiozzi, R.; Puglisi, A.; Laganà, A.

    2015-08-01

    When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let multicomponent liposomes interact with fetal bovine serum (FBS) both statically and dynamically, i.e. in contact with circulating FBS (~40 cm s-1). The structure and composition of the liposome-protein corona, as determined by dynamic light scattering, electrophoretic light scattering and liquid chromatography tandem mass spectrometry, were found to be dependent on the incubation protocol. Specifically, following dynamic exposure to FBS, multicomponent liposomes were less enriched in complement proteins and appreciably more enriched in apolipoproteins and acute phase proteins (e.g. alpha-1-antitrypsin and inter-alpha-trypsin inhibitor heavy chain H3) that are involved in relevant interactions between nanoparticles and living systems. Supported by our results, we speculate that efficient predictive modeling of nanoparticle behavior in vivo will require accurate knowledge of nanoparticle-specific protein fingerprints in circulating biological media.When nanoparticles come into contact with biological media, they are covered by a biomolecular `corona', which confers a new identity to the particles. In all the studies reported so far nanoparticles are incubated with isolated plasma or serum that are used as a model for protein adsorption. Anyway, bodily fluids are dynamic in nature so the question arises on whether the incubation protocol, i.e. dynamic vs. static incubation, could affect the composition and structure of the biomolecular corona. Here we let

  19. Quantum dynamics of bio-molecular systems in noisy environments

    CERN Document Server

    Plenio, M B

    2012-01-01

    We discuss three different aspects of the quantum dynamics of bio-molecular systems and more generally complex networks in the presence of strongly coupled environments. Firstly, we make a case for the systematic study of fundamental structural elements underlying the quantum dynamics of these systems, identify such elements and explore the resulting interplay of quantum dynamics and environmental decoherence. Secondly, we critically examine some existing approaches to the numerical description of system-environment interaction in the non-perturbative regime and present a promising new method that can overcome some limitations of existing methods. Thirdly, we present an approach towards deciding and quantifying the non-classicality of the action of the environment and the observed system-dynamics. We stress the relevance of these tools for strengthening the interplay between theoretical and experimental research in this field.

  20. Hybrid organic semiconductor lasers for bio-molecular sensing.

    Science.gov (United States)

    Haughey, Anne-Marie; Foucher, Caroline; Guilhabert, Benoit; Kanibolotsky, Alexander L; Skabara, Peter J; Burley, Glenn; Dawson, Martin D; Laurand, Nicolas

    2014-01-01

    Bio-functionalised luminescent organic semiconductors are attractive for biophotonics because they can act as efficient laser materials while simultaneously interacting with molecules. In this paper, we present and discuss a laser biosensor platform that utilises a gain layer made of such an organic semiconductor material. The simple structure of the sensor and its operation principle are described. Nanolayer detection is shown experimentally and analysed theoretically in order to assess the potential and the limits of the biosensor. The advantage conferred by the organic semiconductor is explained, and comparisons to laser sensors using alternative dye-doped materials are made. Specific biomolecular sensing is demonstrated, and routes to functionalisation with nucleic acid probes, and future developments opened up by this achievement, are highlighted. Finally, attractive formats for sensing applications are mentioned, as well as colloidal quantum dots, which in the future could be used in conjunction with organic semiconductors.

  1. Scalable Molecular Dynamics for Large Biomolecular Systems

    Directory of Open Access Journals (Sweden)

    Robert K. Brunner

    2000-01-01

    Full Text Available We present an optimized parallelization scheme for molecular dynamics simulations of large biomolecular systems, implemented in the production-quality molecular dynamics program NAMD. With an object-based hybrid force and spatial decomposition scheme, and an aggressive measurement-based predictive load balancing framework, we have attained speeds and speedups that are much higher than any reported in literature so far. The paper first summarizes the broad methodology we are pursuing, and the basic parallelization scheme we used. It then describes the optimizations that were instrumental in increasing performance, and presents performance results on benchmark simulations.

  2. Fundamentos biomoleculares de la diabetes mellitus

    OpenAIRE

    2013-01-01

    La diabetes mellitus es una enfermedad endocrina con importantes implicaciones a nivel sistémico, como: angiopatía, neuropatía, retinopatía y nefropatía, entre otras. Estas  complicaciones tienen su origen en eventos biomoleculares desencadenados por la hiperglicemia.  La presente revisión de tema trata sobre la estructura y síntesis de la insulina en las células β del páncreas; los eventos moleculares y bioquímicos que activan su secreción como respuesta a una alta concentración de glucosa e...

  3. Out-of-equilibrium biomolecular interactions monitored by picosecond fluorescence in microfluidic droplets.

    Science.gov (United States)

    Maillot, Sacha; Carvalho, Alain; Vola, Jean-Pierre; Boudier, Christian; Mély, Yves; Haacke, Stefan; Léonard, Jérémie

    2014-05-21

    We developed a new experimental approach combining Time-Resolved Fluorescence (TRF) spectroscopy and Droplet Microfluidics (DμF) to investigate the relaxation dynamics of structurally heterogeneous biomolecular systems. Here DμF was used to produce with minimal material consumption an out-of-equilibrium, fluorescently labeled biomolecular complex by rapid mixing within the droplets. TRF detection was implemented with a streak camera to monitor the time evolution of the structural heterogeneity of the complex along its relaxation towards equilibrium while it propagates inside the microfluidic channel. The approach was validated by investigating the fluorescence decay kinetics of a model interacting system of bovine serum albumin and Patent Blue V. Fluorescence decay kinetics are acquired with very good signal-to-noise ratio and allow for global, multicomponent fluorescence decay analysis, evidencing heterogeneous structural relaxation over several 100 ms.

  4. Energy dissipation in biomolecular machines

    Energy Technology Data Exchange (ETDEWEB)

    Lervik, Anders

    2012-07-01

    The operation of a molecular pump, the calcium pump of sarcoplasmic reticulum is studied using mesoscopic non-equilibrium thermodynamics and molecular dynamics. The mesoscopic non-equilibrium thermodynamic description of the pump is compared to the description obtained in the framework of Hill for kinetic enzyme cycles. By comparing these two descriptions at isothermal conditions, they are found to be equivalent. This supports the validity of the mesoscopic approach. An extension of the mesoscopic non-equilibrium framework to also include a heat flux and the corresponding temperature difference is proposed. This can be used to model phenomena such as non-shivering thermogenesis, a process which lack a theoretical description in the kinetic cycle picture. Further, the heat transfer in the calcium pump is studied using molecular dynamics. This is done in order to obtain phenomenological parameters that can be used for the modeling of thermogenesis. A non-stationary non-equilibrium molecular dynamics approach is developed, which may be used to study heat transfer between a small object and the surrounding solvent. This methodology is applied to the calcium pump solvated in water. It is found that the thermal conductivity of the protein is low (0.2 W K-1 m-1) compared to water (0.6 WK-1 m-1). This means that the protein may sustain a large temperature gradient across its structure. The simulations also show that the protein-water surface is important for the heat transfer. The time scale for vibrational energy relaxation is found to be of order 10/100 ps which strengthens the local equilibrium assumption of mesoscopic non-equilibrium thermodynamics. Mesoscopic non-equilibrium thermodynamics is also applied to calculate the thermodynamic efficiency of the calcium pump embedded in lipid bilayers of varying length and from different tissues. This is done in order to show the applicability of mesoscopic non-equilibrium thermodynamics to interpret experimental data. The

  5. Photon structure function in supersymmetric QCD revisited

    Energy Technology Data Exchange (ETDEWEB)

    Sahara, Ryo, E-mail: sahara@scphys.kyoto-u.ac.jp [Department of Physics, Graduate School of Science, Kyoto University, Kitashirakawa, Kyoto 606-8502 (Japan); Uematsu, Tsuneo, E-mail: uematsu@scphys.kyoto-u.ac.jp [Department of Physics, Graduate School of Science, Kyoto University, Kitashirakawa, Kyoto 606-8502 (Japan); Kitadono, Yoshio, E-mail: kitadono@phys.sinica.edu.tw [Institute of Physics, Academia Sinica, Taipei, Taiwan (China)

    2012-02-07

    We investigate the virtual photon structure function in the supersymmetric QCD (SQCD), where we have squarks and gluinos in addition to the quarks and gluons. Taking into account the heavy particle mass effects to the leading order in QCD and SQCD we evaluate the photon structure function and numerically study its behavior for the QCD and SQCD cases.

  6. Photon Structure Function in Supersymmetric QCD Revisited

    CERN Document Server

    Sahara, Ryo; Kitadono, Yoshio

    2011-01-01

    We investigate the virtual photon structure function in the supersymmetric QCD (SQCD), where we have squarks and gluinos in addition to the quarks and gluons. Taking into account the heavy particle mass effects to the leading order in QCD and SQCD we evaluate the photon structure function and numerically study its behavior for the QCD and SQCD cases.

  7. WAY TO DETERMINE STIFFNESS FUNCTION OF STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    WANG De-ming; GAI Bing-zheng

    2005-01-01

    For calculating the stiffness function of a structure, the differential equation of the vibration of the structure was divided into the differential equation on the original stiffness function that was known, and Fredholm integral equation of the first kind on the undetermined stiffness function that was unknown. And the stable solutions of the integral equation, when the smooth factor was equal to zero, was solved by the extrapolation with p smooth factors. So the stiffness function of the structure is obtained. Applied examples show that the method is feasible and effective.

  8. Structure and function in flow networks

    CERN Document Server

    Rubido, Nicolás; Baptista, Murilo S

    2013-01-01

    This Letter presents a unified approach for the fundamental relationship between structure and function in flow networks by solving analytically the voltages in a resistor network, transforming the network structure to an effective all-to-all topology, and then measuring the resultant flows. Moreover, it defines a way to study the structural resilience of the graph and to detect possible communities.

  9. Nitrogenase structure and function relationships by density functional theory.

    Science.gov (United States)

    Harris, Travis V; Szilagyi, Robert K

    2011-01-01

    Modern density functional theory has tremendous potential with matching popularity in metalloenzymology to reveal the unseen atomic and molecular details of structural data, spectroscopic measurements, and biochemical experiments by providing insights into unobservable structures and states, while also offering theoretical justifications for observed trends and differences. An often untapped potential of this theoretical approach is to bring together diverse experimental structural and reactivity information and allow for these to be critically evaluated at the same level. This is particularly applicable for the tantalizingly complex problem of the structure and molecular mechanism of biological nitrogen fixation. In this chapter we provide a review with extensive practical details of the compilation and evaluation of experimental data for an unbiased and systematic density functional theory analysis that can lead to remarkable new insights about the structure-function relationships of the iron-sulfur clusters of nitrogenase.

  10. Stochastic Simulation of Biomolecular Reaction Networks Using the Biomolecular Network Simulator Software

    Science.gov (United States)

    2008-02-01

    investigate the simulation of a biomolecular reaction network with BNS, a simple model of a generic self-assembling catalytic ligation reaction in a...Amino Acid Pools Nucleotide Triphosphate Pools Nucleotide Monophosphate Pools Ligation Reaction 1551 517 7 RESULTS Simulation of exemplar...and reaction r8 is the catalytic ligation reaction . In figures 5(B) through 5(F), both the time-averaged event rate for a single simulation run

  11. Biomolecular Markers in Cancer of the Tongue

    Directory of Open Access Journals (Sweden)

    Daris Ferrari

    2009-01-01

    Full Text Available The incidence of tongue cancer is increasing worldwide, and its aggressiveness remains high regardless of treatment. Genetic changes and the expression of abnormal proteins have been frequently reported in the case of head and neck cancers, but the little information that has been published concerning tongue tumours is often contradictory. This review will concentrate on the immunohistochemical expression of biomolecular markers and their relationships with clinical behaviour and prognosis. Most of these proteins are associated with nodal stage, tumour progression and metastases, but there is still controversy concerning their impact on disease-free and overall survival, and treatment response. More extensive clinical studies are needed to identify the patterns of molecular alterations and the most reliable predictors in order to develop tailored anti-tumour strategies based on the targeting of hypoxia markers, vascular and lymphangiogenic factors, epidermal growth factor receptors, intracytoplasmatic signalling and apoptosis.

  12. Biomolecular computing systems: principles, progress and potential.

    Science.gov (United States)

    Benenson, Yaakov

    2012-06-12

    The task of information processing, or computation, can be performed by natural and man-made 'devices'. Man-made computers are made from silicon chips, whereas natural 'computers', such as the brain, use cells and molecules. Computation also occurs on a much smaller scale in regulatory and signalling pathways in individual cells and even within single biomolecules. Indeed, much of what we recognize as life results from the remarkable capacity of biological building blocks to compute in highly sophisticated ways. Rational design and engineering of biological computing systems can greatly enhance our ability to study and to control biological systems. Potential applications include tissue engineering and regeneration and medical treatments. This Review introduces key concepts and discusses recent progress that has been made in biomolecular computing.

  13. Fundamentos biomoleculares de la diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Katiana Mendoza

    2013-12-01

    Full Text Available La diabetes mellitus es una enfermedad endocrina con importantes implicaciones a nivel sistémico, como: angiopatía, neuropatía, retinopatía y nefropatía, entre otras. Estas  complicaciones tienen su origen en eventos biomoleculares desencadenados por la hiperglicemia.  La presente revisión de tema trata sobre la estructura y síntesis de la insulina en las células β del páncreas; los eventos moleculares y bioquímicos que activan su secreción como respuesta a una alta concentración de glucosa en sangre; la cascada de señalización generada por la unión de la insulina a su receptor sobre células diana; y las alteraciones metabólicas que los diferentes tipos de diabetes mellitus producen.

  14. Progress on nuclear modifications of structure functions

    CERN Document Server

    Kumano, S

    2016-01-01

    We report progress on nuclear structure functions, especially on their nuclear modifications and a new tensor structure function for the deuteron. To understand nuclear structure functions is an important step toward describing nuclei and QCD matters from low to high densities and from low to high energies in terms of fundamental quark and gluon degrees of freedom beyond conventional hadron and nuclear physics. It is also practically important for understanding new phenomena in high-energy heavy-ion collisions at RHIC and LHC. Furthermore, since systematic errors of current neutrino-oscillation experiments are dominated by uncertainties of neutrino-nucleus interactions, such studies are valuable for finding new physics beyond current framework. Next, a new tensor-polarized structure function $b_1$ is discussed for the deuteron. There was a measurement by HERMES; however, its data are inconsistent with the conventional convolution estimate based on the standard deuteron model with D-state admixture. This fact ...

  15. Structural and functional properties of designed globins

    Indian Academy of Sciences (India)

    Yasuhiro Isogai; Anna Ishii; Manabu Ishida; Masahiro Mukai; Motonori Ota; Ken Nishikawa; Tetsutaro Iizuka

    2000-06-01

    De novo design of artificial proteins is an essential approach to elucidate the principles of protein architecture and to understand specific functions of natural proteins and also to yield novel molecules for medical and industrial aims. We have designed artificial sequences of 153 amino acids to fit the main-chain framework of the sperm whale myoglobin structure based on the knowledge-based energy functions to evaluate the compatibility between protein tertiary structures and amino acid sequences. The synthesized artificial globins bind a single heme per protein molecule as designed, which show well-defined electrochemical and spectroscopic features characteristic of proteins with a low-spin heme. Redox and ligand binding reactions of the artificial heme proteins were investigated and these heme-related functions were found to vary with their structural uniqueness. Relationships between the structural and functional properties are discussed.

  16. Understanding Microbial Communities: Function, Structure and Dynamics

    Science.gov (United States)

    2015-02-11

    microbial communities: Function, structure and dynamics’, at the Isaac Newton Institute, University of Cambridge, United Kingdom, from August to...dynamics’, at the Isaac Newton Institute, University of Cambridge, United Kingdom, from August to December 2014. The programme involved over 150...Communities: Function, Structure and Dynamics’, at the Isaac Newton Institute, Cambridge University, UK, from 19th August 2014 – 19th December 2014

  17. Recent Structure Function Results from CCFR

    CERN Document Server

    Fleming, B T; Alton, A; Arroyo, C G; Avvakumov, S; De Barbaro, L; De Barbaro, P; Bazarko, A O; Bernstein, R H; Bodek, Arie; Bolton, T; Brau, J E; Buchholz, D; Budd, H S; Bugel, L; Conrad, J; Drucker, R B; Formaggio, J A; Frey, R; Goldman, J; Goncharov, M; Harris, D A; Johnson, R A; Kim, J H; King, B J; Kinnel, T; Koutsoliotas, S; Lamm, M J; Marsh, W; Mason, D; McFarland, K S; McNulty, C; Mishra, S R; Naples, D; Nienaber, P; Romosan, A; Sakumoto, W K; Schellman, H; Sciulli, F J; Seligman, W G; Shaevitz, M H; Smith, W H; Spentzouris, P; Stern, E G; Vakili, M; Vaitaitis, A G; Yang, U K; Yu, J; Zeller, G P; Zimmerman, E D

    2000-01-01

    A new structure function analysis of CCFR deep inelastic nu-N and nubar-N scattering data is presented for previously unexplored kinematic regions down to Bjorken x=0.0045 and Q^2=0.3 GeV^2. Comparisons to charged lepton scattering data from NMC and E665 experiments are made and the behavior of the structure function F2_nu is studied in the limit Q^2 -> 0

  18. Polarized deuteron structure functions at small x

    CERN Document Server

    Edelmann, J; Weise, W

    1997-01-01

    We investigate shadowing corrections to the polarized deuteron structure functions g_1^d and b_1. In the kinematic domain of current fixed target experiments we observe that shadowing effects in g_1^d are approximately twice as large as for the unpolarized structure function F_2^d. Furthermore, we find that b_1 is surprisingly large at x < 0.1 and receives dominant contributions from coherent double scattering.

  19. [Snake venom metalloproteinases: structure, biosynthesis and function(s)].

    Science.gov (United States)

    Limam, I; El Ayeb, M; Marrakchi, N

    2010-01-01

    The biochemical and the pharmacological characterization of snake venoms revealed an important structural and functional polymorphism of proteins which they contain. Among them, snake venom metalloproteases (SVMPs) constitute approximatively 20 to 60% of the whole venom proteins. During the last decades, a significant progress was performed against structure studies and the biosynthesis of the SVMPs. Indeed, several metalloproteases were isolated and characterized against their structural and pharmacological properties. In this review, we report the most important properties concerning the classification, the structure of the various domains of the SVMPs as well as their biosynthesis and their activities as potential therapeutic agents.

  20. Zinc finger structure-function in Ikaros

    Institute of Scientific and Technical Information of China (English)

    Marvin; A; Payne

    2011-01-01

    The zinc finger motif was used as a vehicle for the initial discovery of Ikaros in the context of T-cell differentiation and has been central to all subsequent analyses of Ikaros function.The Ikaros gene is alternately spliced to produce several isoforms that confer diversity of function and consequently have complicated analysis of the function of Ikaros in vivo.Key features of Ikaros in vivo function are associated with six C2H2 zinc fingers;four of which are alternately incorporated in the production of the various Ikaros isoforms.Although no complete structures are available for the Ikaros protein or any of its family members,considerable evidence has accumulated about the structure of zinc fingers and the role that this structure plays in the functions of the Ikaros family of proteins.This review summarizes the structural aspects of Ikaros zinc fingers,individually,and in tandem to provide a structural context for Ikaros function and to provide a structural basis to inform the design of future experiments with Ikaros and its family members.

  1. Next-order structure-function equations

    Science.gov (United States)

    Hill, Reginald J.; Boratav, Olus N.

    2001-01-01

    Kolmogorov's equation [Dokl. Akad. Nauk SSSR 32, 16 (1941)] relates the two-point second- and third-order velocity structure functions and the energy dissipation rate. The analogous next higher-order two-point equation relates the third- and fourth-order velocity structure functions and the structure function of the product of pressure-gradient difference and two factors of velocity difference, denoted Tijk. The equation is simplified on the basis of local isotropy. Laboratory and numerical simulation data are used to evaluate and compare terms in the equation, examine the balance of the equation, and evaluate components of Tijk. Atmospheric surface-layer data are used to evaluate Tijk in the inertial range. Combined with the random sweeping hypothesis, the equation relates components of the fourth-order velocity structure function. Data show the resultant error of this application of random sweeping. The next-order equation constrains the relationships that have been suggested among components of the fourth-order velocity structure function. The pressure structure function, pressure-gradient correlation, and mean-squared pressure gradient are related to Tijk. Inertial range formulas are discussed.

  2. Structure and Structure-activity Relationship of Functional Organic Molecules

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Research theme The group is made up of junior scientists from the State Key Laboratory of Elemento-organic Chemistry, Nankai University.The scientists focus their studis on the structure and structure-activity relationship of functional organic molecules not only because it has been the basis of their research, but also because the functional study of organic compounds is now a major scientific issue for organic chemists around the world.

  3. Investigation of the Human Disease Osteogenesis Imperfecta: A Research-Based Introduction to Concepts and Skills in Biomolecular Analysis

    Science.gov (United States)

    Mate, Karen; Sim, Alistair; Weidenhofer, Judith; Milward, Liz; Scott, Judith

    2013-01-01

    A blended approach encompassing problem-based learning (PBL) and structured inquiry was used in this laboratory exercise based on the congenital disease Osteogenesis imperfecta (OI), to introduce commonly used techniques in biomolecular analysis within a clinical context. During a series of PBL sessions students were presented with several…

  4. Quantitative characterization of biomolecular assemblies and interactions using atomic force microscopy.

    Science.gov (United States)

    Yang, Yong; Wang, Hong; Erie, Dorothy A

    2003-02-01

    Atomic force microscopy (AFM) has been applied in many biological investigations in the past 15 years. This review focuses on the application of AFM for quantitatively characterizing the structural and thermodynamic properties of protein-protein and protein-nucleic acid complexes. AFM can be used to determine the stoichiometries and association constants of multiprotein assemblies and to quantify changes in conformations of proteins and protein-nucleic acid complexes. In addition, AFM in solution permits the observation of the dynamic properties of biomolecular complexes and the measurement of intermolecular forces between biomolecules. Recent advances in cryogenic AFM, AFM on two-dimensional crystals, carbon nanotube probes, solution imaging, high-speed AFM, and manipulation capabilities enhance these applications by improving AFM resolution and the dynamic and operative capabilities of the AFM. These developments make AFM a powerful tool for investigating the biomolecular assemblies and interactions that govern gene regulation.

  5. Huntington's disease : functional and structural biomarkers

    NARCIS (Netherlands)

    Dumas, Eve Marie

    2012-01-01

    The aims of this thesis were to gain insight into specific disease processes in Huntington’s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were

  6. 2004 Structural, Function and Evolutionary Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Douglas L. Brutlag Nancy Ryan Gray

    2005-03-23

    This Gordon conference will cover the areas of structural, functional and evolutionary genomics. It will take a systematic approach to genomics, examining the evolution of proteins, protein functional sites, protein-protein interactions, regulatory networks, and metabolic networks. Emphasis will be placed on what we can learn from comparative genomics and entire genomes and proteomes.

  7. Specificity quantification of biomolecular recognition and its implication for drug discovery

    Science.gov (United States)

    Yan, Zhiqiang; Wang, Jin

    2012-03-01

    Highly efficient and specific biomolecular recognition requires both affinity and specificity. Previous quantitative descriptions of biomolecular recognition were mostly driven by improving the affinity prediction, but lack of quantification of specificity. We developed a novel method SPA (SPecificity and Affinity) based on our funneled energy landscape theory. The strategy is to simultaneously optimize the quantified specificity of the ``native'' protein-ligand complex discriminating against ``non-native'' binding modes and the affinity prediction. The benchmark testing of SPA shows the best performance against 16 other popular scoring functions in industry and academia on both prediction of binding affinity and ``native'' binding pose. For the target COX-2 of nonsteroidal anti-inflammatory drugs, SPA successfully discriminates the drugs from the diversity set, and the selective drugs from non-selective drugs. The remarkable performance demonstrates that SPA has significant potential applications in identifying lead compounds for drug discovery.

  8. Conformation of bovine submaxillary mucin layers on hydrophobic surface as studied by biomolecular probes

    DEFF Research Database (Denmark)

    Pakkanen, Kirsi I.; Madsen, Jan Busk; Lee, Seunghwan

    2015-01-01

    In the present study, the conformational changes of bovine submaxillary mucin (BSM) adsorbed on a hydrophobic surface (polystyrene (PS)) as a function of concentration in bulk solution (up to 2mg/mL) have been investigated with biomolecular probe-based approaches, including bicinchoninic acid (BCA...... solution. Adsorbed masses of BSM onto hydrophobic surface, as probe by BCA, showed a continuously increasing trend up to 2mg/mL. But, the signals from EIA and ELLA, which probe the concentration of available unglycosylatedC-terminals and the central glycosylated regions, respectively, showed complicated...... non-linear responses with increasing surface concentration. The results from this study support the conventional amphiphilic, triblock model of BSM in the adsorption onto hydrophobic surface from aqueous solution.The biomolecular probe-based approaches employed in this study, however, provided further...

  9. Changes in biomolecular profile in a single nucleolus during cell fixation.

    Science.gov (United States)

    Kuzmin, Andrey N; Pliss, Artem; Prasad, Paras N

    2014-11-01

    Fixation of biological sample is an essential technique applied in order to "freeze" in time the intracellular molecular content. However, fixation induces changes of the cellular molecular structure, which mask physiological distribution of biomolecules and bias interpretation of results. Accurate, sensitive, and comprehensive characterization of changes in biomolecular composition, occurring during fixation, is crucial for proper analysis of experimental data. Here we apply biomolecular component analysis for Raman spectra measured in the same nucleoli of HeLa cells before and after fixation by either formaldehyde solution or by chilled ethanol. It is found that fixation in formaldehyde does not strongly affect the Raman spectra of nucleolar biomolecular components, but may significantly decrease the nucleolar RNA concentration. At the same time, ethanol fixation leads to a proportional increase (up to 40%) in concentrations of nucleolar proteins and RNA, most likely due to cell shrinkage occurring in the presence of coagulant fixative. Ethanol fixation also triggers changes in composition of nucleolar proteome, as indicated by an overall reduction of the α-helical structure of proteins and increase in the concentration of proteins containing the β-sheet conformation. We conclude that cross-linking fixation is a more appropriate protocol for mapping of proteins in situ. At the same time, ethanol fixation is preferential for studies of RNA-containing macromolecules. We supplemented our quantitative Raman spectroscopic measurements with mapping of the protein and lipid macromolecular groups in live and fixed cells using coherent anti-Stokes Raman scattering nonlinear optical imaging.

  10. Nanogap biosensors for electrical and label-free detection of biomolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kyu Kim, Sang; Cho, Hyunmin; Park, Hye-Jung; Kwon, Dohyoung; Min Lee, Jeong; Hyun Chung, Bong, E-mail: chungbh@kribb.re.k [BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, PO Box 115, Yuseong, Daejeon 305-600 (Korea, Republic of)

    2009-11-11

    We demonstrate nanogap biosensors for electrical and label-free detection of biomolecular interactions. Parallel fabrication of nanometer distance gaps has been achieved using a silicon anisotropic wet etching technique on a silicon-on-insulator (SOI) wafer with a finely controllable silicon device layer. Since silicon anisotropic wet etching resulted in a trapezoid-shaped structure whose end became narrower during the etching, the nanogap structure was simply fabricated on the device layer of a SOI wafer. The nanogap devices were individually addressable and a gap size of less than 60 nm was obtained. We demonstrate that the nanogap biosensors can electrically detect biomolecular interactions such as biotin/streptavidin and antigen/antibody pairs. The nanogap devices show a current increase when the proteins are bound to the surface. The current increases proportionally depending upon the concentrations of the molecules in the range of 100 fg ml{sup -1}-100 ng ml{sup -1} at 1 V bias. It is expected that the nanogap developed here could be a highly sensitive biosensor platform for label-free detection of biomolecular interactions.

  11. Structure functions in the chiral bag model

    Energy Technology Data Exchange (ETDEWEB)

    Sanjose, V.; Vento, V.

    1989-07-13

    We calculate the structure functions of an isoscalar nuclear target for the deep inelastic scattering by leptons in an extended version of the chiral bag model which incorporates the qanti q structure of the pions in the cloud. Bjorken scaling and Regge behavior are satisfied. The model calculation reproduces the low-x behavior of the data but fails to explain the medium- to large-x behavior. Evolution of the quark structure functions seem inevitable to attempt a connection between the low-energy models and the high-energy behavior of quantum chromodynamics. (orig.).

  12. Biomolecular interactions in HCV nucleocapsid-like particles as revealed by vibrational spectroscopy

    Science.gov (United States)

    Rodríguez-Casado, Arantxa; Molina, Marina; Carmona, Pedro

    2007-05-01

    Hepatitis C virus (HCV) occurs in the form of 55-65 nm spherical particles, but the structure of the virion remains to be clarified. Structural studies of HCV have been hampered by the lack of an appropriate cell culture system. However, structural analyses of HCV components can provide an essential framework for understanding of the molecular mechanism of virion assembly. This article reviews the potential of vibrational spectroscopy aimed at the knowledge of HCV structural biology, particularly regarding biomolecular interactions in nucleocapsid-like particles obtained in vitro.

  13. Predicting protein structure classes from function predictions

    DEFF Research Database (Denmark)

    Sommer, I.; Rahnenfuhrer, J.; de Lichtenberg, Ulrik;

    2004-01-01

    We introduce a new approach to using the information contained in sequence-to-function prediction data in order to recognize protein template classes, a critical step in predicting protein structure. The data on which our method is based comprise probabilities of functional categories; for given...... query sequences these probabilities are obtained by a neural net that has previously been trained on a variety of functionally important features. On a training set of sequences we assess the relevance of individual functional categories for identifying a given structural family. Using a combination...... of the most relevant categories, the likelihood of a query sequence to belong to a specific family can be estimated. Results: The performance of the method is evaluated using cross-validation. For a fixed structural family and for every sequence, a score is calculated that measures the evidence for family...

  14. Magnetism and Structure in Functional Materials

    CERN Document Server

    Planes, Antoni; Saxena, Avadh

    2005-01-01

    Magnetism and Structure in Functional Materials addresses three distinct but related topics: (i) magnetoelastic materials such as magnetic martensites and magnetic shape memory alloys, (ii) the magnetocaloric effect related to magnetostructural transitions, and (iii) colossal magnetoresistance (CMR) and related magnanites. The goal is to identify common underlying principles in these classes of materials that are relevant for optimizing various functionalities. The emergence of apparently different magnetic/structural phenomena in disparate classes of materials clearly points to a need for common concepts in order to achieve a broader understanding of the interplay between magnetism and structure in this general class of new functional materials exhibiting ever more complex microstructure and function. The topic is interdisciplinary in nature and the contributors correspondingly include physicists, materials scientists and engineers. Likewise the book will appeal to scientists from all these areas.

  15. Clustering aspects in nuclear structure functions

    CERN Document Server

    Hirai, M; Saito, K; Watanabe, T

    2010-01-01

    For understanding an anomalous nuclear effect experimentally observed for the beryllium-9 nucleus at the Thomas Jefferson National Accelerator Facility (JLab), clustering aspects are studied in structure functions of deep inelastic lepton-nucleus scattering by using momentum distributions calculated in antisymmetrized (or fermionic) molecular dynamics (AMD) and also in a simple shell model for comparison. According to the AMD, the Be-9 nucleus consists of two alpha-like clusters with a surrounding neutron. The clustering produces high-momentum components in nuclear wave functions, which affects nuclear modifications of the structure functions. We investigated whether clustering features could appear in the structure function F_2 of Be-9 along with studies for other light nuclei. We found that nuclear modifications of F_2 are similar in both AMD and shell models within our simple convolution description although there are slight differences in Be-9. It indicates that the anomalous Be-9 result should be explain...

  16. A starting point for fluorescence-based single-molecule measurements in biomolecular research.

    Science.gov (United States)

    Gust, Alexander; Zander, Adrian; Gietl, Andreas; Holzmeister, Phil; Schulz, Sarah; Lalkens, Birka; Tinnefeld, Philip; Grohmann, Dina

    2014-09-30

    Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET) experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research.

  17. A Starting Point for Fluorescence-Based Single-Molecule Measurements in Biomolecular Research

    Directory of Open Access Journals (Sweden)

    Alexander Gust

    2014-09-01

    Full Text Available Single-molecule fluorescence techniques are ideally suited to provide information about the structure-function-dynamics relationship of a biomolecule as static and dynamic heterogeneity can be easily detected. However, what type of single-molecule fluorescence technique is suited for which kind of biological question and what are the obstacles on the way to a successful single-molecule microscopy experiment? In this review, we provide practical insights into fluorescence-based single-molecule experiments aiming for scientists who wish to take their experiments to the single-molecule level. We especially focus on fluorescence resonance energy transfer (FRET experiments as these are a widely employed tool for the investigation of biomolecular mechanisms. We will guide the reader through the most critical steps that determine the success and quality of diffusion-based confocal and immobilization-based total internal reflection fluorescence microscopy. We discuss the specific chemical and photophysical requirements that make fluorescent dyes suitable for single-molecule fluorescence experiments. Most importantly, we review recently emerged photoprotection systems as well as passivation and immobilization strategies that enable the observation of fluorescently labeled molecules under biocompatible conditions. Moreover, we discuss how the optical single-molecule toolkit has been extended in recent years to capture the physiological complexity of a cell making it even more relevant for biological research.

  18. The proteome: structure, function and evolution.

    Science.gov (United States)

    Fleming, Keiran; Kelley, Lawrence A; Islam, Suhail A; MacCallum, Robert M; Muller, Arne; Pazos, Florencio; Sternberg, Michael J E

    2006-03-29

    This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk. Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein (http://www.e-protein.org/). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

  19. Condutância molecular e biomolecular

    Directory of Open Access Journals (Sweden)

    Gama A. Arnóbio S. da

    2000-01-01

    Full Text Available The concept of molecular conductance is discussed in terms of the propagation of an electronic interaction, between electron donor and acceptor groups, through the bonds of a molecular structure where these groups are embedded. The electronic interaction propagation is described by a Green's function matrix element, in a donor-bridge-acceptor molecular system reduced to a two-level representation.

  20. Structure and Functions of Linker Histones.

    Science.gov (United States)

    Lyubitelev, A V; Nikitin, D V; Shaytan, A K; Studitsky, V M; Kirpichnikov, M P

    2016-03-01

    Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions - from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed.

  1. GRASPs in Golgi Structure and Function

    Directory of Open Access Journals (Sweden)

    Xiaoyan eZhang

    2016-01-01

    Full Text Available The Golgi apparatus is a central intracellular membrane organelle for trafficking and modification of proteins and lipids. Its basic structure is a stack of tightly aligned flat cisternae. In mammalian cells, dozens of stacks are concentrated in the pericentriolar region and laterally connected to form a ribbon. Despite extensive research in the last decades, how this unique structure is formed and why its formation is important for proper Golgi functioning remain largely unknown. The Golgi ReAssembly Stacking Proteins, GRASP65 and GRASP55, are so far the only proteins shown to function in Golgi stacking. They are peripheral membrane proteins on the cytoplasmic face of the Golgi cisternae that form trans-oligomers through their N-terminal GRASP domain, and thereby function as the glue to stick adjacent cisternae together into a stack and to link Golgi stacks into a ribbon. Depletion of GRASPs in cells disrupts the Golgi structure and results in accelerated protein trafficking and defective glycosylation. In this minireview we summarize our current knowledge on how GRASPs function in Golgi structure formation and discuss why Golgi structure formation is important for its function.

  2. PREFACE: India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation

    Science.gov (United States)

    Onoda, Mitsuyoshi; Malhotra, Bansi D.

    2012-04-01

    The 'India-Japan Workshop on Biomolecular Electronics & Organic Nanotechnology for Environment Preservation' (IJWBME 2011) will be held on 7-10 December 2011 at EGRET Himeji, Himeji, Hyogo, Japan. This workshop was held for the first time on 17-19 December 2009 at NPL, New Delhi. Keeping in mind the importance of organic nanotechnology and biomolecular electronics for environmental preservation and their anticipated impact on the economics of both the developing and the developed world, IJWBME 2009 was jointly organized by the Department of Biological Functions, Graduate School of Life Sciences and Systems Engineering, the Kyushu Institute of Technology (KIT), Kitakyushu, Japan, and the Department of Science & Technology Centre on Biomolecular Electronics (DSTCBE), National Physical Laboratory (NPL). Much progress in the field of biomolecular electronics and organic nanotechnology for environmental preservation is expected for the 21st Century. Organic optoelectronic devices, such as organic electroluminescent devices, organic thin-film transistors, organic sensors, biological systems and so on have especially attracted much attention. The main purpose of this workshop is to provide an opportunity for researchers interested in biomolecular electronics and organic nanotechnology for environmental preservation, to come together in an informal and friendly atmosphere and exchange technical knowledge and experience. We are sure that this workshop will be very useful and fruitful for all participants in summarizing the recent progress in biomolecular electronics and organic nanotechnology for environmental preservation and preparing new ground for the next generation. Many papers have been submitted from India and Japan and more than 30 papers have been accepted for presentation. The main topics of interest are as follows: Bioelectronics Biomolecular Electronics Fabrication Techniques Self-assembled Monolayers Nano-sensors Environmental Monitoring Organic Devices

  3. Rational Design of Biomolecular Templates for Synthesizing Multifunctional Noble Metal Nanoclusters toward Personalized Theranostic Applications.

    Science.gov (United States)

    Yu, Yong; Mok, Beverly Y L; Loh, Xian Jun; Tan, Yen Nee

    2016-08-01

    Biomolecule-templated or biotemplated metal nanoclusters (NCs) are ultrasmall (<2 nm) metal (Au, Ag) particles stabilized by a certain type of biomolecular template (e.g., peptides, proteins, and DNA). Due to their unique physiochemical properties, biotemplated metal NCs have been widely used in sensing, imaging, delivery and therapy. The overwhelming applications in these individual areas imply the great promise of harnessing biotemplated metal NCs in more advanced biomedical aspects such as theranostics. Although applications of biotemplated metal NCs as theranostic agents are trending, the rational design of biomolecular templates suitable for the synthesis of multifunctional metal NCs for theranostics is comparatively underexplored. This progress report first identifies the essential attributes of biotemplated metal NCs for theranostics by reviewing the state-of-art applications in each of the four modalities of theranostics, namely sensing, imaging, delivery and therapy. To achieve high efficacy in these modalities, we elucidate the design principles underlying the use of biomolecules (proteins, peptides and nucleic acids) to control the NC size, emission color and surface chemistries for post-functionalization of therapeutic moieties. We then propose a unified strategy to engineer biomolecular templates that combine all these modalities to produce multifunctional biotemplated metal NCs that can serve as the next-generation personalized theranostic agents.

  4. Deep Inelastic Structure Functions at small x

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2006-01-01

    Explicit expressions for the non-singlet and singlet structure functions g_1 in the small-x region are obtained. They include the total resummation of the double- and single- logarithms of x and account for the running QCD coupling effects. Both the non-singlet and singlet structure functions are Regge behavied asymptotically, with the intercepts predicted in agreement with experiments. A detailed comparison with the DGLAP evolution equations for different values of x and Q^2 is performed. Finally, the role played by singular terms in DGLAP fits is discussed and explicitly shown to mimic the resummation of leading logarithms at small x.

  5. Programming biomolecular self-assembly pathways.

    Science.gov (United States)

    Yin, Peng; Choi, Harry M T; Calvert, Colby R; Pierce, Niles A

    2008-01-17

    In nature, self-assembling and disassembling complexes of proteins and nucleic acids bound to a variety of ligands perform intricate and diverse dynamic functions. In contrast, attempts to rationally encode structure and function into synthetic amino acid and nucleic acid sequences have largely focused on engineering molecules that self-assemble into prescribed target structures, rather than on engineering transient system dynamics. To design systems that perform dynamic functions without human intervention, it is necessary to encode within the biopolymer sequences the reaction pathways by which self-assembly occurs. Nucleic acids show promise as a design medium for engineering dynamic functions, including catalytic hybridization, triggered self-assembly and molecular computation. Here, we program diverse molecular self-assembly and disassembly pathways using a 'reaction graph' abstraction to specify complementarity relationships between modular domains in a versatile DNA hairpin motif. Molecular programs are executed for a variety of dynamic functions: catalytic formation of branched junctions, autocatalytic duplex formation by a cross-catalytic circuit, nucleated dendritic growth of a binary molecular 'tree', and autonomous locomotion of a bipedal walker.

  6. Biomolecular transport and separation in nanotubular networks.

    Energy Technology Data Exchange (ETDEWEB)

    Stachowiak, Jeanne C.; Stevens, Mark Jackson (Sandia National Laboratories, Albuquerque, NM); Robinson, David B.; Branda, Steven S.; Zendejas, Frank; Meagher, Robert J.; Sasaki, Darryl Yoshio; Bachand, George David (Sandia National Laboratories, Albuquerque, NM); Hayden, Carl C.; Sinha, Anupama; Abate, Elisa; Wang, Julia; Carroll-Portillo, Amanda (Sandia National Laboratories, Albuquerque, NM); Liu, Haiqing (Sandia National Laboratories, Albuquerque, NM)

    2010-09-01

    Cell membranes are dynamic substrates that achieve a diverse array of functions through multi-scale reconfigurations. We explore the morphological changes that occur upon protein interaction to model membrane systems that induce deformation of their planar structure to yield nanotube assemblies. In the two examples shown in this report we will describe the use of membrane adhesion and particle trajectory to form lipid nanotubes via mechanical stretching, and protein adsorption onto domains and the induction of membrane curvature through steric pressure. Through this work the relationship between membrane bending rigidity, protein affinity, and line tension of phase separated structures were examined and their relationship in biological membranes explored.

  7. Structural and functional insights into Mimivirus ORFans

    Directory of Open Access Journals (Sweden)

    Fischer Daniel

    2007-05-01

    Full Text Available Abstract Background Mimivirus isolated from A. polyphaga is the largest virus discovered so far. It is unique among all the viruses in having genes related to translation, DNA repair and replication which bear close homology to eukaryotic genes. Nevertheless, only a small fraction of the proteins (33% encoded in this genome has been assigned a function. Furthermore, a large fraction of the unassigned protein sequences bear no sequence similarity to proteins from other genomes. These sequences are referred to as ORFans. Because of their lack of sequence similarity to other proteins, they can not be assigned putative functions using standard sequence comparison methods. As part of our genome-wide computational efforts aimed at characterizing Mimivirus ORFans, we have applied fold-recognition methods to predict the structure of these ORFans and further functions were derived based on conservation of functionally important residues in sequence-template alignments. Results Using fold recognition, we have identified highly confident computational 3D structural assignments for 21 Mimivirus ORFans. In addition, highly confident functional predictions for 6 of these ORFans were derived by analyzing the conservation of functional motifs between the predicted structures and proteins of known function. This analysis allowed us to classify these 6 previously unannotated ORFans into their specific protein families: carboxylesterase/thioesterase, metal-dependent deacetylase, P-loop kinases, 3-methyladenine DNA glycosylase, BTB domain and eukaryotic translation initiation factor eIF4E. Conclusion Using stringent fold recognition criteria we have assigned three-dimensional structures for 21 of the ORFans encoded in the Mimivirus genome. Further, based on the 3D models and an analysis of the conservation of functionally important residues and motifs, we were able to derive functional attributes for 6 of the ORFans. Our computational identification of important

  8. The structure of bivariate rational hypergeometric functions

    CERN Document Server

    Cattani, Eduardo; Villegas, Fernando Rodriguez

    2009-01-01

    We describe the structure of all codimension-two lattice configurations $A$ which admit a stable rational $A$-hypergeometric function, that is a rational function $F$ all whose partial derivatives are non zero, and which is a solution of the $A$-hypergeometric system of partial differential equations defined by Gel'fand, Kapranov and Zelevinsky. We show, moreover, that all stable rational $A$-hypergeometric functions may be described by toric residues and apply our results to study the rationality of bivariate series whose coefficients are quotients of factorials of linear forms.

  9. Progress on nuclear modifications of structure functions

    Directory of Open Access Journals (Sweden)

    Kumano S.

    2016-01-01

    Full Text Available We report progress on nuclear structure functions, especially on their nuclear modifications and a new tensor structure function for the deuteron. To understand nuclear structure functions is an important step toward describing nuclei and QCD matters from low to high densities and from low to high energies in terms of fundamental quark and gluon degrees of freedom beyond conventional hadron and nuclear physics. It is also practically important for understanding new phenomena in high-energy heavy-ion collisions at RHIC and LHC. Furthermore, since systematic errors of current neutrinooscillation experiments are dominated by uncertainties of neutrino-nucleus interactions, such studies are valuable for finding new physics beyond current framework. Next, a new tensor-polarized structure function b1 is discussed for the deuteron. There was a measurement by HERMES; however, its data are inconsistent with the conventional convolution estimate based on the standard deuteron model with D-state admixture. This fact suggests that a new hadronic phenomenon should exist in the tensor-polarized deuteron at high energies, and it will be experimentally investigated at JLab from the end of 2010’s.

  10. Structural Functionalism as a Heuristic Device.

    Science.gov (United States)

    Chilcott, John H.

    1998-01-01

    Argues that structural functionalism as a method for conducting fieldwork and as a format for the analysis of ethnographic data remains a powerful model, one that is easily understood by professional educators. As a heuristic device, functionalist theory can help in the solution of a problem that is otherwise incapable of theoretical…

  11. [Structure and functions of glutathione transferases].

    Science.gov (United States)

    Fedets, O M

    2014-01-01

    Data about classification, nomenclature, structure, substrate specificity and role of many glutathione transferase's isoenzymes in cell functions have been summarised. The enzyme has been discovered more than 50 years ago. This family of proteins is updated continuously. It has very different composition and will have demand for system analysis for many years.

  12. Polynomial Structure of Topological String Partition Functions

    CERN Document Server

    Zhou, Jie

    2015-01-01

    We review the polynomial structure of the topological string partition functions as solutions to the holomorphic anomaly equations. We also explain the connection between the ring of propagators defined from special K\\"ahler geometry and the ring of almost-holomorphic modular forms defined on modular curves.

  13. Generalized functions, convergence structures, and their applications

    CERN Document Server

    Pap, Endre; Pilipović, Stevan; Vladimirov, Vasilij; International Conference "Generalized functions, convergence structures and their applications" (GFCA-87)

    1988-01-01

    This Proceedings consists of a collection of papers presented at the International Conference "Generalized functions, convergence structures and their applications" held from June 23-27, 1987 in Dubrovnik, Yugoslavia (GFCA-87): 71 participants from 21 countr~es from allover the world took part in the Conference. Proceedings reflects the work of the Conference. Plenary lectures of J. Burzyk, J. F. Colombeau, W. Gahler, H. Keiter, H. Komatsu, B. Stankovic, H. G. Tillman, V. S. Vladimirov provide an up-to-date account of the cur­ rent state of the subject. All these lectures, except H. G. Tillman's, are published in this volume. The published communications give the contemporary problems and achievements in the theory of generalized functions, in the theory of convergence structures and in their applications, specially in the theory of partial differential equations and in the mathematical physics. New approaches to the theory of generalized functions are presented, moti­ vated by concrete problems of applicat...

  14. Protein tyrosine phosphatases: structure-function relationships.

    Science.gov (United States)

    Tabernero, Lydia; Aricescu, A Radu; Jones, E Yvonne; Szedlacsek, Stefan E

    2008-03-01

    Structural analysis of protein tyrosine phosphatases (PTPs) has expanded considerably in the last several years, producing more than 200 structures in this class of enzymes (from 35 different proteins and their complexes with ligands). The small-medium size of the catalytic domain of approximately 280 residues plus a very compact fold makes it amenable to cloning and overexpression in bacterial systems thus facilitating crystallographic analysis. The low molecular weight PTPs being even smaller, approximately 150 residues, are also perfect targets for NMR analysis. The availability of different structures and complexes of PTPs with substrates and inhibitors has provided a wealth of information with profound effects in the way we understand their biological functions. Developments in mammalian expression technology recently led to the first crystal structure of a receptor-like PTP extracellular region. Altogether, the PTP structural work significantly advanced our knowledge regarding the architecture, regulation and substrate specificity of these enzymes. In this review, we compile the most prominent structural traits that characterize PTPs and their complexes with ligands. We discuss how the data can be used to design further functional experiments and as a basis for drug design given that many PTPs are now considered strategic therapeutic targets for human diseases such as diabetes and cancer.

  15. Nuclear Structure Functions from Constituent Quark Model

    CERN Document Server

    Arash, F; Arash, Firooz; Atashbar-Tehrani, Shahin

    1999-01-01

    We have used the notion of the constituent quark model of nucleon, where a constituent quark carries its own internal structure, and applied it to determine nuclear structure functions ratios. It is found that the description of experimental data require the inclusion of strong shadowing effect for $x<0.01$. Using the idea of vector meson dominance model and other ingredients this effect is calculated in the context of the constituent quark model. It is rather striking that the constituent quark model, used here, gives a good account of the data for a wide range of atomic mass number from A=4 to A=204.

  16. Longitudinal Structure Function FL from Charm Structure Function F2c

    Institute of Scientific and Technical Information of China (English)

    B.Rezaei; G.R.Boroun

    2013-01-01

    We predict the effect of the charm structure function on the longitudinal structure function at small x.In NLO analysis we find that the hard Pomeron behavior gives a good description of FL and Fkc (k =2,L) at small x values.We conclude that a direct relation between FL∝ F2c would provide useful information on how to measure longitudinal structure function at high Q2 values.Having checked that this model gives a good description of the data,when compared with other models.

  17. Proteins with Novel Structure, Function and Dynamics

    Science.gov (United States)

    Pohorille, Andrew

    2014-01-01

    Recently, a small enzyme that ligates two RNA fragments with the rate of 10(exp 6) above background was evolved in vitro (Seelig and Szostak, Nature 448:828-831, 2007). This enzyme does not resemble any contemporary protein (Chao et al., Nature Chem. Biol. 9:81-83, 2013). It consists of a dynamic, catalytic loop, a small, rigid core containing two zinc ions coordinated by neighboring amino acids, and two highly flexible tails that might be unimportant for protein function. In contrast to other proteins, this enzyme does not contain ordered secondary structure elements, such as alpha-helix or beta-sheet. The loop is kept together by just two interactions of a charged residue and a histidine with a zinc ion, which they coordinate on the opposite side of the loop. Such structure appears to be very fragile. Surprisingly, computer simulations indicate otherwise. As the coordinating, charged residue is mutated to alanine, another, nearby charged residue takes its place, thus keeping the structure nearly intact. If this residue is also substituted by alanine a salt bridge involving two other, charged residues on the opposite sides of the loop keeps the loop in place. These adjustments are facilitated by high flexibility of the protein. Computational predictions have been confirmed experimentally, as both mutants retain full activity and overall structure. These results challenge our notions about what is required for protein activity and about the relationship between protein dynamics, stability and robustness. We hypothesize that small, highly dynamic proteins could be both active and fault tolerant in ways that many other proteins are not, i.e. they can adjust to retain their structure and activity even if subjected to mutations in structurally critical regions. This opens the doors for designing proteins with novel functions, structures and dynamics that have not been yet considered.

  18. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Boura, Evzen, E-mail: boura@uochb.cas.cz; Nencka, Radim, E-mail: nencka@uochb.cas.cz

    2015-10-01

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.

  19. Multimodality imaging of structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Townsend, D W [Departments of Medicine and Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920 (United States)], E-mail: dtownsend@mc.utmck.edu

    2008-02-21

    Historically, medical devices to image either anatomical structure or functional processes have developed along somewhat independent paths. The recognition that combining images from different modalities can nevertheless offer significant diagnostic advantages gave rise to sophisticated software techniques to coregister structure and function. Recently, alternatives to retrospective software-based fusion have become available through instrumentation that combines two imaging modalities within a single device, an approach that has since been termed hardware fusion. As a result, following their recent introduction into the clinic, combined PET/CT and SPECT/CT devices are now playing an increasingly important role in the diagnosis and staging of human disease. Recently, although limited to the brain, the first clinical MR scanner with a PET insert, a technically-challenging design, has been undergoing evaluation. This review will follow the development of multimodality instrumentation for clinical use from conception to present-day technology and assess the status and future potential for such devices. (topical review)

  20. Structure and function of mammalian cilia

    DEFF Research Database (Denmark)

    Satir, Peter; Christensen, Søren T

    2008-01-01

    In the past half century, beginning with electron microscopic studies of 9 + 2 motile and 9 + 0 primary cilia, novel insights have been obtained regarding the structure and function of mammalian cilia. All cilia can now be viewed as sensory cellular antennae that coordinate a large number...... of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation. This view has had unanticipated consequences for our understanding of developmental processes and human disease....

  1. General Structures of Block Based Interpolational Function

    Institute of Scientific and Technical Information of China (English)

    ZOU LE; TANG SHUO; Ma Fu-ming

    2012-01-01

    We construct general structures of one and two variable interpolation function,without depending on the existence of divided difference or inverse differences,and we also discuss the block based osculatory interpolation in one variable case.Clearly,our method offers many flexible interpolation schemes for choices.Error terms for the interpolation are determined and numerical examples are given to show the effectiveness of the results.

  2. Truncated Moment Analysis of Nucleon Structure Functions

    Energy Technology Data Exchange (ETDEWEB)

    A. Psaker; W. Melnitchouk; M. E. Christy; C. E. Keppel

    2007-11-16

    We employ a novel new approach using "truncated" moments, or integrals of structure functions over restricted regions of x, to study local quark-hadron duality, and the degree to which individual resonance regions are dominated by leading twists. Because truncated moments obey the same Q^2 evolution equations as the leading twist parton distributions, this approach makes possible for the first time a description of resonance region data and the phenomenon of quark-hadron duality directly from QCD.

  3. Anisotropic nanomaterials: structure, growth, assembly, and functions

    OpenAIRE

    Panikkanvalappil R. Sajanlal; Theruvakkattil S. Sreeprasad; Samal, Akshaya K.; Thalappil Pradeep

    2011-01-01

    Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates...

  4. A mechanical Turing machine: blueprint for a biomolecular computer.

    Science.gov (United States)

    Shapiro, Ehud

    2012-08-06

    We describe a working mechanical device that embodies the theoretical computing machine of Alan Turing, and as such is a universal programmable computer. The device operates on three-dimensional building blocks by applying mechanical analogues of polymer elongation, cleavage and ligation, movement along a polymer, and control by molecular recognition unleashing allosteric conformational changes. Logically, the device is not more complicated than biomolecular machines of the living cell, and all its operations are part of the standard repertoire of these machines; hence, a biomolecular embodiment of the device is not infeasible. If implemented, such a biomolecular device may operate in vivo, interacting with its biochemical environment in a program-controlled manner. In particular, it may 'compute' synthetic biopolymers and release them into its environment in response to input from the environment, a capability that may have broad pharmaceutical and biological applications.

  5. Industrial entrepreneurial network: Structural and functional analysis

    Science.gov (United States)

    Medvedeva, M. A.; Davletbaev, R. H.; Berg, D. B.; Nazarova, J. J.; Parusheva, S. S.

    2016-12-01

    Structure and functioning of two model industrial entrepreneurial networks are investigated in the present paper. One of these networks is forming when implementing an integrated project and consists of eight agents, which interact with each other and external environment. The other one is obtained from the municipal economy and is based on the set of the 12 real business entities. Analysis of the networks is carried out on the basis of the matrix of mutual payments aggregated over the certain time period. The matrix is created by the methods of experimental economics. Social Network Analysis (SNA) methods and instruments were used in the present research. The set of basic structural characteristics was investigated: set of quantitative parameters such as density, diameter, clustering coefficient, different kinds of centrality, and etc. They were compared with the random Bernoulli graphs of the corresponding size and density. Discovered variations of random and entrepreneurial networks structure are explained by the peculiarities of agents functioning in production network. Separately, were identified the closed exchange circuits (cyclically closed contours of graph) forming an autopoietic (self-replicating) network pattern. The purpose of the functional analysis was to identify the contribution of the autopoietic network pattern in its gross product. It was found that the magnitude of this contribution is more than 20%. Such value allows using of the complementary currency in order to stimulate economic activity of network agents.

  6. Structural and functional neuroimaging in intractable epilepsy

    Directory of Open Access Journals (Sweden)

    Chinchure Swati

    2010-01-01

    Full Text Available Medical management remains unsatisfactory in about a third of patients with epilepsy and some of them are candidates for resective epilepsy surgery. Structural and functional neuroimaging plays an important role in the identification of the precise cortical region responsible for seizures and is very crucial for a good surgical outcome. Furthermore, identification of eloquent cortical areas near the region to be resected is essential to avoid postoperative neurologic deficit. The magnetic resonance imaging (MRI protocol for epilepsy can be individually tailored depending on the seizure semiology and possibly electroencephalography. New MRI techniques demonstrate the structure of the brain in fine detail, help in understanding the underlying pathology, and demonstrate functional activity of the brain with high spatial and temporal resolution. Metabolic imaging techniques, such as positron emission tomography (PET and single photon emission tomography (SPECT visualize metabolic alterations of the brain in the ictal and interictal states. In MR-negative epilepsy patients, these techniques may have localizing value. The proper use and interpretation of the findings provided by these new technologies is crucial. In this review article, we discuss various conventional and advanced MRI techniques, interpretation of various findings, and the role of functional imaging modalities, such as functional MRI, PET, and SPECT in the localization of epileptogenic substrate as well as for understanding the pathophysiology, propagation, and neurochemical correlates of epilepsy.

  7. Biomolecular detection using a metal semiconductor field effect transistor

    Science.gov (United States)

    Estephan, Elias; Saab, Marie-Belle; Buzatu, Petre; Aulombard, Roger; Cuisinier, Frédéric J. G.; Gergely, Csilla; Cloitre, Thierry

    2010-04-01

    In this work, our attention was drawn towards developing affinity-based electrical biosensors, using a MESFET (Metal Semiconductor Field Effect Transistor). Semiconductor (SC) surfaces must be prepared before the incubations with biomolecules. The peptides route was adapted to exceed and bypass the limits revealed by other types of surface modification due to the unwanted unspecific interactions. As these peptides reveal specific recognition of materials, then controlled functionalization can be achieved. Peptides were produced by phage display technology using a library of M13 bacteriophage. After several rounds of bio-panning, the phages presenting affinities for GaAs SC were isolated; the DNA of these specific phages were sequenced, and the peptide with the highest affinity was synthesized and biotinylated. To explore the possibility of electrical detection, the MESFET fabricated with the GaAs SC were used to detect the streptavidin via the biotinylated peptide in the presence of the bovine Serum Albumin. After each surface modification step, the IDS (current between the drain and the source) of the transistor was measured and a decrease in the intensity was detected. Furthermore, fluorescent microscopy was used in order to prove the specificity of this peptide and the specific localisation of biomolecules. In conclusion, the feasibility of producing an electrical biosensor using a MESFET has been demonstrated. Controlled placement, specific localization and detection of biomolecules on a MESFET transistor were achieved without covering the drain and the source. This method of functionalization and detection can be of great utility for biosensing application opening a new way for developing bioFETs (Biomolecular Field-Effect Transistor).

  8. Phenylalanine hydroxylase: function, structure, and regulation.

    Science.gov (United States)

    Flydal, Marte I; Martinez, Aurora

    2013-04-01

    Mammalian phenylalanine hydroxylase (PAH) catalyzes the rate-limiting step in the phenylalanine catabolism, consuming about 75% of the phenylalanine input from the diet and protein catabolism under physiological conditions. In humans, mutations in the PAH gene lead to phenylketonuria (PKU), and most mutations are mainly associated with PAH misfolding and instability. The established treatment for PKU is a phenylalanine-restricted diet and, recently, supplementation with preparations of the natural tetrahydrobiopterin cofactor also shows effectiveness for some patients. Since 1997 there has been a significant increase in the understanding of the structure, catalytic mechanism, and regulation of PAH by its substrate and cofactor, in addition to improved correlations between genotype and phenotype in PKU. Importantly, there has also been an increased number of studies on the structure and function of PAH from bacteria and lower eukaryote organisms, revealing an additional anabolic role of the enzyme in the synthesis of melanin-like pigments. In this review, we discuss these recent studies, which contribute to define the evolutionary adaptation of the PAH structure and function leading to sophisticated regulation for effective catabolic processing of phenylalanine in mammalian organisms.

  9. The structure and function of presynaptic endosomes

    Energy Technology Data Exchange (ETDEWEB)

    Jähne, Sebastian, E-mail: sebastian.jaehne1@stud.uni-goettingen.de [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); International Max Planck Research School for Neurosciences, 37077 Göttingen (Germany); Rizzoli, Silvio O. [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); Helm, Martin S., E-mail: martin.helm@med.uni-goettingen.de [Department of Neuro- and Sensory Physiology, University of Göttingen Medical Center, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Humboldtallee 23, 37073 Göttingen (Germany); International Max Planck Research School for Molecular Biology, 37077 Göttingen (Germany)

    2015-07-15

    The function of endosomes and of endosome-like structures in the presynaptic compartment is still controversial. This is in part due to the absence of a consensus on definitions and markers for these compartments. Synaptic endosomes are sometimes seen as stable organelles, permanently present in the synapse. Alternatively, they are seen as short-lived intermediates in synaptic vesicle recycling, arising from the endocytosis of large vesicles from the plasma membrane, or from homotypic fusion of small vesicles. In addition, the potential function of the endosome is largely unknown in the synapse. Some groups have proposed that the endosome is involved in the sorting of synaptic vesicle proteins, albeit others have produced data that deny this possibility. In this review, we present the existing evidence for synaptic endosomes, we discuss their potential functions, and we highlight frequent technical pitfalls in the analysis of this elusive compartment. We also sketch a roadmap to definitely determine the role of synaptic endosomes for the synaptic vesicle cycle. Finally, we propose a common definition of synaptic endosome-like structures.

  10. STRUCTURE AND GRAMMATICAL FUNCTION OF LEO LANGUAGE

    Directory of Open Access Journals (Sweden)

    I Ketut Yudha

    2015-01-01

    Full Text Available Lio language is a language spoken in Central Flores. Having limited morphological process in general and affixation process involving verbs (head marking and nouns (dependent marking in particular, it is classified into an isolating language. The studies exploring the languages spoken in the eastern part of Indonesia using Lexical Functional Grammar and the theory of typology are highly limited. In addition, Lio language is merely an isolating one and does not have cross referencing. It is this which inspired the writer to conduct research in syntax. This study aims at investigating the canonic structure, the types of verbs used as predicates, the grammatical function, the alternate of clausal structure, the mapping and the pivotance in Lio language. The results of analysis show that the clauses in Lio language can be divided into basic clauses with verbal and nonverbal predicates. The  predicates of the verbal clauses are classified into simple, serial, and causative.  The serial verbal constructions are distinguished based on the semantic features of the verbal components forming the serial verbal constructions. These types can be observed from the nature of the relationships among the components forming the serial verbal constructions. A serial verbal construction is made up of more than one verbs and behaves as a simple predicate. There is no dependence marker among the components forming the serial verb.  The causative structure also forms monoclause and biclause. The functional mapping uses the features [+/-r] and [+/-o], the argument uses the features [-r] and [-o] which are mapped to  SUBJ, [-r] and [+o] are mapped to OBJ, [+r] and [+o] are mapped to OBJ2 or OBJ? and [+r] and [-o] are mapped to OBL (Oblique. Lio language has GF SUBJ and OBJ as the nuclear GF (nuclear grammatical function, and OBL, COMP, and ADJ as the nonnuclear grammatical functions. The SUBJ appears before the verb (preverbal position and the OBJ appears after the

  11. Tropomyosin structure and function new insights.

    Science.gov (United States)

    Muthuchamy, M; Rethinasamy, P; Wieczorek, D F

    1997-05-01

    Cardiac muscle contraction is dependent upon a cooperative interaction between thick and thin filament sarcomeric proteins. Tropomyosin (TM), an essential thin filament protein, interacts with actin and the troponin complex to regulate contractile activity. During muscle contraction, an increase of calcium (Ca(2+)) in the myofilament space promotes binding of Ca(2+) to troponin C, which alters the conformational state of TM and facilitates acto-myosin interactions. By coupling classic genetic approaches with recent developments in transgenic animal model systems, new insights have been provided on the functional role of TM isoforms in both normal and disease states. The focus of this article is to review the current state of knowledge on TM structure and function, with a particular emphasis on myocardial expression in transgenic mouse model systems. (Trends Cardiovasc Med 1997;7:124-128). © 1997, Elsevier Science Inc.

  12. MRI in Optic Neuritis: Structure, Function, Interactions

    DEFF Research Database (Denmark)

    Fuglø, Dan

    2011-01-01

    resonance imaging (MRI), and the visual evoked potential (VEP) continues to show a delayed P100 indicating persistent demyelination. The explanation for this apparent discrepancy between structure and function could be due to either a redundancy in the visual pathways so that some degree of signal loss...... are low. Functional MRI (fMRI) is a non-invasive technique that can measure brain activity with a high spatial resolution. Recently, technical and methodological advancements have made it feasible to record VEPs and fMRI simultaneously and the relationship between averaged VEPs and averaged fMRI signals...... have been described. Still, to take full advantage of simultaneously recorded VEP-fMRI one would ideally want to track single-trial changes in the VEP and use this information in the fMRI analysis. In order to do this we examined 10 healthy volunteers with simultaneous VEP-fMRI. Different measures...

  13. Soft matter nanotechnology from structure to function

    CERN Document Server

    Chen, Xiaodong

    2015-01-01

    Using the well-honed tools of nanotechnology, this book presents breakthrough results in soft matter research, benefitting from the synergies between the chemistry, physics, biology, materials science, and engineering communities. The team of international authors delves beyond mere structure-making and places the emphasis firmly on imparting functionality to soft nanomaterials with a focus on devices and applications. Alongside reviewing the current level of knowledge, they also put forward novel ideas to foster research and development in such expanding fields as nanobiotechnology and nanom

  14. The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.

    Directory of Open Access Journals (Sweden)

    Xiliang Zheng

    2015-04-01

    Full Text Available We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity, the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics.

  15. The Universal Statistical Distributions of the Affinity, Equilibrium Constants, Kinetics and Specificity in Biomolecular Recognition

    Science.gov (United States)

    Zheng, Xiliang; Wang, Jin

    2015-01-01

    We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity), the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics. PMID:25885453

  16. Engineering biomolecular microenvironments for cell instructive biomaterials.

    Science.gov (United States)

    Custódio, Catarina A; Reis, Rui L; Mano, João F

    2014-06-01

    Engineered cell instructive microenvironments with the ability to stimulate specific cellular responses are a topic of high interest in the fabrication and development of biomaterials for application in tissue engineering. Cells are inherently sensitive to the in vivo microenvironment that is often designed as the cell "niche." The cell "niche" comprising the extracellular matrix and adjacent cells, influences not only cell architecture and mechanics, but also cell polarity and function. Extensive research has been performed to establish new tools to fabricate biomimetic advanced materials for tissue engineering that incorporate structural, mechanical, and biochemical signals that interact with cells in a controlled manner and to recapitulate the in vivo dynamic microenvironment. Bioactive tunable microenvironments using micro and nanofabrication have been successfully developed and proven to be extremely powerful to control intracellular signaling and cell function. This Review is focused in the assortment of biochemical signals that have been explored to fabricate bioactive cell microenvironments and the main technologies and chemical strategies to encode them in engineered biomaterials with biological information.

  17. Transient response characteristics in a biomolecular integral controller.

    Science.gov (United States)

    Sen, Shaunak

    2016-04-01

    The cellular behaviour of perfect adaptation is achieved through the use of an integral control element in the underlying biomolecular circuit. It is generally unclear how integral action affects the important aspect of transient response in these biomolecular systems, especially in light of the fact that it typically deteriorates the transient response in engineering contexts. To address this issue, the authors investigated the transient response in a computational model of a simple biomolecular integral control system involved in bacterial signalling. They find that the transient response can actually speed up as the integral gain parameter increases. On further analysis, they find that the underlying dynamics are composed of slow and fast modes and the speed-up of the transient response is because of the speed-up of the slow-mode dynamics. Finally, they note how an increase in the integral gain parameter also leads to a decrease in the amplitude of the transient response, consistent with the overall improvement in the transient response. These results should be useful in understanding the overall effect of integral action on system dynamics, particularly for biomolecular systems.

  18. Biomolecular recognition mechanisms studied by NMR spectroscopy and MD simulations

    NARCIS (Netherlands)

    Hsu, Shang-Te Danny

    2004-01-01

    This thesis describes the use of solution Nuclear Magnetic Resonance (NMR) spectroscopy and Molecular Dynamics (MD) simulations to study the mechanism of biomolecular recognition with two model systems: i) lipid II-binding lantibiotics (lanthionine-containing antibiotics) and ii) the human immunodef

  19. Bases biomoleculares do fotoenvelhecimento Molecular basis of photoaging

    Directory of Open Access Journals (Sweden)

    Suelen Montagner

    2009-07-01

    Full Text Available Com o aumento da expectativa de vida, o estudo do processo de envelhecimento orgânico tem sido estimulado. O envelhecimento da pele, órgão que espelha os sinais do tempo, é processo de deterioração progressiva, tempo-dependente, e pode ser intensificado pela exposição solar, então designado fotoenvelhecimento. O dano das radiações sobre diversas estruturas celulares e cutâneas leva a alterações morfológicas nesses componentes, fruto de modificações biomoleculares. Muitas pesquisas são desenvolvidas com o intuito de combater ou minimizar os efeitos do fotoenvelhecimento, porém a principal estratégia nesse sentido continua sendo a prevenção, só conseguida pelo progressivo desvendar dos mecanismos fisiopatogênicos envolvidos nesse processo.As a result of the increase in life expectancy, the study of the organic process of aging has been stimulated. Skin ageing, which reflects the signs of time, is a time-dependent process of progressive deterioration that can be intensified by sun exposure, which is known as photoaging. The damage of radiation on various cell structures and on the skin results in molecular and morphological changes to these components. Many research studies are performed to try to minimize the effects of photoaging; however, the main strategy to manage it is still prevention, which will only be achieved once we learn about the mechanisms involved in the process.

  20. Bridging Nano- and Microtribology in Mechanical and Biomolecular Layers

    Science.gov (United States)

    Tomala, Agnieszka; Göçerler, Hakan; Gebeshuber, Ille C.

    The physical and chemical composition of surfaces determine various important properties of solids such as corrosion rates, adhesive properties, frictional properties, catalytic activity, wettability, contact potential and - finally and most importantly - failure mechanisms. Very thin, weak layers (of man-made and biological origin) on much harder substrates that reduce friction are the focus of the micro- and nanotribological investigations presented in this chapter.Biomolecular layers fulfil various functions in organs of the human body. Examples comprise the skin that provides a protective physical barrier between the body and the environment, preventing unwanted inward and outward passage of water and electrolytes, reducing penetration by destructive chemicals, arresting the penetration of microorganisms and external antigens and absorbing radiation from the sun, or the epithelium of the cornea that blocks the passage of foreign material, such as dust, water and bacteria, into the eye and that contributes to the lubrication layer that ensures smooth movement of the eyelids over the eyeballs.Monomolecular thin films, additive-derived reaction layers and hard coatings are widely used to tailor tribological properties of surfaces. Nanotribological investigations on these substrates can reveal novel properties regarding the orientation of chemisorbed additive layers, development of rubbing films with time and the relation of frictional properties to surface characteristics in diamond coatings.Depending on the questions to be answered with the tribological research, various micro- and nanotribological measurement methods are applied, including scanning probe microscopy (AFM, FFM), scanning electron microscopy, microtribometer investigations, angle-resolved photoelectron spectroscopy and optical microscopy. Thoughts on the feasibility of a unified approach to energy-dissipating systems and how it might be reached (touching upon new ways of scientific publishing

  1. Structure, expression and functions of MTA genes.

    Science.gov (United States)

    Kumar, Rakesh; Wang, Rui-An

    2016-05-15

    Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

  2. The HADDOCK2.2 Web Server: User-Friendly Integrative Modeling of Biomolecular Complexes.

    Science.gov (United States)

    van Zundert, G C P; Rodrigues, J P G L M; Trellet, M; Schmitz, C; Kastritis, P L; Karaca, E; Melquiond, A S J; van Dijk, M; de Vries, S J; Bonvin, A M J J

    2016-02-22

    The prediction of the quaternary structure of biomolecular macromolecules is of paramount importance for fundamental understanding of cellular processes and drug design. In the era of integrative structural biology, one way of increasing the accuracy of modeling methods used to predict the structure of biomolecular complexes is to include as much experimental or predictive information as possible in the process. This has been at the core of our information-driven docking approach HADDOCK. We present here the updated version 2.2 of the HADDOCK portal, which offers new features such as support for mixed molecule types, additional experimental restraints and improved protocols, all of this in a user-friendly interface. With well over 6000 registered users and 108,000 jobs served, an increasing fraction of which on grid resources, we hope that this timely upgrade will help the community to solve important biological questions and further advance the field. The HADDOCK2.2 Web server is freely accessible to non-profit users at http://haddock.science.uu.nl/services/HADDOCK2.2.

  3. Latent structures of female sexual functioning.

    Science.gov (United States)

    Carvalho, Joana; Vieira, Armando Luís; Nobre, Pedro

    2012-08-01

    For the last three decades, male and female sexual responses have been conceptualized as similar, based on separated and sequential phases as proposed by the models of Masters and Johnson (1966) and Kaplan (1979) model. However, there is a growing debate around the need to conceptualize female sexual response and the classification of sexual dysfunction in women, in view of the upcoming editions of the DSM and ICD. The aim of this study was to test, using structural equation modeling, five conceptual, alternative models of female sexual function, using a sample of women with sexual difficulties and a sample of women without sexual problems. A total of 1993 Portuguese women participated in the study and completed a modified version of the Female Sexual Function Index. Findings suggested a four-factor solution as the model that best fit the data regarding women presenting sexual difficulties: (1) desire/arousal; (2) lubrication; (3) orgasm; (4) pain/vaginismus. In relation to sexually healthy women, the best model was a five-factor solution comprising of (1) desire; (2) arousal; (3) lubrication; (4) orgasm; and (5) pain/vaginismus. Discriminant validity between factors was supported, suggesting that these dimensions measure distinct phenomena. Model fit to the data significantly decreased in both samples, as models began to successively consider greater levels of overlap among phases of sexual function, towards a single-factor solution. By suggesting the overlap between pain and vaginismus, results partially support the new classification that is currently being discussed regarding DSM-5. Additionally, results on the relationship between sexual desire and arousal were inconclusive as sexually healthy women were better characterized by a five-factor model that considered the structural independence among these factors, whereas women with sexual difficulties better fit with a four-factor model merging sexual desire and subjective sexual arousal.

  4. Engineering intracellular active transport systems as in vivo biomolecular tools.

    Energy Technology Data Exchange (ETDEWEB)

    Bachand, George David; Carroll-Portillo, Amanda

    2006-11-01

    Active transport systems provide essential functions in terms of cell physiology and metastasis. These systems, however, are also co-opted by invading viruses, enabling directed transport of the virus to and from the cell's nucleus (i.e., the site of virus replication). Based on this concept, fundamentally new approaches for interrogating and manipulating the inner workings of living cells may be achievable by co-opting Nature's active transport systems as an in vivo biomolecular tool. The overall goal of this project was to investigate the ability to engineer kinesin-based transport systems for in vivo applications, specifically the collection of effector proteins (e.g., transcriptional regulators) within single cells. In the first part of this project, a chimeric fusion protein consisting of kinesin and a single chain variable fragment (scFv) of an antibody was successfully produced through a recombinant expression system. The kinesin-scFv retained both catalytic and antigenic functionality, enabling selective capture and transport of target antigens. The incorporation of a rabbit IgG-specific scFv into the kinesin established a generalized system for functionalizing kinesin with a wide range of target-selective antibodies raised in rabbits. The second objective was to develop methods of isolating the intact microtubule network from live cells as a platform for evaluating kinesin-based transport within the cytoskeletal architecture of a cell. Successful isolation of intact microtubule networks from two distinct cell types was demonstrated using glutaraldehyde and methanol fixation methods. This work provides a platform for inferring the ability of kinesin-scFv to function in vivo, and may also serve as a three-dimensional scaffold for evaluating and exploiting kinesin-based transport for nanotechnological applications. Overall, the technology developed in this project represents a first-step in engineering active transport system for in vivo

  5. Biomolecular mechanisms in varicose veins development.

    Science.gov (United States)

    Segiet, Oliwia Anna; Brzozowa-Zasada, Marlena; Piecuch, Adam; Dudek, Damian; Reichman-Warmusz, Edyta; Wojnicz, Romuald

    2015-02-01

    Varicose veins (VVs) can be described as tortuous and dilated palpable veins, which are more than 3 mm in diameter. They are one of the clinical presentations of chronic venous disorders, which are a significant cause of morbidity. The prevalence of VVs has been estimated at 25-33% in women and 10-20% in men and is still increasing at an alarming rate. Family history, older age, female, pregnancy, obesity, standing occupations, and a history of deep venous thrombosis are the predominant risk factors. A great amount of factors are implicated in the pathogenesis of VVs, including changes in hydrostatic pressure, valvular incompetence, deep venous obstruction, ineffective function of calf muscle pump, biochemical and structural alterations of the vessel wall, extracellular matrix abnormalities, impaired balance between growth factors or cytokines, genetic alterations, and several other mechanisms. Nevertheless, the issue of pathogenesis in VVs is still not completely known, even if a great progress has been made in understanding their molecular basis. This kind of studies appears promising and should be encouraged, and perhaps the new insight in this matter may result in targeted therapy or possibly prevention.

  6. Structural and functional diversity of desmosomes.

    Science.gov (United States)

    Harmon, Robert M; Green, Kathleen J

    2013-12-01

    Desmosomes anchor intermediate filaments at sites of cell contact established by the interaction of cadherins extending from opposing cells. The incorporation of cadherins, catenin adaptors, and cytoskeletal elements resembles the closely related adherens junction. However, the recruitment of intermediate filaments distinguishes desmosomes and imparts a unique function. By linking the load-bearing intermediate filaments of neighboring cells, desmosomes create mechanically contiguous cell sheets and, in so doing, confer structural integrity to the tissues they populate. This trait and a well-established role in human disease have long captured the attention of cell biologists, as evidenced by a publication record dating back to the mid-1860s. Likewise, emerging data implicating the desmosome in signaling events pertinent to organismal development, carcinogenesis, and genetic disorders will secure a prominent role for desmosomes in future biological and biomedical investigations.

  7. Structural and Functional Views of Mechatronic Products

    DEFF Research Database (Denmark)

    Nielsen, Kjeld; Petersen, Thomas Ditlev; Jørgensen, Kaj Asbjørn

    2011-01-01

    The development and subsequent production of industrial products are often complicated tasks. The complication increases with combined product as mechatronic products and is further complicated when large variety is required. Modularity is often used to achieve optimum in these complications both...... in the costumer view as well in the production view. In this paper, the relationships in mechatronic products between the functional and structural levels are explored in relation to modularity. A list of commonly used module drivers is presented and a qualitative survey is used to explore significance...... of influence on these module drivers when applying mechatronic product technology and view levels. The result is summarized in a list of which drivers should be addressed in a mechatronic product approach to modularity. Keywords:...

  8. Structure-function relationships in calpains.

    Science.gov (United States)

    Campbell, Robert L; Davies, Peter L

    2012-11-01

    Calpains are a family of complex multi-domain intracellular enzymes that share a calcium-dependent cysteine protease core. These are not degradative enzymes, but instead carry out limited cleavage of target proteins in response to calcium signalling. Selective cutting of cytoskeletal proteins to facilitate cell migration is one such function. The two most abundant and extensively studied members of this family in mammals, calpains 1 and 2, are heterodimers of an isoform-specific 80 kDa large subunit and a common 28 kDa small subunit. Structures of calpain-2, both Ca2+-free and bound to calpastatin in the activated Ca2+-bound state, have provided a wealth of information about the enzyme's structure-function relationships and activation. The main association between the subunits is the pairing of their C-terminal penta-EF-hand domains through extensive intimate hydrophobic contacts. A lesser contact is made between the N-terminal anchor helix of the large subunit and the penta-EF-hand domain of the small subunit. Up to ten Ca2+ ions are co-operatively bound during activation. The anchor helix is released and individual domains change their positions relative to each other to properly align the active site. Because calpains 1 and 2 require ~30 and ~350 μM Ca2+ ions for half-maximal activation respectively, it has long been argued that autoproteolysis, subunit dissociation, post-translational modifications or auxiliary proteins are needed to activate the enzymes in the cell, where Ca2+ levels are in the nanomolar range. In the absence of robust support for these mechanisms, it is possible that under normal conditions calpains are transiently activated by high Ca2+ concentrations in the microenvironment of a Ca2+ influx, and then return to an inactive state ready for reactivation.

  9. Report on result 1998. Research and development on fusion area. Part 3 (biomolecular mechanism and design); 1998 nendo seika hokokusho. Yugo ryoiki kenkyu kaihatsu daisan bunsatsu (bimolecular mechanism and design)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    An organism is a molecular mechanical system consisting of nucleic acid, peptide and protein having a self-forming and a self-repairing function. For the purpose of creating cells, tissues and molecular mechanism alternating these biological functions, their basic technology was developed. Concretely, studies were made on three-dimensional cellular structural module engineering and biomolecular mechanism and design. Studies on biological soft tissue resulted in success by giving atmospheric glow discharge treatment to the inner surface of a tubular PVC. An artificial vitreous body was created using PVA hydrogels. In addition, liver cells were successfully cultured for the first time in the world. Studies on biological hard tissue revealed that osteopontin plays a role of a trigger for the initial differentiation of the osteoblast cell. Further, a basic experiment was carried out on the initial response of the cartilage cell. In the research on the molecular mechanism, examination was made on the mechanism of a double-head molecular motor. Examination was also made on the adjustment of the hydrogenase LB film as an electricity/hydrogen energy conversion element and on the biomolecular mechanism and design. (NEDO)

  10. DockScreen: A Database of In Silico Biomolecular Interactions to Support Computational Toxicology

    Directory of Open Access Journals (Sweden)

    Michael-Rock Goldsmith

    2014-01-01

    Full Text Available We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme binding scores calculated by molecular docking of more than 1000 chemicals into 150 protein targets and contains nearly 135 thousand unique ligand/target binding scores. Obtaining this dataset was achieved using eHiTS (Simbiosys Inc., a fragment-based molecular docking approach with an exhaustive search algorithm, on a heterogeneous distributed high-performance computing framework. The chemical landscape covered in DockScreen comprises selected environmental and therapeutic chemicals. The target landscape covered in DockScreen was selected based on the availability of high-quality crystal structures that covered the assay space of phase I ToxCast in vitro assays. This in silico data provides continuous information that establishes a means for quantitatively comparing, on a structural biophysical basis, a chemical’s profile of biomolecular interactions. The combined minimum-score chemical/target matrix is provided.

  11. Biomolecular detection at ssDNA-conjugated nanoparticles by nano-impact electrochemistry.

    Science.gov (United States)

    Karimi, Anahita; Hayat, Akhtar; Andreescu, Silvana

    2017-01-15

    We describe the use of ssDNA functionalized silver nanoparticle (AgNP) probes for quantitative investigation of biorecognition and real time detection of biomolecular targets using nano-impact electrochemistry. The method is based on measurements of the individual collision events between ssDNA aptamer-functionalized AgNPs and a carbon fiber miroelectrode (CFME). Specific binding events of target analyte induced collision frequency changes enabling ultrasensitive detection of the aptamer target in a single step. These changes are assigned to the surface coverage of the NP by the ssDNA aptamers and subsequent conformational changes of the aptamer probe which affect the electron transfer between the NP and the electrode surface. The method enables sensitive and selective detection of ochratoxin A (OTA), chosen here as a model target, with a limit of detection of 0.05nM and a relative standard deviation of 4.9%. The study provides a means of characterizing bioconjugation of AgNPs with aptamers and assessing biomolecular recognition events with high sensitivity and without the use of exogenous reagents or enzyme amplification steps. This methodology can be broadly applicable to other bioconjugated systems, biosensing and related bioanalytical applications.

  12. The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

    Directory of Open Access Journals (Sweden)

    Giulio Caravagna

    Full Text Available After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii a model of enzymatic futile cycle and (iii a genetic toggle switch. In (ii and (iii we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

  13. Submicrometer Hall sensors for detection of magnetic nanoparticles in biomolecular sensing

    Science.gov (United States)

    Mihajlovic, Goran; Xiong, P.; von Molnar, S.; Ohtani, K.; Ohno, H.; Field, M.; Sullivan, G. J.

    2006-03-01

    Significant progress has been made in the recent years in synthesis and biomolecular functionalization of magnetic nanoparticles. These magnetic bio-nanolabels can be utilized as protein or gene markers in biomolecular sensing assays, in contrast to the much larger micron sized magnetic beads that are usually limited to cell labeling. However, the low magnetic moments of individual nanoparticles (10^4-10^5 μB) render their sensitive detection still a challenging task. In order to address this issue we are developing miniaturized Hall sensors from InAs/AlSb quantum well semiconductor heterostructures with active Hall cross areas down to 300 nm x 300 nm. Our preliminary characterization measurements performed at room temperature show functional devices with magnetic field resolution < 100 μT/√Hz at frequencies above 100 Hz, yielding a moment sensitivity ˜ 10^5 μB. In addition to the progress in improving the moment sensitivity of the submicrometer Hall detectors, we will also present efforts in device integration with on-chip microcoils for the generation of local magnetic excitation fields. Results on nanoparticle detection will also be presented.

  14. The detection of specific biomolecular interactions with micro-Hall magnetic sensors

    Science.gov (United States)

    Manandhar, Pradeep; Chen, Kan-Sheng; Aledealat, Khaled; Mihajlović, Goran; Yun, C. Steven; Field, Mark; Sullivan, Gerard J.; Strouse, Geoffrey F.; Bryant Chase, P.; von Molnár, Stephan; Xiong, Peng

    2009-09-01

    The detection of reagent-free specific biomolecular interactions through sensing of nanoscopic magnetic labels provides one of the most promising routes to biosensing with solid-state devices. In particular, Hall sensors based on semiconductor heterostructures have shown exceptional magnetic moment sensitivity over a large dynamic field range suitable for magnetic biosensing using superparamagnetic labels. Here we demonstrate the capability of such micro-Hall sensors to detect specific molecular binding using biotin-streptavidin as a model system. We apply dip-pen nanolithography to selectively biotinylate the active areas of InAs micro-Hall devices with nanoscale precision. Specific binding of complementarily functionalized streptavidin-coated superparamagnetic beads to the Hall crosses occurs via molecular recognition, and magnetic detection of the assembled beads is achieved at room temperature using phase sensitive micro-Hall magnetometry. The experiment constitutes the first unambiguous demonstration of magnetic detection of specific biomolecular interactions with semiconductor micro-Hall sensors, and the selective molecular functionalization and resulting localized bead assembly demonstrate the possibility of multiplexed sensing of multiple target molecules using a single device with an array of micro-Hall sensors.

  15. Wavelets and Geometric Structure for Function Spaces

    Institute of Scientific and Technical Information of China (English)

    Qi Xiang YANG

    2004-01-01

    With Littlewood-Paley analysis, Peetre and Triebel classified, systematically, almost all the usual function spaces into two classes of spaces: Besov spaces (B)s,q p(s ∈ R,0 < p,q ≤∞) and Triebel-Lizorkin spaces (F)s,q p(s∈R,0<p<∞,0<q≤∞); but the structure of dual spaces (D)s,q p of (F)s,q p(s∈R, 0<p≤1≤q≤∞) is very different from that of Besov spaces or that of Triebel-Lizorkin spaces, and their structure cannot be analysed easily in the Littlewood-Paley analysis. Our main goal is to characterize (D)s,q p (s ∈ R, 0<p= 1≤q≤∞) in tent spaces with wavelets. By the way, some applications are given: (i) Triebel-Lizorkin spaces for p = ∞ defined by Littlewood-Paley analysis cannot serve as the dual spaces of Triebel-Lizorkin spaces for p = 1; (ii) Some inclusion relations among these above spaces and some relations among(B)o,q1,(F)o,q1 and L1 are studied.

  16. Intrinsically disordered proteins: structural and functional dynamics

    Directory of Open Access Journals (Sweden)

    Wallin S

    2017-02-01

    Full Text Available Stefan Wallin Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John’s, NL, Canada Abstract: The classical view holds that proteins fold into essentially unique three-dimensional structures before becoming biologically active. However, studies over the last several years have provided broad and convincing evidence that some proteins do not adopt a single structure and yet are fully functional. These intrinsically disordered proteins (IDPs have been found to be highly prevalent in many genomes, including human, and play key roles in central cellular processes, such as regulation of transcription and translation, cell cycle, and cell signaling. Moreover, IDPs are overrepresented among proteins implicated in disease, including various cancers and neurodegenerative disorders. Intense efforts, by using both experimental and computational approaches, are consequently under way to uncover the molecular mechanisms that underpin the roles of IDPs in biology and disease. This review provides an introduction to the general biophysical properties of IDPs and discusses some of the recent emerging areas in IDP research, including the roles of IDPs in allosteric regulation, regulatory unfolding, and formation of intracellular membrane-less organelles. In addition, recent attempts at therapeutic targeting of IDPs by small molecules, noting in particular that IDPs represent a potentially important source of new drug targets in light of their central role in protein–protein interaction networks, are also reviewed. Keywords: natively unfolded proteins, unstructured proteins, protein folding, protein–protein interaction, cell regulation, signaling, drug development, inhibitors

  17. Structure, Function, and Evolution of Rice Centromeres

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiming

    2010-02-04

    The centromere is the most characteristic landmark of eukaryotic chromosomes. Centromeres function as the site for kinetochore assembly and spindle attachment, allowing for the faithful pairing and segregation of sister chromatids during cell division. Characterization of centromeric DNA is not only essential to understand the structure and organization of plant genomes, but it is also a critical step in the development of plant artificial chromosomes. The centromeres of most model eukaryotic species, consist predominantly of long arrays of satellite DNA. Determining the precise DNA boundary of a centromere has proven to be a difficult task in multicellular eukaryotes. We have successfully cloned and sequenced the centromere of rice chromosome 8 (Cen8), representing the first fully sequenced centromere from any multicellular eukaryotes. The functional core of Cen8 spans ~800 kb of DNA, which was determined by chromatin immunoprecipitation (ChIP) using an antibody against the rice centromere-specific H3 histone. We discovered 16 actively transcribed genes distributed throughout the Cen8 region. In addition to Cen8, we have characterized eight additional rice centromeres using the next generation sequencing technology. We discovered four subfamilies of the CRR retrotransposon that is highly enriched in rice centromeres. CRR elements are constitutively transcribed and different CRR subfamilies are differentially processed by RNAi. These results suggest that different CRR subfamilies may play different roles in the RNAi-mediated pathway for formation and maintenance of centromeric chromatin.

  18. The Structural and Functional Organisation of Cognition.

    Directory of Open Access Journals (Sweden)

    Peter John Snow

    2016-10-01

    Full Text Available This paper proposes that what have been historically and contemporarily defined as different domains of human cognition are served by one of four functionally- and structurally-distinct areas of the prefrontal cortex. Their contributions to human intelligence are as follows: (a BA9, enables our emotional intelligence, engaging the psychosocial domain, (b BA47, enables our practical intelligence, engaging the material domain, (c BA46 (or BA46-9/46, enables our abstract intelligence, engaging the hypothetical domain and (d BA10, enables our temporal intelligence, engaging in planning within any of the other three domains. Given their unique contribution to human cognition, it is proposed that these areas be called the, social (BA9, material (BA47, abstract (BA46-9/46 and temporal (BA10 mind. The evidence that BA47 participates strongly in verbal and gestural communication suggests that language evolved primarily as a consequence of the extreme selective pressure for practicality; an observation supported by the functional connectivity between BA47 and orbital areas that negatively reinforce lying. It is further proposed that the abstract mind (BA46-9/46 is the primary seat of metacognition charged with creating adaptive behavioral strategies by generating higher-order concepts (hypotheses from lower-order concepts originating both from our perceptual representations and the other three domains of cognition.

  19. The Structural and Functional Organization of Cognition.

    Science.gov (United States)

    Snow, Peter J

    2016-01-01

    This article proposes that what have been historically and contemporarily defined as different domains of human cognition are served by one of four functionally- and structurally-distinct areas of the prefrontal cortex (PFC). Their contributions to human intelligence are as follows: (a) BA9, enables our emotional intelligence, engaging the psychosocial domain; (b) BA47, enables our practical intelligence, engaging the material domain; (c) BA46 (or BA46-9/46), enables our abstract intelligence, engaging the hypothetical domain; and (d) BA10, enables our temporal intelligence, engaging in planning within any of the other three domains. Given their unique contribution to human cognition, it is proposed that these areas be called the, social (BA9), material (BA47), abstract (BA46-9/46) and temporal (BA10) mind. The evidence that BA47 participates strongly in verbal and gestural communication suggests that language evolved primarily as a consequence of the extreme selective pressure for practicality; an observation supported by the functional connectivity between BA47 and orbital areas that negatively reinforce lying. It is further proposed that the abstract mind (BA46-9/46) is the primary seat of metacognition charged with creating adaptive behavioral strategies by generating higher-order concepts (hypotheses) from lower-order concepts originating from the other three domains of cognition.

  20. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center.

    Science.gov (United States)

    Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-01

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  1. Structure-based inference of molecular functions of proteins of unknown function from Berkeley Structural Genomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung-Hou; Shin, Dong Hae; Hou, Jingtong; Chandonia, John-Marc; Das, Debanu; Choi, In-Geol; Kim, Rosalind; Kim, Sung-Hou

    2007-09-02

    Advances in sequence genomics have resulted in an accumulation of a huge number of protein sequences derived from genome sequences. However, the functions of a large portion of them cannot be inferred based on the current methods of sequence homology detection to proteins of known functions. Three-dimensional structure can have an important impact in providing inference of molecular function (physical and chemical function) of a protein of unknown function. Structural genomics centers worldwide have been determining many 3-D structures of the proteins of unknown functions, and possible molecular functions of them have been inferred based on their structures. Combined with bioinformatics and enzymatic assay tools, the successful acceleration of the process of protein structure determination through high throughput pipelines enables the rapid functional annotation of a large fraction of hypothetical proteins. We present a brief summary of the process we used at the Berkeley Structural Genomics Center to infer molecular functions of proteins of unknown function.

  2. Anisotropic nanomaterials: structure, growth, assembly, and functions.

    Science.gov (United States)

    Sajanlal, Panikkanvalappil R; Sreeprasad, Theruvakkattil S; Samal, Akshaya K; Pradeep, Thalappil

    2011-01-01

    Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications.

  3. Anisotropic nanomaterials: structure, growth, assembly, and functions

    Directory of Open Access Journals (Sweden)

    Panikkanvalappil R. Sajanlal

    2011-02-01

    Full Text Available Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D, two-dimensional (2D, and three-dimensional (3D arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications.

  4. Biomolecular recognition and detection using gold-based nanoprobes

    Science.gov (United States)

    Crew, Elizabeth

    The ability to control the biomolecular interactions is important for developing bioanalytical probes used in biomolecule and biomarker detections. This work aims at a fundamental understanding of the interactions and reactivities involving DNA, miRNA, and amino acids using gold-based nanoparticles as nanoprobes, which has implications for developing new strategies for the early detection of diseases, such as cancer, and controlled delivery of drugs. Surface modifications of the nanoprobes with DNA, miRNA, and amino acids and the nanoprobe directed biomolecular reactivities, such as complementary-strand binding, enzymatic cutting and amino acid interactions, have been investigated. Among various analytical techniques employed for the analysis of the biomolecule-nanoprobe interactions, surface enhanced Raman scattering spectroscopy (SERS) has been demonstrated to provide a powerful tool for real time monitoring of the DNA assembly and enzymatic cutting processes in solutions. This demonstration harnesses the "hot-spot" characteristic tuned by the interparticle biomolecular-regulated interactions and distances. The assembly of gold nanoparticles has also been exploited as sensing thin films on chemiresistor arrays for the detection of volatile organic compounds, including biomarker molecules associated with diabetes. Important findings of the nanoprobes in delivering miRNA to cells, detecting DNA hybridization kinetics, discerning chiral recognition with enantiomeric cysteines, and sensing biomarker molecules with the nanostructured thin films will be discussed, along with their implications to enhancing sensitivity, selectivity and limits of detection.

  5. Solution influence on biomolecular equilibria - Nucleic acid base associations

    Science.gov (United States)

    Pohorille, A.; Pratt, L. R.; Burt, S. K.; Macelroy, R. D.

    1984-01-01

    Various attempts to construct an understanding of the influence of solution environment on biomolecular equilibria at the molecular level using computer simulation are discussed. First, the application of the formal statistical thermodynamic program for investigating biomolecular equilibria in solution is presented, addressing modeling and conceptual simplications such as perturbative methods, long-range interaction approximations, surface thermodynamics, and hydration shell. Then, Monte Carlo calculations on the associations of nucleic acid bases in both polar and nonpolar solvents such as water and carbon tetrachloride are carried out. The solvent contribution to the enthalpy of base association is positive (destabilizing) in both polar and nonpolar solvents while negative enthalpies for stacked complexes are obtained only when the solute-solute in vacuo energy is added to the total energy. The release upon association of solvent molecules from the first hydration layer around a solute to the bulk is accompanied by an increase in solute-solvent energy and decrease in solvent-solvent energy. The techniques presented are expectd to displace less molecular and more heuristic modeling of biomolecular equilibria in solution.

  6. Single-Molecule Pull-down FRET (SiMPull-FRET) to dissect the mechanisms of biomolecular machines

    Science.gov (United States)

    Kahlscheuer, Matthew L.; Widom, Julia; Walter, Nils G.

    2016-01-01

    Spliceosomes are multi-megadalton RNA-protein complexes responsible for the faithful removal of non-coding segments (introns) from pre-messenger RNAs (pre-mRNAs), a process critical for the maturation of eukaryotic mRNAs for subsequent translation by the ribosome. Both the spliceosome and ribosome, as well as many other RNA and DNA processing machineries, contain central RNA components that endow biomolecular complexes with precise, sequence-specific nucleic acid recognition and versatile structural dynamics. Single molecule fluorescence (or Förster) resonance energy transfer (smFRET) microscopy is a powerful tool for the study of local and global conformational changes of both simple and complex biomolecular systems involving RNA. The integration of biochemical tools such as immunoprecipitation with advanced methods in smFRET microscopy and data analysis has opened up entirely new avenues towards studying the mechanisms of biomolecular machines isolated directly from complex biological specimens such as cell extracts. Here we detail the general steps for using prism-based total internal reflection fluorescence (TIRF) microscopy in exemplary single molecule pull-down FRET (SiMPull-FRET) studies of the yeast spliceosome and discuss the broad application potential of this technique. PMID:26068753

  7. Biomolecular interactions and tools for their recognition: focus on the quartz crystal microbalance and its diverse surface chemistries and applications.

    Science.gov (United States)

    Cheng, Cathy I; Chang, Yi-Pin; Chu, Yen-Ho

    2012-03-07

    Interactions between molecules are ubiquitous and occur in our bodies, the food we eat, the air we breathe, and myriad additional contexts. Although numerous tools are available for the recognition of biomolecular interactions, such tools are often limited in their sensitivity, expensive, and difficult to modify for various uses. In contrast, the quartz crystal microbalance (QCM) has sub-nanogram detection capabilities, is label-free, is inexpensive to create, and can be readily modified with a number of diverse surface chemistries to detect and characterize diverse interactions. To maximize the versatility of the QCM, scientists need to know available methods by which QCM surfaces can be modified. Therefore, in addition to summarizing the various tools currently used for biomolecular recognition, explicating the fundamental principles of the QCM as a tool for biomolecular recognition, and comparing the QCM with other acoustic sensors, we systematically review the numerous types of surface chemistries-including hydrophobic bonds, ionic bonds, hydrogen bonds, self-assembled monolayers, plasma-polymerized films, photochemistry, and sensing ionic liquids-used to functionalize QCMs for various purposes. We also review the QCM's diverse applications, which include the detection of gaseous species, detection of carbohydrates, detection of nucleic acids, detection of non-enzymatic proteins, characterization of enzymatic activity, detection of antigens and antibodies, detection of cells, and detection of drugs. Finally, we discuss the ultimate goals of and potential barriers to the development of future QCMs.

  8. Molecular Models of Genetic and Organismic Structures

    CERN Document Server

    Baianu, I C

    2004-01-01

    In recent studies we showed that the earlier relational theories of organismic sets (Rashevsky,1967), Metabolic-Replication (M,R)-systems (Rosen,1958)and molecular sets (Bartholomay,1968) share a joint foundation that can be studied within a unified categorical framework of functional organismic structures (Baianu,1980. This is possible because all relational theories have a biomolecular basis, that is, complex structures such as genomes, cells,organs and biological organisms are mathematically represented in terms of biomolecular properties and entities,(that are often implicit in their representation axioms. The definition of organismic sets, for example, requires that certain essential quantities be determined from experiment: these are specified by special sets of values of general observables that are derived from physicochemical measurements(Baianu,1970; Baianu,1980; Baianu et al, 2004a.)Such observables are context-dependent and lead directly to natural transformations in categories and Topoi, that are...

  9. Structure and function of the archaeal exosome.

    Science.gov (United States)

    Evguenieva-Hackenberg, Elena; Hou, Linlin; Glaeser, Stefanie; Klug, Gabriele

    2014-01-01

    The RNA-degrading exosome in archaea is structurally very similar to the nine-subunit core of the essential eukaryotic exosome and to bacterial polynucleotide phosphorylase (PNPase). In contrast to the eukaryotic exosome, PNPase and the archaeal exosome exhibit metal ion-dependent, phosphorolytic activities and synthesize heteropolymeric RNA tails in addition to the exoribonucleolytic RNA degradation in 3' → 5' direction. The archaeal nine-subunit exosome consists of four orthologs of eukaryotic exosomal subunits: the RNase PH-domain-containing subunits Rrp41 and Rrp42 form a hexameric ring with three active sites, whereas the S1-domain-containing subunits Rrp4 and Csl4 form an RNA-binding trimeric cap on the top of the ring. In vivo, this cap contains Rrp4 and Csl4 in variable amounts. Rrp4 confers poly(A) specificity to the exosome, whereas Csl4 is involved in the interaction with the archaea-specific subunit of the complex, the homolog of the bacterial primase DnaG. The archaeal DnaG is a highly conserved protein and its gene is present in all sequenced archaeal genomes, although the exosome was lost in halophilic archaea and some methanogens. In exosome-containing archaea, DnaG is tightly associated with the exosome. It functions as an additional RNA-binding subunit with poly(A) specificity in the reconstituted exosome of Sulfolobus solfataricus and enhances the degradation of adenine-rich transcripts in vitro. Not only the RNA-binding cap but also the hexameric Rrp41-Rrp42 ring alone shows substrate selectivity and prefers purines over pyrimidines. This implies a coevolution of the exosome and its RNA substrates resulting in 3'-ends with different affinities to the exosome.

  10. Resolution-Adapted All-Atomic and Coarse-Grained Model for Biomolecular Simulations.

    Science.gov (United States)

    Shen, Lin; Hu, Hao

    2014-06-10

    We develop here an adaptive multiresolution method for the simulation of complex heterogeneous systems such as the protein molecules. The target molecular system is described with the atomistic structure while maintaining concurrently a mapping to the coarse-grained models. The theoretical model, or force field, used to describe the interactions between two sites is automatically adjusted in the simulation processes according to the interaction distance/strength. Therefore, all-atomic, coarse-grained, or mixed all-atomic and coarse-grained models would be used together to describe the interactions between a group of atoms and its surroundings. Because the choice of theory is made on the force field level while the sampling is always carried out in the atomic space, the new adaptive method preserves naturally the atomic structure and thermodynamic properties of the entire system throughout the simulation processes. The new method will be very useful in many biomolecular simulations where atomistic details are critically needed.

  11. Biomolecular papain thin films grown by matrix assisted and conventional pulsed laser deposition: A comparative study

    Science.gov (United States)

    György, E.; Pérez del Pino, A.; Sauthier, G.; Figueras, A.

    2009-12-01

    Biomolecular papain thin films were grown both by matrix assisted pulsed laser evaporation (MAPLE) and conventional pulsed laser deposition (PLD) techniques with the aid of an UV KrF∗ (λ =248 nm, τFWHM≅20 ns) excimer laser source. For the MAPLE experiments the targets submitted to laser radiation consisted on frozen composites obtained by dissolving the biomaterial powder in distilled water at 10 wt % concentration. Conventional pressed biomaterial powder targets were used in the PLD experiments. The surface morphology of the obtained thin films was studied by atomic force microscopy and their structure and composition were investigated by Fourier transform infrared spectroscopy. The possible physical mechanisms implied in the ablation processes of the two techniques, under comparable experimental conditions were identified. The results showed that the growth mode, surface morphology as well as structure of the deposited biomaterial thin films are determined both by the incident laser fluence value as well as target preparation procedure.

  12. Advances in biomolecular surface meshing and its applications to mathematical modeling

    Institute of Scientific and Technical Information of China (English)

    CHEN MinXin; LU BenZhuo

    2013-01-01

    In the field of molecular modeling and simulation,molecular surface meshes are necessary for many problems,such as molecular structure visualization and analysis,docking problem and implicit solvent modeling and simulation.Recently,with the developments of advanced mathematical modeling in the field of implicit solvent modeling and simulation,providing surface meshes with good qualities efficiently for large real biomolecular systems becomes an urgent issue beyond its traditional purposes for visualization and geometry analyses for molecular structure.In this review,we summarize recent works on this issue.First,various definitions of molecular surfaces and corresponding meshing methods are introduced.Second,our recent meshing tool,TMSmesh,and its performances are presented.Finally,we show the applications of the molecular surface mesh in implicit solvent modeling and simulations using boundary element method (BEM) and finite element method (FEM).

  13. Nucleon structure functions in noncommutative space-time

    CERN Document Server

    Rafiei, Ali; Mirjalili, Abolfazl

    2016-01-01

    In the context of noncommutative space-time, we investigate the nucleon structure functions which plays an important role to identify the internal structure of nucleons. We use the corrected vertices and employ new vertices that appear in two approaches of noncommutativity and calculate the proton structure functions in terms of noncommutative tensor \\theta_{\\mu\

  14. Biomolecular and metagenomic analyses of biofouling communities

    Science.gov (United States)

    Despite the decades of research that have focused on understanding the formation of biofouling communities, relatively little is known about the soft fouling consortia that are responsible for their formation and function. In this study, we used PhyloChip microbial profiling, metagenomic DNA sequenc...

  15. Utilizing plasma physics to create biomolecular movies

    Energy Technology Data Exchange (ETDEWEB)

    Hau-Riege, S [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-07-24

    In spring of 2000, the LCLS Scientific Advisory Committee selected the top scientific experiments for LCLS. One of the proposed flagship experiments is atomic-resolution three-dimensional structure determination of isolated biolgical macromolecules and particles, with the ultimate goal of obtaining molecular (snapshot) movies. The key enabling insight was that radiation damage may be overcome by using x-ray pulses that are shorter than the time it takes for damage to manifest itself.

  16. The structural basis of nuclear function.

    Science.gov (United States)

    Jackson, D A; Cook, P R

    1995-01-01

    Most models for transcription and replication involve polymerases that track along the template. We review here experiments that suggest an alternative in which polymerization occurs as the template slides past a polymerase fixed to a large structure in the eukaryotic nucleus--a "factory" attached to a nucleoskeleton. This means that higher-order structure dictates how and when DNA is replicated or transcribed.

  17. Raman microspectroscopic study of biomolecular structure inside living adhesive cells

    Institute of Scientific and Technical Information of China (English)

    李光; 杨红英; 许以明; 张志义

    2002-01-01

    Cells adhesion is very important for many physiological processes. Using advanced Raman microspectroscopic technique, we selected T Leukemia cells (Jurkat) as the materials and obtained simultaneously conformation information of various biomolecules inside the whole living cells. By comparing the Raman microspectroscopic spectra of single and adhesive cancer cells, we found for the first time that when cells adhered, the conformation of the biomolecules (DNA, protein, carbohydrates and lipids) inside the cells had different changes: (i) the backbone of double-stranded DNA maintained orderly B-form or modified B-form conformation, whereas the groups of its deoxyribose and bases were modified; (ii) the conformational changes of the main chain and the side chain in the protein were obviously variant. The lines intensity belonging to α-helix andβ-sheet decreased, while that ofβ-turn increased. Tyrosine and tryptophane residues of the protein changed from "buried state" to "exposed state"; the lines intensity of its sulfhydryl group also increased; the conformation of its disulfide bond changed from two kinds to three kinds. These facts suggest that the cells adhesion causes changes in H-bonds organization of the main chain and environment of the side chain in the protein; (iii) the groups of the carbohydrates were also modified simultaneously; (iv) the conformation of the lipids bilayers of the membranes changed obviously; the order parameter for lateral interaction between chains decreased gradually with the increase of number of the adhesive cells. So cells adhesion resulted in an increase in fluidity of the membrane and ion permeability on the membrane.

  18. Measurement of the Electron Structure Function at LEP energies

    CERN Document Server

    Abdallah, J; Adam, W; Adzic, P; Albrecht, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Amaldi, U; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W-D; Arnoud, Y; Ask, S; Asman, B; Augustin, J E; Augustinus, A; Baillon, P; Ballestrero, A; Bambade, P; Barbier, R; Bardin, D; Barker, G J; Baroncelli, A; Battaglia, M; Baubillier, M; Becks, K-H; Begalli, M; Behrmann, A; Ben-Haim, E; Benekos, N; Benvenuti, A; Berat, C; Berggren, M; Bertrand, D; Besancon, M; Besson, N; Bloch, D; Blom, M; Bluj, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Brenner, R; Brodet, E; Bruckman, P; Brunet, J M; Buschbeck, B; Buschmann, P; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F; Chapkin, M; Charpentier, Ph; Checchia, P; Chierici, R; Chliapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Crennell, D; Cuevas, J; D'Hondt, J; da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; De Boer, W; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; de Paula, L; Di Ciaccio, L; Di Simone, A; Doroba, K; Drees, J; Eigen, G; Ekelof, T; Ellert, M; Elsing, M; Espirito Santo, M C; Fanourakis, G; Fassouliotis, D; Feindt, M; Fernandez, J; Ferrer, A; Ferro, F; Flagmeyer, U; Foeth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J; Gandelman, M; Garcia, C; Gavillet, Ph; Gazis, E; Gokieli, R; Golob, B; Gomez-Ceballos, G; Goncalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Hoffman, J; Holmgren, S-O; Holt, P J; Houlden, M A; Jackson, J N; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Katsanevas, S; Katsoufis, E; Kernel, G; Kersevan, B P; Kerzel, U; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kouznetsov, O; Krumstein, Z; Kucharczyk, M; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; Lopez, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Marechal, B; Margoni, M; Marin, J-C; Mariotti, C; Markou, A; Martinez-Rivero, C; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; Mc Nulty, R; Meroni, C; Migliore, E; Mitaroff, W; Mjoernmark, U; Moa, T; Moch, M; Moenig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Mueller, U; Muenich, K; Mulders, M; Mundim, L; Murray, W; Muryn, B; Myatt, G; Myklebust, T; Nassiakou, M; Navarria, F; Nawrocki, K; Nemecek, S; Nicolaidou, R; Nikolenko, M; Oblakowska-Mucha, A; Obraztsov, V; Olshevski, A; Onofre, A; Orava, R; Osterberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, Th D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Pozdniakov, V; Pukhaeva, N; Pullia, A; Radojicic, D; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P; Richard, F; Ridky, J; Rivero, M; Rodriguez, D; Romero, A; Ronchese, P; Roudeau, P; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovsky, A; Salmi, L; Salt, J; Sander, C; Savoy-Navarro, A; Schwickerath, U; Sekulin, R; Siebel, M; Sisakian, A; Slominski, W; Smadja, G; Smirnova, O; Sokolov, A; Sopczak, A; Sosnowski, R; Spassov, T; Stanitzki, M; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Szwed, J; Tabarelli, T; Tegenfeldt, F; Timmermans, J; Tkatchev, L; Tobin, M; Todorovova, S; Tome, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tzamarias, S; Uvarov, V; Valenti, G; Van Dam, P; Van Eldik, J; van Remortel, N; Van Vulpen, I; Vegni, G; Veloso, F; Venus, W; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weiser, C; Wicke, D; Wickens, J; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O; Zalewska, A; Zalewski, P; Zavrtanik, D; Zhuravlov, V; Zimin, N I; Zintchenko, A; Zupan, M

    2010-01-01

    The hadronic part of the Electron Structure Function (ESF) has been measured for the first time, using e+e- data collected by the DELPHI experiment at LEP, at centre-of-mass energies sqrt(s) = 91.2-209.5 GeV. The data analysis is simpler than that of the measurement of the photon structure function. The ESF data are compared to predictions of phenomenological models based on the photon structure function. It is shown that the quasi-real photon virtuality contribution is significant. The presented data can serve as a cross-check of the photon structure function analyses and help in refining existing parametrizations.

  19. Calculation of the Gluon Distribution Function Using Alternative Method for the Proton Structure Function

    Institute of Scientific and Technical Information of China (English)

    N. Ghahramany; G.R. Boroun

    2003-01-01

    A calculation of the proton structure function F2(x,Q2) is reported with an approximation method that relates the reduced cross section derivative and the F2(x, Q2) scaling violation at low x by using quadratic form for the structure function. This quadratic form approximation method can be used to determine the structure function F2 (x, Q2)from the HERA reduced cross section data taken at low x. This new approach can determine the structure functions F2(x,Q2) with reasonable precision even for low x values which have not been investigated. We observe that the Q2 dependence is quadratic over the full kinematic covered range. To test the validity of our new determined structure functions, wefind the gluon distribution function in the leading order approximation with our new calculation for the structure functions and compare them with the QCD parton distribution functions.

  20. Calculation of the Gluon Distribution Function Using Alternative Method for the Proton Structure Function

    Institute of Scientific and Technical Information of China (English)

    N.Ghahramany; G.R.Boroun

    2003-01-01

    A calculation of the proton structure function F2(x,Q2) is reported with an approximation method that relates the reduced cross section derivative and the F2(x, Q2) scaling violation at low x by using quadratic form for the structure function. This quadratic form approximation method can be used to determine the structure function F2 (x, Q2) from the HERA reduced cross section data taken at low x. This new approach can determine the structure functions F2(x,Q2) with reasonable precision even for low x values which have not been investigated. We observe that the Q2 dependence is quadratic over the full kinematic covered range. To test the validity of our new determined structure functions, we find the gluon distribution function in the leading order approximation with our new calculation for the structure functions and compare them with the QCD parton distribution functions.

  1. Structure and function of yeast alcohol dehydrogenase

    Directory of Open Access Journals (Sweden)

    VLADIMIR LESKOVAC

    2000-04-01

    Full Text Available 1. Introduction 2. Isoenzymes of YADH 3. Substrate specificity 4. Kinetic mechanism 5. Primary structure 6. The active site 7. Mutations in the yeast enzyme 8. Chemical mechanism 9. Binding of coenzymes 10. Hydride transfer

  2. Structure and function of yeast alcohol dehydrogenase

    OpenAIRE

    VLADIMIR LESKOVAC; SVETLANA TRIVIC

    2000-01-01

    1. Introduction 2. Isoenzymes of YADH 3. Substrate specificity 4. Kinetic mechanism 5. Primary structure 6. The active site 7. Mutations in the yeast enzyme 8. Chemical mechanism 9. Binding of coenzymes 10. Hydride transfer

  3. Relativistic density functional for nuclear structure

    CERN Document Server

    2016-01-01

    This book aims to provide a detailed introduction to the state-of-the-art covariant density functional theory, which follows the Lorentz invariance from the very beginning and is able to describe nuclear many-body quantum systems microscopically and self-consistently. Covariant density functional theory was introduced in nuclear physics in the 1970s and has since been developed and used to describe the diversity of nuclear properties and phenomena with great success. In order to provide an advanced and updated textbook of covariant density functional theory for graduate students and nuclear physics researchers, this book summarizes the enormous amount of material that has accumulated in the field of covariant density functional theory over the last few decades as well as the latest developments in this area. Moreover, the book contains enough details for readers to follow the formalism and theoretical results, and provides exhaustive references to explore the research literature.

  4. Scanning probe and optical tweezer investigations of biomolecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Rigby-Singleton, Shellie

    2002-07-01

    A complex array of intermolecular forces controls the interactions between and within biological molecules. The desire to empirically explore the fundamental forces has led to the development of several biophysical techniques. Of these, the atomic force microscope (AFM) and the optical tweezers have been employed throughout this thesis to monitor the intermolecular forces involved in biomolecular interactions. The AFM is a well-established force sensing technique capable of measuring biomolecular interactions at a single molecule level. However, its versatility has not been extrapolated to the investigation of a drug-enzyme complex. The energy landscape for the force induced dissociation of the DHFR-methotrexate complex was studied. Revealing an energy barrier to dissociation located {approx}0.3 nm from the bound state. Unfortunately, the AFM has a limited range of accessible loading rates and in order to profile the complete energy landscape alternative force sensing instrumentation should be considered, for example the BFP and optical tweezers. Thus, this thesis outlines the development and construction an optical trap capable of measuring intermolecular forces between biomolecules at the single molecule level. To demonstrate the force sensing abilities of the optical set up, proof of principle measurements were performed which investigate the interactions between proteins and polymer surfaces subjected to varying degrees of argon plasma treatment. Complementary data was gained from measurements performed independently by the AFM. Changes in polymer resistance to proteins as a response to changes in polymer surface chemistry were detected utilising both AFM and optical tweezers measurements. Finally, the AFM and optical tweezers were employed as ultrasensitive biosensors. Single molecule investigations of the antibody-antigen interaction between the cardiac troponin I marker and its complementary antibody, reveals the impact therapeutic concentrations of heparin

  5. Gold nanoshells with gain-assisted silica core for ultra-sensitive bio-molecular sensors

    Science.gov (United States)

    Tao, Yifei; Guo, Zhongyi; Zhang, Anjun; Zhang, Jingran; Wang, Benyang; Qu, Shiliang

    2015-08-01

    A novel bio-molecular nanostructured sensor composed of Au spherical nanoshell and gain-assisted silica-core has been proposed and investigated theoretically, which shows a superior performance compared to the existing structured sensor. Using quasi-static approximation calculation, it is found that the scattering efficiency and the quality factor of SPR can be enhanced greatly by introducing proper amount of gain. The simulated results demonstrate that our designed Au spherical nanoshell and gain-assisted silica-core can obtain as high as 166.7 nm/RIU for the sensitivity of refractive index, and the sensors' figure of merit is enhanced 2000 times nearly compared to that of g=0, which indicates that the designed spherical core-shell sensors have the powerful ability to detect a subtle change in the concentration of its background medium.

  6. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    Science.gov (United States)

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia.

  7. Connectivity and functional profiling of abnormal brain structures in pedophilia

    Science.gov (United States)

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  8. Protein Structure and Function Prediction Using I-TASSER.

    Science.gov (United States)

    Yang, Jianyi; Zhang, Yang

    2015-12-17

    I-TASSER is a hierarchical protocol for automated protein structure prediction and structure-based function annotation. Starting from the amino acid sequence of target proteins, I-TASSER first generates full-length atomic structural models from multiple threading alignments and iterative structural assembly simulations followed by atomic-level structure refinement. The biological functions of the protein, including ligand-binding sites, enzyme commission number, and gene ontology terms, are then inferred from known protein function databases based on sequence and structure profile comparisons. I-TASSER is freely available as both an on-line server and a stand-alone package. This unit describes how to use the I-TASSER protocol to generate structure and function prediction and how to interpret the prediction results, as well as alternative approaches for further improving the I-TASSER modeling quality for distant-homologous and multi-domain protein targets.

  9. Controlling Function and Structure with DNA

    DEFF Research Database (Denmark)

    Tørring, Thomas

    2011-01-01

    In this thesis, the research on three different topics will be described. The overall area of the research is DNA nanotechnology, and the first chapter is therefore an introduction to DNA, and its advantages as a building material. The first research topic is the development of a new method...... investigated on a two dimensional DNA origami platform. This was done by incorporating functional groups on the surface of the origami, and reacting these with biotin analogues carrying the complementary functional groups. Successful reactions could then be observed using atomic force microscopy after addition...... of the protein streptavidin. While the implementation of chemical functionalities on origami can be achieved during automated DNA synthesis, this is laborious and costly. In a separate research project we aimed at improving the accessibility by applying an enzymatic labelling method. We demonstrated that the DNA...

  10. Nodal Structure of the Electronic Wigner Function

    DEFF Research Database (Denmark)

    Schmider, Hartmut; Dahl, Jens Peder

    1996-01-01

    On the example of several atomic and small molecular systems, the regular behavior of nodal patterns in the electronic one-particle reduced Wigner function is demonstrated. An expression found earlier relates the nodal pattern solely to the dot-product of the position and the momentum vector......, if both arguments are large. An argument analogous to the ``bond-oscillatory principle'' for momentum densities links the nuclear framework in a molecule to an additional oscillatory term in momenta parallel to bonds. It is shown that these are visible in the Wigner function in terms of characteristic...

  11. Structural plasticity upon learning: regulation and functions.

    Science.gov (United States)

    Caroni, Pico; Donato, Flavio; Muller, Dominique

    2012-07-01

    Recent studies have provided long-sought evidence that behavioural learning involves specific synapse gain and elimination processes, which lead to memory traces that influence behaviour. The connectivity rearrangements are preceded by enhanced synapse turnover, which can be modulated through changes in inhibitory connectivity. Behaviourally related synapse rearrangement events tend to co-occur spatially within short stretches of dendrites, and involve signalling pathways partially overlapping with those controlling the functional plasticity of synapses. The new findings suggest that a mechanistic understanding of learning and memory processes will require monitoring ensembles of synapses in situ and the development of synaptic network models that combine changes in synaptic function and connectivity.

  12. Types and Functions of Coastal Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; A. Hughes, Steven

    2003-01-01

    Coastal structures are used in coastal defence schemes with the objective of preventing shoreline erosion and flooding of the hinterland. Other objectives include sheltering of harbour basins and harbour entrances against waves, stabilization of navigation channels at inlets, and protection of wa...... of water intakes and outfalls....

  13. The structure and function of endophilin proteins

    DEFF Research Database (Denmark)

    Kjaerulff, Ole; Brodin, Lennart; Jung, Anita

    2011-01-01

    Members of the BAR domain protein superfamily are essential elements of cellular traffic. Endophilins are among the best studied BAR domain proteins. They have a prominent function in synaptic vesicle endocytosis (SVE), receptor trafficking and apoptosis, and in other processes that require...

  14. NAC transcription factors: structurally distinct, functionally diverse

    DEFF Research Database (Denmark)

    Olsen, Addie Nina; Ernst, Heidi A; Leggio, Leila Lo;

    2005-01-01

    NAC proteins constitute one of the largest families of plant-specific transcription factors, and the family is present in a wide range of land plants. Here, we summarize the biological and molecular functions of the NAC family, paying particular attention to the intricate regulation of NAC protei...

  15. Orbitofrontal cortex function and structure in depression.

    Science.gov (United States)

    Drevets, Wayne C

    2007-12-01

    The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression.

  16. Thermal coupling at aqueous and biomolecular interfaces

    Science.gov (United States)

    Shenogina, Natalia B.

    structural characterization tools. We followed up with studies of models of heterogeneous interfaces where we addressed the issue of independent vs. correlated contributions of hydrophobic and hydrophilic interfacial regions to thermal transfer. Finally we simulated heat flow across lipid bilayers which involve hydrophilic interfaces, but are characterized by relatively high surface roughness and non-saturated hydrocarbon chains. We found that roughness of the interface can significantly enhance thermal transport across the lipid membranes.

  17. Animal Structures and Functions, Science (Experimental): 5314.13.

    Science.gov (United States)

    Silver, Barbara A.

    This unit of instruction was designed to introduce the student to the relationship between structure and function in the animal kingdom, with emphasis given to: (1) the evolution of physiological systems in the major animal phyla, (2) the complementarity of structure and function, and (3) the concept of homeostasis. The booklet lists the relevant…

  18. Studying Membrane Protein Structure and Function Using Nanodiscs

    DEFF Research Database (Denmark)

    Huda, Pie

    The structure and dynamic of membrane proteins can provide valuable information about general functions, diseases and effects of various drugs. Studying membrane proteins are a challenge as an amphiphilic environment is necessary to stabilise the protein in a functionally and structurally relevan...

  19. Structure-function clustering in multiplex brain networks

    Science.gov (United States)

    Crofts, J. J.; Forrester, M.; O'Dea, R. D.

    2016-10-01

    A key question in neuroscience is to understand how a rich functional repertoire of brain activity arises within relatively static networks of structurally connected neural populations: elucidating the subtle interactions between evoked “functional connectivity” and the underlying “structural connectivity” has the potential to address this. These structural-functional networks (and neural networks more generally) are more naturally described using a multilayer or multiplex network approach, in favour of standard single-layer network analyses that are more typically applied to such systems. In this letter, we address such issues by exploring important structure-function relations in the Macaque cortical network by modelling it as a duplex network that comprises an anatomical layer, describing the known (macro-scale) network topology of the Macaque monkey, and a functional layer derived from simulated neural activity. We investigate and characterize correlations between structural and functional layers, as system parameters controlling simulated neural activity are varied, by employing recently described multiplex network measures. Moreover, we propose a novel measure of multiplex structure-function clustering which allows us to investigate the emergence of functional connections that are distinct from the underlying cortical structure, and to highlight the dependence of multiplex structure on the neural dynamical regime.

  20. Small-x asymptotics of structure function $g_2$

    CERN Document Server

    Ermolaev, B I

    1997-01-01

    Nonsinglet structure function g_2(x) for deep inelastic scattering of a lepton on a constituent quark is calculated in the double logarithmic approximation at x<<1. Small-x asymptotics of g_2 is shown to have the same singular behaviour as asymptotics of the nonsinglet structure function g_1.

  1. Nuclear matrix - structure, function and pathogenesis.

    Science.gov (United States)

    Wasąg, Piotr; Lenartowski, Robert

    2016-12-20

    The nuclear matrix (NM), or nuclear skeleton, is the non-chromatin, ribonucleoproteinaceous framework that is resistant to high ionic strength buffers, nonionic detergents, and nucleolytic enzymes. The NM fulfills a structural role in eukaryotic cells and is responsible for maintaining the shape of the nucleus and the spatial organization of chromatin. Moreover, the NM participates in several cellular processes, such as DNA replication/repair, gene expression, RNA transport, cell signaling and differentiation, cell cycle regulation, apoptosis and carcinogenesis. Short nucleotide sequences called scaffold/matrix attachment regions (S/MAR) anchor the chromatin loops to the NM proteins (NMP). The NMP composition is dynamic and depends on the cell type and differentiation stage or metabolic activity. Alterations in the NMP composition affect anchoring of the S/MARs and thus alter gene expression. This review aims to systematize information about the skeletal structure of the nucleus, with particular emphasis on the organization of the NM and its role in selected cellular processes. We also discuss several diseases that are caused by aberrant NM structure or dysfunction of individual NM elements.

  2. Brain Structure-function Couplings (FY11)

    Science.gov (United States)

    2012-01-01

    following have been generated: • Refereed Journal Papers: 1. Lau, T. M.; Gwin, J. T.; McDowell, K.; Ferris, D. P. Weighted Phase Lag Index Stability as an...Environments 3.1 Authors The authors on this project are Scott Kerick from ARL/HRED, Manuel Vindiola from Dynamics Research Corporation ( DRC ), and Kaleb...Project 3: Validating Functional Connectivity Measures Using Neural Mass Models 4.1 Authors The authors on this project are Manuel Vindiola from DRC

  3. Structures and Functions of Selective Attention.

    Science.gov (United States)

    1987-07-20

    range of adjacent locations (Downing & Pinker , 1985, Rizzolatti, Riggio, Dascola, & Umilta, 1987). The size of the area facilitated depends in part on...increasing with eccentricity from the fovea, with an inhibition stronger once one has crossed the midline (Downing & Pinker , 1985). These disputes indicate...0014-86-0289 and by the McDonnell Center for Higher Brain Function. I am grateful to Drs. Mary K. Rothbart, Steven E. Petersen and Jennifer Sandson

  4. Galactosaminoglycan Function and Oligosaccharide Structure Determination

    Directory of Open Access Journals (Sweden)

    Daniela G. Seidler

    2007-01-01

    Full Text Available This review will discuss the importance of sequencing long chondroitin sulfate and dermatan sulfate chains specifically derived from decorin. Decorin is a member of the small leucine-rich repeat proteoglycans and ubiquitously expressed primarily in the skin. Sequence information and diverse function of glycosaminoglycans is further influenced by variable expression through the core protein indicating the importance to analyse glycosaminoglycans from specific proteoglycans.

  5. An inertial range length scale in structure functions

    CERN Document Server

    Kerr, R M; Gotoh, T; Kerr, Robert M.; Meneguzzi, Maurice; Gotoh, Toshiyuki

    2000-01-01

    It is shown using experimental and numerical data that within the traditional inertial subrange defined by where the third order structure function is linear that the higher order structure function scaling exponents for longitudinal and transverse structure functions converge only over larger scales, $r>r_S$, where $r_S$ has scaling intermediate between $\\eta$ and $\\lambda$ as a function of $R_\\lambda$. Below these scales, scaling exponents cannot be determined for any of the structure functions without resorting to procedures such as extended self-similarity (ESS). With ESS, different longitudinal and transverse higher order exponents are obtained that are consistent with earlier results. The relationship of these statistics to derivative and pressure statistics, to turbulent structures and to length scales is discussed.

  6. Knowledge based cluster ensemble for cancer discovery from biomolecular data.

    Science.gov (United States)

    Yu, Zhiwen; Wongb, Hau-San; You, Jane; Yang, Qinmin; Liao, Hongying

    2011-06-01

    The adoption of microarray techniques in biological and medical research provides a new way for cancer diagnosis and treatment. In order to perform successful diagnosis and treatment of cancer, discovering and classifying cancer types correctly is essential. Class discovery is one of the most important tasks in cancer classification using biomolecular data. Most of the existing works adopt single clustering algorithms to perform class discovery from biomolecular data. However, single clustering algorithms have limitations, which include a lack of robustness, stability, and accuracy. In this paper, we propose a new cluster ensemble approach called knowledge based cluster ensemble (KCE) which incorporates the prior knowledge of the data sets into the cluster ensemble framework. Specifically, KCE represents the prior knowledge of a data set in the form of pairwise constraints. Then, the spectral clustering algorithm (SC) is adopted to generate a set of clustering solutions. Next, KCE transforms pairwise constraints into confidence factors for these clustering solutions. After that, a consensus matrix is constructed by considering all the clustering solutions and their corresponding confidence factors. The final clustering result is obtained by partitioning the consensus matrix. Comparison with single clustering algorithms and conventional cluster ensemble approaches, knowledge based cluster ensemble approaches are more robust, stable and accurate. The experiments on cancer data sets show that: 1) KCE works well on these data sets; 2) KCE not only outperforms most of the state-of-the-art single clustering algorithms, but also outperforms most of the state-of-the-art cluster ensemble approaches.

  7. Photochirogenesis: Photochemical Models on the Origin of Biomolecular Homochirality

    Directory of Open Access Journals (Sweden)

    Cornelia Meinert

    2010-05-01

    Full Text Available Current research focuses on a better understanding of the origin of biomolecular asymmetry by the identification and detection of the possibly first chiral molecules that were involved in the appearance and evolution of life on Earth. We have reasons to assume that these molecules were specific chiral amino acids. Chiral amino acids have been identified in both chondritic meteorites and simulated interstellar ices. Present research reasons that circularly polarized electromagnetic radiation was identified in interstellar environments and an asymmetric interstellar photon-molecule interaction might have triggered biomolecular symmetry breaking. We review on the possible prebiotic interaction of ‘chiral photons’ in the form of circularly polarized light, with early chiral organic molecules. We will highlight recent studies on enantioselective photolysis of racemic amino acids by circularly polarized light and experiments on the asymmetric photochemical synthesis of amino acids from only one C and one N containing molecules by simulating interstellar environments. Both approaches are based on circular dichroic transitions of amino acids that will be presented as well.

  8. A graph theoretical approach for assessing bio-macromolecular complex structural stability.

    Science.gov (United States)

    Del Carpio, Carlos Adriel; Iulian Florea, Mihai; Suzuki, Ai; Tsuboi, Hideyuki; Hatakeyama, Nozomu; Endou, Akira; Takaba, Hiromitsu; Ichiishi, Eiichiro; Miyamoto, Akira

    2009-11-01

    Fast and proper assessment of bio macro-molecular complex structural rigidity as a measure of structural stability can be useful in systematic studies to predict molecular function, and can also enable the design of rapid scoring functions to rank automatically generated bio-molecular complexes. Based on the graph theoretical approach of Jacobs et al. [Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF (2001) Protein flexibility predictions using graph theory. Proteins: Struct Funct Genet 44:150-165] for expressing molecular flexibility, we propose a new scheme to analyze the structural stability of bio-molecular complexes. This analysis is performed in terms of the identification in interacting subunits of clusters of flappy amino acids (those constituting regions of potential internal motion) that undergo an increase in rigidity at complex formation. Gains in structural rigidity of the interacting subunits upon bio-molecular complex formation can be evaluated by expansion of the network of intra-molecular inter-atomic interactions to include inter-molecular inter-atomic interaction terms. We propose two indices for quantifying this change: one local, which can express localized (at the amino acid level) structural rigidity, the other global to express overall structural stability for the complex. The new system is validated with a series of protein complex structures reported in the protein data bank. Finally, the indices are used as scoring coefficients to rank automatically generated protein complex decoys.

  9. Three Kinds of Velocity Structure Function in Turbulent Flows

    Institute of Scientific and Technical Information of China (English)

    LIU Wei; JIANG Nan

    2004-01-01

    Based on the local multi-scale eddy structures in turbulent flows, we elucidate the essential difference between the real turbulent field with a finite Reynolds number and the Kolmogorov fully developed random field. The motion of fluid particles in the real turbulent field is not fully random. There exist multi-scale structures due to the effect of viscosity. Actually the movements of fluid particles in the turbulent field are restricted by such eddy structures. Furthermore, concept of the locally averaged velocity structure function is put forward to describe the relative strain distortion of two adjacent turbulent eddy structures at a certain scale. The time sequence of the longitudinal velocity component at different vertical locations in turbulent boundary layer has been elaborately measured by the constant temperature anemometry of model IFA-300 in a wind tunnel. The experiment proves that the locally averaged velocity structure function is in agreement with the wavelet-coefficient structure function.

  10. Turner syndrome: neuroimaging findings: structural and functional.

    LENUS (Irish Health Repository)

    Mullaney, Ronan

    2009-01-01

    Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including the parietal lobe; cerebellum, amygdala, hippocampus; and basal ganglia; and perhaps differences in "connectivity" between frontal and parieto-occipital regions. Finally, there is preliminary evidence that genomic imprinting, sex hormones and growth hormone have significant modulatory effects on brain maturation in TS.

  11. The Structure of Optimum Interpolation Functions.

    Science.gov (United States)

    1983-02-01

    Daniel F . Merriam, ed., Plenum Press, 1970. 2. Hiroshi Akima, "Comments on ’Optimal Contour Mapping Using Universal Kriging’ by Ricardo 0. Olea," (with...Interpolation Scheme," Monthly WeatherReview 109 (1981), 701-721. 22. A. Marechal and J. Serra, "Random Kriging,"pp. 91-112 in Geostatistics, Daniel F . Merriam...ed., Plenum Press, 1970. 23. G. Matheron, "Random Functions and Their Applications in Geology," pp. 79-87 in Geostatistics, Daniel F . Merriam

  12. Fitting EMC structure functions with intrinsic charm

    CERN Document Server

    Rottoli, Luca

    2016-01-01

    A detailed study of the impact of the data collected by the European Muon Collaboration (EMC) on the parton distribution function (PDF) of the charm quark is presented. The analysis is performed in the NNPDF framework, and the charm PDF is freely parametrized on equal footing as light quark and gluon distributions. We find that variations in the treatment of EMC data do not modify the charm PDF and do not affect our previous conclusion on the presence of an intrinsic component in the charm PDF.

  13. Cognitive Adequacy in Structural-Functional Theories of Language

    Science.gov (United States)

    Butler, Christopher S.

    2008-01-01

    This paper discusses the role played by cognition in three linguistic theories which may be labelled as "structural-functional": Functional (Discourse) Grammar, Role and Reference Grammar and Systemic Functional Grammar. It argues that if we are to achieve true cognitive adequacy, we must go well beyond the grammar itself to include the processes…

  14. Hsp70 Structure, Function, Regulation and Influence on Yeast Prions

    OpenAIRE

    D. Sharma; Masison, D. C.

    2009-01-01

    Heat shock proteins protect cells from various conditions of stress. Hsp70, the most ubiquitous and highly conserved Hsp, helps proteins adopt native conformation or regain function after misfolding. Various co-chaperones specify Hsp70 function and broaden its substrate range. We discuss Hsp70 structure and function, regulation by co-factors and influence on propagation of yeast prions.

  15. Structural and functional analysis of rice genome

    Indian Academy of Sciences (India)

    Akhilesh K. Tyagi; Jitendra P. Khurana; Paramjit Khurana; Saurabh Raghuvanshi; Anupama Gaur; Anita Kapur; Vikrant Gupta; Dibyendu Kumar; V. Ravi; Shubha Vij; Parul Khurana; Sulabha Sharma

    2004-04-01

    Rice is an excellent system for plant genomics as it represents a modest size genome of 430 Mb. It feeds more than half the population of the world. Draft sequences of the rice genome, derived by whole-genome shotgun approach at relatively low coverage (4–6 X), were published and the International Rice Genome Sequencing Project (IRGSP) declared high quality (>10 X), genetically anchored, phase 2 level sequence in 2002. In addition, phase 3 level finished sequence of chromosomes 1, 4 and 10 (out of 12 chromosomes of rice) has already been reported by scientists from IRGSP consortium. Various estimates of genes in rice place the number at > 50,000. Already, over 28,000 full-length cDNAs have been sequenced, most of which map to genetically anchored genome sequence. Such information is very useful in revealing novel features of macro- and micro-level synteny of rice genome with other cereals. Microarray analysis is unraveling the identity of rice genes expressing in temporal and spatial manner and should help target candidate genes useful for improving traits of agronomic importance. Simultaneously, functional analysis of rice genome has been initiated by marker-based characterization of useful genes and employing functional knock-outs created by mutation or gene tagging. Integration of this enormous information is expected to catalyze tremendous activity on basic and applied aspects of rice genomics.

  16. Piezo channels: from structure to function.

    Science.gov (United States)

    Volkers, Linda; Mechioukhi, Yasmine; Coste, Bertrand

    2015-01-01

    Mechanotransduction is the conversion of mechanical stimuli into biological signals. It is involved in the modulation of diverse cellular functions such as migration, proliferation, differentiation, and apoptosis as well as in the detection of sensory stimuli such as air vibration and mechanical contact. Therefore, mechanotransduction is crucial for organ development and homeostasis and plays a direct role in hearing, touch, proprioception, and pain. Multiple molecular players involved in mechanotransduction have been identified in the past, among them ion channels directly activated by cell membrane deformation. Most of these channels have well-established roles in lower organisms but are not conserved in mammals or fail to encode mechanically activated channels in mammals due to non-conservation of mechanotransduction property. A family of mechanically activated channels that counts only two members in human, piezo1 and 2, has emerged recently. Given the lack of valid mechanically activated channel candidates in mammals in the past decades, particular attention is given to piezo channels and their potential roles in various biological functions. This review summarizes our current knowledge on these ion channels.

  17. Differential geometry-based solvation and electrolyte transport models for biomolecular modeling: a review

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Guowei; Baker, Nathan A.

    2016-11-11

    This chapter reviews the differential geometry-based solvation and electrolyte transport for biomolecular solvation that have been developed over the past decade. A key component of these methods is the differential geometry of surfaces theory, as applied to the solvent-solute boundary. In these approaches, the solvent-solute boundary is determined by a variational principle that determines the major physical observables of interest, for example, biomolecular surface area, enclosed volume, electrostatic potential, ion density, electron density, etc. Recently, differential geometry theory has been used to define the surfaces that separate the microscopic (solute) domains for biomolecules from the macroscopic (solvent) domains. In these approaches, the microscopic domains are modeled with atomistic or quantum mechanical descriptions, while continuum mechanics models (including fluid mechanics, elastic mechanics, and continuum electrostatics) are applied to the macroscopic domains. This multiphysics description is integrated through an energy functional formalism and the resulting Euler-Lagrange equation is employed to derive a variety of governing partial differential equations for different solvation and transport processes; e.g., the Laplace-Beltrami equation for the solvent-solute interface, Poisson or Poisson-Boltzmann equations for electrostatic potentials, the Nernst-Planck equation for ion densities, and the Kohn-Sham equation for solute electron density. Extensive validation of these models has been carried out over hundreds of molecules, including proteins and ion channels, and the experimental data have been compared in terms of solvation energies, voltage-current curves, and density distributions. We also propose a new quantum model for electrolyte transport.

  18. The RFC clamp loader: structure and function.

    Science.gov (United States)

    Yao, Nina Y; O'Donnell, Mike

    2012-01-01

    The eukaryotic RFC clamp loader couples the energy of ATP hydrolysis to open and close the circular PCNA sliding clamp onto primed sites for use by DNA polymerases and repair factors. Structural studies reveal clamp loaders to be heteropentamers. Each subunit contains a region of homology to AAA+ proteins that defines two domains. The AAA+ domains form a right-handed spiral upon binding ATP. This spiral arrangement generates a DNA binding site within the center of RFC. DNA enters the central chamber through a gap between the AAA+ domains of two subunits. Specificity for a primed template junction is achieved by a third domain that blocks DNA, forcing it to bend sharply. Thus only DNA with a flexible joint can bind the central chamber. DNA entry also requires a slot in the PCNA clamp, which is opened upon binding the AAA+ domains of the clamp loader. ATP hydrolysis enables clamp closing and ejection of RFC, completing the clamp loading reaction.

  19. The structures and functions of oligosaccharins

    Energy Technology Data Exchange (ETDEWEB)

    Albersheim, P.

    1991-08-01

    This document contains a summary of proposed research studying the role of oligosaccharins in developmental biology and in plant-microbe interactions. Research is described in the following areas of developmental biology: Use of the tobacco thin-cell-layer explant bioassay to screen for oligosaccharins that are able to regulate growth and morphogenesis; oligosaccharin receptors - searching for the receptor for biologically active alpha-1,4-oligogalacturnoides; molecular biology studies of endopolygalacturonase in tobacco tissues; investigation of membrane responses induced by oligogalacturonides; the effect of structurally defined oligosaccharins on plant gene expression. In the area of plant-microbe interactions research is focused on: do oligosaccharins elicit the hypersensitive resistance response, and the polygalacturonase-inhibitor protein (PGIP).

  20. [Structure and function of fungal cell wall].

    Science.gov (United States)

    Ohno, Naohito

    2008-12-01

    Cell wall glycans of fungi/yeasts are reviewed. Fungi/yeasts produce various kinds of polysaccharides. As part of the cell wall they are interlinked with other components forming a huge network. The insolubility and complex with multiple components makes the research very tough. Studies on beta-glucan have been performed from various views, such as chemistry, conformation, solubility, tissue distribution and metabolism, biological activity, clinical application, receptor, biosynthesis, and antibody. Studies on mannan focus on immunotoxicity, such as anaphylactoid reaction and coronary arteritis induction. alpha-glucan, chitin, and capsular polysaccharide were also mentioned in relation to structure and genes. Compared with human and animal polysaccharides, fungi/yeasts polysaccharides have very characteristic properties.

  1. History, structure, and function of the Internet.

    Science.gov (United States)

    Glowniak, J

    1998-04-01

    The Internet stands at the forefront of telecommunications in medicine. This worldwide system of computers had its beginnings in networking projects in the United States and western Europe in the 1960s and 1970s. The precursor of the Internet was ARPANET, a long-distance telecommunication network funded by the Department of Defense that linked together computers throughout the United States. In the 1980s, ARPANET was superseded by NSFNET, a series of networks created by the National Science Foundation, which established the present-day structure of the Internet. The physical structure of the Internet resembles and is integrated with the telephone system. Long-distance data transport services are provided by large telecommunication companies, called network service providers (NSPs), through high-capacity, high-speed national and international fiber optic cables. These transport services are accessed through Internet service providers, ISPs. ISPs, the equivalent of regional Bell operating companies, provide the physical link to the NSPs for individuals and organizations. Telecommunications on the Internet are standardized by a set of communications protocols, the TCP/IP protocol suite, that describe routing of messages over the Internet, computer naming conventions, and commonly used Internet services such as e-mail. At present, the Internet consists of over 20 million computer worldwide and is continuing to grow at a rapid rate. Along with the growth of the Internet, higher speed access methods are offering a range of new services such as real-time video and voice communications. Medical education, teaching, and research, as well as clinical practice, will be affected in numerous different ways by these advances.

  2. Small catalytic RNA: Structure, function and application

    Energy Technology Data Exchange (ETDEWEB)

    Monforte, J.A.

    1991-04-01

    We have utilized a combination of photochemical cross-linking techniques and site-directed mutagenesis to obtain secondary and tertiary structure information for the self-cleaving, self-ligating subsequence of RNA from the negative strand of Satellite Tobacco Ringspot Virus. We have found that the helical regions fold about a hinge to promoting four different possible tertiary interactions, creating a molecular of similar shape to a paperclip. A model suggesting that the ``paperclip`` and ``hammerhead`` RNAs share a similar three dimensional structure is proposed. We have used a self-cleaving RNA molecule related to a subsequence of plant viroids, a ``hammerhead,`` to study the length-dependent folding of RNA produced during transcription by RNA polymerase. We have used this method to determine the length of RNA sequestered within elongating E. coli and T7 RNA polymerase complexes. The data show that for E. coli RNA polymerase 12{plus_minus}1 nucleotides are sequestered within the ternary complex, which is consistent with the presence of an RNA-DNA hybrid within the transcription bubble, as proposed by others. The result for T7 RNA polymerase differs from E. coli RNA polymerase, with only 10{plus_minus}1 nucleotides sequestered within the ternary complex, setting a new upper limit for the minimum RNA-DNA required for a stable elongating complex. Comparisons between E. coli and T7 RNA polymerase are made. The relevance of the results to models or transcription termination, abortive initiation, and initiation to elongation mode transitions are discussed.

  3. Small catalytic RNA: Structure, function and application

    Energy Technology Data Exchange (ETDEWEB)

    Monforte, J.A.

    1991-04-01

    We have utilized a combination of photochemical cross-linking techniques and site-directed mutagenesis to obtain secondary and tertiary structure information for the self-cleaving, self-ligating subsequence of RNA from the negative strand of Satellite Tobacco Ringspot Virus. We have found that the helical regions fold about a hinge to promoting four different possible tertiary interactions, creating a molecular of similar shape to a paperclip. A model suggesting that the paperclip'' and hammerhead'' RNAs share a similar three dimensional structure is proposed. We have used a self-cleaving RNA molecule related to a subsequence of plant viroids, a hammerhead,'' to study the length-dependent folding of RNA produced during transcription by RNA polymerase. We have used this method to determine the length of RNA sequestered within elongating E. coli and T7 RNA polymerase complexes. The data show that for E. coli RNA polymerase 12{plus minus}1 nucleotides are sequestered within the ternary complex, which is consistent with the presence of an RNA-DNA hybrid within the transcription bubble, as proposed by others. The result for T7 RNA polymerase differs from E. coli RNA polymerase, with only 10{plus minus}1 nucleotides sequestered within the ternary complex, setting a new upper limit for the minimum RNA-DNA required for a stable elongating complex. Comparisons between E. coli and T7 RNA polymerase are made. The relevance of the results to models or transcription termination, abortive initiation, and initiation to elongation mode transitions are discussed.

  4. [The vestibular system: from structure to function].

    Science.gov (United States)

    Collard, M

    1994-02-01

    The two vestibular receptors, right and left, hidden in the petrous part of the temporal bone with the cochlear receptors, receive information from angular and linear movements of the head and transform them into a nerve message sent to the nuclei of the brainstem, which are connected directly on the one hand to the oculomotor nuclei, at the origin of the oculovestibular reflex (induction of nystagmus), and on the other hand, to the spinal motor neurons, at the origin of the vestibulospinal reflex. These reflexes are associated with responses to visual and somaesthetic information for maintenance or return to the standing position, which characterises the function of equilibrium. Vertigo and disorders of balance reflect a conflict of information between these two labyrinths, or between the vestibular apparatus and the messages issued by other captors, and sometimes also dysfunction of central nervous system treatment of information or a lesion of the effector motor systems.

  5. Joint Modelling of Structural and Functional Brain Networks

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther; Herlau, Tue; Mørup, Morten

    Functional and structural magnetic resonance imaging have become the most important noninvasive windows to the human brain. A major challenge in the analysis of brain networks is to establish the similarities and dissimilarities between functional and structural connectivity. We formulate a non...... significant structures that are consistently shared across subjects and data splits. This provides an unsupervised approach for modeling of structure-function relations in the brain and provides a general framework for multimodal integration.......-parametric Bayesian network model which allows for joint modelling and integration of multiple networks. We demonstrate the model’s ability to detect vertices that share structure across networks jointly in functional MRI (fMRI) and diffusion MRI (dMRI) data. Using two fMRI and dMRI scans per subject, we establish...

  6. On a useful functional representation of control system structure

    Science.gov (United States)

    Malchow, Harvey L.

    1988-01-01

    An alternative structure for control systems is proposed. The structure is represented by a three-element block diagram and three functional definitions. It is argued that the three functional elements form a canonical set. The set includes the functions description, estimation and control. General overlay of the structure on parallel state and nested-state control systems is discussed. Breakdown of two real nested-state control systems into the proposed functional format is displayed. Application of the process to the mapping of complex control systems R and D efforts is explained with the Mars Rover Sample and Return mission as an example. A previous application of this basic functional structure to Space Station performance requirements organization is discussed.

  7. Structural properties of prokaryotic promoter regions correlate with functional features.

    Directory of Open Access Journals (Sweden)

    Pieter Meysman

    Full Text Available The structural properties of the DNA molecule are known to play a critical role in transcription. In this paper, the structural profiles of promoter regions were studied within the context of their diversity and their function for eleven prokaryotic species; Escherichia coli, Klebsiella pneumoniae, Salmonella Typhimurium, Pseudomonas auroginosa, Geobacter sulfurreducens Helicobacter pylori, Chlamydophila pneumoniae, Synechocystis sp., Synechoccocus elongates, Bacillus anthracis, and the archaea Sulfolobus solfataricus. The main anchor point for these promoter regions were transcription start sites identified through high-throughput experiments or collected within large curated databases. Prokaryotic promoter regions were found to be less stable and less flexible than the genomic mean across all studied species. However, direct comparison between species revealed differences in their structural profiles that can not solely be explained by the difference in genomic GC content. In addition, comparison with functional data revealed that there are patterns in the promoter structural profiles that can be linked to specific functional loci, such as sigma factor regulation or transcription factor binding. Interestingly, a novel structural element clearly visible near the transcription start site was found in genes associated with essential cellular functions and growth in several species. Our analyses reveals the great diversity in promoter structural profiles both between and within prokaryotic species. We observed relationships between structural diversity and functional features that are interesting prospects for further research to yet uncharacterized functional loci defined by DNA structural properties.

  8. Novel mechanisms that regulate clot structure/function.

    Science.gov (United States)

    Ariëns, Robert A S

    2016-05-01

    The structure and function of the blood clot has been associated with altered risk of thrombosis. Dense fibrin structures with small pores increase the risk of thrombosis, and have major functional consequences by increasing the resistance to fibrinolysis and altering the visco-elastic properties of the clot. However, while the structural changes to the overall fibrin network have been extensively characterised, little is known regarding the intrafibrillar structure of fibrin, the way protofibrils are arranged inside the fibrin fibers and the functional consequences of this. This brief paper aims to review recent findings regarding novel mechanisms that regulate fibrin intrafibrillar structure, including the degree of protofibril packing, their functional consequences, and the effects of FXIII activation on clot structure and thrombosis. It is concluded that fibrin intrafibrillar structure represents a major novel mechanism that influences clot structure and stability. Future studies are required to investigate the role of fibrin intrafibrillar structure in the functional characteristics of the blood clot, and in diseases of bleeding and thrombosis.

  9. Structure/function relationships in cellulolytic enzymes

    Institute of Scientific and Technical Information of China (English)

    Marc Claeyssens

    2004-01-01

    @@ Cellulose and hemicellulose (mostly xylan), together with lignin, are the major polymeric constituents of plant cell walls and from the largest reservoir of fixed carbon in nature. The enzymatic hydrolysis of polymeric substances by extracellular enzymes, such as cellulases, hemicellulases and laccases, is preferred to chemical depolymerisation to avoid the production of toxic by-products and waste that are expensive to treat. The monosaccharides released through enzymatic hydrolysis can subsequently be microbially converted to commercial commodities, such as bio-ethanol (fuel extender) or microbial protein as feed supplements. The individual depolymerisering enzymes used, such as cellulases,xylanases and laccases, also have industrial application in (i) biobleaching in the paper and pulp industry, (ii) improvement of animal feed (poultry and ruminants) digestibility in feed industries, and (iii) dough rheology and bread volume in the baking process, and beer viscosity and filtration velocity during brewing. The cloning of the genes, coding for several xylan degrading enzymes, and their expression in Baker' s yeast (Saccharomyces cerevisiae) and filamentous fungi (Aspergillus species)opened the possibility to study the pure enzymes, without contaminating activity.Trichoderma reesei produces several of these enzymes and detailed information on their specificity,synergies and structure/activity relationships is known. An overview will be presented.

  10. Engineering structure and function using thermoresponsive biopolymers.

    Science.gov (United States)

    Pastuszka, Martha K; MacKay, J Andrew

    2016-01-01

    Self-assembly enables exquisite control at the smallest scale and generates order among macromolecular-building blocks that remain too small to be manipulated individually. Environmental cues, such as heating, can trigger the organization of these materials from individual molecules to multipartixcle assemblies with a variety of compositions and functions. Synthetic as well as biological polymers have been engineered for these purposes; however, biological strategies can offer unparalleled control over the composition of these macromolecular-building blocks. Biologic polymers are macromolecules composed of monomeric units that can be precisely tailored at the genetic level; furthermore, they can often utilize endogenous biodegradation pathways, which may enhance their potential clinical applications. DNA (nucleotides), polysaccharides (carbohydrates), and proteins (amino acids) have all been engineered to self-assemble into nanostructures in response to a change in temperature. This focus article reviews the growing body of literature exploring temperature-dependent nano-assembly of these biological macromolecules, summarizes some of their physical properties, and discusses future directions.

  11. The rhodopsins: structure and function. Introduction

    Science.gov (United States)

    Lanyi, J. K.

    1992-01-01

    Nature makes use of the propensity of retinal for light-dependent double-bond isomerization in a number of systems and in a variety of ways. The common theme for light receptors based on this kind of chemistry is that (1) the retinal is bound in most cases to a small membrane protein via a protonated lysine-retinal Schiff base, (2) the absorption maximum in the visible is tuned to a suitable wavelength largely by electrostatic interaction with polar protein residues, and (3) the light-induced bond rotations and strains in the retinal set off reaction chains during which at least part of the excess free energy acquired is transferred to the protein and causes pK shifts of acidic residues and/or backbone conformational changes. The physiological consequence of the process initiated by absorption of light is either the activation of an information transfer chain (sensory and visual rhodopsins) or energy transduction which drives the electrogenic movement of ions across the membrane (ion-motive rhodopsins). Rhodopsins with these functions occur in bacteria and in higher organisms; from an evolutionary standpoint they are not related to one another. Nevertheless, all of these proteins are remarkably similar and form a distinct family.

  12. Significance tests for functional data with complex dependence structure

    KAUST Repository

    Staicu, Ana-Maria

    2015-01-01

    We propose an L (2)-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups-clusters or subjects-units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment.

  13. Deep inelastic structure functions in the chiral bag model

    Energy Technology Data Exchange (ETDEWEB)

    Sanjose, V. (Valencia Univ. (Spain). Dept. de Didactica de las Ciencias Experimentales); Vento, V. (Valencia Univ. (Spain). Dept. de Fisica Teorica; Centro Mixto CSIC/Valencia Univ., Valencia (Spain). Inst. de Fisica Corpuscular)

    1989-10-02

    We calculate the structure functions for deep inelastic scattering on baryons in the cavity approximation to the chiral bag model. The behavior of these structure functions is analyzed in the Bjorken limit. We conclude that scaling is satisfied, but not Regge behavior. A trivial extension as a parton model can be achieved by introducing the structure function for the pion in a convolution picture. In this extended version of the model not only scaling but also Regge behavior is satisfied. Conclusions are drawn from the comparison of our results with experimental data. (orig.).

  14. A structural biology perspective on NMDA receptor pharmacology and function.

    Science.gov (United States)

    Regan, Michael C; Romero-Hernandez, Annabel; Furukawa, Hiro

    2015-08-01

    N-methyld-aspartate receptors (NMDARs) belong to the large family of ionotropic glutamate receptors (iGluRs), which are critically involved in basic brain functions as well as multiple neurological diseases and disorders. The NMDARs are large heterotetrameric membrane protein complexes. The extensive extracellular domains recognize neurotransmitter ligands and allosteric compounds and translate the binding information to regulate activity of the transmembrane ion channel. Here, we review recent advances in the structural biology of NMDARs with a focus on pharmacology and function. Structural analysis of the isolated extracellular domains in combination with the intact heterotetrameric NMDAR structure provides important insights into how this sophisticated ligand-gated ion channel may function.

  15. Functional substitution of coordination polyhedron in crystal structure of silicates

    Institute of Scientific and Technical Information of China (English)

    叶大年; 马哲生; 赫伟; 李哲; 施倪承; D.Pushcharovsky

    2002-01-01

    On the bases of the study of comparative crystal chemistry of silicates it has been concluded that the octahedra and square pyramids of Ti-0 and Zr-O play functional role of tetrahedra of Si-O in the construction of crystal structures. Therefore, those silicates may be named titano-and zircono-silicates. Because of the functional similarity of coordination polyhedra, the structures of cristobalite and feldspar have been compared with those of perovskite and garnet, respectively. As a new concept, the functional replacement of tetrahedra by octahedra and/or pyramids is defined by the authors of this paper for favorable comparison of relative crystal structures.

  16. Cellular regulation of the structure and function of aortic valves

    Directory of Open Access Journals (Sweden)

    Ismail El-Hamamsy

    2010-01-01

    Full Text Available The aortic valve was long considered a passive structure that opens and closes in response to changes in transvalvular pressure. Recent evidence suggests that the aortic valve performs highly sophisticated functions as a result of its unique microscopic structure. These functions allow it to adapt to its hemodynamic and mechanical environment. Understanding the cellular and molecular mechanisms involved in normal valve physiology is essential to elucidate the mechanisms behind valve disease. We here review the structure and developmental biology of aortic valves; we examine the role of its cellular parts in regulating its function and describe potential pathophysiological and clinical implications.

  17. MODY - calculation of ordered structures by symmetry-adapted functions

    Science.gov (United States)

    Białas, Franciszek; Pytlik, Lucjan; Sikora, Wiesława

    2016-01-01

    In this paper we focus on the new version of computer program MODY for calculations of symmetryadapted functions based on the theory of groups and representations. The choice of such a functional frame of coordinates for description of ordered structures leads to a minimal number of parameters which must be used for presentation of such structures and investigations of their properties. The aim of this work is to find those parameters, which are coefficients of a linear combination of calculated functions, leading to construction of different types of structure ordering with a given symmetry. A spreadsheet script for simplification of this work has been created and attached to the program.

  18. Structure-function relationship in novel polyphenolics

    Science.gov (United States)

    Banerjee, Sukanta

    The synthesis, properties and applications of hydroxyaromatic polymers, synthesized enzymatically in AOT/Water/Isooctane water-in-oil microemulsion is the subject of this dissertation. The enzymatic polymerization in such microstructured media furnishes the final polymer product with the unusual morphology of interconnected microspheres. Fundamental characterization of the nature of interaction of a model polymer, poly(4-ethylphenol), with the surfactant AOT, as well as various solvents was carried out to elucidate the molecular mechanism of the morphology development. From an applied perspective, presynthesized poly(4-ethylphenol) was precipitated using AOT/Water/Isooctane water-in-oil microemulsion as the non-solvent to give spherical microparticles. Of specific interest was the encapsulation of macromolecules and nanoparticles initially solubilized in the water droplets by the precipitating polymer matrix. This technique was utilized to synthesize catalytically active and superparamagnetic microspheres, containing entrapped enzyme and nanoparticulate ferrites, respectively. The enzymatically synthesized polymers possess a fully aromatic backbone and hence are expected to have unique pi conjugated structure. On the basis of this hypothesis several conjugated luminescent polymers were synthesized using 2-naphthol and 2,6-dihydroxynaphthalene as the starting monomer. Chemical tuning of the emission properties of these polymers were achieved by copolymerization with 4-ethylphenol which is not a luminescent molecule. Addition of 2,6-dihydroxynaphthalene in dry reversed micellar solutions of AOT induced a dramatic phase transition to a clear luminescent organogel. Hydrogen bonding interaction between the hydroxyl groups and the head group of AOT form the basis of such gels. The microstructure of the gel was probed using NMR and FTIR spectroscopy. Finally, thiol group containing polymers were synthesized to bind nanoparticulate CdS, forming novel photoresponsive

  19. Factor structure of functional state of primary school age children

    Directory of Open Access Journals (Sweden)

    Davidenko O.V.

    2011-02-01

    Full Text Available The examination of primary school children to determine the ranking of significant factors that determine the structure of their functional state depending on the level of physical health. It is shown that the main factor in the structure of the functional state of younger schoolchildren in low-and lower-middle level of physical fitness is selected morpho-functional status, which characterizes the functions of the body at rest. For children with average or above average level of physical fitness is a leading factor in physical fitness of schoolchildren.

  20. Extinction order and altered community structure rapidly disrupt ecosystem functioning.

    Science.gov (United States)

    Larsen, Trond H; Williams, Neal M; Kremen, Claire

    2005-05-01

    By causing extinctions and altering community structure, anthropogenic disturbances can disrupt processes that maintain ecosystem integrity. However, the relationship between community structure and ecosystem functioning in natural systems is poorly understood. Here we show that habitat loss appeared to disrupt ecosystem functioning by affecting extinction order, species richness and abundance. We studied pollination by bees in a mosaic of agricultural and natural habitats in California and dung burial by dung beetles on recently created islands in Venezuela. We found that large-bodied bee and beetle species tended to be both most extinction-prone and most functionally efficient, contributing to rapid functional loss. Simulations confirmed that extinction order led to greater disruption of function than predicted by random species loss. Total abundance declined with richness and also appeared to contribute to loss of function. We demonstrate conceptually and empirically how the non-random response of communities to disturbance can have unexpectedly large functional consequences.

  1. Towards a calculus of biomolecular complexes at equilibrium.

    Science.gov (United States)

    Mjolsness, Eric

    2007-07-01

    An overview is presented of the construction and use of algebraic partition functions to represent the equilibrium statistical mechanics of multimolecular complexes and their action within a larger regulatory network. Unlike many applications of equilibrium statistical mechanics, multimolecular complexes may operate with various subsets of their components present and connected to the others, the rest remaining in solution. Thus they are variable-structure systems. This aspect of their behavior may be accounted for by the use of 'fugacity' variables as a representation within the partition functions. Four principles are proposed by which the combinatorics of molecular complex construction can be reflected in the construction of their partition functions. The corresponding algebraic operations on partition functions are multiplication, addition, function composition and a less commonly used operation called contraction. Each has a natural interpretation in terms of probability distributions on multimolecular structures. Possible generalizations to nonequilibrium statistical mechanics are briefly discussed.

  2. Functional oxide structures on a surface of metals and alloys

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ The investigations of the plasma electrolytic processes in our laboratory are aimed to the development of conditions of formation of oxide layers with determined composition, structure and functional properties on the surface of valve metals (Al, Ti) and their alloys.

  3. Squark Contributions to Photon Structure Functions and Positivity Constraints

    CERN Document Server

    Kitadono, Yoshio; Uematsu, Tsuneo; Yoshida, Yutaka

    2011-01-01

    Photon structure functions in supersymmetric QCD are investigated in terms of the parton model where squark contributions are evaluated. We calculate the eight virtual photon structure functions by taking the discontinuity of the squark massive one-loop diagrams of the photon-photon forward amplitude. The model-independent positivity constraints derived from the Cauchy-Schwarz inequalities are satisfied by the squark parton model calculation and actually the two equality relations hold for the squark contribution. We also show that our polarized photon structure function $g_1^\\gamma$ for the real photon leads to the vanishing 1st moment sum rule, and the constraint $|g_1^\\gamma|\\leq F_1^\\gamma$ is satisfied by the real photon. We also discuss a squark signature in the structure function $W_{TT}^\\tau$.

  4. The nonsinglet structure function evolution by Laplace method

    Energy Technology Data Exchange (ETDEWEB)

    Boroun, G. R., E-mail: grboroun@gmail.com, E-mail: boroun@razi.ac.ir; Zarrin, S. [Razi University, Physics Department (Iran, Islamic Republic of)

    2015-12-15

    We derive a general scheme for the evolution of the nonsinglet structure function at the leadingorder (LO) and next-to-leading-order (NLO) by using the Laplace-transform technique. Results for the nonsinglet structure function are compared with MSTW2008, GRV, and CKMT parameterizations and also EMC experimental data in the LO and NLO analysis. The results are in good agreement with the experimental data and other parameterizations in the low- and large-x regions.

  5. Simulation of Parallel Logical Operations with Biomolecular Computing

    Directory of Open Access Journals (Sweden)

    Mahnaz Kadkhoda

    2008-01-01

    Full Text Available Biomolecular computing is the computational method that uses the potential of DNA as a parallel computing device. DNA computing can be used to solve NP-complete problems. An appropriate application of DNA computation is large-scale evaluation of parallel computation models such as Boolean Circuits. In this study, we present a molecular-based algorithm for evaluation of Nand-based Boolean Circuits. The contribution of this paper is that the proposed algorithm has been implemented using only three molecular operations and the number of passes in each level is decreased to less than half of previously addressed in the literature. Thus, the proposed algorithm is much easier to implement in the laboratory.

  6. Biomolecular Network-Based Synergistic Drug Combination Discovery

    Directory of Open Access Journals (Sweden)

    Xiangyi Li

    2016-01-01

    Full Text Available Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

  7. Biomolecular decision-making process for self assembly.

    Energy Technology Data Exchange (ETDEWEB)

    Osbourn, Gordon Cecil

    2005-01-01

    The brain is often identified with decision-making processes in the biological world. In fact, single cells, single macromolecules (proteins) and populations of molecules also make simple decisions. These decision processes are essential to survival and to the biological self-assembly and self-repair processes that we seek to emulate. How do these tiny systems make effective decisions? How do they make decisions in concert with a cooperative network of other molecules or cells? How can we emulate the decision-making behaviors of small-scale biological systems to program and self-assemble microsystems? This LDRD supported research to answer these questions. Our work included modeling and simulation of protein populations to help us understand, mimic, and categorize molecular decision-making mechanisms that nonequilibrium systems can exhibit. This work is an early step towards mimicking such nanoscale and microscale biomolecular decision-making processes in inorganic systems.

  8. Design and implementation of a biomolecular concentration tracker.

    Science.gov (United States)

    Hsiao, Victoria; de los Santos, Emmanuel L C; Whitaker, Weston R; Dueber, John E; Murray, Richard M

    2015-02-20

    As a field, synthetic biology strives to engineer increasingly complex artificial systems in living cells. Active feedback in closed loop systems offers a dynamic and adaptive way to ensure constant relative activity independent of intrinsic and extrinsic noise. In this work, we use synthetic protein scaffolds as a modular and tunable mechanism for concentration tracking through negative feedback. Input to the circuit initiates scaffold production, leading to colocalization of a two-component system and resulting in the production of an inhibitory antiscaffold protein. Using a combination of modeling and experimental work, we show that the biomolecular concentration tracker circuit achieves dynamic protein concentration tracking in Escherichia coli and that steady state outputs can be tuned.

  9. Ion irradiation and biomolecular radiation damage II. Indirect effect

    CERN Document Server

    Wang, Wei; Su, Wenhui

    2010-01-01

    It has been reported that damage of genome in a living cell by ionizing radiation is about one-third direct and two-thirds indirect. The former which has been introduced in our last paper, concerns direct energy deposition and ionizing reactions in the biomolecules; the latter results from radiation induced reactive species (mainly radicals) in the medium (mainly water) surrounding the biomolecules. In this review, a short description of ion implantation induced radical formation in water is presented. Then we summarize the aqueous radical reaction chemistry of DNA, protein and their components, followed by a brief introduction of biomolecular damage induced by secondary particles (ions and electron). Some downstream biological effects are also discussed.

  10. Current-mode analog nonlinear function synthesizer structures

    CERN Document Server

    Popa, Cosmin Radu

    2013-01-01

    This book is dedicated to the analysis and design of analog CMOS nonlinear function synthesizer structures, based on original superior-order approximation functions. A variety of analog function synthesizer structures are discussed, based on accurate approximation functions.  Readers will be enabled to implement numerous circuit functions with applications in analog signal processing, including exponential, Gaussian or hyperbolic functions. Generalizing the methods for obtaining these particular functions, the author analyzes superior-order approximation functions, which represent the core for developing CMOS analog nonlinear function synthesizers.   ·         Describes novel methods for generating a multitude of circuit functions, based on superior-order improved accuracy approximation functions; ·         Presents techniques for analog function synthesizers that can be applied easily to a wide variety of analog signal processing circuits; ·         Enables the design of analog s...

  11. Target selection and determination of function in structural genomics.

    Science.gov (United States)

    Watson, James D; Todd, Annabel E; Bray, James; Laskowski, Roman A; Edwards, Aled; Joachimiak, Andrzej; Orengo, Christine A; Thornton, Janet M

    2003-01-01

    The first crucial step in any structural genomics project is the selection and prioritization of target proteins for structure determination. There may be a number of selection criteria to be satisfied, including that the proteins have novel folds, that they be representatives of large families for which no structure is known, and so on. The better the selection at this stage, the greater is the value of the structures obtained at the end of the experimental process. This value can be further enhanced once the protein structures have been solved if the functions of the given proteins can also be determined. Here we describe the methods used at either end of the experimental process: firstly, sensitive sequence comparison techniques for selecting a high-quality list of target proteins, and secondly the various computational methods that can be applied to the eventual 3D structures to determine the most likely biochemical function of the proteins in question.

  12. Automatic structures and growth functions for finitely generated abelian groups

    CERN Document Server

    Kamei, Satoshi

    2011-01-01

    In this paper, we consider the formal power series whose n-th coefficient is the number of copies of a given finite graph in the ball of radius n centred at the identity element in the Cayley graph of a finitely generated group and call it the growth function. Epstein, Iano-Fletcher and Uri Zwick proved that the growth function is a rational function if the group has a geodesic automatic structure. We compute the growth function in the case where the group is abelian and see that the denominator of the rational function is determined from the rank of the group.

  13. Tactile Teaching: Exploring Protein Structure/Function Using Physical Models

    Science.gov (United States)

    Herman, Tim; Morris, Jennifer; Colton, Shannon; Batiza, Ann; Patrick, Michael; Franzen, Margaret; Goodsell, David S.

    2006-01-01

    The technology now exists to construct physical models of proteins based on atomic coordinates of solved structures. We review here our recent experiences in using physical models to teach concepts of protein structure and function at both the high school and the undergraduate levels. At the high school level, physical models are used in a…

  14. Network-level structure-function relationships in human neocortex

    NARCIS (Netherlands)

    Miŝic, Bratislav; Betzel, Richard F.; De Reus, Marcel A.; Van Den Heuvel, Martijn P.; Berman, Marc G.; McIntosh, Anthony R.; Sporns, Olaf

    2016-01-01

    The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional netw

  15. Using computational models to relate structural and functional brain connectivity.

    Science.gov (United States)

    Hlinka, Jaroslav; Coombes, Stephen

    2012-07-01

    Modern imaging methods allow a non-invasive assessment of both structural and functional brain connectivity. This has lead to the identification of disease-related alterations affecting functional connectivity. The mechanism of how such alterations in functional connectivity arise in a structured network of interacting neural populations is as yet poorly understood. Here we use a modeling approach to explore the way in which this can arise and to highlight the important role that local population dynamics can have in shaping emergent spatial functional connectivity patterns. The local dynamics for a neural population is taken to be of the Wilson-Cowan type, whilst the structural connectivity patterns used, describing long-range anatomical connections, cover both realistic scenarios (from the CoComac database) and idealized ones that allow for more detailed theoretical study. We have calculated graph-theoretic measures of functional network topology from numerical simulations of model networks. The effect of the form of local dynamics on the observed network state is quantified by examining the correlation between structural and functional connectivity. We document a profound and systematic dependence of the simulated functional connectivity patterns on the parameters controlling the dynamics. Importantly, we show that a weakly coupled oscillator theory explaining these correlations and their variation across parameter space can be developed. This theoretical development provides a novel way to characterize the mechanisms for the breakdown of functional connectivity in diseases through changes in local dynamics.

  16. The ING family tumor suppressors: from structure to function.

    Science.gov (United States)

    Aguissa-Touré, Almass-Houd; Wong, Ronald P C; Li, Gang

    2011-01-01

    The Inhibitor of Growth (ING) proteins belong to a well-conserved family which presents in diverse organisms with several structural and functional domains for each protein. The ING family members are found in association with many cellular processes. Thus, the ING family proteins are involved in regulation of gene transcription, DNA repair, tumorigenesis, apoptosis, cellular senescence and cell cycle arrest. The ING proteins have multiple domains that are potentially capable of binding to many partners. It is conceivable, therefore, that such proteins could function similarly within protein complexes. In this case, within this family, each function could be attributed to a specific domain. However, the role of ING domains is not definitively clear. In this review, we summarize recent advances in structure-function relationships in ING proteins. For each domain, we describe the known biological functions and the approaches utilized to identify the functions associated with ING proteins.

  17. Computing the partition function for kinetically trapped RNA secondary structures.

    Directory of Open Access Journals (Sweden)

    William A Lorenz

    Full Text Available An RNA secondary structure is locally optimal if there is no lower energy structure that can be obtained by the addition or removal of a single base pair, where energy is defined according to the widely accepted Turner nearest neighbor model. Locally optimal structures form kinetic traps, since any evolution away from a locally optimal structure must involve energetically unfavorable folding steps. Here, we present a novel, efficient algorithm to compute the partition function over all locally optimal secondary structures of a given RNA sequence. Our software, RNAlocopt runs in O(n3 time and O(n2 space. Additionally, RNAlocopt samples a user-specified number of structures from the Boltzmann subensemble of all locally optimal structures. We apply RNAlocopt to show that (1 the number of locally optimal structures is far fewer than the total number of structures--indeed, the number of locally optimal structures approximately equal to the square root of the number of all structures, (2 the structural diversity of this subensemble may be either similar to or quite different from the structural diversity of the entire Boltzmann ensemble, a situation that depends on the type of input RNA, (3 the (modified maximum expected accuracy structure, computed by taking into account base pairing frequencies of locally optimal structures, is a more accurate prediction of the native structure than other current thermodynamics-based methods. The software RNAlocopt constitutes a technical breakthrough in our study of the folding landscape for RNA secondary structures. For the first time, locally optimal structures (kinetic traps in the Turner energy model can be rapidly generated for long RNA sequences, previously impossible with methods that involved exhaustive enumeration. Use of locally optimal structure leads to state-of-the-art secondary structure prediction, as benchmarked against methods involving the computation of minimum free energy and of maximum expected

  18. [Function of surface membrane structures in Thiobacillus thiooxidans].

    Science.gov (United States)

    Pivovarova, T A; Karavaĭko, G I

    1975-01-01

    The function of the surface membrane structures was studied with cytochemical techniques on ultrathin sections of Thiobacillus thiooxidans. The transport of elementary sulphur inside the cell involves the surface membrane structures, while oxidation of the sulphur to sulphuric acid takes place on the outer surface of the cytoplasmic membrane. The surface membrane structures are supposed also to participate in the primary dissolution of elementary sulphur at the site of contact of the cells with the mineral.

  19. Spin Structure Functions in a Covariant Spectator Quark Model

    Energy Technology Data Exchange (ETDEWEB)

    G. Ramalho, Franz Gross and M. T. Peña

    2010-12-01

    We apply the covariant spectator quark–diquark model, already probed in the description of the nucleon elastic form factors, to the calculation of the deep inelastic scattering (DIS) spin-independent and spin-dependent structure functions of the nucleon. The nucleon wave function is given by a combination of quark–diquark orbital states, corresponding to S, D and P-waves. A simple form for the quark distribution function associated to the P and D waves is tested.

  20. SARA: a server for function annotation of RNA structures.

    Science.gov (United States)

    Capriotti, Emidio; Marti-Renom, Marc A

    2009-07-01

    Recent interest in non-coding RNA transcripts has resulted in a rapid increase of deposited RNA structures in the Protein Data Bank. However, a characterization and functional classification of the RNA structure and function space have only been partially addressed. Here, we introduce the SARA program for pair-wise alignment of RNA structures as a web server for structure-based RNA function assignment. The SARA server relies on the SARA program, which aligns two RNA structures based on a unit-vector root-mean-square approach. The likely accuracy of the SARA alignments is assessed by three different P-values estimating the statistical significance of the sequence, secondary structure and tertiary structure identity scores, respectively. Our benchmarks, which relied on a set of 419 RNA structures with known SCOR structural class, indicate that at a negative logarithm of mean P-value higher or equal than 2.5, SARA can assign the correct or a similar SCOR class to 81.4% and 95.3% of the benchmark set, respectively. The SARA server is freely accessible via the World Wide Web at http://sgu.bioinfo.cipf.es/services/SARA/.

  1. Extensions of PDZ domains as important structural and functional elements

    OpenAIRE

    Wang, Conan K.; Pan, Lifeng; Chen, Jia; Zhang, Mingjie

    2010-01-01

    ‘Divide and conquer’ has been the guiding strategy for the study of protein structure and function. Proteins are divided into domains with each domain having a canonical structural definition depending on its type. In this review, we push forward with the interesting observation that many domains have regions outside of their canonical definition that affect their structure and function; we call these regions ‘extensions’. We focus on the highly abundant PDZ (PSD-95, DLG1 and ZO-1) domain. Us...

  2. Matrix Transfer Function Design for Flexible Structures: An Application

    Science.gov (United States)

    Brennan, T. J.; Compito, A. V.; Doran, A. L.; Gustafson, C. L.; Wong, C. L.

    1985-01-01

    The application of matrix transfer function design techniques to the problem of disturbance rejection on a flexible space structure is demonstrated. The design approach is based on parameterizing a class of stabilizing compensators for the plant and formulating the design specifications as a constrained minimization problem in terms of these parameters. The solution yields a matrix transfer function representation of the compensator. A state space realization of the compensator is constructed to investigate performance and stability on the nominal and perturbed models. The application is made to the ACOSSA (Active Control of Space Structures) optical structure.

  3. Proceedings Fourth Workshop on Mathematically Structured Functional Programming

    CERN Document Server

    Chapman, James; 10.4204/EPTCS.76

    2012-01-01

    This volume contains the proceedings of the Fourth Workshop on Mathematically Structured Functional Programming (MSFP 2012), taking place on 25 March, 2012 in Tallinn, Estonia, as a satellite event of the European Joint Conferences on Theory and Practice of Software, ETAPS 2012. MSFP is devoted to the derivation of functionality from structure. It highlights concepts from algebra, semantics and type theory as they are increasingly reflected in programming practice, especially functional programming. The workshop consists of two invited presentations and eight contributed papers on a range of topics at that interface.

  4. Structure and function of the skeletal muscle extracellular matrix.

    Science.gov (United States)

    Gillies, Allison R; Lieber, Richard L

    2011-09-01

    The skeletal muscle extracellular matrix (ECM) plays an important role in muscle fiber force transmission, maintenance, and repair. In both injured and diseased states, ECM adapts dramatically, a property that has clinical manifestations and alters muscle function. Here we review the structure, composition, and mechanical properties of skeletal muscle ECM; describe the cells that contribute to the maintenance of the ECM; and, finally, overview changes that occur with pathology. New scanning electron micrographs of ECM structure are also presented with hypotheses about ECM structure–function relationships. Detailed structure–function relationships of the ECM have yet to be defined and, as a result, we propose areas for future study.

  5. Rational Design of a Structural and Functional Nitric Oxide Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Yeung, N.; Lin, Y; Gao, Y; Zhao, X; Russell, B; Lei, L; Miner, L; Robinson, H; Lu, Y

    2009-01-01

    Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally, it is more difficult to design functional proteins. In comparison to recent successes in designing non-metalloproteins, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem FeB centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.

  6. Electron crystallography for structural and functional studies of membrane proteins.

    Science.gov (United States)

    Fujiyoshi, Yoshinori

    2011-01-01

    Membrane proteins are important research targets for basic biological sciences and drug design, but studies of their structure and function are considered difficult to perform. Studies of membrane structures have been greatly facilitated by technological and instrumental advancements in electron microscopy together with methodological advancements in biology. Electron crystallography is especially useful in studying the structure and function of membrane proteins. Electron crystallography is now an established method of analyzing the structures of membrane proteins in lipid bilayers, which resembles their natural biological environment. To better understand the neural system function from a structural point of view, we developed the cryo-electron microscope with a helium-cooled specimen stage, which allows for analysis of the structures of membrane proteins at a resolution higher than 3 Å. This review introduces recent instrumental advances in cryo-electron microscopy and presents some examples of structure analyses of membrane proteins, such as bacteriorhodopsin, water channels and gap junction channels. This review has two objectives: first, to provide a personal historical background to describe how we came to develop the cryo-electron microscope and second, to discuss some of the technology required for the structural analysis of membrane proteins based on cryo-electron microscopy.

  7. Molecular Structures and Functional Relationships in Clostridial Neurotoxins

    Energy Technology Data Exchange (ETDEWEB)

    Swaminathan S.

    2011-12-01

    The seven serotypes of Clostridium botulinum neurotoxins (A-G) are the deadliest poison known to humans. They share significant sequence homology and hence possess similar structure-function relationships. Botulinum neurotoxins (BoNT) act via a four-step mechanism, viz., binding and internalization to neuronal cells, translocation of the catalytic domain into the cytosol and finally cleavage of one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) causing blockage of neurotransmitter release leading to flaccid paralysis. Crystal structures of three holotoxins, BoNT/A, B and E, are available to date. Although the individual domains are remarkably similar, their domain organization is different. These structures have helped in correlating the structural and functional domains. This has led to the determination of structures of individual domains and combinations of them. Crystal structures of catalytic domains of all serotypes and several binding domains are now available. The catalytic domains are zinc endopeptidases and share significant sequence and structural homology. The active site architecture and the catalytic mechanism are similar although the binding mode of individual substrates may be different, dictating substrate specificity and peptide cleavage selectivity. Crystal structures of catalytic domains with substrate peptides provide clues to specificity and selectivity unique to BoNTs. Crystal structures of the receptor domain in complex with ganglioside or the protein receptor have provided information about the binding of botulinum neurotoxin to the neuronal cell. An overview of the structure-function relationship correlating the 3D structures with biochemical and biophysical data and how they can be used for structure-based drug discovery is presented here.

  8. High-Throughput, Protein-Targeted Biomolecular Detection Using Frequency-Domain Faraday Rotation Spectroscopy.

    Science.gov (United States)

    Murdock, Richard J; Putnam, Shawn A; Das, Soumen; Gupta, Ankur; Chase, Elyse D Z; Seal, Sudipta

    2017-01-16

    A clinically relevant magneto-optical technique (fd-FRS, frequency-domain Faraday rotation spectroscopy) for characterizing proteins using antibody-functionalized magnetic nanoparticles (MNPs) is demonstrated. This technique distinguishes between the Faraday rotation of the solvent, iron oxide core, and functionalization layers of polyethylene glycol polymers (spacer) and model antibody-antigen complexes (anti-BSA/BSA, bovine serum albumin). A detection sensitivity of ≈10 pg mL(-1) and broad detection range of 10 pg mL(-1) ≲ cBSA ≲ 100 µg mL(-1) are observed. Combining this technique with predictive analyte binding models quantifies (within an order of magnitude) the number of active binding sites on functionalized MNPs. Comparative enzyme-linked immunosorbent assay (ELISA) studies are conducted, reproducing the manufacturer advertised BSA ELISA detection limits from 1 ng mL(-1) ≲ cBSA ≲ 500 ng mL(-1) . In addition to the increased sensitivity, broader detection range, and similar specificity, fd-FRS can be conducted in less than ≈30 min, compared to ≈4 h with ELISA. Thus, fd-FRS is shown to be a sensitive optical technique with potential to become an efficient diagnostic in the chemical and biomolecular sciences.

  9. Differential geometry-based solvation and electrolyte transport models for biomolecular modeling: a review

    OpenAIRE

    Wei, Guo Wei; Baker, Nathan A.

    2014-01-01

    This chapter reviews the differential geometry-based solvation and electrolyte transport for biomolecular solvation that have been developed over the past decade. A key component of these methods is the differential geometry of surfaces theory, as applied to the solvent-solute boundary. In these approaches, the solvent-solute boundary is determined by a variational principle that determines the major physical observables of interest, for example, biomolecular surface area, enclosed volume, el...

  10. Differential Effects of Brain Disorders on Structural and Functional Connectivity

    Science.gov (United States)

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2017-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate. PMID:28119556

  11. The structure function as a metric for roughness and figure

    Science.gov (United States)

    Parks, Robert E.; Tuell, Michael T.

    2016-09-01

    As optical designs become more sophisticated and incorporate aspheric and free form surfaces, the need to specify limits on mid-spatial frequency manufacturing errors becomes more critical, particularly as we better understand the effects of these errors on image quality. While there already exist methods based on Fourier analysis to specify these errors in most commercial interferometry software, the method of calculation and the power spectral density (PSD) results remain obscure to many in the optical design and manufacturing field. We suggest that the structure functions (SF) contains the same information as in the Fourier based PSD but in a way that is much more transparent to analysis, interpretation and application as a specification. The units of measure are more familiar and the concept behind the analysis is simpler to understand. Further, the information contained in the structure function (or PSD) allows a complete specification of an optical surface from the finest measurable detail of roughness to the overall figure. We discuss the origin of the structure function in the field of astronomy to describe the effects of air turbulence on image quality, the simple mathematical definition of the structure function and its easy means of calculation and how its results should be scaled depending on the location of the optical surface in a system from pupil to image plane. Finally, we give an example of how to write a specification of an optical surface using the structure function.

  12. Generating function approach to reliability analysis of structural systems

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The generating function approach is an important tool for performance assessment in multi-state systems. Aiming at strength reliability analysis of structural systems, generating function approach is introduced and developed. Static reliability models of statically determinate, indeterminate systems and fatigue reliability models are built by constructing special generating functions, which are used to describe probability distributions of strength (resistance), stress (load) and fatigue life, by defining composite operators of generating functions and performance structure functions thereof. When composition operators are executed, computational costs can be reduced by a big margin by means of collecting like terms. The results of theoretical analysis and numerical simulation show that the generating function approach can be widely used for probability modeling of large complex systems with hierarchical structures due to the unified form, compact expression, computer program realizability and high universality. Because the new method considers twin loads giving rise to component failure dependency, it can provide a theoretical reference and act as a powerful tool for static, dynamic reliability analysis in civil engineering structures and mechanical equipment systems with multi-mode damage coupling.

  13. Process-Structure-Function Relations of Pectin in Food.

    Science.gov (United States)

    Christiaens, Stefanie; Van Buggenhout, Sandy; Houben, Ken; Jamsazzadeh Kermani, Zahra; Moelants, Katlijn R N; Ngouémazong, Eugénie D; Van Loey, Ann; Hendrickx, Marc E G

    2016-01-01

    Pectin, a complex polysaccharide rich in galacturonic acid, has been identified as a critical structural component of plant cell walls. The functionality of this intricate macromolecule in fruit- and vegetable-based-derived products and ingredients is strongly determined by the nanostructure of its most abundant polymer, homogalacturonan. During food processing, pectic homogalacturonan is susceptible to various enzymatic as well as nonenzymatic conversion reactions modifying its structural and, hence, its functional properties. Consequently, a profound understanding of the various process-structure-function relations of pectin aids food scientists to tailor the functional properties of plant-based derived products and ingredients. This review describes the current knowledge on process-structure-function relations of pectin in foods with special focus on pectin's functionality with regard to textural attributes of solid plant-based foods and rheological properties of particulated fruit- and vegetable-derived products. In this context, both pectin research performed via traditional, ex situ physicochemical analyses of fractionated walls and isolated polymers and pectin investigation through in situ pectin localization are considered.

  14. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili

    2011-11-01

    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  15. Adaptation of brain functional and structural networks in aging.

    Science.gov (United States)

    Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2015-01-01

    The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  16. Adaptation of brain functional and structural networks in aging.

    Directory of Open Access Journals (Sweden)

    Annie Lee

    Full Text Available The human brain, especially the prefrontal cortex (PFC, is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI, and high angular resolution diffusion imaging (HARDI, and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

  17. Nanomechanical force transducers for biomolecular and intracellular measurements: is there room to shrink and why do it?

    Science.gov (United States)

    Sirbuly, Donald J; Friddle, Raymond W; Villanueva, Joshua; Huang, Qian

    2015-02-01

    Over the past couple of decades there has been a tremendous amount of progress on the development of ultrasensitive nanomechanical instruments, which has enabled scientists to peer for the first time into the mechanical world of biomolecular systems. Currently, work-horse instruments such as the atomic force microscope and optical/magnetic tweezers have provided the resolution necessary to extract quantitative force data from various molecular systems down to the femtonewton range, but it remains difficult to access the intracellular environment with these analytical tools as they have fairly large sizes and complicated feedback systems. This review is focused on highlighting some of the major milestones and discoveries in the field of biomolecular mechanics that have been made possible by the development of advanced atomic force microscope and tweezer techniques as well as on introducing emerging state-of-the-art nanomechanical force transducers that are addressing the size limitations presented by these standard tools. We will first briefly cover the basic setup and operation of these instruments, and then focus heavily on summarizing advances in in vitro force studies at both the molecular and cellular level. The last part of this review will include strategies for shrinking down the size of force transducers and provide insight into why this may be important for gaining a more complete understanding of cellular activity and function.

  18. Functional substitution of coordination polyhedron in crystal structure of silicates

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    On the bases of the study of comparative crystal chemistry of silicates it has been concluded that the octahedra and square pyramids of Ti-O and Zr-O play functional role of tetrahedra of Si-O in the construction of crystal structures.Therefore,those silicates may be named titano- and zircono-silicates.Because of the functional similarity of coordination polyhedra,the structures of cristobalite and feldspar have been compared with those of perovskite and garnet,respectively.As a new concept,the functional replacement of tetrahedra by octahedra and/or pyramids is defined by the authors of this paper for favorable comparison of relative crystal structures.

  19. Emerging approaches to probing ion channel structure and function

    Institute of Scientific and Technical Information of China (English)

    Wei-Guang Li; Tian-Le Xu

    2012-01-01

    Ion channels,as membrane proteins,are the sensors of the cell.They act as the first line of communication with the world beyond the plasma membrane and transduce changes in the external and internal environments into unique electrical signals to shape the responses of excitable cells.Because of their importance in cellular communication,ion channels have been intensively studied at the structural and functional levels.Here,we summarize the diverse approaches,including molecular and cellular,chemical,optical,biophysical,and computational,used to probe the structural and functional rearrangements that occur during channel activation (or sensitization),inactivation (or desensitization),and various forms of modulation.The emerging insights into the structure and function of ion channels by multidisciplinary approaches allow the development of new pharmacotherapies as well as new tools useful in controlling cellular activity.

  20. Performance analysis, quality function deployment and structured methods

    Science.gov (United States)

    Maier, M. W.

    Quality function deployment, (QFD), an approach to synthesizing several elements of system modeling and design into a single unit, is presented. Behavioral, physical, and performance modeling are usually considered as separate aspects of system design without explicit linkages. Structured methodologies have developed linkages between behavioral and physical models before, but have not considered the integration of performance models. QFD integrates performance models with traditional structured models. In this method, performance requirements such as cost, weight, and detection range are partitioned into matrices. Partitioning is done by developing a performance model, preferably quantitative, for each requirement. The parameters of the model become the engineering objectives in a QFD analysis and the models are embedded in a spreadsheet version of the traditional QFD matrices. The performance model and its parameters are used to derive part of the functional model by recognizing that a given performance model implies some structure to the functionality of the system.

  1. New insights into plastid nucleoid structure and functionality.

    Science.gov (United States)

    Krupinska, Karin; Melonek, Joanna; Krause, Kirsten

    2013-03-01

    Investigations over many decades have revealed that nucleoids of higher plant plastids are highly dynamic with regard to their number, their structural organization and protein composition. Membrane attachment and environmental cues seem to determine the activity and functionality of the nucleoids and point to a highly regulated structure-function relationship. The heterogeneous composition and the many functions that are seemingly associated with the plastid nucleoids could be related to the high number of chromosomes per plastid. Recent proteomic studies have brought novel nucleoid-associated proteins into the spotlight and indicated that plastid nucleoids are an evolutionary hybrid possessing prokaryotic nucleoid features and eukaryotic (nuclear) chromatin components, several of which are dually targeted to the nucleus and chloroplasts. Future studies need to unravel if and how plastid-nucleus communication depends on nucleoid structure and plastid gene expression.

  2. Intercepts of the non-singlet structure functions

    CERN Document Server

    Ermolaev, B I; Troyan, S I

    2001-01-01

    Infrared evolution equations for small-$x$ behaviour of the non-singlet structure functions $f_1^{NS}$ and $g_1^{NS}$ are obtained and solved in the next-to-leading approximation, to all orders in $\\alpha_s$, and including running $\\alpha_s$ effects. The intercepts of these structure functions, i.e. the exponents of the power-like small-$x$ behaviour, are calculated. A detailed comparison with the leading logarithmic approximation (LLA) and DGLAP is made. We explain why the LLA predictions for the small-$x$ dependence of the structure functions may be more reliable than the prediction for the $Q^2$ dependence in the range of $Q^2$ explored at HERA.

  3. Deuteron Spin Structure Functions at Small Bjorken-x

    CERN Document Server

    Edelmann, J; Weise, W

    1998-01-01

    We investigate polarized deuteron structure functions at small values of the Bjorken variable, x < 0.1. In this region contributions from the coherent interaction of diffractively excited hadronic states with both nucleons become important. A proper treatment of this process requires an extension of the Glauber-Gribov multiple scattering theory to include spin degrees of freedom. In the kinematic domain of current fixed target experiments we observe that shadowing effects in g_1^d are approximately a factor 2-3 larger than for the unpolarized structure function F_2^d. Furthermore the tensor structure function b_1 is found to be surprisingly large at x < 0.1 due to coherent double scattering contributions.

  4. Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

    Science.gov (United States)

    Chirvi, Sajal

    Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi

  5. Unified approach to partition functions of RNA secondary structures.

    Science.gov (United States)

    Bundschuh, Ralf

    2014-11-01

    RNA secondary structure formation is a field of considerable biological interest as well as a model system for understanding generic properties of heteropolymer folding. This system is particularly attractive because the partition function and thus all thermodynamic properties of RNA secondary structure ensembles can be calculated numerically in polynomial time for arbitrary sequences and homopolymer models admit analytical solutions. Such solutions for many different aspects of the combinatorics of RNA secondary structure formation share the property that the final solution depends on differences of statistical weights rather than on the weights alone. Here, we present a unified approach to a large class of problems in the field of RNA secondary structure formation. We prove a generic theorem for the calculation of RNA folding partition functions. Then, we show that this approach can be applied to the study of the molten-native transition, denaturation of RNA molecules, as well as to studies of the glass phase of random RNA sequences.

  6. Optimizing an emperical scoring function for transmembrane protein structure determination.

    Energy Technology Data Exchange (ETDEWEB)

    Young, Malin M.; Sale, Kenneth L.; Gray, Genetha Anne; Kolda, Tamara Gibson

    2003-10-01

    We examine the problem of transmembrane protein structure determination. Like many other questions that arise in biological research, this problem cannot be addressed by traditional laboratory experimentation alone. An approach that integrates experiment and computation is required. We investigate a procedure which states the transmembrane protein structure determination problem as a bound constrained optimization problem using a special empirical scoring function, called Bundler, as the objective function. In this paper, we describe the optimization problem and some of its mathematical properties. We compare and contrast results obtained using two different derivative free optimization algorithms.

  7. Functional and Structural Brain Changes Associated with Methamphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Bruce R. Russell

    2012-10-01

    Full Text Available Methamphetamine (MA is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET and functional and structural magnetic resonance imaging (MRI. The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

  8. A measurement of the photon structure function F sub 2

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, T.; Ishi, Y.; Miyano, K.; Miyata, H. (Niigata Univ. (Japan)); Yamagishi, Y.; Tanaka, R.; Kojima, T.; Matsumoto, S.; Yasuda, T. (Chuo Univ., Tokyo (Japan)); Kirk, P.; Lim, J.; McNeil, R.R.; Metcalf, W.; Myung, S.S. (Louisiana State Univ., Baton Rouge (USA)); Cheng, C.P.; Gu, P.; Ye, M.H.; Zhu, Y.C. (Academia Sinica, Beijing (China). Inst. of High Energy Physics); Abashian, A.; Gotow, K.; Hu, K.P.; Lai, A.Z.; Low, E.H.; Mattson, M.E.; Piilonen, L.; Sterner, K.L. (Virginia Polytechnic Inst. and State Univ., Blacksburg (USA)); Li, Y.K.; Lusin, S.; Rosenfeld, C.; Wang, A.T.M.; Wilson, S. (South Carolina Univ., Columbia (USA)); Frautschi, M.; Kagan, H.; Kass, R. (Ohio State Univ., Columbus (USA)); Breedon, R.E.; Kim, G.N. (California Univ., Davis (USA) National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan)); Ko, W.; Lander, R.L.; Maeshima, K.; Malchow, R.L.; Rowe, J.; Smith, J.R.; Stuart, D. (California Univ., Davis (USA)); Abe, K.; Fujii, Y.; Higashi, Y.; Kim, S.K.; AMY Collaboration

    1990-12-20

    The photon structure function F{sub 2} has been measured at average Q{sup 2} values of 73, 160 and 390 (GeV/c){sup 2}. We compare the x dependence of the Q{sup 2}=73(GeV/c){sup 2} data with thereotical expectations based on QCD. In addition we present results on the Q{sup 2} evolution of the structure function for the intermediate x range (0.3{le}x{le}0.8). The results are consistent with QCD. (orig.).

  9. [Structure and function of arbuscular mycorrhiza: a review].

    Science.gov (United States)

    Tian, Mi; Chen, Ying-long; Li, Min; Liu, Run-jin

    2013-08-01

    Arbuscular mycorrhiza (AM) is one of the most widely distributed and the most important mutualistic symbionts in terrestrial ecosystems, playing a significant role in enhancing plant resistance to stresses, remediating polluted environments, and maintaining ecosystem stabilization and sustainable productivity. The structural characteristics of AM are the main indicators determining the mycorrhizal formation in root system, and have close relations to the mycorrhizal functions. This paper summarized the structural characteristics of arbuscules, vesicles, mycelia and invasion points of AM, and analyzed the relationships between the Arum (A) type arbuscules, Paris (P) type arbuscules, vesicles, and external mycelia and their functions in improving plant nutrient acquisition and growth, enhancing plant resistance to drought, waterlogging, salinity, high temperature, diseases, heavy metals toxicity, and promoting toxic organic substances decomposition and polluted and degraded soil remediation. The factors affecting the AM structure and functions as well as the action mechanisms of mycorrhizal functions were also discussed. This review would provide a basis for the systemic study of AM structural characteristics and functional mechanisms and for evaluating and screening efficient AM fungal species.

  10. Correlation function as a measure of the structure

    OpenAIRE

    Buryak, O.; Doroshkevich, A.

    1995-01-01

    Geometrical model of structure of the universe is examined to obtain analytical expression for the two points nonlinear correlation function. According to the model the objects (galaxies) are concentrated into two types of structure elements - filaments and sheets. We considered the filaments ( similar to galaxy filaments ) simply as straight lines and the sheets ( similar to superclusters of galaxies ) simply as planes. The homogeneously distributed objects are also taken into consideration....

  11. Density functional theory study on the molecular structure of loganin

    OpenAIRE

    Pandey, Anoop Kumar; Siddiqui, Shamoon Ahmad; Dwivedi, Apoorva; Raj, Kanwal; Misra, Neeraj

    2011-01-01

    The computational Quantum Chemistry (QC) has been used for different types of problems, for example: structural biology, surface phenomena and liquid phase. In this paper we have employed the density functional method for the study of molecular structure of loganin. The equilibrium geometry, harmonic vibrational frequencies and infrared intensities were calculated by B3LYP/6-311G (d, p) method and basis set combinations. It was found that the optimized parameters obtained by the DFT/B3LYP met...

  12. Structure-Function Relationships in Semiconducting Polymers for Organic Photovoltaics

    OpenAIRE

    Kavulak, David Fredric Joel

    2010-01-01

    The major body of this work investigates how the chemical structure of conjugated polymers relates to the fundamental operating mechanism of organic photovoltaic devices. New conjugated polymers were characterized and their optical and electronic properties tested and correlated with their power conversion efficiencies as the active layer in polymer solar cells. From these experiments general structure/function relationships are drawn with an eye toward developing universal guidelines for con...

  13. Silicon Photodetectors Matrix Coordinate Bipolar Functionally Integrated Structures

    Directory of Open Access Journals (Sweden)

    V.N. Murashev

    2015-03-01

    Full Text Available In this paper a new approach for solving the detection and coordinate the detection of radiation in the optical range of 0.3-1.1 microns, based on the use of so-called bipolar functionally integrated structures (BI-FIS in pixels photodetector arrays is discussed. Variants of new technical solutions based on photo-detectors matrix pixel BI-FIS structures are shown. Their effectiveness and scope are evaluated.

  14. Computational Recipe for Efficient Description of Large-Scale Conformational Changes in Biomolecular Systems.

    Science.gov (United States)

    Moradi, Mahmoud; Tajkhorshid, Emad

    2014-07-01

    Characterizing large-scale structural transitions in biomolecular systems poses major technical challenges to both experimental and computational approaches. On the computational side, efficient sampling of the configuration space along the transition pathway remains the most daunting challenge. Recognizing this issue, we introduce a knowledge-based computational approach toward describing large-scale conformational transitions using (i) nonequilibrium, driven simulations combined with work measurements and (ii) free energy calculations using empirically optimized biasing protocols. The first part is based on designing mechanistically relevant, system-specific reaction coordinates whose usefulness and applicability in inducing the transition of interest are examined using knowledge-based, qualitative assessments along with nonequilirbrium work measurements which provide an empirical framework for optimizing the biasing protocol. The second part employs the optimized biasing protocol resulting from the first part to initiate free energy calculations and characterize the transition quantitatively. Using a biasing protocol fine-tuned to a particular transition not only improves the accuracy of the resulting free energies but also speeds up the convergence. The efficiency of the sampling will be assessed by employing dimensionality reduction techniques to help detect possible flaws and provide potential improvements in the design of the biasing protocol. Structural transition of a membrane transporter will be used as an example to illustrate the workings of the proposed approach.

  15. The structure and function of bacterial light-harvesting complexes.

    Science.gov (United States)

    Law, Christopher J; Roszak, Aleksander W; Southall, June; Gardiner, Alastair T; Isaacs, Neil W; Cogdell, Richard J

    2004-01-01

    The harvesting of solar radiation by purple photosynthetic bacteria is achieved by circular, integral membrane pigment-protein complexes. There are two main types of light-harvesting complex, termed LH2 and LH1, that function to absorb light energy and to transfer that energy rapidly and efficiently to the photochemical reaction centres where it is trapped. This mini-review describes our present understanding of the structure and function of the purple bacterial light-harvesting complexes.

  16. A no extensive statistical model for the nucleon structure function

    Science.gov (United States)

    Trevisan, Luis A.; Mirez, Carlos

    2013-03-01

    We studied an application of nonextensive thermodynamics to describe the structure function of nucleon, in a model where the usual Fermi-Dirac and Bose-Einstein energy distribution were replaced by the equivalent functions of the q-statistical. The parameters of the model are given by an effective temperature T, the q parameter (from Tsallis statistics), and two chemical potentials given by the corresponding up (u) and down (d) quark normalization in the nucleon.

  17. Quantitative Analysis of the Effective Functional Structure in Yeast Glycolysis

    Science.gov (United States)

    De la Fuente, Ildefonso M.; Cortes, Jesus M.

    2012-01-01

    The understanding of the effective functionality that governs the enzymatic self-organized processes in cellular conditions is a crucial topic in the post-genomic era. In recent studies, Transfer Entropy has been proposed as a rigorous, robust and self-consistent method for the causal quantification of the functional information flow among nonlinear processes. Here, in order to quantify the functional connectivity for the glycolytic enzymes in dissipative conditions we have analyzed different catalytic patterns using the technique of Transfer Entropy. The data were obtained by means of a yeast glycolytic model formed by three delay differential equations where the enzymatic rate equations of the irreversible stages have been explicitly considered. These enzymatic activity functions were previously modeled and tested experimentally by other different groups. The results show the emergence of a new kind of dynamical functional structure, characterized by changing connectivity flows and a metabolic invariant that constrains the activity of the irreversible enzymes. In addition to the classical topological structure characterized by the specific location of enzymes, substrates, products and feedback-regulatory metabolites, an effective functional structure emerges in the modeled glycolytic system, which is dynamical and characterized by notable variations of the functional interactions. The dynamical structure also exhibits a metabolic invariant which constrains the functional attributes of the enzymes. Finally, in accordance with the classical biochemical studies, our numerical analysis reveals in a quantitative manner that the enzyme phosphofructokinase is the key-core of the metabolic system, behaving for all conditions as the main source of the effective causal flows in yeast glycolysis. PMID:22393350

  18. EM vs Weak Structure Functions in DIS processes

    CERN Document Server

    Athar, M Sajjad; Simo, I Ruiz; Vacas, M J Vicente

    2013-01-01

    We obatin the ratio $F_i^A/F_i^{D}$(i=2,3, A=Be, C, Fe, Pb; D=Deuteron) in the case of weak and electromagnetic nuclear structure functions. For this, relativistic nuclear spectral function which incorporate the effects of Fermi motion, binding and nucleon correlations is used. We also consider the pion and rho meson cloud contributions and shadowing and antishadowing effects.

  19. Determination of the pion and kaon structure functions

    Energy Technology Data Exchange (ETDEWEB)

    Aitkenhead, W.; Barton, D.S.; Brandenburg, G.W.; Busza, W.; Dobrowolski, T.; Friedman, J.I.; Kendall, H.W.; Lyons, T.; Nelson, B.; Rosenson, L.; Toy, W.; Verdier, R.; Votta, L.; Chiaradia, M.T.; DeMarzo, C.; Favuzzi, C.; Germinario, G.; Guerriero, L.; LaVopa, P.; Maggi, G.; Posa, F.; Selvaggi, G.; Spinelli, P.; Waldner, F.; Brenner, A.E.; Carey, D.C.; Elias, J.E.; Garbincius, P.H.; Mikenberg, G.; Polychronakos, V.A.; Meunier, R.; Cutts, D.; Dulude, R.S.; Lanou, R.E. Jr.; Massimo, J.T.

    1980-07-21

    Quark structure functions have been extracted from low-p/sub T/ inclusive hadron production data for the pion and kaon with use of the recombination model. n/sup ..pi../=1.0 +- 0.1 and n/sup K/=2.5 +- 0.6 is obtained, where n is the leading (1-x) power of the nonstrange--valence-quark distribution. Both the pion and kaon nonstrange--sea-quark functions have napprox. =3.5.

  20. Study on Dielectric Function Models for Surface Plasmon Resonance Structure

    Directory of Open Access Journals (Sweden)

    Peyman Jahanshahi

    2014-01-01

    Full Text Available The most common permittivity function models are compared and identifying the best model for further studies is desired. For this study, simulations using several different models and an analytical analysis on a practical surface Plasmon structure were done with an accuracy of ∼94.4% with respect to experimental data. Finite element method, combined with dielectric properties extracted from the Brendel-Bormann function model, was utilized, the latter being chosen from a comparative study on four available models.

  1. The impact of structural and functional parameters in glaucoma patients on patient-reported visual functioning.

    Directory of Open Access Journals (Sweden)

    Christoph Hirneiß

    Full Text Available BACKGROUND: To evaluate the impact of structural changes of the retinal nerve fiber layer (RNFL, and visual field loss, on functional impairment assessed by patient-reported visual functioning in glaucoma. METHODS: Patients with glaucomatous optic nerve damage were enrolled in this cross-sectional study. Peripapillary RNFL thickness was obtained with spectral-domain optical coherence tomography (SD-OCT. Function was assessed by patient-reported visual functioning using the Rasch-calibrated Glaucoma Activity Limitation 9 (GAL-9 questionnaire and standard automated perimetry. The impact of peripapillary RNFL loss on functional impairment was analyzed with correlation and linear regression analyses. RESULTS: A total of 176 eyes from 88 glaucoma patients were included. The SD-OCT assessed temporal-superior and temporal-inferior RNFL sector of the worse eye revealed significant correlation with the GAL-9 scores (r=-0.298, p=0.011 and r=-0.251, p=0.033, respectively. In mutivariate regression analysis, the best predictors for patient-reported visual functioning were visual acuity of the better eye and mean defect of the worse eye (R(2=0.334, while structural parameters could not enhance the prediction of GAL-9 scores. CONCLUSIONS: Self-reported visual functioning of patients with glaucoma is better predicted by visual performance data than structural parameters. However, some structural changes of the worse eye are significantly correlated with patient-reported visual functioning.

  2. The impact of structural and functional characteristics of social relations as determinants of functional decline

    DEFF Research Database (Denmark)

    Avlund, Kirsten; Lund, Rikke; Holstein, Bjørn E;

    2004-01-01

    pattern (n = 565); and third, mortality (n = 651). Social relations were measured at baseline by several items focusing on the structure and function of the social network. RESULTS: In men, no weekly telephone contact was related to functional decline and mortality. Among women, less than weekly telephone...

  3. A coarse-grained model for the simulations of biomolecular interactions in cellular environments

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao, E-mail: yinghao.wu@einstein.yu.edu [Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)

    2014-02-07

    The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments.

  4. A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis Regulation.

    Science.gov (United States)

    Wu, Songlin; Wang, Pei; Xiao, Chen; Li, Zheng; Yang, Bing; Fu, Jieyang; Chen, Jing; Wan, Neng; Ma, Cong; Li, Maoteng; Yang, Xiangliang; Zhan, Yi

    2016-08-10

    Physiological processes such as metabolism, cell apoptosis and immune responses, must be strictly regulated to maintain their homeostasis and achieve their normal physiological functions. The speed with which bio-molecular homeostatic regulation occurs directly determines the ability of an organism to adapt to conditional changes. To produce a quick-responsive regulatory system that can be easily utilized for various types of homeostasis, a device called nano-fingers that facilitates the regulation of physiological processes was constructed using DNA origami nanotechnology. This nano-fingers device functioned in linked open and closed phases using two types of DNA tweezers, which were covalently coupled with aptamers that captured specific molecules when the tweezer arms were sufficiently close. Via this specific interaction mechanism, certain physiological processes could be simultaneously regulated from two directions by capturing one biofactor and releasing the other to enhance the regulatory capacity of the device. To validate the universal application of this device, regulation of the homeostasis of the blood coagulant thrombin was attempted using the nano-fingers device. It was successfully demonstrated that this nano-fingers device achieved coagulation buffering upon the input of fuel DNA. This nano-device could also be utilized to regulate the homeostasis of other types of bio-molecules.

  5. AFMPB: An adaptive fast multipole Poisson-Boltzmann solver for calculating electrostatics in biomolecular systems

    Science.gov (United States)

    Lu, Benzhuo; Cheng, Xiaolin; Huang, Jingfang; McCammon, J. Andrew

    2013-11-01

    A Fortran program package is introduced for rapid evaluation of the electrostatic potentials and forces in biomolecular systems modeled by the linearized Poisson-Boltzmann equation. The numerical solver utilizes a well-conditioned boundary integral equation (BIE) formulation, a node-patch discretization scheme, a Krylov subspace iterative solver package with reverse communication protocols, and an adaptive new version of the fast multipole method in which the exponential expansions are used to diagonalize the multipole-to-local translations. The program and its full description, as well as several closely related libraries and utility tools are available at http://lsec.cc.ac.cn/~lubz/afmpb.html and a mirror site at http://mccammon.ucsd.edu/. This paper is a brief summary of the program: the algorithms, the implementation and the usage. Restrictions: Only three or six significant digits options are provided in this version. Unusual features: Most of the codes are in Fortran77 style. Memory allocation functions from Fortran90 and above are used in a few subroutines. Additional comments: The current version of the codes is designed and written for single core/processor desktop machines. Check http://lsec.cc.ac.cn/lubz/afmpb.html for updates and changes. Running time: The running time varies with the number of discretized elements (N) in the system and their distributions. In most cases, it scales linearly as a function of N.

  6. Linking community size structure and ecosystem functioning using metabolic theory.

    Science.gov (United States)

    Yvon-Durocher, Gabriel; Allen, Andrew P

    2012-11-05

    Understanding how biogeochemical cycles relate to the structure of ecological communities is a central research question in ecology. Here we approach this problem by focusing on body size, which is an easily measured species trait that has a pervasive influence on multiple aspects of community structure and ecosystem functioning. We test the predictions of a model derived from metabolic theory using data on ecosystem metabolism and community size structure. These data were collected as part of an aquatic mesocosm experiment that was designed to simulate future environmental warming. Our analyses demonstrate significant linkages between community size structure and ecosystem functioning, and the effects of warming on these links. Specifically, we show that carbon fluxes were significantly influenced by seasonal variation in temperature, and yielded activation energies remarkably similar to those predicted based on the temperature dependencies of individual-level photosynthesis and respiration. We also show that community size structure significantly influenced fluxes of ecosystem respiration and gross primary production, particularly at the annual time-scale. Assessing size structure and the factors that control it, both empirically and theoretically, therefore promises to aid in understanding links between individual organisms and biogeochemical cycles, and in predicting the responses of key ecosystem functions to future environmental change.

  7. Molecular modeling of mechanosensory ion channel structural and functional features.

    Science.gov (United States)

    Gessmann, Renate; Kourtis, Nikos; Petratos, Kyriacos; Tavernarakis, Nektarios

    2010-09-16

    The DEG/ENaC (Degenerin/Epithelial Sodium Channel) protein family comprises related ion channel subunits from all metazoans, including humans. Members of this protein family play roles in several important biological processes such as transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Several blocks of amino acid sequence are conserved in DEG/ENaC proteins, but structure/function relations in this channel class are poorly understood. Given the considerable experimental limitations associated with the crystallization of integral membrane proteins, knowledge-based modeling is often the only route towards obtaining reliable structural information. To gain insight into the structural characteristics of DEG/ENaC ion channels, we derived three-dimensional models of MEC-4 and UNC-8, based on the available crystal structures of ASIC1 (Acid Sensing Ion Channel 1). MEC-4 and UNC-8 are two DEG/ENaC family members involved in mechanosensation and proprioception respectively, in the nematode Caenorhabditis elegans. We used these models to examine the structural effects of specific mutations that alter channel function in vivo. The trimeric MEC-4 model provides insight into the mechanism by which gain-of-function mutations cause structural alterations that result in increased channel permeability, which trigger cell degeneration. Our analysis provides an introductory framework to further investigate the multimeric organization of the DEG/ENaC ion channel complex.

  8. Molecular modeling of mechanosensory ion channel structural and functional features.

    Directory of Open Access Journals (Sweden)

    Renate Gessmann

    Full Text Available The DEG/ENaC (Degenerin/Epithelial Sodium Channel protein family comprises related ion channel subunits from all metazoans, including humans. Members of this protein family play roles in several important biological processes such as transduction of mechanical stimuli, sodium re-absorption and blood pressure regulation. Several blocks of amino acid sequence are conserved in DEG/ENaC proteins, but structure/function relations in this channel class are poorly understood. Given the considerable experimental limitations associated with the crystallization of integral membrane proteins, knowledge-based modeling is often the only route towards obtaining reliable structural information. To gain insight into the structural characteristics of DEG/ENaC ion channels, we derived three-dimensional models of MEC-4 and UNC-8, based on the available crystal structures of ASIC1 (Acid Sensing Ion Channel 1. MEC-4 and UNC-8 are two DEG/ENaC family members involved in mechanosensation and proprioception respectively, in the nematode Caenorhabditis elegans. We used these models to examine the structural effects of specific mutations that alter channel function in vivo. The trimeric MEC-4 model provides insight into the mechanism by which gain-of-function mutations cause structural alterations that result in increased channel permeability, which trigger cell degeneration. Our analysis provides an introductory framework to further investigate the multimeric organization of the DEG/ENaC ion channel complex.

  9. Soil-borne microbial functional structure across different land uses.

    Science.gov (United States)

    Kuramae, Eiko E; Zhou, Jizhong Z; Kowalchuk, George A; van Veen, Johannes A

    2014-01-01

    Land use change alters the structure and composition of microbial communities. However, the links between environmental factors and microbial functions are not well understood. Here we interrogated the functional structure of soil microbial communities across different land uses. In a multivariate regression tree analysis of soil physicochemical properties and genes detected by functional microarrays, the main factor that explained the different microbial community functional structures was C : N ratio. C : N ratio showed a significant positive correlation with clay and soil pH. Fields with low C : N ratio had an overrepresentation of genes for carbon degradation, carbon fixation, metal reductase, and organic remediation categories, while fields with high C : N ratio had an overrepresentation of genes encoding dissimilatory sulfate reductase, methane oxidation, nitrification, and nitrogen fixation. The most abundant genes related to carbon degradation comprised bacterial and fungal cellulases; bacterial and fungal chitinases; fungal laccases; and bacterial, fungal, and oomycete polygalacturonases. The high number of genes related to organic remediation was probably driven by high phosphate content, while the high number of genes for nitrification was probably explained by high total nitrogen content. The functional gene diversity found in different soils did not group the sites accordingly to land management. Rather, the soil factors, C : N ratio, phosphate, and total N, were the main factors driving the differences in functional genes across the fields examined.

  10. Osteoblast functions in functionally graded Ti-6Al-4 V mesh structures.

    Science.gov (United States)

    Nune, K C; Kumar, A; Misra, R D K; Li, S J; Hao, Y L; Yang, R

    2016-03-01

    We describe here the combined efforts of engineering and biological sciences as a systemic approach to fundamentally elucidate osteoblast functions in functionally graded Ti-6Al-4 V mesh structures in relation to uniform/monolithic mesh arrays. First, the interconnecting porous architecture of functionally graded mesh arrays was conducive to cellular functions including attachment, proliferation, and mineralization. The underlying reason is that the graded fabricated structure with cells seeded from the large pore size side provided a channel for efficient transfer of nutrients to other end of the structure (small pore size), leading to the generation of mineralized extracellular matrix by differentiating pre-osteoblasts. Second, a comparative and parametric study indicated that gradient mesh structure had a pronounced effect on cell adhesion and mineralization, and strongly influenced the proliferation phase. High intensity and near-uniform distribution of proteins (actin and vinculin) on struts of the gradient mesh structure (cells seeded from large pore side) implied signal transduction during cell adhesion and was responsible for superior cellular activity, in comparison to the uniform mesh structure and non-porous titanium alloy. Cells adhered to the mesh struts by forming a sheet, bridging the pores through numerous cytoplasmic extensions, in the case of porous mesh structures. Intercellular interaction in porous structures provided a pathway for cells to communicate and mature to a differentiated phenotype. Furthermore, the capability of cells to migrate through the interconnecting porous architecture on mesh structures led to colonization of the entire structure. Cells were embedded layer-by-layer in the extracellular matrix as the matrix mineralized. The outcomes of the study are expected to address challenges associated with the treatment of segmental bone defects and bone-remodeling through favorable modulation of cellular response. Moreover, the study

  11. Lung morphometry: the link between structure and function.

    Science.gov (United States)

    Weibel, Ewald R

    2017-03-01

    The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.

  12. Forecasting Urban Forest Ecosystem Structure, Function, and Vulnerability

    Science.gov (United States)

    Steenberg, James W. N.; Millward, Andrew A.; Nowak, David J.; Robinson, Pamela J.; Ellis, Alexis

    2017-03-01

    The benefits derived from urban forest ecosystems are garnering increasing attention in ecological research and municipal planning. However, because of their location in heterogeneous and highly-altered urban landscapes, urban forests are vulnerable and commonly suffer disproportionate and varying levels of stress and disturbance. The objective of this study is to assess and analyze the spatial and temporal changes, and potential vulnerability, of the urban forest resource in Toronto, Canada. This research was conducted using a spatially-explicit, indicator-based assessment of vulnerability and i-Tree Forecast modeling of temporal changes in forest structure and function. Nine scenarios were simulated for 45 years and model output was analyzed at the ecosystem and municipal scale. Substantial mismatches in ecological processes between spatial scales were found, which can translate into unanticipated loss of function and social inequities if not accounted for in planning and management. At the municipal scale, the effects of Asian longhorned beetle and ice storm disturbance were far less influential on structure and function than changes in management actions. The strategic goals of removing invasive species and increasing tree planting resulted in a decline in carbon storage and leaf biomass. Introducing vulnerability parameters in the modeling increased the spatial heterogeneity in structure and function while expanding the disparities of resident access to ecosystem services. There was often a variable and uncertain relationship between vulnerability and ecosystem structure and function. Vulnerability assessment and analysis can provide strategic planning initiatives with valuable insight into the processes of structural and functional change resulting from management intervention.

  13. Structure and function of large-scale brain systems.

    Science.gov (United States)

    Koziol, Leonard F; Barker, Lauren A; Joyce, Arthur W; Hrin, Skip

    2014-01-01

    This article introduces the functional neuroanatomy of large-scale brain systems. Both the structure and functions of these brain networks are presented. All human behavior is the result of interactions within and between these brain systems. This system of brain function completely changes our understanding of how cognition and behavior are organized within the brain, replacing the traditional lesion model. Understanding behavior within the context of brain network interactions has profound implications for modifying abstract constructs such as attention, learning, and memory. These constructs also must be understood within the framework of a paradigm shift, which emphasizes ongoing interactions within a dynamically changing environment.

  14. Structure and regulatory function of plant transcription factors

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The expression of inducible genes in plants is regulated byspecific transcription factors at the transcriptional level. A typical transcription factor usually contains a DNA-binding domain, a transcription regulation domain, a dimerization site and a nuclear localization domain. These functional domains define the characteristic, localization and regulatory role of a transcription factor. Transcription factors recognize and bind to specific cis-acting elements or interact with other proteins, and then activate or repress the transcription of target genes by their functional domains. In recent years, elucidation on the structure and function of transcription factors has become an important subject in plant molecular biology.

  15. Protein mechanics: a route from structure to function

    Indian Academy of Sciences (India)

    Richard Lavery; Sophie Sacquin-Mora

    2007-08-01

    In order to better understand the mechanical properties of proteins, we have developed simulation tools which enable these properties to be analysed on a residue-by-residue basis. Although these calculations are relatively expensive with all-atom protein models, good results can be obtained much faster using coarse-grained approaches. The results show that proteins are surprisingly heterogeneous from a mechanical point of view and that functionally important residues often exhibit unusual mechanical behaviour. This finding offers a novel means for detecting functional sites and also potentially provides a route for understanding the links between structure and function in more general terms.

  16. Improved protein structure selection using decoy-dependent discriminatory functions

    Directory of Open Access Journals (Sweden)

    Levitt Michael

    2004-06-01

    Full Text Available Abstract Background A key component in protein structure prediction is a scoring or discriminatory function that can distinguish near-native conformations from misfolded ones. Various types of scoring functions have been developed to accomplish this goal, but their performance is not adequate to solve the structure selection problem. In addition, there is poor correlation between the scores and the accuracy of the generated conformations. Results We present a simple and nonparametric formula to estimate the accuracy of predicted conformations (or decoys. This scoring function, called the density score function, evaluates decoy conformations by performing an all-against-all Cα RMSD (Root Mean Square Deviation calculation in a given decoy set. We tested the density score function on 83 decoy sets grouped by their generation methods (4state_reduced, fisa, fisa_casp3, lmds, lattice_ssfit, semfold and Rosetta. The density scores have correlations as high as 0.9 with the Cα RMSDs of the decoy conformations, measured relative to the experimental conformation for each decoy. We previously developed a residue-specific all-atom probability discriminatory function (RAPDF, which compiles statistics from a database of experimentally determined conformations, to aid in structure selection. Here, we present a decoy-dependent discriminatory function called self-RAPDF, where we compiled the atom-atom contact probabilities from all the conformations in a decoy set instead of using an ensemble of native conformations, with a weighting scheme based on the density scores. The self-RAPDF has a higher correlation with Cα RMSD than RAPDF for 76/83 decoy sets, and selects better near-native conformations for 62/83 decoy sets. Self-RAPDF may be useful not only for selecting near-native conformations from decoy sets, but also for fold simulations and protein structure refinement. Conclusions Both the density score and the self-RAPDF functions are decoy

  17. [Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Implications for pathology].

    Science.gov (United States)

    Viertler, C; Zatloukal, K

    2008-11-01

    High quality human biological samples (e.g. blood, tissue or DNA) with associated, well documented clinical and research data are key resources for advancement of life sciences, biotechnology, clinical medicine, drug development and also molecular pathology. Millions of samples of diseased tissues have been collected in the context of routine histopathological diagnosis and are stored in the archives of hospitals and institutes of pathology. A concerted effort is necessary to overcome the current fragmentation of the European biobanking community in order to tap the full research potential of existing biobanks. A pan-European research infrastructure for biobanking and biomolecular resources (BBMRI) is currently in its planning phase. The mission is to link and provide access to local biobanks of different formats, including tissue collections, harmonize standards, establish operational procedures which properly consider ethical, legal, societal aspects, and to secure sustainable funding. Pathology plays a key role in development and administration of tissue banks and is, thus, a major partner for collaboration, expertise and construction of this pan-European research infrastructure.

  18. Biomolecular Evidence of Silk from 8,500 Years Ago.

    Science.gov (United States)

    Gong, Yuxuan; Li, Li; Gong, Decai; Yin, Hao; Zhang, Juzhong

    2016-01-01

    Pottery, bone implements, and stone tools are routinely found at Neolithic sites. However, the integrity of textiles or silk is susceptible to degradation, and it is therefore very difficult for such materials to be preserved for 8,000 years. Although previous studies have provided important evidence of the emergence of weaving skills and tools, such as figuline spinning wheels and osseous lamellas with traces of filament winding, there is a lack of direct evidence proving the existence of silk. In this paper, we explored evidence of prehistoric silk fibroin through the analysis of soil samples collected from three tombs at the Neolithic site of Jiahu. Mass spectrometry was employed and integrated with proteomics to characterize the key peptides of silk fibroin. The direct biomolecular evidence reported here showed the existence of prehistoric silk fibroin, which was found in 8,500-year-old tombs. Rough weaving tools and bone needles were also excavated, indicating the possibility that the Jiahu residents may possess the basic weaving and sewing skills in making textile. This finding may advance the study of the history of silk, and the civilization of the Neolithic Age.

  19. Label-free screening of bio-molecular interactions.

    Science.gov (United States)

    Cooper, Matthew A

    2003-11-01

    The majority of techniques currently employed to interrogate a biomolecular interaction require some type of radio- or enzymatic- or fluorescent-labelling to report the binding event. However, there is an increasing awareness of novel techniques that do not require labelling of the ligand or the receptor, and that allow virtually any complex to be screened with minimal assay development. This review focuses on three major label-free screening platforms: surface plasmon resonance biosensors, acoustic biosensors, and calorimetric biosensors. Scientists in both academia and industry are using biosensors in areas that encompass almost all areas drug discovery, diagnostics, and the life sciences. The capabilities and advantages of each technique are compared and key applications involving small molecules, proteins, oligonucleotides, bacteriophage, viruses, bacteria, and cells are reviewed. The role of the interface between the biosensor surface (in the case of SPR and acoustic biosensors) and the chemical or biological systems to be studied is also covered with attention to the covalent and non-covalent coupling chemistries commonly employed.

  20. Stochastic Simulation of Biomolecular Networks in Dynamic Environments.

    Directory of Open Access Journals (Sweden)

    Margaritis Voliotis

    2016-06-01

    Full Text Available Simulation of biomolecular networks is now indispensable for studying biological systems, from small reaction networks to large ensembles of cells. Here we present a novel approach for stochastic simulation of networks embedded in the dynamic environment of the cell and its surroundings. We thus sample trajectories of the stochastic process described by the chemical master equation with time-varying propensities. A comparative analysis shows that existing approaches can either fail dramatically, or else can impose impractical computational burdens due to numerical integration of reaction propensities, especially when cell ensembles are studied. Here we introduce the Extrande method which, given a simulated time course of dynamic network inputs, provides a conditionally exact and several orders-of-magnitude faster simulation solution. The new approach makes it feasible to demonstrate-using decision-making by a large population of quorum sensing bacteria-that robustness to fluctuations from upstream signaling places strong constraints on the design of networks determining cell fate. Our approach has the potential to significantly advance both understanding of molecular systems biology and design of synthetic circuits.

  1. Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions.

    Science.gov (United States)

    Seidel, Susanne A I; Dijkman, Patricia M; Lea, Wendy A; van den Bogaart, Geert; Jerabek-Willemsen, Moran; Lazic, Ana; Joseph, Jeremiah S; Srinivasan, Prakash; Baaske, Philipp; Simeonov, Anton; Katritch, Ilia; Melo, Fernando A; Ladbury, John E; Schreiber, Gideon; Watts, Anthony; Braun, Dieter; Duhr, Stefan

    2013-03-01

    Microscale thermophoresis (MST) allows for quantitative analysis of protein interactions in free solution and with low sample consumption. The technique is based on thermophoresis, the directed motion of molecules in temperature gradients. Thermophoresis is highly sensitive to all types of binding-induced changes of molecular properties, be it in size, charge, hydration shell or conformation. In an all-optical approach, an infrared laser is used for local heating, and molecule mobility in the temperature gradient is analyzed via fluorescence. In standard MST one binding partner is fluorescently labeled. However, MST can also be performed label-free by exploiting intrinsic protein UV-fluorescence. Despite the high molecular weight ratio, the interaction of small molecules and peptides with proteins is readily accessible by MST. Furthermore, MST assays are highly adaptable to fit to the diverse requirements of different biomolecules, such as membrane proteins to be stabilized in solution. The type of buffer and additives can be chosen freely. Measuring is even possible in complex bioliquids like cell lysate allowing close to in vivo conditions without sample purification. Binding modes that are quantifiable via MST include dimerization, cooperativity and competition. Thus, its flexibility in assay design qualifies MST for analysis of biomolecular interactions in complex experimental settings, which we herein demonstrate by addressing typically challenging types of binding events from various fields of life science.

  2. The fidelity of dynamic signaling by noisy biomolecular networks.

    Directory of Open Access Journals (Sweden)

    Clive G Bowsher

    Full Text Available Cells live in changing, dynamic environments. To understand cellular decision-making, we must therefore understand how fluctuating inputs are processed by noisy biomolecular networks. Here we present a general methodology for analyzing the fidelity with which different statistics of a fluctuating input are represented, or encoded, in the output of a signaling system over time. We identify two orthogonal sources of error that corrupt perfect representation of the signal: dynamical error, which occurs when the network responds on average to other features of the input trajectory as well as to the signal of interest, and mechanistic error, which occurs because biochemical reactions comprising the signaling mechanism are stochastic. Trade-offs between these two errors can determine the system's fidelity. By developing mathematical approaches to derive dynamics conditional on input trajectories we can show, for example, that increased biochemical noise (mechanistic error can improve fidelity and that both negative and positive feedback degrade fidelity, for standard models of genetic autoregulation. For a group of cells, the fidelity of the collective output exceeds that of an individual cell and negative feedback then typically becomes beneficial. We can also predict the dynamic signal for which a given system has highest fidelity and, conversely, how to modify the network design to maximize fidelity for a given dynamic signal. Our approach is general, has applications to both systems and synthetic biology, and will help underpin studies of cellular behavior in natural, dynamic environments.

  3. A fast mollified impulse method for biomolecular atomistic simulations

    Science.gov (United States)

    Fath, L.; Hochbruck, M.; Singh, C. V.

    2017-03-01

    Classical integration methods for molecular dynamics are inherently limited due to resonance phenomena occurring at certain time-step sizes. The mollified impulse method can partially avoid this problem by using appropriate filters based on averaging or projection techniques. However, existing filters are computationally expensive and tedious in implementation since they require either analytical Hessians or they need to solve nonlinear systems from constraints. In this work we follow a different approach based on corotation for the construction of a new filter for (flexible) biomolecular simulations. The main advantages of the proposed filter are its excellent stability properties and ease of implementation in standard softwares without Hessians or solving constraint systems. By simulating multiple realistic examples such as peptide, protein, ice equilibrium and ice-ice friction, the new filter is shown to speed up the computations of long-range interactions by approximately 20%. The proposed filtered integrators allow step sizes as large as 10 fs while keeping the energy drift less than 1% on a 50 ps simulation.

  4. Twist decomposition of Drell-Yan structure functions: phenomenological implications

    Science.gov (United States)

    Brzemiński, Dawid; Motyka, Leszek; Sadzikowski, Mariusz; Stebel, Tomasz

    2017-01-01

    The forward Drell-Yan process in pp scattering at the LHC at √{S} = 14 TeV is considered. We analyze the Drell-Yan structure functions assuming the dominance of a Compton-like emission of a virtual photon from a fast quark scattering off the small x gluons. The color dipole framework is applied to perform quantitatively the twist decomposition of all the Drell-Yan structure functions. Two models of the color dipole scattering are applied: the Golec-Biernat-Wüsthoff model and the dipole cross section obtained from the Balitsky-Fadin-Kuraev-Lipatov evolution equation. The two models have essentially different higher twist content and the gluon transverse momentum distribution and lead to different significant effects beyond the collinear leading twist description. It is found that the gluon transverse momentum effects are significant in the Drell-Yan structure functions for all Drell-Yan pair masses M, and the higher twist effects become important for M ≲ 10GeV. It is found that the structure function W TT related to the A 2 angular coefficient and the Lam-Tung observable A 0 - A 2 are particularly sensitive to the gluon k T effects and to the higher twist effects. A procedure is suggested how to disentangle the higher twist effects from the gluon transverse momentum effects.

  5. The Intestinal Tract: Structure, Function, Disorders and Related Medication.

    Science.gov (United States)

    Wagner, Dianne M.

    This instructional guide is intended for use within inservice or continuing education programs for people who work in long-term care facilities. This module includes an overview of the normal functions of the small and large intestines and discusses the structures of the intestines, absorption in the intestines, and commonly occurring conditions…

  6. Structure and function relationship of human heart from DENSE MRI

    Science.gov (United States)

    Moghaddam, Abbas N.; Gharib, Morteza

    2007-03-01

    The study here, suggests a macroscopic structure for the Left Ventricle (LV), based on the heart kinematics which is obtained through imaging. The measurement of the heart muscle deformation using the Displacement ENcoding with Stimulated Echoes (DENSE) MRI, which describes the heart kinematics in the Lagrangian frame work, is used to determine the high resolution patterns of true myocardial strain. Subsequently, the tangential Shortening Index (SI) and the thickening of the LV wall are calculated for each data point. Considering the heart as a positive-displacement pump, the contribution of each segment of LV in the heart function, can be determined by the SI and thickening of the wall in the same portion. Hence the SI isosurfaces show the extent and spatial distribution of the heart activity and reveals its macro structure. The structure and function of the heart are, therefore, related which in turn results in a macroscopic model for the LV. In particular, it was observed that the heart functionality is not uniformly distributed in the LV, and the regions with greater effect on the pumping process, form a band which wraps around the heart. These results, which are supported by the established histological evidence, may be considered as a landmark in connecting the structure and function of the heart through imaging. Furthermore, the compatibility of this model with microscopic observations about the fiber direction is investigated. This method may be used for planning as well as post evaluation of the ventriculoplasty.

  7. Two-level convolution formula for nuclear structure function

    Science.gov (United States)

    Ma, Boqiang

    1990-05-01

    A two-level convolution formula for the nuclear structure function is derived in considering the nucleus as a composite system of baryon-mesons which are also composite systems of quark-gluons again. The results show that the European Muon Colaboration effect can not be explained by the nuclear effects as nucleon Fermi motion and nuclear binding contributions.

  8. Multi-functional Anti-pollution Construction Structure for Drilling

    Institute of Scientific and Technical Information of China (English)

    Chen Lirong; Yin Weidong; Yang Ping; Wang Rong

    1997-01-01

    @@ Treatment of drilling waste water is the focus of environmental protection for the East Sichuan Drilling Corporation. The three-functional (consists of settling pit, oil interceptor,cistern) construction structure against pollution from drilling waste water was preliminarily improved in 1989.

  9. Structural and functional models for [NiFe] hydrogenase

    NARCIS (Netherlands)

    Angamuthu, Raja

    2009-01-01

    The main goal of the research presented in this thesis is the synthesis of suitable structural and functional models for the enzyme [NiFe] hydrogenase, which can reduce protons into dihydrogen. A brief survey of the roles of all the known nickel containing enzymes in biological systems with a focus

  10. THE CRUSTAL STRUCTURE OF ELLESMERE ISLAND FROM RECEIVER FUNCTION MODELLING

    DEFF Research Database (Denmark)

    Schiffer, Christian; Stephenson, Randell Alexander; Oakey, Gordon

    . Preliminary results give estimates of Moho depths and crustal velocity structure and these are discussed with a focus on the relationship to topography, regional geological units and fault zones. The receiver functions reveal crustal roots underneath the Victoria and Albert Mountains (45km) and the Grantland...

  11. Mass-spectrometric exploration of proteome structure and function

    DEFF Research Database (Denmark)

    Aebersold, Ruedi; Mann, Matthias

    2016-01-01

    , the structures and functions of selected proteins have been studied using biochemical and biophysical methods. However, the properties and behaviour of the proteome as an integrated system have largely remained elusive. Powerful mass-spectrometry-based technologies now provide unprecedented insights...

  12. Functional oxide structures on a surface of metals and alloys

    Institute of Scientific and Technical Information of China (English)

    Rudnev; V.; S.; Yarovaya; T.; P.; Boguta; D.; L.; Lukiyanchuk; I.; V.; Tyrina; L.; M.; Morozova; V.; P.; Nedozorov; P.; M.; Vasilyeva; M.; S.; Kondrikov; N.; B.

    2005-01-01

    The investigations of the plasma electrolytic processes in our laboratory are aimed to the development of conditions of formation of oxide layers with determined composition, structure and functional properties on the surface of valve metals (Al, Ti) and their alloys.……

  13. Regarding Chilcott's "Structural Functionalism as a Heuristic Device" Heuristically.

    Science.gov (United States)

    Blot, Richard K.

    1998-01-01

    The heuristic value of Chilcott's essay lies less in its support for structural functionalism and more in its concern to reexamine theory in the work of earlier educational anthropologists for what earlier theories and practices can add to current research. (SLD)

  14. Studies on the structure and function of pyruvate dehydrogenase complexes

    NARCIS (Netherlands)

    Abreu, de R.A.

    1978-01-01

    The aim of the present investigation was to obtain more information of the structure and function of the pyruvate dehydrogenase complexes from Azotobacter vinelandii and Escherichia coli.In chapter 2 a survey is given of the recent literature on pyruvate dehydrogenase complexes.In chapter 3 results

  15. Glucoamylase: structure/function relationships, and protein engineering

    DEFF Research Database (Denmark)

    Sauer, J; Sigurskjold, B W; Christensen, U;

    2000-01-01

    fundamental structure/function relationships in the binding and catalytic mechanisms. In parallel, issues of relevance for application have been pursued using protein engineering to improve the industrial properties. The present review focuses on recent findings on the catalytic site, mechanism of action...

  16. From structure to function : Protein assemblies dissected by mass spectrometry

    NARCIS (Netherlands)

    Lorenzen, K.

    2008-01-01

    This thesis demonstrates some of the possibilities mass spectrometry can provide to gain new insight into structure and function of protein complexes. While technologies in native mass spectrometry are still under development, it already allows research on complete proteins and protein complexes up

  17. The Polarized Structure Function $g_{2} A Lattice Study Revisited

    CERN Document Server

    Göckeler, M; Kürzinger, W; Oelrich, H; Rakow, P; Schierholz, G

    1999-01-01

    A recent lattice calculation of the spin-dependent structure function g_2 is revisited. It has been recognized that the twist-three operator, which gives rise to d_2, mixes non-perturbatively with operators of lower dimensions under renormalization. This changes the results substantially.

  18. From Protein Structure to Function via Single Crystal Optical Spectroscopy

    Directory of Open Access Journals (Sweden)

    Luca eRonda

    2015-04-01

    Full Text Available The more than 100.000 protein structures determined by X-ray crystallography provide a wealth of information for the characterization of biological processes at the molecular level. However, several crystallographic artifacts, including conformational selection, crystallization conditions and radiation damages, may affect the quality and the interpretation of the electron density map, thus limiting the relevance of structure determinations. Moreover, for most of these structures no functional data have been obtained in the crystalline state, thus posing serious questions on their validity in the inference for protein mechanisms. In order to solve these issues, spectroscopic methods have been applied for the determination of equilibrium and kinetic properties of proteins in the crystalline state. These methods are UV-vis spectrophotometry, spectrofluorimetry, IR, EPR, Raman and resonance Raman spectroscopy. Some of these approaches have been implemented with on-line instruments at X-ray synchrotron beamlines. Here, we provide an overview of investigations predominantly carried out in our laboratory by single crystal polarized absorption UV-vis microspectrophotometry, the most applied technique for the functional characterization of proteins in the crystalline state. Studies on hemoglobins, pyridoxal 5’-phosphate dependent enzymes and green fluorescent protein in the crystalline state have addressed key biological issues, leading to either straightforward structure-function correlations or limitations to structure-based mechanisms.

  19. Structure-Function Studies on the Prolactin Receptor

    DEFF Research Database (Denmark)

    Haxholm, Gitte Wolfsberg

    Class 1 Cytokine receptors are involved in important biological functions mediated through complex networks of intracellular signaling. However, the molecular details of how signaling is regulated are poorly understood. One of the primary reasons for this limited knowledge is the lack of structural...... information on the intracellular domains (ICDs) of these receptors. The overall aim of this study was to obtain an improved understanding of cytokine receptor signaling through structure-function studies on the prolactin receptor (PRLR). The primary focus of this thesis was to structurally characterize...... the PRLR-ICD and the ICD of the related growth hormone receptor (GHR). We showed that both ICDs were intrinsically disordered throughout their entire lengths and that they associated with lipids characteristic of the inner plasma membrane leaflet through conserved motifs, implicating the membrane...

  20. CNS structures presumably involved in vagal control of ovarian function.

    Science.gov (United States)

    Gerendai, I; Tóth, I E; Boldogköi, Z; Medveczky, I; Halász, B

    2000-04-12

    The contribution of the vagus nerve to viral transneuronal labeling of brain structures from the ovaries demonstrated recently by us was investigated. Unilateral vagotomy was performed prior to ipsilateral intraovarian virus injection. Virus-infected neurons were visualized by immunostaining. In vagotomized rats such neurons were detected only in certain cell groups of the brain (parapyramidal nucleus, A(1), A(5) cell group, caudal raphe nuclei, hypothalamic paraventricular nucleus, lateral hypothalamus). Vagotomy interfered with labeling of several structures that were labeled in controls, including area postrema, nucleus of the solitary tract, dorsal vagal complex, nucleus ambiguus, A(7) cell group, Barrington's nucleus, locus coeruleus, periaqueductal gray, dorsal hypothalamus. Findings provide a morphological basis to study the functional significance of brain structures presumably involved in the control of ovarian function and acting via the vagus or the sympathetic nerves.

  1. The Structure and Function of Non-Collagenous Bone Proteins

    Science.gov (United States)

    Hook, Magnus; McQuillan, David J.

    1997-01-01

    The research done under the cooperative research agreement for the project titled 'The structure and function of non-collagenous bone proteins' represented the first phase of an ongoing program to define the structural and functional relationships of the principal noncollagenous proteins in bone. An ultimate goal of this research is to enable design and execution of useful pharmacological compounds that will have a beneficial effect in treatment of osteoporosis, both land-based and induced by long-duration space travel. The goals of the now complete first phase were as follows: 1. Establish and/or develop powerful recombinant protein expression systems; 2. Develop and refine isolation and purification of recombinant proteins; 3. Express wild-type non-collagenous bone proteins; 4. Express site-specific mutant proteins and domains of wild-type proteins to enhance likelihood of crystal formation for subsequent solution of structure.

  2. DMPD: Structural and functional analyses of bacterial lipopolysaccharides. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12106784 Structural and functional analyses of bacterial lipopolysaccharides. Carof...html) (.csml) Show Structural and functional analyses of bacterial lipopolysaccharides. PubmedID 12106784 Ti...tle Structural and functional analyses of bacterial lipopolysaccharides. Authors

  3. Correlation function as a measure of the structure

    CERN Document Server

    Buryak, O E

    1995-01-01

    Geometrical model of structure of the universe is examined to obtain analytical expression for the two points nonlinear correlation function. According to the model the objects (galaxies) are concentrated into two types of structure elements - filaments and sheets. We considered the filaments ( similar to galaxy filaments ) simply as straight lines and the sheets ( similar to superclusters of galaxies ) simply as planes. The homogeneously distributed objects are also taken into consideration. The spatial distribution of lines, planes and points is uncorrelated. The nonlinear correlation function depends on four parameters and is similar to the observed and simulated ones for different samples. It describes quite well the correlation of galaxies, clusters of galaxies and dark matter distribution. Possible interpretation of the parameters of nonlinear correlation function is discussed.

  4. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  5. A-dependence of weak nuclear structure functions

    Energy Technology Data Exchange (ETDEWEB)

    Haider, H.; Athar, M. Sajjad [Department of Physics, Aligarh Muslim University, Aligarh-202 002 (India); Simo, I. Ruiz [Dipartimento di Fisica, Universitá degli studi di Trento Via Sommarive 14, Povo (Trento) I-38123 (Italy)

    2015-05-15

    Effect of nuclear medium on the weak structure functions F{sub 2}{sup A}(x, Q{sup 2}) and F{sub 3}{sup A}(x, Q{sup 2}) have been studied using charged current (anti)neutrino deep inelastic scattering on various nuclear targets. Relativistic nuclear spectral function which incorporate Fermi motion, binding and nucleon correlations are used for the calculations. We also consider the pion and rho meson cloud contributions calculated from a microscopic model for meson-nucleus self-energies. Using these structure functions, F{sub i}{sup A}/F{sub i}{sup proton} and F{sub i}{sup A}/F{sub i}{sup deuteron}(i=2,3, A={sup 12}C, {sup 16}O, CH and H{sub 2}O) are obtained.

  6. R-ratios and moments of nuclear structure functions

    CERN Document Server

    Rinat, A S

    2000-01-01

    We study implications of a model, which links nuclear and nucleon structure functions. Computed Callen-Gross functions $\\kappa^A(x,Q^2)= 2xF_1^A(x,Q^2)/F_2^A(x,Q^2)$ appear for finite $Q^2$ to be close to their asymptotic value 1. Using those $\\kappa$, we compure $R$ ratios for $Q^2\\ge 5 GeV^2$. We review approximate methods in use for the extraction of $R$ from inclusive scattering and ENC data. Further we calcuate ratios of the moments of $F_k$ and find these to describe the data, in particular their $Q^2$ dependence. The above observables, as well as inclusive cross sections, are sensitive tests for the underlying relation between nucleonic and nuclear structure functions. In view of the overall agreement, we speculate that the above relation effectively circumvents a QCD calculation.

  7. Structure Function Sum rules for Systems with Large Scattering Lengths

    CERN Document Server

    Goldberger, Walter D

    2010-01-01

    We use a dispersion relation in conjunction with the operator product expansion (OPE) to derive model independent sum rules for the dynamic structure functions of systems with large scattering lengths. We present an explicit sum rule for the structure functions that control the density and spin response of the many-body ground state. Our methods are general, and apply to either fermions or bosons which interact through two-body contact interactions with large scattering lengths. By employing a Borel transform of the OPE, the relevant integrals are weighted towards infrared frequencies, thus allowing for greater overlap low energy data. Similar sum rules can be derived for other response functions. The sum rules can be used to extract the contact parameter introduced by Tan, including universality violating corrections at finite scattering lengths.

  8. Towards fully automated structure-based function prediction in structural genomics: a case study.

    Science.gov (United States)

    Watson, James D; Sanderson, Steve; Ezersky, Alexandra; Savchenko, Alexei; Edwards, Aled; Orengo, Christine; Joachimiak, Andrzej; Laskowski, Roman A; Thornton, Janet M

    2007-04-13

    As the global Structural Genomics projects have picked up pace, the number of structures annotated in the Protein Data Bank as hypothetical protein or unknown function has grown significantly. A major challenge now involves the development of computational methods to assign functions to these proteins accurately and automatically. As part of the Midwest Center for Structural Genomics (MCSG) we have developed a fully automated functional analysis server, ProFunc, which performs a battery of analyses on a submitted structure. The analyses combine a number of sequence-based and structure-based methods to identify functional clues. After the first stage of the Protein Structure Initiative (PSI), we review the success of the pipeline and the importance of structure-based function prediction. As a dataset, we have chosen all structures solved by the MCSG during the 5 years of the first PSI. Our analysis suggests that two of the structure-based methods are particularly successful and provide examples of local similarity that is difficult to identify using current sequence-based methods. No one method is successful in all cases, so, through the use of a number of complementary sequence and structural approaches, the ProFunc server increases the chances that at least one method will find a significant hit that can help elucidate function. Manual assessment of the results is a time-consuming process and subject to individual interpretation and human error. We present a method based on the Gene Ontology (GO) schema using GO-slims that can allow the automated assessment of hits with a success rate approaching that of expert manual assessment.

  9. Structural Bases of Stability-Function Tradeoffs in Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Beadle, Beth M; Shoichet, Brian K [NWU, MED

    2010-03-05

    The structures of enzymes reflect two tendencies that appear opposed. On one hand, they fold into compact, stable structures; on the other hand, they bind a ligand and catalyze a reaction. To be stable, enzymes fold to maximize favorable interactions, forming a tightly packed hydrophobic core, exposing hydrophilic groups, and optimizing intramolecular hydrogen-bonding. To be functional, enzymes carve out an active site for ligand binding, exposing hydrophobic surface area, clustering like charges, and providing unfulfilled hydrogen bond donors and acceptors. Using AmpC {beta}-lactamase, an enzyme that is well-characterized structurally and mechanistically, the relationship between enzyme stability and function was investigated by substituting key active-site residues and measuring the changes in stability and activity. Substitutions of catalytic residues Ser64, Lys67, Tyr150, Asn152, and Lys315 decrease the activity of the enzyme by 10{sup 3}-10{sup 5}-fold compared to wild-type. Concomitantly, many of these substitutions increase the stability of the enzyme significantly, by up to 4.7 kcal/mol. To determine the structural origins of stabilization, the crystal structures of four mutant enzymes were determined to between 1.90 {angstrom} and 1.50 {angstrom} resolution. These structures revealed several mechanisms by which stability was increased, including mimicry of the substrate by the substituted residue (S64D), relief of steric strain (S64G), relief of electrostatic strain (K67Q), and improved polar complementarity (N152H). These results suggest that the preorganization of functionality characteristic of active sites has come at a considerable cost to enzyme stability. In proteins of unknown function, the presence of such destabilized regions may indicate the presence of a binding site.

  10. Origins, structures, and functions of circulating DNA in oncology.

    Science.gov (United States)

    Thierry, A R; El Messaoudi, S; Gahan, P B; Anker, P; Stroun, M

    2016-09-01

    While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown to be composed of many "kinds." This structural description goes hand-in-hand with the mechanisms of its origins such as apoptosis, necrosis, active release, phagocytosis, and exocytose. There are multiple structural forms of cirDNA depending upon the mechanism of release: particulate structures (exosomes, microparticles, apoptotic bodies) or macromolecular structures (nucleosomes, virtosomes/proteolipidonucleic acid complexes, DNA traps, links with serum proteins or to the cell-free membrane parts). In addition, cirDNA concerns both nuclear and/or mitochondrial DNA with both species exhibiting different structural characteristics that potentially reveal different forms of biological stability or diagnostic significance. This review focuses on the origins, structures and functional aspects that are paradoxically less well described in the literature while numerous reviews are directed to the clinical application of cirDNA. Differentiation of the various structures and better knowledge of the fate of cirDNA would considerably expand the diagnostic power of cirDNA analysis especially with regard to the patient follow-up enlarging the scope of personalized medicine. A better understanding of the subsequent fate of cirDNA would also help in deciphering its functional aspects such as their capacity for either genometastasis or their pro-inflammatory and immunological effects.

  11. Surface Appendages of Archaea: Structure, Function, Genetics and Assembly

    Directory of Open Access Journals (Sweden)

    Sarah Siu

    2013-01-01

    Full Text Available Organisms representing diverse subgroupings of the Domain Archaea are known to possess unusual surface structures. These can include ones unique to Archaea such as cannulae and hami as well as archaella (archaeal flagella and various types of pili that superficially resemble their namesakes in Bacteria, although with significant differences. Major advances have occurred particularly in the study of archaella and pili using model organisms with recently developed advanced genetic tools. There is common use of a type IV pili-model of assembly for several archaeal surface structures including archaella, certain pili and sugar binding structures termed bindosomes. In addition, there are widespread posttranslational modifications of archaellins and pilins with N-linked glycans, with some containing novel sugars. Archaeal surface structures are involved in such diverse functions as swimming, attachment to surfaces, cell to cell contact resulting in genetic transfer, biofilm formation, and possible intercellular communication. Sometimes functions are co-dependent on other surface structures. These structures and the regulation of their assembly are important features that allow various Archaea, including thermoacidophilic, hyperthermophilic, halophilic, and anaerobic ones, to survive and thrive in the extreme environments that are commonly inhabited by members of this domain.

  12. Protein Function Prediction Based on Sequence and Structure Information

    KAUST Repository

    Smaili, Fatima Z.

    2016-05-25

    The number of available protein sequences in public databases is increasing exponentially. However, a significant fraction of these sequences lack functional annotation which is essential to our understanding of how biological systems and processes operate. In this master thesis project, we worked on inferring protein functions based on the primary protein sequence. In the approach we follow, 3D models are first constructed using I-TASSER. Functions are then deduced by structurally matching these predicted models, using global and local similarities, through three independent enzyme commission (EC) and gene ontology (GO) function libraries. The method was tested on 250 “hard” proteins, which lack homologous templates in both structure and function libraries. The results show that this method outperforms the conventional prediction methods based on sequence similarity or threading. Additionally, our method could be improved even further by incorporating protein-protein interaction information. Overall, the method we use provides an efficient approach for automated functional annotation of non-homologous proteins, starting from their sequence.

  13. Improved Left Ventricular Structure and Function After Successful Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Bernd Hewing

    2016-10-01

    Full Text Available Background/Aims: Cardiac changes observed in chronic kidney disease patients are of multifactorial origin including chronic uremia, hemodynamics or inflammation. Restoration of renal function by kidney transplantation (KTX may reverse cardiac changes. Novel echocardiographic methods such as speckle tracking echocardiography (STE allow early and sensitive detection of subtle changes of cardiac parameters. We evaluated changes of cardiac structure and function after KTX by advanced echocardiographic modalities. Methods: Thirty-one KTX recipients (female n=11 were evaluated by medical examination, laboratory testing and echocardiography before and after KTX (median follow-up 19 months. Left ventricular (LV and right ventricular (RV diameters and function were assessed by echocardiographic standard parameters. Longitudinal 2D strain of the LV (GLPS and left atrium (LA was determined by 2D STE. Results: After KTX, median serum creatinine level was 1.3 mg/dl (IQR, 1.2-1.5. Systolic blood pressure decreased significantly after KTX. Echocardiography showed a significant reduction in LV end-diastolic septal and posterior wall thickness and LV mass index after KTX, which was accompanied by an improvement of GLPS. There were no relevant changes in parameters of LA (reservoir, conduit or contractile function, LV diastolic or RV function after KTX. Conclusion: LV hypertrophy reversed after successful KTX and was accompanied by an improvement in longitudinal LV function as assessed by STE. Diastolic function and STE-derived LA function parameters did not change significantly after KTX.

  14. Indirect readout in protein-peptide recognition: a different story from classical biomolecular recognition.

    Science.gov (United States)

    Yu, Hua; Zhou, Peng; Deng, Maolin; Shang, Zhicai

    2014-07-28

    Protein-peptide interactions are prevalent and play essential roles in many living activities. Peptides recognize their protein partners by direct nonbonded interactions and indirect adjustment of conformations. Although processes of protein-peptide recognition have been comprehensively studied in both sequences and structures recently, flexibility of peptides and the configuration entropy penalty in recognition did not get enough attention. In this study, 20 protein-peptide complexes and their corresponding unbound peptides were investigated by molecular dynamics simulations. Energy analysis revealed that configurational entropy penalty introduced by restriction of the degrees of freedom of peptides in indirect readout process of protein-peptide recognition is significant. Configurational entropy penalty has become the main content of the indirect readout energy in protein-peptide recognition instead of deformation energy which is the main source of the indirect readout energy in classical biomolecular recognition phenomena, such as protein-DNA binding. These results provide us a better understanding of protein-peptide recognition and give us some implications in peptide ligand design.

  15. A method for rapid quantitative assessment of biofilms with biomolecular staining and image analysis.

    Science.gov (United States)

    Larimer, Curtis; Winder, Eric; Jeters, Robert; Prowant, Matthew; Nettleship, Ian; Addleman, Raymond Shane; Bonheyo, George T

    2016-01-01

    The accumulation of bacteria in surface-attached biofilms can be detrimental to human health, dental hygiene, and many industrial processes. Natural biofilms are soft and often transparent, and they have heterogeneous biological composition and structure over micro- and macroscales. As a result, it is challenging to quantify the spatial distribution and overall intensity of biofilms. In this work, a new method was developed to enhance the visibility and quantification of bacterial biofilms. First, broad-spectrum biomolecular staining was used to enhance the visibility of the cells, nucleic acids, and proteins that make up biofilms. Then, an image analysis algorithm was developed to objectively and quantitatively measure biofilm accumulation from digital photographs and results were compared to independent measurements of cell density. This new method was used to quantify the growth intensity of Pseudomonas putida biofilms as they grew over time. This method is simple and fast, and can quantify biofilm growth over a large area with approximately the same precision as the more laborious cell counting method. Stained and processed images facilitate assessment of spatial heterogeneity of a biofilm across a surface. This new approach to biofilm analysis could be applied in studies of natural, industrial, and environmental biofilms.

  16. Nanoscale Biomolecular Detection Limit for Gold Nanoparticles Based on Near-Infrared Response

    Directory of Open Access Journals (Sweden)

    Mario D’Acunto

    2012-01-01

    Full Text Available Gold nanoparticles have been widely used during the past few years in various technical and biomedical applications. In particular, the resonance optical properties of nanometer-sized particles have been employed to design biochips and biosensors used as analytical tools. The optical properties of nonfunctionalized gold nanoparticles and core-gold nanoshells play a crucial role for the design of biosensors where gold surface is used as a sensing component. Gold nanoparticles exhibit excellent optical tunability at visible and near-infrared frequencies leading to sharp peaks in their spectral extinction. In this paper, we study how the optical properties of gold nanoparticles and core-gold nanoshells are changed as a function of different sizes, shapes, composition, and biomolecular coating with characteristic shifts towards the near-infrared region. We show that the optical tenability can be carefully tailored for particle sizes falling in the range 100–150 nm. The results should improve the design of sensors working at the detection limit.

  17. Co-Immobilization of Proteins and DNA Origami Nanoplates to Produce High-Contrast Biomolecular Nanoarrays.

    Science.gov (United States)

    Hager, Roland; Burns, Jonathan R; Grydlik, Martyna J; Halilovic, Alma; Haselgrübler, Thomas; Schäffler, Friedrich; Howorka, Stefan

    2016-06-01

    The biofunctionalization of nanopatterned surfaces with DNA origami nanostructures is an important topic in nanobiotechnology. An unexplored challenge is, however, to co-immobilize proteins with DNA origami at pre-determined substrate sites in high contrast relative to the nontarget areas. The immobilization should, in addition, preferably be achieved on a transparent substrate to allow ultrasensitive optical detection. If successful, specific co-binding would be a step towards stoichiometrically defined arrays with few to individual protein molecules per site. Here, we successfully immobilize with high specificity positively charged avidin proteins and negatively charged DNA origami nanoplates on 100 nm-wide carbon nanoislands while suppressing undesired adsorption to surrounding nontarget areas. The arrays on glass slides achieve unprecedented selectivity factors of up to 4000 and allow ultrasensitive fluorescence read-out. The co-immobilization onto the nanoislands leads to layered biomolecular architectures, which are functional because bound DNA origami influences the number of capturing sites on the nanopatches for other proteins. The novel hybrid DNA origami-protein nanoarrays allow the fabrication of versatile research platforms for applications in biosensing, biophysics, and cell biology, and, in addition, represent an important step towards single-molecule protein arrays.

  18. Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires

    Science.gov (United States)

    Liu, Xiao-Yuan; Ma, Wei; Zhou, Hao; Cao, Xiao-Ming; Long, Yi-Tao

    2015-05-01

    Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.

  19. Class I Cytokine Receptors: Structure and function in the Membrane

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard

    Class I cytokine receptors are involved in important biological functions of both physiological and pathological nature in mammals. However, the molecular details of the cross-membrane signal transduction through these receptors remain obscure. One of the major reasons for this is the lack...... of structural knowledge on their membrane-embedded transmembrane domains (TMDs), which connect the extracellular ligand binding domains to the intracellular signaling platforms. The overall aim of this thesis work was to improve our understanding of the class I cytokine receptor signaling across the membrane...... ample material of high quality for structural studies with NMR spectroscopy of several class I cytokine receptor TMDs. Furthermore, the structure of a class I cytokine receptor TMD in DHPC micelles was solved with solution-state NMR spectroscopy. Additionally, since structural studies of intact proteins...

  20. Structural and functional significance of water permeation through cotransporters

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Gorraitz, Edurne; Her, Ka;

    2016-01-01

    to be due to alterations in steric hindrance to water and urea, and/or changes in protein folding caused by mismatching of side chains in the water pathway. Water permeation through SGLT1 and other transporters bears directly on the structural mechanism for the transport of polar solutes through......Membrane transporters, in addition to their major role as specific carriers for ions and small molecules, can also behave as water channels. However, neither the location of the water pathway in the protein nor their functional importance is known. Here, we map the pathway for water and urea...... through the intestinal sodium/glucose cotransporter SGLT1. Molecular dynamics simulations using the atomic structure of the bacterial transporter vSGLT suggest that water permeates the same path as Na+ and sugar. On a structural model of SGLT1, based on the homology structure of vSGLT, we identified...

  1. Surface structure of polymer Gels and emerging functions

    CERN Document Server

    Kobiki, Y

    1999-01-01

    We report the surface structure of polymer gels on a submicrometer scale during the volume phase transition. Sponge-like domains with a mesoscopic scale were directly observed in water by using at atomic force microscope (AFM). The surface structure characterized by the domains is discussed in terms of the root-mean-square roughness and the auto-correlation function, which were calculated from the AFM images. In order to demonstrate the role of surface structure in determining the macroscopic properties of film-like poly (N-isopropylacrylamide: NIPA) gels. It was found that the temperature dependence, as well as the absolute values of the static contact angle, were strongly dependent on the bulk network inhomogeneities. The relation between the mesoscopic structure and the macroscopic properties is qualitatively discussed in terms of not only the changes in the chemical, but also in the physical, surface properties of the NIPA gels in response to a temperature change.

  2. Structural determinants of Smad function in TGF-β signaling.

    Science.gov (United States)

    Macias, Maria J; Martin-Malpartida, Pau; Massagué, Joan

    2015-06-01

    Smad transcription factors are central to the signal transduction pathway that mediates the numerous effects of the transforming growth factor β (TGF-β) superfamily of cytokines in metazoan embryo development as well as in adult tissue regeneration and homeostasis. Although Smad proteins are conserved, recent genome-sequencing projects have revealed their sequence variation in metazoan evolution, human polymorphisms, and cancer. Structural studies of Smads bound to partner proteins and target DNA provide a framework for understanding the significance of these evolutionary and pathologic sequence variations. We synthesize the extant mutational and structural data to suggest how genetic variation in Smads may affect the structure, regulation, and function of these proteins. We also present a web application that compares Smad sequences and displays Smad protein structures and their disease-associated variants.

  3. Structure to function: Spider silk and human collagen

    Science.gov (United States)

    Rabotyagova, Olena S.

    Nature has the ability to assemble a variety of simple molecules into complex functional structures with diverse properties. Collagens, silks and muscles fibers are some examples of fibrous proteins with self-assembling properties. One of the great challenges facing Science is to mimic these designs in Nature to find a way to construct molecules that are capable of organizing into functional supra-structures by self-assembly. In order to do so, a construction kit consisting of molecular building blocks along with a complete understanding on how to form functional materials is required. In this current research, the focus is on spider silk and collagen as fibrous protein-based biopolymers that can shed light on how to generate nanostructures through the complex process of self-assembly. Spider silk in fiber form offers a unique combination of high elasticity, toughness, and mechanical strength, along with biological compatibility and biodegrability. Spider silk is an example of a natural block copolymer, in which hydrophobic and hydrophilic blocks are linked together generating polymers that organize into functional materials with extraordinary properties. Since silks resemble synthetic block copolymer systems, we adopted the principles of block copolymer design from the synthetic polymer literature to build block copolymers based on spider silk sequences. Moreover, we consider spider silk to be an important model with which to study the relationships between structure and properties in our system. Thus, the first part of this work was dedicated to a novel family of spider silk block copolymers, where we generated a new family of functional spider silk-like block copolymers through recombinant DNA technology. To provide fundamental insight into relationships between peptide primary sequence, block composition, and block length and observed morphological and structural features, we used these bioengineered spider silk block copolymers to study secondary structure

  4. Structure and function of nucleotide sugar transporters: Current progress

    Directory of Open Access Journals (Sweden)

    Barbara Hadley

    2014-06-01

    Full Text Available The proteomes of eukaryotes, bacteria and archaea are highly diverse due, in part, to the complex post-translational modification of protein glycosylation. The diversity of glycosylation in eukaryotes is reliant on nucleotide sugar transporters to translocate specific nucleotide sugars that are synthesised in the cytosol and nucleus, into the endoplasmic reticulum and Golgi apparatus where glycosylation reactions occur. Thirty years of research utilising multidisciplinary approaches has contributed to our current understanding of NST function and structure. In this review, the structure and function, with reference to various disease states, of several NSTs including the UDP-galactose, UDP-N-acetylglucosamine, UDP-N-acetylgalactosamine, GDP-fucose, UDP-N-acetylglucosamine/UDP-glucose/GDP-mannose and CMP-sialic acid transporters will be described. Little is known regarding the exact structure of NSTs due to difficulties associated with crystallising membrane proteins. To date, no three-dimensional structure of any NST has been elucidated. What is known is based on computer predictions, mutagenesis experiments, epitope-tagging studies, in-vitro assays and phylogenetic analysis. In this regard the best-characterised NST to date is the CMP-sialic acid transporter (CST. Therefore in this review we will provide the current state-of-play with respect to the structure–function relationship of the (CST. In particular we have summarised work performed by a number groups detailing the affect of various mutations on CST transport activity, efficiency, and substrate specificity.

  5. Structure-function investigations of bacterial photosynthetic reaction centers.

    Science.gov (United States)

    Leonova, M M; Fufina, T Yu; Vasilieva, L G; Shuvalov, V A

    2011-12-01

    During photosynthesis light energy is converted into energy of chemical bonds through a series of electron and proton transfer reactions. Over the first ultrafast steps of photosynthesis that take place in the reaction center (RC) the quantum efficiency of the light energy transduction is nearly 100%. Compared to the plant and cyanobacterial photosystems, bacterial RCs are well studied and have relatively simple structure. Therefore they represent a useful model system both for manipulating of the electron transfer parameters to study detailed mechanisms of its separate steps as well as to investigate the common principles of the photosynthetic RC structure, function, and evolution. This review is focused on the research papers devoted to chemical and genetic modifications of the RCs of purple bacteria in order to study principles and mechanisms of their functioning. Investigations of the last two decades show that the maximal rates of the electron transfer reactions in the RC depend on a number of parameters. Chemical structure of the cofactors, distances between them, their relative orientation, and interactions to each other are of great importance for this process. By means of genetic and spectral methods, it was demonstrated that RC protein is also an essential factor affecting the efficiency of the photochemical charge separation. Finally, some of conservative water molecules found in RC not only contribute to stability of the protein structure, but are directly involved in the functioning of the complex.

  6. Structure and Function of the LmbE-like Superfamily

    Directory of Open Access Journals (Sweden)

    Shane Viars

    2014-05-01

    Full Text Available The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis of various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossmann fold similar to lactate dehydrogenase, which represented a novel fold for (zinc metallohydrolases at the time the initial structure was solved. The structural diversity of the N-acetylglucosamine containing substrates affords functional diversity for the LmbE-like enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, predominantly zinc. The catalytic zinc is coordinated to proteins via His2-Asp-solvent binding site. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.

  7. Structural and functional loss in restored wetland ecosystems.

    Science.gov (United States)

    Moreno-Mateos, David; Power, Mary E; Comín, Francisco A; Yockteng, Roxana

    2012-01-01

    Wetlands are among the most productive and economically valuable ecosystems in the world. However, because of human activities, over half of the wetland ecosystems existing in North America, Europe, Australia, and China in the early 20th century have been lost. Ecological restoration to recover critical ecosystem services has been widely attempted, but the degree of actual recovery of ecosystem functioning and structure from these efforts remains uncertain. Our results from a meta-analysis of 621 wetland sites from throughout the world show that even a century after restoration efforts, biological structure (driven mostly by plant assemblages), and biogeochemical functioning (driven primarily by the storage of carbon in wetland soils), remained on average 26% and 23% lower, respectively, than in reference sites. Either recovery has been very slow, or postdisturbance systems have moved towards alternative states that differ from reference conditions. We also found significant effects of environmental settings on the rate and degree of recovery. Large wetland areas (>100 ha) and wetlands restored in warm (temperate and tropical) climates recovered more rapidly than smaller wetlands and wetlands restored in cold climates. Also, wetlands experiencing more (riverine and tidal) hydrologic exchange recovered more rapidly than depressional wetlands. Restoration performance is limited: current restoration practice fails to recover original levels of wetland ecosystem functions, even after many decades. If restoration as currently practiced is used to justify further degradation, global loss of wetland ecosystem function and structure will spread.

  8. Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy : a rapid diagnostic method for studying cellular responses to stress and disease.

    Energy Technology Data Exchange (ETDEWEB)

    Yaffe, Michael P. (University of California, San Diego, CA); Gourley, Paul Lee; Copeland, Robert Guild; McDonald, Anthony Eugene; Hendricks, Judy K.; Naviaux, Robert K. (Univesity of California, San Diego, CA)

    2006-12-01

    We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions with a single peak. In contrast, mutant cells and mitochondria produce leptokurtotic distributions that are asymmetric and highly skewed to the right. These distribution changes could be self-consistently modeled with a single, log-normal distribution undergoing a thousand-fold increase in variance of biomolecular composition. These features reflect a new state of stressed or diseased cells that we call a reactive biomolecular divergence (RBD) that reflects the vital interdependence of mitochondria and the nucleus.

  9. An Analysis of Biomolecular Force Fields for Simulations of Polyglutamine in Solution

    Energy Technology Data Exchange (ETDEWEB)

    Fluitt, Aaron M. [Univ. of Chicago, IL (United States); de Pablo, Juan J. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    Polyglutamine (polyQ) peptides are a useful model system for biophysical studies of protein folding and aggregation, both for their intriguing aggregation properties and their own relevance to human disease. The genetic expansion of a polyQ tract triggers the formation of amyloid aggregates associated with nine neurodegenerative diseases. Several clearly identifiable and separable factors, notably the length of the polyQ tract, influence the mechanism of aggregation, its associated kinetics, and the ensemble of structures formed. Atomistic simulations are well positioned to answer open questions regarding the thermodynamics and kinetics of polyQ folding and aggregation. The additional, explicit representation of water permits deeper investigation of the role of solvent dynamics, and it permits a direct comparison of simulation results with infrared spectroscopy experiments. The generation of meaningful simulation results hinges on satisfying two essential criteria: achieving sufficient conformational sampling to draw statistically valid conclusions, and accurately reproducing the intermolecular forces that govern system structure and dynamics. In this work, we examine the ability of 12 biomolecular force fields to reproduce the properties of a simple, 30-residue polyQ peptide (Q30) in explicit water. In addition to secondary and tertiary structure, we consider generic structural properties of polymers that provide additional dimensions for analysis of the highly degenerate disordered states of the molecule. We find that the 12 force fields produce a wide range of predictions. We identify AMBER ff99SB, AMBER ff99SB*, and OPLS-AA/L to be most suitable for studies of polyQ folding and aggregation.

  10. Structural and functional diversity of native brain neuronal nicotinic receptors.

    Science.gov (United States)

    Gotti, Cecilia; Clementi, Francesco; Fornari, Alice; Gaimarri, Annalisa; Guiducci, Stefania; Manfredi, Irene; Moretti, Milena; Pedrazzi, Patrizia; Pucci, Luca; Zoli, Michele

    2009-10-01

    Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels present in the central and peripheral nervous systems, that are permeable to mono- and divalent cations. They share a common basic structure but their pharmacological and functional properties arise from the wide range of different subunit combinations making up distinctive subtypes. nAChRs are involved in many physiological functions in the central and peripheral nervous systems, and are the targets of the widely used drug of abuse nicotine. In addition to tobacco dependence, changes in their number and/or function are associated with neuropsychiatric disorders, ranging from epilepsy to dementia. Although some of the neural circuits involved in the acute and chronic effects of nicotine have been identified, much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions. We briefly review some recent findings concerning the structure and function of native nAChRs, focusing on the subtypes identified in the mesostriatal and habenulo-interpeduncular pathways, two systems involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the effect of chronic nicotine on the expression of native subtypes.

  11. Structural and functional topography of the human ribosome

    Institute of Scientific and Technical Information of China (English)

    Dmitri Graifer; Galina Karpova

    2012-01-01

    This review covers data on the structural organization of functional sites in the human ribosome,namely,the messenger RNA binding center,the binding site of the hepatitis C virus RNA internal ribosome entry site,and the peptidyl transferase center.The data summarized here have been obtained primarily by means of a site-directed crosslinking approach with application of the analogs of the respective ribosomal ligands bearing cross-linkers at the designed positions.These data are discussed taking into consideration available structural data on ribosomes from various kingdoms obtained with the use of cryo-electron microscopy,X-ray crystallography,and other approaches.

  12. Structure-Function-Property-Design Interplay in Biopolymers: Spider Silk

    Science.gov (United States)

    Tokareva, Olena; Jacobsen, Matthew; Buehler, Markus; Wong, Joyce; Kaplan, David L.

    2013-01-01

    Spider silks have been a focus of research for almost two decades due to their outstanding mechanical and biophysical properties. Recent advances in genetic engineering have led to the synthesis of recombinant spider silks, thus helping to unravel a fundamental understanding of structure-function-property relationships. The relationships between molecular composition, secondary structures, and mechanical properties found in different types of spider silks are described, along with a discussion of artificial spinning of these proteins and their bioapplications, including the role of silks in biomineralization and fabrication of biomaterials with controlled properties. PMID:23962644

  13. Structure-function-property-design interplay in biopolymers: spider silk.

    Science.gov (United States)

    Tokareva, Olena; Jacobsen, Matthew; Buehler, Markus; Wong, Joyce; Kaplan, David L

    2014-04-01

    Spider silks have been a focus of research for almost two decades due to their outstanding mechanical and biophysical properties. Recent advances in genetic engineering have led to the synthesis of recombinant spider silks, thus helping to unravel a fundamental understanding of structure-function-property relationships. The relationships between molecular composition, secondary structures and mechanical properties found in different types of spider silks are described, along with a discussion of artificial spinning of these proteins and their bioapplications, including the role of silks in biomineralization and fabrication of biomaterials with controlled properties.

  14. Effects of Tai Ji Exercise on Bone Structure and Function

    Institute of Scientific and Technical Information of China (English)

    Xu Hong; David Lawson

    2005-01-01

    To evaluated the effects of the 24 movements Tai Ji exercise on bone structure and function. Broadband Ultrsonic Attenuation (BUA) and velocity of sound (VOS), bone formation marker Osteocalcin (OSTN) and bone resorption markers urinary Pyridum crosslinks (PYR and D-PYR) were studied before and after four months of Tai Ji exercise. Improved bone structure and increased bone density in menopausal women were reflected by BUA results. The increased BUA appears to be associated with increased bone formation rather than decreased bone resorption.

  15. Phospholipase A2 structure/function, mechanism, and signaling1

    OpenAIRE

    Burke, John E.; Dennis, Edward A.

    2009-01-01

    Tremendous advances in understanding the structure and function of the superfamily of phospholipase A2 (PLA2) enzymes has occurred in the twenty-first century. The superfamily includes 15 groups comprising four main types including the secreted sPLA2, cytosolic cPLA2, calcium-independent iPLA2, and platelet activating factor (PAF) acetyl hydrolase/oxidized lipid lipoprotein associated (Lp)PLA2. We review herein our current understanding of the structure and interaction with substrate phosphol...

  16. Artificial Metalloproteins Exploiting Vacant Space: Preparation, Structures, and Functions

    Science.gov (United States)

    Abe, Satoshi; Ueno, Takafumi; Watanabe, Yoshihito

    Molecular design of artificial metalloproteins is one of the most attractive subjects in bioinorganic chemistry. Protein vacant space has been utilized to prepare metalloproteins because it provides a unique chemical environment for application to catalysts and to biomaterials bearing electronic, magnetic, and medical properties. Recently, X-ray crystal structural analysis has increased in this research area because it is a powerful tool for understanding the interactions of metal complexes and protein scaffolds, and for providing rational design of these composites. This chapter reviews the recent studies on the preparation methods and X-ray crystal structural analyses of metal/protein composites, and their functions as catalysts, metal-drugs, etc.

  17. Human cytosolic glutathione transferases: structure, function, and drug discovery.

    Science.gov (United States)

    Wu, Baojian; Dong, Dong

    2012-12-01

    Glutathione transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of electrophilic substrates to glutathione. In recent years, GSTs have been of great interest in pharmacology and drug development because of their involvement in many important biological processes such as steroid and prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. This review describes crystal structures for cytosolic GSTs and correlates active-site features with enzyme functions (e.g., steroid synthesis, tyrosine degradation, and dehydroascorbate reduction) and substrate selectivity. Use of these crystal structures for the design of specific inhibitors for several GST enzymes is also discussed.

  18. Nucleon effective mass and the A dependence of structure functions

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Canal, C.A.; Santangelo, E.M.; Vucetich, H.

    1984-10-08

    The nucleon effective mass was successfully used, as the only free parameter, to adjust the ratio R(A) of structure functions measured in a nucleus of mass number A and in the deuteron, for each A value in the SLAC set of experimental data. The resulting A dependence of the effective mass, being linear in A/sup -1/3/, is consistent with the behavior expected from nuclear structure considerations. The extrapolated value of the effective mass for nuclear matter agrees with previous estimations.

  19. Combing genomic DNA for structural and functional studies.

    Science.gov (United States)

    Schurra, Catherine; Bensimon, Aaron

    2009-01-01

    Molecular combing is a process whereby single DNA molecules bind by their extremities to a silanised surface and are then uniformly stretched and aligned by a receding air/water interface (1). This method, with a high resolution ranging from a few kilobases to megabases, has many applications in the field of molecular cytogenetics, allowing structural and functional analysis at the genome level. Here we describe protocols for preparing DNA for combing and for the use of fluorescent hybridisation (FH) applied to combed DNA to conduct physical mapping or genomic structural analysis. We also present the methodology for visualising and studying DNA replication using combed DNA.

  20. Na+ channel function, regulation, structure, trafficking and sequestration

    Science.gov (United States)

    Chen-Izu, Ye; Shaw, Robin M; Pitt, Geoffrey S; Yarov-Yarovoy, Vladimir; Sack, Jon T; Abriel, Hugues; Aldrich, Richard W; Belardinelli, Luiz; Cannell, Mark B; Catterall, William A; Chazin, Walter J; Chiamvimonvat, Nipavan; Deschenes, Isabelle; Grandi, Eleonora; Hund, Thomas J; Izu, Leighton T; Maier, Lars S; Maltsev, Victor A; Marionneau, Celine; Mohler, Peter J; Rajamani, Sridharan; Rasmusson, Randall L; Sobie, Eric A; Clancy, Colleen E; Bers, Donald M

    2015-01-01

    This paper is the second of a series of three reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation–contraction coupling and arrhythmias: Na+ channel and Na+ transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on Na+ channel function and regulation, Na+ channel structure and function, and Na+ channel trafficking, sequestration and complexing. PMID:25772290

  1. Molecular structure and biological function of proliferating cell nuclear antigen

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Proliferating cell nuclear antigen (PCNA) is the core component of replication complex in eukaryote.As a processive factor of DNA polymerase delta, PCNA coordinates the replication process by interacting with various replication proteins. PCNA appears to play an essential role in many cell events, such as DNA damage repair, cell cycle regulation, and apoptosis, through the coordination or organization of different partners. PCNA is an essential factor in cell proliferation, and has clinical significance in tumor research. In this article we review the functional structure of PCNA, which acts as a function switch in different cell events.

  2. Nuclear medium modification of the F2 structure function

    CERN Document Server

    Athar, M Sajjad; Vacas, M J Vicente

    2009-01-01

    We study the nuclear effects in the electromagnetic structure function $F_{2}(x, Q^2)$ in nuclei in the deep inelastic lepton nucleus scattering process by taking into account Fermi motion, binding, pion and rho meson cloud contributions. Calculations have been done in a local density approximation using relativistic nuclear spectral functions which include nucleon correlations for nuclear matter. The ratios $R_{F2}^A(x,Q^2)=\\frac{2F_2^A(x,Q^2)}{AF_{2}^{Deut}(x,Q^2)}$ are obtained and compared with the recent JLAB results for light nuclei that show a non trivial A dependence.

  3. Nuclear effects in F_3 structure function of nucleon

    CERN Document Server

    Athar, M Sajjad; Vacas, M J Vicente

    2007-01-01

    We study nuclear effects in the $F^A_3(x)$ structure function in the deep inelastic neutrino reactions on iron by using a relativistic framework to describe the nucleon spectral functions in the nucleus. The results for the ratio $R(x,Q^2)=\\frac{F^A_3(x,Q^2)}{AF^N_3(x, Q^2)}$ and the Gross-Llewellyn Smith(GLS) integral $G(x,Q^2)=\\int_x^1 dx F^A_3(x,Q^2)$ in nuclei are discussed and compared with the recent results available in literature from theoretical and phenomenological analyses of experimental data.

  4. Cytoskeleton Molecular Motors: Structures and Their Functions in Neuron.

    Science.gov (United States)

    Xiao, Qingpin; Hu, Xiaohui; Wei, Zhiyi; Tam, Kin Yip

    2016-01-01

    Cells make use of molecular motors to transport small molecules, macromolecules and cellular organelles to target region to execute biological functions, which is utmost important for polarized cells, such as neurons. In particular, cytoskeleton motors play fundamental roles in neuron polarization, extension, shape and neurotransmission. Cytoskeleton motors comprise of myosin, kinesin and cytoplasmic dynein. F-actin filaments act as myosin track, while kinesin and cytoplasmic dynein move on microtubules. Cytoskeleton motors work together to build a highly polarized and regulated system in neuronal cells via different molecular mechanisms and functional regulations. This review discusses the structures and working mechanisms of the cytoskeleton motors in neurons.

  5. Emerging Relationships Between Structure and Ecological Function in the Landscape

    Directory of Open Access Journals (Sweden)

    Robert Brown

    2004-06-01

    Full Text Available The concepts of landscape ecology are theoretically applicable to landscapes anywhere in the world. Much information has been generated relating sizes, shapes, and composition of patches and corridors in the landscape to their ecological function. Many patterns related to ecological processes are emerging that can be applied with increasing confidence in landscape planning and design. In this context, we developed a comprehensive approach that makes use of three-dimensional (3-D models to describe visually the structural properties of landscape elements. This approach may be used by landscape architects so that the patterns they create also have an appropriate ecological function.

  6. Habitat structure, trophic structure and ecosystem function: interactive effects in a bromeliad-insect community.

    Science.gov (United States)

    Srivastava, Diane S

    2006-09-01

    Although previous studies have shown that ecosystem functions are affected by either trophic structure or habitat structure, there has been little consideration of their combined effects. Such interactions may be particularly important in systems where habitat and trophic structure covary. I use the aquatic insects in bromeliads to examine the combined effects of trophic structure and habitat structure on a key ecosystem function: detrital processing. In Costa Rican bromeliads, trophic structure naturally covaries with both habitat complexity and habitat size, precluding any observational analysis of interactions between factors. I therefore designed mesocosms that allowed each factor to be manipulated separately. Increases in mesocosm complexity reduced predator (damselfly larva) efficiency, resulting in high detritivore abundances, indirectly increasing detrital processing rates. However, increased complexity also directly reduced the per capita foraging efficiency of the detritivores. Over short time periods, these trends effectively cancelled each other out in terms of detrital processing. Over longer time periods, more complex patterns emerged. Increases in mesocosm size also reduced both predator efficiency and detritivore efficiency, leading to no net effect on detrital processing. In many systems, ecosystem functions may be impacted by strong interactions between trophic structure and habitat structure, cautioning against examining either effect in isolation.

  7. Alu element-containing RNAs maintain nucleolar structure and function.

    Science.gov (United States)

    Caudron-Herger, Maïwen; Pankert, Teresa; Seiler, Jeanette; Németh, Attila; Voit, Renate; Grummt, Ingrid; Rippe, Karsten

    2015-11-12

    Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production.

  8. Myoglobin structure and function: A multiweek biochemistry laboratory project.

    Science.gov (United States)

    Silverstein, Todd P; Kirk, Sarah R; Meyer, Scott C; Holman, Karen L McFarlane

    2015-01-01

    We have developed a multiweek laboratory project in which students isolate myoglobin and characterize its structure, function, and redox state. The important laboratory techniques covered in this project include size-exclusion chromatography, electrophoresis, spectrophotometric titration, and FTIR spectroscopy. Regarding protein structure, students work with computer modeling and visualization of myoglobin and its homologues, after which they spectroscopically characterize its thermal denaturation. Students also study protein function (ligand binding equilibrium) and are instructed on topics in data analysis (calibration curves, nonlinear vs. linear regression). This upper division biochemistry laboratory project is a challenging and rewarding one that not only exposes students to a wide variety of important biochemical laboratory techniques but also ties those techniques together to work with a single readily available and easily characterized protein, myoglobin.

  9. Relating structure and function of inner hair cell ribbon synapses.

    Science.gov (United States)

    Wichmann, C; Moser, T

    2015-07-01

    In the mammalian cochlea, sound is encoded at synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Each SGN receives input from a single IHC ribbon-type active zone (AZ) and yet SGNs indefatigably spike up to hundreds of Hz to encode acoustic stimuli with submillisecond precision. Accumulating evidence indicates a highly specialized molecular composition and structure of the presynapse, adapted to suit these high functional demands. However, we are only beginning to understand key features such as stimulus-secretion coupling, exocytosis mechanisms, exo-endocytosis coupling, modes of endocytosis and vesicle reformation, as well as replenishment of the readily releasable pool. Relating structure and function has become an important avenue in addressing these points and has been applied to normal and genetically manipulated hair cell synapses. Here, we review some of the exciting new insights gained from recent studies of the molecular anatomy and physiology of IHC ribbon synapses.

  10. Structural and functional characterization of barium zirconium titanate / epoxy composites

    Directory of Open Access Journals (Sweden)

    Filiberto González Garcia

    2011-12-01

    Full Text Available The dielectric behavior of composite materials (barium zirconium titanate / epoxy system was analyzed as a function of ceramic concentration. Structure and morphologic behavior of the composites was investigated by X-ray Diffraction (XRD, Fourier transformed infrared spectroscopy (FT-IR, Raman spectroscopy, field emission scanning electron microscopy (FE-SEM and transmission electron microscopy (TEM analyses. Composites were prepared by mixing the components and pouring them into suitable moulds. It was demonstrated that the amount of inorganic phase affects the morphology of the presented composites. XRD revealed the presence of a single phase while Raman scattering confirmed structural transitions as a function of ceramic concentration. Changes in the ceramic concentration affected Raman modes and the distribution of particles along into in epoxy matrix. Dielectric permittivity and dielectric losses were influenced by filler concentration.

  11. TOPICAL REVIEW: Multimodality imaging of structure and function

    Science.gov (United States)

    Townsend, D. W.

    2008-02-01

    Historically, medical devices to image either anatomical structure or functional processes have developed along somewhat independent paths. The recognition that combining images from different modalities can nevertheless offer significant diagnostic advantages gave rise to sophisticated software techniques to coregister structure and function. Recently, alternatives to retrospective software-based fusion have become available through instrumentation that combines two imaging modalities within a single device, an approach that has since been termed hardware fusion. As a result, following their recent introduction into the clinic, combined PET/CT and SPECT/CT devices are now playing an increasingly important role in the diagnosis and staging of human disease. Recently, although limited to the brain, the first clinical MR scanner with a PET insert, a technically-challenging design, has been undergoing evaluation. This review will follow the development of multimodality instrumentation for clinical use from conception to present-day technology and assess the status and future potential for such devices.

  12. ADAM-15 Disintegrin-Like Domain Structure and Function

    Directory of Open Access Journals (Sweden)

    Dong Lu

    2010-10-01

    Full Text Available The ADAM (a disintegrin-like and metalloproteinase proteins are a family of transmembrane cell-surface proteins with important functions in adhesion and proteolytic processing in all animals. Human ADAM-15 is the only member of the ADAM family with the integrin binding motif Arg-Gly-Asp (RGD in its disintegrin-like domain. This motif is also found in most snake venom disintegrins and other disintegrin-like proteins. This unique RGD motif within ADAM-15 serves as an integrin ligand binding site, through which it plays a pivotal role in interacting with integrin receptors, a large family of heterodimeric transmembrane glycoproteins. This manuscript will present a review of the RGD-containing disintegrin-like domain structures and the structural features responsible for their activity as antagonists of integrin function in relation to the canonical RGD template.

  13. NbIT--a new information theory-based analysis of allosteric mechanisms reveals residues that underlie function in the leucine transporter LeuT.

    Directory of Open Access Journals (Sweden)

    Michael V LeVine

    2014-05-01

    Full Text Available Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i-channels for long-distance information sharing between functional sites, and (ii-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems.

  14. NbIT--a new information theory-based analysis of allosteric mechanisms reveals residues that underlie function in the leucine transporter LeuT.

    Science.gov (United States)

    LeVine, Michael V; Weinstein, Harel

    2014-05-01

    Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems.

  15. NbIT - A New Information Theory-Based Analysis of Allosteric Mechanisms Reveals Residues that Underlie Function in the Leucine Transporter LeuT

    Science.gov (United States)

    LeVine, Michael V.; Weinstein, Harel

    2014-01-01

    Complex networks of interacting residues and microdomains in the structures of biomolecular systems underlie the reliable propagation of information from an input signal, such as the concentration of a ligand, to sites that generate the appropriate output signal, such as enzymatic activity. This information transduction often carries the signal across relatively large distances at the molecular scale in a form of allostery that is essential for the physiological functions performed by biomolecules. While allosteric behaviors have been documented from experiments and computation, the mechanism of this form of allostery proved difficult to identify at the molecular level. Here, we introduce a novel analysis framework, called N-body Information Theory (NbIT) analysis, which is based on information theory and uses measures of configurational entropy in a biomolecular system to identify microdomains and individual residues that act as (i)-channels for long-distance information sharing between functional sites, and (ii)-coordinators that organize dynamics within functional sites. Application of the new method to molecular dynamics (MD) trajectories of the occluded state of the bacterial leucine transporter LeuT identifies a channel of allosteric coupling between the functionally important intracellular gate and the substrate binding sites known to modulate it. NbIT analysis is shown also to differentiate residues involved primarily in stabilizing the functional sites, from those that contribute to allosteric couplings between sites. NbIT analysis of MD data thus reveals rigorous mechanistic elements of allostery underlying the dynamics of biomolecular systems. PMID:24785005

  16. Precision measurement of the neutron spin dependent structure functions

    Energy Technology Data Exchange (ETDEWEB)

    Kolomensky, Y.G.

    1997-02-01

    In experiment E154 at the Stanford Linear Accelerator Center the spin dependent structure function g{sub 1}{sup n} (x, Q{sup 2}) of the neutron was measured by scattering longitudinally polarized 48.3 GeV electrons off a longitudinally polarized {sup 3}He target. The high beam energy allowed the author to extend the kinematic coverage compared to the previous SLAC experiments to 0.014 {le} x {le} 0.7 with an average Q{sup 2} of 5 GeV{sup 2}. The author reports the integral of the spin dependent structure function in the measured range to be {integral}{sub 0.014}{sup 0.7} dx g{sub 1}{sup n}(x, 5 GeV{sup 2}) = {minus}0.036 {+-} 0.004(stat.) {+-} 0.005(syst.). The author observes relatively large values of g{sub 1}{sup n} at low x that call into question the reliability of data extrapolation to x {r_arrow} 0. Such divergent behavior disagrees with predictions of the conventional Regge theory, but is qualitatively explained by perturbative QCD. The author performs a Next-to-Leading Order perturbative QCD analysis of the world data on the nucleon spin dependent structure functions g{sub 1}{sup p} and g{sub 1}{sup n} paying careful attention to the experimental and theoretical uncertainties. Using the parameterizations of the helicity-dependent parton distributions obtained in the analysis, the author evolves the data to Q{sup 2} = 5 GeV{sup 2}, determines the first moments of the polarized structure functions of the proton and neutron, and finds agreement with the Bjorken sum rule.

  17. Structural and Function Prediction of Musa acuminata subsp. Malaccensis Protein

    Directory of Open Access Journals (Sweden)

    Anum Munir

    2016-03-01

    Full Text Available Hypothetical proteins (HPs are the proteins whose presence has been anticipated, yet in vivo function has not been built up. Illustrating the structural and functional privileged insights of these HPs might likewise prompt a superior comprehension of the protein-protein associations or networks in diverse types of life. Bananas (Musa acuminata spp., including sweet and cooking types, are giant perennial monocotyledonous herbs of the order Zingiberales, a sister grouped to the all-around considered Poales, which incorporate oats. Bananas are crucial for nourishment security in numerous tropical and subtropical nations and the most prominent organic product in industrialized nations. In the present study, the hypothetical protein of M. acuminata (Banana was chosen for analysis and modeling by distinctive bioinformatics apparatuses and databases. As indicated by primary and secondary structure analysis, XP_009393594.1 is a stable hydrophobic protein containing a noteworthy extent of α-helices; Homology modeling was done utilizing SWISS-MODEL server where the templates identity with XP_009393594.1 protein was less which demonstrated novelty of our protein. Ab initio strategy was conducted to produce its 3D structure. A few evaluations of quality assessment and validation parameters determined the generated protein model as stable with genuinely great quality. Functional analysis was completed by ProtFun 2.2, and KEGG (KAAS, recommended that the hypothetical protein is a transcription factor with cytoplasmic domain as zinc finger. The protein was observed to be vital for translation process, involved in metabolism, signaling and cellular processes, genetic information processing and Zinc ion binding. It is suggested that further test approval would help to anticipate the structures and functions of other uncharacterized proteins of different plants and living being.

  18. Understanding the structure and function of Bacillus thuringiensis toxins.

    Science.gov (United States)

    Palma, Leopoldo; Berry, Colin

    2016-01-01

    As biological control agents take an expanding share of the pesticides market and the production of insect-resistant crops increases, it is essential to understand the structure and function of the active agents, the invertebrate-active toxins that are the fundamental ingredients of these control systems. The potential for these agents in industry, agriculture and medicine necessitates a thorough investigation of their activity.

  19. Structure-function relations of carbohydrates by neoglycolipid arrays.

    Science.gov (United States)

    Huang, Gang-Liang; Huang, Hua-Liang; Zhang, Hou-Cheng; Wang, Peng-George

    2006-06-01

    The work presented herein is a new noncovalent glycoarray assembly method for microplates created by simply mixing together a carbohydrate and a tetradecylamine. alpha-D-Mannopyranoside, alpha-D-glucopyranoside, and alpha-D-galactopyranoside were utilized in model studies and product formations were detected by lectin binding. The method can be extended to study the steric hindrance effect of carbohydrate-protein interactions, namely the structure-function relations of carbohydrates.

  20. In Medium Nucleon Structure Functions, SRC, and the EMC effect

    CERN Document Server

    Hen, O; Gilad, S; Wood, S A

    2014-01-01

    A proposal approved by the Jefferson Lab PAC to study semi-inclusive deep inelastic scattering (DIS) off the deuteron, tagged with high momentum recoiling protons or neutrons emitted at large angle relative to the momentum transfer. This experiment aims at studying the virtuality dependence of the bound nucleon structure function as a possible cause to the EMC effect and the EMC-SRC correlations. The experiment was approved in 2011 for a total run time of 40 days.

  1. Proton Spin Structure Functions and Quark-Hadron Duality

    Institute of Scientific and Technical Information of China (English)

    DONG Yu-Bing

    2006-01-01

    @@ Quark-hadron duality of three proton spin structure functions g1, g2 and gT are discussed simultaneously. It is found that the onsets of the quark-hadron dualities of g1p, g2p and g3p are similar and they are expected to be at about Q2 ~ 2 GeV2. In addition, our results show that the elastic peak remarkably breaks local quark-hadron duality.

  2. Theoretical description of biomolecular hydration - Application to A-DNA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.E.; Hummer, G. [Los Alamos National Laboratory, NM (United States); Soumpasis, D.M. [Max Planck Inst. for Biophysical Chemistry, Goettingen (Germany)

    1994-12-31

    The local density of water molecules around a biomolecule is constructed from calculated two- and three-points correlation functions of polar solvents in water using a Potential-of-Mean-Force (PMF) expansion. As a simple approximation, the hydration of all polar (including charged) groups in a biomolecule is represented by the hydration of water oxygen in bulk water, and the effect of non-polar groups on hydration are neglected, except for excluded volume effects. Pair and triplet correlation functions are calculated by molecular dynamics simulations. We present calculations of the structural hydration for ideal A-DNA molecules with sequences [d(CG){sub 5}]{sub 2} and [d(C{sub 5}G{sub 5})]{sub 2}. We find that this method can accurately reproduce the hydration patterns of A-DNA observed in neutron diffraction experiments on oriented DNA fibers.

  3. Abdominal Pain, the Adolescent and Altered Brain Structure and Function.

    Directory of Open Access Journals (Sweden)

    Catherine S Hubbard

    Full Text Available Irritable bowel syndrome (IBS is a functional gastrointestinal (GI disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL. Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC, whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC. In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI, whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease

  4. Twist decomposition of Drell-Yan structure functions: phenomenological implications

    CERN Document Server

    Brzeminski, Dawid; Sadzikowski, Mariusz; Stebel, Tomasz

    2016-01-01

    The forward Drell--Yan process in $pp$ scattering at the LHC at $\\sqrt{S}=14$ TeV is considered. We analyze the Drell--Yan structure functions assuming the dominance of a Compton-like emission of a virtual photon from a fast quark scattering off the small $x$ gluons. The color dipole framework is applied to perform quantitatively the twist decomposition of all the Drell--Yan structure functions. Two models of the color dipole scattering are applied: the Golec-Biernat--W\\"{u}sthoff model and the dipole cross section obtained from the Balitsky--Fadin--Kuraev--Lipatov evolution equation. The two models have essentially different higher twist content and the gluon transverse momentum distribution and lead to different significant effects beyond the collinear leading twist description. It is found that the gluon transverse momentum effects are significant in the Drell--Yan structure functions for all Drell--Yan pair masses $M$, and the higher twist effects become important for $M \\lesssim 10$ GeV. It is found that...

  5. Detailed Measurements of Structure Functions from Nucleons and Nuclei

    CERN Multimedia

    2002-01-01

    The experiment will study deep inelastic muon nucleon scattering in a wide range of Q|2~(1-200 (GeV/c)|2) and x~(0.005-0.75). The main aims of the experiment are: \\item a)~~~~Detailed measurements of the nuclear dependence of the structure function F^2|A, of R~=~@s^L/@s^T and of the cross-section for J/@y production. They will provide a basis for the understanding of the EMC effect: the modification of quark and gluon distributions due to the nuclear environment. \\item b)~~~~A simultaneous high luminosity measurement of the structure function F^2 on hydrogen and deuterium. This will provide substantially improved accuracy in the knowledge of the neutron structure function F^2|n, of F^2|p-F^2|n and F^2|n/F^2|p and their Q|2 dependence. Furthermore, the data will allow a determination of the strong coupling constant @a^s(Q|2) with reduced experimental and theoretical uncertainties as well as of the ratio of the down to up quark distributions in the valence region. Due to the large x range covered by the experim...

  6. Influence of nutrient delivery on gut structure and function.

    Science.gov (United States)

    Bragg, L E; Thompson, J S; Rikkers, L F

    1991-01-01

    Food is an important stimulus for the growth of gastrointestinal mucosa. Gut structure is influenced by the route of nutrient administration, dietary composition and the availability of specific nutrients. The alterations in intestinal structure and function that occur when enteral nutrition is withheld suggests that the ingestion of food results in physiologic responses that are responsible for the maintenance of gut mass during the fed state. The mechanism of mucosal suppression that occurs during starvation, stress, and total parenteral nutrition is not completely understood but may involve the absence of luminal substrates, decreased pancreaticobiliary secretions and alterations in the endocrine or paracrine events that normally accompany eating, digestion, and absorption. Enterocytes prefer glutamine and ketone bodies as oxidative fuels, whereas colonocytes utilize short chain fatty acids. Although enteral delivery of nutrients is the preferred route for maintenance of intestinal mass, provision of specific nutrients and hormonal stimulation during parenteral alimentation has been shown to be important in maintaining mucosal structure and function. If not adequately maintained, the intestine becomes susceptible to a variety of injuries which may result in impaired ability to digest and absorb nutrients and loss of mucosal barrier function.

  7. In silico predicted structural and functional robustness of piscine steroidogenesis.

    Science.gov (United States)

    Hala, D; Huggett, D B

    2014-03-21

    Assessments of metabolic robustness or susceptibility are inherently dependent on quantitative descriptions of network structure and associated function. In this paper a stoichiometric model of piscine steroidogenesis was constructed and constrained with productions of selected steroid hormones. Structural and flux metrics of this in silico model were quantified by calculating extreme pathways and optimal flux distributions (using linear programming). Extreme pathway analysis showed progestin and corticosteroid synthesis reactions to be highly participant in extreme pathways. Furthermore, reaction participation in extreme pathways also fitted a power law distribution (degree exponent γ=2.3), which suggested that progestin and corticosteroid reactions act as 'hubs' capable of generating other functionally relevant pathways required to maintain steady-state functionality of the network. Analysis of cofactor usage (O2 and NADPH) showed progestin synthesis reactions to exhibit high robustness, whereas estrogen productions showed highest energetic demands with low associated robustness to maintain such demands. Linear programming calculated optimal flux distributions showed high heterogeneity of flux values with a near-random power law distribution (degree exponent γ≥2.7). Subsequently, network robustness was tested by assessing maintenance of metabolite flux-sum subject to targeted deletions of rank-ordered (low to high metric) extreme pathway participant and optimal flux reactions. Network robustness was susceptible to deletions of extreme pathway participant reactions, whereas minimal impact of high flux reaction deletion was observed. This analysis shows that the steroid network is susceptible to perturbation of structurally relevant (extreme pathway) reactions rather than those carrying high flux.

  8. Enthalpy-entropy compensation in biomolecular halogen bonds measured in DNA junctions.

    Science.gov (United States)

    Carter, Megan; Voth, Andrea Regier; Scholfield, Matthew R; Rummel, Brittany; Sowers, Lawrence C; Ho, P Shing

    2013-07-23

    Interest in noncovalent interactions involving halogens, particularly halogen bonds (X-bonds), has grown dramatically in the past decade, propelled by the use of X-bonding in molecular engineering and drug design. However, it is clear that a complete analysis of the structure-energy relationship must be established in biological systems to fully exploit X-bonds for biomolecular engineering. We present here the first comprehensive experimental study to correlate geometries with their stabilizing potentials for fluorine (F), chlorine (Cl), bromine (Br), or iodine (I) X-bonds in a biological context. For these studies, we determine the single-crystal structures of DNA Holliday junctions containing halogenated uracil bases that compete X-bonds against classic hydrogen bonds (H-bonds), estimate the enthalpic energies of the competing interactions in the crystal system through crystallographic titrations, and compare the enthalpic and entropic energies of bromine and iodine X-bonds in solution by differential scanning calorimetry. The culmination of these studies demonstrates that enthalpic stabilization of X-bonds increases with increasing polarizability from F to Cl to Br to I, which is consistent with the σ-hole theory of X-bonding. Furthermore, an increase in the X-bonding potential is seen to direct the interaction toward a more ideal geometry. However, the entropic contributions to the total free energies must also be considered to determine how each halogen potentially contributes to the overall stability of the interaction. We find that bromine has the optimal balance between enthalpic and entropic energy components, resulting in the lowest free energy for X-bonding in this DNA system. The X-bond formed by iodine is more enthalpically stable, but this comes with an entropic cost, which we attribute to crowding effects. Thus, the overall free energy of an X-bonding interaction balances the stabilizing electrostatic effects of the σ-hole against the competing

  9. Alternative Conformations of Cytochrome c: Structure, Function, and Detection.

    Science.gov (United States)

    Hannibal, Luciana; Tomasina, Florencia; Capdevila, Daiana A; Demicheli, Verónica; Tórtora, Verónica; Alvarez-Paggi, Damián; Jemmerson, Ronald; Murgida, Daniel H; Radi, Rafael

    2016-01-26

    Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.

  10. Plant lessons: exploring ABCB functionality through structural modeling

    Directory of Open Access Journals (Sweden)

    Aurélien eBailly

    2012-01-01

    Full Text Available In contrast to mammalian ABCB1 proteins, narrow substrate specificity has been extensively documented for plant orthologs shown to catalyze the transport of the plant hormone, auxin. Using the crystal structures of the multidrug exporters Sav1866 and MmABCB1 as templates, we have developed structural models of plant ABCB proteins with a common architecture. Comparisons of these structures identified kingdom-specific candidate substrate-binding regions within the translocation chamber formed by the transmembrane domains of ABCBs from the model plant Arabidopsis. These results suggest an early evolutionary divergence of plant and mammalian ABCBs. Validation of these models becomes a priority for efforts to elucidate ABCB function and manipulate this class of transporters to enhance plant productivity and quality.

  11. Structure-Function of Falcipains: Malarial Cysteine Proteases

    Directory of Open Access Journals (Sweden)

    Kailash C. Pandey

    2012-01-01

    Full Text Available Evidence indicates that cysteine proteases play essential role in malaria parasites; therefore an obvious area of investigation is the inhibition of these enzymes to treat malaria. Studies with cysteine protease inhibitors and manipulating cysteine proteases genes have suggested a role for cysteine proteases in hemoglobin hydrolysis. The best characterized Plasmodium cysteine proteases are falcipains, which are papain family enzymes. Falcipain-2 and falcipain-3 are major hemoglobinases of P. falciparum. Structural and functional analysis of falcipains showed that they have unique domains including a refolding domain and a hemoglobin binding domain. Overall, the complexes of falcipain-2 and falcipain-3 with small and macromolecular inhibitors provide structural insight to facilitate the design or modification of effective drug treatment against malaria. Drug development targeting falcipains should be aided by a strong foundation of biochemical and structural studies.

  12. Interpenetration in coordination polymers: structural diversities toward porous functional materials

    Directory of Open Access Journals (Sweden)

    Ritesh Haldar

    2015-03-01

    Full Text Available Interpenetration is a natural phenomenon frequently encountered in porous coordination polymers (PCPs or metal-organic frameworks (MOFs. Traditionally interpenetration has been considered as a threat to permanent porosity and several strategies have been adopted to control the framework interpenetration. Recent literature reports have unveiled that interpenetration has paramount importance in several material properties particularly in storage and separation of small gas molecules. Such frameworks also show interesting structural flexibility based on shearing or movement of the nets and also reveals guest induced dynamic structural transformation for modulated specific functions. In this review, we will emphasize several interpenetration phenomena observed in coordination polymers, their intriguing structural aspects and fascinating material properties.

  13. A structural and functional perspective of alphavirus replication and assembly.

    Science.gov (United States)

    Jose, Joyce; Snyder, Jonathan E; Kuhn, Richard J

    2009-09-01

    Alphaviruses are small, spherical, enveloped, positive-sense ssRNA viruses responsible for a considerable number of human and animal diseases. Alphavirus members include Chikungunya virus, Sindbis virus, Semliki Forest virus, the western, eastern and Venezuelan equine encephalitis viruses, and the Ross River virus. Alphaviruses can cause arthritic diseases and encephalitis in humans and animals and continue to be a worldwide threat. The viruses are transmitted by blood-sucking arthropods, and replicate in both arthropod and vertebrate hosts. Alphaviruses form spherical particles (65-70 nm in diameter) with icosahedral symmetry and a triangulation number of four. The icosahedral structures of alphaviruses have been defined to very high resolutions by cryo-electron microscopy and crystallographic studies. In this review, we summarize the major events in alphavirus infection: entry, replication, assembly and budding. We focus on data acquired from structural and functional studies of the alphaviruses. These structural and functional data provide a broader perspective of the virus lifecycle and structure, and allow additional insight into these important viruses.

  14. Food webs: reconciling the structure and function of biodiversity.

    Science.gov (United States)

    Thompson, Ross M; Brose, Ulrich; Dunne, Jennifer A; Hall, Robert O; Hladyz, Sally; Kitching, Roger L; Martinez, Neo D; Rantala, Heidi; Romanuk, Tamara N; Stouffer, Daniel B; Tylianakis, Jason M

    2012-12-01

    The global biodiversity crisis concerns not only unprecedented loss of species within communities, but also related consequences for ecosystem function. Community ecology focuses on patterns of species richness and community composition, whereas ecosystem ecology focuses on fluxes of energy and materials. Food webs provide a quantitative framework to combine these approaches and unify the study of biodiversity and ecosystem function. We summarise the progression of food-web ecology and the challenges in using the food-web approach. We identify five areas of research where these advances can continue, and be applied to global challenges. Finally, we describe what data are needed in the next generation of food-web studies to reconcile the structure and function of biodiversity.

  15. Quark mass functions and pion structure in Minkowski space

    Energy Technology Data Exchange (ETDEWEB)

    Biernat, Elmer P. [CFTP, Institute Superior Tecnico; Gross, Franz L. [JLAB; Pena, Maria Teresa [CFTP, Institute Superior Tecnico; Stadler, Alfred [University of Evora

    2014-03-01

    We present a study of the dressed quark mass function and the pion structure in Minkowski space using the Covariant Spectator Theory (CST). The quark propagators are dressed with the same kernel that describes the interaction between different quarks. We use an interaction kernel in momentum space that is a relativistic generalization of the linear confining q-qbar potential and a constant potential shift that defines the energy scale. The confining interaction has a Lorentz scalar part that is not chirally invariant by itself but decouples from the equations in the chiral limit and therefore allows the Nambu--Jona-Lasinio (NJL) mechanism to work. We adjust the parameters of our quark mass function calculated in Minkowski-space to agree with LQCD data obtained in Euclidean space. Results of a calculation of the pion electromagnetic form factor in the relativistic impulse approximation using the same mass function are presented and compared with experimental data.

  16. Effects of soccer heading on brain structure and function

    Directory of Open Access Journals (Sweden)

    Ana Carolina Oliveira Rodrigues

    2016-03-01

    Full Text Available Soccer is the most popular sport in the world, with more than 265 million players worldwide, including professional and amateur ones. Soccer is unique in comparison to other sports, as it is the only sport in which participants purposely use their head to hit the ball. Heading is considered an offensive or defensive move whereby the player’s unprotected head is used to deliberately impact the ball and direct it during play. A soccer player can be subjected to an average of six to twelve incidents of heading the ball per competitive game, where the ball reaches high velocities. Moreover, in practice sessions, heading training, which involves heading the ball repeatedly at low velocities, is common. Although the scientific community, as well as the media, has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The purpose of this study is to review the existing literature regarding the effects of soccer heading on brain structure and function. Only in the last years some investigations have addressed the impact of heading on brain structure, by using neuroimaging techniques. Similarly, there have been some recent studies investigating biochemical markers of brain injury in soccer players. There is evidence of association between heading and abnormal brain structure, but the data are still preliminary. Also, some studies have suggested that subconcussive head impacts, as heading, could cause cognitive impairment, whereas others have not corroborated this finding. Questions persist as to whether or not heading is deleterious to cognitive functioning. Further studies, especially with longitudinal designs, are needed to clarify the clinical significance of heading as a cause of brain injury and to identify risk factors. Such investigations might contribute to the

  17. Study of structure function correlation of chemokine receptor CXCR4

    Institute of Scientific and Technical Information of China (English)

    ZHENG Hong; Stephen C PEIPER; ZHU Xi-hua

    2002-01-01

    Objective: To explore the correlation between structure domains and functions of chemokine receptor CXCR4. Methods: After the establishment of wild type chemokine receptor CXCR4 and CXCR2 expressing cell lines, 5 CXCR4/CXCR2 chimeras, 2 CXCR4 mutants were stably expressed on CHO cell line.Binding activities of all variants with the ligand, recombinant human SDF-1β, signal transduction ability after stimulation and their function as coreceptor for HIV-1 were studied with ligand-binding assay, Cytosensor/microphysiometry and cell-cell reporter gene fusion assay. Results: Among all 7 changed CXCR4 receptors, 3 chimeras (2444a, 4442, 4122), and 1 mutant (CXCR4-Tr) bond with SDF-1β in varying degrees, of which only 2444a totally and CXCR4-Tr partially maintain signaling. All changed receptors except for 4222 could act as coreceptors for HIV-1(LAI) in varying degrees. Conclusion: Several structure domains of CXCR4 are involved in the binding with SDF-1β, among which, N-terminal extracellular domain has high affinity of binding with SDF-1β, and the 3rd extracellular loop contributes to the binding, too. Although the C-terminal intracellular domain has no association with the maintenance of the overall structure of the receptor and ligand binding capability, the signaling is decreased when this domain is truncated. For CXCR4 signaling, not only is the conserved motif DRY box needed, but also the characterized conformation of the whole molecule must be formed when activation is required. There are some overlaps between SDF-1β binding domains and coreceptor function domains in molecular structure of CXCR4.

  18. Brain structural and functional correlates of resilience to Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Sophia eFrangou

    2012-01-01

    Full Text Available Background: Resilient adaptation can be construed in different ways, but as used here it refers to the adaptive brain changes associated with avoidance of psychopathology despite familiar risk for Bipolar Disorder (BD. Although family history of BD is associated with elevated risk of affective morbidity a significant proportion of first-degree relatives of BD patients remains free of psychopathology. Examination of brain structure and function in these individuals may inform on adaptive changes that may pre-empt disease expression. Methods: Data presented here are derived from the Vulnerability to Bipolar Disorders (VIBES study which includes patients with BD, asymptomatic relatives and healthy controls. Participants underwent extensive investigations including brain structural (sMRI and functional magnetic resonance imaging (fMRI. The data presented here focus on sMRI voxel-based-morphometry and on conventional and connectivity analyses of fMRI data obtained during the Stroop Colour Word Test (SCWT, a task of cognitive control during conflict resolution. All analyses were implemented in SPM (www.fil.ion.ucl.ac.uk/spm. Resilience in relatives was operationalized as the absence of clinical-range symptoms.Results: Resilient relatives of BD patients expressed structural, functional and connectivity changes reflecting the effect of genetic risk on the brain. These included increased insular volume, decreased activation within the posterior and inferior parietal regions involved in selective attention during the SCWT, and reduced fronto-insular and fronto-cingulate connectivity.Resilience was associated with increased cerebellar vermal volume and enhanced functional coupling between the dorsal and the ventral prefrontal cortex. Conclusions: Our findings suggests the presence of biological mechanisms associated with resilient adaptation of brain networks and pave the way for the identification of outcome-specific trajectories given a particular

  19. Gene function prediction based on the Gene Ontology hierarchical structure.

    Science.gov (United States)

    Cheng, Liangxi; Lin, Hongfei; Hu, Yuncui; Wang, Jian; Yang, Zhihao

    2014-01-01

    The information of the Gene Ontology annotation is helpful in the explanation of life science phenomena, and can provide great support for the research of the biomedical field. The use of the Gene Ontology is gradually affecting the way people store and understand bioinformatic data. To facilitate the prediction of gene functions with the aid of text mining methods and existing resources, we transform it into a multi-label top-down classification problem and develop a method that uses the hierarchical relationships in the Gene Ontology structure to relieve the quantitative imbalance of positive and negative training samples. Meanwhile the method enhances the discriminating ability of classifiers by retaining and highlighting the key training samples. Additionally, the top-down classifier based on a tree structure takes the relationship of target classes into consideration and thus solves the incompatibility between the classification results and the Gene Ontology structure. Our experiment on the Gene Ontology annotation corpus achieves an F-value performance of 50.7% (precision: 52.7% recall: 48.9%). The experimental results demonstrate that when the size of training set is small, it can be expanded via topological propagation of associated documents between the parent and child nodes in the tree structure. The top-down classification model applies to the set of texts in an ontology structure or with a hierarchical relationship.

  20. iBIOMES: managing and sharing biomolecular simulation data in a distributed environment.

    Science.gov (United States)

    Thibault, Julien C; Facelli, Julio C; Cheatham, Thomas E

    2013-03-25

    Biomolecular simulations, which were once batch queue or compute limited, have now become data analysis and management limited. In this paper we introduce a new management system for large biomolecular simulation and computational chemistry data sets. The system can be easily deployed on distributed servers to create a mini-grid at the researcher's site. The system not only offers a simple data deposition mechanism but also a way to register data into the system without moving the data from their original location. Any registered data set can be searched and downloaded using a set of defined metadata for molecular dynamics and quantum mechanics and visualized through a dynamic Web interface.

  1. The nuclear matrix: a structural milieu for genomic function.

    Science.gov (United States)

    Berezney, R; Mortillaro, M J; Ma, H; Wei, X; Samarabandu, J

    1995-01-01

    While significant progress has been made in elucidating molecular properties of specific genes and their regulation, our understanding of how the whole genome is coordinated has lagged behind. To understand how the genome functions as a coordinated whole, we must understand how the nucleus is put together and functions as a whole. An important step in that direction occurred with the isolation and characterization of the nuclear matrix. Aside from the plethora of functional properties associated with these isolated nuclear structures, they have enabled the first direct examination and molecular cloning of specific nuclear matrix proteins. The isolated nuclear matrix can be used for providing an in vitro model for understanding nuclear matrix organization in whole cells. Recent development of high-resolution and three-dimensional approaches for visualizing domains of genomic organization and function in situ has provided corroborative evidence for the nuclear matrix as the site of organization for replication, transcription, and post-transcriptional processing. As more is learned about these in situ functional sites, appropriate experiments could be designed to test molecular mechanisms with the in vitro nuclear matrix systems. This is illustrated in this chapter by the studies of nuclear matrix-associated DNA replication which have evolved from biochemical studies of in vitro nuclear matrix systems toward three-dimensional computer image analysis of replication sites for individual genes.

  2. Structural and functional analysis of multi-interface domains.

    Directory of Open Access Journals (Sweden)

    Liang Zhao

    Full Text Available A multi-interface domain is a domain that can shape multiple and distinctive binding sites to contact with many other domains, forming a hub in domain-domain interaction networks. The functions played by the multiple interfaces are usually different, but there is no strict bijection between the functions and interfaces as some subsets of the interfaces play the same function. This work applies graph theory and algorithms to discover fingerprints for the multiple interfaces of a domain and to establish associations between the interfaces and functions, based on a huge set of multi-interface proteins from PDB. We found that about 40% of proteins have the multi-interface property, however the involved multi-interface domains account for only a tiny fraction (1.8% of the total number of domains. The interfaces of these domains are distinguishable in terms of their fingerprints, indicating the functional specificity of the multiple interfaces in a domain. Furthermore, we observed that both cooperative and distinctive structural patterns, which will be useful for protein engineering, exist in the multiple interfaces of a domain.

  3. Evolution, structure and function of hydrologic subsystems in hillslopes

    Science.gov (United States)

    Troch, P. A.; Brooks, P.; Chorover, J.; Huxman, T.; McDonnell, J. J.; Rasmussen, C.; Sivapalan, M.

    2007-12-01

    Hillslopes offer a useful elementary scale to construct catchment hydrologic models, and to understand the role of water in the landscape. However, hillslopes exhibit enormous complexity and heterogeneity, much of which is not easily observable. The complexity is driven by the interactions between water, biogeochemistry, ecology and soils, within the constraints set by the climate and the geologic history of the system. These interactions create complex, non-random patterns and structures in space-time. Current models have difficulty accounting for these interactions and unobserved structural complexity. A new approach may ask: why do the complex structures exist at all? Taking the view that the hydrology of a landscape has evolved along with its soils, ecology and geomorphology, we may ask if the hydrologic subsystem of a hillslope has a functional role in the maintenance of the overall system. This functional role may be expressed as an organizing principle - a constraint on possible ways that the hydrologic flowpaths may be organized such that the functional role is met. If a relationship can be established between an organizing principle and the structure of hydrologic flow-paths and storages, it can form the basis for developing closure relations at the hillslope scale that have meaningful relationships to the underlying dynamics. In this way, heterogeneity and complexity of hillslopes are no longer problems to be overcome, but rather are keys to making meaningful predictions. Formulating and testing organizing principles will necessarily require the synthesis of knowledge from many disciplines. One approach is to construct artificial hillslopes in a controlled environment, and use them to ask, given a set of observable constraints (climate, soil, ecologic and biogeochemical parameters) which structures and responses are "behavioral" - in the sense that they fulfill the function set by the organizing principle. Such artificial hillslopes will be constructed at

  4. Plant Surfaces: Structures and Functions for Biomimetic Innovations

    Science.gov (United States)

    Barthlott, Wilhelm; Mail, Matthias; Bhushan, Bharat; Koch, Kerstin

    2017-04-01

    An overview of plant surface structures and their evolution is presented. It combines surface chemistry and architecture with their functions and refers to possible biomimetic applications. Within some 3.5 billion years biological species evolved highly complex multifunctional surfaces for interacting with their environments: some 10 million living prototypes (i.e., estimated number of existing plants and animals) for engineers. The complexity of the hierarchical structures and their functionality in biological organisms surpasses all abiotic natural surfaces: even superhydrophobicity is restricted in nature to living organisms and was probably a key evolutionary step with the invasion of terrestrial habitats some 350-450 million years ago in plants and insects. Special attention should be paid to the fact that global environmental change implies a dramatic loss of species and with it the biological role models. Plants, the dominating group of organisms on our planet, are sessile organisms with large multifunctional surfaces and thus exhibit particular intriguing features. Superhydrophilicity and superhydrophobicity are focal points in this work. We estimate that superhydrophobic plant leaves (e.g., grasses) comprise in total an area of around 250 million km2, which is about 50% of the total surface of our planet. A survey of structures and functions based on own examinations of almost 20,000 species is provided, for further references we refer to Barthlott et al. (Philos. Trans. R. Soc. A 374: 20160191, 1). A basic difference exists between aquatic non-vascular and land-living vascular plants; the latter exhibit a particular intriguing surface chemistry and architecture. The diversity of features is described in detail according to their hierarchical structural order. The first underlying and essential feature is the polymer cuticle superimposed by epicuticular wax and the curvature of single cells up to complex multicellular structures. A descriptive terminology

  5. Output-input ratio in thermally fluctuating biomolecular machines.

    Science.gov (United States)

    Kurzynski, Michal; Torchala, Mieczyslaw; Chelminiak, Przemyslaw

    2014-01-01

    Biological molecular machines are proteins that operate under isothermal conditions and hence are referred to as free energy transducers. They can be formally considered as enzymes that simultaneously catalyze two chemical reactions: the free energy-donating (input) reaction and the free energy-accepting (output) one. Most if not all biologically active proteins display a slow stochastic dynamics of transitions between a variety of conformational substates composing their native state. This makes the description of the enzymatic reaction kinetics in terms of conventional rate constants insufficient. In the steady state, upon taking advantage of the assumption that each reaction proceeds through a single pair (the gate) of transition conformational substates of the enzyme-substrates complex, the degree of coupling between the output and the input reaction fluxes has been expressed in terms of the mean first-passage times on a conformational transition network between the distinguished substates. The theory is confronted with the results of random-walk simulations on the five-dimensional hypercube. The formal proof is given that, for single input and output gates, the output-input degree of coupling cannot exceed unity. As some experiments suggest such exceeding, looking for the conditions for increasing the degree of coupling value over unity challenges the theory. Performed simulations of random walks on several model networks involving more extended gates indicate that the case of the degree of coupling value higher than 1 is realized in a natural way on critical branching trees extended by long-range shortcuts. Such networks are scale-free and display the property of the small world. For short-range shortcuts, the networks are scale-free and fractal, representing a reasonable model for biomolecular machines displaying tight coupling, i.e., the degree of coupling equal exactly to unity. A hypothesis is stated that the protein conformational transition networks, as

  6. Optimizing Scoring Function of Protein-Nucleic Acid Interactions with Both Affinity and Specificity

    Science.gov (United States)

    Yan, Zhiqiang; Wang, Jin

    2013-01-01

    Protein-nucleic acid (protein-DNA and protein-RNA) recognition is fundamental to the regulation of gene expression. Determination of the structures of the protein-nucleic acid recognition and insight into their interactions at molecular level are vital to understanding the regulation function. Recently, quantitative computational approach has been becoming an alternative of experimental technique for predicting the structures and interactions of biomolecular recognition. However, the progress of protein-nucleic acid structure prediction, especially protein-RNA, is far behind that of the protein-ligand and protein-protein structure predictions due to the lack of reliable and accurate scoring function for quantifying the protein-nucleic acid interactions. In this work, we developed an accurate scoring function (named as SPA-PN, SPecificity and Affinity of the Protein-Nucleic acid interactions) for protein-nucleic acid interactions by incorporating both the specificity and affinity into the optimization strategy. Specificity and affinity are two requirements of highly efficient and specific biomolecular recognition. Previous quantitative descriptions of the biomolecular interactions considered the affinity, but often ignored the specificity owing to the challenge of specificity quantification. We applied our concept of intrinsic specificity to connect the conventional specificity, which circumvents the challenge of specificity quantification. In addition to the affinity optimization, we incorporated the quantified intrinsic specificity into the optimization strategy of SPA-PN. The testing results and comparisons with other scoring functions validated that SPA-PN performs well on both the prediction of binding affinity and identification of native conformation. In terms of its performance, SPA-PN can be widely used to predict the protein-nucleic acid structures and quantify their interactions. PMID:24098651

  7. A Comparative Study on Optimal Structural Dynamics Using Wavelet Functions

    Directory of Open Access Journals (Sweden)

    Seyed Hossein Mahdavi

    2015-01-01

    Full Text Available Wavelet solution techniques have become the focus of interest among researchers in different disciplines of science and technology. In this paper, implementation of two different wavelet basis functions has been comparatively considered for dynamic analysis of structures. For this aim, computational technique is developed by using free scale of simple Haar wavelet, initially. Later, complex and continuous Chebyshev wavelet basis functions are presented to improve the time history analysis of structures. Free-scaled Chebyshev coefficient matrix and operation of integration are derived to directly approximate displacements of the corresponding system. In addition, stability of responses has been investigated for the proposed algorithm of discrete Haar wavelet compared against continuous Chebyshev wavelet. To demonstrate the validity of the wavelet-based algorithms, aforesaid schemes have been extended to the linear and nonlinear structural dynamics. The effectiveness of free-scaled Chebyshev wavelet has been compared with simple Haar wavelet and two common integration methods. It is deduced that either indirect method proposed for discrete Haar wavelet or direct approach for continuous Chebyshev wavelet is unconditionally stable. Finally, it is concluded that numerical solution is highly benefited by the least computation time involved and high accuracy of response, particularly using low scale of complex Chebyshev wavelet.

  8. Structure and function of the hearts of lizards and snakes.

    Science.gov (United States)

    Jensen, Bjarke; Moorman, Antoon F M; Wang, Tobias

    2014-05-01

    With approximately 7000 species, snakes and lizards, collectively known as squamates, are by far the most species-rich group of reptiles. It was from reptile-like ancestors that mammals and birds evolved and squamates can be viewed as phylogenetically positioned between them and fishes. Hence, their hearts have been studied for more than a century yielding insights into the group itself and into the independent evolution of the fully divided four-chambered hearts of mammals and birds. Structurally the heart is complex and debates persist on rudimentary issues such as identifying structures critical to understanding ventricle function. In seeking to resolve these controversies we have generated three-dimensional (3D) models in portable digital format (pdf) of the anaconda and anole lizard hearts ('typical' squamate hearts) and the uniquely specialized python heart with comprehensive annotations of structures and cavities. We review the anatomy and physiology of squamate hearts in general and emphasize the unique features of pythonid and varanid lizard hearts that endow them with mammal-like blood pressures. Excluding pythons and varanid lizards it is concluded that the squamate heart has a highly consistent design including a disproportionately large right side (systemic venous) probably due to prevailing pulmonary bypass (intraventricular shunting). Unfortunately, investigations on rudimentary features are sparse. We therefore point out gaps in our knowledge, such as the size and functional importance of the coronary vasculature and of the first cardiac chamber, the sinus venosus, and highlight areas with implications for vertebrate cardiac evolution.

  9. Methylglyoxal-induced modifications of hemoglobin: structural and functional characteristics.

    Science.gov (United States)

    Bose, Tania; Bhattacherjee, Abhishek; Banerjee, Sauradipta; Chakraborti, Abhay Sankar

    2013-01-15

    Methylglyoxal (MG) reacts with proteins to form advanced glycation end products (AGEs). Although hemoglobin modification by MG is known, the modified protein is not yet characterized. We have studied the nature of AGE formed by MG on human hemoglobin (HbA(0)) and its effect on structure and function of the protein. After reaction of HbA(0) with MG, the modified protein (MG-Hb) was separated and its properties were compared with those of the unmodified protein HbA(0). As shown by MALDI-mass spectrometry, MG converted Arg-92α and Arg-104β to hydroimidazolones in MG-Hb. Compared to HbA(0), MG-Hb exhibited decreased absorbance around 280nm, reduced tryptophan fluorescence (excitation 285nm) and increased α-helix content. However, MG modification did not change the quaternary structure of the heme protein. MG-Hb appeared to be more thermolabile than HbA(0). The modified protein was found to be more effective than HbA(0) in H(2)O(2)-mediated iron release and oxidative damages involving Fenton reaction. MG-Hb exhibited less peroxidase activity and more esterase activity than HbA(0). MG-induced structural and functional changes of hemoglobin may enhance oxidative stress and associated complications, particularly in diabetes mellitus with increased level of MG.

  10. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain

    Directory of Open Access Journals (Sweden)

    Becky Wong

    2016-01-01

    Full Text Available Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1 whether the language neural network is different for first (dominant versus second (nondominant language processing; (2 the effects of bilinguals’ executive functioning on the structure and function of the “universal” language neural network; (3 the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4 the effects of age of acquisition and proficiency of the user’s second language in the bilingual brain, and how these have implications for future research in neurolinguistics.

  11. Cell-based composite materials with programmed structures and functions

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-03-01

    The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

  12. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

    Science.gov (United States)

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics.

  13. Understanding structure, function, and mutations in the mitochondrial ATP synthase

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2015-03-01

    Full Text Available The mitochondrial ATP synthase is a multimeric enzyme complex with an overall molecular weight of about 600,000 Da. The ATP synthase is a molecular motor composed of two separable parts: F1 and Fo. The F1 portion contains the catalytic sites for ATP synthesis and protrudes into the mitochondrial matrix. Fo forms a proton turbine that is embedded in the inner membrane and connected to the rotor of F1. The flux of protons flowing down a potential gradient powers the rotation of the rotor driving the synthesis of ATP. Thus, the flow of protons though Fo is coupled to the synthesis of ATP. This review will discuss the structure/function relationship in the ATP synthase as determined by biochemical, crystallographic, and genetic studies. An emphasis will be placed on linking the structure/function relationship with understanding how disease causing mutations or putative single nucleotide polymorphisms (SNPs in genes encoding the subunits of the ATP synthase, will affect the function of the enzyme and the health of the individual. The review will start by summarizing the current understanding of the subunit composition of the enzyme and the role of the subunits followed by a discussion on known mutations and their effect on the activity of the ATP synthase. The review will conclude with a summary of mutations in genes encoding subunits of the ATP synthase that are known to be responsible for human disease, and a brief discussion on SNPs.

  14. Overexpression of neurofilament H disrupts normal cell structure and function

    Science.gov (United States)

    Szebenyi, Gyorgyi; Smith, George M.; Li, Ping; Brady, Scott T.

    2002-01-01

    Studying exogenously expressed tagged proteins in live cells has become a standard technique for evaluating protein distribution and function. Typically, expression levels of experimentally introduced proteins are not regulated, and high levels are often preferred to facilitate detection. However, overexpression of many proteins leads to mislocalization and pathologies. Therefore, for normative studies, moderate levels of expression may be more suitable. To understand better the dynamics of intermediate filament formation, transport, and stability in a healthy, living cell, we inserted neurofilament heavy chain (NFH)-green fluorescent protein (GFP) fusion constructs in adenoviral vectors with tetracycline (tet)-regulated promoters. This system allows for turning on or off the synthesis of NFH-GFP at a selected time, for a defined period, in a dose-dependent manner. We used this inducible system for live cell imaging of changes in filament structure and cell shape, motility, and transport associated with increasing NFH-GFP expression. Cells with low to intermediate levels of NFH-GFP were structurally and functionally similar to neighboring, nonexpressing cells. In contrast, overexpression led to pathological alterations in both filament organization and cell function. Copyright 2002 Wiley-Liss, Inc.

  15. Structure/Function/Dynamics of Photosystem II Plastoquinone Binding Sites

    Science.gov (United States)

    Lambreva, Maya D.; Russo, Daniela; Polticelli, Fabio; Scognamiglio, Viviana; Antonacci, Amina; Zobnina, Veranika; Campi, Gaetano; Rea, Giuseppina

    2014-01-01

    Photosystem II (PSII) continuously attracts the attention of researchers aiming to unravel the riddle of its functioning and efficiency fundamental for all life on Earth. Besides, an increasing number of biotechnological applications have been envisaged exploiting and mimicking the unique properties of this macromolecular pigment-protein complex. The PSII organization and working principles have inspired the design of electrochemical water splitting schemes and charge separating triads in energy storage systems as well as biochips and sensors for environmental, agricultural and industrial screening of toxic compounds. An intriguing opportunity is the development of sensor devices, exploiting native or manipulated PSII complexes or ad hoc synthesized polypeptides mimicking the PSII reaction centre proteins as bio-sensing elements. This review offers a concise overview of the recent improvements in the understanding of structure and function of PSII donor side, with focus on the interactions of the plastoquinone cofactors with the surrounding environment and operational features. Furthermore, studies focused on photosynthetic proteins structure/function/dynamics and computational analyses aimed at rational design of high-quality bio-recognition elements in biosensor devices are discussed. PMID:24678671

  16. A compilation of structure functions in deep inelastic scattering

    CERN Document Server

    Gehrmann, T; Whalley, M R

    1999-01-01

    A compilation of all the available data on the unpolarized structure functions F/sub 2/ and xF/sub 3/, R=( sigma /sub L// sigma /sub T/), the virtual photon asymmetries A/sub 1/ and A/sub 2/ and the polarized structure functions g/sub 1/ and g/sub 2/, from deep inelastic lepton scattering off protons, deuterium and nuclei is presented. The relevant experiments at CERN, DESY, Fermilab and SLAC from 1991, the date of our earlier review, to the present day are covered. A brief general theoretical introduction is given followed by the data presented both in tabular and graphical form and, for the F/sub 2/ and XF/sub 3/ data, the predictions based on the MRST98 and CTEQ4 parton distribution functions are also displayed. All the data in this review, together with data on a wide variety of other reactions, can be found in and retrieved from the Durham-RAL HEP Databases on the World-Wide-Web (http://durpdg.dur.ac.uk/HEPDATA). (76 refs).

  17. Structural and Functional Changes With the Aging Kidney.

    Science.gov (United States)

    Denic, Aleksandar; Glassock, Richard J; Rule, Andrew D

    2016-01-01

    Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

  18. Structure and functional annotation of hypothetical proteins having putative Rubisco activase function from Vitis vinifera.

    Science.gov (United States)

    Kumar, Suresh

    2015-01-01

    Rubisco is a very large, complex and one of the most abundant proteins in the world and comprises up to 50% of all soluble protein in plants. The activity of Rubisco, the enzyme that catalyzes CO2 assimilation in photosynthesis, is regulated by Rubisco activase (Rca). In the present study, we searched for hypothetical protein of Vitis vinifera which has putative Rubisco activase function. The Arabidopsis and tobacco Rubisco activase protein sequences were used as seed sequences to search against Vitis vinifera in UniprotKB database. The selected hypothetical proteins of Vitis vinifera were subjected to sequence, structural and functional annotation. Subcellular localization predictions suggested it to be cytoplasmic protein. Homology modelling was used to define the three-dimensional (3D) structure of selected hypothetical proteins of Vitis vinifera. Template search revealed that all the hypothetical proteins share more than 80% sequence identity with structure of green-type Rubisco activase from tobacco, indicating proteins are evolutionary conserved. The homology modelling was generated using SWISS-MODEL. Several quality assessment and validation parameters computed indicated that homology models are reliable. Further, functional annotation through PFAM, CATH, SUPERFAMILY, CDART suggested that selected hypothetical proteins of Vitis vinifera contain ATPase family associated with various cellular activities (AAA) and belong to the AAA+ super family of ring-shaped P-loop containing nucleoside triphosphate hydrolases. This study will lead to research in the optimization of the functionality of Rubisco which has large implication in the improvement of plant productivity and resource use efficiency.

  19. Fundamental behavior of a model biomolecular amphiphile system

    Science.gov (United States)

    Haverstick, Kraig Leonard

    An interest in the fundamental interactions between protein components, in the form of either single amino acids or peptides, unifies the work represented in this thesis. These fundamental interactions drive protein folding, enzyme-substrate binding, and cell adhesion to extracellular ligands. The technology of lipidation was used to isolate these protein interactions. Lipidation of a water-soluble amino acid or peptide sequence confined the protein component to the air-water interface or to a self-assembled structure in water. Compression of the molecules at the air-water interface ordered them into a solid-like monolayer, and Langmuir-Blodgett deposition produced a surface modification with protein component presented in a controlled, orderly manner. These molecules have potential applications as biomaterials coatings or drug delivery devices. A method for determination of specific hydrogen bonding interactions through cocrystallization of two complementary peptide sequences is also described. In order to understand the effect of lipidation and lipid structure on peptide behavior, a comprehensive study of tail designs was first undertaken. Tail length, linkage group, linker, spacer length, and headgroup chirality, orientation, and terminal group were systematically varied in simple amino acid amphiphiles. Monolayer assembly, thermal stability, and structure were studied with Langmuir isotherms and Fourier transform infrared spectroscopy. Each part of the tail structure was found to affect monolayer behavior. With lipid effects better understood, peptide amphiphiles were designed, synthesized, and studied using peptide sequences of importance for cell adhesion. The sequences [IV-H1] from type IV collagen and Arg-Gly-Asp (RGD) were lipidated and characterized in monolayers by Langmuir isotherms and Fourier transform infrared spectroscopy. Biological functionality was determined by melanoma cell spreading assays. Peptide presentation was found to be critical for

  20. Computational Electronic Structure of Antiferromagnetic Centers in Metalloproteins.

    Science.gov (United States)

    Rodriguez, Jorge H.

    2003-03-01

    Nature uses the properties of transition metal ions to carry out a variety of functions associated with vital life processes such as respiration and the transport of oxygen. Oxo-bridged diiron centers are intriguing structural motifs which are present in dioxygen transporting proteins and display antiferromagnetic ordering. We have performed a comprehensive study of the electronic structure and magnetic properties of structurally characterized models for diiron-oxo proteins. Results from Kohn-Sham density functional theory show that the models are antiferromagnetically coupled in agreement with experiment. The physical origin of the spin coupling has been elucidated as the main superexchange pathways responsible for magnetic ordering have been identified. In addition, the exchange constants that parameterize the Heisenberg Hamiltonian, H=JS_1.S_2, have been predicted in excellent agreement with experiment. Our results are important for establishing correlations between electronic structure and biomolecular function and show that computational electronic structure can be used as a powerful tool for the investigation of biomolecular magnetism.

  1. Adaptive resolution simulation of a biomolecule and its hydration shell: Structural and dynamical properties

    Science.gov (United States)

    Fogarty, Aoife C.; Potestio, Raffaello; Kremer, Kurt

    2015-05-01

    A fully atomistic modelling of many biophysical and biochemical processes at biologically relevant length- and time scales is beyond our reach with current computational resources, and one approach to overcome this difficulty is the use of multiscale simulation techniques. In such simulations, when system properties necessitate a boundary between resolutions that falls within the solvent region, one can use an approach such as the Adaptive Resolution Scheme (AdResS), in which solvent particles change their resolution on the fly during the simulation. Here, we apply the existing AdResS methodology to biomolecular systems, simulating a fully atomistic protein with an atomistic hydration shell, solvated in a coarse-grained particle reservoir and heat bath. Using as a test case an aqueous solution of the regulatory protein ubiquitin, we first confirm the validity of the AdResS approach for such systems, via an examination of protein and solvent structural and dynamical properties. We then demonstrate how, in addition to providing a computational speedup, such a multiscale AdResS approach can yield otherwise inaccessible physical insights into biomolecular function. We use our methodology to show that protein structure and dynamics can still be correctly modelled using only a few shells of atomistic water molecules. We also discuss aspects of the AdResS methodology peculiar to biomolecular simulations.

  2. Adaptive resolution simulation of a biomolecule and its hydration shell: Structural and dynamical properties

    Energy Technology Data Exchange (ETDEWEB)

    Fogarty, Aoife C., E-mail: fogarty@mpip-mainz.mpg.de; Potestio, Raffaello, E-mail: potestio@mpip-mainz.mpg.de; Kremer, Kurt, E-mail: kremer@mpip-mainz.mpg.de [Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz (Germany)

    2015-05-21

    A fully atomistic modelling of many biophysical and biochemical processes at biologically relevant length- and time scales is beyond our reach with current computational resources, and one approach to overcome this difficulty is the use of multiscale simulation techniques. In such simulations, when system properties necessitate a boundary between resolutions that falls within the solvent region, one can use an approach such as the Adaptive Resolution Scheme (AdResS), in which solvent particles change their resolution on the fly during the simulation. Here, we apply the existing AdResS methodology to biomolecular systems, simulating a fully atomistic protein with an atomistic hydration shell, solvated in a coarse-grained particle reservoir and heat bath. Using as a test case an aqueous solution of the regulatory protein ubiquitin, we first confirm the validity of the AdResS approach for such systems, via an examination of protein and solvent structural and dynamical properties. We then demonstrate how, in addition to providing a computational speedup, such a multiscale AdResS approach can yield otherwise inaccessible physical insights into biomolecular function. We use our methodology to show that protein structure and dynamics can still be correctly modelled using only a few shells of atomistic water molecules. We also discuss aspects of the AdResS methodology peculiar to biomolecular simulations.

  3. The structure and function of auditory chordotonal organs in insects.

    Science.gov (United States)

    Yack, Jayne E

    2004-04-15

    Insects are capable of detecting a broad range of acoustic signals transmitted through air, water, or solids. Auditory sensory organs are morphologically diverse with respect to their body location, accessory structures, and number of sensilla, but remarkably uniform in that most are innervated by chordotonal organs. Chordotonal organs are structurally complex Type I mechanoreceptors that are distributed throughout the insect body and function to detect a wide range of mechanical stimuli, from gross motor movements to air-borne sounds. At present, little is known about how chordotonal organs in general function to convert mechanical stimuli to nerve impulses, and our limited understanding of this process represents one of the major challenges to the study of insect auditory systems today. This report reviews the literature on chordotonal organs innervating insect ears, with the broad intention of uncovering some common structural specializations of peripheral auditory systems, and identifying new avenues for research. A general overview of chordotonal organ ultrastructure is presented, followed by a summary of the current theories on mechanical coupling and transduction in monodynal, mononematic, Type 1 scolopidia, which characteristically innervate insect ears. Auditory organs of different insect taxa are reviewed, focusing primarily on tympanal organs, and with some consideration to Johnston's and subgenual organs. It is widely accepted that insect hearing organs evolved from pre-existing proprioceptive chordotonal organs. In addition to certain non-neural adaptations for hearing, such as tracheal expansion and cuticular thinning, the chordotonal organs themselves may have intrinsic specializations for sound reception and transduction, and these are discussed. In the future, an integrated approach, using traditional anatomical and physiological techniques in combination with new methodologies in immunohistochemistry, genetics, and biophysics, will assist in

  4. ESSENCE, STRUCTURE AND FUNCTIONS OF THE REGIONAL FINANCIAL SYSTEM

    Directory of Open Access Journals (Sweden)

    A. V. Milenkov

    2015-01-01

    Full Text Available The scientific themes of the article is relevant, as in the domestic and foreign economic literature, the term "financial system" does not comply with the fundamental theory of systems in which the system views revealed as a set of interrelated and interacting elements in accordance with the set to achieve the goal. Each of the elements of multi-level financial system has its own organizational structure, consisting of institutions and organizations within the jurisdiction of the entity government. In the article the author's interpretation of the concepts of "institutional framework," "organizational structure" of the regional financial system, defined the task of the financial system was to create rules and regulations of its operation, set out the basic functions of the institutions and organizations of the regional financial system, analyzes the external communication of the financial system, the implementation of which is one of the basic conditions for the effective functioning of the financial system in the region due to its inclusion in the federal and international financial sector. The contribution of the author in the development of the theme of the article is to specify and clarify the concepts of "the financial system", "institutional and organizational structure of the regional financial system," the development of methodological approaches to the formulation and use of methods of solving the institutional and organizational problems of the financial system in the region, the rationalization of the rules and regulations it current operation and future development, the definition of the composition of the basic functions that are adequate specialization and features of the institutes and organizations of the regional financial system.

  5. Roll, adhere, spread and contract: structural mechanics of platelet function.

    Science.gov (United States)

    Sorrentino, Simona; Studt, Jan-Dirk; Medalia, Ohad; Tanuj Sapra, K

    2015-01-01

    Platelets are involved in life-sustaining processes such as hemostasis, wound healing, atherothrombosis and angiogenesis. Mechanical trauma to blood vessels causes platelet activation resulting in their adherence and clot formation at the damaged site, culminating in clot retraction and tissue repair. Two of the major players underlying this process are the cytoskeleton, i.e., actin and microtubules, and the membrane integrin receptors. Rare congenital bleeding disorders such as Glanzmann thrombasthenia and Bernard-Soulier syndrome are associated with genetic alterations of platelet surface receptors, also affecting the platelet cytoskeletal structure. In this review, we summarize the current knowledge about platelet structure and adhesion, and delve into the mechanical aspects of platelet function. Platelets lack a nucleus, and can thus provide a minimal model of a biological cell. New biophysical tools may help to scrutinize platelets anew and to extend the existing knowledge on cell biology.

  6. Hantaviral proteins: structure, functions and role in hantavirus infection

    Directory of Open Access Journals (Sweden)

    Musalwa eMuyangwa

    2015-11-01

    Full Text Available Hantaviruses are the members of the family Bunyaviridae that are naturally maintained in the populations of small mammals, mostly rodents. Most of these viruses can easily infect humans through contact with aerosols or dust generated by contaminated animal waste products. Depending on the particular hantavirus involved, human infection could result in either Hemorrhagic Fever with Renal Syndrome (HFRS or in Hantavirus Cardiopulmonary Syndrome (HCPS. In the past few years, clinical cases of the hantavirus caused diseases have been on the rise. Understanding structure of the hantavirus genome and the functions of the key viral proteins is critical for the therapeutic agents’ research. This paper gives a brief overview of the current knowledge on the structure and properties of the hantavirus nucleoprotein and the glycoproteins.

  7. [Structural and functional findings in experimental blind loop syndrome].

    Science.gov (United States)

    Riecken, E O

    1984-01-01

    Proximal and distal the blindsack a villus and crypt prolongation connected with a decreasing absorption of octanoate could be pointed out. The structural changes are very likely a hyperplasia of the mucosa. Within the blindsack a hyperplasia in connection with an accelerated proliferation of cells and an almost three and a halffold enlargement of the surface of the villi could be found. Simultaneously, the mucosa was damaged. An artificial bile duct as well as a neomycin therapy caused a decrease of the structural and functional changes but did not prevent the mucosal hyperplasia. These results are explained with adaptive processes of the small intestinal mucosa in a sense of hyperregeneration alterations of sprue typus.

  8. Improving the Network Structure can lead to Functional Failures

    CERN Document Server

    Pade, Jan Philipp

    2014-01-01

    In many real-world networks the ability to synchronize is a key property for its performance. Examples include power-grid, sensor, and neuron networks as well as consensus formation. Recent work on undirected networks with diffusive interaction revealed that improvements in the network connectivity such as making the network more connected and homogeneous enhances synchronization. However, real-world networks have directed and weighted connections. In such directed networks, understanding the impact of structural changes on the network performance remains a major challenge. Here, we show that improving the structure of a directed network can lead to a failure in the network function. For instance, introducing new links to reduce the minimum distance between nodes can lead to instabilities in the synchronized motion. This counter-intuitive effect only occurs in directed networks. Our results allow to identify the dynamical importance of a link and thereby have a major impact on the design and control of direct...

  9. Ocean plankton. Structure and function of the global ocean microbiome.

    Science.gov (United States)

    Sunagawa, Shinichi; Coelho, Luis Pedro; Chaffron, Samuel; Kultima, Jens Roat; Labadie, Karine; Salazar, Guillem; Djahanschiri, Bardya; Zeller, Georg; Mende, Daniel R; Alberti, Adriana; Cornejo-Castillo, Francisco M; Costea, Paul I; Cruaud, Corinne; d'Ovidio, Francesco; Engelen, Stefan; Ferrera, Isabel; Gasol, Josep M; Guidi, Lionel; Hildebrand, Falk; Kokoszka, Florian; Lepoivre, Cyrille; Lima-Mendez, Gipsi; Poulain, Julie; Poulos, Bonnie T; Royo-Llonch, Marta; Sarmento, Hugo; Vieira-Silva, Sara; Dimier, Céline; Picheral, Marc; Searson, Sarah; Kandels-Lewis, Stefanie; Bowler, Chris; de Vargas, Colomban; Gorsky, Gabriel; Grimsley, Nigel; Hingamp, Pascal; Iudicone, Daniele; Jaillon, Olivier; Not, Fabrice; Ogata, Hiroyuki; Pesant, Stephane; Speich, Sabrina; Stemmann, Lars; Sullivan, Matthew B; Weissenbach, Jean; Wincker, Patrick; Karsenti, Eric; Raes, Jeroen; Acinas, Silvia G; Bork, Peer

    2015-05-22

    Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems.

  10. Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

    Directory of Open Access Journals (Sweden)

    Svetlana A Dambinova

    2016-10-01

    Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

  11. Molecular tools for investigating ANME community structure and function

    Energy Technology Data Exchange (ETDEWEB)

    Hallam, Steven J.; Page, Antoine P.; Constan, Lea; Song, Young C.; Norbeck, Angela D.; Brewer, Heather M.; Pasa-Tolic, Ljiljana

    2011-05-20

    Methane production and consumption in anaerobic marine sediments 1 is catalyzed by a series of reversible tetramethanopterin (H4MPT)-linked C1 transfer reactions. Although many of these reactions are conserved between one-carbon compound utilizing microorganisms, two remain diagnostic for archaeal methane metabolism. These include reactions catalyzed by N5-methyltetrahydromethanopterin: coenzyme M methyltransferase and methyl coenzyme M reductase. The latter enzyme is central to C-H bond formation and cleavage underlying methanogenic and reverse methanogenic phenotypes. Here we describe a set of novel tools for the detection and functional analysis of H4MPT-linked C1 transfer reactions mediated by uncultivated anaerobic methane oxidizing archaea (ANME). These tools include polymerase chain reaction primers targeting ANME methyl coenzyme M reductase subunit A subgroups and protein extraction methods from marine sediments compatible with high-resolution mass spectrometry for profiling population structure and functional dynamics. [910, 1,043

  12. The influence of gravity on structure and function of animals

    Science.gov (United States)

    Ross, M. D.

    1984-01-01

    Gravity is the only environmental parameter that has remained constant during the period of evolution of living matter on earth. Thus, it must have been a major force in shaping living things. The influence of gravitational loading on evolution of the vertebrate skeleton is well recognized, and scale effects have been studied. This paper, however, considers in addition four pivotal events in early evolution that would seem to have been significant for the later success and diversifcation of animal life. These are evolution of the cytoskeleton, cell motility (flagellae and cilia), gravity detecting devices (accelerometers), and biomineralization. All are functionally calcium dependent in eukaryotes and all occurred or were foreshadowed in prokaryotes. A major question is why calcium was selected as an ion of great importance to the structure and function of living matter; another is whether gravity played a role in its selection.

  13. The blood-nerve barrier: structure and functional significance.

    Science.gov (United States)

    Weerasuriya, Ananda; Mizisin, Andrew P

    2011-01-01

    The blood-nerve barrier (BNB) defines the physiological space within which the axons, Schwann cells, and other associated cells of a peripheral nerve function. The BNB consists of the endoneurial microvessels within the nerve fascicle and the investing perineurium. The restricted permeability of these two barriers protects the endoneurial microenvironment from drastic concentration changes in the vascular and other extracellular spaces. It is postulated that endoneurial homeostatic mechanisms regulate the milieu intérieur of peripheral axons and associated Schwann cells. These mechanisms are discussed in relation to nerve development, Wallerian degeneration and nerve regeneration, and lead neuropathy. Finally, the putative factors responsible for the cellular and molecular control of BNB permeability are discussed. Given the dynamic nature of the regulation of the permeability of the perineurium and endoneurial capillaries, it is suggested that the term blood-nerve interface (BNI) better reflects the functional significance of these structures in the maintenance of homeostasis within the endoneurial microenvironment.

  14. An overview of bovine α-lactalbumin structure and functionality

    Directory of Open Access Journals (Sweden)

    Nicoleta STĂNCIUC

    2010-12-01

    Full Text Available α-Lactalbumin is the second major protein in bovine milk (2-5% of the total protein in bovine milk. The human variant has several physiologic functions in the neonatal period. In the mammary gland, itparticipates in lactose synthesis and facilitates milk production and secretion. α-Lactalbumin binds divalent cations (Ca2+, Zn2+ and may facilitate the absorption of essential minerals. Also, it provides awell-balanced supply of essential amino acids for the growing infant. During its digestion, peptides with antibacterial and imunostimulatory properties are formed, thereby possibly helping in the protection against infection. The protein fractions enriched with α-lactalbumin may be added to infant formula to provide some of the benefits of this protein. This article reviews a number of studies which may contribute to a more coherent understanding of the structure and some functional properties of α-lactalbumin.

  15. Multi functional roof structures of the energy efficient buildings

    Directory of Open Access Journals (Sweden)

    Krstić Aleksandra

    2006-01-01

    Full Text Available Modern architectural concepts, which are based on rational energy consumption of buildings and the use of solar energy as a renewable energy source, give the new and significant role to the roofs that become multifunctional structures. Various energy efficient roof structures and elements, beside the role of protection, provide thermal and electric energy supply, natural ventilation and cooling of a building, natural lighting of the indoor space sunbeam protection, water supply for technical use, thus according to the above mentioned functions, classification and analysis of such roof structures and elements are made in this paper. The search for new architectural values and optimization in total energy balance of a building or the likewise for the urban complex, gave to roofs the role of "climatic membranes". Contemporary roof forms and materials clearly exemplify their multifunctional features. There are numerous possibilities to achieve the new and attractive roof design which broadens to the whole construction. With such inducement, this paper principally analyze the configuration characteristics of the energy efficient roof structures and elements, as well as the visual effects that may be achieved by their application.

  16. Structural basis for functional tetramerization of lentiviral integrase.

    Directory of Open Access Journals (Sweden)

    Stephen Hare

    2009-07-01

    Full Text Available Experimental evidence suggests that a tetramer of integrase (IN is the protagonist of the concerted strand transfer reaction, whereby both ends of retroviral DNA are inserted into a host cell chromosome. Herein we present two crystal structures containing the N-terminal and the catalytic core domains of maedi-visna virus IN in complex with the IN binding domain of the common lentiviral integration co-factor LEDGF. The structures reveal that the dimer-of-dimers architecture of the IN tetramer is stabilized by swapping N-terminal domains between the inner pair of monomers poised to execute catalytic function. Comparison of four independent IN tetramers in our crystal structures elucidate the basis for the closure of the highly flexible dimer-dimer interface, allowing us to model how a pair of active sites become situated for concerted integration. Using a range of complementary approaches, we demonstrate that the dimer-dimer interface is essential for HIV-1 IN tetramerization, concerted integration in vitro, and virus infectivity. Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor.

  17. Measurement of the longitudinal proton structure function at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

    2009-03-15

    The reduced cross sections for ep deep inelastic scattering have been measured with the ZEUS detector at HERA at three different centre-of-mass energies, 318, 251 and 225 GeV. From the cross sections, measured double differentially in Bjorken x and the virtuality, Q{sup 2}, the proton structure functions F{sub L} and F{sub 2} have been extracted in the region 5 x 10{sup -4}

  18. Advances on statistical/thermodynamical models for unpolarized structure functions

    Science.gov (United States)

    Trevisan, Luis A.; Mirez, Carlos; Tomio, Lauro

    2013-03-01

    During the eights and nineties many statistical/thermodynamical models were proposed to describe the nucleons' structure functions and distribution of the quarks in the hadrons. Most of these models describe the compound quarks and gluons inside the nucleon as a Fermi / Bose gas respectively, confined in a MIT bag[1] with continuous energy levels. Another models considers discrete spectrum. Some interesting features of the nucleons are obtained by these models, like the sea asymmetries ¯d/¯u and ¯d-¯u.

  19. Wave Function Structure in Two-Body Random Matrix Ensembles

    CERN Document Server

    Kaplan, L; Kaplan, Lev; Papenbrock, Thomas

    2000-01-01

    We study the structure of eigenstates in two-body interaction random matrix ensembles and find significant deviations from random matrix theory expectations. The deviations are most prominent in the tails of the spectral density and indicate localization of the eigenstates in Fock space. Using ideas related to scar theory we derive an analytical formula that relates fluctuations in wave function intensities to fluctuations of the two-body interaction matrix elements. Numerical results for many-body fermion systems agree well with the theoretical predictions.

  20. The QCD gluon ladders and HERA structure function

    CERN Document Server

    Lengyel, A I

    2002-01-01

    We report on the extension of the data fitting considering the QCD inspired model based on the summation of gluon ladders applied to the $ep$ scattering. In lines of a two Pomeron approach, the structure function $F_2$ has a hard piece given by the model and the remaining soft contribution: a soft Pomeron and non-singlet content. In this contribution, we carefully estimate the relative role of the hard and the soft pieces from a global fit in a large span of $x$ and $Q^2$.