WorldWideScience

Sample records for aptamer-derived molecular adaptors

  1. Molecular physiology of the tensin brotherhood of integrin adaptor proteins.

    Science.gov (United States)

    Haynie, Donald T

    2014-07-01

    Numerous proteins have been identified as constituents of the adhesome, the totality of molecular components in the supramolecular assemblies known as focal adhesions, fibrillar adhesions and other kinds of adhesive contact. The transmembrane receptor proteins called integrins are pivotal adhesome members, providing a physical link between the extracellular matrix (ECM) and the actin cytoskeleton. Tensins are ever more widely investigated intracellular adhesome constituents. Involved in cell attachment and migration, cytoskeleton reorganization, signal transduction and other processes relevant to cancer research, tensins have recently been linked to functional properties of deleted in liver cancer 1 (DLC1) and a mitogen-activated protein kinases (MAPK), to cell migration in breast cancer, and to metastasis suppression in the kidney. Tensins are close relatives of phosphatase homolog/tensin homolog (PTEN), an extensively studied tumor suppressor. Such findings are recasting the earlier vision of tensin (TNS) as an actin-filament (F-actin) capping protein in a different light. This critical review aims to summarize current knowledge on tensins and thus to highlight key points concerning the expression, structure, function, and evolution of the various members of the TNS brotherhood. Insight is sought by comparisons with homologous proteins. Some historical points are added for perspective. PMID:24634006

  2. Molecular protein adaptor with genetically encoded interaction sites guiding the hierarchical assembly of plasmonically active nanoparticle architectures

    Science.gov (United States)

    Schreiber, Andreas; Huber, Matthias C.; Cölfen, Helmut; Schiller, Stefan M.

    2015-03-01

    The control over the defined assembly of nano-objects with nm-precision is important to create systems and materials with enhanced properties, for example, metamaterials. In nature, the precise assembly of inorganic nano-objects with unique features, for example, magnetosomes, is accomplished by efficient and reliable recognition schemes involving protein effectors. Here we present a molecular approach using protein-based ‘adaptors/connectors’ with genetically encoded interaction sites to guide the assembly and functionality of different plasmonically active gold nanoparticle architectures (AuNP). The interaction of the defined geometricaly shaped protein adaptors with the AuNP induces the self-assembly of nanoarchitectures ranging from AuNP encapsulation to one-dimensional chain-like structures, complex networks and stars. Synthetic biology and bionanotechnology are applied to co-translationally encode unnatural amino acids as additional site-specific modification sites to generate functionalized biohybrid nanoarchitectures. This protein adaptor-based nano-object assembly approach might be expanded to other inorganic nano-objects creating biohybrid materials with unique electronic, photonic, plasmonic and magnetic properties.

  3. Multiple molecular forms of adaptor protein Ruk/CIN85 specifically associate with different subcellular compartments in human breast adenocarcinoma MCF-7 cells.

    Science.gov (United States)

    Vynnytska-Myronovska, B O; Bobak, Ya P; Pasichnyk, G V; Igumentseva, N I; Samoylenko, A A; Drobot, L B

    2014-01-01

    Ruk/CIN85 is a receptor-proximal 'signalling' adaptor that possesses three SH3 domains, Pro- and Ser-rich regions and C-terminal coiled-coil domain. It employs distinct domains and motifs to act as a transducer platform in intracellular signaling. Based on cDNA analysis, various isoforms of Ruk/CIN85 with different combination of protein-protein interaction domains as well as additional Ruk/CIN85 forms that are the products of post-translational modifications have been demonstrated. Nevertheless, there is no precise information regarding both the subcellular distribution and the role of Ruk/CIN85 multiple molecular forms in cellular responses. Using MCF-7 human breast adenocarcinoma cells and cell fractionation technique, specific association of Ruk/CIN85 molecular forms with different subcellular compartments was demonstrated. Induction of apoptosis of MCF-7 cells by doxorubicin treatment or by serum deprivation resulted in the system changes of Ruk/CIN85 molecular forms intracellular localization as well as their ratio. The data obtained provide a new insight into potential physiological significance of Ruk/CIN85 molecular forms in the regulation of various cellular functions. PMID:25816594

  4. Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection

    OpenAIRE

    Valkov, Eugene; Stamp, Anna; DiMaio, Frank; Baker, David; Verstak, Brett; Roversi, Pietro; Kellie, Stuart; Sweet, Matthew J.; Mansell, Ashley; Gay, Nicholas J.; Jennifer L Martin; Kobe, Bostjan

    2011-01-01

    Initiation of the innate immune response requires agonist recognition by pathogen-recognition receptors such as the Toll-like receptors (TLRs). Toll/interleukin-1 receptor (TIR) domain-containing adaptors are critical in orchestrating the signal transduction pathways after TLR and interleukin-1 receptor activation. Myeloid differentiation primary response gene 88 (MyD88) adaptor-like (MAL)/TIR domain-containing adaptor protein (TIRAP) is involved in bridging MyD88 to TLR2 and TLR4 in response...

  5. PAG - a multipurpose transmembrane adaptor protein

    Czech Academy of Sciences Publication Activity Database

    Hrdinka, Matouš; Hořejší, Václav

    2014-01-01

    Roč. 33, č. 41 (2014), s. 4881-4892. ISSN 0950-9232 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : PAG * adaptor protein * membrane raft Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.459, year: 2014

  6. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    Czech Academy of Sciences Publication Activity Database

    Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav

    2014-01-01

    Roč. 26, č. 5 (2014), s. 895-902. ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  7. Triplex molecular beacons for sensitive recognition of melamine based on abasic-site-containing DNA and fluorescent silver nanoclusters.

    Science.gov (United States)

    Wang, Ya; Sun, Qianqian; Zhu, Linling; Zhang, Junying; Wang, Fengyang; Lu, Linlin; Yu, Haijun; Xu, Zhiai; Zhang, Wen

    2015-05-01

    A melamine aptamer derived from an abasic-site-containing triplex molecular beacon (tMB) was designed and developed for sensitive recognition of melamine by integrating tMBs and fluorescent silver nanoclusters (Ag NCs). PMID:25865656

  8. The fifth adaptor protein complex.

    OpenAIRE

    Jennifer Hirst; Barlow, Lael D.; Gabriel Casey Francisco; Sahlender, Daniela A.; Seaman, Matthew N.J.; Dacks, Joel B.; Robinson, Margaret S.

    2011-01-01

    Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent manno...

  9. The Fifth Adaptor Protein Complex

    OpenAIRE

    Hirst, Jennifer; D. Barlow, Lael; Francisco, Gabriel Casey; Sahlender, Daniela A.; Seaman, Matthew N.J.; Dacks, Joel B.; Robinson, Margaret S.

    2011-01-01

    Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent manno...

  10. The fifth adaptor protein complex.

    Directory of Open Access Journals (Sweden)

    Jennifer Hirst

    2011-10-01

    Full Text Available Adaptor protein (AP complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia.

  11. Adaptor protein complexes and intracellular transport

    OpenAIRE

    2014-01-01

    The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers th...

  12. Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing

    OpenAIRE

    Matos, Maria F.; Xu, Yibin; Dulubova, Irina; Otwinowski, Zbyszek; Richardson, John M.; Tomchick, Diana R.; Rizo, Josep; Ho, Angela

    2012-01-01

    Mint adaptor proteins bind to the amyloid precursor protein (APP) and regulate APP processing associated with Alzheimer’s disease; however, the molecular mechanisms underlying Mint regulation in APP binding and processing remain unclear. Biochemical, biophysical, and cellular experiments now show that the Mint1 phosphotyrosine binding (PTB) domain that binds to APP is intramolecularly inhibited by the adjacent C-terminal linker region. The crystal structure of a C-terminally extended Mint1 PT...

  13. Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire

    OpenAIRE

    Roy, Edwige; Togbe, Dieudonnée; Holdorf, Amy D.; Trubetskoy, Dmitry; Nabti, Sabrina; Küblbeck, Günter; Klevenz, Alexandra; Kopp-Schneider, Annette; Leithäuser, Frank; Möller, Peter; Bladt, Friedhelm; Hämmerling, Günter; Arnold, Bernd; Pawson, Tony; Tafuri, Anna

    2010-01-01

    The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, pe...

  14. Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire.

    Science.gov (United States)

    Roy, Edwige; Togbe, Dieudonnée; Holdorf, Amy D; Trubetskoy, Dmitry; Nabti, Sabrina; Küblbeck, Günter; Klevenz, Alexandra; Kopp-Schneider, Annette; Leithäuser, Frank; Möller, Peter; Bladt, Friedhelm; Hämmerling, Günter; Arnold, Bernd; Pawson, Tony; Tafuri, Anna

    2010-08-31

    The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability. PMID:20709959

  15. Selective autophagy of non-ubiquitylated targets in plants: looking for cognate receptor/adaptor proteins

    Directory of Open Access Journals (Sweden)

    Vasko eVeljanovski

    2014-06-01

    Full Text Available Cellular homeostasis is essential for the physiology of eukaryotic cells. Eukaryotic cells, including plant cells, utilize two main pathways to adjust the level of cytoplasmic components, namely the proteasomal and the lysosomal/vacuolar pathways. Macroautophagy is a lysosomal/vacuolar pathway which, until recently, was thought to be non-specific and a bulk degradation process. However, selective autophagy which can be activated in the cell under various physiological conditions, involves the specific degradation of defined macromolecules or organelles by a conserved molecular mechanism. For this process to be efficient, the mechanisms underlying the recognition and selection of the cargo to be engulfed by the double-membrane autophagosome are critical, and not yet well understood. Ubiquitin (poly-ubiquitin conjugation to the target appears to be a conserved ligand mechanism in many types of selective autophagy, and defined receptors/adaptors recognizing and regulating the autophagosomal capture of the ubiquitylated target have been characterized. However, non-proteinaceous and non-ubiquitylated cargoes are also selectively degraded by this pathway. This ubiquitin-independent selective autophagic pathway also involves receptor and/or adaptor proteins linking the cargo to the autophagic machinery. Some of these receptor/adaptor proteins including accessory autophagy-related (Atg and non-Atg proteins have been described in yeast and animal cells but not yet in plants. In this review we discuss the ubiquitin-independent cargo selection mechanisms in selective autophagy degradation of organelles and macromolecules and speculate on potential plant receptor/adaptor proteins.

  16. The Transmembrane Adaptor Protein SIT Inhibits TCR-Mediated Signaling

    OpenAIRE

    Arndt, Börge; Krieger, Tina; Kalinski, Thomas; Thielitz, Anja; Reinhold, Dirk; Roessner, Albert; Schraven, Burkhart; Simeoni, Luca

    2011-01-01

    Transmembrane adaptor proteins (TRAPs) organize signaling complexes at the plasma membrane, and thus function as critical linkers and integrators of signaling cascades downstream of antigen receptors. We have previously shown that the transmembrane adaptor protein SIT regulates the threshold for thymocyte selection. Moreover, T cells from SIT-deficient mice are hyperresponsive to CD3 stimulation and undergo enhanced lymphopenia-induced homeostatic proliferation, thus indicating that SIT inhib...

  17. The adaptor molecule CARD9 is essential for tuberculosis control

    OpenAIRE

    Dorhoi, Anca; Desel, Christiane; Yeremeev, Vladimir; Pradl, Lydia; Brinkmann, Volker; Mollenkopf, Hans J; Hanke, Karin; Gross, Olaf; Ruland, Jürgen; Stefan H. E. Kaufmann

    2010-01-01

    The cross talk between host and pathogen starts with recognition of bacterial signatures through pattern recognition receptors (PRRs), which mobilize downstream signaling cascades. We investigated the role of the cytosolic adaptor caspase recruitment domain family, member 9 (CARD9) in tuberculosis. This adaptor was critical for full activation of innate immunity by converging signals downstream of multiple PRRs. Card9(-/-) mice succumbed early after aerosol infection, with higher mycobacteria...

  18. Transmembrane adaptor proteins in the high-affinity IgE receptor signaling

    Czech Academy of Sciences Publication Activity Database

    Dráber, Petr; Hálová, Ivana; Levi-Schaffer, F.; Dráberová, Lubica

    2012-01-01

    Roč. 2, 11.1. (2012), s. 95. ISSN 1664-3224 R&D Projects: GA MŠk 1M0506; GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA AV ČR KAN200520701 Grant ostatní: AV ČR(CZ) M200520901 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : IgE receptor * LAT/LAT1 * LAX * NTAL/Lab/LAT2 * PAG/Cbp * mast cells * plasma membrane * transmembrane adaptor proteins Subject RIV: EB - Genetics ; Molecular Biology

  19. Chemical-genetic disruption of clathrin function spares adaptor complex 3–dependent endosome vesicle biogenesis

    OpenAIRE

    Zlatic, Stephanie A.; Grossniklaus, Emily J.; Ryder, Pearl V.; Salazar, Gloria; Mattheyses, Alexa L.; Peden, Andrew A.; Faundez, Victor

    2013-01-01

    A role for clathrin in AP-3–dependent vesicle biogenesis has been inferred from biochemical interactions and colocalization between this adaptor and clathrin. The functionality of these molecular associations, however, is controversial. We comprehensively explore the role of clathrin in AP-3–dependent vesicle budding, using rapid chemical-genetic perturbation of clathrin function with a clathrin light chain–FKBP chimera oligomerizable by the drug AP20187. We find that AP-3 interacts and coloc...

  20. Optimized Adaptor Polymerase Chain Reaction Method for Efficient Genomic Walking

    Institute of Scientific and Technical Information of China (English)

    Peng XU; Rui-Ying HU; Xiao-Yan DING

    2006-01-01

    Genomic walking is one of the most useful approaches in genome-related research. Three kinds of PCR-based methods are available for this purpose. However, none of them has been generally applied because they are either insensitive or inefficient. Here we present an efficient PCR protocol, an optimized adaptor PCR method for genomic walking. Using a combination of a touchdown PCR program and a special adaptor, the optimized adaptor PCR protocol achieves high sensitivity with low background noise. By applying this protocol, the insertion sites of a gene trap mouse line and two gene promoters from the incompletely sequenced Xenopus laevis genome were successfully identified with high efficiency. The general application of this protocol in genomic walking was promising.

  1. The Clathrin Adaptor AP-1A Mediates Basolateral Polarity

    OpenAIRE

    Gravotta, Diego; Carvajal-Gonzalez, Jose Maria; Mattera, Rafael; Deborde, Sylvie; Banfelder, Jason R.; Bonifacino, Juan S.; Rodriguez-Boulan, Enrique

    2012-01-01

    Clathrin and the epithelial-specific clathrin adaptor AP-1B mediate basolateral trafficking in epithelia. However, several epithelia lack AP-1B and mice knocked-out for AP-1B are viable, suggesting the existence of additional mechanisms that control basolateral polarity. Here, we demonstrate a distinct role of the ubiquitous clathrin adaptor AP-1A in basolateral protein sorting. Knock-down of AP-1A causes missorting of basolateral proteins in MDCK cells but only after knock-down of AP-1B, sug...

  2. Cytosol- and clathrin-dependent stimulation of endocytosis in vitro by purified adaptors

    OpenAIRE

    1992-01-01

    Using stage-specific assays for receptor-mediated endocytosis of transferrin (Tfn) into perforated A431 cells we show that purified adaptors stimulate coated pit assembly and ligand sequestration into deeply invaginated coated pits. Late events in endocytosis involving membrane fission and coated vesicle budding which lead to the internalization of Tfn are unaffected. AP2, plasma membrane adaptors, are active at physiological concentrations, whereas AP1, Golgi adaptors, are inactive. Adaptor-...

  3. DMPD: The SAP family of adaptors in immune regulation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15541655 The SAP family of adaptors in immune regulation. Latour S, Veillette A. Se...min Immunol. 2004 Dec;16(6):409-19. (.png) (.svg) (.html) (.csml) Show The SAP family of adaptors in immune ...regulation. PubmedID 15541655 Title The SAP family of adaptors in immune regulation. Authors Latour S, Veill

  4. A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins.

    Directory of Open Access Journals (Sweden)

    Ricardo Núñez Miguel

    Full Text Available The Toll-like receptor 4 (TLR4 is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3 and nuclear factor kappaB (NFkappaB respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu.

  5. Spiral biasing adaptor for use in Si drift detectors and Si drift detector arrays

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zheng; Chen, Wei

    2016-07-05

    A drift detector array, preferably a silicon drift detector (SDD) array, that uses a low current biasing adaptor is disclosed. The biasing adaptor is customizable for any desired geometry of the drift detector single cell with minimum drift time of carriers. The biasing adaptor has spiral shaped ion-implants that generate the desired voltage profile. The biasing adaptor can be processed on the same wafer as the drift detector array and only one biasing adaptor chip/side is needed for one drift detector array to generate the voltage profiles on the front side and back side of the detector array.

  6. The Cytoplasmic Adaptor Protein Dok7 Activates the Receptor Tyrosine Kinase MuSK via Dimerization

    Energy Technology Data Exchange (ETDEWEB)

    Bergamin, E.; Hallock, P; Burden, S; Hubbard, S

    2010-01-01

    Formation of the vertebrate neuromuscular junction requires, among others proteins, Agrin, a neuronally derived ligand, and the following muscle proteins: LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7 (or Dok-7), a cytoplasmic adaptor protein. Dok7 comprises a pleckstrin-homology (PH) domain, a phosphotyrosine-binding (PTB) domain, and C-terminal sites of tyrosine phosphorylation. Unique among adaptor proteins recruited to RTKs, Dok7 is not only a substrate of MuSK, but also an activator of MuSK's kinase activity. Here, we present the crystal structure of the Dok7 PH-PTB domains in complex with a phosphopeptide representing the Dok7-binding site on MuSK. The structure and biochemical data reveal a dimeric arrangement of Dok7 PH-PTB that facilitates trans-autophosphorylation of the kinase activation loop. The structure provides the molecular basis for MuSK activation by Dok7 and for rationalizing several Dok7 loss-of-function mutations found in patients with congenital myasthenic syndromes.

  7. Motors and Adaptors : Transport Regulation within Neurons

    OpenAIRE

    van Spronsen, C.S.A.M.

    2012-01-01

    Human thoughts and behavior are the outcome of communication between neurons in our brains. There is an entire world inside each of these neurons where transactions are established and meeting points are set. By using molecular motors to transport proteins and organelles along cytoskeletal tracks, neurons create the internal order of the bustling community of macromolecules. Given the challenging geometry of the neuron, the mechanisms that deliver fuel and materials to sustain the distant syn...

  8. Role of adaptor proteins in secretory granule biogenesis and maturation

    Directory of Open Access Journals (Sweden)

    RichardEMains

    2013-08-01

    Full Text Available In the regulated secretory pathway, secretory granules (SGs store peptide hormones that are released on demand. SGs are formed at the trans-Golgi network (TGN and must undergo a maturation process to become responsive to secretagogues. The production of mature SGs requires concentrating newly synthesized soluble content proteins in granules whose membranes contain the appropriate integral membrane proteins. The mechanisms underlying the sorting of soluble and integral membrane proteins destined for SGs from other proteins are not yet well understood. For soluble proteins, luminal pH and divalent metals can affect aggregation and interaction with surrounding membranes. The trafficking of granule membrane proteins can be controlled by both luminal and cytosolic factors. Cytosolic adaptor proteins, which recognize the cytosolic domains of proteins that span the SG membrane, have been shown to play essential roles in the assembly of functional SGs. Adaptor protein 1A (AP-1A is known to interact with specific motifs in its cargo proteins and with the clathrin heavy chain, contributing to the formation of a clathrin coat. AP-1A is present in patches on immature SG membranes, where it removes cargo and facilitates SG maturation. AP-1A recruitment to membranes can be modulated by PACS-1 (Phosphofurin Acidic Cluster Sorting protein 1, a cytosolic protein which interacts with both AP-1A and cargo that has been phosphorylated by casein kinase II. A cargo/PACS-1/AP-1A complex is necessary to drive the appropriate transport of several cargo proteins within the regulated secretory pathway. The GGA (Golgi-localized, -ear containing, ADP-ribosylation factor binding family of adaptor proteins serve a similar role. We review the functions of AP-1A, PACS-1 and GGAs in facilitating the retrieval of proteins from immature SGs and review examples of cargo proteins whose trafficking within the regulated secretory pathway is governed by adaptor proteins.

  9. PRR7 Is a transmembrane adaptor protein expressed in activated T cells involved in regulation of T cell receptor signaling and apoptosis

    Czech Academy of Sciences Publication Activity Database

    Hrdinka, Matouš; Dráber, Peter; Štěpánek, Ondřej; Ormsby, Tereza; Otáhal, Pavel; Angelisová, Pavla; Brdička, Tomáš; Pačes, Jan; Hořejší, Václav; Drbal, Karel

    2011-01-01

    Roč. 286, č. 22 (2011), s. 19617-19629. ISSN 0021-9258 R&D Projects: GA MŠk 1M0506 Grant ostatní: GAČR(CZ) MEM/09/E011 Institutional research plan: CEZ:AV0Z50520514 Keywords : PRR7 * transmembrane adaptor protein * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.773, year: 2011

  10. Phosphorylation-Dependent Regulation of the DNA Damage Response of Adaptor Protein KIBRA in Cancer Cells.

    Science.gov (United States)

    Mavuluri, Jayadev; Beesetti, Swarnalatha; Surabhi, Rohan; Kremerskothen, Joachim; Venkatraman, Ganesh; Rayala, Suresh K

    2016-05-01

    Multifunctional adaptor proteins encompassing various protein-protein interaction domains play a central role in the DNA damage response pathway. In this report, we show that KIBRA is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase. We identified the site of phosphorylation in KIBRA as threonine 1006, which is embedded within the serine/threonine (S/T) Q consensus motif, by site-directed mutagenesis, and we further confirmed the same with a phospho-(S/T) Q motif-specific antibody. Results from DNA repair functional assays such as the γ-H2AX assay, pulsed-field gel electrophoresis (PFGE), Comet assay, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and clonogenic cell survival assay using stable overexpression clones of wild-type (wt.) KIBRA and active (T1006E) and inactive (T1006A) KIBRA phosphorylation mutants showed that T1006 phosphorylation on KIBRA is essential for optimal DNA double-strand break repair in cancer cells. Further, results from stable retroviral short hairpin RNA-mediated knockdown (KD) clones of KIBRA and KIBRA knockout (KO) model cells generated by a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that depleting KIBRA levels compromised the DNA repair functions in cancer cells upon inducing DNA damage. All these phenotypic events were reversed upon reconstitution of KIBRA into cells lacking KIBRA knock-in (KI) model cells. All these results point to the fact that phosphorylated KIBRA might be functioning as a scaffolding protein/adaptor protein facilitating the platform for further recruitment of other DNA damage response factors. In summary, these data demonstrate the imperative functional role of KIBRAper se(KIBRA phosphorylation at T1006 site as a molecular switch that regulates the DNA damage response, possibly via the nonhomologous end joining [NHEJ] pathway), suggesting that KIBRA could be a potential

  11. A Big-Five Personality Profile of the Adaptor and Innovator.

    Science.gov (United States)

    Kwang, Ng Aik; Rodrigues, Daphne

    2002-01-01

    A study explored the relationship between two creative types (adaptor and innovator) and the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), in 164 teachers in Singapore. Adaptors were significantly more conscientious than innovators, while innovators were significantly more…

  12. Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump.

    Science.gov (United States)

    Hinchliffe, Philip; Greene, Nicholas P; Paterson, Neil G; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

    2014-08-25

    Periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. The 2.85 Å resolution structure of an MFS (major facilitator superfamily) pump adaptor, Aquifex aeolicus EmrA, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. The adaptor α-hairpin, which binds outer membrane TolC, is exceptionally long at 127 Å, and the β-barrel contains a conserved disordered loop. The structure extends the view of adaptors as flexible, modular components that mediate diverse pump assembly, and suggests that in MFS tripartite pumps a hexamer of adaptors could provide a periplasmic seal. PMID:24996185

  13. Crystal structure of the mammalian Grb2 adaptor.

    Science.gov (United States)

    Maignan, S; Guilloteau, J P; Fromage, N; Arnoux, B; Becquart, J; Ducruix, A

    1995-04-14

    The mammalian growth factor receptor-binding protein Grb2 is an adaptor that mediates activation of guanine nucleotide exchange on Ras. Grb2 binds to the receptor through its SH2 domain and to the carboxyl-terminal domain of Son of sevenless through its two SH3 domains. It is thus a key element in the signal transduction pathway. The crystal structure of Grb2 was determined to 3.1 angstrom resolution. The asymmetric unit is composed of an embedded dimer. The interlaced junctions between the SH2 and SH3 domains bring the two adjacent faces of the SH3 domains in van der Waals contact but leave room for the binding of proline-rich peptides. PMID:7716522

  14. Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump

    OpenAIRE

    Hinchliffe, Philip; Greene, Nicholas P.; Paterson, Neil G.; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

    2014-01-01

    Periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. The 2.85 Å resolution structure of an MFS (major facilitator superfamily) pump adaptor, Aquifex aeolicus EmrA, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. The adaptor α-hairpin, which binds outer membrane TolC, is exceptionally long at 127 Å, and the β-barrel co...

  15. Study on the isothermal forging process of MB26 magnesium alloy adaptor

    Directory of Open Access Journals (Sweden)

    Xu Wenchen

    2015-01-01

    Full Text Available The isothermal forging process is an effective method to manufacture complex-shaped components of hard-to-work materials, such as magnesium alloys. This study investigates the isothermal forging process of an MB26 magnesium alloy adaptor with three branches. The results show that two-step forging process is appropriate to form the adaptor forging, which not only improves the filling quality but also reduces the forging load compared with one-step forging process. Moreover, the flow line is distributed along the contour of the complex-shaped adaptor forging.

  16. Adaptor protein LNK is a negative regulator of brain neural stem cell proliferation after stroke.

    Science.gov (United States)

    Ahlenius, Henrik; Devaraju, Karthikeyan; Monni, Emanuela; Oki, Koichi; Wattananit, Somsak; Darsalia, Vladimer; Iosif, Robert E; Torper, Olof; Wood, James C; Braun, Sebastian; Jagemann, Lucas; Nuber, Ulrike A; Englund, Elisabet; Jacobsen, Sten-Eirik W; Lindvall, Olle; Kokaia, Zaal

    2012-04-11

    Ischemic stroke causes transient increase of neural stem and progenitor cell (NSPC) proliferation in the subventricular zone (SVZ), and migration of newly formed neuroblasts toward the damaged area where they mature to striatal neurons. The molecular mechanisms regulating this plastic response, probably involved in structural reorganization and functional recovery, are poorly understood. The adaptor protein LNK suppresses hematopoietic stem cell self-renewal, but its presence and role in the brain are poorly understood. Here we demonstrate that LNK is expressed in NSPCs in the adult mouse and human SVZ. Lnk(-/-) mice exhibited increased NSPC proliferation after stroke, but not in intact brain or following status epilepticus. Deletion of Lnk caused increased NSPC proliferation while overexpression decreased mitotic activity of these cells in vitro. We found that Lnk expression after stroke increased in SVZ through the transcription factors STAT1/3. LNK attenuated insulin-like growth factor 1 signaling by inhibition of AKT phosphorylation, resulting in reduced NSPC proliferation. Our findings identify LNK as a stroke-specific, endogenous negative regulator of NSPC proliferation, and suggest that LNK signaling is a novel mechanism influencing plastic responses in postischemic brain. PMID:22496561

  17. Study on the isothermal forging process of MB26 magnesium alloy adaptor

    OpenAIRE

    Xu Wenchen; Yang Chuan; Shaninst Debin; Xu Fuchang; Wang Guan; Guo Bin

    2015-01-01

    The isothermal forging process is an effective method to manufacture complex-shaped components of hard-to-work materials, such as magnesium alloys. This study investigates the isothermal forging process of an MB26 magnesium alloy adaptor with three branches. The results show that two-step forging process is appropriate to form the adaptor forging, which not only improves the filling quality but also reduces the forging load compared with one-step forging process. Moreover, the flow line is di...

  18. N-terminal tyrosine modulation of the endocytic adaptor function of the beta-arrestins.

    Science.gov (United States)

    Marion, Sébastien; Fralish, Gregory B; Laporte, Stéphane; Caron, Marc G; Barak, Larry S

    2007-06-29

    The highly homologous beta-arrestin1 and -2 adaptor proteins play important roles in the function of G protein-coupled receptors. Either beta-arrestin variant can function as a molecular chaperone for clathrin-mediated receptor internalization. This role depends primarily upon two distinct, contiguous C-terminal beta-arrestin motifs recognizing clathrin and the beta-adaptin subunit of AP2. However, a molecular basis is lacking to explain the different endocytic efficacies of the two beta-arrestin isoforms and the observation that beta-arrestin N-terminal substitution mutants can act as dominant negative inhibitors of receptor endocytosis. Despite the near identity of the beta-arrestins throughout their N termini, sequence variability is present at a small number of residues and includes tyrosine to phenylalanine substitutions. Here we show that corresponding N-terminal (Y/F)VTL sequences in beta-arrestin1 and -2 differentially regulate mu-adaptin binding. Our results indicate that the beta-arrestin1 Tyr-54 lessens the interaction with mu-adaptin and moreover is a Src phosphorylation site. A gain of endocytic function is obtained with the beta-arrestin1 Y54F substitution, which improves both the beta-arrestin1 interaction with mu-adaptin and the ability to enhance beta2-adrenergic receptor internalization. These data indicate that beta-arrestin2 utilizes mu-adaptin as an endocytic partner, and that the inability of beta-arrestin1 to sustain a similar degree of interaction with mu-adaptin may result from coordination of Tyr-54 by neighboring residues or its modification by Src kinase. Additionally, these naturally occurring variations in beta-arrestins may also differentially regulate the composition of the signaling complexes organized on the receptor. PMID:17456469

  19. The TIR-domain containing adaptor TRAM is required for TLR7 mediated RANTES production.

    Directory of Open Access Journals (Sweden)

    Enda Shevlin

    Full Text Available Toll-like receptor 7 (TLR7 plays a vital role in the immune response to ssRNA viruses such as human rhinovirus (HRV and Influenza, against which there are currently no treatments or vaccines with long term efficacy available. Clearly, a more comprehensive understanding of the TLR7 signaling axis will contribute to its molecular targeting. TRIF related adaptor molecule (TRAM plays a vital role in TLR4 signaling by recruiting TRIF to TLR4, followed by endosomal trafficking of the complex and initiation of IRF3 dependent type I interferon production as well as NF-κB dependent pro-inflammatory cytokine production. Towards understanding the molecular mechanisms that regulate TLR7 functionality, we found that TRAM(-/- murine macrophages exhibited a transcriptional and translational impairment in TLR7 mediated RANTES, but not TNFα, production. Suppression of TRAM expression in human macrophages also resulted in an impairment in TLR7 mediated CCL5 and IFN-β, but not TNFα, gene induction. Furthermore, suppression of endogenous human TRAM expression in human macrophages significantly impaired RV16 induced CCL5 and IFNβ, but not TNFα gene induction. Additionally, TRAM-G2A dose-dependently inhibited TLR7 mediated activation of CCL5, IFNβ and IFNα reporter genes. TLR7-mediated phosphorylation and nuclear translocation of IRF3 was impaired in TRAM(-/- cells. Finally, co-immunoprecipitation studies indicated that TRAM physically interacts with MyD88 upon TLR7 stimulation, but not under basal conditions. Our results clearly demonstrate that TRAM plays a, hitherto unappreciated, role in TLR7 signaling through a novel signaling axis containing, but not limited to, MyD88, TRAM and IRF3 towards the activation of anti-viral immunity.

  20. Stepping motor adaptor actuator for a commercial uhv linear motion feedthrough

    International Nuclear Information System (INIS)

    An adaptor coupling has been developed that will allow the attachment of a standard stepping motor to a precision commercial (Varian) uhv linear motion feedthrough. The assembly, consisting of the motor, motor adaptor, limit switches, etc. is clamped to the feedthrough body which can be done under vacuum conditions if necessary. With a 500 step/rev. stepping motor the resolution is 1.27 μm per step. We presently use this assembly in a remote location for the precise positioning of a beam sensing monitor. 2 refs., 3 figs

  1. DMPD: Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17667936 Structure, function and regulation of the Toll/IL-1 receptor adaptor prote... (.svg) (.html) (.csml) Show Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. ...PubmedID 17667936 Title Structure, function and regulation of the Toll/IL-1 recep

  2. SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export.

    Science.gov (United States)

    Müller-McNicoll, Michaela; Botti, Valentina; de Jesus Domingues, Antonio M; Brandl, Holger; Schwich, Oliver D; Steiner, Michaela C; Curk, Tomaz; Poser, Ina; Zarnack, Kathi; Neugebauer, Karla M

    2016-03-01

    Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends. PMID:26944680

  3. The AP-3 adaptor complex is required for vacuolar function in Arabidopsis

    NARCIS (Netherlands)

    Zwiewka, M.; Feraru, E.; Moller, B.K.; Hwang, I.; Feraru, M.I.; Kleine-Vehn, J.; Weijers, D.; Friml, J.

    2011-01-01

    Subcellular trafficking is required for a multitude of functions in eukaryotic cells. It involves regulation of cargo sorting, vesicle formation, trafficking and fusion processes at multiple levels. Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals

  4. Transmembrane adaptor molecules: a new category of lymphoid-cell markers

    Czech Academy of Sciences Publication Activity Database

    Tedoldi, S.; Paterson, J.C.; Hansmann, M.-L.; Natkunam, Y.; Rüdiger, T.; Angelisová, Pavla; Du, M.Q.; Roberton, H.; Roncador, G.; Sanchez, L.; Pozzobon, M.; Masir, N.; Barry, R.; Pileri, S.; Mason, D.Y.; Marafioti, T.; Hořejší, Václav

    2006-01-01

    Roč. 107, č. 1 (2006), s. 213-221. ISSN 0006-4971 R&D Projects: GA MŠk(CZ) 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : transmembrane adaptors * PAG * LIME Subject RIV: EC - Immunology Impact factor: 10.370, year: 2006

  5. Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

    Science.gov (United States)

    Becker, Marc A.; Ibrahim, Yasir H.; Oh, Annabell S.; Fagan, Dedra H.; Byron, Sara A.; Sarver, Aaron L.; Lee, Adrian V.; Shaw, Leslie M.; Fan, Cheng; Perou, Charles M.; Yee, Douglas

    2016-01-01

    Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID:26991655

  6. Expression of Chicken Toll-Like Receptors and Signal Adaptors in Spleen and Cecum of Young Chickens Infected with Eimeria tenella

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zuo-yong; HU Shi-jun; WANG Zhi-ying; GUO Zhi-li; QIN Bo; NIE Kui

    2014-01-01

    Toll-like receptors (TLRs) are a group of highly conserved molecules which initiate the innate immune response to pathogens by recognizing structural motifs of microbes. Understanding the changes in chicken Toll-like receptors (ChTLRs) and signal adaptors expression that occur with Eimeria tenella infection will help to elucidate the molecular basis of immune control of coccidiosis caused by Eimeria. The present study detected the dynamic changes in the expression of ChTLRs and associated signal adaptors in the spleen and cecum of E. tenella-infected chickens during the early stage of infection. The results showed that the expression peak for ChTLRs, MyD88 and TRIF occurred at 12 h post-infection (hpi), ChTLR3, ChTLR15 and MyD88 mRNA expression in the spleen of E. tenella infected chickens were signiifcantly higher (P<0.05) than that of negative control chickens, and there were similar tendencies of these molecules expression in the cecum and spleen of E. tenella-infected chickens. The expression of MyD88 was upregulated at four time points in the cecum of E. tenella-infected chickens. The results of this study indicate that ChTLR3, ChTLR15 and MyD88 play a role in young chickens infected with E. tenella.

  7. ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2016-02-01

    Full Text Available Stimulator of interferon genes (STING, also known as MITA, ERIS or MPYS induces the activation of TBK1 kinase and IRF3 transcription factor, upon sensing of microbial DNAs. How IRF3 is recruited onto the STING signalosome remains unknown. We report here that silencing of the ER adaptor SCAP markedly impairs the IRF3-responsive gene expression induced by STING. Scap knockdown mice are more susceptible to HSV-1 infection. Interestingly, SCAP translocates from ER, via Golgi, to perinuclear microsome in a STING-dependent manner. Mechanistically, the N-terminal transmembrane domain of SCAP interacts with STING, and the C-terminal cytosolic domain of SCAP binds to IRF3, thus recruiting IRF3 onto STING signalosome. Mis-localization of SCAP abolishes its antiviral function. Collectively, this study characterizes SCAP as an essential adaptor in the STING signaling pathway, uncovering a critical missing link in DNAs-triggered host antiviral responses.

  8. The interaction between the adaptor protein APS and Enigma is involved in actin organisation

    DEFF Research Database (Denmark)

    Barres, Romain; Gonzalez, Teresa; Le Marchand-Brustel, Yannick; Tanti, Jean-François

    2005-01-01

    APS (adaptor protein with PH and SH2 domains) is an adaptor protein phosphorylated by several tyrosine kinase receptors including the insulin receptor. To identify novel binding partners of APS, we performed yeast two-hybrid screening. We identified Enigma, a PDZ and LIM domain-containing protein...... that was previously shown to be associated with the actin cytoskeleton. In HEK 293 cells, Enigma interacted specifically with APS, but not with the APS-related protein SH2-B. This interaction required the NPTY motif of APS and the LIM domains of Enigma. In NIH-3T3 cells that express the insulin...... receptor, Enigma and APS were partially co-localised with F-actin in small ruffling structures. Insulin increased the complex formation between APS and Enigma and their co-localisation in large F-actin containing ruffles. While in NIH-3T3 and HeLa cells the co-expression of both Enigma and APS did not...

  9. PIP2: choreographer of actin-adaptor proteins in the HIV-1 dance

    Science.gov (United States)

    Rocha-Perugini, Vera; Gordon-Alonso, Mónica; Sánchez-Madrid, Francisco

    2014-01-01

    The actin cytoskeleton plays a key role during the replication cycle of human immunodeficiency virus-1 (HIV-1). HIV-1 infection is affected by cellular proteins that influence the clustering of viral receptors or the subcortical actin cytoskeleton. Several of these actin-adaptor proteins are controlled by the second messenger phosphatidylinositol 4,5-biphosphate (PIP2), an important regulator of actin organization. PIP2 production is induced by HIV-1 attachment and facilitates viral infection. However, the importance of PIP2 in regulating cytoskeletal proteins and thus HIV-1 infection has been overlooked. This review examines recent reports describing the roles played by actin-adaptor proteins during HIV-1 infection of CD4+ T cells, highlighting the influence of the signaling lipid PIP2 in this process. PMID:24768560

  10. Chromatin Adaptor Brd4 Modulates E2 Transcription Activity and Protein Stability*

    OpenAIRE

    Lee, A-Young; Chiang, Cheng-Ming

    2009-01-01

    Brd4 is a chromatin adaptor containing tandem bromodomains binding to acetylated histone H3 and H4. Although Brd4 has been implicated in the transcriptional control of papillomavirus-encoded E2 protein, it is unclear how Brd4 regulates E2 function and whether the involvement of Brd4 in transactivation and transrepression is common to different types of E2 proteins. Using DNase I footprinting performed with in vitro reconstituted human papillomavirus (HPV) chromatin and...

  11. Clathrin and HA2 adaptors: effects of potassium depletion, hypertonic medium, and cytosol acidification

    OpenAIRE

    1993-01-01

    The effects of methods known to perturb endocytosis from clathrin- coated pits on the localization of clathrin and HA2 adaptors in HEp-2 carcinoma cells have been studied by immunofluorescence and ultrastructural immunogold microscopy, using internalization of transferrin as a functional assay. Potassium depletion, as well as incubation in hypertonic medium, remove membrane-associated clathrin lattices: flat clathrin lattices and coated pits from the plasma membrane, and clathrin-coated vesic...

  12. Biochemical and Structural Studies on the Adaptor Protein p130Cas

    OpenAIRE

    Nasertorabi, Fariborz

    2005-01-01

    Crk associated substrate (Cas) is an adaptor protein that becomes phosphorylated upon integrin signaling and influences regulation of cell processes such as migration, proliferation and survival. It consists of multiple domains and regions that can interact with several signaling proteins involved in different signaling pathways. Cas was first discovered as a highly phosphorylated protein in v-Src and v-Crk transformed cells, showing involvement of this protein in cell transformation High lev...

  13. The adaptor molecule Trif contributes to murine host defense during Leptospiral infection.

    Science.gov (United States)

    Jayaraman, Priya A; Devlin, Amy A; Miller, Jennifer C; Scholle, Frank

    2016-09-01

    Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon β (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans. PMID:27259371

  14. New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Ebbe Toftgaard Poulsen

    2015-12-01

    Full Text Available The Amyloid Precursor Protein (APP has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ in Alzheimer’s disease (AD. However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc and its Adaptor Protein 2 (AP-2. Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.

  15. Science Signaling Podcast for 12 July 2016: Adaptor proteins limit signaling.

    Science.gov (United States)

    Wiley, H Steven; VanHook, Annalisa M

    2016-01-01

    This Podcast features an interview with Steven Wiley, senior author of a Research Article that appears in the 12 July 2016 issue of Science Signaling, about how the abundance of adaptor proteins and feedback regulators affect the flow of information downstream of the epidermal growth factor receptor (EGFR). Information flows through a signaling pathway by sequential interactions between core components of the pathway, many of which have enzymatic activity. Adaptor proteins do not directly participate in relaying the signal and do not have enzymatic activity, but are important for signaling because they facilitate interactions between the core components. Using quantitative methods, Shi et al demonstrated that core components of the EGFR pathway were highly abundant in both normal cells and cancer cells. However, adaptor proteins were present in much lower abundance in both cell types, indicating that it is the abundance of these proteins that limit signaling downstream of EGFR. The authors also found that differences in EGFR signaling between different cell types likely resulted from the variable abundance of feedback regulators.Listen to Podcast. PMID:27405978

  16. Proteins recruited by SH3 domains of Ruk/CIN85 adaptor identified by LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Havrylov Serhiy

    2009-06-01

    Full Text Available Abstract Background Ruk/CIN85 is a mammalian adaptor molecule with three SH3 domains. Using its SH3 domains Ruk/CIN85 can cluster multiple proteins and protein complexes, and, consequently, facilitates organisation of elaborate protein interaction networks with diverse regulatory roles. Previous research linked Ruk/CIN85 with the regulation of vesicle-mediated transport and cancer cell invasiveness. Despite the recent findings, precise molecular functions of Ruk/CIN85 in these processes remain largely elusive and further research is hampered by a lack of complete lists of its partner proteins. Results In the present study we employed a LC-MS/MS-based experimental pipeline to identify a considerable number (over 100 of proteins recruited by the SH3 domains of Ruk/CIN85 in vitro. Most of these identifications are novel Ruk/CIN85 interaction candidates. The identified proteins have diverse molecular architectures and can interact with other proteins, as well as with lipids and nucleic acids. Some of the identified proteins possess enzymatic activities. Functional profiling analyses and literature mining demonstrate that many of the proteins recruited by the SH3 domains of Ruk/CIN85 identified in this work were involved in the regulation of membranes and cytoskeletal structures necessary for vesicle-mediated transport and cancer cell invasiveness. Several groups of the proteins were also associated with few other cellular processes not previously related to Ruk/CIN85, most prominently with cell division. Conclusion Obtained data support the notion that Ruk/CIN85 regulates vesicle-mediated transport and cancer cell invasiveness through the assembly of multimeric protein complexes governing coordinated remodelling of membranes and underlying cytoskeletal structures, and imply its important roles in formation of coated vesicles and biogenesis of invadopodia. In addition, this study points to potential involvement of Ruk/CIN85 in other cellular

  17. Regulation and function of the CD3¿ DxxxLL motif: a binding site for adaptor protein-1 and adaptor protein-2 in vitro

    DEFF Research Database (Denmark)

    Dietrich, J; Kastrup, J; Nielsen, B L;

    1997-01-01

    /CD3gamma chimeras; and in vitro by binding CD3gamma peptides to clathrin-coated vesicle adaptor proteins (APs). We find that the CD3gamma D127xxxLL131/132 sequence represents one united motif for binding of both AP-1 and AP-2, and that this motif functions as an active sorting motif in monomeric CD4...... and for AP binding in vitro. Furthermore, we provide evidence indicating that phosphorylation of CD3gamma S126 in the context of the complete TCR induces a conformational change that exposes the DxxxLL sequence for AP binding. Exposure of the DxxxLL motif causes an increase in the TCR internalization...

  18. Evidence for an evolutionary relationship between the large adaptor nucleoporin Nup192 and karyopherins.

    Science.gov (United States)

    Stuwe, Tobias; Lin, Daniel H; Collins, Leslie N; Hurt, Ed; Hoelz, André

    2014-02-18

    Nucleocytoplasmic transport is facilitated by nuclear pore complexes (NPCs), which are massive proteinaceous transport channels embedded in the nuclear envelope. Nup192 is a major component of an adaptor nucleoporin subcomplex proposed to link the NPC coat with the central transport channel. Here, we present the structure of the ∼110-kDa N-terminal domain (NTD) of Nup192 at 2.7-Å resolution. The structure reveals an open ring-shaped architecture composed of Huntingtin, EF3, PP2A, and TOR1 (HEAT) and Armadillo (ARM) repeats. A comparison of different conformations indicates that the NTD consists of two rigid halves connected by a flexible hinge. Unexpectedly, the two halves of the ring are structurally related to karyopherin-α (Kap-α) and β-karyopherin family members. Biochemically, we identify a conserved patch that binds an unstructured segment in Nup53 and show that a C-terminal tail region binds to a putative helical fragment in Nic96. The Nup53 segment that binds Nup192 is a classical nuclear localization-like sequence that interacts with Kap-α in a mutually exclusive and mechanistically distinct manner. The disruption of the Nup53 and Nic96 binding sites in vivo yields growth and mRNA export defects, revealing their critical role in proper NPC function. Surprisingly, both interactions are dispensable for NPC localization, suggesting that Nup192 possesses another nucleoporin interaction partner. These data indicate that the structured domains in the adaptor nucleoporin complex are held together by peptide interactions that resemble those found in karyopherin•cargo complexes and support the proposal that the adaptor nucleoporins arose from ancestral karyopherins. PMID:24505056

  19. DNA as Tunable Adaptor for siRNA Polyplex Stabilization and Functionalization.

    Science.gov (United States)

    Heissig, Philipp; Klein, Philipp M; Hadwiger, Philipp; Wagner, Ernst

    2016-01-01

    siRNA and microRNA are promising therapeutic agents, which are engaged in a natural mechanism called RNA interference that modulates gene expression posttranscriptionally. For intracellular delivery of such nucleic acid triggers, we use sequence-defined cationic polymers manufactured through solid phase chemistry. They consist of an oligoethanamino amide core for siRNA complexation and optional domains for nanoparticle shielding and cell targeting. Due to the small size of siRNA, electrostatic complexes with polycations are less stable, and consequently intracellular delivery is less efficient. Here we use DNA oligomers as adaptors to increase size and charge of cargo siRNA, resulting in increased polyplex stability, which in turn boosts transfection efficiency. Extending a single siRNA with a 181-nucleotide DNA adaptor is sufficient to provide maximum gene silencing aided by cationic polymers. Interestingly, this simple strategy was far more effective than merging defined numbers (4-10) of siRNA units into one DNA scaffolded construct. For DNA attachment, the 3' end of the siRNA passenger strand was beneficial over the 5' end. The impact of the attachment site however was resolved by introducing bioreducible disulfides at the connection point. We also show that DNA adaptors provide the opportunity to readily link additional functional domains to siRNA. Exemplified by the covalent conjugation of the endosomolytic influenza peptide INF-7 to siRNA via a DNA backbone strand and complexing this construct with a targeting polymer, we could form a highly functional polyethylene glycol-shielded polyplex to downregulate a luciferase gene in folate receptor-positive cells. PMID:26928236

  20. The clathrin adaptor complexes as a paradigm for membrane-associated allostery

    OpenAIRE

    Canagarajah, Bertram J.; Ren, Xuefeng; Bonifacino, Juan S.; Hurley, James H.

    2013-01-01

    The clathrin-associated adaptor protein (AP) complexes AP-1 and AP-2 are two members of a family of heterotetrameric assemblies that connect transmembrane protein cargo to vesicular coats. Cargo binding by AP-1 is activated by the small GTPase Arf1, while AP-2 is activated by the phosphoinositide PI(4,5)P2. The structures of both AP-1 and AP-2 have been determined in their locked and unlocked conformations. The structures show how different activators use different mechanisms to trigger simil...

  1. The role of small adaptor proteins in the control of oncogenic signaling driven by tyrosine kinases in human cancer

    Science.gov (United States)

    Naudin, Cécile; Chevalier, Clément; Roche, Serge

    2016-01-01

    Protein phosphorylation on tyrosine (Tyr) residues has evolved as an important mechanism to coordinate cell communication in multicellular organisms. The importance of this process has been revealed by the discovery of the prominent oncogenic properties of tyrosine kinases (TK) upon deregulation of their physiological activities, often due to protein overexpression and/or somatic mutation. Recent reports suggest that TK oncogenic signaling is also under the control of small adaptor proteins. These cytosolic proteins lack intrinsic catalytic activity and signal by linking two functional members of a catalytic pathway. While most adaptors display positive regulatory functions, a small group of this family exerts negative regulatory functions by targeting several components of the TK signaling cascade. Here, we review how these less studied adaptor proteins negatively control TK activities and how their loss of function induces abnormal TK signaling, promoting tumor formation. We also discuss the therapeutic consequences of this novel regulatory mechanism in human oncology. PMID:26788993

  2. Effectiveness of Needleless Vial Adaptors and Blunt Cannulas for Drug Administration in a Microgravity Environment

    Science.gov (United States)

    Hailey, M.; Bayuse, T.

    2010-01-01

    Fluid Isolation in the medication vial: Air/ fluid isolation maneuvers were used to move the medication to the septum end of vial. This isolation may be achieved in multiple ways based on the experience of the astronaut with fluid management in microgravity. If vial adaptors/blunt cannula or syringe assembly is inserted into the to vial before fluid isolation commences, the stability of this assembly should be considered in an effort to limit the risk of "slinging off" of the vial during isolation. Alternatively, fluid isolation can be performed prior to attaching the syringe/vial adaptor assembly. Terrestrial practices for medication withdrawal from a nonvented vial require injection of an equivalent amount of air as the expected medication volume prior to withdrawing liquid. In microgravity, this action is still valid, however the injection of additional air into the vial creates a multitude of micro bubbles and increases the volume of medication mixed with air that then must be withdrawn to achieve the desired drug volume in syringe. This practice is more likely to be required when using vials >30ml in size and injection volumes >10mL. It is felt that based on the microgravity flight, the practice of air injection is more of a hindrance than help.

  3. The Adaptor Protein Rai/ShcC Promotes Astrocyte-Dependent Inflammation during Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Ulivieri, Cristina; Savino, Maria Teresa; Luccarini, Ilaria; Fanigliulo, Emanuela; Aldinucci, Alessandra; Bonechi, Elena; Benagiano, Marisa; Ortensi, Barbara; Pelicci, Giuliana; D'Elios, Mario Milco; Ballerini, Clara; Baldari, Cosima Tatiana

    2016-07-15

    Th17 cells have been casually associated to the pathogenesis of autoimmune disease. We have previously demonstrated that Rai/ShcC, a member of the Shc family of adaptor proteins, negatively regulates Th17 cell differentiation and lupus autoimmunity. In this study, we have investigated the pathogenic outcome of the Th17 bias associated with Rai deficiency on multiple sclerosis development, using the experimental autoimmune encephalomyelitis (EAE) mouse model. We found that, unexpectedly, EAE was less severe in Rai(-/-) mice compared with their wild-type counterparts despite an enhanced generation of myelin-specific Th17 cells that infiltrated into the CNS. Nevertheless, when adoptively transferred into immunodeficient Rai(+/+) mice, these cells promoted a more severe disease compared with wild-type encephalitogenic Th17 cells. This paradoxical phenotype was caused by a dampened inflammatory response of astrocytes, which were found to express Rai, to IL-17. The results provide evidence that Rai plays opposite roles in Th17 cell differentiation and astrocyte activation, with the latter dominant over the former in EAE, highlighting this adaptor as a potential novel target for the therapy of multiple sclerosis. PMID:27288534

  4. Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2 activation via BACH1 repressor turnover.

    Science.gov (United States)

    Tan, Meng-Kwang Marcus; Lim, Hui-Jun; Bennett, Eric J; Shi, Yang; Harper, J Wade

    2013-10-10

    Modular cullin-RING E3 ubiquitin ligases (CRLs) use substrate binding adaptor proteins to specify target ubiquitylation. Many of the ~200 human CRL adaptor proteins remain poorly studied due to a shortage of efficient methods to identify biologically relevant substrates. Here, we report the development of parallel adaptor capture (PAC) proteomics and its use to systematically identify candidate targets for the leucine-rich repeat family of F-box proteins (FBXLs) that function with SKP1-CUL1-F-box protein (SCF) E3s. In validation experiments, we identify the unstudied F-box protein FBXL17 as a regulator of the NFR2 oxidative stress pathway. We demonstrate that FBXL17 controls the transcription of the NRF2 target HMOX1 via turnover of the transcriptional repressor BACH1 in the absence or presence of extrinsic oxidative stress. This work identifies a role for SCF(FBXL17) in controlling the threshold for NRF2-dependent gene activation and provides a framework for elucidating the functions of CRL adaptor proteins. PMID:24035498

  5. Effectiveness of Needles Vial Adaptors and Blunt Cannulas for Drug Administration in a Microgravity Environment

    Science.gov (United States)

    Hailey, Melinda; Bayuse, Tina

    2009-01-01

    The need for a new system of injectable medications aboard the International Space Station (ISS) was identified. It is desired that this system fly medications in their original manufacturer's packaging, allowing the system to comply with United States Pharmacopeia (USP) guidelines while minimizing the resupply frequency due to medication expiration. Pre-filled syringes are desired, however, the evolving nature of the healthcare marketplace requires flexibility in the redesign. If medications must be supplied in a vial, a system is required that allows for the safe withdrawal of medication from the vial into a syringe for administration in microgravity. During two reduced gravity flights, the effectiveness of two versions of a blunt cannula and needleless vial adaptors was evaluated to facilitate the withdrawal of liquid medication from a vial into a syringe for injection. Other parameters assessed included the ability to withdraw the required amount of medication and whether this is dependent on vial size, liquid, or the total volume of fluid within the vial. Injectable medications proposed for flight on ISS were used for this evaluation. Due to differing sizes of vials and the fluid properties of the medications, the needleless vial adaptors proved to be too cumbersome to recommend for use on the ISS. The blunt cannula, specifically the plastic version, proved to be more effective at removing medication from the various sizes of vials and are the recommended hardware for ISS. Fluid isolation within the vials and syringes is an important step in preparing medication for injection regardless of the hardware used. Although isolation is a challenge in the relatively short parabolas during flight, it is not an obstacle for sustained microgravity. This presentation will provide an overview of the products tested as well as the challenges identified during the microgravity flights.

  6. The Influences of Connectors and Adaptors to Fiber-To-The-Home Network Performance

    Directory of Open Access Journals (Sweden)

    Mohammad S. Ab-Rahman

    2012-01-01

    Full Text Available Problem statement: The reliability of the entire communications network was dependent on the reliability of each single element. Connector was important devices that can affect the performance of the fiber communication. There were a large number of issues that affect the performance of fiber optic connectors in todays networks. These factors were increasingly as data rates, the number of wavelengths and transmission distances continue to escalate. Approach: Therefore this study was carried out to test on the influence of connectors and adapters to the performance of the optical network. Initially the actual attenuation of connector and adaptor were tested by using multifunction loss tester. The first two 1 m corning optical fibers with a connector at each end are measured. Then, both the 1 m corning optical fibers were joined together by an adaptor and connected to the Multifunction loss tester. Three types of wavelength are used as the source to test the attenuation of the fiber which is 1310, 1490-1550 nm. In order to measure the Bit Error Rate (BER and the power loss in optical fiber communication, a simple simulation was carried out by using software opti sys. Results: The attenuation on the connector was caused mainly by existence of impurities in the connector, less perfect connection, scattering of beam and others. These causes the parameter such as power received, Q-factor, minimum BER and also the eye-height to change. Changes in these parameters also affect the performance at the user end. It was very critical that causes of attenuation to be eliminated. Conclusion/Recommendations: From the result it can be concluded that, the greater the attenuation, the greater the decrease in power received. It also affects the Q-factor of the system where as the attenuation increase, the maximum Q-factor decreases. As for the minimum BER, minimum BER changes as the attenuation increase initially, after a maximum value it decreases as the

  7. Comparison Study on Finite Element Model for Structural Analysis of Lower CTS Cylinder Lifting Adaptor in ITER Assembly Tool

    International Nuclear Information System (INIS)

    The ITER tokamak assembly tools are purpose-built and specially designed to complete the ITER tokamak machine which includes; Vacuum Vessel (VV), VV Thermal Shield (VVTS) and Cryostat Thermal Shield (CTS), Toroidal Field Coil (TFC) and Poloidal Field (PF) coils, and other components contained in the cryostat. Based on the engineering design and design description documents prepared by the ITER organization (IO). In this paper, FE models to verify the structural integrity of the Lower Cryostat Thermal Shield (LCTS) Lifting Adaptor are prepared and compared with their structure analysis result. In the paper, each analysis result with difference BC applied was compared with the equivalent stress and the results of analysis were evaluated according to SM490YB's allowable stress. And the conclusions of this paper are summarized as following. - The structural stabilities of the LCTS lift adaptor have been studied using ANSYS codes for verifying structural strength for this tool

  8. LIME: a new membrane raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling

    Czech Academy of Sciences Publication Activity Database

    Brdičková, Naděžda; Brdička, Tomáš; Angelisová, Pavla; Horváth, Ondřej; Špička, Jiří; Hilgert, Ivan; Pačes, Jan; Simeoni, L.; Kliche, S.; Merten, C.; Schraven, B.; Hořejší, Václav

    2003-01-01

    Roč. 198, č. 10 (2003), s. 1453-1462. ISSN 0022-1007 R&D Projects: GA MŠk LN00A079; GA MŠk LN00A026 Grant ostatní: Wellcome Trust(GB) J1116W24Z Institutional research plan: CEZ:AV0Z5052915 Keywords : immunology * T-lymphocyte * adaptor protein Subject RIV: EC - Immunology Impact factor: 15.302, year: 2003

  9. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

    Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  10. The role of palmitoylation and transmembrane domain in sorting of transmembrane adaptor proteins.

    Science.gov (United States)

    Chum, Tomáš; Glatzová, Daniela; Kvíčalová, Zuzana; Malínský, Jan; Brdička, Tomáš; Cebecauer, Marek

    2016-01-01

    Plasma membrane proteins synthesised at the endoplasmic reticulum are delivered to the cell surface via sorting pathways. Hydrophobic mismatch theory based on the length of the transmembrane domain (TMD) dominates discussion about determinants required for protein sorting to the plasma membrane. Transmembrane adaptor proteins (TRAP) are involved in signalling events which take place at the plasma membrane. Members of this protein family have TMDs of varying length. We were interested in whether palmitoylation or other motifs contribute to the effective sorting of TRAP proteins. We found that palmitoylation is essential for some, but not all, TRAP proteins independent of their TMD length. We also provide evidence that palmitoylation and proximal sequences can modulate sorting of artificial proteins with TMDs of suboptimal length. Our observations point to a unique character of each TMD defined by its primary amino acid sequence and its impact on membrane protein localisation. We conclude that, in addition to the TMD length, secondary sorting determinants such as palmitoylation or flanking sequences have evolved for the localisation of membrane proteins. PMID:26585312

  11. Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52

    Science.gov (United States)

    Jo, Chulman; Gundemir, Soner; Pritchard, Susanne; Jin, Youngnam N.; Rahman, Irfan; Johnson, Gail V. W.

    2014-03-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo.

  12. Tetraspanins and Transmembrane Adaptor Proteins As Plasma Membrane Organizers—Mast Cell Case

    Science.gov (United States)

    Halova, Ivana; Draber, Petr

    2016-01-01

    The plasma membrane contains diverse and specialized membrane domains, which include tetraspanin-enriched domains (TEMs) and transmembrane adaptor protein (TRAP)-enriched domains. Recent biophysical, microscopic, and functional studies indicated that TEMs and TRAP-enriched domains are involved in compartmentalization of physicochemical events of such important processes as immunoreceptor signal transduction and chemotaxis. Moreover, there is evidence of a cross-talk between TEMs and TRAP-enriched domains. In this review we discuss the presence and function of such domains and their crosstalk using mast cells as a model. The combined data based on analysis of selected mast cell-expressed tetraspanins [cluster of differentiation (CD)9, CD53, CD63, CD81, CD151)] or TRAPs [linker for activation of T cells (LAT), non-T cell activation linker (NTAL), and phosphoprotein associated with glycosphingolipid-enriched membrane microdomains (PAG)] using knockout mice or specific antibodies point to a diversity within these two families and bring evidence of the important roles of these molecules in signaling events. An example of this diversity is physical separation of two TRAPs, LAT and NTAL, which are in many aspects similar but show plasma membrane location in different microdomains in both non-activated and activated cells. Although our understanding of TEMs and TRAP-enriched domains is far from complete, pharmaceutical applications of the knowledge about these domains are under way.

  13. Cysteine-based regulation of the CUL3 adaptor protein Keap1

    International Nuclear Information System (INIS)

    Nrf2 (NF-E2-related factor 2) is a master transcription factor containing a powerful acidic transcriptional activation domain. Nrf2-dependent gene expression impacts cancer chemoprevention strategies, inflammatory responses, and progression of neurodegenerative diseases. Under basal conditions, association of Nrf2 with the CUL3 adaptor protein Keap1 results in the rapid Nrf2 ubiquitylation and proteasome-dependent degradation. Inhibition of Keap1 function blocks ubiquitylation of Nrf2, allowing newly synthesized Nrf2 to translocate into the nucleus, bind to ARE sites and direct target gene expression. Site-directed mutagenesis experiments coupled with proteomic analysis support a model in which Keap1 contains at least 2 distinct cysteine motifs. The first is located at Cys 151 in the BTB domain. The second is located in the intervening domain and centers around Cys 273 and 288. Adduction or oxidation at Cys151 has been shown to produce a conformational change in Keap1 that results in dissociation of Keap1 from CUL3, thereby inhibiting Nrf2 ubiquitylation. Thus, adduction captures specific chemical information and translates it into biochemical information via changes in structural conformation.

  14. Canine hepacivirus NS3 serine protease can cleave the human adaptor proteins MAVS and TRIF.

    Directory of Open Access Journals (Sweden)

    Mariona Parera

    Full Text Available Canine hepacivirus (CHV was recently identified in domestic dogs and horses. The finding that CHV is genetically the virus most closely related to hepatitis C virus (HCV has raised the question of whether HCV might have evolved as the result of close contact between dogs and/or horses and humans. The aim of this study was to investigate whether the NS3/4A serine protease of CHV specifically cleaves human mitochondrial antiviral signaling protein (MAVS and Toll-IL-1 receptor domain-containing adaptor inducing interferon-beta (TRIF. The proteolytic activity of CHV NS3/4A was evaluated using a bacteriophage lambda genetic screen. Human MAVS- and TRIF-specific cleavage sites were engineered into the lambda cI repressor. Upon infection of Escherichia coli cells coexpressing these repressors and a CHV NS3/4A construct, lambda phage replicated up to 2000-fold more efficiently than in cells expressing a CHV protease variant carrying the inactivating substitution S139A. Comparable results were obtained when several HCV NS3/4A constructs of genotype 1b were assayed. This indicates that CHV can disrupt the human innate antiviral defense signaling pathway and suggests a possible evolutionary relationship between CHV and HCV.

  15. Transmembrane adaptor molecules: a new category of lymphoid-cell markers.

    Science.gov (United States)

    Tedoldi, Sara; Paterson, Jennifer C; Hansmann, Martin-Leo; Natkunam, Yasodha; Rüdiger, Thomas; Angelisova, Pavla; Du, Ming Q; Roberton, Helen; Roncador, Giovanna; Sanchez, Lydia; Pozzobon, Michela; Masir, Noraidah; Barry, Richard; Pileri, Stefano; Mason, David Y; Marafioti, Teresa; Horejsí, Václav

    2006-01-01

    Transmembrane adaptor proteins (of which 7 have been identified so far) are involved in receptor signaling in immune cells. They have only a short extracellular region, with most of the molecule comprising a substantial intracytoplasmic region carrying multiple tyrosine residues that can be phosphorylated by Src- or Syk-family kinases. In this paper, we report an immunohistologic study of 6 of these molecules in normal and neoplastic human tissue sections and show that they are restricted to subpopulations of lymphoid cells, being present in either T cells (LAT, LIME, and TRIM), B cells (NTAL), or subsets of both cell types (PAG and SIT). Their expression in neoplastic lymphoid cells broadly reflects that of normal lymphoid tissue, including the positivity of plasma cells and myeloma/plasmacytoma for LIME, NTAL, PAG, and SIT. However, this study also revealed some reactions that may be of diagnostic/prognostic value. For example, lymphocytic lymphoma and mantle-cell lymphoma showed similar profiles but differed clearly from follicle-center lymphoma, whereas PAG tended to be selectively expressed in germinal center-derived subsets of diffuse large B-cell lymphoma. These molecules represent a potentially important addition to the panel of immunophenotypic markers detectable in routine biopsies that can be used in hematopathologic studies. PMID:16160011

  16. The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

    Directory of Open Access Journals (Sweden)

    Fubito Nakatsu

    2014-11-01

    Full Text Available The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis. Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells.

  17. Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein.

    Science.gov (United States)

    Ylösmäki, Leena; Fagerlund, Riku; Kuisma, Inka; Julkunen, Ilkka; Saksela, Kalle

    2016-01-01

    The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif. PMID:27092521

  18. Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein

    Directory of Open Access Journals (Sweden)

    Leena Ylösmäki

    2016-04-01

    Full Text Available The non-structural protein-1 (NS1 of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10 regulator of kinase and Crk-like adapter protein (CrkL. This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K, but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif.

  19. Nuclear Translocation of Crk Adaptor Proteins by the Influenza A Virus NS1 Protein

    Science.gov (United States)

    Ylösmäki, Leena; Fagerlund, Riku; Kuisma, Inka; Julkunen, Ilkka; Saksela, Kalle

    2016-01-01

    The non-structural protein-1 (NS1) of many influenza A strains, especially those of avian origin, contains an SH3 ligand motif, which binds tightly to the cellular adaptor proteins Crk (Chicken tumor virus number 10 (CT10) regulator of kinase) and Crk-like adapter protein (CrkL). This interaction has been shown to potentiate NS1-induced activation of the phosphatidylinositol 3-kinase (PI3K), but additional effects on the host cell physiology may exist. Here we show that NS1 can induce an efficient translocation of Crk proteins from the cytoplasm into the nucleus, which results in an altered pattern of nuclear protein tyrosine phosphorylation. This was not observed using NS1 proteins deficient in SH3 binding or engineered to be exclusively cytoplasmic, indicating a physical role for NS1 as a carrier in the nuclear translocation of Crk. These data further emphasize the role of Crk proteins as host cell interaction partners of NS1, and highlight the potential for host cell manipulation gained by a viral protein simply via acquiring a short SH3 binding motif. PMID:27092521

  20. Adaptor protein CRK induces epithelial–mesenchymal transition and metastasis of bladder cancer cells through HGF/c-Met feedback loop

    Science.gov (United States)

    Matsumoto, Ryuji; Tsuda, Masumi; Wang, Lei; Maishi, Nako; Abe, Takashige; Kimura, Taichi; Tanino, Mishie; Nishihara, Hiroshi; Hida, Kyoko; Ohba, Yusuke; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2015-01-01

    We have previously reported that an adaptor protein CRK, including CRK-I and CRK-II, plays essential roles in the malignant potential of various aggressive human cancers, suggesting the validity of targeting CRK in molecular targeted therapy of a wide range of cancers. Nevertheless, the role of CRK in human bladder cancer with marked invasion, characterized by distant metastasis and poor prognosis, remains obscure. In the present study, immunohistochemistry indicated a striking enhancement of CRK-I/-II, but not CRK-like, in human bladder cancer tissues compared to normal urothelium. We established CRK-knockdown bladder cancer cells using 5637 and UM-UC-3, which showed a significant decline in cell migration, invasion, and proliferation. It is noteworthy that an elimination of CRK conferred suppressed phosphorylation of c-Met and the downstream scaffold protein Gab1 in a hepatocyte growth factor-dependent and -independent manner. In epithelial–mesenchymal transition-related molecules, E-cadherin was upregulated by CRK elimination, whereas N-cadherin, vimentin, and Zeb1 were downregulated. A similar effect was observed following treatment with c-Met inhibitor SU11274. Depletion of CRK significantly decreased cell proliferation of 5637 and UM-UC-3, consistent with reduced activity of ERK. An orthotopic xenograft model with bioluminescent imaging revealed that CRK knockdown significantly attenuated not only tumor volume but also the number of circulating tumor cells, resulted in a complete abrogation of metastasis. Taken together, this evidence uncovered essential roles of CRK in invasive bladder cancer through the hepatocyte growth factor/c-Met/CRK feedback loop for epithelial–mesenchymal transition induction. Thus, CRK might be a potent molecular target in bladder cancer, particularly for preventing metastasis, leading to the resolution of clinically longstanding critical issues. PMID:25816892

  1. Surfactant Protein A Enhances Constitutive Immune Functions of Clathrin Heavy Chain and Clathrin Adaptor Protein 2.

    Science.gov (United States)

    Moulakakis, Christina; Steinhäuser, Christine; Biedziak, Dominika; Freundt, Katja; Reiling, Norbert; Stamme, Cordula

    2016-07-01

    NF-κB transcription factors are key regulators of pulmonary inflammatory disorders and repair. Constitutive lung cell type- and microenvironment-specific NF-κB/inhibitor κBα (IκB-α) regulation, however, is poorly understood. Surfactant protein (SP)-A provides both a critical homeostatic and lung defense control, in part by immune instruction of alveolar macrophages (AMs) via clathrin-mediated endocytosis. The central endocytic proteins, clathrin heavy chain (CHC) and the clathrin adaptor protein (AP) complex AP2, have pivotal alternative roles in cellular homeostasis that are endocytosis independent. Here, we dissect endocytic from alternative functions of CHC, the α-subunit of AP2, and dynamin in basal and SP-A-modified LPS signaling of macrophages. As revealed by pharmacological inhibition and RNA interference in primary AMs and RAW264.7 macrophages, respectively, CHC and α-adaptin, but not dynamin, prevent IκB-α degradation and TNF-α release, independent of their canonical role in membrane trafficking. Kinetics studies employing confocal microscopy, Western analysis, and immunomagnetic sorting revealed that SP-A transiently enhances the basal protein expression of CHC and α-adaptin, depending on early activation of protein kinase CK2 (former casein kinase II) and Akt1 in primary AMs from rats, SP-A(+/+), and SP-A(-/-) mice, as well as in vivo when intratracheally administered to SP-A(+/+) mice. Constitutive immunomodulation by SP-A, but not SP-A-mediated inhibition of LPS-induced NF-κB activity and TNF-α release, requires CHC, α-adaptin, and dynamin. Our data demonstrate that endocytic proteins constitutively restrict NF-κB activity in macrophages and provide evidence that SP-A enhances the immune regulatory capacity of these proteins, revealing a previously unknown pathway of microenvironment-specific NF-κB regulation in the lung. PMID:26771574

  2. Genetic Deletion of the Clathrin Adaptor GGA3 Reduces Anxiety and Alters GABAergic Transmission

    Science.gov (United States)

    Albrecht, David; Lomoio, Selene; Haydon, Philip G.; Moss, Stephen J.; Tesco, Giuseppina

    2016-01-01

    Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer’s disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates. PMID:27192432

  3. The AP-3 adaptor complex is required for vacuolar function in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Maria Zwiewka; Elena Feraru; Barbara M(o)ller; Inhwan Hwang; Mugurel I Feraru; Jürgen Kleine-Vehn; Dolf Weijers; Ji(n) Friml

    2011-01-01

    Subcellular trafficking is required for a multitude of functions in eukaryotic cells.It involves regulation of cargo sorting,vesicle formation,trafficking and fusion processes at multiple levels.Adaptor protein (AP) complexes are key regulators of cargo sorting into vesicles in yeast and mammals but their existence and function in plants have not been demonstrated.Here we report the identification of the protein-affected trafficking 4 (pat4) mutant defective in the putative δ subunit of the AP-3 complex.pat4 and pat2,a mutant isolated from the same GFP imaging-based forward genetic screen that lacks a functional putative AP-3 β,as well as dominant negative AP-3 μ transgenic lines display undistinguishable phenotypes characterized by largely normal morphology and development,but strong intracellular accumulation of membrane proteins in aberrant vacuolar structures.All mutants are defective in morphology and function of lytic and protein storage vacuoles (PSVs) but show normal sorting of reserve proteins to PSVs.Immunoprecipitation experiments and genetic studies revealed tight functional and physical associations of putative AP-3 β and AP-3 δ subunits.Furthermore,both proteins are closely linked with putative AP-3 μ and σ subunits and several components of the clathrin and dynamin machineries.Taken together,these results demonstrate that AP complexes,similar to those in other eukaryotes,exist in plants,and that AP-3 plays a specific role in the regulation of biogenesis and function of vacuoles in plant cells.

  4. The Toll-Like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery

    Directory of Open Access Journals (Sweden)

    Pak Kwang

    2009-08-01

    Full Text Available Abstract Background Toll-like receptor (TLR signalling is crucial for innate immune responses to infection. The involvement of TLRs in otitis media (OM, the most prevalent childhood disease in developed countries, has been implicated by studies in middle ear cell lines, by association studies of TLR-related gene polymorphisms, and by altered OM in mice bearing mutations in TLR genes. Activated TLRs signal via two alternative intracellular signaling molecules with differing effects; MyD88 (Myeloid differentiation primary response gene 88 inducing primarily interleukin expression and TRIF (Tir-domain-containing adaptor inducing interferon β mediating type I interferon (IFN expression. We tested the hypothesis that TRIF and type I IFN signaling play a role in OM, using a murine model of OM induced by non-typeable Haemophilus influenzae (NTHi. The ME inflammatory response to NTHi was examined in wild-type (WT and TRIF-/- mice by qPCR, gene microarray, histopathology and bacterial culture. Results Expression of TRIF mRNA was only modesty enhanced during OM, but both type I IFN signalling genes and type I IFN-inducible genes were significantly up-regulated in WT mice. TRIF-deficient mice showed reduced but more persistent mucosal hyperplasia and less leukocyte infiltration into the ME in response to NTHi infection than did WT animals. Viable bacteria could be cultured from MEs of TRIF-/- mice for much longer in the course of disease than was the case for middle ears of WT mice. Conclusion Our results demonstrate that activation of TRIF/type I IFN responses is important in both the pathogenesis and resolution of NTHi-induced OM.

  5. Cooperative and independent roles of the Drp1 adaptors Mff, MiD49 and MiD51 in mitochondrial fission.

    Science.gov (United States)

    Osellame, Laura D; Singh, Abeer P; Stroud, David A; Palmer, Catherine S; Stojanovski, Diana; Ramachandran, Rajesh; Ryan, Michael T

    2016-06-01

    Cytosolic dynamin-related protein 1 (Drp1, also known as DNM1L) is required for both mitochondrial and peroxisomal fission. Drp1-dependent division of these organelles is facilitated by a number of adaptor proteins at mitochondrial and peroxisomal surfaces. To investigate the interplay of these adaptor proteins, we used gene-editing technology to create a suite of cell lines lacking the adaptors MiD49 (also known as MIEF2), MiD51 (also known as MIEF1), Mff and Fis1. Increased mitochondrial connectivity was observed following loss of individual adaptors, and this was further enhanced following the combined loss of MiD51 and Mff. Moreover, loss of adaptors also conferred increased resistance of cells to intrinsic apoptotic stimuli, with MiD49 and MiD51 showing the more prominent role. Using a proximity-based biotin labeling approach, we found close associations between MiD51, Mff and Drp1, but not Fis1. Furthermore, we found that MiD51 can suppress Mff-dependent enhancement of Drp1 GTPase activity. Our data indicates that Mff and MiD51 regulate Drp1 in specific ways to promote mitochondrial fission. PMID:27076521

  6. The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains

    OpenAIRE

    Fölsch, Heike; Pypaert, Marc; Maday, Sandra; Pelletier, Laurence; Mellman, Ira

    2003-01-01

    Most epithelial cells contain two AP-1 clathrin adaptor complexes. AP-1A is ubiquitously expressed and involved in transport between the TGN and endosomes. AP-1B is expressed only in epithelia and mediates the polarized targeting of membrane proteins to the basolateral surface. Both AP-1 complexes are heterotetramers and differ only in their 50-kD μ1A or μ1B subunits. Here, we show that AP-1A and AP-1B, together with their respective cargoes, define physically and functionally distinct membra...

  7. Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF

    OpenAIRE

    Tunnicliffe, Richard B.; Hautbergue, Guillaume M.; Wilson, Stuart A.; Priti Kalra; Golovanov, Alexander P.

    2014-01-01

    The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX) complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range o...

  8. Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

    Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

  9. Characterization, genomic organization, and expression profiles of MyD88, a key adaptor molecule in the TLR signaling pathways in miiuy croaker (Miichthys miiuy).

    Science.gov (United States)

    Tang, Da; Gao, Yunhang; Wang, Rixin; Sun, Yuena; Xu, Tianjun

    2012-12-01

    Myeloid differentiation factor 88 (MyD88) is an important adaptor protein in the TLR signaling pathways. In the present study, we firstly cloned and characterized Miichthys miiuy MyD88 (Mimi-MyD88) cDNA and gene. The Mimi-MyD88 gene was 3,470 bp consisting of five exons and four introns. The cDNA was composed of 1,627 bp with an 867-bp open reading frame encoding a polypeptide of 288 amino acid residues. The theoretical molecular mass and isoelectric point of this polypeptide were 33.25 and 4.96 kDa. Comparison of the deduced amino acid sequence showed that the conserved death domain and the typical Toll/IL-1 receptor domain are very similar to those presented in other mammals, amphibians, and fishes. To identify potential role of MyD88 in fish innate immunological surveillance, the constitutive Mimi-MyD88 mRNA is detected by real-time quantitative polymerase chain reaction. Results demonstrated that Mimi-MyD88 is broadly expressed in ten normal tissues, with the lowest expression was observed in kidney and the highest was in liver. The transcriptional expression also revealed that Mimi-MyD88 was significantly up-regulated in liver, kidney, and spleen after challenge by Gram-negative bacteria, Vibrio anguillarum. Via contrasted the expression of MyD88 and TLR2 in kidney, we evaluated TLR2 plays an indispensable role in MyD88 transcription, but not absolutely dominant. The combined expression still indicated that MyD88 plays a universal role in keeping immune surveillance for pathogens. Phylogenetic analysis suggested that Mimi-MyD88 gene is classified into the piscine cluster and most closely related to large yellow croaker Larimichthys crocea. PMID:23053604

  10. Structural and functional insights into CARDs of zebrafish (Danio rerio) NOD1 and NOD2, and their interaction with adaptor protein RIP2.

    Science.gov (United States)

    Maharana, Jitendra; Dehury, Budheswar; Sahoo, Jyoti Ranjan; Jena, Itishree; Bej, Aritra; Panda, Debashis; Sahoo, Bikash Ranjan; Patra, Mahesh Chandra; Pradhan, Sukanta Kumar

    2015-08-01

    Nucleotide-binding and oligomerization domain-containing protein 1 (NOD1) and NOD2 are cytosolic pattern-recognition receptors (PRRs) composed of an N-terminal caspase activation and recruitment domain (CARD), a central NACHT domain and C-terminal leucine-rich repeats (LRRs). They play a vital role in innate immune signaling by activating the NF-κB pathway via recognition of peptidoglycans by LRRs, and ATP-dependent self-oligomerization of NACHT followed by downstream signaling. After oligomerization, CARD/s play a crucial role in activating downstream signaling via the adaptor molecule, RIP2. Due to the inadequacy of experimental 3D structures of CARD/s of NOD2 and RIP2, and results from differential experimental setups, the RIP2-mediated CARD-CARD interaction has remained as a contradictory statement. We employed a combinatorial approach involving protein modeling, docking, molecular dynamics simulation, and binding free energy calculation to illuminate the molecular mechanism that shows the possible involvement of either the acidic or basic patch of zebrafish NOD1/2-CARD/a and RIP2-CARD in CARD-CARD interaction. Herein, we have hypothesized 'type-I' mode of CARD-CARD interaction in NOD1 and NOD2, where NOD1/2-CARD/a involve their acidic surfaces to interact with RIP2. Asp37 and Glu51 (of NOD1) and Arg477, Arg521 and Arg529 (of RIP2) were identified to be crucial for NOD1-RIP2 interaction. However, in NOD2-RIP2, Asp32 (of NOD2) and Arg477 and Arg521 (of RIP2) were anticipated to be significant for downstream signaling. Furthermore, we found that strong electrostatic contacts and salt bridges are crucial for protein-protein interactions. Altogether, our study has provided novel insights into the RIP2-mediated CARD-CARD interaction in zebrafish NOD1 and NOD2, which will be helpful to understand the molecular basis of the NOD1/2 signaling mechanism. PMID:26079944

  11. VgrG C terminus confers the type VI effector transport specificity and is required for binding with PAAR and adaptor-effector complex.

    Science.gov (United States)

    Bondage, Devanand D; Lin, Jer-Sheng; Ma, Lay-Sun; Kuo, Chih-Horng; Lai, Erh-Min

    2016-07-01

    Type VI secretion system (T6SS) is a macromolecular machine used by many Gram-negative bacteria to inject effectors/toxins into eukaryotic hosts or prokaryotic competitors for survival and fitness. To date, our knowledge of the molecular determinants and mechanisms underlying the transport of these effectors remains limited. Here, we report that two T6SS encoded valine-glycine repeat protein G (VgrG) paralogs in Agrobacterium tumefaciens C58 specifically control the secretion and interbacterial competition activity of the type VI DNase toxins Tde1 and Tde2. Deletion and domain-swapping analysis identified that the C-terminal extension of VgrG1 specifically confers Tde1 secretion and Tde1-dependent interbacterial competition activity in planta, and the C-terminal variable region of VgrG2 governs this specificity for Tde2. Functional studies of VgrG1 and VgrG2 variants with stepwise deletion of the C terminus revealed that the C-terminal 31 aa (C31) of VgrG1 and 8 aa (C8) of VgrG2 are the molecular determinants specifically required for delivery of each cognate Tde toxin. Further in-depth studies on Tde toxin delivery mechanisms revealed that VgrG1 interacts with the adaptor/chaperone-effector complex (Tap-1-Tde1) in the absence of proline-alanine-alanine-arginine (PAAR) and the VgrG1-PAAR complex forms independent of Tap-1 and Tde1. Importantly, we identified the regions involved in these interactions. Although the entire C31 segment is required for binding with the Tap-1-Tde1 complex, only the first 15 aa of this region are necessary for PAAR binding. These results suggest that the VgrG1 C terminus interacts sequentially or simultaneously with the Tap-1-Tde1 complex and PAAR to govern Tde1 translocation across bacterial membranes and delivery into target cells for antibacterial activity. PMID:27313214

  12. Disruption of adaptor protein 2mu (AP-2mu) in cochlear hair cells impairs vesicle reloading of synaptic release sites and hearing

    NARCIS (Netherlands)

    Jung, S.; Maritzen, T.; Wichmann, C.; Jing, Z.; Neef, A.; Revelo, N.H.; Al-Moyed, H.; Meese, S.; Wojcik, S.M.; Panou, I.; Bulut, H.; Schu, P.; Ficner, R.; Reisinger, E.; Rizzoli, S.O.; Neef, J.; Strenzke, N.; Haucke, V.; Moser, T.

    2015-01-01

    Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2mu (AP-2mu) is required for release site replenishment and hearing. We show that

  13. Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

    Directory of Open Access Journals (Sweden)

    Marks David R

    2009-01-01

    Full Text Available Abstract Background Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF activation of neurotrophin receptor tyrosine kinase B (TrkB suppresses the Shaker voltage-gated potassium channel (Kv1.3 via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity. Results We report the co-localization of two adaptor proteins, neuronal Src homology and collagen (nShc and growth factor receptor-binding protein 10 (Grb10, with Kv1.3 channel as demonstrated through immunocytochemical approaches in the olfactory bulb (OB neural lamina. To further explore the specificity and functional ramification of adaptor/channel co-localization, we performed immunoprecipitation and Western analysis of channel, kinase, and adaptor transfected human embryonic kidney 293 cells (HEK 293. nShc formed a direct protein-protein interaction with Kv1.3 that was independent of BDNF-induced phosphorylation of Kv1.3, whereas Grb10 did not complex with Kv1.3 in HEK 293 cells. Both adaptors, however, co-immunoprecipitated with Kv1.3 in native OB. Grb10 was interestingly able to decrease the total expression of Kv1.3, particularly at the membrane surface, and subsequently eliminated the BDNF-induced phosphorylation of Kv1.3. To examine the possibility that the Src homology 2 (SH2 domains of Grb10 were directly binding to basally phosphorylated tyrosines in Kv1.3, we utilized point mutations to substitute multiple tyrosine residues with phenylalanine. Removal of the tyrosines 111–113 and 449 prevented Grb10 from decreasing Kv1.3 expression. In the absence of either adaptor protein

  14. Shc adaptor proteins are key transducers of mitogenic signaling mediated by the G protein-coupled thrombin receptor

    DEFF Research Database (Denmark)

    Chen, Y; Grall, D; Salcini, A E; Pelicci, P G; Pouysségur, J; Van Obberghen-Schilling, E

    1996-01-01

    The serine protease thrombin activates G protein signaling systems that lead to Ras activation and, in certain cells, proliferation. Whereas the steps leading to Ras activation by G protein-coupled receptors are not well defined, the mechanisms of Ras activation by receptor tyrosine kinases have...... kinase activation, gene induction and cell growth. From these data, we conclude that Shc represents a crucial point of convergence between signaling pathways activated by receptor tyrosine kinases and G protein-coupled receptors....... recently been elucidated biochemically and genetically. The present study was undertaken to determine whether common signaling components are used by these two distinct classes of receptors. Here we report that the adaptor protein Shc, is phosphorylated on tyrosine residues following stimulation of the...

  15. A Patient-Controlled Analgesia Adaptor to Mitigate Postsurgical Pain for Combat Casualties With Multiple Limb Amputation: A Case Series.

    Science.gov (United States)

    Pasquina, Paul F; Isaacson, Brad M; Johnson, Elizabeth; Rhoades, Daniel S; Lindholm, Mark P; Grindle, Garrett G; Cooper, Rory A

    2016-08-01

    The use of explosive armaments during Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn has resulted in a significant number of injured U.S. service members. These weapons often generate substantial extremity trauma requiring multiple surgical procedures to preserve life, limb, and restore function. For those individuals who require multiple surgeries, the use of patient-controlled analgesia (PCA) devices can be an effective way to achieve adequate pain management and promote successful rehabilitation and recovery during inpatient treatment. A subpopulation of patients are unable to independently control a PCA device because of severe multiple limb dysfunction and/or loss. In response to the needs of these patients, our team designed and developed a custom adaptor to assist service members who would otherwise not be able to use a PCA. Patient feedback of the device indicated a positive response, improved independence, and overall satisfaction during inpatient hospitalization. PMID:27483540

  16. Competitive and cooperative interactions mediate RNA transfer from herpesvirus saimiri ORF57 to the mammalian export adaptor ALYREF.

    Directory of Open Access Journals (Sweden)

    Richard B Tunnicliffe

    2014-02-01

    Full Text Available The essential herpesvirus adaptor protein HVS ORF57, which has homologs in all other herpesviruses, promotes viral mRNA export by utilizing the cellular mRNA export machinery. ORF57 protein specifically recognizes viral mRNA transcripts, and binds to proteins of the cellular transcription-export (TREX complex, in particular ALYREF. This interaction introduces viral mRNA to the NXF1 pathway, subsequently directing it to the nuclear pore for export to the cytoplasm. Here we have used a range of techniques to reveal the sites for direct contact between RNA and ORF57 in the absence and presence of ALYREF. A binding site within ORF57 was characterized which recognizes specific viral mRNA motifs. When ALYREF is present, part of this ORF57 RNA binding site, composed of an α-helix, binds preferentially to ALYREF. This competitively displaces viral RNA from the α-helix, but contact with RNA is still maintained by a flanking region. At the same time, the flexible N-terminal domain of ALYREF comes into contact with the viral RNA, which becomes engaged in an extensive network of synergistic interactions with both ALYREF and ORF57. Transfer of RNA to ALYREF in the ternary complex, and involvement of individual ORF57 residues in RNA recognition, were confirmed by UV cross-linking and mutagenesis. The atomic-resolution structure of the ORF57-ALYREF interface was determined, which noticeably differed from the homologous ICP27-ALYREF structure. Together, the data provides the first site-specific description of how viral mRNA is locked by a herpes viral adaptor protein in complex with cellular ALYREF, giving herpesvirus access to the cellular mRNA export machinery. The NMR strategy used may be more generally applicable to the study of fuzzy protein-protein-RNA complexes which involve flexible polypeptide regions.

  17. The transmembrane region is responsible for targeting of adaptor protein LAX into "heavy rafts''

    Czech Academy of Sciences Publication Activity Database

    Hrdinka, Matouš; Otáhal, Pavel; Hořejší, Václav

    2012-01-01

    Roč. 7, č. 5 (2012), e36330. E-ISSN 1932-6203 R&D Projects: GA ČR GEMEM/09/E011; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50520514 Keywords : LAX * transmembrane domain * DRM Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  18. CD2v interacts with Adaptor Protein AP-1 during African swine fever infection

    OpenAIRE

    Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez Bonet, Marta; Nogal París, María Luisa; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

    2015-01-01

    African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golg...

  19. Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation

    International Nuclear Information System (INIS)

    Highlights: ► Calcineurin/NFAT inhibitors FK506 and VIVIT treated human PBMC derived osteoclasts in vitro. ► Differential regulation of ITAM receptors and adaptor molecules by calcineurin/NFAT inhibitors. ► FK506 and VIVIT suppress ITAM factors during late phase osteoclast differentiation. -- Abstract: Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcRγ) and DNAX-activating protein 12 kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin (β3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10 days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that FK506 treatment

  20. Regulation of ITAM adaptor molecules and their receptors by inhibition of calcineurin-NFAT signalling during late stage osteoclast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Zawawi, M.S.F. [Universiti Sains Malaysia (USM) (Malaysia); Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); Dharmapatni, A.A.S.S.K.; Cantley, M.D. [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); McHugh, K.P. [University of Florida, College of Dentistry, Fl (United States); Haynes, D.R. [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia); Crotti, T.N., E-mail: tania.crotti@adelaide.edu.au [Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005 (Australia)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Calcineurin/NFAT inhibitors FK506 and VIVIT treated human PBMC derived osteoclasts in vitro. Black-Right-Pointing-Pointer Differential regulation of ITAM receptors and adaptor molecules by calcineurin/NFAT inhibitors. Black-Right-Pointing-Pointer FK506 and VIVIT suppress ITAM factors during late phase osteoclast differentiation. -- Abstract: Osteoclasts are specialised bone resorptive cells responsible for both physiological and pathological bone loss. Osteoclast differentiation and activity is dependent upon receptor activator NF-kappa-B ligand (RANKL) interacting with its receptor RANK to induce the transcription factor, nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1). The immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway has been identified as a co-stimulatory pathway in osteoclasts. Osteoclast-associated receptor (OSCAR) and triggering receptor expressed in myeloid cells (TREM2) are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FcR{gamma}) and DNAX-activating protein 12 kDa (DAP12) respectively to induce calcium signalling. Treatment with calcineurin-NFAT inhibitors, Tacrolimus (FK506) and the 11R-VIVIT (VIVIT) peptide, reduces NFATc1 expression consistent with a reduction in osteoclast differentiation and activity. This study aimed to investigate the effects of inhibiting calcineurin-NFAT signalling on the expression of ITAM factors and late stage osteoclast genes including cathepsin K (CathK), Beta 3 integrin ({beta}3) and Annexin VIII (AnnVIII). Human peripheral blood mononuclear cells (PBMCs) were differentiated with RANKL and macrophage-colony stimulating factor (M-CSF) over 10 days in the presence or absence of FK506 or VIVIT. Osteoclast formation (as assessed by tartrate resistant acid phosphatase (TRAP)) and activity (assessed by dentine pit resorption) were significantly reduced with treatment. Quantitative real

  1. Molecular Structure, Function, and Dynamics of Clathrin-Mediated Membrane Traffic

    OpenAIRE

    Kirchhausen, Tom; Owen, David; Harrison, Stephen C.

    2014-01-01

    Clathrin is a molecular scaffold for vesicular uptake of cargo at the plasma membrane, where its assembly into cage-like lattices underlies the clathrin-coated pits of classical endocytosis. This review describes the structures of clathrin, major cargo adaptors, and other proteins that participate in forming a clathrin-coated pit, loading its contents, pinching off the membrane as a lattice-enclosed vesicle, and recycling the components. It integrates as much of the structural information as ...

  2. Protein Interaction Profiling of the p97 Adaptor UBXD1 Points to a Role for the Complex in Modulating ERGIC-53 Trafficking*

    OpenAIRE

    Haines, Dale S.; Lee, J. Eugene; Beauparlant, Stephen L.; Kyle, Dane B.; den Besten, Willem; Sweredoski, Michael J.; Graham, Robert L. J.; Hess, Sonja; Deshaies, Raymond J

    2012-01-01

    UBXD1 is a member of the poorly understood subfamily of p97 adaptors that do not harbor a ubiquitin association domain or bind ubiquitin-modified proteins. Of clinical importance, p97 mutants found in familial neurodegenerative conditions Inclusion Body Myopathy Paget's disease of the bone and/or Frontotemporal Dementia and Amyotrophic Lateral Sclerosis are defective at interacting with UBXD1, indicating that functions regulated by a p97-UBXD1 complex are altered in these diseases. We have pe...

  3. Syk Kinase-Coupled C-type Lectin Receptors Engage Protein Kinase C-δ to Elicit Card9 Adaptor-Mediated Innate Immunity

    OpenAIRE

    Strasser, Dominikus; Neumann, Konstantin; Bergmann, Hanna; Marakalala, Mohlopheni J.; Guler, Reto; Rojowska, Anna; Hopfner, Karl-Peter; Brombacher, Frank; Urlaub, Henning; Baier, Gottfried; Brown, Gordon D.; Leitges, Michael; Ruland, Jürgen

    2012-01-01

    Summary C-type lectin receptors (CLRs) that couple with the kinase Syk are major pattern recognition receptors for the activation of innate immunity and host defense. CLRs recognize fungi and other forms of microbial or sterile danger, and they induce inflammatory responses through the adaptor protein Card9. The mechanisms relaying CLR proximal signals to the core Card9 module are unknown. Here we demonstrated that protein kinase C-δ (PKCδ) was activated upon Dectin-1-Syk signaling, mediated ...

  4. Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors.

    Science.gov (United States)

    Bougdour, Alexandre; Cunning, Christofer; Baptiste, Patrick Jean; Elliott, Thomas; Gottesman, Susan

    2008-04-01

    SigmaS, the stationary phase sigma factor of Escherichia coli and Salmonella, is regulated at multiple levels. The sigmaS protein is unstable during exponential growth and is stabilized during stationary phase and after various stress treatments. Degradation requires both the ClpXP protease and the adaptor RssB. The small antiadaptor protein IraP is made in response to phosphate starvation and interacts with RssB, causing sigmaS stabilization under this stress condition. IraP is essential for sigmaS stabilization in some but not all starvation conditions, suggesting the existence of other anti-adaptor proteins. We report here the identification of new regulators of sigmaS stability, important under other stress conditions. IraM (inhibitor of RssB activity during Magnesium starvation) and IraD (inhibitor of RssB activity after DNA damage) inhibit sigmaS proteolysis both in vivo and in vitro. Our results reveal that multiple anti-adaptor proteins allow the regulation of sigmaS stability through the regulation of RssB activity under a variety of stress conditions. PMID:18383615

  5. Adaptor protein complexes AP-1 and AP-3 are required by the HHV-7 Immunoevasin U21 for rerouting of class I MHC molecules to the lysosomal compartment.

    Directory of Open Access Journals (Sweden)

    Lisa A Kimpler

    Full Text Available The human herpesvirus-7 (HHV-7 U21 gene product binds to class I major histocompatibility complex (MHC molecules and reroutes them to a lysosomal compartment. Trafficking of integral membrane proteins to lysosomes is mediated through cytoplasmic sorting signals that recruit heterotetrameric clathrin adaptor protein (AP complexes, which in turn mediate protein sorting in post-Golgi vesicular transport. Since U21 can mediate rerouting of class I molecules to lysosomes even when lacking its cytoplasmic tail, we hypothesize the existence of a cellular protein that contains the lysosomal sorting information required to escort class I molecules to the lysosomal compartment. If such a protein exists, we expect that it might recruit clathrin adaptor protein complexes as a means of lysosomal sorting. Here we describe experiments demonstrating that the μ adaptins from AP-1 and AP-3 are involved in U21-mediated trafficking of class I molecules to lysosomes. These experiments support the idea that a cellular protein(s is necessary for U21-mediated lysosomal sorting of class I molecules. We also examine the impact of transient versus chronic knockdown of these adaptor protein complexes, and show that the few remaining μ subunits in the cells are eventually able to reroute class I molecules to lysosomes.

  6. Functional interaction of megalin with the megalinbinding protein (MegBP), a novel tetratrico peptide repeat-containing adaptor molecule.

    Science.gov (United States)

    Petersen, Helle Heibroch; Hilpert, Jan; Militz, Daniel; Zandler, Valerie; Jacobsen, Christian; Roebroek, Anton J M; Willnow, Thomas E

    2003-02-01

    Megalin is a member of the LDL receptor gene family that plays an important role in forebrain development and in cellular vitamin D metabolism through endocytic uptake of vitamin D metabolites. Similar to other receptors in this gene family, megalin is believed to functionally interact with intracellular proteins through adaptors that bind to the receptor tail and regulate its endocytic and signal transducing activities. Using yeast two-hybrid screens, we identified a novel scaffold protein with tetratrico peptide repeats, the megalin-binding protein (MegBP) that associates with the receptor. The binding site of MegBP was mapped to an N-terminal region on the receptor tail harboring a proline-rich peptide element. MegBP binding did not block the endocytic activity of the receptor; however, overexpression resulted in cellular lethality. In further screens, we identified proteins that bound to MegBP and thus might be recruited to the megalin tail. MegBP-interacting partners included several transcriptional regulators such as the SKI-interacting protein (SKIP), a co-activator of the vitamin D receptor. These finding suggest a model whereby megalin directly participates in transcriptional regulation through controlled sequestration or release of transcription factors via MegBP. PMID:12508107

  7. Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of muscle, nerve and other tissues

    Institute of Scientific and Technical Information of China (English)

    va Korpos; Ferenc Dek; Ibolya Kiss

    2015-01-01

    The extracellular matrix (ECM) performs essential functions in the differentiation, maintenance and remodeling of tissues during development and regeneration, and it undergoes dynamic chang-es during remodeling concomitant to alterations in the cell-ECM interactions. Here we discuss recent data addressing the critical role of the widely expressed ECM protein, matrilin-2 (Matn2) in the timely onset of differentiation and regeneration processes in myogenic, neural and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it interacts with other ECM proteins and integrins. Matn2 promotes neurite outgrowth, Schwann cell migration, neuromuscular junc-tion formation, skeletal muscle and liver regeneration and skin wound healing. Matn2 deposition by myoblasts is crucial for the timely induction of the global switch toward terminal myogenic differentiation during muscle regeneration by affecting transforming growth factor beta/bone morphogenetic protein 7/Smad and other signal transduction pathways. Depending on the type of tissue and the pathomechanism, Matn2 can also promote or suppress tumor growth.

  8. Early Loss of Telomerase Action in Yeast Creates a Dependence on the DNA Damage Response Adaptor Proteins.

    Science.gov (United States)

    Jay, Kyle A; Smith, Dana L; Blackburn, Elizabeth H

    2016-07-15

    Telomeres cap the ends of chromosomes, protecting them from degradation and inappropriate DNA repair processes that can lead to genomic instability. A short telomere elicits increased telomerase action on itself that replenishes telomere length, thereby stabilizing the telomere. In the prolonged absence of telomerase activity in dividing cells, telomeres eventually become critically short, inducing a permanent cell cycle arrest (senescence). We recently showed that even early after telomerase inactivation (ETI), yeast cells have accelerated mother cell aging and mildly perturbed cell cycles. Here, we show that the complete disruption of DNA damage response (DDR) adaptor proteins in ETI cells causes severe growth defects. This synthetic-lethality phenotype was as pronounced as that caused by extensive DNA damage in wild-type cells but showed genetic dependencies distinct from such damage and was completely alleviated by SML1 deletion, which increases deoxynucleoside triphosphate (dNTP) pools. Our results indicated that these deleterious effects in ETI cells cannot be accounted for solely by the slow erosion of telomeres due to incomplete replication that leads to senescence. We propose that normally occurring telomeric DNA replication stress is resolved by telomerase activity and the DDR in two parallel pathways and that deletion of Sml1 prevents this stress. PMID:27161319

  9. The Adaptor Protein-1 μ1B Subunit Expands the Repertoire of Basolateral Sorting Signal Recognition in Epithelial Cells

    Science.gov (United States)

    Guo, Xiaoli; Mattera, Rafael; Ren, Xuefeng; Chen, Yu; Retamal, Claudio; González, Alfonso; Bonifacino, Juan S.

    2014-01-01

    SUMMARY An outstanding question in protein sorting is why polarized epithelial cells express two isoforms of the μ1 subunit of the AP-1 clathrin adaptor complex: the ubiquitous μ1A and the epithelial-specific μ1B. Previous studies led to the notion that μ1A and μ1B mediate basolateral sorting predominantly from the trans-Golgi network (TGN) and recycling endosomes, respectively. Using improved analytical tools, however, we find that μ1A and μ1B largely colocalize with each other. They also colocalize to similar extents with TGN and recycling endosome markers, as well as with basolateral cargoes transiting biosynthetic and endocytic-recycling routes. Instead, the two isoforms differ in their signal-recognition specificity. In particular, μ1B preferentially binds a subset of signals from cargoes that are sorted basolaterally in a μ1B-dependent manner. We conclude that expression of distinct μ1 isoforms in epithelial cells expands the repertoire of signals recognized by AP-1 for sorting of a broader range of cargoes to the basolateral surface. PMID:24229647

  10. The cytoskeleton adaptor protein ankyrin-1 is upregulated by p53 following DNA damage and alters cell migration.

    Science.gov (United States)

    Hall, A E; Lu, W-T; Godfrey, J D; Antonov, A V; Paicu, C; Moxon, S; Dalmay, T; Wilczynska, A; Muller, P A J; Bushell, M

    2016-01-01

    The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway. PMID:27054339

  11. A Cyclic di-GMP-binding Adaptor Protein Interacts with Histidine Kinase to Regulate Two-component Signaling.

    Science.gov (United States)

    Xu, Linghui; Venkataramani, Prabhadevi; Ding, Yichen; Liu, Yang; Deng, Yinyue; Yong, Grace Lisi; Xin, Lingyi; Ye, Ruijuan; Zhang, Lianhui; Yang, Liang; Liang, Zhao-Xun

    2016-07-29

    The bacterial messenger cyclic di-GMP (c-di-GMP) binds to a diverse range of effectors to exert its biological effect. Despite the fact that free-standing PilZ proteins are by far the most prevalent c-di-GMP effectors known to date, their physiological function and mechanism of action remain largely unknown. Here we report that the free-standing PilZ protein PA2799 from the opportunistic pathogen Pseudomonas aeruginosa interacts directly with the hybrid histidine kinase SagS. We show that PA2799 (named as HapZ: histidine kinase associated PilZ) binds directly to the phosphoreceiver (REC) domain of SagS, and that the SagS-HapZ interaction is further enhanced at elevated c-di-GMP concentration. We demonstrate that binding of HapZ to SagS inhibits the phosphotransfer between SagS and the downstream protein HptB in a c-di-GMP-dependent manner. In accordance with the role of SagS as a motile-sessile switch and biofilm growth factor, we show that HapZ impacts surface attachment and biofilm formation most likely by regulating the expression of a large number of genes. The observations suggest a previously unknown mechanism whereby c-di-GMP mediates two-component signaling through a PilZ adaptor protein. PMID:27231351

  12. CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

    Directory of Open Access Journals (Sweden)

    Daniel Pérez-Núñez

    Full Text Available African swine fever virus (ASFV CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

  13. Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy.

    Science.gov (United States)

    Neveling, Kornelia; Martinez-Carrera, Lilian A; Hölker, Irmgard; Heister, Angelien; Verrips, Aad; Hosseini-Barkooie, Seyyed Mohsen; Gilissen, Christian; Vermeer, Sascha; Pennings, Maartje; Meijer, Rowdy; te Riele, Margot; Frijns, Catharina J M; Suchowersky, Oksana; MacLaren, Linda; Rudnik-Schöneborn, Sabine; Sinke, Richard J; Zerres, Klaus; Lowry, R Brian; Lemmink, Henny H; Garbes, Lutz; Veltman, Joris A; Schelhaas, Helenius J; Scheffer, Hans; Wirth, Brunhilde

    2013-06-01

    Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA. Affected individuals displayed congenital slowly progressive muscle weakness mainly of the lower limbs and congenital contractures. In a large Dutch family, linkage analysis identified a 9q22.3 locus in which exome sequencing uncovered c.320C>T (p.Ser107Leu) in BICD2. Sequencing of 23 additional families affected by dominant SMA led to the identification of pathogenic variants in one family from Canada (c.2108C>T [p.Thr703Met]) and one from the Netherlands (c.563A>C [p.Asn188Thr]). BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport. Transient transfection of HeLa cells with all three mutant BICD2 cDNAs caused massive Golgi fragmentation. This observation was even more prominent in primary fibroblasts from an individual harboring c.2108C>T (p.Thr703Met) (affecting the C-terminal coiled-coil domain) and slightly less evident in individuals with c.563A>C (p.Asn188Thr) (affecting the N-terminal coiled-coil domain). Furthermore, BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi. Previous studies have shown that Drosophila mutant BicD causes reduced larvae locomotion by impaired clathrin-mediated synaptic endocytosis in neuromuscular junctions. These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA. PMID:23664116

  14. A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor.

    Directory of Open Access Journals (Sweden)

    Crystal M Botham

    2008-05-01

    Full Text Available Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS. Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW. These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function.

  15. The adaptor molecule Nck localizes the WAVE complex to promote actin polymerization during CEACAM3-mediated phagocytosis of bacteria.

    Directory of Open Access Journals (Sweden)

    Stefan Pils

    Full Text Available BACKGROUND: CEACAM3 is a granulocyte receptor mediating the opsonin-independent recognition and phagocytosis of human-restricted CEACAM-binding bacteria. CEACAM3 function depends on an intracellular immunoreceptor tyrosine-based activation motif (ITAM-like sequence that is tyrosine phosphorylated by Src family kinases upon receptor engagement. The phosphorylated ITAM-like sequence triggers GTP-loading of Rac by directly associating with the guanine nucleotide exchange factor (GEF Vav. Rac stimulation in turn is critical for actin cytoskeleton rearrangements that generate lamellipodial protrusions and lead to bacterial uptake. PRINCIPAL FINDINGS: In our present study we provide biochemical and microscopic evidence that the adaptor proteins Nck1 and Nck2, but not CrkL, Grb2 or SLP-76, bind to tyrosine phosphorylated CEACAM3. The association is phosphorylation-dependent and requires the Nck SH2 domain. Overexpression of the isolated Nck1 SH2 domain, RNAi-mediated knock-down of Nck1, or genetic deletion of Nck1 and Nck2 interfere with CEACAM3-mediated bacterial internalization and with the formation of lamellipodial protrusions. Nck is constitutively associated with WAVE2 and directs the actin nucleation promoting WAVE complex to tyrosine phosphorylated CEACAM3. In turn, dominant-negative WAVE2 as well as shRNA-mediated knock-down of WAVE2 or the WAVE-complex component Nap1 reduce internalization of bacteria. CONCLUSIONS: Our results provide novel mechanistic insight into CEACAM3-initiated phagocytosis. We suggest that the CEACAM3 ITAM-like sequence is optimized to co-ordinate a minimal set of cellular factors needed to efficiently trigger actin-based lamellipodial protrusions and rapid pathogen engulfment.

  16. Dephosphorylation of the adaptor LAT and phospholipase C-γ by SHP-1 inhibits natural killer cell cytotoxicity.

    Science.gov (United States)

    Matalon, Omri; Fried, Sophia; Ben-Shmuel, Aviad; Pauker, Maor H; Joseph, Noah; Keizer, Danielle; Piterburg, Marina; Barda-Saad, Mira

    2016-01-01

    Natural killer (NK) cells discriminate between healthy cells and virally infected or transformed self-cells by tuning activating and inhibitory signals received through cell surface receptors. Inhibitory receptors inhibit NK cell function by recruiting and activating the tyrosine phosphatase Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-1 (SHP-1) to the plasma membrane. However, to date, the guanine nucleotide exchange factor VAV1 is the only direct SHP-1 substrate identified in NK cells. We reveal that the adaptor protein linker for activation of T cells (LAT) as well as phospholipase C-γ1 (PLC-γ1) and PLC-γ2 are SHP-1 substrates. Dephosphorylation of Tyr(132) in LAT by SHP-1 in NK cells abrogated the recruitment of PLC-γ1 and PLC-γ2 to the immunological synapse between the NK cell and a cancer cell target, which reduced NK cell degranulation and target cell killing. Furthermore, the ubiquitylation of LAT by the E3 ubiquitin ligases c-Cbl and Cbl-b, which was induced by LAT phosphorylation, led to the degradation of LAT in response to the engagement of inhibitory receptors on NK cells, which abrogated NK cell cytotoxicity. Knockdown of the Cbl proteins blocked LAT ubiquitylation, which promoted NK cell function. Expression of a ubiquitylation-resistant mutant LAT blocked inhibitory receptor signaling, enabling cells to become activated. Together, these data identify previously uncharacterized SHP-1 substrates and inhibitory mechanisms that determine the response of NK cells. PMID:27221712

  17. The adaptor CARD9 is required for adaptive but not innate immunity to oral mucosal Candida albicans infections.

    Science.gov (United States)

    Bishu, Shrinivas; Hernández-Santos, Nydiaris; Simpson-Abelson, Michelle R; Huppler, Anna R; Conti, Heather R; Ghilardi, Nico; Mamo, Anna J; Gaffen, Sarah L

    2014-03-01

    Oropharyngeal candidiasis (OPC [thrush]) is an opportunistic infection caused by the commensal fungus Candida albicans. OPC is common in individuals with HIV/AIDS, infants, patients on chemotherapy, and individuals with congenital immune defects. Immunity to OPC is strongly dependent on the interleukin-23 (IL-23)/IL-17R axis, as mice and humans with defects in IL-17R signaling (IL17F, ACT1, IL-17RA) or in genes that direct Th17 differentiation (STAT3, STAT1, CARD9) are prone to mucocutaneous candidiasis. Conventional Th17 cells are induced in response to C. albicans infection via signals from C-type lectin receptors, which signal through the adaptor CARD9, leading to production of Th17-inducing cytokines such as IL-6, IL-1β, and IL-23. Recent data indicate that IL-17 can also be made by numerous innate cell subsets. These innate "type 17" cells resemble conventional Th17 cells, but they can be activated without need for prior antigen exposure. Because C. albicans is not a commensal organism in rodents and mice are thus naive to this fungus, we had the opportunity to assess the role of CARD9 in innate versus adaptive responses using an OPC infection model. As expected, CARD9(-/-) mice failed to mount an adaptive Th17 response following oral Candida infection. Surprisingly, however, CARD9(-/-) mice had preserved innate IL-17-dependent responses to Candida and were almost fully resistant to OPC. Thus, CARD9 is important primarily for adaptive immunity to C. albicans, whereas alternate recognition systems appear to be needed for effective innate responses. PMID:24379290

  18. Development of novel on-chip, customer-design spiral biasing adaptor on for Si drift detectors and detector arrays for X-ray and nuclear physics experiments

    International Nuclear Information System (INIS)

    A novel on-chip, customer-design spiral biasing adaptor (SBA) has been developed. A single SBA is used for biasing a Si drift detector (SDD) and SDD array. The use of an SBA reduces the biasing current. This paper shows the calculation of the geometry of an SBA and an SDD to get the best drift field in the SDD and SDD array. Prototype SBAs have been fabricated to verify the concept. Electrical measurements on these SBAs are in agreement with the expectations. The new SDD array with an SBA can be used for X-ray detection and in nuclear physics experiments

  19. Enigma interacts with adaptor protein with PH and SH2 domains to control insulin-induced actin cytoskeleton remodeling and glucose transporter 4 translocation

    DEFF Research Database (Denmark)

    Barres, Romain; Grémeaux, Thierry; Gual, Philippe;

    2006-01-01

    and Glut 4 translocation without alterations in proximal insulin signaling. This inhibitory effect was prevented with the deletion of the LIM domains of Enigma. Using time-lapse fluorescent microscopy of green fluorescent protein-actin, we demonstrated that the overexpression of Enigma altered insulin......APS (adaptor protein with PH and SH2 domains) initiates a phosphatidylinositol 3-kinase-independent pathway involved in insulin-stimulated glucose transport. We recently identified Enigma, a PDZ and LIM domain-containing protein, as a partner of APS and showed that APS-Enigma complex plays...

  20. Mutations in the Gene Encoding the Sigma 2 Subunit of the Adaptor Protein 1 Complex, AP1S2, Cause X-Linked Mental Retardation

    OpenAIRE

    Tarpey, Patrick S. ; Stevens, Claire ; Teague, Jon ; Edkins, Sarah ; O’Meara, Sarah ; Avis, Tim ; Barthorpe, Syd ; Buck, Gemma ; Butler, Adam ; Cole, Jennifer ; Dicks, Ed ; Gray, Kristian ; Halliday, Kelly ; Harrison, Rachel ; Hills, Katy 

    2006-01-01

    In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found ...

  1. Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding

    Directory of Open Access Journals (Sweden)

    Lovestone Simon

    2007-12-01

    Full Text Available Abstract Background Shedding of the Alzheimer amyloid precursor protein (APP ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as α-secretase(s. However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES responsible for regulated shedding has been challenging. Here, we examined the effects on APP ectodomain shedding of four phorbol-sensitive proteins involved in regulation of vesicular membrane trafficking of APP: Munc13-1, Munc18, NSF, and Eve-1. Results Overexpression of either phorbol-sensitive wildtype Munc13-1 or phorbol-insensitive Munc13-1 H567K resulted in increased basal APP ectodomain shedding. However, in contrast to the report of Roßner et al (2004, phorbol ester-dependent APP ectodomain shedding from cells overexpressing APP and Munc13-1 wildtype was indistinguishable from that observed following application of phorbol to cells overexpressing APP and Munc13-1 H567K mutant. This pattern of similar effects on basal and stimulated APP shedding was also observed for Munc18 and NSF. Eve-1, an ADAM adaptor protein reported to be essential for PKC-regulated shedding of pro-EGF, was found to play no obvious role in regulated shedding of sAPPα. Conclusion Our results indicate that, in the HEK293 system, Munc13-1, Munc18, NSF, and EVE-1 fail to meet essential criteria for identity as PMES for APP.

  2. TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite.

    Science.gov (United States)

    Sukhumavasi, Woraporn; Egan, Charlotte E; Warren, Amy L; Taylor, Gregory A; Fox, Barbara A; Bzik, David J; Denkers, Eric Y

    2008-09-01

    TLR adaptor MyD88 activation is important in host resistance to Toxoplasma gondii during i.p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. In this study, we show that MyD88(-/-) mice fail to control the parasite and succumb within 2 wk of oral infection. Early during infection, T cell IFN-gamma production, recruitment of neutrophils and induction of p47 GTPase IGTP (Irgm3) in the intestinal mucosa were dependent upon functional MyD88. Unexpectedly, these responses were MyD88-independent later during acute infection. In particular, CD4(+) T cell IFN-gamma reached normal levels independently of MyD88, despite continued absence of IL-12 in these animals. The i.p. vaccination of MyD88(-/-) mice with an avirulent T. gondii uracil auxotroph elicited robust IFN-gamma responses and protective immunity to challenge with a high virulence T. gondii strain. Our results demonstrate that MyD88 is required to control Toxoplasma infection, but that the parasite can trigger adaptive immunity without the need for this TLR adaptor molecule. PMID:18714019

  3. Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role--relevance for Alzheimer pathology.

    Science.gov (United States)

    Schettini, Gennaro; Govoni, Stefano; Racchi, Marco; Rodriguez, Guido

    2010-12-01

    In recent decades, the study of the amyloid precursor protein (APP) and of its proteolytic products carboxy terminal fragment (CTF), APP intracellular C-terminal domain (AICD) and amyloid beta has been mostly focussed on the role of APP as a producer of the toxic amyloid beta peptide. Here, we reconsider the role of APP suggesting, in a provocative way, the protein as a central player in a putative signalling pathway. We highlight the presence in the cytosolic tail of APP of the YENPTY motif which is typical of tyrosine kinase receptors, the phosphorylation of the tyrosine, serine and threonine residues, the kinases involved and the interaction with intracellular adaptor proteins. In particular, we examine the interaction with Shc and Grb2 regulators, which through the activation of Ras proteins elicit downstream signalling events such as the MAPK pathway. The review also addresses the interaction of APP, CTFs and AICD with other adaptor proteins and in particular with Fe65 for nuclear transcriptional activity and the importance of phosphorylation for sorting the secretases involved in the amyloidogenic or non-amyloidogenic pathways. We provide a novel perspective on Alzheimer's disease pathogenesis, focussing on the perturbation of the physiological activities of APP-CTFs and AICD as an alternative perspective from that which normally focuses on the accumulation of neurotoxic proteolytic fragments. PMID:21039524

  4. Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation.

    Science.gov (United States)

    Tarpey, Patrick S; Stevens, Claire; Teague, Jon; Edkins, Sarah; O'Meara, Sarah; Avis, Tim; Barthorpe, Syd; Buck, Gemma; Butler, Adam; Cole, Jennifer; Dicks, Ed; Gray, Kristian; Halliday, Kelly; Harrison, Rachel; Hills, Katy; Hinton, Jonathon; Jones, David; Menzies, Andrew; Mironenko, Tatiana; Perry, Janet; Raine, Keiran; Richardson, David; Shepherd, Rebecca; Small, Alexandra; Tofts, Calli; Varian, Jennifer; West, Sofie; Widaa, Sara; Yates, Andy; Catford, Rachael; Butler, Julia; Mallya, Uma; Moon, Jenny; Luo, Ying; Dorkins, Huw; Thompson, Deborah; Easton, Douglas F; Wooster, Richard; Bobrow, Martin; Carpenter, Nancy; Simensen, Richard J; Schwartz, Charles E; Stevenson, Roger E; Turner, Gillian; Partington, Michael; Gecz, Jozef; Stratton, Michael R; Futreal, P Andrew; Raymond, F Lucy

    2006-12-01

    In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles. PMID:17186471

  5. Molecular characterization of transgenic shallots (Allium cepa L.) by adaptor ligation PCR (AL-PCR) and sequencing of genomic DNA flanking T-DNA borders

    NARCIS (Netherlands)

    Zheng, S.J.; Henken, G.; Sofiari, E.; Jacobsen, E.; Krens, F.A.

    2001-01-01

    Genomic DNA blot hybridization is traditionally used to demonstrate that, via genetic transformation, foreign genes are integrated into host genomes. However, in large genome species, such as Allium cepa L., the use of genomic DNA blot hybridization is pushed towards its limits, because a considerab

  6. Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2010-01-01

    X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. AbetaPP-Tg2576 mice produce high levels of brain Abeta and develop age-related defects in memory function that correlate with increasing Abeta load. Overexpression of X11alpha alone had no detectable adverse effect upon behavior. However, X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha\\/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer\\'s disease.

  7. A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining: cell body to cell size ratio

    Directory of Open Access Journals (Sweden)

    Iris Bertha Hovens

    2014-09-01

    Full Text Available Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1 stained brain sections. Methods: The novel method was compared to currently used analysis methods, visual characterization of activation stage and optical density measurement, in brain sections of young and aged rats that had undergone surgery or remained naοve. Results: The cell body to cell size ratio of microglia was strongly correlated to the visual characterization activation stage. In addition, we observed specific surgery and age-related changes in cell body size, size of the dendritic processes and cell body to cell size ratio. Conclusion: The novel analysis method provides a sensitive marker for microglial activation in the rat brain, which is quick and easy to perform and provides additional information about microglial morphology.

  8. Adaptor bypass mutations of Bacillus subtilis spx suggest a mechanism for YjbH-enhanced proteolysis of the regulator Spx by ClpXP

    Science.gov (United States)

    Chan, Chio Mui; Hahn, Erik; Zuber, Peter

    2014-01-01

    Summary The global regulator, Spx, is under proteolytic control exerted by the adaptor YjbH and ATP-dependent protease ClpXP in Bacillus subtilis. While YjbH is observed to bind the Spx C-terminus, YjbH shows little affinity for ClpXP, indicating adaptor activity that does not operate by tethering. Chimeric proteins derived from B. subtilis AbrB and the Spx C-terminus showed that a 28 residue C-terminal section of Spx (AbrB28), but not the last 12 or 16 residues (AbrB12, AbrB16), was required for YjbH interaction and for ClpXP proteolysis, although the rate of AbrB28 proteolysis was not affected by YjbH addition. The result suggested that the YjbH-targeted 28 residue segment of the Spx C-terminus bears a ClpXP-recognition element(s) that is hidden in the intact Spx protein. Residue substitutions in the conserved helix α6 of the C-terminal region generated Spx substrates that were degraded by ClpXP at accelerated rates compared to wild type Spx, and showed reduced dependency on the YjbH activity. The residue substitutions also weakened the interaction between Spx and YjbH. The results suggest a model in which YjbH, through interaction with residues of α6 helix, exposes the C-terminus of Spx for recognition and proteolysis by ClpXP. PMID:24942655

  9. The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL

    Czech Academy of Sciences Publication Activity Database

    Svojgr, K.; Kalina, T.; Kanderová, V.; Skopcová, Tereza; Brdička, Tomáš; Zuna, J.

    2012-01-01

    Roč. 40, č. 5 (2012), s. 379-385. ISSN 0301-472X R&D Projects: GA MŠk 2B06064 Institutional support: RVO:68378050 Keywords : acute lymphoblastic leukemia * TCR signaling * NTAL * ERK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.907, year: 2012

  10. Multiple Regulatory Roles of the Mouse Transmembrane Adaptor Protein NTAL in Gene Transcription and Mast Cell Physiology

    Czech Academy of Sciences Publication Activity Database

    Polakovičová, Iva; Dráberová, Lubica; Šimíček, Michal; Dráber, Petr

    2014-01-01

    Roč. 9, č. 8 (2014), e105539. E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GBP302/12/G101; GA MŠk LD12073 Institutional support: RVO:68378050 Keywords : mast cells * NTAL * microarray gene-expression profiling * spreading * chemotaxis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2014

  11. Assembling Fe/S-clusters and modifying tRNAs: ancient co-factors meet ancient adaptors

    Czech Academy of Sciences Publication Activity Database

    Alfonzo, J. D.; Lukeš, Julius

    2011-01-01

    Roč. 27, č. 6 (2011), 234-237. ISSN 1471-4922 R&D Projects: GA MŠk LC07032; GA MŠk 2B06129; GA ČR GA204/09/1667 Institutional research plan: CEZ:AV0Z60220518 Keywords : IRON-SULFUR CLUSTERS * TRYPANOSOMA-BRUCEI * MITOCHONDRIAL * PROTEIN * FRATAXIN * BIOSYNTHESIS * SYNTHETASES * BIOGENESIS * THIOLATION * ANTICODON Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.144, year: 2011

  12. Molecular physics

    CERN Document Server

    Williams, Dudley

    2013-01-01

    Methods of Experimental Physics, Volume 3: Molecular Physics focuses on molecular theory, spectroscopy, resonance, molecular beams, and electric and thermodynamic properties. The manuscript first considers the origins of molecular theory, molecular physics, and molecular spectroscopy, as well as microwave spectroscopy, electronic spectra, and Raman effect. The text then ponders on diffraction methods of molecular structure determination and resonance studies. Topics include techniques of electron, neutron, and x-ray diffraction and nuclear magnetic, nuclear quadropole, and electron spin reson

  13. Transmembrane Adaptor Protein PAG/CBP Is Involved in both Positive and Negative Regulation of Mast Cell Signaling

    Czech Academy of Sciences Publication Activity Database

    Dráberová, Lubica; Bugajev, Viktor; Potůčková, Lucie; Hálová, Ivana; Bambousková, Monika; Polakovičová, Iva; Xavier, R.J.; Seed, B.; Dráber, Petr

    2014-01-01

    Roč. 34, č. 23 (2014), s. 4285-4300. ISSN 0270-7306 R&D Projects: GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GD204/09/H084; GA MŠk LD12073; GA ČR(CZ) GA14-00703S; GA ČR(CZ) GA14-09807S Institutional support: RVO:68378050 Keywords : plasma membrane * cel signaling * IgE receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.777, year: 2014

  14. Human kidney anion exchanger 1 interacts with adaptor-related protein complex 1 {mu}1A (AP-1 mu1A)

    Energy Technology Data Exchange (ETDEWEB)

    Sawasdee, Nunghathai; Junking, Mutita [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Ngaojanlar, Piengpaga [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Immunology and Graduate Program in Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sukomon, Nattakan; Ungsupravate, Duangporn [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Limjindaporn, Thawornchai [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Akkarapatumwong, Varaporn [Institute of Molecular Biosciences, Mahidol University at Salaya Campus, Nakorn Pathom 73170 (Thailand); Noisakran, Sansanee [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai, E-mail: grpye@mahidol.ac.th [Division of Medical Molecular Biology and BIOTEC-Medical Biotechnology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand)

    2010-10-08

    Research highlights: {yields} Trafficking defect of kAE1 is a cause of dRTA but trafficking pathway of kAE1 has not been clearly described. {yields} Adaptor-related protein complex 1 {mu}1A (AP-1 mu1A) was firstly reported to interact with kAE1. {yields} The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. {yields} AP-1 mu1A knockdown showed a marked reduction of kAE1 on the cell membrane and its accumulation in endoplasmic reticulum. {yields} AP-1 mu1A has a critical role in kAE1 trafficking to the plasma membrane. -- Abstract: Kidney anion exchanger 1 (kAE1) mediates chloride (Cl{sup -}) and bicarbonate (HCO{sub 3}{sup -}) exchange at the basolateral membrane of kidney {alpha}-intercalated cells. Impaired trafficking of kAE1 leads to defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange at the basolateral membrane and failure of proton (H{sup +}) secretion at the apical membrane, causing a kidney disease - distal renal tubular acidosis (dRTA). To gain a better insight into kAE1 trafficking, we searched for proteins physically interacting with the C-terminal region of kAE1 (Ct-kAE1), which contains motifs crucial for intracellular trafficking, by a yeast two-hybrid (Y2H) system. An adaptor-related protein complex 1 {mu}1A (AP-1 mu1A) subunit was found to interact with Ct-kAE1. The interaction between either Ct-kAE1 or full-length kAE1 and AP-1 mu1A were confirmed in human embryonic kidney (HEK) 293T by co-immunoprecipitation, affinity co-purification, co-localization, yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA) and GST pull-down assay. The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. Interestingly, suppression of endogenous AP-1 mu1A in HEK 293T by small interfering RNA (siRNA) decreased membrane localization of kAE1 and increased its intracellular accumulation, suggesting for the first time that AP-1 mu1A is involved in the kAE1

  15. Human kidney anion exchanger 1 interacts with adaptor-related protein complex 1 μ1A (AP-1 mu1A)

    International Nuclear Information System (INIS)

    Research highlights: → Trafficking defect of kAE1 is a cause of dRTA but trafficking pathway of kAE1 has not been clearly described. → Adaptor-related protein complex 1 μ1A (AP-1 mu1A) was firstly reported to interact with kAE1. → The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. → AP-1 mu1A knockdown showed a marked reduction of kAE1 on the cell membrane and its accumulation in endoplasmic reticulum. → AP-1 mu1A has a critical role in kAE1 trafficking to the plasma membrane. -- Abstract: Kidney anion exchanger 1 (kAE1) mediates chloride (Cl-) and bicarbonate (HCO3-) exchange at the basolateral membrane of kidney α-intercalated cells. Impaired trafficking of kAE1 leads to defect of the Cl-/HCO3- exchange at the basolateral membrane and failure of proton (H+) secretion at the apical membrane, causing a kidney disease - distal renal tubular acidosis (dRTA). To gain a better insight into kAE1 trafficking, we searched for proteins physically interacting with the C-terminal region of kAE1 (Ct-kAE1), which contains motifs crucial for intracellular trafficking, by a yeast two-hybrid (Y2H) system. An adaptor-related protein complex 1 μ1A (AP-1 mu1A) subunit was found to interact with Ct-kAE1. The interaction between either Ct-kAE1 or full-length kAE1 and AP-1 mu1A were confirmed in human embryonic kidney (HEK) 293T by co-immunoprecipitation, affinity co-purification, co-localization, yellow fluorescent protein (YFP)-based protein fragment complementation assay (PCA) and GST pull-down assay. The interacting site for AP-1 mu1A on Ct-kAE1 was found to be Y904DEV907, a subset of YXXO motif. Interestingly, suppression of endogenous AP-1 mu1A in HEK 293T by small interfering RNA (siRNA) decreased membrane localization of kAE1 and increased its intracellular accumulation, suggesting for the first time that AP-1 mu1A is involved in the kAE1 trafficking of kidney α-intercalated cells.

  16. The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability.

    Directory of Open Access Journals (Sweden)

    Min Zong

    Full Text Available BACKGROUND: The TRAPP (Transport protein particle complex is a conserved protein complex functioning at various steps in vesicle transport. Although yeast has three functionally and structurally distinct forms, TRAPPI, II and III, emerging evidence suggests that mammalian TRAPP complex may be different. Mutations in the TRAPP complex subunit 2 (TRAPPC2 cause X-linked spondyloepiphyseal dysplasia tarda, while mutations in the TRAPP complex subunit 9 (TRAPPC9 cause postnatal mental retardation with microcephaly. The structural interplay between these subunits found in mammalian equivalent of TRAPPI and those specific to TRAPPII and TRAPPIII remains largely unknown and we undertook the present study to examine the interaction between these subunits. Here, we reveal that the mammalian equivalent of the TRAPPII complex is structurally distinct from the yeast counterpart thus leading to insight into mechanism of disease. PRINCIPAL FINDINGS: We analyzed how TRAPPII- or TRAPPIII- specific subunits interact with the six-subunit core complex of TRAPP by co-immunoprecipitation in mammalian cells. TRAPPC2 binds to TRAPPII-specific subunit TRAPPC9, which in turn binds to TRAPPC10. Unexpectedly, TRAPPC2 can also bind to the putative TRAPPIII-specific subunit, TRAPPC8. Endogenous TRAPPC9-positive TRAPPII complex does not contain TRAPPC8, suggesting that TRAPPC2 binds to either TRAPPC9 or TRAPPC8 during the formation of the mammalian equivalents of TRAPPII or TRAPPIII, respectively. Therefore, TRAPPC2 serves as an adaptor for the formation of these complexes. A disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8, mediating the formation of TRAPPII and/or TRAPPIII. Furthermore, disease-causing deletional mutants of TRAPPC9 all failed to interact with TRAPPC2 and TRAPPC10. CONCLUSIONS: TRAPPC2 serves as an adaptor for the

  17. Increased abundance of the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1) in patients with obesity and type 2 diabetes: evidence for altered adiponectin signalling

    OpenAIRE

    Holmes, R.M.; Yi, Z; De Filippis, E.; Berria, R.; S. Shahani; P. Sathyanarayana; Sherman, V.; K. Fujiwara; Meyer, C.; Christ-Roberts, C.; Hwang, H; Finlayson, J.; Dong, L. Q.; Mandarino, L. J.; Bajaj, M.

    2011-01-01

    Aims/hypothesis The adiponectin signalling pathway is largely unknown, but recently the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif (APPL1), has been shown to interact directly with adiponectin receptor (ADIPOR)1. APPL1 is present in C2C12 myoblasts and mouse skeletal muscle, but its presence in human skeletal muscle has not been investigated. Methods Samples from type 2 diabetic, and lean and non-diabetic obese participants w...

  18. Combinatorial H3K9acS10ph Histone Modification in IgH Locus S Regions Targets 14-3-3 Adaptors and AID to Specify Antibody Class-Switch DNA Recombination

    Directory of Open Access Journals (Sweden)

    Guideng Li

    2013-11-01

    Full Text Available Class-switch DNA recombination (CSR is central to the antibody response, in that it changes the immunoglobulin heavy chain (IgH constant region, thereby diversifying biological effector functions of antibodies. The activation-induced cytidine deaminase (AID-centered CSR machinery excises and rejoins DNA between an upstream (donor and a downstream (acceptor S region, which precede the respective constant region DNA. AID is stabilized on S regions by 14-3-3 adaptors. These adaptors display a high affinity for 5′-AGCT-3′ repeats, which recur in all S regions. However, how 14-3-3, AID, and the CSR machinery target exclusively the donor and acceptor S regions is poorly understood. Here, we show that histone methyltransferases and acetyltransferases are induced by CD40 or Toll-like receptor signaling and catalyze H3K4me3 and H3K9ac/K14ac histone modifications, which are enriched in S regions but do not specify the S region targets of CSR. By contrast, the combinatorial H3K9acS10ph modification specifically marks the S regions set to recombine and directly recruits 14-3-3 adaptors for AID stabilization there. Inhibition of the enzymatic activity of GCN5 and PCAF histone acetyltransferases reduces H3K9acS10ph in S regions, 14-3-3 and AID stabilization, and CSR. Thus, H3K9acS10ph is a histone code that is “written” specifically in S regions and is “read” by 14-3-3 adaptors to target AID for CSR as an important biological outcome.

  19. The non-palindromic adaptor-PCR method for the identification of the T-cell receptor genes of an interferon-gamma-secreting T-cell hybridomaspecific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen

    Directory of Open Access Journals (Sweden)

    M.I. Hiyane

    2006-03-01

    Full Text Available Cloning of the T-cell receptor genes is a critical step when generating T-cell receptor transgenic mice. Because T-cell receptor molecules are clonotypical, isolation of their genes requires reverse transcriptase-assisted PCR using primers specific for each different Valpha or Vß genes or by the screening of cDNA libraries generated from RNA obtained from each individual T-cell clone. Although feasible, these approaches are laborious and costly. The aim of the present study was to test the application of the non-palindromic adaptor-PCR method as an alternative to isolate the genes encoding the T-cell receptor of an antigen-specific T-cell hybridoma. For this purpose, we established hybridomas specific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen. These T-cell hybridomas were characterized with regard to their ability to secrete interferon-gamma, IL-4, and IL-10 after stimulation with the antigen. A CD3+, CD4+, CD8- interferon-gamma-producing hybridoma was selected for the identification of the variable regions of the T-cell receptor by the non-palindromic adaptor-PCR method. Using this methodology, we were able to rapidly and efficiently determine the variable regions of both T-cell receptor chains. The results obtained by the non-palindromic adaptor-PCR method were confirmed by the isolation and sequencing of the complete cDNA genes and by the recognition with a specific antibody against the T-cell receptor variable ß chain. We conclude that the non-palindromic adaptor-PCR method can be a valuable tool for the identification of the T-cell receptor transcripts of T-cell hybridomas and may facilitate the generation of T-cell receptor transgenic mice.

  20. Interplays between Sumoylation, SUMO-Targeted Ubiquitin Ligases, and the Ubiquitin-Adaptor Protein Ufd1 in Fission Yeast

    DEFF Research Database (Denmark)

    Køhler, Julie Bonne

    and the specific molecular interactions and sequence of events linking sumoylation, ubiquitylation and substrate degradation, has been largely uncovered. Using the fission yeast model organism I here present evidence for a role of the Ufd1 (ubiquitinfusion degradation 1) protein, and by extension of the Cdc48-Ufd1...... other downstream fates. My work provides insight into how Cdc48-Ufd1-Npl4 also contributes to the processing of SUMO conjugates and suggests that at least some of these activities are coordinated with STUbL function. To gain insight into the sumoylated species regulated by Ufd1 and/or by STUbLs, I made......-Npl4 activities are coupled to dynamically regulate cellular processes....

  1. A conserved serine residue regulates the stability of Drosophila Salvador and human WW domain-containing adaptor 45 through proteasomal degradation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Di, E-mail: DiWu@mail.nankai.edu.cn; Wu, Shian

    2013-04-19

    Highlights: •Ser-17 is key for the stability of Drosophila Sav. •Ala mutation of Ser-17 promotes the proteasomal degradation of Sav. •Ser-17 residue is not the main target of Hpo-induced Sav stabilization. •Hpo-dependent and -independent mechanisms regulate Sav stability. •This mechanism is conserved in the homologue of Sav, human WW45. -- Abstract: The Hippo (Hpo) pathway is a conserved tumor suppressor pathway that controls organ size through the coordinated regulation of apoptosis and proliferation. Drosophila Salvador (Sav), which limits organ size, is a core component of the Hpo pathway. In this study, Ser-17 was shown to be important for the stability of Sav. Alanine mutation of Ser-17 promoted the proteasomal degradation of Sav. Destabilization and stabilization of the Sav protein mediated by alanine mutation of Ser-17 and by Hpo, respectively, were independent of each other. This implies that the stability of Sav is controlled by two mechanisms, one that is Ser-17-dependent and Hpo-independent, and another that is Ser-17-independent and Hpo-dependent. These dual mechanisms also regulated the human counterpart of Drosophila Sav, WW domain-containing adaptor 45 (WW45). The conservation of this regulation adds to its significance in normal physiology and tumorigenesis.

  2. The adaptor protein DCAF7 mediates the interaction of the adenovirus E1A oncoprotein with the protein kinases DYRK1A and HIPK2.

    Science.gov (United States)

    Glenewinkel, Florian; Cohen, Michael J; King, Cason R; Kaspar, Sophie; Bamberg-Lemper, Simone; Mymryk, Joe S; Becker, Walter

    2016-01-01

    DYRK1A is a constitutively active protein kinase that has a critical role in growth and development which functions by regulating cell proliferation, differentiation and survival. DCAF7 (also termed WDR68 or HAN11) is a cellular binding partner of DYRK1A and also regulates signalling by the protein kinase HIPK2. DCAF7 is an evolutionarily conserved protein with a single WD40 repeat domain and has no catalytic activity. We have defined a DCAF7 binding motif of 12 amino acids in the N-terminal domain of class 1 DYRKs that is functionally conserved in DYRK1 orthologs from Xenopus, Danio rerio and the slime mold Dictyostelium discoideum. A similar sequence was essential for DCAF7 binding to HIPK2, whereas the closely related HIPK1 family member did not bind DCAF7. Immunoprecipitation and pulldown experiments identified DCAF7 as an adaptor for the association of the adenovirus E1A protein with DYRK1A and HIPK2. Furthermore, DCAF7 was required for the hyperphosphorylation of E1A in DYRK1A or HIPK2 overexpressing cells. Our results characterize DCAF7 as a substrate recruiting subunit of DYRK1A and HIPK2 and suggest that it is required for the negative effect of DYRK1A on E1A-induced oncogenic transformation. PMID:27307198

  3. Skb5, an SH3 adaptor protein, regulates Pmk1 MAPK signaling by controlling the intracellular localization of the MAPKKK Mkh1.

    Science.gov (United States)

    Kanda, Yuki; Satoh, Ryosuke; Matsumoto, Saki; Ikeda, Chisato; Inutsuka, Natsumi; Hagihara, Kanako; Matzno, Sumio; Tsujimoto, Sho; Kita, Ayako; Sugiura, Reiko

    2016-08-15

    The mitogen-activated protein kinase (MAPK) cascade is a highly conserved signaling module composed of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKK) and MAPKs. The MAPKKK Mkh1 is an initiating kinase in Pmk1 MAPK signaling, which regulates cell integrity in fission yeast (Schizosaccharomyces pombe). Our genetic screen for regulators of Pmk1 signaling identified Shk1 kinase binding protein 5 (Skb5), an SH3-domain-containing adaptor protein. Here, we show that Skb5 serves as an inhibitor of Pmk1 MAPK signaling activation by downregulating Mkh1 localization to cell tips through its interaction with the SH3 domain. Consistent with this, the Mkh1(3PA) mutant protein, with impaired Skb5 binding, remained in the cell tips, even when Skb5 was overproduced. Intriguingly, Skb5 needs Mkh1 to localize to the growing ends as Mkh1 deletion and disruption of Mkh1 binding impairs Skb5 localization. Deletion of Pck2, an upstream activator of Mkh1, impaired the cell tip localization of Mkh1 and Skb5 as well as the Mkh1-Skb5 interaction. Interestingly, both Pck2 and Mkh1 localized to the cell tips at the G1/S phase, which coincided with Pmk1 MAPK activation. Taken together, Mkh1 localization to cell tips is important for transmitting upstream signaling to Pmk1, and Skb5 spatially regulates this process. PMID:27451356

  4. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  5. Involvement of β3A Subunit of Adaptor Protein-3 in Intracellular Trafficking of Receptor-like Protein Tyrosine Phosphatase PCP-2

    Institute of Scientific and Technical Information of China (English)

    Hui DONG; Hong YUAN; Weirong JIN; Yan SHEN; Xiaojing XU; Hongyang WANG

    2007-01-01

    PCP-2 is a human receptor-like protein tyrosine phosphatase and a member of the MAM domain family cloned in human pancreatic adenocarcinoma cells. Previous studies showed that PCP-2 directly interacted with β-catenin through the juxtamembrane domain, dephosphorylated β-catenin and played an important role in the regulation of cell adhesion. Recent study showed that PCP-2 was also involved in the repression of β-catenin-induced transcriptional activity. Here we describe the interactions of PCP-2 with the β3A subunit of adaptor protein (AP)-3 and sorting nexin (SNX) 3. These protein complexes were detected using the yeast two-hybrid assay with the juxtamembrane and membrane-proximal catalytic domain of PCP-2 as "bait". Both AP-3 and SNX3 are molecules involved in intracellular trafficking of membrane receptors. The association between the β3A subunit of AP-3 and PCP-2 was further confirmed in mammalian cells. Our results suggested a possible mechanism of intracellular trafficking of PCP-2 mediated by AP-3 and SNX3 which might participate in the regulation of PCP-2 functions.

  6. Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter

    Directory of Open Access Journals (Sweden)

    Akio Nakashima

    2014-05-01

    Full Text Available The Tsc1–Tsc2 complex homologous to human tuberous sclerosis complex proteins governs amino acid uptake by regulating the expression and intracellular distribution of amino acid transporters in Schizosaccharomyces pombe. Here, we performed a genetic screening for molecules that are involved in amino acid uptake and found Arn1 (also known as Any1. Arn1 is homologous to ART1, an arrestin-related trafficking adaptor (ART in Saccharomyces cerevisiae, and contains a conserved arrestin motif, a ubiquitination site, and two PY motifs. Overexpression of arn1+ confers canavanine resistance on cells, whereas its disruption causes hypersensitivity to canavanine. We also show that Arn1 regulates endocytosis of the Cat1 amino acid transporter. Furthermore, deletion of arn1+ suppresses a defect of amino acid uptake and the aberrant Cat1 localization in tsc2Δ. Arn1 interacts with and is ubiquitinated by the Pub1 ubiquitin ligase, which is necessary to regulate Cat1 endocytosis. Cat1 undergoes ubiquitinations on lysine residues within the N-terminus, which are mediated, in part, by Arn1 to determine Cat1 localization. Correctively, Arn1 is an ART in S. pombe and contributes to amino acid uptake through regulating Cat1 endocytosis in which Tsc2 is involved.

  7. The Src homology and collagen A (ShcA) adaptor protein is required for the spatial organization of the costamere/Z-disk network during heart development.

    Science.gov (United States)

    Mlih, Mohamed; Host, Lionel; Martin, Sophie; Niederhoffer, Nathalie; Monassier, Laurent; Terrand, Jérôme; Messaddeq, Nadia; Radke, Michael; Gotthardt, Michael; Bruban, Véronique; Kober, Frank; Bernard, Monique; Canet-Soulas, Emmanuelle; Abt-Jijon, Francisco; Boucher, Philippe; Matz, Rachel L

    2015-01-23

    Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca(2+)/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere. PMID:25488665

  8. The Src Homology and Collagen A (ShcA) Adaptor Protein Is Required for the Spatial Organization of the Costamere/Z-disk Network during Heart Development*

    Science.gov (United States)

    Mlih, Mohamed; Host, Lionel; Martin, Sophie; Niederhoffer, Nathalie; Monassier, Laurent; Terrand, Jérôme; Messaddeq, Nadia; Radke, Michael; Gotthardt, Michael; Bruban, Véronique; Kober, Frank; Bernard, Monique; Canet-Soulas, Emmanuelle; Abt-Jijon, Francisco; Boucher, Philippe; Matz, Rachel L.

    2015-01-01

    Src homology and collagen A (ShcA) is an adaptor protein that binds to tyrosine kinase receptors. Its germ line deletion is embryonic lethal with abnormal cardiovascular system formation, and its role in cardiovascular development is unknown. To investigate its functional role in cardiovascular development in mice, ShcA was deleted in cardiomyocytes and vascular smooth muscle cells by crossing ShcA flox mice with SM22a-Cre transgenic mice. Conditional mutant mice developed signs of severe dilated cardiomyopathy, myocardial infarctions, and premature death. No evidence of a vascular contribution to the phenotype was observed. Histological analysis of the heart revealed aberrant sarcomeric Z-disk and M-band structures, and misalignments of T-tubules with Z-disks. We find that not only the ErbB3/Neuregulin signaling pathway but also the baroreceptor reflex response, which have been functionally associated, are altered in the mutant mice. We further demonstrate that ShcA interacts with Caveolin-1 and the costameric protein plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA), and that its deletion leads to abnormal dystrophin signaling. Collectively, these results demonstrate that ShcA interacts with crucial proteins and pathways that link Z-disk and costamere. PMID:25488665

  9. DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks.

    Science.gov (United States)

    Mosbech, Anna; Gibbs-Seymour, Ian; Kagias, Konstantinos; Thorslund, Tina; Beli, Petra; Povlsen, Lou; Nielsen, Sofie Vincents; Smedegaard, Stine; Sedgwick, Garry; Lukas, Claudia; Hartmann-Petersen, Rasmus; Lukas, Jiri; Choudhary, Chunaram; Pocock, Roger; Bekker-Jensen, Simon; Mailand, Niels

    2012-11-01

    Ubiquitin-mediated processes orchestrate critical DNA-damage signaling and repair pathways. We identify human DVC1 (C1orf124; Spartan) as a cell cycle-regulated anaphase-promoting complex (APC) substrate that accumulates at stalled replication forks. DVC1 recruitment to sites of replication stress requires its ubiquitin-binding UBZ domain and PCNA-binding PIP box motif but is independent of RAD18-mediated PCNA monoubiquitylation. Via a conserved SHP box, DVC1 recruits the ubiquitin-selective chaperone p97 to blocked replication forks, which may facilitate p97-dependent removal of translesion synthesis (TLS) DNA polymerase η (Pol η) from monoubiquitylated PCNA. DVC1 knockdown enhances UV light-induced mutagenesis, and depletion of human DVC1 or the Caenorhabditis elegans ortholog DVC-1 causes hypersensitivity to replication stress-inducing agents. Our findings establish DVC1 as a DNA damage-targeting p97 adaptor that protects cells from deleterious consequences of replication blocks and suggest an important role of p97 in ubiquitin-dependent regulation of TLS. PMID:23042605

  10. Identification and Characterization of KCASH2 and KCASH3, 2 Novel Cullin3 Adaptors Suppressing Histone Deacetylase and Hedgehog Activity in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2011-04-01

    Full Text Available Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor RENKCTD11 acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two RENKCTD11 homologues, defining a new family of proteins named KCASH, as “KCTD containing, Cullin3 adaptor, suppressor of Hedgehog.” Indeed, the novel genes (KCASH2KCTD21 and KCASH3KCTD6 share with RENKCTD11 a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous “agents” through which this pathway may be targeted.

  11. Cul3 and the BTB adaptor insomniac are key regulators of sleep homeostasis and a dopamine arousal pathway in Drosophila.

    Directory of Open Access Journals (Sweden)

    Cory Pfeiffenberger

    Full Text Available Sleep is homeostatically regulated, such that sleep drive reflects the duration of prior wakefulness. However, despite the discovery of genes important for sleep, a coherent molecular model for sleep homeostasis has yet to emerge. To better understand the function and regulation of sleep, we employed a reverse-genetics approach in Drosophila. An insertion in the BTB domain protein CG32810/insomniac (inc exhibited one of the strongest baseline sleep phenotypes thus far observed, a ~10 h sleep reduction. Importantly, this is coupled to a reduced homeostatic response to sleep deprivation, consistent with a disrupted sleep homeostat. Knockdown of the INC-interacting protein, the E3 ubiquitin ligase Cul3, results in reduced sleep duration, consolidation, and homeostasis, suggesting an important role for protein turnover in mediating INC effects. Interestingly, inc and Cul3 expression in post-mitotic neurons during development contributes to their adult sleep functions. Similar to flies with increased dopaminergic signaling, loss of inc and Cul3 result in hyper-arousability to a mechanical stimulus in adult flies. Furthermore, the inc sleep duration phenotype can be rescued by pharmacological inhibition of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. Taken together, these results establish inc and Cul3 as important new players in setting the sleep homeostat and a dopaminergic arousal pathway in Drosophila.

  12. Magnetismo Molecular (Molecular Magentism)

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Mario S [Universidade Federal Fluminense, Brasil; Moreira Dos Santos, Antonio F [ORNL

    2010-07-01

    The new synthesis processes in chemistry open a new world of research, new and surprising materials never before found in nature can now be synthesized and, as a wonderful result, observed a series of physical phenomena never before imagined. Among these are many new materials the molecular magnets, the subject of this book and magnetic properties that are often reflections of the quantum behavior of these materials. Aside from the wonderful experience of exploring something new, the theoretical models that describe the behavior these magnetic materials are, in most cases, soluble analytically, which allows us to know in detail the physical mechanisms governing these materials. Still, the academic interest in parallel this subject, these materials have a number of properties that are promising to be used in technological devices, such as in computers quantum magnetic recording, magnetocaloric effect, spintronics and many other devices. This volume will journey through the world of molecular magnets, from the structural description of these materials to state of the art research.

  13. Impaired Lysosomal Integral Membrane Protein 2-dependent Peroxiredoxin 6 Delivery to Lamellar Bodies Accounts for Altered Alveolar Phospholipid Content in Adaptor Protein-3-deficient pearl Mice.

    Science.gov (United States)

    Kook, Seunghyi; Wang, Ping; Young, Lisa R; Schwake, Michael; Saftig, Paul; Weng, Xialian; Meng, Ying; Neculai, Dante; Marks, Michael S; Gonzales, Linda; Beers, Michael F; Guttentag, Susan

    2016-04-15

    The Hermansky Pudlak syndromes (HPS) constitute a family of disorders characterized by oculocutaneous albinism and bleeding diathesis, often associated with lethal lung fibrosis. HPS results from mutations in genes of membrane trafficking complexes that facilitate delivery of cargo to lysosome-related organelles. Among the affected lysosome-related organelles are lamellar bodies (LB) within alveolar type 2 cells (AT2) in which surfactant components are assembled, modified, and stored. AT2 from HPS patients and mouse models of HPS exhibit enlarged LB with increased phospholipid content, but the mechanism underlying these defects is unknown. We now show that AT2 in the pearl mouse model of HPS type 2 lacking the adaptor protein 3 complex (AP-3) fails to accumulate the soluble enzyme peroxiredoxin 6 (PRDX6) in LB. This defect reflects impaired AP-3-dependent trafficking of PRDX6 to LB, because pearl mouse AT2 cells harbor a normal total PRDX6 content. AP-3-dependent targeting of PRDX6 to LB requires the transmembrane protein LIMP-2/SCARB2, a known AP-3-dependent cargo protein that functions as a carrier for lysosomal proteins in other cell types. Depletion of LB PRDX6 in AP-3- or LIMP-2/SCARB2-deficient mice correlates with phospholipid accumulation in lamellar bodies and with defective intraluminal degradation of LB disaturated phosphatidylcholine. Furthermore, AP-3-dependent LB targeting is facilitated by protein/protein interaction between LIMP-2/SCARB2 and PRDX6 in vitro and in vivo Our data provide the first evidence for an AP-3-dependent cargo protein required for the maturation of LB in AT2 and suggest that the loss of PRDX6 activity contributes to the pathogenic changes in LB phospholipid homeostasis found HPS2 patients. PMID:26907692

  14. The Ras suppressor Rsu-1 binds to the LIM 5 domain of the adaptor protein PINCH1 and participates in adhesion-related functions

    International Nuclear Information System (INIS)

    Rsu-1 is a highly conserved leucine rich repeat (LRR) protein that is expressed ubiquitously in mammalian cells. Rsu-1 was identified based on its ability to inhibit transformation by Ras, and previous studies demonstrated that ectopic expression of Rsu-1 inhibited anchorage-independent growth of Ras-transformed cells and human tumor cell lines. Using GAL4-based yeast two-hybrid screening, the LIM domain protein, PINCH1, was identified as the binding partner of Rsu-1. PINCH1 is an adaptor protein that localizes to focal adhesions and it has been implicated in the regulation of adhesion functions. Subdomain mapping in yeast revealed that Rsu-1 binds to the LIM 5 domain of PINCH1, a region not previously identified as a specific binding domain for any other protein. Additional testing demonstrated that PINCH2, which is highly homologous to PINCH1, except in the LIM 5 domain, does not interact with Rsu-1. Glutathione transferase fusion protein binding studies determined that the LRR region of Rsu-1 interacts with PINCH1. Transient expression studies using epitope-tagged Rsu-1 and PINCH1 revealed that Rsu-1 co-immunoprecipitated with PINCH1 and colocalized with vinculin at sites of focal adhesions in mammalian cells. In addition, endogenous P33 Rsu-1 from 293T cells co-immunoprecipitated with transiently expressed myc-tagged PINCH1. Furthermore, RNAi-induced reduction in Rsu-1 RNA and protein inhibited cell attachment, and while previous studies demonstrated that ectopic expression of Rsu-1 inhibited Jun kinase activation, the depletion of Rsu-1 resulted in activation of Jun and p38 stress kinases. These studies demonstrate that Rsu-1 interacts with PINCH1 in mammalian cells and functions, in part, by altering cell adhesion

  15. Molecular Electronics

    OpenAIRE

    Heath, James R.

    2009-01-01

    Molecular electronics describes the field in which molecules are utilized as the active (switching, sensing, etc.) or passive (current rectifiers, surface passivants) elements in electronic devices. This review focuses on experimental aspects of molecular electronics that researchers have elucidated over the past decade or so and that relate to the fabrication of molecular electronic devices in which the molecular components are readily distinguished within the electronic properties of the de...

  16. Molecular Gastronomy

    OpenAIRE

    Burke, Roisin; This, Herve; Kelly, Alan

    2016-01-01

    Molecular gastronomy may be defined as the scientific discipline that explores the phenomena occurring during culinary transformations. In contrast with traditional approaches of food science and technology, which considered mostly the chemistry, physics, or biology of food ingredients and industrial transformations, the focus is on phenomena occurring during the preparation of dishes. Applications building on the principles of molecular gastronomy, such as ‘Molecular Cooking’ and ‘Note-by-No...

  17. Molecular beams

    International Nuclear Information System (INIS)

    This book is a timeless and rather complete theoretical and experimental treatment of electric and magnetic resonance molecular-beam experiments for studying the radio frequency spectra of atoms and molecules. The theory of interactions of the nucleus with atomic and molecular fields is extensively presented. Measurements of atomic and nuclear magnetic moments, electric multipole moments, and atomic fine and hyperfine structure are detailed. Useful but somewhat outdated chapters on gas kinetics, molecular beam design, and experimental techniques are also included

  18. Molecular Spintronics

    OpenAIRE

    Shiraishi, Masashi; Ikoma, Tadaaki

    2011-01-01

    Molecular spintronics is recognized to as an attractive new research direction in a field of spintronics, following to metallic spintronics and inorganic semiconductor spintronics, and attracts many people in recent decades. The purpose of this manuscript is to describe the history of molecular spintronics by introducing important achievements and to show the current status of this field. In addition, the authors briefly introduce several theories for implementing studies in molecular spintro...

  19. Molecular Magnetocapacitance

    OpenAIRE

    Wu, Yu-ning; Zhang, Xiao-Guang; Cheng, Hai-Ping

    2012-01-01

    Capacitance of a nanoscale system is usually thought of having two contributions, a classical electrostatic contribution and a quantum contribution dependent on the density of states and/or molecular orbitals close to the Fermi energy. In this letter we demonstrate that in molecular nano-magnets and other magnetic nanoscale systems, the quantum part of the capacitance becomes spin-dependent, and is tunable by an external magnetic field. This molecular magnetocapacitance can be realized using ...

  20. Molecular pharmacognosy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This article analyzes the background and significance of molecular pharmacognosy,including the molecular identification of medicinal raw materials,phylogenetic evolution of medicinal plants and animals,evaluation and preservation of germplasm resources for medicinal plants and animals,etiology of endangerment and protection of endangered medicinal plants and animals,biosynthesis and bioregulation of active components in medicinal plants,and characteristics and the molecular bases of top-geoherbs.

  1. Molecular Diagnostics

    OpenAIRE

    Choe, Hyonmin; Deirmengian, Carl A; Hickok, Noreen J.; Morrison, Tiffany N.; Tuan, Rocky S.

    2015-01-01

    Orthopaedic infections are complex conditions that require immediate diagnosis and accurate identification of the causative organisms to facilitate appropriate management. Conventional methodologies for diagnosis of these infections sometimes lack accuracy or sufficient rapidity. Current molecular diagnostics are an emerging area of bench-to-bedside research in orthopaedic infections. Examples of promising molecular diagnostics include measurement of a specific biomarker in the synovial fluid...

  2. Molecular geometry

    CERN Document Server

    Rodger, Alison

    1995-01-01

    Molecular Geometry discusses topics relevant to the arrangement of atoms. The book is comprised of seven chapters that tackle several areas of molecular geometry. Chapter 1 reviews the definition and determination of molecular geometry, while Chapter 2 discusses the unified view of stereochemistry and stereochemical changes. Chapter 3 covers the geometry of molecules of second row atoms, and Chapter 4 deals with the main group elements beyond the second row. The book also talks about the complexes of transition metals and f-block elements, and then covers the organometallic compounds and trans

  3. Molecular sciences

    International Nuclear Information System (INIS)

    The research in molecular sciences summarized includes photochemistry, radiation chemistry, geophysics, electromechanics, heavy-element oxidizers , heavy element chemistry collisions, atoms, organic solids. A list of publications is included

  4. Molecular Electronics

    DEFF Research Database (Denmark)

    Jennum, Karsten Stein

    This thesis includes the synthesis and characterisation of organic compounds designed for molecular electronics. The synthesised organic molecules are mainly based on two motifs, the obigo(phenyleneethynylenes) (OPE)s and tetrathiafulvalene (TTF) as shown below. These two scaffolds (OPE and TTF......) are chemically merged together to form cruciform-like structures that are an essential part of the thesis. The cruciform molecules were subjected to molecular conductance measurements to explore their capability towards single-crystal field-effect transistors (Part 1), molecular wires, and single electron......, however, was obtained by a study of a single molecular transistor. The investigated OPE5-TTF compound was captured in a three-terminal experiment, whereby manipulation of the molecule’s electronic spin was possible in different charge states. Thus, we demonstrated how the cruciform molecules could...

  5. Molecular farming

    OpenAIRE

    Merck, K.B.; Vereijken, J M

    2006-01-01

    Molecular Farming is a new and emerging technology that promises relatively cheap and flexible production of large quantities of pharmaceuticals in genetically modified plants. Many stakeholders are involved in the production of pharmaceuticals in plants, which complicates the discussion on the possible benefits and disadvantages to a great extent. Discussions about Molecular Farming are often about technical and economic aspects, but other aspects like safety and ethical and societal aspects...

  6. Molecular printing

    OpenAIRE

    Braunschweig, Adam B.; Huo, Fengwei; Mirkin, Chad A.

    2009-01-01

    Molecular printing techniques, which involve the direct transfer of molecules to a substrate with submicrometre resolution, have been extensively developed over the past decade and have enabled many applications. Arrays of features on this scale have been used to direct materials assembly, in nanoelectronics, and as tools for genetic analysis and disease detection. The past decade has witnessed the maturation of molecular printing led by two synergistic technologies: dip-pen nanolithography a...

  7. Molecular Nanoelectronics

    OpenAIRE

    Vuillaume, Dominique

    2010-01-01

    Molecular electronics is envisioned as a promising candidate for the nanoelectronics of the future. More than a possible answer to ultimate miniaturization problem in nanoelectronics, molecular electronics is foreseen as a possible way to assemble a large numbers of nanoscale objects (molecules, nanoparticules, nanotubes and nanowires) to form new devices and circuit architectures. It is also an interesting approach to significantly reduce the fabrication costs, as well as the energetical cos...

  8. Molecular Spintronics using Molecular Nanomagnets

    Science.gov (United States)

    Wernsdorfer, Wolfgang

    2009-03-01

    A revolution in electronics is in view, with the contemporary evolution of two novel disciplines, spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets [1], which combine the classic macroscale properties of a magnet with the quantum properties of a nanoscale entity. The resulting field, molecular spintronics aims at manipulating spins and charges in electronic devices containing one or more molecules. In this context, we want to fabricate, characterize and study molecular devices (molecular spin-transistor, molecular spin-valve and spin filter, molecular double-dot devices, carbon nanotube nano-SQUIDs, etc.) in order to read and manipulate the spin states of the molecule and to perform basic quantum operations. The talk will discuss this--still largely unexplored--field and present our the first important results [2,3].[4pt] [1] L. Bogani & W. Wernsdorfer, Nature Mat. 7, 179 (2008).[0pt] [2] J.-P. Cleuziou, W. Wernsdorfer, V. Bouchiat, T. Ondarcuhu, M. Monthioux, Nature Nanotech. 1, 53-59 (2006).[0pt] [3] N. Roch, S. Florens, V. Bouchiat, W. Wernsdorfer, F. Balestro, Nature 453, 633 (2008).

  9. Structural Molecular Components of Septate Junctions in Cnidarians Point to the Origin of Epithelial Junctions in Eukaryotes

    KAUST Repository

    Ganot, P.

    2014-09-21

    Septate junctions (SJs) insure barrier properties and control paracellular diffusion of solutes across epithelia in invertebrates. However, the origin and evolution of their molecular constituents in Metazoa have not been firmly established. Here, we investigated the genomes of early branching metazoan representatives to reconstruct the phylogeny of the molecular components of SJs. Although Claudins and SJ cytoplasmic adaptor components appeared successively throughout metazoan evolution, the structural components of SJs arose at the time of Placozoa/Cnidaria/Bilateria radiation. We also show that in the scleractinian coral Stylophora pistillata, the structural SJ component Neurexin IV colocalizes with the cortical actin network at the apical border of the cells, at the place of SJs. We propose a model for SJ components in Cnidaria. Moreover, our study reveals an unanticipated diversity of SJ structural component variants in cnidarians. This diversity correlates with gene-specific expression in calcifying and noncalcifying tissues, suggesting specific paracellular pathways across the cell layers of these diploblastic animals.

  10. Molecular modeling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-01-01

    Full Text Available The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular modeling. Molecular modeling is a rapidly developing discipline, and has been supported by the dramatic improvements in computer hardware and software in recent years.

  11. Molecular physics

    CERN Document Server

    Demtröder, Wolfgang

    2008-01-01

    The richly illustrated book comprehensively explains the important principles of diatomic and polyatomic molecules and their spectra in two separate, distinct parts. The first part concentrates on the theoretical aspects of molecular physics, such as the vibration, rotation, electronic states, potential curves, and spectra of molecules. The different methods of approximation for the calculation of electronic wave functions and their energy are also covered. The introduction of basics terms used in group theory and their meaning in molecular physics enables an elegant description of polyatomic

  12. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection of...... fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  13. Molecular Crystals

    Science.gov (United States)

    Wright, John D.

    1995-02-01

    This book describes the chemical and physical structure of molecular crystals, their optical and electronic properties, and the reactions between neighboring molecules in crystals. In the second edition, the author has taken into account research that has undergone extremely rapid development since the first edition was published in 1987. For instance, he gives extensive coverage to the applications of molecular materials in high-technology devices (e.g. optical communications, laser printers, photocopiers, liquid crystal displays, solar cells, and more). There is also an entirely new chapter on the recently discovered Buckminsterfullerene carbon molecule (C60) and organic non-linear optic materials.

  14. Molecular photobiology.

    OpenAIRE

    Nikkels, Arjen; Pierard, Claudine; Pierard, Gérald

    2005-01-01

    Photochemical reactions are numerous in the skin. They generate reactive oxygen species and other biochemical alterations as well. According to their nature, the molecular components of the skin which have been altered by these mechanisms can be repaired with various degrees of efficacy. Peer reviewed

  15. Molecular photovoltaics

    OpenAIRE

    Moser, Jacques E.; Bonnôte, Pierre; Grätzel, Michael

    1998-01-01

    Photoinduced charge transfer processes involving molecules adsorbed at interfaces are a fascinating topic which is presently attracting wide attention. Our investigations have focused on the identification of the factors that control the dynamics of such processes. The goal is to design molecular electronic devices that achieve efficient light-induced charge separation. Applications of similar systems in photochromic and electrochromic devices also appear feasible.

  16. Molecular gastronomy

    Science.gov (United States)

    This, Hervé

    2005-01-01

    For centuries, cooks have been applying recipes without looking for the mechanisms of the culinary transformations. A scientific discipline that explores these changes from raw ingredients to eating the final dish, is developing into its own field, termed molecular gastronomy. Here, one of the founders of the discipline discusses its aims and importance.

  17. Ubiquitination and Degradation of CFTR by the E3 Ubiquitin Ligase MARCH2 through Its Association with Adaptor Proteins CAL and STX6

    OpenAIRE

    Jie Cheng; William Guggino

    2013-01-01

    Golgi-localized cystic fibrosis transmembrane conductance regulator (CFTR)-associated ligand (CAL) and syntaxin 6 (STX6) regulate the abundance of mature, post-ER CFTR by forming a CAL/STX6/CFTR complex (CAL complex) that promotes CFTR degradation in lysosomes. However, the molecular mechanism underlying this degradation is unknown. Here we investigated the interaction of a Golgi-localized, membrane-associated RING-CH E3 ubiquitin ligase, MARCH2, with the CAL complex and the consequent bindin...

  18. Molecular Modelling

    Directory of Open Access Journals (Sweden)

    Aarti Sharma

    2009-12-01

    Full Text Available

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important
    tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and
    the exponential growth of the knowledge of protein structures have made it possible for organic compounds to tailored to
    decrease harmful side effects and increase the potency. This article provides a detailed description of the techniques
    employed in molecular modeling. Molecular modelling is a rapidly developing discipline, and has been supported from
    the dramatic improvements in computer hardware and software in recent years.

  19. Molecular modeling

    OpenAIRE

    Aarti Sharma; Himanshu Gupta

    2009-01-01

    The use of computational chemistry in the development of novel pharmaceuticals is becoming an increasingly important tool. In the past, drugs were simply screened for effectiveness. The recent advances in computing power and the exponential growth of the knowledge of protein structures have made it possible for organic compounds to be tailored to decrease the harmful side effects and increase the potency. This article provides a detailed description of the techniques employed in molecular mod...

  20. Molecular Mechanics

    OpenAIRE

    Vanommeslaeghe, Kenno; Guvench, Olgun; Alexander D MacKerell

    2014-01-01

    Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This section introduces the reader to the fundamentals of MM, with a special emphasis on how the target data used in the parametrization of force fields determine their strengths and wea...

  1. Molecular Quarkonium

    OpenAIRE

    Voloshin, M. B.

    2006-01-01

    I discuss topics related to four-quark states of the `molecular quarkonium' type, i.e. resonances that could be considered as (dominantly) made from a heavy meson and antimeson. Of the so far observed resonances such picture is very likely applicable to the state X(3872), and I also discuss its possible relevance to the peak near the $D^* {\\bar D}^*$ threshold in $e^+e^-$ annihilation.

  2. Molecular Morphology

    OpenAIRE

    Donath, Alexander

    2011-01-01

    A fundamental problem in biology is the reconstruction of the relatedness of all (extant) species. Traditionally, systematists employ visually recognizable characters of organisms for classification and evolutionary analysis. Recent developments in molecular and computational biology, however, lead to a whole different perspective on how to address the problem of inferring relatedness. The discovery of molecules, carrying genetic information, and the comparison of their primary structure h...

  3. Molecular Diagnosis

    OpenAIRE

    Hoar, David I.

    1987-01-01

    Recombinant DNA technology, one of the major controversial areas of biological research in the late 1970s, is now rapidly providing new avenues for diagnosis and treatment. With the early recognition that extensive DNA variation exists in human populations, molecular genetic diagnosis of a variety of common hereditary diseases has become a reality. Recent identification of the location of the gene (or genes) for cystic fibrosis and adult polycystic kidney disease, and characterization of the ...

  4. Molecular Modeling

    Science.gov (United States)

    Holmes, Jon L.

    1999-06-01

    Molecular modeling has trickled down from the realm of pharmaceutical and research laboratories into the realm of undergraduate chemistry instruction. It has opened avenues for the visualization of chemical concepts that previously were difficult or impossible to convey. I am sure that many of you have developed exercises using the various molecular modeling tools. It is the desire of this Journal to become an avenue for you to share these exercises among your colleagues. It is to this end that Ron Starkey has agreed to edit such a column and to publish not only the description of such exercises, but also the software documents they use. The WWW is the obvious medium to distribute this combination and so accepted submissions will appear online as a feature of JCE Internet. Typical molecular modeling exercise: finding conformation energies. Molecular Modeling Exercises and Experiments is the latest feature column of JCE Internet, joining Conceptual Questions and Challenge Problems, Hal's Picks, and Mathcad in the Chemistry Curriculum. JCE Internet continues to seek submissions in these areas of interest and submissions of general interest. If you have developed materials and would like to submit them, please see our Guide to Submissions for more information. The Chemical Education Resource Shelf, Equipment Buyers Guide, and WWW Site Review would also like to hear about chemistry textbooks and software, equipment, and WWW sites, respectively. Please consult JCE Internet Features to learn more about these resources at JCE Online. Email Announcements Would you like to be informed by email when the latest issue of the Journal is available online? when a new JCE Software title is shipping? when a new JCE Internet article has been published or is available for Open Review? when your subscription is about to expire? A new feature of JCE Online makes this possible. Visit our Guestbook to learn how. When you submit the form on this page, which includes your email address

  5. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C on the regulation of Toll-like receptors, adaptor proteins and inflammatory response

    Directory of Open Access Journals (Sweden)

    Weith Andreas

    2005-11-01

    Full Text Available Abstract Background Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR. Methods The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Results Our data demonstrate that poly(I:C, a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C decreased the expression of TLR5, TLR6 and TOLLIP. Conclusion Poly(I:C, an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type

  6. [Molecular mechanisms underlying the formation of neuromuscular junction].

    Science.gov (United States)

    Higuchi, Osamu; Yamanashi, Yuji

    2011-07-01

    The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle. The contraction of skeletal muscle is controlled by the neurotransmitter acetylcholine (ACh), which is released from the motor nerve terminal. To achieve efficient neuromuscular transmission, acetylcholine receptors (AChRs) must be densely clustered on the muscle membrane of the NMJ. Failure of AChR clustering is associated with disorders of neuromuscular transmission such as congenital myasthenic syndromes (CMS) and myasthenia gravis (MG). Motoneuronal agrin and muscle-specific receptor tyrosine kinase (MuSK) are known to play essential roles in the formation and maintenance of NMJs in the central region of each muscle. However, it had been unclear how agrin activates MuSK. Recent studies have elucidated the roles of several key molecules, including the cytoplasmic adaptor protein Dok-7 and LDL receptor-related protein 4 (Lrp4), in agrin-induced MuSK activation. Moreover, new evidence indicates that cyclin-dependent kinase 5 (Cdk5) regulates postsynaptic differentiation. In this review, we summarize the latest developments in molecular mechanisms underlying NMJ formation in vertebrates. PMID:21747134

  7. Yeast Golgi-localized, γ-Ear–containing, ADP-Ribosylation Factor-binding Proteins Are but Adaptor Protein-1 Is Not Required for Cell-free Transport of Membrane Proteins from the Trans-Golgi Network to the Prevacuolar Compartment

    OpenAIRE

    Abazeed, Mohamed E.; Fuller, Robert S.

    2008-01-01

    Golgi-localized, γ-Ear–containing, ADP-ribosylation factor-binding proteins (GGAs) and adaptor protein-1 (AP-1) mediate clathrin-dependent trafficking of transmembrane proteins between the trans-Golgi network (TGN) and endosomes. In yeast, the vacuolar sorting receptor Vps10p follows a direct pathway from the TGN to the late endosome/prevacuolar compartment (PVC), whereas, the processing protease Kex2p partitions between the direct pathway and an indirect pathway through the early endosome. T...

  8. Cross-talk between Tetraspanin CD9 and Transmembrane Adaptor Protein Non-T Cell Activation Linker (NTAL) in Mast Cell Activation and Chemotaxis

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Bambousková, Monika; Machyna, Martin; Stegurová, Lucie; Smrž, Daniel; Dráber, Petr

    2013-01-01

    Roč. 288, č. 14 (2013), s. 9801-9814. ISSN 0021-9258 R&D Projects: GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GD204/09/H084; GA MŠk LD12073; GA TA ČR TA01010436; GA MPO FR-TI3/067 Grant ostatní: European Cooperation in Science and Technology(XE) Action BM1007 Institutional support: RVO:68378050 Keywords : mast cell * chemotaxis * Fc receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.600, year: 2013

  9. Toll-Like Receptor Adaptor MyD88 is Essential for Pathogen Control During Oral Toxoplasma gondii Infection but not Adaptive Immunity Induced by a Vaccine Strain of the Parasite1

    Science.gov (United States)

    Sukhumavasi, Woraporn; Egan, Charlotte E.; Warren, Amy L.; Taylor, Gregory A.; Fox, Barbara A.; Bzik, David J.; Denkers, Eric Y.

    2008-01-01

    Toll-like receptor (TLR)/MyD88 activation is important in host resistance to Toxoplasma gondii during i. p. infection, but the function of this signaling pathway during oral infection, in which mucosal immunity assumes a predominant role, has not been examined. Here, we show that MyD88−/− mice fail to control the parasite and succumb within two weeks of oral infection. Early during infection, T cell IFN-γ production, recruitment of neutrophils and induction of p47 GTPase Irgm3/IGTP in the intestinal mucosa were dependent upon functional MyD88. Unexpectedly, these responses were MyD88-independent later during acute infection. In particular, CD4+ T cell IFN-γ reached normal levels independently of MyD88, despite continued absence of IL-12 in these animals. Intraperitoneal vaccination of MyD88−/− mice with an avirulent T. gondii uracil axotroph elicited robust IFN-γ responses and protective immunity to challenge with a high virulence T. gondii strain. Our results demonstrate that MyD88 is required to control Toxoplasma infection, but that the parasite can trigger adaptive immunity without the need for this TLR adaptor molecule. PMID:18714019

  10. A novel interaction between the SH2 domain of signaling adaptor protein Nck-1 and the upstream regulator of the Rho family GTPase Rac1 engulfment and cell motility 1 (ELMO1) promotes Rac1 activation and cell motility.

    Science.gov (United States)

    Zhang, Guo; Chen, Xia; Qiu, Fanghua; Zhu, Fengxin; Lei, Wenjing; Nie, Jing

    2014-08-15

    Nck family proteins function as adaptors to couple tyrosine phosphorylation signals to actin cytoskeleton reorganization. Several lines of evidence indicate that Nck family proteins involve in regulating the activity of Rho family GTPases. In the present study, we characterized a novel interaction between Nck-1 with engulfment and cell motility 1 (ELMO1). GST pull-down and co-immunoprecipitation assay demonstrated that the Nck-1-ELMO1 interaction is mediated by the SH2 domain of Nck-1 and the phosphotyrosine residues at position 18, 216, 395, and 511 of ELMO1. A R308K mutant of Nck-1 (in which the SH2 domain was inactive), or a 4YF mutant of ELMO1 lacking these four phosphotyrosine residues, diminished Nck-1-ELMO1 interaction. Conversely, tyrosine phosphatase inhibitor treatment and overexpression of Src family kinase Hck significantly enhanced Nck-1-ELMO1 interaction. Moreover, wild type Nck-1, but not R308K mutant, significantly augmented the interaction between ELMO1 and constitutively active RhoG (RhoG(V12A)), thus promoted Rac1 activation and cell motility. Taken together, the present study characterized a novel Nck-1-ELMO1 interaction and defined a new role for Nck-1 in regulating Rac1 activity. PMID:24928514

  11. The proteolysis adaptor, NblA, is essential for degradation of the core pigment of the cyanobacterial light-harvesting complex.

    Science.gov (United States)

    Sendersky, Eleonora; Kozer, Noga; Levi, Mali; Moizik, Michael; Garini, Yuval; Shav-Tal, Yaron; Schwarz, Rakefet

    2015-09-01

    The cyanobacterial light-harvesting complex, the phycobilisome, is degraded under nutrient limitation, allowing the cell to adjust light absorbance to its metabolic capacity. This large light-harvesting antenna comprises a core complex of the pigment allophycocyanin, and rod-shaped pigment assemblies emanating from the core. NblA, a low-molecular-weight protein, is essential for degradation of the phycobilisome. NblA mutants exhibit high absorbance of rod pigments under conditions that generally elicit phycobilisome degradation, implicating NblA in degradation of these pigments. However, the vast abundance of rod pigments and the substantial overlap between the absorbance spectra of rod and core pigments has made it difficult to directly associate NblA with proteolysis of the phycobilisome core. Furthermore, lack of allophycocyanin degradation in an NblA mutant may reflect a requirement for rod degradation preceding core degradation, and does not prove direct involvement of NblA in proteolysis of the core pigment. Therefore, in this study, we used a mutant lacking phycocyanin, the rod pigment of Synechococcus elongatusPCC7942, to examine whether NblA is required for allophycocyanin degradation. We demonstrate that NblA is essential for degradation of the core complex of the phycobilisome. Furthermore, fluorescence lifetime imaging microscopy provided in situ evidence for the interaction of NblA with allophycocyanin, and indicated that NblA interacts with allophycocyanin complexes that are associated with the photosynthetic membranes. Based on these data, as well as previous observations indicating interaction of NblA with phycobilisomes attached to the photosynthetic membranes, we suggest a model for sequential phycobilisome disassembly by NblA. PMID:26173720

  12. Structural analysis of intermolecular interactions in the kinesin adaptor complex fasciculation and elongation protein zeta 1/ short coiled-coil protein (FEZ1/SCOCO.

    Directory of Open Access Journals (Sweden)

    Marcos Rodrigo Alborghetti

    Full Text Available Cytoskeleton and protein trafficking processes, including vesicle transport to synapses, are key processes in neuronal differentiation and axon outgrowth. The human protein FEZ1 (fasciculation and elongation protein zeta 1 / UNC-76, in C. elegans, SCOCO (short coiled-coil protein / UNC-69 and kinesins (e.g. kinesin heavy chain / UNC116 are involved in these processes. Exploiting the feature of FEZ1 protein as a bivalent adapter of transport mediated by kinesins and FEZ1 protein interaction with SCOCO (proteins involved in the same path of axonal growth, we investigated the structural aspects of intermolecular interactions involved in this complex formation by NMR (Nuclear Magnetic Resonance, cross-linking coupled with mass spectrometry (MS, SAXS (Small Angle X-ray Scattering and molecular modelling. The topology of homodimerization was accessed through NMR (Nuclear Magnetic Resonance studies of the region involved in this process, corresponding to FEZ1 (92-194. Through studies involving the protein in its monomeric configuration (reduced and dimeric state, we propose that homodimerization occurs with FEZ1 chains oriented in an anti-parallel topology. We demonstrate that the interaction interface of FEZ1 and SCOCO defined by MS and computational modelling is in accordance with that previously demonstrated for UNC-76 and UNC-69. SAXS and literature data support a heterotetrameric complex model. These data provide details about the interaction interfaces probably involved in the transport machinery assembly and open perspectives to understand and interfere in this assembly and its involvement in neuronal differentiation and axon outgrowth.

  13. Challenges in using cultured primary rodent hepatocytes or cell lines to study hepatic HDL receptor SR-BI regulation by its cytoplasmic adaptor PDZK1.

    Directory of Open Access Journals (Sweden)

    Kosuke Tsukamoto

    Full Text Available BACKGROUND: PDZK1 is a four PDZ-domain containing cytoplasmic protein that binds to a variety of membrane proteins via their C-termini and can influence the abundance, localization and/or function of its target proteins. One of these targets in hepatocytes in vivo is the HDL receptor SR-BI. Normal hepatic expression of SR-BI protein requires PDZK1 - <5% of normal hepatic SR-BI is seen in the livers of PDZK1 knockout mice. Progress has been made in identifying features of PDZK1 required to control hepatic SR-BI in vivo using hepatic expression of wild-type and mutant forms of PDZK1 in wild-type and PDZK1 KO transgenic mice. Such in vivo studies are time consuming and expensive, and cannot readily be used to explore many features of the underlying molecular and cellular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Here we have explored the potential to use either primary rodent hepatocytes in culture using 2D collagen gels with newly developed optimized conditions or PDZK1/SR-BI co-transfected cultured cell lines (COS, HEK293 for such studies. SR-BI and PDZK1 protein and mRNA expression levels fell rapidly in primary hepatocyte cultures, indicating this system does not adequately mimic hepatocytes in vivo for analysis of the PDZK1 dependence of SR-BI. Although PDZK1 did alter SR-BI protein expression in the cell lines, its influence was independent of SR-BI's C-terminus, and thus is not likely to occur via the same mechanism as that which occurs in hepatocytes in vivo. CONCLUSIONS/SIGNIFICANCE: Caution must be exercised in using primary hepatocytes or cultured cell lines when studying the mechanism underlying the regulation of hepatic SR-BI by PDZK1. It may be possible to use SR-BI and PDZK1 expression as sensitive markers for the in vivo-like state of hepatocytes to further improve primary hepatocyte cell culture conditions.

  14. Differential Association of the Na+/H+ Exchanger Regulatory Factor (NHERF Family of Adaptor Proteins with the Raft- and the Non-Raft Brush Border Membrane Fractions of NHE3

    Directory of Open Access Journals (Sweden)

    Ayesha Sultan

    2013-11-01

    Full Text Available Background/Aims: Trafficking, brush border membrane (BBM retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50, NHERF2 (E3KARP, and NHERF3 (PDZK1 with lipid rafts in murine small intestinal BBM. Methods: Detergent resistant membranes (“lipid rafts” were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3- mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results: NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions: The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs.

  15. Correlated Flexible Molecular Coding and Molecular Evolvability

    OpenAIRE

    Husimi, Y; Aita, T.; Tabuchi, I.

    2002-01-01

    Evolvability of biopolymers is based on molecular coding. The molecular coding is represented by biopolymer function vs monomeric sequence relationship, that is, a proper fitness landscape on the sequence space. On the other hand, molecular coding is mostly realized by monomeric sequence vs biopolymer structure relationship. We suggest the evolution of evolvability based on flexible or multiplex coding originating from flexible or polymorphic conformation of evolving biopolymers. We report a ...

  16. Adaptive molecular convergence: Molecular evolution versus molecular phylogenetics

    OpenAIRE

    Castoe, Todd A.; de Koning, A. P. Jason; Pollock, David D.

    2010-01-01

    Definitive identification of convergent evolution, the acquisition of the same biological trait in unrelated lineages, provides one of the most compelling sources of evidence for natural selection. Although numerous examples of convergent morphological evolution are well known (such as the independent development of wings in birds and mammals), cases of convergent evolution at the molecular-genetic level appear to be quite rare. We recently discovered a remarkable case of convergent molecular...

  17. Molecular sensors and molecular logic gates

    International Nuclear Information System (INIS)

    Full text: The rapid grow of nanotechnology field extended the concept of a macroscopic device to the molecular level. Because of this reason the design and synthesis of (supra)-molecular species capable of mimicking the functions of macroscopic devices are currently of great interest. Molecular devices operate via electronic and/or nuclear rearrangements and, like macroscopic devices, need energy to operate and communicate between their elements. The energy needed to make a device work can be supplied as chemical energy, electrical energy, or light. Luminescence is one of the most useful techniques to monitor the operation of molecular-level devices. This fact determinates the synthesis of novel fluorescence compounds as a considerable and inseparable part of nanoscience development. Further miniaturization of semiconductors in electronic field reaches their limit. Therefore the design and construction of molecular systems capable of performing complex logic functions is of great scientific interest now. In semiconductor devices the logic gates work using binary logic, where the signals are encoded as 0 and 1 (low and high current). This process is executable on molecular level by several ways, but the most common are based on the optical properties of the molecule switches encoding the low and high concentrations of the input guest molecules and the output fluorescent intensities with binary 0 and 1 respectively. The first proposal to execute logic operations at the molecular level was made in 1988, but the field developed only five years later when the analogy between molecular switches and logic gates was experimentally demonstrated by de Silva. There are seven basic logic gates: AND, OR, XOR, NOT, NAND, NOR and XNOR and all of them were achieved by molecules, the fluorescence switching as well. key words: fluorescence, molecular sensors, molecular logic gates

  18. Transmembrane adaptor proteins: organizers of immunoreceptor signalling

    Czech Academy of Sciences Publication Activity Database

    Hořejší, Václav; Zhang, W.; Schraven, B.

    2004-01-01

    Roč. 4, č. 8 (2004), s. 603-616. ISSN 1474-1733 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : immunoreceptor * signalling Subject RIV: EC - Immunology Impact factor: 32.695, year: 2004

  19. Advancement of Molecular Morphology

    Institute of Scientific and Technical Information of China (English)

    顾江

    2004-01-01

    @@ Molecular morphology is a new discipline of medical science that studies morphology at the molecular level. This includes the investigation of occurrence and distribution of proteins, peptides, DNA and RNA sequences at the tissue, cellular, and ultrastructural levels.

  20. Basic molecular spectroscopy

    CERN Document Server

    Gorry, PA

    1985-01-01

    BASIC Molecular Spectroscopy discusses the utilization of the Beginner's All-purpose Symbolic Instruction Code (BASIC) programming language in molecular spectroscopy. The book is comprised of five chapters that provide an introduction to molecular spectroscopy through programs written in BASIC. The coverage of the text includes rotational spectra, vibrational spectra, and Raman and electronic spectra. The book will be of great use to students who are currently taking a course in molecular spectroscopy.

  1. Polymer friction Molecular Dynamics

    OpenAIRE

    Sivebæk, Ion Marius; Samoilov, Vladimir N.; Persson, Bo N. J.

    2010-01-01

    We present molecular dynamics friction calculations for confined hydrocarbon solids with molecular lengths from 20 to 1400 carbon atoms. Two cases are considered: a) polymer sliding against a hard substrate, and b) polymer sliding on polymer. In the first setup the shear stresses are relatively independent of molecular length. For polymer sliding on polymer the friction is significantly larger, and dependent on the molecular chain length. In both cases, the shear stresses are proportional to ...

  2. Cardiovascular molecular MR imaging

    OpenAIRE

    Lamb, H J; van der Meer, R. W.; Roos, A. (Anna); Bax, J J

    2007-01-01

    Introduction Cardiovascular molecular imaging is a rapidly evolving field of research, aiming to image and quantify molecular and cellular targets in vivo. MR imaging has some inherent properties that make it very suitable for cardiovascular molecular imaging. Until now, only a limited number of studies have been published on cardiovascular molecular imaging using MR imaging. Review In the current review, MR techniques that have already shown potential are discussed. Metabolic MR imaging can ...

  3. Physical Chemistry of Molecular

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Established in 2009, the group consists of six researchers and more than 70 research assistants and graduate students from the CAS Key Laboratory of Molecular Nanostructures and Nanotechnologies at the CAS Institute of Chemistry.Its research focuses on the physical chemistry involved in molecular assembly, molecular nanostructures, functional nanomaterials and conceptual nano-devices.

  4. Molecular Graphics and Chemistry.

    Science.gov (United States)

    Weber, Jacques; And Others

    1992-01-01

    Explains molecular graphics, i.e., the application of computer graphics techniques to investigate molecular structure, function, and interaction. Structural models and molecular surfaces are discussed, and a theoretical model that can be used for the evaluation of intermolecular interaction energies for organometallics is described. (45…

  5. Engineering molecular machines

    Science.gov (United States)

    Erman, Burak

    2016-04-01

    Biological molecular motors use chemical energy, mostly in the form of ATP hydrolysis, and convert it to mechanical energy. Correlated thermal fluctuations are essential for the function of a molecular machine and it is the hydrolysis of ATP that modifies the correlated fluctuations of the system. Correlations are consequences of the molecular architecture of the protein. The idea that synthetic molecular machines may be constructed by designing the proper molecular architecture is challenging. In their paper, Sarkar et al (2016 New J. Phys. 18 043006) propose a synthetic molecular motor based on the coarse grained elastic network model of proteins and show by numerical simulations that motor function is realized, ranging from deterministic to thermal, depending on temperature. This work opens up a new range of possibilities of molecular architecture based engine design.

  6. Standardized molecular typing.

    Science.gov (United States)

    Müller, F M; Lischewski, A; Harmsen, D; Hacker, J

    1999-01-01

    Molecular typing methods are useful tools in molecular mycology. The results of these biotyping procedures may help to identify pathogenic strains in order to detect sources of nosocomial infection and for the investigation of epidemiological relationships. With respect to the facultative pathogen, Candida albicans, various methods such as pulse-field gel electrophoresis (PFGE), restriction fragment length polymorphism (RFLP), DNA fingerprinting methods and hybridization with repetitive DNA elements have been described as useful tools in molecular epidemiology. The previously described hybridization method with the Candida albicans specific CARE-2 probe and subsequent rehybridization with a molecular size marker is a standardized reproducible typing method for comparison of results obtained in different laboratories. In a larger epidemiological study conducted at the University Hospital of Würzburg analysing clinical C. albicans isolates, we were able to describe relationships between sequential patient isolates. These findings demonstrate that standardized molecular typing methods are a powerful tool in molecular mycology studies. PMID:10865907

  7. Sober Topological Molecular Lattices

    Institute of Scientific and Technical Information of China (English)

    张德学; 李永明

    2003-01-01

    A topological molecular lattice (TML) is a pair (L, T), where L is a completely distributive lattice and r is a subframe of L. There is an obvious forgetful functor from the category TML of TML's to the category Loc of locales. In this note,it is showed that this forgetful functor has a right adjoint. Then, by this adjunction,a special kind of topological molecular lattices called sober topological molecular lattices is introduced and investigated.

  8. Molecular imaging in oncology

    OpenAIRE

    Dzik-Jurasz, A S K

    2004-01-01

    Cancer is a genetic disease that manifests in loss of normal cellular homeostatic mechanisms. The biology and therapeutic modulation of neoplasia occurs at the molecular level. An understanding of these molecular processes is therefore required to develop novel prognostic and early biomarkers of response. In addition to clinical applications, increased impetus for the development of such technologies has been catalysed by pharmaceutical companies investing in the development of molecular ther...

  9. Molecular dynamics simulations

    OpenAIRE

    Tarmyshov, Konstantin B.

    2007-01-01

    Molecular simulations can provide a detailed picture of a desired chemical, physical, or biological process. It has been developed over last 50 years and is being used now to solve a large variety of problems in many different fields. In particular, quantum calculations are very helpful to study small systems at a high resolution where electronic structure of compounds is accounted for. Molecular dynamics simulations, in turn, are employed to study development of a certain molecular ensemble ...

  10. Molecular Epidemiology of Rotaviruses

    OpenAIRE

    Nakagomi, Osamu

    2004-01-01

    Molecular epidemiology of rotaviruses emerged a little over 25 years ago as a fascinating branch of science that utilized then cutting-edge technology of RNA polyacrylamide gel electrophoresis. Molecular epidemiology, as I have observed it closely almost since its dawn, is an ever-evolving discipline which has incorporated the advances of the related sciences including molecular evolutionary biology and ecology, while it is firmly and deeply rooted in the edifice of epidemiology of infectious...

  11. Polymer friction Molecular Dynamics

    DEFF Research Database (Denmark)

    Sivebæk, Ion Marius; Samoilov, Vladimir N.; Persson, Bo N. J.

    We present molecular dynamics friction calculations for confined hydrocarbon solids with molecular lengths from 20 to 1400 carbon atoms. Two cases are considered: a) polymer sliding against a hard substrate, and b) polymer sliding on polymer. In the first setup the shear stresses are relatively...... independent of molecular length. For polymer sliding on polymer the friction is significantly larger, and dependent on the molecular chain length. In both cases, the shear stresses are proportional to the squeezing pressure and finite at zero load, indicating an adhesional contribution to the friction force....

  12. Dense molecular thermodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, J.D.; Shaw, M.S.; Holian, B.L.

    1983-01-01

    We are examining the thermodynamics of dense molecular fluids from the theoretical view. Our interests range from modeling single-species, spherically symmetric, atomic systems, through adding the complication of nonspherical molecular potentials, to mixing various molecular species with the inclusion of chemistry. We discuss what has been accomplished and evaluate the directions to be taken in attacking the unsolved problems. The various theoretical approaches, both analytic and numerical, are presented. We finish with a discussion of the recent advance in treating nonspherical molecular potentials with effective spherical potentials in the calculation of thermodynamics.

  13. Advancement of Molecular Morphology

    Institute of Scientific and Technical Information of China (English)

    顾江

    2004-01-01

    Molecular morphology is a new discipline of medical science that studies morphology at the molecular level. This includes the investigation of occurrence and distribution of proteins, peptides, DNA and RNA sequences at the tissue, cellular, and uhrastructural levels. Morphology is defined as a field of science investigating the shape,

  14. Accelerating Fermionic Molecular Dynamics

    OpenAIRE

    Clark, M. A.; Kennedy, A. D.

    2004-01-01

    We consider how to accelerate fermionic molecular dynamics algorithms by introducing n pseudofermion fields coupled with the nth root of the fermionic kernel. This reduces the maximum pseudofermionic force, and thus allows a larger molecular dynamics integration step size without hitting an instability in the integrator.

  15. Fragment oriented molecular shapes.

    Science.gov (United States)

    Hain, Ethan; Camacho, Carlos J; Koes, David Ryan

    2016-05-01

    Molecular shape is an important concept in drug design and virtual screening. Shape similarity typically uses either alignment methods, which dynamically optimize molecular poses with respect to the query molecular shape, or feature vector methods, which are computationally less demanding but less accurate. The computational cost of alignment can be reduced by pre-aligning shapes, as is done with the Volumetric-Aligned Molecular Shapes (VAMS) method. Here, we introduce and evaluate fragment oriented molecular shapes (FOMS), where shapes are aligned based on molecular fragments. FOMS enables the use of shape constraints, a novel method for precisely specifying molecular shape queries that provides the ability to perform partial shape matching and supports search algorithms that function on an interactive time scale. When evaluated using the challenging Maximum Unbiased Validation dataset, shape constraints were able to extract significantly enriched subsets of compounds for the majority of targets, and FOMS matched or exceeded the performance of both VAMS and an optimizing alignment method of shape similarity search. PMID:27085751

  16. Molecular Engineering of DNA: Molecular Beacons

    OpenAIRE

    Wang, Kemin; Tang, Zhiwen; Yang, Chaoyong James; Kim, Youngmi; Fang, Xiaohong; Li, Wei; Wu, Yanrong; Medley, Colin D.; Cao, Zehui; Jun LI; Colon, Patrick; Lin, Hui; Tan, Weihong

    2009-01-01

    Molecular beacons (MBs) are specifically designed DNA hairpin structures that are widely used as fluorescent probes. Applications of MBs range from genetic screening, biosensor development, biochip construction, and the detection of single-nucleotide polymorphisms to mRNA monitoring in living cells. The inherent signal-transduction mechanism of MBs enables the analysis of target oligonucleotides without the separation of unbound probes. The MB stem–loop structure holds the fluorescence-donor ...

  17. Modeling of molecular properties

    CERN Document Server

    Comba, Peter

    2011-01-01

    Molecular modeling encompasses applied theoretical approaches and computational techniques to model structures and properties of molecular compounds and materials in order to predict and / or interpret their properties. The modeling covered in this book ranges from methods for small chemical to large biological molecules and materials. With its comprehensive coverage of important research fields in molecular and materials science, this is a must-have for all organic, inorganic and biochemists as well as materials scientists interested in applied theoretical and computational chemistry. The 28

  18. Energetics of molecular interfaces

    Directory of Open Access Journals (Sweden)

    David Cahen

    2005-07-01

    Full Text Available Transport of charge carriers through interfaces is crucial to all electronic and optoelectronic devices, in particular devices based on organic molecular films and, especially, monomolecular layers and single molecules. The energetics of molecular interfaces are exceedingly important, therefore, and must be understood in detail so that we can model and control their behavior. This knowledge, however, is not always sufficient, as the very physics of charge carrier transport through molecular interfaces remains, at times, unclear. This article provides an overview of the main issues being researched actively in the field of interfaces involving organic molecules, and points out areas where progress has been made and where basic questions remain unanswered.

  19. Atomic and Molecular Interactions

    International Nuclear Information System (INIS)

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

  20. Are there molecular signatures?

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, W.P.

    1995-10-01

    This report describes molecular signatures and mutational spectrum analysis. The mutation spectrum is defined as the type and location of DNA base change. There are currently about five well documented cases. Mutations and radon-associated tumors are discussed.

  1. Molecular Mechanisms of Preeclampsia

    OpenAIRE

    Vitoratos, N.; Hassiakos, D.; C. Iavazzo

    2012-01-01

    Preeclampsia is one of the leading causes of maternal morbidity/mortality. The pathogenesis of preeclampsia is still under investigation. The aim of this paper is to present the molecular mechanisms implicating in the pathway leading to preeclampsia.

  2. Molecular Gastronomy: An Introduction

    OpenAIRE

    Burke, Roisin; Kelly, Alan L.; This, Hervé

    2016-01-01

    Abstract In the world of food science, Molecular Gastronomy is a term which is relatively new, but describes the convergence of the two long-established core food disciplines, i.e., food science and the art of the chef.

  3. Appendix II. Molecular Analysis

    Science.gov (United States)

    The study of crop evolution, origins, and conservation entails the assessment of genetic variability with and between populations and species at different genetic, evolutionary, and taxonomic hierarchical levels. Molecular biology has greatly increased the amount of data and computational intensity...

  4. Molecular ion photofragment spectroscopy

    International Nuclear Information System (INIS)

    A new molecular ion photofragment spectrometer is described which features a supersonic molecular beam ion source and a radio frequency octapole ion trap interaction region. This unique combination allows several techniques to be applied to the problem of detecting a photon absorption event of a molecular ion. In particular, it may be possible to obtain low resolution survey spectra of exotic molecular ions by using a direct vibrational predissociation process, or by using other more indirect detection methods. The use of the spectrometer is demonstrated by measuring the lifetime of the O2+(4π/sub u/) metastable state which is found to consist of two main components: the 4π/sub 5/2/ and 4π/sub -1/2/ spin components having a long lifetime (approx. 129 ms) and the 4π/sub 3/2/ and 4π/sub 1/2/ spin components having a short lifetime (approx. 6 ms)

  5. Ontologies for molecular biology.

    Science.gov (United States)

    Schulze-Kremer, S

    1998-01-01

    Molecular biology has a communication problem. There are many databases using their own labels and categories for storing data objects and some using identical labels and categories but with a different meaning. A prominent example is the concept "gene" which is used with different semantics by major international genomic databases. Ontologies are one means to provide a semantic repository to systematically order relevant concepts in molecular biology and to bridge the different notions in various databases by explicitly specifying the meaning of and relation between the fundamental concepts in an application domain. Here, the upper level and a database branch of a prospective ontology for molecular biology (OMB) is presented and compared to other ontologies with respect to suitability for molecular biology (http:/(/)igd.rz-berlin.mpg.de/approximately www/oe/mbo.html). PMID:9697223

  6. Nonequilibrium molecular dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hoover, W.G. (California Univ., Davis, CA (USA). Dept. of Applied Science Lawrence Livermore National Lab., CA (USA))

    1990-11-01

    The development of nonequilibrium molecular dynamics is described, with emphasis on massively-parallel simulations involving the motion of millions, soon to be billions, of atoms. Corresponding continuum simulations are also discussed. 14 refs., 8 figs.

  7. Molecular electronic junction transport

    DEFF Research Database (Denmark)

    Solomon, Gemma C.; Herrmann, Carmen; Ratner, Mark

    2012-01-01

    Whenasinglemolecule,oracollectionofmolecules,isplacedbetween two electrodes and voltage is applied, one has a molecular transport junction. We discuss such junctions, their properties, their description, and some of their applications. The discussion is qualitative rather than quantitative......, and focuses on mechanism, structure/function relations, regimes and mechanisms of transport, some molecular regularities, and some substantial challenges facing the field. Because there are many regimes and mechanisms in transport junctions, we will discuss time scales, geometries, and inelastic scattering...

  8. Phylogenetic molecular function annotation

    OpenAIRE

    Barbara E Engelhardt; Jordan, Michael I.; Repo, Susanna T; Brenner, Steven E

    2009-01-01

    It is now easier to discover thousands of protein sequences in a new microbial genome than it is to biochemically characterize the specific activity of a single protein of unknown function. The molecular functions of protein sequences have typically been predicted using homology-based computational methods, which rely on the principle that homologous proteins share a similar function. However, some protein families include groups of proteins with different molecular functions. A phylogenetic ...

  9. Cardiovascular Molecular Imaging

    OpenAIRE

    Khanicheh, Elham

    2009-01-01

    Although there have been significant improvements in the treatment of cardiovascular diseases they still remain the main cause of morbidity and mortality globally. Currently available diagnostic approaches may not be adequate to detect pathologic changes during the early disease stages, which may be valuable for risk stratification and also to assess a response to a therapy. Therefore molecular imaging techniques such as Contrast Enhanced Ultrasound (CEU) molecular imaging to noninvasively i...

  10. MOLECULAR REPLICATOR DYNAMICS

    OpenAIRE

    BÄRBEL M. R. STADLER; Stadler, Peter F

    2003-01-01

    Template-dependent replication at the molecular level is the basis of reproduction in nature. A detailed understanding of the peculiarities of the chemical reaction kinetics associated with replication processes is therefore an indispensible prerequisite for any understanding of evolution at the molecular level. Networks of interacting self-replicating species can give rise to a wealth of different dynamical phenomena, from competitive exclusion to permanent coexistence, from global stability...

  11. Nearby Molecular Hydrogen

    Science.gov (United States)

    Lebrun, F.

    1984-01-01

    If the gas-to-dust ratio is sufficiently uniform throughout the local interstellar medium, galaxy counts may provide a useful probe of the large scale structure of the interstellar gas. This idea substantiated by gamma ray observations led to the discovery of nearby molecular cloud complexes. The reddening studies indicate that one of them lies between 80 and 140 pc from the Sun. From CO observations, its molecular mass is estimated to be a few 1000 stellar mass units.

  12. Towards molecular photochemionics

    OpenAIRE

    Margherita Venturi; Vincenzo Balzani; Roberto Ballardini; Alberto Credi; M. Teresa Gandolfi

    2004-01-01

    In the last few years there has been a great interest in developing electronics at a molecular level (molecular electronics), e.g. to construct miniaturized electric circuits that would be much smaller than the corresponding micron-scale digital logic circuits fabricated on conventional solid-state semiconductor chips. An alternative possibility to the use of electron fluxes as a means for information processing (electronics) is that of using optical beams (photonics), but up until now scarce...

  13. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

    2013-02-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  14. Molecular Programming Pseudo-code Representation to Molecular Electronics

    CERN Document Server

    Pradhan, Manas Ranjan

    2010-01-01

    This research paper is proposing the idea of pseudo code representation to molecular programming used in designing molecular electronics devices. Already the schematic representation of logical gates like AND, OR, NOT etc.from molecular diodes or resonant tunneling diode are available. This paper is setting a generic pseudo code model so that various logic gates can be formulated. These molecular diodes have designed from organic molecules or Bio-molecules. Our focus is on to give a scenario of molecular computation through molecular programming. We have restricted our study to molecular rectifying diode and logic device as AND gate from organic molecules only.

  15. Quantum Molecular Magnetism

    Science.gov (United States)

    Brechet, Sylvain; Reuse, Francois; Maschke, Klaus; Ansermet, Jean-Philippe

    2015-03-01

    Our theoretical description of quantum molecular magnetism is based on the quantum master equations, where the system consists of the electronic spin degrees of freedom and the bath consists of the remaining degrees of freedom. The system is weakly coupled and weakly correlated to the bath, which is at equilibrium on an appropriate time scale. The electrons satisfy the exclusion principle, which requires the tensorial product of the spin and orbital parts of the state to be antisymmetric under permutation. However, the symmetries of the parts of the state taken separately are determined by the irreducible unitary representations of the permutation group. The structure of the quantum master equations is also determined by these representations. The coupling between different isotypic components of the permutation group appearing in the quantum master equations leads to a description of magnetic dissipation at the molecular level and defines molecular spin selection rules. Thus, this theoretical description is expected to bring new and fundamental insight for molecular magnetism. In particular, it is expected to predict the non-trivial deflection of molecular clusters in a field gradient.

  16. Molecular MR imaging

    International Nuclear Information System (INIS)

    Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.)

  17. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  18. Theoretical Molecular Biophysics

    CERN Document Server

    Scherer, Philipp

    2010-01-01

    "Theoretical Molecular Biophysics" is an advanced study book for students, shortly before or after completing undergraduate studies, in physics, chemistry or biology. It provides the tools for an understanding of elementary processes in biology, such as photosynthesis on a molecular level. A basic knowledge in mechanics, electrostatics, quantum theory and statistical physics is desirable. The reader will be exposed to basic concepts in modern biophysics such as entropic forces, phase separation, potentials of mean force, proton and electron transfer, heterogeneous reactions coherent and incoherent energy transfer as well as molecular motors. Basic concepts such as phase transitions of biopolymers, electrostatics, protonation equilibria, ion transport, radiationless transitions as well as energy- and electron transfer are discussed within the frame of simple models.

  19. Molecular pathogenesis of cholangiocarcinoma.

    Science.gov (United States)

    Fava, G; Lorenzini, I

    2012-01-01

    Epidemiological data from the last years show an increasing trend of incidence and mortality of cholangiocarcinoma (CC) worldwide. Many pathophysiologic aspects of this neoplasia are still unknown and need to be fully discovered. However, several progresses were recently made in order to establish the molecular mechanisms involved in the transformation and growth of malignant cholangiocytes. The principal concept that at least seems to be established is that cholangiocarcinogenesis is a multistep cellular process evolving from a normal condition of the epithelial biliary cells through a chronic inflammation status ending with malignant transformation. The bad prognosis related to CC justifies why a better identification of the molecular mechanisms involved in the growth and progression of this cancer is required for the development of effective preventive measures and valid treatment regimens. This Paper describes the scientific progresses made in the last years in defining the molecular pathways implicated in the generation of this devastating disease. PMID:21994887

  20. Molecular mechanisms of cholangiocarcinoma.

    Science.gov (United States)

    Fava, Giammarco

    2010-04-15

    Cholangiocarcinoma (CC), the malignant tumor of the epithelial cells lining the biliary ducts, has undergone a worldwide increase in incidence and mortality. The malignant transformation of the biliary cells originates from a multistep process evolving through chronic inflammation of the biliary tract to CC. In the last few years several advances have been towards understanding and clarifying the molecular mechanisms implicated in the cholangiocarcinogenesis process. However, many pathophysiologic aspects governing the growth of CC are still undefined. The poor prognosis of this tumor underlines the urgent need to codify the underlying molecular mechanisms involved in the growth and progression of CC in order to design effective preventive measures and valid treatment regimens. This review reports on progresses made in the last few years in clarifying the molecular pathways involved in the process of cholangiocarcinogenesis. PMID:21607138

  1. Engines at molecular scales

    CERN Document Server

    Krishnan, R; Krishnan, Raishma

    2004-01-01

    In recent literature there has been a lot of interest in the phenomena of noise induced transport in the absence of an average bias occurring in spatially periodic systems far from equilibrium. One of the main motivations in this area is to understand the mechanism behind the operation of biological motors at molecular scale. These molecular motors convert chemical energy available during the hydrolysis of ATP into mechanical motion to transport cargo and vesicles in living cells with very high reliability, adaptability and efficiency in a very noisy environment. The basic principle behind such a motion, namely the Brownian ratchet principle, has applications in nanotechnology as novel nanoparticle separation devices. Also, the mechanism of ratchet operation finds applications in game theory. Here, we briefly focus on the physical concepts underlying the constructive role of noise in assisting transport at a molecular level. The nature of particle currents, the energetic efficiency of these motors, the entrop...

  2. Molecular effects of radiation

    International Nuclear Information System (INIS)

    The basis of radiobiology based on the effects of radiation in cells and tissues. Though the primary constituents of tissues are DNA and chromosomes, thus we need to know the effects of radiation in its molecular level before going for its effect in tissue level. The most abundant molecule inside the body is water molecule, and any type of radiation effect to water molecule might affect the whole body functionality. Brief knowledge about the effect of radiation in molecular level on the basis of hydrolysis of water; and radiation damage to DNA and chromosome will be helpful to understand the basics of radiobiology. (author)

  3. Molecular cardiovascular imaging

    International Nuclear Information System (INIS)

    Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

  4. Molecular Rotors as Switches

    Directory of Open Access Journals (Sweden)

    Kang L. Wang

    2012-08-01

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

  5. Valency and molecular structure

    CERN Document Server

    Cartmell, E

    1977-01-01

    Valency and Molecular Structure, Fourth Edition provides a comprehensive historical background and experimental foundations of theories and methods relating to valency and molecular structures. In this edition, the chapter on Bohr theory has been removed while some sections, such as structures of crystalline solids, have been expanded. Details of structures have also been revised and extended using the best available values for bond lengths and bond angles. Recent developments are mostly noted in the chapter on complex compounds, while a new chapter has been added to serve as an introduction t

  6. Substructured multibody molecular dynamics.

    Energy Technology Data Exchange (ETDEWEB)

    Grest, Gary Stephen; Stevens, Mark Jackson; Plimpton, Steven James; Woolf, Thomas B. (Johns Hopkins University, Baltimore, MD); Lehoucq, Richard B.; Crozier, Paul Stewart; Ismail, Ahmed E.; Mukherjee, Rudranarayan M. (Rensselaer Polytechnic Institute, Troy, NY); Draganescu, Andrei I.

    2006-11-01

    We have enhanced our parallel molecular dynamics (MD) simulation software LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator, lammps.sandia.gov) to include many new features for accelerated simulation including articulated rigid body dynamics via coupling to the Rensselaer Polytechnic Institute code POEMS (Parallelizable Open-source Efficient Multibody Software). We use new features of the LAMMPS software package to investigate rhodopsin photoisomerization, and water model surface tension and capillary waves at the vapor-liquid interface. Finally, we motivate the recipes of MD for practitioners and researchers in numerical analysis and computational mechanics.

  7. Molecular beam epitaxy

    CERN Document Server

    Pamplin, Brian R

    1980-01-01

    Molecular Beam Epitaxy introduces the reader to the use of molecular beam epitaxy (MBE) in the generation of III-V and IV-VI compounds and alloys and describes the semiconductor and integrated optics reasons for using the technique. Topics covered include semiconductor superlattices by MBE; design considerations for MBE systems; periodic doping structure in gallium arsenide (GaAs); nonstoichiometry and carrier concentration control in MBE of compound semiconductors; and MBE techniques for IV-VI optoelectronic devices. The use of MBE to fabricate integrated optical devices and to study semicond

  8. Synthetic Mechanochemical Molecular Swimmer

    CERN Document Server

    Golestanian, Ramin

    2010-01-01

    A minimal design for a molecular swimmer is proposed that is a based on a mechanochemical propulsion mechanism. Conformational changes are induced by electrostatic actuation when specific parts of the molecule temporarily acquire net charges through catalyzed chemical reactions involving ionic components. The mechanochemical cycle is designed such that the resulting conformational changes would be sufficient for achieving low Reynolds number propulsion. The system is analyzed within the recently developed framework of stochastic swimmers to take account of the noisy environment at the molecular scale. The swimming velocity of the device is found to depend on the concentration of the fuel molecule according to the Michaelis-Menten rule in enzymatic reactions.

  9. SOYBEAN - MOLECULAR ASPECTS OF BREEDING

    OpenAIRE

    Aleksandra Sudarić

    2012-01-01

    The book Soybean: Molecular Aspects of Breedingfocuses recent progress in our understanding of thegenetics and molecular biology of soybean. This book isdivided into four parts and contains 22 chapters. Part I,Molecular Biology and Biotechnology focuses advancesin molecular biology and laboratory procedures thathave been developed recently to manipulate DNA.Part II, Breeding for abiotic stress covers proteomicsapproaches form as a powerful tool for investigatingthe molecular mechanisms of the...

  10. Molecular gastronomy in Spain

    DEFF Research Database (Denmark)

    García-Segovia, P.; Garrido, M. D.; Vercet, A.;

    2014-01-01

    Beyond the overwhelming international success of Ferrán Adria, Spain has been one of the countries with a more active implication in molecular gastronomy as a scientific discipline but also in the use of ingredients, technologies, and equipment from the scientific and technological universe in th...... scientists for facing the future of Spanish gastronomy. © Taylor & Francis Group, LLC....

  11. Molecular theory of capillarity

    CERN Document Server

    Rowlinson, J S

    2002-01-01

    History of thought on molecular origins of surface phenomena offers a critical and detailed examination and assessment of modern theories, focusing on statistical mechanics and application of results in mean-field approximation to model systems. Emphasis on liquid-gas surface, with a focus on liquid-liquid surfaces in the final chapters. 1989 edition.

  12. Molecular dynamics for fermions

    International Nuclear Information System (INIS)

    The time-dependent variational principle for many-body trial states is used to discuss the relation between the approaches of different molecular dynamics models to describe indistinguishable fermions. Early attempts to include effects of the Pauli principle by means of nonlocal potentials as well as more recent models which work with antisymmetrized many-body states are reviewed under these premises. (orig.)

  13. Molecular and macromolecular gastronomy

    Czech Academy of Sciences Publication Activity Database

    Raab, Miroslav

    Praha : Ústav makromolekulární chemie AV ČR, 2010. CL_1. ISBN 978-80-85009-62-0. [Workshop "Career in Polymers" /2./. 23.07.2010-24.07.2010, Praha] Institutional research plan: CEZ:AV0Z40500505 Keywords : molecular and macromolecular gastronomy Subject RIV: CD - Macromolecular Chemistry

  14. Gymnastics of molecular chaperones.

    Science.gov (United States)

    Mayer, Matthias P

    2010-08-13

    Molecular chaperones assist folding processes and conformational changes in many proteins. In order to do so, they progress through complex conformational cycles themselves. In this review, I discuss the diverse conformational dynamics of the ATP-dependent chaperones of the Hsp60, Hsp70, Hsp90, and Hsp100 families. PMID:20705236

  15. Molecular Adsorber Coating

    Science.gov (United States)

    Straka, Sharon; Peters, Wanda; Hasegawa, Mark; Hedgeland, Randy; Petro, John; Novo-Gradac, Kevin; Wong, Alfred; Triolo, Jack; Miller, Cory

    2011-01-01

    A document discusses a zeolite-based sprayable molecular adsorber coating that has been developed to alleviate the size and weight issues of current ceramic puck-based technology, while providing a configuration that more projects can use to protect against degradation from outgassed materials within a spacecraft, particularly contamination-sensitive instruments. This coating system demonstrates five times the adsorption capacity of previously developed adsorber coating slurries. The molecular adsorber formulation was developed and refined, and a procedure for spray application was developed. Samples were spray-coated and tested for capacity, thermal optical/radiative properties, coating adhesion, and thermal cycling. Work performed during this study indicates that the molecular adsorber formulation can be applied to aluminum, stainless steel, or other metal substrates that can accept silicate-based coatings. The coating can also function as a thermal- control coating. This adsorber will dramatically reduce the mass and volume restrictions, and is less expensive than the currently used molecular adsorber puck design.

  16. Molecular epidemiology of ascariasis

    DEFF Research Database (Denmark)

    Betson, Martha; Halstead, Fennella; Nejsum, Peter;

      We are using molecular epidemiology techniques to study the population structure of Ascaris obtained from humans and pigs. Worms were obtained from human hosts on Zanzibar and in Uganda, Bangladesh, Guatemala and Nepal and Ascaris from pigs were collected from in Uganda, Tanzania, Denmark...

  17. Biophysics of molecular gastronomy.

    Science.gov (United States)

    Brenner, Michael P; Sörensen, Pia M

    2015-03-26

    Chefs and scientists exploring biophysical processes have given rise to molecular gastronomy. In this Commentary, we describe how a scientific understanding of recipes and techniques facilitates the development of new textures and expands the flavor palette. The new dishes that result engage our senses in unexpected ways. PAPERCLIP. PMID:25815978

  18. Molecular cluster magnets

    CERN Document Server

    Winpenny, Richard

    2011-01-01

    This work covers new developments in the field of molecular nanomagnetism, complementing previous books in this area (for example the volume by Gatteschi, Sessoli and Villain on Single Molecule Magnets). The book is written by experts in the field and is intended as a compilation of critical reviews of new areas rather than a comprehensive text.

  19. Molecular studies of achondroplasia

    Directory of Open Access Journals (Sweden)

    Nahar Risha

    2009-01-01

    Full Text Available Background: Achondroplasia (ACH is the most frequent form of short-limbed dwarfi sm, caused by mutations in the FGFR3 gene. It follows an autosomal dominant inheritance, though most cases are sporadic. The molecular techniques are the only available methods to confi rm the diagnosis of a skeletal dysplasia. Clinical and radiological features are only suggestive and not confi rmatory. The present study was conducted to fi nd out how often the clinical diagnosis of achondroplasia is verifi ed on molecular studies. Materials and Methods: From 1998 through 2007, we carried out molecular analysis for the two common mutations in the FGFR3 gene in 130 cases clinically suspected to have ACH. Results: A diagnostic mutation was identifi ed in 53 (40.8% cases. The common mutation (1138G>A was present in 50 (94.7% of the positive cases, while the rare 1138 G>C substitution was found in three (5.3%. Conclusion: This study shows that confi rmation of clinical diagnosis of ACH by molecular genetic testing is essential to distinguish it from other skeletal dysplasias, to plan therapeutic options, and to offer genetic counseling. Management (medical and surgical in patients confi rmed to have ACH, is briefl y discussed.

  20. Molecular Programming Pseudo-code Representation to Molecular Electronics

    OpenAIRE

    Pradhan, Manas Ranjan; E G Rajan

    2010-01-01

    This research paper is proposing the idea of pseudo code representation to molecular programming used in designing molecular electronics devices. Already the schematic representation of logical gates like AND, OR, NOT etc.from molecular diodes or resonant tunneling diode are available. This paper is setting a generic pseudo code model so that various logic gates can be formulated. These molecular diodes have designed from organic molecules or Bio-molecules. Our focus is on to give a scenario ...

  1. Molecular and Cellular Signaling

    CERN Document Server

    Beckerman, Martin

    2005-01-01

    A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

  2. Molecular mechanisms in gliomagenesis

    DEFF Research Database (Denmark)

    Hulleman, Esther; Helin, Kristian

    2005-01-01

    , in order to design novel therapies and treatments for GBM, research has recently intensified to identify the cellular and molecular mechanisms leading to GBM formation. Modeling of astrocytomas by genetic manipulation of mice suggests that deregulation of the pathways that control gliogenesis during...... pathways. The expression of several of the components of these signaling cascades has been found altered in GBM, and recent data indicate that combinations of mutations in these pathways may contribute to GBM formation, although the exact mechanisms are still to be uncovered. Use of novel techniques...... including large-scale genomics and proteomics in combination with relevant mouse models will most likely provide novel insights into the molecular mechanisms underlying glioma formation and will hopefully lead to development of treatment modalities for GBM....

  3. Wholly Synthetic Molecular Machines.

    Science.gov (United States)

    Cheng, Chuyang; Stoddart, J Fraser

    2016-06-17

    The past quarter of a century has witnessed an increasing engagement on the part of physicists and chemists in the design and synthesis of molecular machines de novo. This minireview traces the development of artificial molecular machines from their prototypes in the form of shuttles and switches to their emergence as motors and pumps where supplies of energy in the form of chemical fuel, electrochemical potential and light activation become a minimum requirement for them to function away from equilibrium. The challenge facing this rapidly growing community of scientists and engineers today is one of putting wholly synthetic molecules to work, both individually and as collections. Here, we highlight some of the recent conceptual and practical advances relating to the operation of wholly synthetic rotary and linear motors. PMID:26833859

  4. FORT Molecular Ecology Laboratory

    Science.gov (United States)

    Oyler-McCance, Sara J.; Stevens, P.D.

    2011-01-01

    The mission of the U.S. Geological Survey (USGS) at the Fort Collins Science Center Molecular Ecology Laboratory is to use the tools and concepts of molecular genetics to address a variety of complex management questions and conservation issues facing the management of the Nation's fish and wildlife resources. Together with our partners, we design and implement studies to document genetic diversity and the distribution of genetic variation among individuals, populations, and species. Information from these studies is used to support wildlife-management planning and conservation actions. Current and past studies have provided information to assess taxonomic boundaries, inform listing decisions made under the Endangered Species Act, identify unique or genetically depauperate populations, estimate population size or survival rates, develop management or recovery plans, breed wildlife in captivity, relocate wildlife from one location to another, and assess the effects of environmental change.

  5. Interactive molecular dynamics

    CERN Document Server

    Schroeder, Daniel V

    2015-01-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in HTML5 and JavaScript for running within any modern Web browser, is provided as an online supplement.

  6. Interactive molecular dynamics

    Science.gov (United States)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

  7. Welding Molecular Crystals.

    Science.gov (United States)

    Adolf, Cyril R R; Ferlay, Sylvie; Kyritsakas, Nathalie; Hosseini, Mir Wais

    2015-12-16

    Both for fundamental and applied sciences, the design of complex molecular systems in the crystalline phase with strict control of order and periodicity at both microscopic and macroscopic levels is of prime importance for development of new solid-state materials and devices. The design and fabrication of complex crystalline systems as networks of crystals displaying task-specific properties is a step toward smart materials. Here we report on isostructural and almost isometric molecular crystals of different colors, their use for fabrication of core-shell crystals, and their welding by 3D epitaxial growth into networks of crystals as single-crystalline entities. Welding of crystals by self-assembly processes into macroscopic networks of crystals is a powerful strategy for the design of hierarchically organized periodic complex architectures composed of different subdomains displaying targeted characteristics. Crystal welding may be regarded as a first step toward the design of new hierarchically organized complex crystalline systems. PMID:26581391

  8. Mesoporous molecular sieve catalysts

    DEFF Research Database (Denmark)

    Højholt, Karen Thrane

    the micropores. Furthermore, preliminary work was done using mesoporous ZSM-5 zeolites as support material for anchoring molecular CoMo6 species for the application as potential bi-functional catalyst in simultaneous hydrodesulfurisation (HDS) and hydrocracking. HDS activity tests revealed that the...... of different catalytic applications. Primarily the zeolites were modified regarding the porosity and the introduction of metals to the framework. The obtained materials were used as solid acid catalysts, as an inert matrix for stabilising metal nanoparticles and as an anchoring material for molecular...... only be used as solid acid catalysts but can also be used as a size-selective matrix. It was shown that it is possible to encapsulate 1-2 nm sized gold nanoparticles by silicalite-1 or ZSM-5 zeolite crystals thereby forming a sintering-stable and substrate size-selective oxidation catalyst. After...

  9. Topology in Molecular Biology

    CERN Document Server

    Monastyrsky, Michail Ilych

    2007-01-01

    The book presents a class of new results in molecular biology for which topological methods and ideas are important. These include: the large-scale conformation properties of DNA; computational methods (Monte Carlo) allowing the simulation of large-scale properties of DNA; the tangle model of DNA recombination and other applications of Knot theory; dynamics of supercoiled DNA and biocatalitic properties of DNA; the structure of proteins; and other very recent problems in molecular biology. The text also provides a short course of modern topology intended for the broad audience of biologists and physicists. The authors are renowned specialists in their fields and some of the new results presented here are documented for the first time in monographic form.

  10. Communication: Molecular gears.

    Science.gov (United States)

    Burnell, E Elliott; de Lange, Cornelis A; Meerts, W Leo

    2016-09-01

    The (1)H nuclear magnetic resonance spectrum of hexamethylbenzene orientationally ordered in the nematic liquid crystal ZLI-1132 is analysed using covariance matrix adaptation evolution strategy. The spectrum contains over 350 000 lines with many overlapping transitions, from which four independent direct dipolar couplings are obtained. The rotations of the six methyl groups appear to be correlated due to mutual steric hindrance. Adjacent methyl groups show counter-rotating or geared motion. Hexamethylbenzene thus behaves as a molecular hexagonal gear. PMID:27608981

  11. Molecular-beam scattering

    Energy Technology Data Exchange (ETDEWEB)

    Vernon, M.F.

    1983-07-01

    The molecular-beam technique has been used in three different experimental arrangements to study a wide range of inter-atomic and molecular forces. Chapter 1 reports results of a low-energy (0.2 kcal/mole) elastic-scattering study of the He-Ar pair potential. The purpose of the study was to accurately characterize the shape of the potential in the well region, by scattering slow He atoms produced by expanding a mixture of He in N/sub 2/ from a cooled nozzle. Chapter 2 contains measurements of the vibrational predissociation spectra and product translational energy for clusters of water, benzene, and ammonia. The experiments show that most of the product energy remains in the internal molecular motions. Chapter 3 presents measurements of the reaction Na + HCl ..-->.. NaCl + H at collision energies of 5.38 and 19.4 kcal/mole. This is the first study to resolve both scattering angle and velocity for the reaction of a short lived (16 nsec) electronic excited state. Descriptions are given of computer programs written to analyze molecular-beam expansions to extract information characterizing their velocity distributions, and to calculate accurate laboratory elastic-scattering differential cross sections accounting for the finite apparatus resolution. Experimental results which attempted to determine the efficiency of optically pumping the Li(2/sup 2/P/sub 3/2/) and Na(3/sup 2/P/sub 3/2/) excited states are given. A simple three-level model for predicting the steady-state fraction of atoms in the excited state is included.

  12. Genetic and molecular epidemiology

    OpenAIRE

    John P A Ioannidis

    2007-01-01

    Genetic and molecular epidemiology covers a vast area of research. Given the rapid changes in this field, discussing a research agenda is a precarious and ambitious task. A representative set of high‐priority concepts will be presented here, each of which alone could be the topic of a long series of essays. The wish list includes issues of full transparency and integration of information, dealing efficiently with complex multidimensional biology, juxtaposing the genome and environmental expos...

  13. Molecular Information Technology

    OpenAIRE

    Zauner, Klaus-Peter

    2005-01-01

    Molecular materials are endowed with unique properties of unrivaled potential for high density integration of computing systems. Present applications of molecules range from organic semiconductor materials for low-cost circuits to genetically modified proteins for commercial imaging equipment. To fully realize the potential of molecules in computation, information processing concepts that relinquish narrow prescriptive control over elementary structures and functions are needed, and self-orga...

  14. Switching in molecular systems

    Czech Academy of Sciences Publication Activity Database

    Nešpůrek, Stanislav; Wang, Geng; Sworakowski, J.

    Lanškroun : IMAPS, Brno University of Technology, 2004 - (Šikula, J.), s. 215-220 ISBN 80-239-2835-X. [European Microelectronics and Packaging Symposium /3./. Prague (CZ), 16.06.2004-18.06.2004] R&D Projects: GA MŠk OC D14.30 Institutional research plan: CEZ:AV0Z4050913 Keywords : poly[3,4-(ethylenedioxy)thiophene] * electrical conductivity * charge carrier transport Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  15. Molecular Dynamics of Acetylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Shen, T Y.; Tai, Kaihsu; Henchman, Richard H.; Mccammon, Andy

    2002-06-01

    Molecular dynamics simulations are leading to a deeper understanding of the activity of the enzyme acetylcholinesterase. Simulations have shown how breathing motions in the enzyme facilitate the displacement of substrate from the surface of the enzyme to the buried active site. The most recent work points to the complex and spatially extensive nature of such motions and suggests possible modes of regulation of the activity of the enzyme.

  16. Glycobiology Current Molecular Biology

    OpenAIRE

    Sabire KARAÇALI

    2003-01-01

    Carbohydrate chemistry evolved into carbohydrate biochemistry and gradually into the biology of carbohydrates, or glycobiology, at the end of the last century. Glycobiology is the new research area of modern molecular biology, and it investigates the structure, biosynthesis and biological functions of glycans. The numbers, linkage types (a or b), positions, binding points and functional group differences of monosaccharides create microheterogeneity. Thus, numerous glycoforms with precise stru...

  17. Molecular opacities for exoplanets.

    Science.gov (United States)

    Bernath, Peter F

    2014-04-28

    Spectroscopic observations of exoplanets are now possible by transit methods and direct emission. Spectroscopic requirements for exoplanets are reviewed based on existing measurements and model predictions for hot Jupiters and super-Earths. Molecular opacities needed to simulate astronomical observations can be obtained from laboratory measurements, ab initio calculations or a combination of the two approaches. This discussion article focuses mainly on laboratory measurements of hot molecules as needed for exoplanet spectroscopy. PMID:24664921

  18. Atomic and molecular theory

    Energy Technology Data Exchange (ETDEWEB)

    Inokuti, Mitio.

    1990-01-01

    The multifaceted role of theoretical physics in understanding the earliest stages of radiation action is discussed. Scientific topics chosen for the present discourse include photoabsorption, electron collisions, and ionic collisions, and electron transport theory, Connections of atomic and molecular physics with condensed-matter physics are also discussed. The present article includes some historical perspective and an outlook for the future. 114 refs., 3 figs.

  19. Molecular opacities for exoplanets

    OpenAIRE

    Bernath, Peter F.

    2014-01-01

    Spectroscopic observations of exoplanets are now possible by transit methods and direct emission. Spectroscopic requirements for exoplanets are reviewed based on existing measurements and model predictions for hot Jupiters and super-Earths. Molecular opacities needed to simulate astronomical observations can be obtained from laboratory measurements, ab initio calculations or a combination of the two approaches. This discussion article focuses mainly on laboratory measurements of hot molecules...

  20. Exploring guanidinoglycoside molecular transporters

    OpenAIRE

    Dix, Andrew Vincent

    2011-01-01

    Guanidinium-rich molecular transporters have been shown to deliver otherwise non-permeable biologically relevant cargo into cells. While many such transporters have been reported, the studies reported here focus on guanidinoglycosides, which have been shown to permeate the cell-membrane in a heparan sulfate-dependent manner. In attempt to promote a cooperative interaction with cell- surface heparan sulfate, dimeric guanidinoglycosides were synthesized and studied for their cellular uptake pro...

  1. Molecular Aspects of Capacitation

    OpenAIRE

    Gulfidan Zulfikaroglu; Hulya Ozgur; Sait Polaturkey

    2010-01-01

    Male and female gamets are derived from the primordial germ cells, which migrate from the wall of the yolk sac toward the developing gonads. Following a series of mitotic divisions these cells increase in number at the gonads. The primordial germ cells differentiate into spermatogonia and take the form of mature spermatozoa after spermotogensis and spermotogenesis at puberty. Capacitation is the reaction, which includes all of the molecular and physiological events of mature sperm to gain the...

  2. Molecular Pathogenesis of Cholangiocarcinoma

    OpenAIRE

    Fava, G.; Lorenzini, I.

    2011-01-01

    Epidemiological data from the last years show an increasing trend of incidence and mortality of cholangiocarcinoma (CC) worldwide. Many pathophysiologic aspects of this neoplasia are still unknown and need to be fully discovered. However, several progresses were recently made in order to establish the molecular mechanisms involved in the transformation and growth of malignant cholangiocytes. The principal concept that at least seems to be established is that cholangiocarcinogenesis is a multi...

  3. Molecular mechanisms of cholangiocarcinoma

    OpenAIRE

    Fava, Giammarco

    2010-01-01

    Cholangiocarcinoma (CC), the malignant tumor of the epithelial cells lining the biliary ducts, has undergone a worldwide increase in incidence and mortality. The malignant transformation of the biliary cells originates from a multistep process evolving through chronic inflammation of the biliary tract to CC. In the last few years several advances have been towards understanding and clarifying the molecular mechanisms implicated in the cholangiocarcinogenesis process. However, many pathophysio...

  4. Primer on molecular genetics

    Energy Technology Data Exchange (ETDEWEB)

    1992-04-01

    This report is taken from the April 1992 draft of the DOE Human Genome 1991--1992 Program Report, which is expected to be published in May 1992. The primer is intended to be an introduction to basic principles of molecular genetics pertaining to the genome project. The material contained herein is not final and may be incomplete. Techniques of genetic mapping and DNA sequencing are described.

  5. MOLECULARLY IMPRINTED POLYMERS

    OpenAIRE

    Hall, Andrew J.

    2014-01-01

    The present invention refers to new classes of polymerisable monomers targeting biotin, a biotin derivative, a biotin analogue or a biotinylated molecule and related structures, as well as molecularly imprinted polymers obtainable by polymerisation of at least one of these monomers and at least one cross-linking monomer in the presence of a suitable template molecule. The obtained polymers may be used for separation of biotin and related small molecules, together with larger biotinylated mole...

  6. Molecular studies of achondroplasia

    OpenAIRE

    Nahar Risha; Saxena Renu; Kohli Sudha; Puri Ratna; Verma Ishwar

    2009-01-01

    Background: Achondroplasia (ACH) is the most frequent form of short-limbed dwarfi sm, caused by mutations in the FGFR3 gene. It follows an autosomal dominant inheritance, though most cases are sporadic. The molecular techniques are the only available methods to confi rm the diagnosis of a skeletal dysplasia. Clinical and radiological features are only suggestive and not confi rmatory. The present study was conducted to fi nd out how often the clinical diagnosis of achondroplasia is verifi ed ...

  7. Molecular Simulations of Dewetting

    OpenAIRE

    Koplik, Joel; Banavar, Jayanth R.

    1999-01-01

    We have studied the breakup and subsequent fluid flow in very thin films of partially wetting liquid on solid substrates, using molecular dynamics simulations. The liquid is made of short chain molecules interacting with Lennard-Jones interactions, and the solid is modeled as a clean crystal lattice whose atoms have thermal oscillations. Films below a critical thickness are found to exhibit a spontaneous spinodal-like instability leading to dry patches, as predicted theoretically and observed...

  8. Untying molecular friction knots

    OpenAIRE

    Kirmizialtin, Serdal; Makarov, Dmitrii E.

    2006-01-01

    Motivated by recent advances in single molecule manipulation techniques that enabled several groups to tie knots in individual polymer strands and to monitor their dynamics, we have used computer simulations to study "friction knots" joining a pair of polymer strands. The key property of a friction knot splicing two ropes is that it becomes jammed when the ropes are pulled apart. In contrast, molecular friction knots eventually become undone by thermal motion. We show that depending on the kn...

  9. Molecular diagnostics in endodontics

    OpenAIRE

    Rechenberg, Dan-Krister; Zehnder, Matthias

    2014-01-01

    Recent systematic reviews have substantiated the fact that current testing methods to assess the inflammatory state of the pulp and the periapical tissues are of limited value. Consequently, it may be time to search for alternative routes in endodontic diagnostics. Molecular assessment methods could be the future. However, in the field of endodontics, the research in that direction is only about to evolve. Because pulpal and periradicular diseases are related to opportunistic infections, diag...

  10. Atomic and molecular theory

    International Nuclear Information System (INIS)

    The multifaceted role of theoretical physics in understanding the earliest stages of radiation action is discussed. Scientific topics chosen for the present discourse include photoabsorption, electron collisions, and ionic collisions, and electron transport theory, Connections of atomic and molecular physics with condensed-matter physics are also discussed. The present article includes some historical perspective and an outlook for the future. 114 refs., 3 figs

  11. Open boundary molecular dynamics

    Science.gov (United States)

    Delgado-Buscalioni, R.; Sablić, J.; Praprotnik, M.

    2015-09-01

    This contribution analyzes several strategies and combination of methodologies to perform molecular dynamic simulations in open systems. Here, the term open indicates that the total system has boundaries where transfer of mass, momentum and energy can take place. This formalism, which we call Open Boundary Molecular Dynamics (OBMD), can act as interface of different schemes, such as Adaptive Resolution Scheme (AdResS) and Hybrid continuum-particle dynamics to link atomistic, coarse-grained (CG) and continuum (Eulerian) fluid dynamics in the general framework of fluctuating Navier-Stokes equations. The core domain of the simulation box is solved using all-atom descriptions. The CG layer introduced using AdResS is located at the outer part of the open box to make feasible the insertion of large molecules into the system. Communications between the molecular system and the outer world are carried out in the outer layers, called buffers. These coupling preserve momentum and mass conservation laws and can thus be linked with Eulerian hydro- dynamic solvers. In its simpler form, OBMD allows, however, to impose a local pressure tensor and a heat flux across the system's boundaries. For a one component molecular system, the external normal pressure and temperature determine the external chemical potential and thus the independent parameters of a grand-canonical ensemble simulation. Extended ensembles under non-equilibrium stationary states can also be simulated as well as time dependent forcings (e.g. oscillatory rheology). To illustrate the robustness of the combined OBMD-AdResS method, we present simulations of star-polymer melts at equilibrium and in sheared flow.

  12. Molecular-beam scattering

    International Nuclear Information System (INIS)

    The molecular-beam technique has been used in three different experimental arrangements to study a wide range of inter-atomic and molecular forces. Chapter 1 reports results of a low-energy (0.2 kcal/mole) elastic-scattering study of the He-Ar pair potential. The purpose of the study was to accurately characterize the shape of the potential in the well region, by scattering slow He atoms produced by expanding a mixture of He in N2 from a cooled nozzle. Chapter 2 contains measurements of the vibrational predissociation spectra and product translational energy for clusters of water, benzene, and ammonia. The experiments show that most of the product energy remains in the internal molecular motions. Chapter 3 presents measurements of the reaction Na + HCl → NaCl + H at collision energies of 5.38 and 19.4 kcal/mole. This is the first study to resolve both scattering angle and velocity for the reaction of a short lived (16 nsec) electronic excited state. Descriptions are given of computer programs written to analyze molecular-beam expansions to extract information characterizing their velocity distributions, and to calculate accurate laboratory elastic-scattering differential cross sections accounting for the finite apparatus resolution. Experimental results which attempted to determine the efficiency of optically pumping the Li(22P/sub 3/2/) and Na(32P/sub 3/2/) excited states are given. A simple three-level model for predicting the steady-state fraction of atoms in the excited state is included

  13. Molecular Gastronomy in Ireland

    OpenAIRE

    Burke, Roisin; Traynor, Mark; Valverde, Juan

    2011-01-01

    This article summarizes the activities of molecular gastronomy (MG) in Ireland since the scientific discipline was first introduced in the country. MG has been developing over the last five years,however, the authors of this article have been trying to establish a strong MG infrastructure in Ireland. Indeed, a lot of work still needs to be done, but public interest and positive perceptions of“chemistry” have increased very quickly; consequently, there is great potential for further developmen...

  14. Molecular current switch

    Czech Academy of Sciences Publication Activity Database

    Nešpůrek, Stanislav; Sworakowski, J.

    Brno : Faculty of Chemistry, Brno University of Technology, 2002 - (Schauer, F.), s. 89-96 ISBN 80-214-2265-3. [Seminar on Physics and Chemistry of Molecular Systems /7./. Brno (CZ), 13.12.2001] R&D Projects: GA AV ČR IAA1050901; GA ČR GA202/01/0518 Institutional research plan: CEZ:AV0Z4050913 Keywords : current switch * local states * dipolar species Subject RIV: BM - Solid Matter Physics ; Magnetism

  15. Molecular adsorption on graphene

    Science.gov (United States)

    Kong, Lingmei; Enders, Axel; Rahman, Talat S.; Dowben, Peter A.

    2014-11-01

    Current studies addressing the engineering of charge carrier concentration and the electronic band gap in epitaxial graphene using molecular adsorbates are reviewed. The focus here is on interactions between the graphene surface and the adsorbed molecules, including small gas molecules (H2O, H2, O2, CO, NO2, NO, and NH3), aromatic, and non-aromatic molecules (F4-TCNQ, PTCDA, TPA, Na-NH2, An-CH3, An-Br, Poly (ethylene imine) (PEI), and diazonium salts), and various biomolecules such as peptides, DNA fragments, and other derivatives. This is followed by a discussion on graphene-based gas sensor concepts. In reviewing the studies of the effects of molecular adsorption on graphene, it is evident that the strong manipulation of graphene’s electronic structure, including p- and n-doping, is not only possible with molecular adsorbates, but that this approach appears to be superior compared to these exploiting edge effects, local defects, or strain. However, graphene-based gas sensors, albeit feasible because huge adsorbate-induced variations in the relative conductivity are possible, generally suffer from the lack of chemical selectivity.

  16. Molecular biology of hearing [

    Directory of Open Access Journals (Sweden)

    Diensthuber, Marc

    2012-04-01

    Full Text Available [english] The inner ear is our most sensitive sensory organ and can be subdivided into three functional units: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound, which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear houses the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In recent years there has been significant progress in research on the molecular basis of hearing. An increasing number of genes and proteins related to hearing are being identified and characterized. The growing knowledge of these genes contributes not only to greater appreciation of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss.

  17. Orbital free molecular dynamics

    International Nuclear Information System (INIS)

    The microscopic properties of hot and dense plasmas stay a field essentially studied thanks to classical theories like the One Component Plasma, models which rely on free parameters, particularly ionization. In order to investigate these systems, we have used, in this PhD work, a semi-classical model, without free parameters, that is based on coupling consistently classical molecular dynamics for the nuclei and orbital free density functional theory for the electrons. The electronic fluid is represented by a free energy entirely determined by the local density. This approximation was validated by a comparison with an ab initio technique, quantum molecular dynamics. This one is identical to the previous except for the description of the free energy that depends on a quantum-independent-particle model. Orbital free molecular dynamics was then used to compute equation of state of boron and iron plasmas in the hot and dense regime. Furthermore, comparisons with classical theories were performed on structural and dynamical properties. Finally, equation of state and transport coefficients mixing laws were studied by direct simulation of a plasma composed of deuterium and copper. (author)

  18. Molecular Basis of Phosphatidylinositol 4-Phosphate and ARF1 GTPase Recognition by the FAPP1 Pleckstrin Homology (PH) Domain

    Energy Technology Data Exchange (ETDEWEB)

    He, J.; Heroux, A.; Scott, J. L.; Roy, S.; Lenoir, M.; Overduin, M.; Stahelin, R. V.; Kutateladze, T. G.

    2011-05-27

    Four-phosphate-adaptor protein 1 (FAPP1) regulates secretory transport from the trans-Golgi network (TGN) to the plasma membrane. FAPP1 is recruited to the Golgi through binding of its pleckstrin homology (PH) domain to phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor 1 (ARF1). Despite the critical role of FAPP1 in membrane trafficking, the molecular basis of its dual function remains unclear. Here, we report a 1.9 {angstrom} resolution crystal structure of the FAPP1 PH domain and detail the molecular mechanisms of the PtdIns(4)P and ARF1 recognition. The FAPP1 PH domain folds into a seven-stranded {beta}-barrel capped by an {alpha}-helix at one edge, whereas the opposite edge is flanked by three loops and the {beta}4 and {beta}7 strands that form a lipid-binding pocket within the {beta}-barrel. The ARF1-binding site is located on the outer side of the {beta}-barrel as determined by NMR resonance perturbation analysis, mutagenesis, and measurements of binding affinities. The two binding sites have little overlap, allowing FAPP1 PH to associate with both ligands simultaneously and independently. Binding to PtdIns(4)P is enhanced in an acidic environment and is required for membrane penetration and tubulation activity of FAPP1, whereas the GTP-bound conformation of the GTPase is necessary for the interaction with ARF1. Together, these findings provide structural and biochemical insight into the multivalent membrane anchoring by the PH domain that may augment affinity and selectivity of FAPP1 toward the TGN membranes enriched in both PtdIns(4)P and GTP-bound ARF1.

  19. Thermoelectric properties of molecular nanostructures

    OpenAIRE

    Ermakov, Vladimir N.; Kruchinin, Sergei P.; Kim, Hyun Taki; Pruschke, Thomas

    2011-01-01

    We use the concept of resonant tunneling to calculate the thermopower of molecular nanosystems. It turns out that the sign of the thermovoltage under resonant tunneling conditions depends sensitively on the participating molecular orbital, and one finds a sign change when the transport channel switches from the highest occupied molecular orbital to the lowest unoccupied molecular orbital. Comparing our results to recent experimental data obtained for a BDT molecule contacted with an STM tip, ...

  20. An improved molecular connectivity index

    Institute of Scientific and Technical Information of China (English)

    李新华; 俞庆森; 朱龙观

    2000-01-01

    Through modification of the delta values of the molecular connectivity indexes, and connecting the quantum chemistry with topology method effectively, the molecular connectivity indexes are converted into quantum-topology indexes. The modified indexes not only keep all information obtained from the original molecular connectivity method but also have their own virtue in application, and at the same time make up some disadvantages of the quantum and molecular connectivity methods.

  1. SOYBEAN - MOLECULAR ASPECTS OF BREEDING

    OpenAIRE

    Aleksandra Sudarić

    2012-01-01

    The book Soybean: Molecular Aspects of Breeding focuses recent progress in our understanding of the genetics and molecular biology of soybean. This book is divided into four parts and contains 22 chapters. Part I, Molecular Biology and Biotechnology focuses advances in molecular biology and laboratory procedures that have been developed recently to manipulate DNA. Part II, Breeding for abiotic stress covers proteomics approaches form as a powerful tool for investigatin...

  2. A Molecular Biology Database Digest

    OpenAIRE

    Bry, François; Kröger, Peer

    2000-01-01

    Computational Biology or Bioinformatics has been defined as the application of mathematical and Computer Science methods to solving problems in Molecular Biology that require large scale data, computation, and analysis [18]. As expected, Molecular Biology databases play an essential role in Computational Biology research and development. This paper introduces into current Molecular Biology databases, stressing data modeling, data acquisition, data retrieval, and the integration...

  3. Chaos Behaviour of Molecular Orbit

    Institute of Scientific and Technical Information of China (English)

    LIU Shu-Tang; SUN Fu-Yan; SHEN Shu-Lan

    2007-01-01

    Based on H(u)ckel's molecular orbit theory,the chaos and;bifurcation behaviour of a molecular orbit modelled by a nonlinear dynamic system is studied.The relationship between molecular orbit and its energy level in the nonlinear dynamic system is obtained.

  4. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

    This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

  5. Molecular collision theory

    CERN Document Server

    Child, M S

    2010-01-01

    This high-level monograph offers an excellent introduction to the theory required for interpretation of an increasingly sophisticated range of molecular scattering experiments. There are five helpful appendixes dealing with continuum wavefunctions, Green's functions, semi-classical connection formulae, curve-crossing in the momentum representation, and elements of classical mechanics.The contents of this volume have been chosen to emphasize the quantum mechanical and semi-classical nature of collision events, with little attention given to purely classical behavior. The treatment is essentiall

  6. NMR molecular photography

    OpenAIRE

    Khitrin, Anatoly K.; Ermakov, Vladimir L.; Fung, B M

    2002-01-01

    A procedure is described for storing a 2D pattern consisting of 32x32 = 1024 bits in a spin state of a molecular system and then retrieving the stored information as a stack of NMR spectra. The system used is a nematic liquid crystal, the protons of which act as spin clusters with strong intramolecular interactions. The technique used is a programmable multi-frequency irradiation with low amplitude. When it is applied to the liquid crystal, a large number of coherent long-lived 1H response si...

  7. Handbook of molecular plasmonics

    CERN Document Server

    Sala, Fabio Della

    2013-01-01

    While several reviews and books on surface nanophotonics and fluorescence spectroscopy are available, an updated focus on molecular plasmonics, including both theoretical methods and experimental aspects, is still lacking. This handbook is a comprehensive overview on the physics of the plasmon-emitter interaction, ranging from electromagnetism to quantum mechanics, from metal-enhanced fluorescence to surface-enhanced Raman scattering, from optical microscopy to synthesis of metal nanoparticles, filling the gap in the literature of this merging field. It allows experimentalists to have a solid

  8. Bienvenida la Medicina Molecular

    OpenAIRE

    Orlando R. Serrano-Barrera

    2015-01-01

    No ha cambiado la medicina, sino que ha avanzado. Los métodos clínico-epidemiológicos  incluyen hoy y se benefician del conocimiento de las bases moleculares del proceso salud-enfermedad, tanto las variaciones individuales, como los caracteres compartidos por comunidades y poblaciones, que las hacen resistentes o vulnerables a una enfermedad. La estimación presintomática e, incluso, prenatal del riesgo de enfermar, el diagnóstico, el pronóstico, la elección del tratamiento más ajustado al pac...

  9. The nonequilibrium molecular dynamics

    International Nuclear Information System (INIS)

    MOLECULAR DYNAMICS has been generalized in order to simulate a variety of NONEQUILIBRIUM systems. This generalization has been achieved by adopting microscopic mechanical definitions of macroscopic thermodynamic and hydrodynamic variables, such as temperature and stress. Some of the problems already treated include rapid plastic deformation, intense heat conduction, strong shockwaves simulation, and far-from-equilibrium phase transformations. Continuing advances in technique and in the modeling of interatomic forces, coupled with qualitative improvements in computer hardware, are enabling such simulations to approximate real-world microscale and nanoscale experiments

  10. Molecular water oxidation catalysis

    CERN Document Server

    Llobet, Antoni

    2014-01-01

    Photocatalytic water splitting is a promising strategy for capturing energy from the sun by coupling light harvesting and the oxidation of water, in order to create clean hydrogen fuel. Thus a deep knowledge of the water oxidation catalysis field is essential to be able to come up with useful energy conversion devices based on sunlight and water splitting. Molecular Water Oxidation Catalysis: A Key Topic for New Sustainable Energy Conversion Schemes presents a comprehensive and state-of-the-art overview of water oxidation catalysis in homogeneous phase, describing in detail the most importan

  11. Nuclear molecular states

    International Nuclear Information System (INIS)

    The effects of polarization on the stability of α-cluster structures in 8Be and 12C nuclei are studied in the intrinsic states. The extent of the polarization of α-clusters is investigated by employing a molecular-orbital model. Two α-cluster structure of 8Be is shown to be extremely stable, and a triangular configuration of three α-clusters is also shown to be stable, but the polarizations of α-clusters are found rather large. Gruemmer--Faessler's method is discussed and their results are shown to be trivial

  12. Medical physics: molecular aspects

    International Nuclear Information System (INIS)

    Actual problems in medical physics have been considered. Features in the cell membrane structure promoting the action of anticancer drugs are studied. The mechanism of an invasive method for measuring the blood pressure is analyzed. The tension distribution in the left ventricle wall was calculated. Conditions that prevent magnetic particles, nanodiamonds, and fullerene molecules, which are used to transport drugs in human body, to aggregate in liquid systems are determined. A molecular mechanism of electric welding of biological tissues has been proposed, as well as a method to study the surface of biological structures, by using ultrasound. The origin of structural changes in human hair under the influence of chemicals is determined

  13. Molecular Pathogenesis of Spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing

    This dissertation includes a presentation of knowledge on the molecular pathogenesis of spondyloarthritis achieved through a PhD programme at Aalborg University from 1.12.2011 - 1.12.2014. Work was carried out in the Laboratory of Medical Mass Spectrometry, headed by: Professor Svend Birkelund...... Associate Professor Allan Stensballe The output of this PhD programme, besides from this dissertation, includes 5 published papers, 30 ECTS PhD courses, oral presentations of posters in national and international research environment and a short-term scholarship at the La Jolla Institute for Allergy and...

  14. Massive molecular outflows

    OpenAIRE

    Beuther, H.; Schilke, P.; Menten, K. M.; Walmsley, C. M.; Sridharan, T. K.; Wyrowski, F.

    2001-01-01

    We present a mapping study of massive molecular outflows in 26 high-mass star-forming regions at 11'' spatial resolution. Bipolar morpholgy is found in 80% of the sources and the collimation is higher than previously thought. Additionally, we find that well known low-mass correlations continue up to the high-mass regime, and accretion rates are around 10^(-4) Msun/yr rising as high as 10^(-3) Msun/yr. A tight correlation between the outflow and the core mass is established, implying that the ...

  15. Molecular origin of friction

    Institute of Scientific and Technical Information of China (English)

    WANG; Hui; ZHANG; Tao; HU; Yuanzhong

    2004-01-01

    The wearless friction originating from molecular interactions has been discussed in this paper. We find that the frictional properties are closely related to the structural match of two surfaces in relative motion. For the surfaces with incommensurate structure and week inter-surface interaction, zero static and kinetic friction can be achieved. In a sliding considered as in a quasi-static state, the energy dissipation initiates when interfacial particles move in a discontinuous fashion, which gives rise to a finite kinetic friction. The state of superlubricity is a result of computer simulations, but the prediction will encourage people to look for a technical approach to realizing the state of super low friction.

  16. The California Molecular Cloud

    OpenAIRE

    Lada, Charles J.; Lombardi, Marco; Alves, Joao F.

    2009-01-01

    We present an analysis of wide-field infrared extinction maps of a region in Perseus just north of the Taurus-Auriga dark cloud complex. From this analysis we have identified a massive, nearby, but previously unrecognized, giant molecular cloud (GMC). From comparison of foreground star counts with Galactic models we derive a distance of 450 +/- 23 parsecs to the cloud. At this distance the cloud extends over roughly 80 pc and has a mass of approximately 10^5 solar masses, rivaling the Orion (...

  17. Molecular Urban Revolutions?

    DEFF Research Database (Denmark)

    Samson, Kristine

    capitalism today? How can we identify the modes of spatial production in global cities today, and in what degree can we see spatial singularity in the three cases? Are they at the same time part of mass culture and spatial means of rejecting capitalist modes of established urban encoding?...... created by means of affective and assembled spaces. Finally, the paper will discuss notions of (spatial) singularization by elaborating on Suely Rolnik and Félix Guattari’s travel book, Molecular Revolutions in Brazil (2007). How, for instance, does spatial interventions relate to and transform global...

  18. Molecular Comb Development

    Energy Technology Data Exchange (ETDEWEB)

    Ferrell, T.L.; Thundat, G.T.; Witkowski, C.E., III (Protein Discovery, Inc.)

    2007-07-17

    This CRADA was developed to enable ORNL to assist Protein Discovery, Inc. to develop a novel biomolecular separation system based on an ORNL patent application 'Photoelectrochemical Molecular Comb' by Thundat, Ferrell, and Brown. The Molecular Comb concept is based on creating light-induced charge carriers at a semiconductor-liquid interface, which is kept at a potential control such that a depletion layer is formed in the semiconductor. Focusing light from a low-power illumination source creates electron-hole pairs, which get separated in the depletion layer. The light-induced charge carriers reaching the surface attract oppositely charged biomolecules present in the solution. The solution is a buffer solution with very small concentrations of biomolecules. As the focused light is moved across the surface of the semiconductor-liquid interface, the accumulated biomolecules follow the light beam. A thin layer of gel or other similar material on the surface of the semiconductor can act as a sieving medium for separating the biomolecules according to their sizes.

  19. Towards graphyne molecular electronics.

    Science.gov (United States)

    Li, Zhihai; Smeu, Manuel; Rives, Arnaud; Maraval, Valérie; Chauvin, Remi; Ratner, Mark A; Borguet, Eric

    2015-01-01

    α-Graphyne, a carbon-expanded version of graphene ('carbo-graphene') that was recently evidenced as an alternative zero-gap semiconductor, remains a theoretical material. Nevertheless, using specific synthesis methods, molecular units of α-graphyne ('carbo-benzene' macrocycles) can be inserted between two anilinyl (4-NH2-C6H4)-anchoring groups that allow these fragments to form molecular junctions between gold electrodes. Here, electrical measurements by the scanning tunnelling microscopy (STM) break junction technique and electron transport calculations are carried out on such a carbo-benzene, providing unprecedented single molecule conductance values: 106 nS through a 1.94-nm N-N distance, essentially 10 times the conductance of a shorter nanographenic hexabenzocoronene analogue. Deleting a C4 edge of the rigid C18 carbo-benzene circuit results in a flexible 'carbo-butadiene' molecule that has a conductance 40 times lower. Furthermore, carbo-benzene junctions exhibit field-effect transistor behaviour when an electrochemical gate potential is applied, opening the way for device applications. All the results are interpreted on the basis of theoretical calculations. PMID:25699991

  20. Yeast Golgi-localized, gamma-Ear-containing, ADP-ribosylation factor-binding proteins are but adaptor protein-1 is not required for cell-free transport of membrane proteins from the trans-Golgi network to the prevacuolar compartment.

    Science.gov (United States)

    Abazeed, Mohamed E; Fuller, Robert S

    2008-11-01

    Golgi-localized, gamma-Ear-containing, ADP-ribosylation factor-binding proteins (GGAs) and adaptor protein-1 (AP-1) mediate clathrin-dependent trafficking of transmembrane proteins between the trans-Golgi network (TGN) and endosomes. In yeast, the vacuolar sorting receptor Vps10p follows a direct pathway from the TGN to the late endosome/prevacuolar compartment (PVC), whereas, the processing protease Kex2p partitions between the direct pathway and an indirect pathway through the early endosome. To examine the roles of the Ggas and AP-1 in TGN-PVC transport, we used a cell-free assay that measures delivery to the PVC of either Kex2p or a chimeric protein (K-V), in which the Vps10p cytosolic tail replaces the Kex2p tail. Either antibody inhibition or dominant-negative Gga2p completely blocked K-V transport but only partially blocked Kex2p transport. Deletion of APL2, encoding the beta subunit of AP-1, did not affect K-V transport but partially blocked Kex2p transport. Residual Kex2p transport seen with apl2Delta membranes was insensitive to dominant-negative Gga2p, suggesting that the apl2Delta mutation causes Kex2p to localize to a compartment that precludes Gga-dependent trafficking. These results suggest that yeast Ggas facilitate the specific and direct delivery of Vps10p and Kex2p from the TGN to the PVC and that AP-1 modulates Kex2p trafficking through a distinct pathway, presumably involving the early endosome. PMID:18784256

  1. Yeast Golgi-localized, γ-Ear–containing, ADP-Ribosylation Factor-binding Proteins Are but Adaptor Protein-1 Is Not Required for Cell-free Transport of Membrane Proteins from the Trans-Golgi Network to the Prevacuolar Compartment

    Science.gov (United States)

    Abazeed, Mohamed E.

    2008-01-01

    Golgi-localized, γ-Ear–containing, ADP-ribosylation factor-binding proteins (GGAs) and adaptor protein-1 (AP-1) mediate clathrin-dependent trafficking of transmembrane proteins between the trans-Golgi network (TGN) and endosomes. In yeast, the vacuolar sorting receptor Vps10p follows a direct pathway from the TGN to the late endosome/prevacuolar compartment (PVC), whereas, the processing protease Kex2p partitions between the direct pathway and an indirect pathway through the early endosome. To examine the roles of the Ggas and AP-1 in TGN–PVC transport, we used a cell-free assay that measures delivery to the PVC of either Kex2p or a chimeric protein (K-V), in which the Vps10p cytosolic tail replaces the Kex2p tail. Either antibody inhibition or dominant-negative Gga2p completely blocked K-V transport but only partially blocked Kex2p transport. Deletion of APL2, encoding the β subunit of AP-1, did not affect K-V transport but partially blocked Kex2p transport. Residual Kex2p transport seen with apl2Δ membranes was insensitive to dominant-negative Gga2p, suggesting that the apl2Δ mutation causes Kex2p to localize to a compartment that precludes Gga-dependent trafficking. These results suggest that yeast Ggas facilitate the specific and direct delivery of Vps10p and Kex2p from the TGN to the PVC and that AP-1 modulates Kex2p trafficking through a distinct pathway, presumably involving the early endosome. PMID:18784256

  2. Assessment of Molecular Modeling & Simulation

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-01-03

    This report reviews the development and applications of molecular and materials modeling in Europe and Japan in comparison to those in the United States. Topics covered include computational quantum chemistry, molecular simulations by molecular dynamics and Monte Carlo methods, mesoscale modeling of material domains, molecular-structure/macroscale property correlations like QSARs and QSPRs, and related information technologies like informatics and special-purpose molecular-modeling computers. The panel's findings include the following: The United States leads this field in many scientific areas. However, Canada has particular strengths in DFT methods and homogeneous catalysis; Europe in heterogeneous catalysis, mesoscale, and materials modeling; and Japan in materials modeling and special-purpose computing. Major government-industry initiatives are underway in Europe and Japan, notably in multi-scale materials modeling and in development of chemistry-capable ab-initio molecular dynamics codes.

  3. Multiphotochromic molecular systems.

    Science.gov (United States)

    Fihey, Arnaud; Perrier, Aurélie; Browne, Wesley R; Jacquemin, Denis

    2015-06-01

    Molecular systems encompassing more than one photochromic entity can be used to build highly functional materials, thanks to their potential multi-addressability and/or multi-response properties. Over the last decade, the synthesis and spectroscopic and kinetic characterisation as well as the modeling of a wide range of multiphotochromes have been achieved in a field that is emerging as a distinct branch of photochemistry. In this review, we provide an overview of the available multiphotochromic compounds which use a variety of photoactive building blocks, e.g., diarylethene, azobenzene, spiropyran, naphthopyran or fulgimide derivatives. Their efficiency in terms of multi-responsiveness is discussed and several strategies to circumvent the most common limitation (i.e., the loss of photochromism of one part) are described. PMID:25921433

  4. Atomic and molecular manipulation

    CERN Document Server

    Mayne, Andrew J

    2011-01-01

    Work with individual atoms and molecules aims to demonstrate that miniaturized electronic, optical, magnetic, and mechanical devices can operate ultimately even at the level of a single atom or molecule. As such, atomic and molecular manipulation has played an emblematic role in the development of the field of nanoscience. New methods based on the use of the scanning tunnelling microscope (STM) have been developed to characterize and manipulate all the degrees of freedom of individual atoms and molecules with an unprecedented precision. In the meantime, new concepts have emerged to design molecules and substrates having specific optical, mechanical and electronic functions, thus opening the way to the fabrication of real nano-machines. Manipulation of individual atoms and molecules has also opened up completely new areas of research and knowledge, raising fundamental questions of "Optics at the atomic scale", "Mechanics at the atomic scale", Electronics at the atomic scale", "Quantum physics at the atomic sca...

  5. Molecular dynamics simulations

    International Nuclear Information System (INIS)

    The molecular dynamics computer simulation discovery of the slow decay of the velocity autocorrelation function in fluids is briefly reviewed in order to contrast that long time tail with those observed for the stress autocorrelation function in fluids and the velocity autocorrelation function in the Lorentz gas. For a non-localized particle in the Lorentz gas it is made plausible that even if it behaved quantum mechanically its long time tail would be the same as the classical one. The generalization of Fick's law for diffusion for the Lorentz gas, necessary to avoid divergences due to the slow decay of correlations, is presented. For fluids, that generalization has not yet been established, but the region of validity of generalized hydrodynamics is discussed. 20 refs., 5 figs

  6. Interstellar molecular hydrogen

    Science.gov (United States)

    Shull, J. M.; Beckwith, S.

    1982-01-01

    Recent progress in the detection of H2 in the interstellar medium is reviewed. The hydrogen molecule is discussed in terms of properties, and collisional excitation and dissociation rates. Molecular hydrogen formation and cooling and heating by H2 are also discussed. Ultraviolet studies provided information for the study of the formation-destruction equilibrium of H2, the kinetic temperature of the cloud, the hydrogen particle density, and the ultraviolet radiation field. Infrared observations in Orion and the planetary nebula NGC 7027 reveal two detections of vibrationally excited H2. In addition, thermal and nonthermal excitation mechanisms are discussed. Finally, it is noted that increased ultraviolet sensitivity is necessary for thorough H2 studies.

  7. Molecular Dynamics Calculations

    Science.gov (United States)

    1996-01-01

    The development of thermodynamics and statistical mechanics is very important in the history of physics, and it underlines the difficulty in dealing with systems involving many bodies, even if those bodies are identical. Macroscopic systems of atoms typically contain so many particles that it would be virtually impossible to follow the behavior of all of the particles involved. Therefore, the behavior of a complete system can only be described or predicted in statistical ways. Under a grant to the NASA Lewis Research Center, scientists at the Case Western Reserve University have been examining the use of modern computing techniques that may be able to investigate and find the behavior of complete systems that have a large number of particles by tracking each particle individually. This is the study of molecular dynamics. In contrast to Monte Carlo techniques, which incorporate uncertainty from the outset, molecular dynamics calculations are fully deterministic. Although it is still impossible to track, even on high-speed computers, each particle in a system of a trillion trillion particles, it has been found that such systems can be well simulated by calculating the trajectories of a few thousand particles. Modern computers and efficient computing strategies have been used to calculate the behavior of a few physical systems and are now being employed to study important problems such as supersonic flows in the laboratory and in space. In particular, an animated video (available in mpeg format--4.4 MB) was produced by Dr. M.J. Woo, now a National Research Council fellow at Lewis, and the G-VIS laboratory at Lewis. This video shows the behavior of supersonic shocks produced by pistons in enclosed cylinders by following exactly the behavior of thousands of particles. The major assumptions made were that the particles involved were hard spheres and that all collisions with the walls and with other particles were fully elastic. The animated video was voted one of two

  8. Gas Phase Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Hall, G.E.; Prrese, J.M.; Sears, T.J.; Weston, R.E.

    1999-05-21

    The goal of this research is the understanding of elementary chemical and physical processes important in the combustion of fossil fuels. Interest centers on reactions involving short-lived chemical intermediates and their properties. High-resolution high-sensitivity laser absorption methods are augmented by high temperature flow-tube reaction kinetics studies with mass spectrometric sampling. These experiments provide information on the energy levels, structures and reactivity of molecular flee radical species and, in turn, provide new tools for the study of energy flow and chemical bond cleavage in the radicals in chemical systems. The experimental work is supported by theoretical and computational work using time-dependent quantum wavepacket calculations that provide insights into energy flow between the vibrational modes of the molecule.

  9. Molecular conduction: paradigms and possibilities

    OpenAIRE

    Ghosh, A. W.; Datta, S

    2003-01-01

    We discuss the factors that determine the overall shape and magnitude of the current-voltage (I-V) characteristics of a variety of molecular conductors sandwiched between two metallic contacts. We analyze the individual influences of the contact geometry, the molecular chemistry, the electrostatics of the environment, and charging on molecular conduction. Current conduction depends sensitively on the experimental geometry, as well as on the theoretical model for the molecule and the contacts....

  10. Time-resolved molecular imaging

    Science.gov (United States)

    Xu, Junliang; Blaga, Cosmin I.; Agostini, Pierre; DiMauro, Louis F.

    2016-06-01

    Time-resolved molecular imaging is a frontier of ultrafast optical science and physical chemistry. In this article, we review present and future key spectroscopic and microscopic techniques for ultrafast imaging of molecular dynamics and show their differences and connections. The advent of femtosecond lasers and free electron x-ray lasers bring us closer to this goal, which eventually will extend our knowledge about molecular dynamics to the attosecond time domain.

  11. POPULAR MOLECULAR MARKERS IN BACTERIA

    OpenAIRE

    Weilong, Liu; Lv, Li; MD. ASADUZZAMAN KHAN AND FEIZHOU ZHU

    2012-01-01

    Molecular markers are defined as the fragments of DNA sequence associated with a genome, which are used to identify a particular DNA sequence. Nowadays, with the explosive growth of genetic research and bacterial classification, molecular marker is an important tool to identify bacterial species. Taking account to its significant roles in clinic, medicine and food industry, in this review article, we summarize the traditional research and new development about molecular markers (also called g...

  12. Metal-mediated molecular machines

    OpenAIRE

    Howgego, David Christopher

    2013-01-01

    Nature abounds with ingenious nanoscopic machines employed to carry out all of the requisite tasks that collectively contribute to the molecular basis of life. This thesis focuses primarily on a sub-set known as "molecular walkers" which can perambulate along intracellular molecular motorways carrying out such essential tasks as vesicle transport and muscle contraction. A summary of these incredible natural motors is presented in Chapter I along with a review of the artificial ...

  13. Electrical properties of molecular crystals

    International Nuclear Information System (INIS)

    This literature survey summarizes the electrical properties of molecular crystals: molecular crystal structure, transport and excitation mechanisms of charge-carriers, and differences compared to inorganic semi-conductors. The main results concerning the electrical conductivity of the most-studied molecular crystals are presented, together with the optical and photo-electrical properties of these crystals. Finally the different types of electrical measurements used are reviewed, as well as the limits of each method. (author)

  14. Information engineering for molecular diagnostics.

    OpenAIRE

    Sorace, J. M.; Ritondo, M.; Canfield, K.

    1994-01-01

    Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Seve...

  15. Interface-assisted molecular spintronics

    International Nuclear Information System (INIS)

    Molecular spintronics, a field that utilizes the spin state of organic molecules to develop magneto-electronic devices, has shown an enormous scientific activity for more than a decade. But, in the last couple of years, new insights in understanding the fundamental phenomena of molecular interaction on magnetic surfaces, forming a hybrid interface, are presenting a new pathway for developing the subfield of interface-assisted molecular spintronics. The recent exploration of such hybrid interfaces involving carbon based aromatic molecules shows a significant excitement and promise over the previously studied single molecular magnets. In the above new scenario, hybridization of the molecular orbitals with the spin-polarized bands of the surface creates new interface states with unique electronic and magnetic character. This study opens up a molecular-genome initiative in designing new handles to functionalize the spin dependent electronic properties of the hybrid interface to construct spin-functional tailor-made devices. Through this article, we review this subject by presenting a fundamental understanding of the interface spin-chemistry and spin-physics by taking support of advanced computational and spectroscopy tools to investigate molecular spin responses with demonstration of new interface phenomena. Spin-polarized scanning tunneling spectroscopy is favorably considered to be an important tool to investigate these hybrid interfaces with intra-molecular spatial resolution. Finally, by addressing some of the recent findings, we propose novel device schemes towards building interface tailored molecular spintronic devices for applications in sensor, memory, and quantum computing

  16. Thermally driven molecular linear motors - A molecular dynamics study

    DEFF Research Database (Denmark)

    Zambrano, Harvey A; Walther, Jens Honore; Jaffe, Richard Lawrence

    2009-01-01

    We conduct molecular dynamics simulations of a molecular linear motor consisting of coaxial carbon nanotubes with a long outer carbon nanotube confining and guiding the motion of an inner short, capsule-like nanotube. The simulations indicate that the motion of the capsule can be controlled by th...

  17. Bienvenida la Medicina Molecular

    Directory of Open Access Journals (Sweden)

    Orlando R. Serrano-Barrera

    2015-11-01

    Full Text Available No ha cambiado la medicina, sino que ha avanzado. Los métodos clínico-epidemiológicos  incluyen hoy y se benefician del conocimiento de las bases moleculares del proceso salud-enfermedad, tanto las variaciones individuales, como los caracteres compartidos por comunidades y poblaciones, que las hacen resistentes o vulnerables a una enfermedad. La estimación presintomática e, incluso, prenatal del riesgo de enfermar, el diagnóstico, el pronóstico, la elección del tratamiento más ajustado al paciente, las posibilidades de rehabilitación y reinserción social, la educación y promoción sanitarias son todos momentos del proceso de toma de decisiones, que el médico debe asumir en el nuevo escenario de una ciencia que ha logrado discernir las implicaciones de un número creciente de moléculas, sus variantes, sus formas mutadas y sus interacciones con otras moléculas y con factores ambientales. (1 ¿Cuán lejos está tal panorama de nuestra práctica clínica? También en nuestros escenarios se hace medicina molecular. Así ha sido desde que en 1949 Pauling catalogara la primera enfermedad molecular: la anemia drepanocítica. (2 La más temprana acción de prevención, la vacunación, se realiza a diario en las áreas de salud e incluye preparados conformados por moléculas obtenidas por vía recombinante o síntesis química, como el antígeno de superficie del virus de la hepatitis B y el polisacárido de membrana del Haemophilus influenzae, respectivamente. (3 La pesquisa poblacional de cáncer de próstata, enfocado hacia los hombres mayores de 50 años o con síntomas sugestivos, se auxilia de la cuantificación en sangre del antígeno prostático específico. (4 El tratamiento del infarto agudo del miocardio, ahora la segunda causa de muerte en Cuba, incluye la trombolisis con estreptocinasa, otra biomolécula recombinante. (5 En desarrollo, en etapa de ensayos clínicos o ya como productos registrados algunas vacunas terap

  18. Molecular digital pathology: progress and potential of exchanging molecular data.

    Science.gov (United States)

    Roy, Somak; Pfeifer, John D; LaFramboise, William A; Pantanowitz, Liron

    2016-09-01

    Many of the demands to perform next generation sequencing (NGS) in the clinical laboratory can be resolved using the principles of telepathology. Molecular telepathology can allow facilities to outsource all or a portion of their NGS operation such as cloud computing, bioinformatics pipelines, variant data management, and knowledge curation. Clinical pathology laboratories can electronically share diverse types of molecular data with reference laboratories, technology service providers, and/or regulatory agencies. Exchange of electronic molecular data allows laboratories to perform validation of rare diseases using foreign data, check the accuracy of their test results against benchmarks, and leverage in silico proficiency testing. This review covers the emerging subject of molecular telepathology, describes clinical use cases for the appropriate exchange of molecular data, and highlights key issues such as data integrity, interoperable formats for massive genomic datasets, security, malpractice and emerging regulations involved with this novel practice. PMID:27471996

  19. Molecular sensors for MEMS

    Science.gov (United States)

    Huang, Chih-Yung

    Molecular sensors, known as pressure-sensitive paint and temperature-sensitive paint, are applied inside MEMS devices to obtain the internal and external flow fields. The spatial resolution for the PSP and TSP measurements has improved to 5 mum. The low-pressure PSP sensor has been investigated for use in MEMS measurements, with an application range from continuum flow to transition flow. PSP and TSP measurements in different micro devices have been obtained with the flow fields covering steady and unsteady, subsonic and supersonic flow. In microchannel measurements, the pressure distributions inside the microchannel have been obtained for Knudsen number from 0.006 to 0.8. Compressibility and rarefaction effects can be observed in the PSP data. Detailed information at the channel inlet was also collected to discuss the entrance effect for different flow regimes. For micronozzle experiments, four different micronozzles have been fabricated to study geometry effects at the micro scale. The pressure maps inside the micronozzle devices have been obtained with PSP sensors. A modified schlieren technique is used to compare the PSP results and investigate the shock wave behavior at high- and low-pressure conditions. Thick viscous layers in the micronozzle have been observed in the low-pressure measurements. For microjet impingements, heat transfer measurements have been collected with different microjet devices by using TSP sensors. For supersonic impinging microjet measurements, both pressure and temperature data have been obtained at different pressure ratios, impingement angles and impingement distances. Measurements reveal that the magnitude and number of shock cells decreases in the micro scale due to strong viscous effects. For microturbine measurements, averaged results of PSP and TSP measurements have been obtained for a rotation speed from 1300 to 4000 rpm. Phase-averaged results have been collected by using a laser triggering system at rotation speed of 1400 rpm

  20. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  1. Optically controllable molecular logic circuits

    International Nuclear Information System (INIS)

    Molecular logic circuits represent a promising technology for observation and manipulation of biological systems at the molecular level. However, the implementation of molecular logic circuits for temporal and programmable operation remains challenging. In this paper, we demonstrate an optically controllable logic circuit that uses fluorescence resonance energy transfer (FRET) for signaling. The FRET-based signaling process is modulated by both molecular and optical inputs. Based on the distance dependence of FRET, the FRET pathways required to execute molecular logic operations are formed on a DNA nanostructure as a circuit based on its molecular inputs. In addition, the FRET pathways on the DNA nanostructure are controlled optically, using photoswitching fluorescent molecules to instruct the execution of the desired operation and the related timings. The behavior of the circuit can thus be controlled using external optical signals. As an example, a molecular logic circuit capable of executing two different logic operations was studied. The circuit contains functional DNAs and a DNA scaffold to construct two FRET routes for executing Input 1 AND Input 2 and Input 1 AND NOT Input 3 operations on molecular inputs. The circuit produced the correct outputs with all possible combinations of the inputs by following the light signals. Moreover, the operation execution timings were controlled based on light irradiation and the circuit responded to time-dependent inputs. The experimental results demonstrate that the circuit changes the output for the required operations following the input of temporal light signals

  2. Optically controllable molecular logic circuits

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Takahiro, E-mail: t-nishimura@ist.osaka-u.ac.jp; Fujii, Ryo; Ogura, Yusuke; Tanida, Jun [Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2015-07-06

    Molecular logic circuits represent a promising technology for observation and manipulation of biological systems at the molecular level. However, the implementation of molecular logic circuits for temporal and programmable operation remains challenging. In this paper, we demonstrate an optically controllable logic circuit that uses fluorescence resonance energy transfer (FRET) for signaling. The FRET-based signaling process is modulated by both molecular and optical inputs. Based on the distance dependence of FRET, the FRET pathways required to execute molecular logic operations are formed on a DNA nanostructure as a circuit based on its molecular inputs. In addition, the FRET pathways on the DNA nanostructure are controlled optically, using photoswitching fluorescent molecules to instruct the execution of the desired operation and the related timings. The behavior of the circuit can thus be controlled using external optical signals. As an example, a molecular logic circuit capable of executing two different logic operations was studied. The circuit contains functional DNAs and a DNA scaffold to construct two FRET routes for executing Input 1 AND Input 2 and Input 1 AND NOT Input 3 operations on molecular inputs. The circuit produced the correct outputs with all possible combinations of the inputs by following the light signals. Moreover, the operation execution timings were controlled based on light irradiation and the circuit responded to time-dependent inputs. The experimental results demonstrate that the circuit changes the output for the required operations following the input of temporal light signals.

  3. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  4. Chemical evolution of molecular clouds

    Science.gov (United States)

    Prasad, Sheo S.; Tarafdar, Sankar P.; Villere, Karen R.; Huntress, Wesley T., Jr.

    1987-01-01

    The principles behind the coupled chemical-dynamical evolution of molecular clouds are described. Particular attention is given to current problems involving the simplest species (i.e., C. CO, O2, and H2) in quiescent clouds. The results of a comparison made between the molecular abundances in the Orion ridge and the hot core (Blake, 1986) are presented.

  5. From Molecular Biology to Biomedicine

    International Nuclear Information System (INIS)

    From Molecular Biology to Biomedicine. The well known molecular biologist Margarita Salas offered an informative conference at the CSN on progress in these areas since the discovery, more than half a century ago, of the structure of the molecule carrying genetic information, DNA, work that is having an enormous impact in areas such as biomedicine and foodstuff production. (Author)

  6. Teaching Molecular Biology with Microcomputers.

    Science.gov (United States)

    Reiss, Rebecca; Jameson, David

    1984-01-01

    Describes a series of computer programs that use simulation and gaming techniques to present the basic principles of the central dogma of molecular genetics, mutation, and the genetic code. A history of discoveries in molecular biology is presented and the evolution of these computer assisted instructional programs is described. (MBR)

  7. Molecular ecology of aquatic microbes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    Abstracts of reports are presented from a meeting on Molecular Ecology of Aquatic Microbes. Topics included: opportunities offered to aquatic ecology by molecular biology; the role of aquatic microbes in biogeochemical cycles; characterization of the microbial community; the effect of the environment on aquatic microbes; and the targeting of specific biological processes.

  8. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  9. Molecular path for ligand search

    Institute of Scientific and Technical Information of China (English)

    Tao Lu; Yuan Yuan Qiao; Pan Wen Shen

    2011-01-01

    A ligand is a small molecule bind to several residues of a receptor. We adapt the concept of molecular path for effective ligand search with its contacting residues. Additionally, we allow wild type definitions on atoms and bonds of molecular paths for fuzzy algorithms on structural match. We choose hydrogen bond interactions to characterize the binding mode of a ligand by several proper molecular paths and use them to query the deposited ligands in PDBe that interact with their residues in the same way. Expression of molecular path and format of database entries are described with examples. Our molecular path provides a new approach to explore the ligand-receptor interactions and to provide structural framework reference on new ligand design.

  10. Handbook of Molecular Force Spectroscopy

    CERN Document Server

    Noy, Aleksandr

    2008-01-01

    "...Noy's Handbook of Molecular Force Spectroscopy is both a timely and useful summary of fundamental aspects of molecular force spectroscopy, and I believe it would make a worthwhile addition to any good scientific library. New research groups that are entering this field would be well advisedto study this handbook in detail before venturing into the exciting and challenging world of molecular force spectroscopy." Matthew F. Paige, University of Saskatchewan, Journal of the American Chemical Society Modern materials science and biophysics are increasingly focused on studying and controlling intermolecular interactions on the single-molecule level. Molecular force spectroscopy was developed in the past decade as the result of several unprecedented advances in the capabilities of modern scientific instrumentation, and defines a number of techniques that use mechanical force measurements to study interactions between single molecules and molecular assemblies in chemical and biological systems. Examples of these...

  11. Similarity of molecular shape.

    Science.gov (United States)

    Meyer, A Y; Richards, W G

    1991-10-01

    The similarity of one molecule to another has usually been defined in terms of electron densities or electrostatic potentials or fields. Here it is expressed as a function of the molecular shape. Formulations of similarity (S) reduce to very simple forms, thus rendering the computerised calculation straightforward and fast. 'Elements of similarity' are identified, in the same spirit as 'elements of chirality', except that the former are understood to be variable rather than present-or-absent. Methods are presented which bypass the time-consuming mathematical optimisation of the relative orientation of the molecules. Numerical results are presented and examined, with emphasis on the similarity of isomers. At the extreme, enantiomeric pairs are considered, where it is the dissimilarity (D = 1 - S) that is of consequence. We argue that chiral molecules can be graded by dissimilarity, and show that D is the shape-analog of the 'chirality coefficient', with the simple form of the former opening up numerical access to the latter. PMID:1770379

  12. Molecular genetics of ependymoma

    Institute of Scientific and Technical Information of China (English)

    Yuan Yao; Stephen C.Mack; Michael D.Taylor

    2011-01-01

    Brain tumors are the leading cause of cancer death in children,with ependymoma being the third most common and posing a significant clinical burden.Its mechanism of pathogenesis,reliable prognostic indicators,and effective treatments other than surgical resection have all remained elusive.Until recently,cytogenetic techniques,and lack of cell lines and animal models.Ependymoma heterogeneity,which manifests as variations in tumor location,patient age,histological grade,and clinical behavior,together with the observation of a balanced genomic profile in up to 50% of cases,presents additional challenges in understanding the development and progression of this disease.Despite these difficulties,we have made significant headway in the past decade in identifying the genetic alterations and pathways involved in ependymoma tumorigenesis through collaborative efforts and the application of microarray-based genetic (copy number) and transcriptome profiling platforms.Genetic characterization of ependymoma unraveled distinct mRNA-defined subclasses and led to the identification of radial glial cells as its cell type of origin.This review summarizes our current knowledge in the molecular genetics of ependymoma and proposesfuture research directions necessary to further advance this field.

  13. Molecular screening in galactosemia

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Singh, R.; Fernhoff, P.M. [Emory Univ., Atlanta, GA (United States)] [and others

    1994-09-01

    Classical galactosemia (G/G) is caused by the absence of galactose-1-phosphate uridyl transferase (GALT) activity while the Duarte allele produces partial impairment and a specific biochemical phenotype. Cloning and sequencing of the human GALT gene has enabled the identification of prevalent mutations for both Classical and Duarte alleles. The G allele is caused by a Q188R codon mutation in exon 6 in 70% of a Caucasian population while the D allele is caused by an N134D codon mutation in exon 10. Since the Q188R sequence creates a new Hpa II site and the N314D sequence creates a new Sin I site, it is relatively easy to screen for both mutations by multiplex PCR and restriction digest. Here we describe a method for detection of new mutations producing impaired GALT. Patient DNAs are subjected to SSCP (single strand conformational polymorphism) analysis of their 11 GALT exons. Direct sequencing of the exons targeted by SSCP has revealed many codon changes: IVSC 956 (a splice acceptor site loss), S135L, V151A, E203K, A320T, and Y323D. Two of these codon changes, V151A and S135L, have been confirmed as mutations by finding impaired GALT activity in a yeast expression system. We conclude that molecular screening of GALT DNA will clarify the structural biology of GALT and the pathophysiology of galactosemia.

  14. [Advances in Molecular Cloning].

    Science.gov (United States)

    Ashwini, M; Murugan, S B; Balamurugan, S; Sathishkumar, R

    2016-01-01

    "Molecular cloning" meaning creation of recombinant DNA molecules has impelled advancement throughout life sciences. DNA manipulation has become easy due to powerful tools showing exponential growth in applications and sophistication of recombinant DNA technology. Cloning genes has become simple what led to an explosion in the understanding of gene function by seamlessly stitching together multiple DNA fragments or by the use of swappable gene cassettes, maximizing swiftness and litheness. A novel archetype might materialize in the near future with synthetic biology techniques that will facilitate quicker assembly and iteration of DNA clones, accelerating the progress of gene therapy vectors, recombinant protein production processes and new vaccines by in vitro chemical synthesis of any in silico-specified DNA construct. The advent of innovative cloning techniques has opened the door to more refined applications such as identification and mapping of epigenetic modifications and high-throughput assembly of combinatorial libraries. In this review, we will examine the major breakthroughs in cloning techniques and their applications in various areas of biological research that have evolved mainly due to easy construction of novel expression systems. PMID:27028806

  15. Radically enhanced molecular recognition

    KAUST Repository

    Trabolsi, Ali

    2009-12-17

    The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication. © 2010 Macmillan Publishers Limited. All rights reserved.

  16. Molecular Motors and Apical CFTR Traffic in Epithelia

    Directory of Open Access Journals (Sweden)

    Dmitri V. Kravtsov

    2013-05-01

    Full Text Available Intracellular protein traffic plays an important role in the regulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR chloride channels. Microtubule and actin-based motor proteins direct CFTR movement along trafficking pathways. As shown for other regulatory proteins such as adaptors, the involvement of protein motors in CFTR traffic is cell-type specific. Understanding motor specificity provides insight into the biology of the channel and opens opportunity for discovery of organ-specific drug targets for treating CFTR-mediated diseases.

  17. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  18. Molecular imaging in atherosclerosis

    International Nuclear Information System (INIS)

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  19. Department of Molecular Biology

    International Nuclear Information System (INIS)

    Full text. The majority of our studies are centered on (i) mechanisms of mutagenesis and DNA repair (including MFD) in Escherichia coli, M13, and lambda phages; (ii) inhibitory and miscoding properties of modified bases in DNA; (iii) synthesis and properties of pyrimidine nucleosides and nucleotide analogues with potential anti-tumor, anti-virus and anti-parasite activities, including their conformation and substrate/inhibitor properties in some enzyme systems of relevance to chemotherapy; (iv) molecular mechanisms of PUVA (psoralen + UVA) treatment in psoriasis photo-chemotherapy in particular its action on cell membrane; (v) specificity and methods for assays of N-alkyl-purine DNA glycosylase. The spectrum of mutagens tested includes: MMS, DMS, ultraviolet or halogen light and hydroxyl radicals. The enzymes and repair systems investigated include: DNA polymerases and the proofreading activity of DNA pol III, UvrABC-endonuclease, mismatch repair system, and methyl DNA glycosylases. Much attention is focussed on the role of UmuDC proteins in mutagenesis (dependent and independent on DNA replication) and DNA repair, and on the effect of the Tn10 transposon on the survival and mutation frequency of halogen light irradiated bacteria. A new class of nucleosides containing C(2)-hydroxymethyl-ribose (hamamelose) was synthesized, and it was found that uracil and 5-fluorouracil derivatives show a significant antitumor activity. It was found that 2CDA (2-deoxy-2-chloro-adenosine) an anti-lymphoid drug does not induce mutations, when incorporated into DNA, but significantly inhibits DNA replication. In studies with oxidized M13 DNA it was found that Fapy- (formamidopyrimidine)-residues in DNA selectively inhibits DNA synthesis, and the effect depends on the neighboring sequences and the DNA polymerase tested. Highly unstable derivatives of lecithin-psoralen adducts were characterized and their role in PUVA photochemotherapy is being studied. (author)

  20. SOYBEAN - MOLECULAR ASPECTS OF BREEDING

    Directory of Open Access Journals (Sweden)

    Aleksandra Sudarić

    2012-12-01

    Full Text Available The book Soybean: Molecular Aspects of Breeding focuses recent progress in our understanding of the genetics and molecular biology of soybean. This book is divided into four parts and contains 22 chapters. Part I, Molecular Biology and Biotechnology focuses advances in molecular biology and laboratory procedures that have been developed recently to manipulate DNA. Part II, Breeding for abiotic stress covers proteomics approaches form as a powerful tool for investigating the molecular mechanisms of the plant responses to various types of abiotic stresses. Part III, Breeding for biotic stress addresses issues related to application of molecular based strategies in order to increase soybean resistance to various biotic factors. Part IV, Recent Technology reviews recent technologies into the realm of soybean monitoring, processing and product use. While the information accumulated in this book is of primary interest for plant breeders, valuable insights are also offered to agronomists, molecular biologists, physiologists, plant pathologists, food scientists and students. The book is a result of efforts made by many experts from different countries (USA, Japan, Croatia, Serbia, China, Canada, Malawi, Iran, Hong Kong, Brasil, Mexico.

  1. [Molecular Subtypes of Gastric Cancer].

    Science.gov (United States)

    Hatogai, Ken; Doi, Toshihiko

    2016-03-01

    Gastric cancer has been classified based on the pathological characteristics including microscopic configuration and growth pattern. Although these classifications have been used in studies investigating prognosis and recurrence pattern, they are not considered for decisions regarding the therapeutic strategy. In the ToGA study, trastuzumab, an anti-HER2 monoclonal antibody, demonstrated clinical efficacy for gastric cancer with HER2 overexpression or HER2 gene amplification. Based on these findings of the ToGA study, the definition of HER2-positive gastric cancer was established. Thereafter, several molecular targeted agents, including agents targeting other receptor tyrosine kinases, have been investigated in gastric cancer. However, to date no biomarker, except HER2, has been established. Based on the recent technological development in the field of gene analysis, a comprehensive molecular evaluation of gastric cancer was performed as part of The Cancer Genome Atlas (TCGA)project, and a new molecular classification was proposed that divided gastric cancer into the following 4 subtypes: tumors positive for Epstein-Barr virus, microsatellite instability tumors, genomically stable tumors, and tumors with chromosomal instability. Each subtype has specific molecular alterations including gene mutation and amplification, DNA methylation, and protein overexpression. Additionally, some subtypes were suggested to be correlated with the clinicopathological characteristics or as targets of some molecular targeted agents that are currently under development. The new molecular classification is expected to be a roadmap for patient stratification and clinical trials on molecular targeted therapies in gastric cancer. PMID:27067842

  2. Molecular breast imaging. An update

    International Nuclear Information System (INIS)

    The aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging. Currently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy (1H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI). Recently, novel techniques for molecular imaging of breast tumors, such as sodium imaging (23Na-MRI), phosphorus spectroscopy (31P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation. It can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible. (orig.)

  3. Molecular-Coherent-States and Molecular-Fundamental-States

    OpenAIRE

    Irac-Astaud, Michele

    2000-01-01

    New families of Molecular-Coherent-States are constructed by the Perelomov group-method. Each family is generated by a Molecular-Fundamental-State that depends on an arbitrary sequence of complex numbers cj. Two of these families were already obtained by D.Janssen and by J. A. Morales, E. Deumens and Y. Ohrn. The properties of these families are investigated and we show that most of them are independent on the cj.

  4. Molecular electronic-structure theory

    CERN Document Server

    Helgaker, Trygve; Olsen, Jeppe

    2014-01-01

    Ab initio quantum chemistry has emerged as an important tool in chemical research and is appliced to a wide variety of problems in chemistry and molecular physics. Recent developments of computational methods have enabled previously intractable chemical problems to be solved using rigorous quantum-mechanical methods. This is the first comprehensive, up-to-date and technical work to cover all the important aspects of modern molecular electronic-structure theory. Topics covered in the book include: * Second quantization with spin adaptation * Gaussian basis sets and molecular-integral evaluati

  5. Molecular thermodynamics of nonideal fluids

    CERN Document Server

    Lee, Lloyd L

    2013-01-01

    Molecular Thermodynamics of Nonideal Fluids serves as an introductory presentation for engineers to the concepts and principles behind and the advances in molecular thermodynamics of nonideal fluids. The book covers related topics such as the laws of thermodynamics; entropy; its ensembles; the different properties of the ideal gas; and the structure of liquids. Also covered in the book are topics such as integral equation theories; theories for polar fluids; solution thermodynamics; and molecular dynamics. The text is recommended for engineers who would like to be familiarized with the concept

  6. Molecular Hydrodynamics from Memory Kernels

    Science.gov (United States)

    Lesnicki, Dominika; Vuilleumier, Rodolphe; Carof, Antoine; Rotenberg, Benjamin

    2016-04-01

    The memory kernel for a tagged particle in a fluid, computed from molecular dynamics simulations, decays algebraically as t-3 /2 . We show how the hydrodynamic Basset-Boussinesq force naturally emerges from this long-time tail and generalize the concept of hydrodynamic added mass. This mass term is negative in the present case of a molecular solute, which is at odds with incompressible hydrodynamics predictions. Lastly, we discuss the various contributions to the friction, the associated time scales, and the crossover between the molecular and hydrodynamic regimes upon increasing the solute radius.

  7. Photoelectron photoion molecular beam spectroscopy

    International Nuclear Information System (INIS)

    The use of supersonic molecular beams in photoionization mass spectroscopy and photoelectron spectroscopy to assist in the understanding of photoexcitation in the vacuum ultraviolet is described. Rotational relaxation and condensation due to supersonic expansion were shown to offer new possibilities for molecular photoionization studies. Molecular beam photoionization mass spectroscopy has been extended above 21 eV photon energy by the use of Stanford Synchrotron Radiation Laboratory (SSRL) facilities. Design considerations are discussed that have advanced the state-of-the-art in high resolution vuv photoelectron spectroscopy. To extend gas-phase studies to 160 eV photon energy, a windowless vuv-xuv beam line design is proposed

  8. An introduction to molecular spintronics

    Institute of Scientific and Technical Information of China (English)

    JIANG ShangDa; GOβ Karin; CERVETTI Christian; BOGANI Lapo

    2012-01-01

    We review the progress and future possibilities in the emerging area of molecular spintronics,we nrst provide an overview of the different transport regimes in which electronic nanodevices can operate,then briefly overview the important characteristics of molecular magnetic materials that can be useful for application in spintronics and we eventually present several schemes to include such systems into spintronic nanodevices.We hightlight the importance of a chemical approach to the area,and in the last section we showcase some approaches to the creation of hybrids made of carbon nanostructures and molecular magnets,which are gaining increasing attention.

  9. Introduction to Accelerated Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Danny [Los Alamos National Laboratory

    2012-07-10

    Molecular Dynamics is the numerical solution of the equations of motion of a set of atoms, given an interatomic potential V and some boundary and initial conditions. Molecular Dynamics is the largest scale model that gives unbiased dynamics [x(t),p(t)] in full atomistic detail. Molecular Dynamics: is simple; is 'exact' for classical dynamics (with respect to a given V); can be used to compute any (atomistic) thermodynamical or dynamical properties; naturally handles complexity -- the system does the right thing at the right time. The physics derives only from the interatomic potential.

  10. Time Delay in Molecular Photoionization

    CERN Document Server

    Hockett, P; Villeneuve, D M; Corkum, P B

    2015-01-01

    Time-delays in the photoionization of molecules are investigated. As compared to atomic ionization, the time-delays expected from molecular ionization present a much richer phenomenon, with a strong spatial dependence due to the anisotropic nature of the molecular scattering potential. We investigate this from a scattering theory perspective, and make use of molecular photoionization calculations to examine this effect in representative homonuclear and hetronuclear diatomic molecules, nitrogen and carbon monoxide. We present energy and angle-resolved maps of the Wigner delay time for single-photon valence ionization, and discuss the possibilities for experimental measurements.

  11. Bilingual teaching of molecular biology

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Recently bilingual teaching in China's universities has been widely carried out and become a popular subject for study. In this paper, the reasons for bilingual teaching of molecular biology are pointed out, the textbook of molecular biology and teaching method in bilingual teaching classes are determined after investigation and the practice of bilingually teaching molecular biology use both English and Chinese in a class. The effect has proved good. The bilingual teaching methods, the problem of bilingual teaching, the importance of understanding its significance and the possibilities of improving such teaching of the subject are also discussed.

  12. Molecular hydrodynamics from memory kernels

    CERN Document Server

    Lesnicki, Dominika; Carof, Antoine; Rotenberg, Benjamin

    2016-01-01

    The memory kernel for a tagged particle in a fluid, computed from molecular dynamics simulations, decays algebraically as $t^{-3/2}$. We show how the hydrodynamic Basset-Boussinesq force naturally emerges from this long-time tail and generalize the concept of hydrodynamic added mass. This mass term is negative in the present case of a molecular solute, at odds with incompressible hydrodynamics predictions. We finally discuss the various contributions to the friction, the associated time scales and the cross-over between the molecular and hydrodynamic regimes upon increasing the solute radius.

  13. NASA Applications of Molecular Nanotechnology

    Science.gov (United States)

    Globus, Al; Bailey, David; Han, Jie; Jaffe, Richard; Levit, Creon; Merkle, Ralph; Srivastava, Deepak

    1998-01-01

    Laboratories throughout the world are rapidly gaining atomically precise control over matter. As this control extends to an ever wider variety of materials, processes and devices, opportunities for applications relevant to NASA's missions will be created. This document surveys a number of future molecular nanotechnology capabilities of aerospace interest. Computer applications, launch vehicle improvements, and active materials appear to be of particular interest. We also list a number of applications for each of NASA's enterprises. If advanced molecular nanotechnology can be developed, almost all of NASA's endeavors will be radically improved. In particular, a sufficiently advanced molecular nanotechnology can arguably bring large scale space colonization within our grasp.

  14. Molecular Aggregation in Disodium Cromoglycate

    Science.gov (United States)

    Singh, Gautam; Agra-Kooijman, D.; Collings, P. J.; Kumar, Satyendra

    2012-02-01

    Details of molecular aggregation in the mesophases of the anti-asthmatic drug disodium cromoglycate (DSCG) have been studied using x-ray synchrotron scattering. The results show two reflections, one at wide angles corresponding to π-π stacking (3.32 å) of molecules, and the other at small angles which is perpendicular to the direction of molecular stacking and corresponds to the distance between the molecular aggregates. The latter varies from 35 - 41 å in the nematic (N) phase and 27 -- 32 å in the columnar (M) phase. The temperature evolution of the stack height, positional order correlations in the lateral direction, and orientation order parameter were determined in the N, M, and biphasic regions. The structure of the N and M phases and the nature of the molecular aggregation, together with their dependence on temperature and concentration, will be presented.

  15. Electron microscopy at molecular dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Baumeister, W.; Vogell, W.

    1980-01-01

    This book gives a survey of recent trends and activities in molcular microscopy . This branch of electron microscopy which is aimed at determining the structure of biological macromolecules and supramolecular assemblies has made significant progress during the past few years and promises to play a major role in the future of molecular biology. The thirty nine chapters fall into two general groups: The first group discusses the state-of-the-art illustrated by a wide range of molecular specimens containing new material. The second group reviews recent developments in image recording, low dose microscopy and image processing which are of potential interest to those seeking to overcome present limitations in obtaining more detailed structural information. The final five chapters deal with a subject which will surely emerge as a major area of practical interest in molecular microscopy: the artifical assembly of ordered molecular arrays.

  16. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Siddharth Gautam; S Mitra; R Mukhopadhyay

    2008-10-01

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time scales involved in the motion and the geometry of motion can be studied using QENS. Molecular dynamics (MD) simulation not only provides insight into the details of the different types of motion possible but also does not suffer limitations of the experimental set-up. Here we report the effect of confinement on molecular dynamics in various restricted geometries as studied by QENS and MD simulations: An example where the QENS technique provided direct evidence of phase transition associated with change in the dynamical behaviour of the molecules is also discussed.

  17. Physical adsorption and molecular dynamics

    International Nuclear Information System (INIS)

    Some aspects of noble gases adsorption (except He) on graphite substracts are reviewed. Experimental results from this adsorption are analyzed and compared with molecular dynamics calculations. (L.C.)

  18. Molecular imaging in myocardial fibrosis

    International Nuclear Information System (INIS)

    With the development of life science and medical technology, myocardial fibrosis is being increasingly recognized as a new therapeutic target for heart diseases. However, traditional methods for detection of myocardial fibrosis, such as myocardial biopsy and laboratory assay of serum metabolites or enzymes, are not satisfactory in meeting the clinical demands because of their intrinsic limitations. Molecular imaging may non-invasively and quantitatively evaluate the presence/absence, degree and turnover of myocardial fibrosis in vivo with good specificity, thus being useful for clinical assessment and intervention. Currently, the commonly used molecular imaging modalities for evaluation of myocardial fibrosis include SPECT, PET and MRI. It is hopeful that the molecular probe for targeted ultrasound technology may also be developed in the near future. This review highlights the current status and future trends of molecular imaging in myocardial fibrosis. (authors)

  19. Transport properties of molecular junctions

    CERN Document Server

    Zimbovskaya, Natalya A

    2013-01-01

    A comprehensive overview of the physical mechanisms that control electron transport and the characteristics of metal-molecule-metal (MMM) junctions is presented. As far as possible, methods and formalisms presented elsewhere to analyze electron transport through molecules are avoided. This title introduces basic concepts—a description of the electron transport through molecular junctions—and briefly describes relevant experimental methods. Theoretical methods commonly used to analyze the electron transport through molecules are presented. Various effects that manifest in the electron transport through MMMs, as well as the basics of density-functional theory and its applications to electronic structure calculations in molecules are presented. Nanoelectronic applications of molecular junctions and similar systems are discussed as well. Molecular electronics is a diverse and rapidly growing field. Transport Properties of Molecular Junctions presents an up-to-date survey of the field suitable for researchers ...

  20. Quantum logic with molecular ions

    CERN Document Server

    Wolf, Fabian; Heip, Jan C; Gebert, Florian; Shi, Chunyan; Schmidt, Piet O

    2015-01-01

    Laser spectroscopy of cold and trapped molecular ions is a powerful tool for fundamental physics, including the determination of fundamental constants, the laboratory test for their possible variation, and the search for a possible electric dipole moment of the electron. Optical clocks based on molecular ions sensitive to some of these effects are expected to achieve uncertainties approaching the $10^{-18}$ level. While the complexity of molecular structure facilitates these applications, the absence of cycling transitions poses a challenge for direct laser cooling, quantum state control, and detection. Previously employed state detection techniques based on photo-dissociation or chemical reactions are destructive and therefore inefficient. Here we experimentally demonstrate non-destructive state detection of a single trapped molecular ion through its strong Coulomb coupling to a well-controlled co-trapped atomic ion. An algorithm based on a state-dependent optical dipole force(ODF) changes the internal state...

  1. Emerging molecular phenotypes of asthma.

    Science.gov (United States)

    Ray, Anuradha; Oriss, Timothy B; Wenzel, Sally E

    2015-01-15

    Although asthma has long been considered a heterogeneous disease, attempts to define subgroups of asthma have been limited. In recent years, both clinical and statistical approaches have been utilized to better merge clinical characteristics, biology, and genetics. These combined characteristics have been used to define phenotypes of asthma, the observable characteristics of a patient determined by the interaction of genes and environment. Identification of consistent clinical phenotypes has now been reported across studies. Now the addition of various 'omics and identification of specific molecular pathways have moved the concept of clinical phenotypes toward the concept of molecular phenotypes. The importance of these molecular phenotypes is being confirmed through the integration of molecularly targeted biological therapies. Thus the global term asthma is poised to become obsolete, being replaced by terms that more specifically identify the pathology associated with the disease. PMID:25326577

  2. AN OVERVIEW ON MOLECULAR DOCKING

    Directory of Open Access Journals (Sweden)

    Gaba Monika

    2010-06-01

    Full Text Available Molecular Docking is the computational modeling of the structure of complexes formed by two or more interacting molecules. The goal of molecular docking is the prediction of the three dimensional structures of interest. Docking itself only produces plausible candidate structures. These candidates are ranked using methods such as scoring functions to identify structures that are most likely to occur in nature. The state of the art of various computational aspects of molecular docking based virtual screening of database of small molecules is presented. This review encompasses molecular docking approaches, different search algorithms and the scoring functions used in docking methods and their applications to protein and nucleic acid drug targets. Limitations of current technologies as well as future prospects are also presented

  3. Computer representation of molecular surfaces

    International Nuclear Information System (INIS)

    This review article surveys recent work on computer representation of molecular surfaces. Several different algorithms are discussed for producing vector or raster drawings of space-filling models formed as the union of spheres. Other smoother surfaces are also considered

  4. Molecular Biomedical Imaging Laboratory (MBIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Molecular Biomedical Imaging Laboratory (MBIL) is adjacent-a nd has access-to the Department of Radiology and Imaging Sciences clinical imaging facilities. MBIL...

  5. Molecular orbital excitations in cuprates

    OpenAIRE

    Kim, Young-June; Hill, J. P.; Gu, G. D.; Chou, F. C.; Wakimoto, S.; Birgeneau, R. J.; Komiya, Seiki; Ando, Yoichi; Motoyama, N.; Kojima, K. M.; Uchida, S; Casa, D.; Gog, T.

    2004-01-01

    We report resonant inelastic x-ray scattering studies of electronic excitations in a wide variety of cuprate compounds. Specifically, we focus on the charge-transfer type excitation of an electron from a bonding molecular orbital to an antibonding molecular orbital in a copper oxygen plaquette. Both the excitation energy and the amount of dispersion are found to increase significantly as the copper oxygen bond-length is reduced. We also find that the estimated bond-length dependence of the ho...

  6. Biological communication via molecular surfaces

    OpenAIRE

    Clark, Tim; Byler, K; de Groot, M

    2006-01-01

    The use and characteristics of local properties designed to describe intermolecular interactions projected onto molecular surfaces and based on semiempirical molecular orbital theory are described. After a discussion of the local properties themselves and their relationship to intermolecular interactions and chemical reactivity, two applications are described. The first, surface-integral models for physical properties, involve integrating a functional of the local properties over the molecula...

  7. Molecular Imaging in Genetic Medicine

    Science.gov (United States)

    Jacob, Ayden; Van Gestel, Frederick; Yaghoubi, Shahriar

    2016-01-01

    The field of biomedical imaging has made significant advances in recent times. This includes extremely high-resolution anatomic imaging and functional imaging of physiologic and pathologic processes as well as novel modalities in optical imaging to evaluate molecular features within the cellular environment. The latter has made it possible to image phenotypic markers of various genotypes that are implicated in human development, behavior, and disease. This article discusses the role of molecular imaging in genetic and precision medicine. 

  8. Theoretical Aspects of Molecular Recognition

    OpenAIRE

    Harmat, Veronika; Náray-Szabó, Gábor

    2009-01-01

    Molecular recognition is a key process in non-covalent interactions, which determines, among others, host-guest complexation, drug action and protein-protein interaction. A simple and attractive formulation is the lock-and-key analogy defining the host as a lock accommodating the guest as a key. We stress three major aspects of molecular recognition, determining both complementarity between host and guest and similarity within a group of guest molecules. These aspects are: steric, i.e. maximi...

  9. MINT: the Molecular INTeraction database

    OpenAIRE

    Chatr-aryamontri, Andrew; Ceol, Arnaud; Palazzi, Luisa Montecchi; Nardelli, Giuliano; Schneider, Maria Victoria; Castagnoli, Luisa; Cesareni, Gianni

    2006-01-01

    The Molecular INTeraction database (MINT, ) aims at storing, in a structured format, information about molecular interactions (MIs) by extracting experimental details from work published in peer-reviewed journals. At present the MINT team focuses the curation work on physical interactions between proteins. Genetic or computationally inferred interactions are not included in the database. Over the past four years MINT has undergone extensive revision. The new version of MINT is based on a comp...

  10. Variable molecular clocks in hominoids

    OpenAIRE

    Elango, Navin; Thomas, James W.; Yi, Soojin V.

    2006-01-01

    Generation time is an important determinant of a neutral molecular clock. There are several human-specific life history traits that led to a substantially longer generation time in humans than in other hominoids. Indeed, a long generation time is considered an important trait that distinguishes humans from their closest relatives. Therefore, humans may exhibit a significantly slower molecular clock as compared to other hominoids. To investigate this hypothesis, we performed a large-scale anal...

  11. Molecular theory of graphene oxide

    OpenAIRE

    Sheka, Elena F.; Popova, Nadezhda A

    2012-01-01

    Applying to graphene oxides, molecular theory of graphene is based on the oxide molecular origin when it is considered as a final product in the succession of a graphene molecule polyderivatives related to a particular oxidation reaction. The graphene oxide structure is created in due course of calculations following the algorithms that take into account the graphene molecules natural radicalization, correlation of odd electrons, an extremely strong influence of structure on properties, a sha...

  12. [Knowledgebases in postgenomic molecular biology].

    Science.gov (United States)

    Lisitsa, A V; Shilov, B V; Evdokimov, P A; Gusev, S A

    2010-01-01

    Knowledgebases can become an effective tool essentially raising quality of information retrieval in molecular biology, promoting the development of new methods of education and forecasting of the biomedical R&D. Knowledge-based technologies should induce "paradigm shift" in the life science due to integrative focusing of research groups towards the challenges of postgenomic era. This paper debates concept of the knowledgebase, which exploits web usage mining to personalize the access of molecular biologist to the Internet resources. PMID:21328913

  13. Molecular Epidemiology and Air Pollution

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Binková, B.; Rössnerová, Andrea; Šrám, Radim

    Rieka: InTech, 2015 - (Nejadkoorki, F.), s. 609-643 ISBN 978-953-51-2180-0 R&D Projects: GA ČR GA13-13458S Institutional support: RVO:68378041 Keywords : molecular epidemiology * biomarkers * human populations * in vitro studies Subject RIV: DN - Health Impact of the Environment Quality http://www.intechopen.com/books/current-air-quality-issues/molecular-epidemiology-and-air- pollution

  14. Molecular mechanisms of rosacea pathogenesis

    Directory of Open Access Journals (Sweden)

    Davydova A.M.

    2013-09-01

    Full Text Available The article presents possible molecular mechanisms for rosacea pathogenesis from current domestic and foreign clinical observations and laboratory research: regulation and expression defects of antimicrobial peptides, vascular endothelial growth factor, the effect of serine proteases, oxidative stress, reactive oxygen species and ferritin on the occurrence and course of rosacea. New developments in molecular biology and genetics are advanced for researching the interaction of multiple factors involved in rosacea pathogenesis, as well as providing the bases for potentially new therapies.

  15. Molecular epidemiology in environmental carcinogenesis.

    OpenAIRE

    Perera, F P; Mooney, L A; Dickey, C P; Santella, R. M.; Bell, D.; Blaner, W; Tang, D; Whyatt, R M

    1996-01-01

    Molecular epidemiology has significant potential in preventing cancer and other diseases caused by environmental exposures (related to lifestyle, occupation, or ambient pollution). This approach attempts to prevent cancer by incorporating laboratory methods to document the molecular dose and preclinical effects of carcinogens, as well as factors that increases individual susceptibility to carcinogens. Recently we have carried out validation studies of biologic markers such as carcinogen--DNA ...

  16. Visualization Software for Molecular Assemblies

    OpenAIRE

    Goddard, Thomas D; Ferrin, Thomas E.

    2007-01-01

    Software for viewing three-dimensional models and maps of viruses, ribosomes, filaments and other molecular assemblies is advancing on many fronts. New developments include molecular representations that offer better control over level of detail, lighting that improves the perception of depth, and two-dimensional projections that simplify data interpretation. Programmable graphics processors offer quality, speed and visual effects not previously possible, while 3D printers, haptic interaction...

  17. Molecular deformation mechanisms in polyethylene.

    OpenAIRE

    Coutry, Sandry

    2001-01-01

    This work is concerned with details of the molecular changes caused by deformation and also establishes any conformational differences between linear and branched polyethylene before, during and after deformation. Four blends of isotopically labelled polymers of different types, rapidly quenched from the melt, have been studied by Mixed Crystal Infra-red Spectroscopy and Small Angle Neutron Scattering (SANS), in order to clarify any differences in the molecular basis of drawing...

  18. Molecular analysis of Sarcoptes scabiei

    OpenAIRE

    Ljunggren, Erland L.

    2005-01-01

    The mite Sarcoptes scabiei (Acari), causes sarcoptic mange or scabies that globally affects animals and humans. Although scabies and mange are recognised as important diseases in human and veterinary medicine the amount of molecular studies of S. scabiei have been limited, which has been attributed to a shortage of parasitic material. This thesis is based on four studies that make use of molecular techniques with the aims to overcome the problems associated with a scarcity of mites, gain insi...

  19. Molecular diagnostics of neurodegenerative disorders

    OpenAIRE

    Agrawal, Megha; Biswas, Abhijit

    2015-01-01

    Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular ...

  20. Molecular Tweezers Targeting Transthyretin Amyloidosis

    OpenAIRE

    Ferreira, N; Pereira-Henriques, A; Attar, A.; Klärner, FG; Schrader, T; Bitan, G.; L. Gales; Saraiva, MJ; Almeida, de, J.R.

    2014-01-01

    Transthyretin (TTR) amyloidoses comprise a wide spectrum of acquired and hereditary diseases triggered by extracellular deposition of toxic TTR aggregates in various organs. Despite recent advances regarding the elucidation of the molecular mechanisms underlying TTR misfolding and pathogenic self-assembly, there is still no effective therapy for treatment of these fatal disorders. Recently, the “molecular tweezers”, CLR01, has been reported to inhibit self-assembly and toxicity of different a...

  1. Electron transport through molecular junctions

    International Nuclear Information System (INIS)

    At present, metal–molecular tunnel junctions are recognized as important active elements in molecular electronics. This gives a strong motivation to explore physical mechanisms controlling electron transport through molecules. In the last two decades, an unceasing progress in both experimental and theoretical studies of molecular conductance has been demonstrated. In the present work we give an overview of theoretical methods used to analyze the transport properties of metal–molecular junctions as well as some relevant experiments and applications. After a brief general description of the electron transport through molecules we introduce a Hamiltonian which can be used to analyze electron–electron, electron–phonon and spin–orbit interactions. Then we turn to description of the commonly used transport theory formalisms including the nonequilibrium Green’s functions based approach and the approach based on the “master” equations. We discuss the most important effects which could be manifested through molecules in electron transport phenomena such as Coulomb, spin and Frank–Condon blockades, Kondo peak in the molecular conductance, negative differential resistance and some others. Bearing in mind that first principles electronic structure calculations are recognized as the indispensable basis of the theory of electron transport through molecules, we briefly discuss the main equations and some relevant applications of the density functional theory which presently is often used to analyze important characteristics of molecules and molecular clusters. Finally, we discuss some kinds of nanoelectronic devices built using molecules and similar systems such as carbon nanotubes, various nanowires and quantum dots.

  2. SOYBEAN - MOLECULAR ASPECTS OF BREEDING

    Directory of Open Access Journals (Sweden)

    Aleksandra Sudarić

    2012-12-01

    Full Text Available The book Soybean: Molecular Aspects of Breedingfocuses recent progress in our understanding of thegenetics and molecular biology of soybean. This book isdivided into four parts and contains 22 chapters. Part I,Molecular Biology and Biotechnology focuses advancesin molecular biology and laboratory procedures thathave been developed recently to manipulate DNA.Part II, Breeding for abiotic stress covers proteomicsapproaches form as a powerful tool for investigatingthe molecular mechanisms of the plant responses tovarious types of abiotic stresses. Part III, Breeding forbiotic stress addresses issues related to application ofmolecular based strategies in order to increase soybeanresistance to various biotic factors. Part IV, RecentTechnology reviews recent technologies into the realmof soybean monitoring, processing and product use.While the information accumulated in this book is ofprimary interest for plant breeders, valuable insightsare also offered to agronomists, molecular biologists,physiologists, plant pathologists, food scientists andstudents. The book is a result of efforts made by manyexperts from different countries (USA, Japan, Croatia,Serbia, China, Canada, Malawi, Iran, Hong Kong, Brasil,Mexico.

  3. Molecular Simulations in Astrobiology

    Science.gov (United States)

    Pohorille, Andrew; Wilson, Michael A.; Schweighofer, Karl; Chipot, Christophe; New, Michael H.; Vincenzi, Donald L. (Technical Monitor)

    2001-01-01

    One of the main goals of astrobiology is to understand the origin of cellular life. In the absence of any record of the earliest ancestors of contemporary cells, protocells, the most direct way to test our understanding of their characteristics is to construct laboratory models of protocells. Such efforts, currently underway in the NASA Astrobiology Program, are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs of molecules that are capable of performing protocellular functions. Many of these functions, such as importing nutrients, capturing and storing energy, and responding to changes in the environment, are carried out by proteins bound to membranes. We use computer simulations to address the following, questions about these proteins: (1) How do small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes? (2) How do peptides aggregate to form membrane-spannin(y structures (e.g., channels)? (3) By what mechanisms do such aggregates perform their functions? The simulations are performed using the molecular dynamics (MD) method. In this method, Newton's equations of motion for each atom in the system are solved iteratively. At each time step, the forces exerted on each atom by the remaining atoms are evaluated by dividing them into two parts. Short-range forces are calculated directly in real space while long-range forces are evaluated in reciprocal space, usually using a particle-mesh algorithm which is of order O(NlnN). Currently, a time step of 2 femtoseconds is typically used, thereby making studies of problems occurring on multi-nanosecond time scales (10(exp 6) - 10(exp 8) time steps) accessible. To address a broader range of problems, simulations need to be extended by three orders of magnitude. Such an extension requires both algorithmic improvements and codes scalable to a large number of parallel

  4. Synapse formation is regulated by the signaling adaptor GIT1

    OpenAIRE

    Zhang, Huaye; Webb, Donna J.; Asmussen, Hannelore; Horwitz, Alan F.

    2003-01-01

    Dendritic spines in the central nervous system undergo rapid actin-based shape changes, making actin regulators potential modulators of spine morphology and synapse formation. Although several potential regulators and effectors for actin organization have been identified, the mechanisms by which these molecules assemble and localize are not understood. Here we show that the G protein–coupled receptor kinase–interacting protein (GIT)1 serves such a function by targeting actin regulators and lo...

  5. [Molecular and Cellular Pathogenesis of Cherubism].

    Science.gov (United States)

    Ueki, Yasuyoshi

    2016-06-01

    Study of rare genetic disorder often provides fundamental insights into the pathology of common diseases. Cherubism is a rare craniofacial disorder in children characterized by the destruction of maxillary and mandibular bones due to expansile fibrous inflammatory lesions. Genetic study of cherubism families discovered that gain-of-function mutations in the signaling adaptor protein SH3BP2 are responsible for cherubism. Analysis of the mouse model revealed that cherubism is an autoinflammatory disorder that is caused by dysregulated signaling pathway mediated by toll-like receptors and spleen tyrosine kinase. Recent study of the SH3BP2-deficient mice showed that SH3BP2 plays important roles in bone resorption in mouse models of inflammatory arthritis. These results establish SH3BP2 as a key player in the osteoimmune system beyond its role in a rare inherited disorder and suggest that the signaling pathway mediated by SH3BP2 is involved in the pathogenesis of common inflammatory bone diseases such as rheumatoid arthritis. PMID:27230848

  6. Molecular structure by Coulomb explosion imaging of stored molecular ions

    International Nuclear Information System (INIS)

    An experimental scheme, which combines Coulomb explosion imaging (CEI) with storage of fast molecular ions, has been introduced recently at the TSR heavy ion storage ring facility in Heidelberg. CEI is an experimental technique that provides direct observation of the nuclear conformations within small molecules. The combination of CEI with the storage ring technique enables the control of the internal excitation of the measured molecules, which is an essential condition to the interpretation of CEI results in terms of ''structure'' assigned to specific molecular states. This structure is measured as a function of storage time, thus enabling one to study processes of slow intramolecular dynamics such as isomerization, metastable states, etc. Moreover in this scheme, CEI can be used as a diagnostic tool for the intramolecular excitation, while other molecular interactions (e.g. with electrons or photons) are investigated. In this report, the CEI principle and the new experimental setup are described with an emphasis on the new prospects for studies in molecular physics. CEI measurements of stored CH2+ and NH2+ molecular ions are presented. The study of the angular distribution in these molecules as a function of their vibrational relaxation to the ground state, reveals unexpected behavior near the linear conformation which is inconsistent with the current adiabatic theories

  7. Molecular modeling of inelastic electron transport in molecular junctions

    International Nuclear Information System (INIS)

    A quantum chemical approach for the modeling of inelastic electron tunneling spectroscopy of molecular junctions based on scattering theory is presented. Within a harmonic approximation, the proposed method allows us to calculate the electron-vibration coupling strength analytically, which makes it applicable to many different systems. The calculated inelastic electron transport spectra are often in very good agreement with their experimental counterparts, allowing the revelation of detailed information about molecular conformations inside the junction, molecule-metal contact structures, and intermolecular interaction that is largely inaccessible experimentally

  8. Molecular imaging of tumour hypoxia

    International Nuclear Information System (INIS)

    By allowing an earlier diagnosis and a more exhaustive assessment of extension of the disease, the tomography by emission of positrons (PET) transforms the care of numerous cancers. At present, 18F-fluorodeoxyglucose ([18F]-F.D.G.) imaging appears as the only one available but new molecular markers are being developed. In the next future they would modify the approach of cancers. In this context, the molecular imaging of the hypoxia and especially the 18Fluoromisonidazole PET ([18F]-MISO PET) can give supplementary information allowing the mapping of hypoxic regions within the tumour. Because of the links, which exist between tumour hypoxia and treatment resistance of very numerous cancers, this information can have an interest, for determination of prognosis as well as for the delineation, volumes to be irradiated. Head and neck tumours are doubtless those for which the literature gives the most elements on the therapeutic impact of tumour hypoxia. Targeted therapies, based on hypoxia, already exist and the contribution of the molecular imaging could be decisive in the evaluation of the impact of such treatment. Molecular imaging of brain tumours remains to be developed. The potential contributions of the [18F]-MISO PET for the care of these patients need to be confirmed. In this context, we propose a review of hypoxia molecular imaging taking as examples head and neck tumours and glioblastomas (GB), two tumours for which hypoxia is one of the key factors to overcome in order to increase therapeutics results

  9. Molecular classification of gastric cancer.

    Science.gov (United States)

    Chia, N-Y; Tan, P

    2016-05-01

    Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID:26861606

  10. Molecular modelling of betalactamic antibiotic

    Directory of Open Access Journals (Sweden)

    Elso Manuel Cruz Cruz

    2010-02-01

    Full Text Available Background: The antibacterial properties of a compound are the result of its molecular structure. To establish the structural and electronic characteristics makes possible to understand the mechanisms of its action and becomes paramount for the rational design new drugs. Objective: To model some of the molecular properties of betalactamic antibiotics and inhibitors of the betalactamases and to relate them with their pharmacological actions. Method: The molecular structures were optimized with PM3• semiempiric calculus. The structure of the betalactamic ring in the different compounds was compared. The molecular properties were calculated according to the Density Functional Theory at a B3LYP/6-31G(d level. The density of the atomic charges and the frontier orbitals were analyzed. Results There are variations in the calculated properties that make possible to define two groups of compounds: one for the monobactams and the inhibitors of the betalactamases, with less planarity in the ring and less reactivity and another one with the penicillins, cephalosporins and carbapenems, planer, more structurally stable and reactive. Conclusions: The modelled molecular properties of the betalactamic antibiotics and inhibitors of the betalactamases show agreement with its pharmacological action.

  11. Laser ionization of molecular clusters

    International Nuclear Information System (INIS)

    Multiphoton ionization coupled with mass spectrometry was used to investigate molecular cluster distributions. Three examples will be discussed in this presentation. First, in studies of neat nitric oxide clusters, (NO)m, an interesting odd-even intensity alternation was observed and will be discussed in terms of electron-pairing considerations. In a separate study, the binary clusters comprising nitric oxide and methane preferentially form a stoichiometric cluster made up of repeating units of (NO)2CH4. These presumably represent a particularly strongly bound open-quotes van der Waalsclose quotes subunit. Finally, in similar studies of neat carbon disulfide clusters, (CS2)m, additional photon absorption after the two-photon ionization step stimulates a series of intracluster ion-molecular reactions leading to formation of Sm+ and (CS)m+ polymers, as well as intermediate species such as Sm+ (CS2). This molecular cluster analogue of open-quotes laser snowclose quotes will be described in detail

  12. Ab-Initio Molecular Dynamics

    CERN Document Server

    Kühne, Thomas D

    2012-01-01

    Computer simulations and molecular dynamics in particular, is a very powerful method to provide detailed and essentially exact informations of classical many-body problems. With the advent of \\textit{ab-initio} molecular dynamics, where the forces are computed on-the-fly by accurate electronic structure calculations, the scope of either method has been greatly extended. This new approach, which unifies Newton's and Schr\\"odinger's equations, allows for complex simulations without relying on any adjustable parameter. This review is intended to outline the basic principles as well as a survey of the field. Beginning with the derivation of Born-Oppenheimer molecular dynamics, the Car-Parrinello method as well as novel hybrid scheme that unifies best of either approach are discussed. The predictive power is demonstrated by a series of applications ranging from insulators to semiconductors and even metals in condensed phases.

  13. State-Dependent Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Ciann-Dong Yang

    2014-10-01

    Full Text Available This paper proposes a new mixed quantum mechanics (QM—molecular mechanics (MM approach, where MM is replaced by quantum Hamilton mechanics (QHM, which inherits the modeling capability of MM, while preserving the state-dependent nature of QM. QHM, a single mechanics playing the roles of QM and MM simultaneously, will be employed here to derive the three-dimensional quantum dynamics of diatomic molecules. The resulting state-dependent molecular dynamics including vibration, rotation and spin are shown to completely agree with the QM description and well match the experimental vibration-rotation spectrum. QHM can be incorporated into the framework of a mixed quantum-classical Bohmian method to enable a trajectory interpretation of orbital-spin interaction and spin entanglement in molecular dynamics.

  14. Microwave regeneration of molecular sieves

    International Nuclear Information System (INIS)

    Molecular sieve driers have been included in the design of tritium handling systems for fusion reactors. In these systems there is a need to maintain extremely low exit dew points from the driers as well as a capability to rapidly reduce tritium concentrations following an accident. The required capacity of the driers is very high. The conventional method of regenerating these sieves after a water adsorption cycle is with hot air. However, because water is rapidly heated by microwave energy, this technology may be suitable for decreasing the bed regeneration time and hence may allow reduced capital and operating costs associated with a smaller bed. The present study was conducted to obtain preliminary information on the technical feasibility of regenerating molecular sieves with microwave energy. The study concentrated on Type 4A molecular sieve with a few tests on Type 13X sieve and also a silica gel adsorbent

  15. Molecular Architectonic on Metal Surfaces

    Science.gov (United States)

    Barth, Johannes V.

    2007-05-01

    The engineering of highly organized systems from instructed molecular building blocks opens up new vistas for the control of matter and the exploration of nanodevice concepts. Recent investigations demonstrate that well-defined surfaces provide versatile platforms for steering and monitoring the assembly of molecular nanoarchitectures in exquisite detail. This review delineates the principles of noncovalent synthesis on metal substrates under ultrahigh vacuum conditions and briefly assesses the pertaining terminology—self-assembly, self-organization, and self-organized growth. It presents exemplary scanning-tunneling-microscopy observations, providing atomistic insight into the self-assembly of organic clusters, chains, and superlattices, and the metal-directed assembly of low-dimensional coordination architectures. This review also describes hierarchic-assembly protocols leading to intricate multilevel order. Molecular architectonic on metal surfaces represents a versatile rationale to realize structurally complex nanosystems with specific shape, composition, and functional properties, which bear promise for technological applications.

  16. Molecular imaging in cancer treatment

    International Nuclear Information System (INIS)

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  17. Electron transport in molecular junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun

    charge position are in quantitative agreement with the experiments, while pure DFT is not. This is the consequence of the accurate energy level alignment, where the DFT+∑ method corrects the self-interaction error in the standard DFT functional and uses a static image charge model to include the image......This thesis addresses the electron transport in molecular junctions, focusing on the energy level alignment and correlation effects. Various levels of theory have been applied to study the structural and electronic effects in different molecular junctions, starting from the single particle density...... the lowest unoccupied molecular level (LUMO) of the 44BP molecule hybridizes strongly with Ni 3d orbitals, the gating is auxiliary by the so-called spinterface. Finally, the correlation effect of the image charge beyond the energy level renormalization has been studied. It is shown that the finite response...

  18. Molecular diagnostics of foodborne pathogens

    DEFF Research Database (Denmark)

    Hansen, Trine

    of pathogens are needed. The introduction of the molecular diagnostics methods based on detection of the organisms nucleic acids have made detection, identification and characterization of foodborne pathogens faster and with greater specificity and sensitivity. The objectives of research in this thesis were...... to investigate the use of different nucleic acid based methods for molecular diagnostics of foodborne pathogens focusing on Salmonellaand Bacillus cereuswith respect to improve food safety. The work represents two parts of molecular diagnostics; the characterization Salmonellafor better understanding of its...... for screening of unknown bacteria in bottled water without prior cultivation. B. cereusartificially inoculated in bottled water was used as a model. The results revealed that the method was able to detect B. cereusat levels of 105-106 CFU/L, a detection level low enough for detection in outbreaks situations...

  19. Molecular morphology of cyanobacterial phycobilisomes

    Energy Technology Data Exchange (ETDEWEB)

    Siegelman, H.W.; Kycia, J.H.

    1982-09-01

    Phycobilisomes were isolated from several cyanobacteria following cell lysis with Triton X-100. They were purified by phosphate precipitation and hydrophobic-interaction chromatography. Their phycobiliprotein compositions were quantitatively determined by application of sets of simultaneous absorbance equations to gel chromatographic separations of the chromoproteins. Phycobilisomes purified from several cyanobacteria had characteristic elution times on agarose gel chromatography. Combining electron microscope observations of phycobilisome structure, phycobiliprotein composition, and agarose gel chromatography estimates of molecular weight permitted the calculation of many details of phycobilisome molecular structure. Complementary chromatic adaptation resulted in a change of phycobilisome composition and structure. The polypeptide compositions of phycobilisomes were examined by sodium dodecyl sulfate-agarose gel chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The phycobilisomes were composed of phycobilipeptides derived from the constituent phycobiliproteins. Higher molecular-weight phycobilipeptide aggregates were also observed. The dominant forces responsible for the maintenance of phycobilisome structure are concluded to be hydropohobic interactions.

  20. Laser Ablation Molecular Isotopic Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Richard E., E-mail: rerusso@lbl.gov [Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States); Applied Spectra, Inc., 46661 Fremont Boulevard, Fremont, CA 94538 (United States); Bol' shakov, Alexander A. [Applied Spectra, Inc., 46661 Fremont Boulevard, Fremont, CA 94538 (United States); Mao Xianglei [Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States); McKay, Christopher P. [NASA-Ames Research Center, Moffett Field, CA 94035 (United States); Perry, Dale L.; Sorkhabi, Osman [Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States)

    2011-02-15

    A new method of performing optical isotopic analysis of condensed samples in ambient air and at ambient pressure has been developed: Laser Ablation Molecular Isotopic Spectrometry (LAMIS). The technique uses radiative transitions from molecular species either directly vaporized from a sample or formed by associative mechanisms of atoms or ions in a laser ablation plume. This method is an advanced modification of a known atomic emission technique called laser-induced breakdown spectroscopy (LIBS). The new method - LAMIS - can determine not only chemical composition but also isotopic ratios of elements in the sample. Isotopic measurements are enabled by significantly larger isotopic shifts found in molecular spectra relative to atomic spectra. Analysis can be performed from a distance and in real time. No sample preparation or pre-treatment is required. Detection of the isotopes of hydrogen, boron, carbon, and oxygen are discussed to illustrate the technique.

  1. Laser Ablation Molecular Isotopic Spectrometry

    Science.gov (United States)

    Russo, Richard E.; Bol'shakov, Alexander A.; Mao, Xianglei; McKay, Christopher P.; Perry, Dale L.; Sorkhabi, Osman

    2011-02-01

    A new method of performing optical isotopic analysis of condensed samples in ambient air and at ambient pressure has been developed: Laser Ablation Molecular Isotopic Spectrometry (LAMIS). The technique uses radiative transitions from molecular species either directly vaporized from a sample or formed by associative mechanisms of atoms or ions in a laser ablation plume. This method is an advanced modification of a known atomic emission technique called laser-induced breakdown spectroscopy (LIBS). The new method — LAMIS — can determine not only chemical composition but also isotopic ratios of elements in the sample. Isotopic measurements are enabled by significantly larger isotopic shifts found in molecular spectra relative to atomic spectra. Analysis can be performed from a distance and in real time. No sample preparation or pre-treatment is required. Detection of the isotopes of hydrogen, boron, carbon, and oxygen are discussed to illustrate the technique.

  2. OH+ in Diffuse Molecular Clouds

    CERN Document Server

    Porras, A J; Welty, D E; Ritchey, A M

    2013-01-01

    Near ultraviolet observations of OH+ and OH in diffuse molecular clouds reveal a preference for different environments. The dominant absorption feature in OH+ arises from a main component seen in CH+ (that with the highest CH+/CH column density ratio), while OH follows CN absorption. This distinction provides new constraints on OH chemistry in these clouds. Since CH+ detections favor low-density gas with small fractions of molecular hydrogen, this must be true for OH+ as well, confirming OH+ and H2O+ observations with the Herschel Space Telescope. Our observed correspondence indicates that the cosmic ray ionization rate derived from these measurements pertains to mainly atomic gas. The association of OH absorption with gas rich in CN is attributed to the need for high enough density and molecular fraction before detectable amounts are seen. Thus, while OH+ leads to OH production, chemical arguments suggest that their abundances are controlled by different sets of conditions and that they coexist with differen...

  3. Nanofriction properties of molecular deposition films

    Institute of Scientific and Technical Information of China (English)

    王强斌; 高芒来; 张嗣伟

    2000-01-01

    The nanofriction properties of Au substrate and monolayer molecular deposition film and multilayer molecular deposition films on Au substrate and the molecular deposition films modified with alkyl-terminal molecule have been investigated by using an atomic force microscope. It is concluded that ( i ) the deposition of molecular deposition films on Au substrate and the modification of alkyl-terminal molecule to the molecular deposition films can reduce the frictional force; (ii) the molecular deposition films with the same terminal exhibit similar nanofriction properties, which has nothing to do with the molecular chain-length and the layer number; (iii) the unstable nanofriction properties of molecular deposition films are contributed to the active terminal of the molecular deposition film, which can be eliminated by decorating the active molecular deposition film with alkyl-terminal molecule, moreover, the decoration of alkyl-terminal molecule can lower the frictional force conspicuously; (iv) the relat

  4. Molecular replacement: tricks and treats

    International Nuclear Information System (INIS)

    To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% of the total structure and the Cα r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples

  5. Molecular transport junctions: vibrational effects

    International Nuclear Information System (INIS)

    Transport of electrons in a single molecule junction is the simplest problem in the general subject area of molecular electronics. In the past few years, this area has been extended to probe beyond the simple tunnelling associated with large energy gaps between electrode Fermi level and molecular levels, to deal with smaller gaps, with near-resonance tunnelling and, particularly, with effects due to interaction of electronic and vibrational degrees of freedom. This overview is devoted to the theoretical and computational approaches that have been taken to understanding transport in molecular junctions when these vibronic interactions are involved. After a short experimental overview, and discussion of different test beds and measurements, we define a particular microscopic model Hamiltonian. That overall Hamiltonian can be used to discuss all of the phenomena dealt with subsequently. These include transition from coherent to incoherent transport as electron/vibration interaction increases in strength, inelastic electron tunnelling spectroscopy and its interpretation and measurement, affects of interelectronic repulsion treated at the Hubbard level, noise in molecular transport junctions, non-linear conductance phenomena, heating and heat conduction in molecular transport junctions and current-induced chemical reactions. In each of these areas, we use the same simple model Hamiltonian to analyse energetics and dynamics. While this overview does not attempt survey the literature exhaustively, it does provide appropriate references to the current literature (both experimental and theoretical). We also attempt to point out directions in which further research is required to answer cardinal questions concerning the behaviour and understanding of vibrational effects in molecular transport junctions. (topical review)

  6. Molecular clouds near supernova remnants

    International Nuclear Information System (INIS)

    The physical properties of molecular clouds near supernova remnants were investigated. Various properties of the structure and kinematics of these clouds are used to establish their physical association with well-known remmnants. An infrared survey of the most massive clouds revealed embedded objects, probably stars whose formation was induced by the supernova blast wave. In order to understand the relationship between these and other molecular clouds, a control group of clouds was also observed. Excitation models for dense regions of all the clouds are constructed to evaluate molecular abundances in these regions. Those clouds that have embedded stars have lower molecular abundances than the clouds that do not. A cloud near the W28 supernova remnant also has low abundances. Molecular abundances are used to measure an important parameter, the electron density, which is not directly observable. In some clouds extensive deuterium fractionation is observed which confirms electron density measurements in those clouds. Where large deuterium fractionation is observed, the ionization rate in the cloud interior can also be measured. The electron density and ionization rate in the cloud near W28 are higher than in most clouds. The molecular abundances and electron densities are functions of the chemical and dynamical state of evolution of the cloud. Those clouds with lowest abundances are probably the youngest clouds. As low-abundance clouds, some clouds near supernova remnants may have been recently swept from the local interstellar material. Supernova remnants provide sites for star formation in ambient clouds by compressing them, and they sweep new clouds from more diffuse local matter

  7. Light and Redox Switchable Molecular Components for Molecular Electronics

    NARCIS (Netherlands)

    Browne, Wesley R.; Feringa, Bernard

    2010-01-01

    The field of molecular and organic electronics has seen rapid progress in recent years, developing from concept and design to actual demonstration devices in which both single molecules and self-assembled monolayers are employed as light-responsive components. Research in this field has seen numerou

  8. Molecular Modeling of Estrogen Receptor Using Molecular Operating Environment

    Science.gov (United States)

    Roy, Urmi; Luck, Linda A.

    2007-01-01

    Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where…

  9. A sampling of molecular dynamics

    Science.gov (United States)

    Sindhikara, Daniel Jon

    The sheer vastness of the number of computations required to simulate a biological molecule puts incredible pressure on algorithms to be efficient while maintaining sufficient accuracy. This dissertation summarizes various projects whose purposes address the large span of types of problems in molecular dynamics simulations of biological systems including: increasing efficiency, measuring convergence, avoiding pitfalls, and an application and analysis of a biological system. Chapters 3 and 4 deal with an enhanced sampling algorithm called "replica exchange molecular dynamics" which is designed to speed-up molecular dynamics simulations. The optimization of a key parameter of these simulations is analyzed. In these successive projects, it was found conclusively that maximizing "exchange attempt frequency" is the most efficient way to run a replica exchange molecular dynamics simulation. Chapter 5 describes an enhanced metric for convergence in parallel simulations called the normalized ergodic measure. The metric is applied to several properties for several replica exchange simulations. Advantages of this metric over other methods are described. Chapter 6 describes the implementation and optimization of an enhanced sampling algorithm similar to replica exchange molecular dynamics called multicanonical algorithm replica exchange molecular dynamics. The algorithm was implemented into a biomolecular simulation suite called AMBER. Additionally several parameters were analyzed and optimized. In Chapter 7, a pitfall in molecular dynamics is observed in biological systems that is caused by negligent use of a simulation's "thermostat". It was found that if the same pseudorandom number seed were used for multiple systems, they eventually synchronize. In this project, synchronization was observed in biological molecules. Various negative effects including corruption of data are pointed out. Chapter 8 describes molecular dynamics simulation of NikR, a homotetrameric nickel

  10. Industrial Applications of Molecular Simulations

    CERN Document Server

    Meunier, Marc

    2011-01-01

    The field of quantum and molecular simulations has experienced strong growth since the time of the early software packages. A recent study, showed a large increase in the number of people publishing papers based on ab initio methods from about 3,000 in 1991 to roughly 20,000 in 2009, with particularly strong growth in East Asia. Looking to the future, the question remains as to how these methods can be further integrated into the R&D value chain, bridging the gap from engineering to manufacturing. Using successful case studies as a framework, Industrial Applications of Molecular Simulations de

  11. Asymmetric interference in molecular photoprocesses

    International Nuclear Information System (INIS)

    For the first time, the Coulomb continuum effects in asymmetric molecular interference have been studied analytically in photoionization, photorecombination, bremsstrahlung and Compton ionization. Simple, closed-form factors describe the interference not only in monochromatic photoprocesses, but also in the continuous photoelectron spectra generated by attosecond x-ray pulses with a frequency-dependent phase and broad bandwidth. Using HeH2+ molecular ion as an example, we show how the plane wave interference pattern is strongly modified by the two-centre Coulomb continuum. Asymmetric Coulomb continuum introduces qualitative changes in a photoionization process

  12. Molecular catalytic coal liquid conversion

    Energy Technology Data Exchange (ETDEWEB)

    Stock, L.M.; Yang, Shiyong [Univ. of Chicago, IL (United States)

    1995-12-31

    This research, which is relevant to the development of new catalytic systems for the improvement of the quality of coal liquids by the addition of dihydrogen, is divided into two tasks. Task 1 centers on the activation of dihydrogen by molecular basic reagents such as hydroxide ion to convert it into a reactive adduct (OH{center_dot}H{sub 2}){sup {minus}} that can reduce organic molecules. Such species should be robust withstanding severe conditions and chemical poisons. Task 2 is focused on an entirely different approach that exploits molecular catalysts, derived from organometallic compounds that are capable of reducing monocyclic aromatic compounds under very mild conditions. Accomplishments and conclusions are discussed.

  13. Inverse strategies for molecular design

    International Nuclear Information System (INIS)

    An 'inverse' molecular design strategy is described to assist in the development of new molecules with optimized properties. This approach is based on a molecular orbital view and can be used to tailor ground state or excited state properties subject to particular constrains. In this scheme, wave functions are sought that optimize a chemical or electronic property, and then a Hamiltonian is constructed that generates these optimized wave functions. Analysis of the chemical properties in the optimized systems may suggest new synthetic targets. Examples are presented that optimize the transition dipole moment in some simple structures. 15 refs., 6 figs

  14. Hydrogen storage in molecular compounds

    OpenAIRE

    Mao, Wendy L.; Mao, Ho-kwang

    2004-01-01

    At low temperature (T) and high pressure (P), gas molecules can be held in ice cages to form crystalline molecular compounds that may have application for energy storage. We synthesized a hydrogen clathrate hydrate, H2(H2O)2, that holds 50 g/liter hydrogen by volume or 5.3 wt %. The clathrate, synthesized at 200–300 MPa and 240–249 K, can be preserved to ambient P at 77 K. The stored hydrogen is released when the clathrate is warmed to 140 K at ambient P. Low T also stabilizes other molecular...

  15. Oscillations in molecular motor assemblies

    CERN Document Server

    Vilfan, A; Vilfan, Andrej; Frey, Erwin

    2005-01-01

    Autonomous oscillations in biological systems may have a biochemical origin or result from an interplay between force-generating and visco-elastic elements. In molecular motor assemblies the force-generating elements are molecular engines and the visco-elastic elements are stiff cytoskeletal polymers. The physical mechanism leading to oscillations depends on the particular architecture of the assembly. Existing models can be grouped into two distinct categories: systems with a {\\em delayed force activation} and {\\em anomalous force-velocity relations}. We discuss these systems within phase plane analysis known from the theory of dynamic systems and by adopting methods from control theory, the Nyquist criterion.

  16. Molecular calculations with B functions

    CERN Document Server

    Steinborn, E O; Ema, I; López, R; Ramírez, G

    1998-01-01

    A program for molecular calculations with B functions is reported and its performance is analyzed. All the one- and two-center integrals, and the three-center nuclear attraction integrals are computed by direct procedures, using previously developed algorithms. The three- and four-center electron repulsion integrals are computed by means of Gaussian expansions of the B functions. A new procedure for obtaining these expansions is also reported. Some results on full molecular calculations are included to show the capabilities of the program and the quality of the B functions to represent the electronic functions in molecules.

  17. [Opportunity and challenge on molecular epidemiology].

    Science.gov (United States)

    Duan, G C; Chen, S Y

    2016-08-10

    Molecular epidemiology, a branch of epidemiology, combines the theories and methods, both in epidemiology and molecular biology. Molecular epidemiology mainly focuses on biological markers, describing the distribution, occurrence, development and prognosis of diseases at the molecular level. The completion of Human Genome Project and rapid development of Precision Medicine and Big Data not only offer the new development opportunities but also bring about a higher demand and new challenge for molecular epidemiology. PMID:27539332

  18. Molecular outflows in starburst nuclei

    CERN Document Server

    Roy, Arpita; Sharma, Prateek; Shchekinov, Yuri

    2016-01-01

    Recent observations have detected molecular outflows in a few nearby starburst nuclei. We discuss the physical processes at work in such an environment in order to outline a scenario that can explain the observed parameters of the phenomenon, such as the molecular mass, speed and size of the outflows. We show that outflows triggered by OB associations, with $N_{OB}\\ge 10^5$ (corresponding to a star formation rate (SFR)$\\ge 1$ M$_{\\odot}$ yr$^{-1}$ in the nuclear region), in a stratified disk with mid-plane density $n_0\\sim 200\\hbox{--}1000$ cm$^{-3}$ and scale height $z_0\\ge 200 (n_0/10^2 \\, {\\rm cm}^{-3})^{-3/5}$ pc, can form molecules in a cool dense and expanding shell. The associated molecular mass is $\\ge 10^7$ M$_\\odot$ at a distance of a few hundred pc, with a speed of several tens of km s$^{-1}$. We show that a SFR surface density of $10 \\le \\Sigma_{SFR} \\le 50$ M$_\\odot$ yr$^{-1}$ kpc$^{-2}$ favours the production of molecular outflows, consistent with observed values.

  19. Light-Powered Molecular Engineering

    DEFF Research Database (Denmark)

    Neves Petersen, Teresa; Crookshanks, Meg; Skovsen, Esben;

    2007-01-01

    We present a new photonic technology and demonstrate that it allows for precise immobilisation of biomolecules to sensor surfaces. The technology secures spatially controlled molecular immobilisation since immobilisation of each molecule to a support surface can be limited to the focal point of t...

  20. Electron scattering on molecular hydrogen

    International Nuclear Information System (INIS)

    The author considers scattering phenomena which occur when a beam of electrons interacts with a molecular hydrogen gas of low density. Depending on the energy loss of the scattered electrons one can distinguish elastic scattering, excitation and (auto)ionization of the H2-molecule. The latter processes may also lead to dissociation. These processes are investigated in four experiments in increasing detail. (Auth.)

  1. Ordered structures of molecular bottlebrushes

    NARCIS (Netherlands)

    ten Brinke, G.; Ikkala, O.

    1997-01-01

    In this review 'molecular bottlebrushes' are flexible polymers densely loaded with equally flexible side chains. Interest in these structures arises from the possibility of lyotropic behaviour in dilute solution in a good solvent, as well as the possibility, of highly, ordered microphase-separated s

  2. Ordered Structures of Molecular Bottlebrushes

    NARCIS (Netherlands)

    Brinke, Gerrit ten; Ikkala, Olli

    1997-01-01

    In this review 'molecular bottlebrushes' are flexible polymers densely loaded with equally flexible side chains. Interest in these structures arises from the possibility of lyotropic behaviour in dilute solution in a good solvent, as well as the possibility of highly ordered microphase-separated sta

  3. Molecular imaging in cardiovascular diseases

    International Nuclear Information System (INIS)

    Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

  4. Coherently Controlled Nanoscale Molecular Deposition

    OpenAIRE

    Dey, Bijoy K.; Shapiro, Moshe; Brumer, Paul

    2000-01-01

    Quantum interference effects are shown to provide a means of controlling and enhancing the focusing a collimated neutral molecular beam onto a surface. The nature of the aperiodic pattern formed can be altered by varying laser field characteristics and the system geometry.

  5. Molecular Mobility in Sugar Glasses

    NARCIS (Netherlands)

    Dries, van den I.J.

    2000-01-01

    Glasses are liquids that exhibit solid state behavior as a result of their extremely high viscosity. Regarding their application to foods, glasses play a role in the preservation of foods, due to their high viscosity and the concomitant low molecular mobility. This thesis focuses on sugar glasses. S

  6. Alligator clips to molecular dimensions

    International Nuclear Information System (INIS)

    Techniques for fabricating nanospaced electrodes suitable for studying electron tunneling through metal-molecule-metal junctions are described. In one approach, top contacts are deposited/placed on a self-assembled monolayer or Langmuir-Blodgett film resting on a conducting substrate, the bottom contact. The molecular component serves as a permanent spacer that controls and limits the electrode separations. The top contact can be a thermally deposited metal film, liquid mercury drop, scanning probe tip, metallic wire or particle. Introduction of the top contact can greatly affect the electrical conductance of the intervening molecular film by chemical reaction, exerting pressure, or simply migrating through the organic layer. Alternatively, vacant nanogaps can be fabricated and the molecular component subsequently inserted. Strategies for constructing vacant nanogaps include mechanical break junction, electromigration, shadow mask lithography, focused ion beam deposition, chemical and electrochemical plating techniques, electron-beam lithography, and molecular and atomic rulers. The size of the nanogaps must be small enough to allow the molecule to connect both leads and large enough to keep the molecules in a relaxed and undistorted state. A significant advantage of using vacant nanogaps in the construction of metal-molecule-metal devices is that the junction can be characterized with and without the molecule in place. Any electrical artifacts introduced by the electrode fabrication process are more easily deconvoluted from the intrinsic properties of the molecule

  7. Molecular outflows in starburst nuclei

    Science.gov (United States)

    Roy, Arpita; Nath, Biman B.; Sharma, Prateek; Shchekinov, Yuri

    2016-08-01

    Recent observations have detected molecular outflows in a few nearby starburst nuclei. We discuss the physical processes at work in such an environment in order to outline a scenario that can explain the observed parameters of the phenomenon, such as the molecular mass, speed and size of the outflows. We show that outflows triggered by OB associations, with NOB ≥ 105 (corresponding to a star formation rate (SFR)≥1 M⊙ yr-1 in the nuclear region), in a stratified disk with mid-plane density n0 ˜ 200-1000 cm-3 and scale height z0 ≥ 200(n0/102 cm-3)-3/5 pc, can form molecules in a cool dense and expanding shell. The associated molecular mass is ≥107 M⊙ at a distance of a few hundred pc, with a speed of several tens of km s-1. We show that a SFR surface density of 10 ≤ ΣSFR ≤ 50 M⊙ yr-1 kpc-2 favours the production of molecular outflows, consistent with observed values.

  8. Molecular diagnosis of intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Haga, Hiroaki; Patel, Tushar

    2015-01-01

    Intrahepatic cholangiocarcinomas (iCCA) are primary intrahepatic malignancies originating from biliary epithelia. While both hepatocellular cancer and iCCA can present as mass lesions within the liver, these cancers are distinct in their morphology, etiology, pathology, natural history and response to therapy. There is a need for accurate and sensitive molecular markers for the diagnosis of iCCA. Recent advances in elucidating molecular and genetic characteristics of iCCA offer the potential of molecular-based diagnosis of iCCA. Specific genetic mutations of IDH1/2, BAP1, p53, and KRAS, FGFR gene fusions and alterations in microRNA have all been described in iCCA. Although there are no accurate serum or biliary biomarkers currently available for diagnosis of iCCA, several potential candidates have been identified. Knowledge of specific genetic or molecular abnormalities offers potential for individualized approaches for the treatment of patients with iCCA in the future. PMID:25267595

  9. Molecular biology of Plasmodiophora brassicae

    DEFF Research Database (Denmark)

    Siemens, Johannes; Bulman, Simon; Rehn, Frank;

    2009-01-01

    of several genes have been revealed, and the expression of those genes has been linked to development of clubroot to some extent. In addition, the sequence data have reinforced the inclusion of the plasmodiophorids within the Cercozoa. The recent successes in molecular biology have produced new approaches...

  10. Insect symbionts and molecular phylogenetics

    Czech Academy of Sciences Publication Activity Database

    Hypša, Václav; Nováková, Eva

    Vol. 3. Boca Raton, FL: CRC Press, 2008 - (Bourtzis, K.; Miller, T.), s. 1-32. (Contemporary Topics in Entomology. 4). ISBN 1-4200-6410-X R&D Projects: GA AV ČR IAA601410708; GA MŠk LC06073 Institutional research plan: CEZ:AV0Z60220518 Keywords : symbiosis * molecular phylogeny * insect symbionts * coevolution Subject RIV: EG - Zoology

  11. Rethinking a Mysterious Molecular Cloud

    CERN Document Server

    Imara, Nia

    2015-01-01

    I present high-resolution column density maps of two molecular clouds having strikingly different star formation rates. To better understand the unusual, massive G216-2.5, a molecular cloud with no massive star formation, the distribution of its molecular gas is compared to that of the Rosette Molecular Cloud. Far-infrared data from Herschel are used to derive $N(\\mathrm{H}_2)$ maps of each cloud and are combined with $I_{\\mathrm{CO}}$ data to determine the CO-to-H$_2$ ratio, $X_{\\mathrm{CO}}$. In addition, the probability distribution functions (PDFs) and cumulative mass fractions of the clouds are compared. For G216-2.5, $=7.8\\times 10^{20} cm^{-2}$ and $ =2.2\\times 10^{20} (K km s^{-1})^{-1}$; for the Rosette, $ =1.8\\times 10^{21} cm^{-2}$ and $ =2.8\\times 10^{20} (K km s^{-1})^{-1}$. The PDFs of both clouds are log-normal for extinctions below $\\sim 2$ mag and both show departures from log-normality at high extinctions. Although it is the less-massive cloud, the Rosette has a higher fraction of its mass ...

  12. OH+ IN DIFFUSE MOLECULAR CLOUDS

    International Nuclear Information System (INIS)

    Near ultraviolet observations of OH+ and OH in diffuse molecular clouds reveal a preference for different environments. The dominant absorption feature in OH+ arises from a main component seen in CH+ (that with the highest CH+/CH column density ratio), while OH follows CN absorption. This distinction provides new constraints on OH chemistry in these clouds. Since CH+ detections favor low-density gas with small fractions of molecular hydrogen, this must be true for OH+ as well, confirming OH+ and H2O+ observations with the Herschel Space Telescope. Our observed correspondence indicates that the cosmic ray ionization rate derived from these measurements pertains to mainly atomic gas. The association of OH absorption with gas rich in CN is attributed to the need for a high enough density and molecular fraction before detectable amounts are seen. Thus, while OH+ leads to OH production, chemical arguments suggest that their abundances are controlled by different sets of conditions and that they coexist with different sets of observed species. Of particular note is that non-thermal chemistry appears to play a limited role in the synthesis of OH in diffuse molecular clouds

  13. Cancer Stratification by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Justus Weber

    2015-03-01

    Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

  14. Low-dimensional molecular metals

    CERN Document Server

    Toyota, Naoki; Muller, Jens

    2007-01-01

    Assimilating research in the field of low-dimensional metals, this monograph provides an overview of the status of research on quasi-one- and two-dimensional molecular metals, describing normal-state properties, magnetic field effects, superconductivity, and the phenomena of interacting p and d electrons.

  15. Molecular dynamics simulation of diffusivity

    Institute of Scientific and Technical Information of China (English)

    Juanfang LIU; Danling ZENG; Qin LI; Hong GAO

    2008-01-01

    Equilibrium molecular dynamics simulation was performed on water to calculate its diffusivity by adopting different potential models. The results show that the potential models have great influence on the simulated results. In addition, the diffusivities obtained by the SPCE model conform well to the experimental values.

  16. Molecular chaperones and neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates that result from conformational changes in proteins. These diseases may result from an imbalance between the production of misfolded proteins and normal chaperone capacity. Molecular chaperones provide a first line of defence against misfolded, aggregation-prone proteins and are, therefore, promising therapeutic targets for neurodegenerative diseases.

  17. Molecular Properties through Polarizable Embedding

    DEFF Research Database (Denmark)

    Olsen, Jógvan Magnus Haugaard; Kongsted, Jacob

    2011-01-01

    We review the theory related to the calculation of electric and magnetic molecular properties through polarizable embedding. In particular, we derive the expressions for the response functions up to the level of cubic response within the density functional theory-based polarizable embedding (PE...

  18. Molecularly imprinted polymers for mycotoxins

    Science.gov (United States)

    Molecularly imprinted polymers (MIPs) are a class of synthetic receptors capable of selective recognition of analytes. Recent developments in imprinting technology have made it possible to apply this technology in a range of applications, including mycotoxin detection. Structure-activity relations...

  19. Molecular Foundry, Berkeley, California (Revised)

    Energy Technology Data Exchange (ETDEWEB)

    Carlisle, N.

    2008-03-01

    This case study provides information on the Molecular Foundry, which incorporates Labs21 principles in its design and construction. The design includes many of the strategies researched at Lawrence Berkeley Laboratory for energy efficient cleanroom and data centers. The result is an energy efficient high-performing sustainable laboratory.

  20. A synthetic molecular pentafoil knot

    Science.gov (United States)

    Ayme, Jean-François; Beves, Jonathon E.; Leigh, David A.; McBurney, Roy T.; Rissanen, Kari; Schultz, David

    2012-01-01

    Knots are being discovered with increasing frequency in both biological and synthetic macromolecules and have been fundamental topological targets for chemical synthesis for the past two decades. Here, we report on the synthesis of the most complex non-DNA molecular knot prepared to date: the self-assembly of five bis-aldehyde and five bis-amine building blocks about five metal cations and one chloride anion to form a 160-atom-loop molecular pentafoil knot (five crossing points). The structure and topology of the knot is established by NMR spectroscopy, mass spectrometry and X-ray crystallography, revealing a symmetrical closed-loop double helicate with the chloride anion held at the centre of the pentafoil knot by ten CH···Cl- hydrogen bonds. The one-pot self-assembly reaction features an exceptional number of different design elements—some well precedented and others less well known within the context of directing the formation of (supra)molecular species. We anticipate that the strategies and tactics used here can be applied to the rational synthesis of other higher-order interlocked molecular architectures.

  1. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...

  2. Progress in quantum molecular dynamics

    International Nuclear Information System (INIS)

    In this paper a microscopic simulation method of the quantum molecular dynamics (QMD) and its extensions to high- and low-energy regions are reported. Combined with the statistical decay calculation, QMD can reproduce experimental data with fixed and very few parameters. (J.P.N.)

  3. Thermoelectric efficiency of molecular junctions.

    Science.gov (United States)

    Perroni, C A; Ninno, D; Cataudella, V

    2016-09-21

    Focus of the review is on experimental set-ups and theoretical proposals aimed to enhance thermoelectric performances of molecular junctions. In addition to charge conductance, the thermoelectric parameter commonly measured in these systems is the thermopower, which is typically rather low. We review recent experimental outcomes relative to several junction configurations used to optimize the thermopower. On the other hand, theoretical calculations provide estimations of all the thermoelectric parameters in the linear and non-linear regime, in particular of the thermoelectric figure of merit and efficiency, completing our knowledge of molecular thermoelectricity. For this reason, the review will mainly focus on theoretical studies analyzing the role of not only electronic, but also of the vibrational degrees of freedom. Theoretical results about thermoelectric phenomena in the coherent regime are reviewed focusing on interference effects which play a significant role in enhancing the figure of merit. Moreover, we review theoretical studies including the effects of molecular many-body interactions, such as electron-vibration couplings, which typically tend to reduce the efficiency. Since a fine tuning of many parameters and coupling strengths is required to optimize the thermoelectric conversion in molecular junctions, new theoretically proposed set-ups are discussed in the conclusions. PMID:27420149

  4. Molecular detection technologies for arboviruses

    Science.gov (United States)

    Arthropod-borne animal viruses (arboviruses) cause significant livestock and economic losses to world agriculture. This paper discusses the current and potential impact of these viruses, as well as the current and developing molecular diagnostic tools for these emerging and re-emerging insect transm...

  5. An invitation to molecular magnetism.

    Science.gov (United States)

    Pinkowicz, Dawid; Chorazy, Szymon; Stefańczyk, Olaf

    2011-01-01

    Molecular magnetism is a new and extremely fascinating field on the borders of chemistry, physics and materials science. The design and synthesis of molecule-based magnets requires the chemist to exert considerable control over the molecules to arrange them appropriately. It also demands the development of new theories to explain the complex magneto-structural behaviour of these intriguing solids. Molecular magnetism is still at a very early stage of development. The main challenge is to increase the strength of the magnetic interactions between spin carriers so the resulting materials can be usable at room temperature. However molecular magnets exhibit true potential to become multifunctional materials. They show some considerable advantages over conventional magnets: optical transparency, chemical sensitivity and low weight to name just a few. The following article is not a complete review of the field. Its aim is rather to show how beautiful and versatile magnetic molecular solids can be, and to encourage the in-depth study of the subject. PMID:21805910

  6. A Comparison of Molecular Vibrational Theory to Huckel Molecular Orbital Theory.

    Science.gov (United States)

    Keeports, David

    1986-01-01

    Compares the similar mathematical problems of molecular vibrational calculations (at any intermediate level of sophistication) and molecular orbital calculations (at the Huckel level). Discusses how the generalizations of Huckel treatment of molecular orbitals apply to vibrational theory. (TW)

  7. Nonlinear conductance in molecular devices: Molecular length dependence

    Science.gov (United States)

    Crljen, Ž.; Grigoriev, A.; Wendin, G.; Stokbro, K.

    2005-04-01

    We theoretically study the electronic transport in the monolayer of dithiolated phenylene vinylene oligomeres coupled to the (111) surfaces of gold electrodes. We use nonequilibrium Green’s functions and density-functional theory implemented in the TranSIESTA package to obtain a full ab initio self-consistent description of the transport current through the molecular nanostructure with different electrochemical bias potentials. The calculated current-voltage characteristics of the systems for the same contact geometry have shown a systematic decrease of the conductivity with the increased length of the molecules. We analyze the results in terms of transmission eigenchannels and find that besides the delocalization of molecular orbitals the distance between gold electrodes also determines the transport properties.

  8. HTMD: High-Throughput Molecular Dynamics for Molecular Discovery.

    Science.gov (United States)

    Doerr, S; Harvey, M J; Noé, Frank; De Fabritiis, G

    2016-04-12

    Recent advances in molecular simulations have allowed scientists to investigate slower biological processes than ever before. Together with these advances came an explosion of data that has transformed a traditionally computing-bound into a data-bound problem. Here, we present HTMD, a programmable, extensible platform written in Python that aims to solve the data generation and analysis problem as well as increase reproducibility by providing a complete workspace for simulation-based discovery. So far, HTMD includes system building for CHARMM and AMBER force fields, projection methods, clustering, molecular simulation production, adaptive sampling, an Amazon cloud interface, Markov state models, and visualization. As a result, a single, short HTMD script can lead from a PDB structure to useful quantities such as relaxation time scales, equilibrium populations, metastable conformations, and kinetic rates. In this paper, we focus on the adaptive sampling and Markov state modeling features. PMID:26949976

  9. Advances in molecular vibrations and collision dynamics molecular clusters

    CERN Document Server

    Bacic, Zatko

    1998-01-01

    This volume focuses on molecular clusters, bound by van der Waals interactions and hydrogen bonds. Twelve chapters review a wide range of recent theoretical and experimental advances in the areas of cluster vibrations, spectroscopy, and reaction dynamics. The authors are leading experts, who have made significant contributions to these topics.The first chapter describes exciting results and new insights in the solvent effects on the short-time photo fragmentation dynamics of small molecules, obtained by combining heteroclusters with femtosecond laser excitation. The second is on theoretical work on effects of single solvent (argon) atom on the photodissociation dynamics of the solute H2O molecule. The next two chapters cover experimental and theoretical aspects of the energetics and vibrations of small clusters. Chapter 5 describes diffusion quantum Monte Carlo calculations and non additive three-body potential terms in molecular clusters. The next six chapters deal with hydrogen-bonded clusters, refle...

  10. Research Status of Molecular Biology in Flax

    Institute of Scientific and Technical Information of China (English)

    Wu Jian-zhong

    2016-01-01

    Flax is a kind of worldwide fiber and oil crops, and it has a very important role in economic crop production in the world. With the development of molecular biology techniques, the research of flax molecular level has a very big breakthrough. But, flax molecular biology researches are less reported due to the later starting. This paper summarized the latest research progress of molecular biology of flax, including molecular marker technology, construction of genetic map, gene engineering and omics researches, in order to provide the reference to understand the development and research status for flax molecular breeding researchers.

  11. Nonlinear conductance in molecular devices: molecular length dependence

    OpenAIRE

    Crljen, Z.; Grigoriev, A.; Wendin, G.; Stokbro, K.

    2004-01-01

    We theoretically study the electronic transport in the monolayer of dithiolated phenylene vinylene oligomeres coupled to the (111) surfaces of gold electrodes. We use non-equilibrium Green functions (NEGF) and density functional theory(DFT) implemented in the TranSIESTA package to obtain a full ab initio self-consistent description ofthe transport current through the molecular nanostructure with different electrochemical bias potentials. The calculated current-voltage characteristics (IVC) of...

  12. Molecular Engineering of dosimetric materials; Ingenieria Molecular de materiales dosimetricos

    Energy Technology Data Exchange (ETDEWEB)

    Salas, P.; Castano, V.M. [Instituto de Fisica, UNAM, A.P. 1-1010, Queretaro (Mexico); Mendoza, D.; Gonzalez, P. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027 Mexico D.F. (Mexico)

    1999-07-01

    It was studied the thermoluminescent response to the gamma radiation of a new family of solid materials of zircon-silica. In this study some materials have been prepared by the sol-gel method with different stoichiometric relations, finding that it is possible to control, at least, partially, the thermoluminescent behavior starting from the Molecular Engineering of those materials, since the mixture of both ceramics allows to produce materials with different spatial structures. (Author)

  13. Viscosity kernel of molecular fluids

    DEFF Research Database (Denmark)

    Puscasu, Ruslan; Todd, Billy; Daivis, Peter;

    2010-01-01

    The wave-vector dependent shear viscosities for butane and freely jointed chains have been determined. The transverse momentum density and stress autocorrelation functions have been determined by equilibrium molecular dynamics in both atomic and molecular hydrodynamic formalisms. The density......, temperature, and chain length dependencies of the reciprocal and real-space viscosity kernels are presented. We find that the density has a major effect on the shape of the kernel. The temperature range and chain lengths considered here have by contrast less impact on the overall normalized shape. Functional...... forms that fit the wave-vector-dependent kernel data over a large density and wave-vector range have also been tested. Finally, a structural normalization of the kernels in physical space is considered. Overall, the real-space viscosity kernel has a width of roughly 3–6 atomic diameters, which means...

  14. Laser Controlled Molecular Orientation Dynamics

    International Nuclear Information System (INIS)

    Molecular orientation is a challenging control issue covering a wide range of applications from reactive collisions, high order harmonic generation, surface processing and catalysis, to nanotechnologies. The laser control scenario rests on the following three steps: (i) depict some basic mechanisms producing dynamical orientation; (ii) use them both as computational and interpretative tools in optimal control schemes involving genetic algorithms; (iii) apply what is learnt from optimal control to improve the basic mechanisms. The existence of a target molecular rotational state combining the advantages of efficient and post-pulse long duration orientation is shown. A strategy is developed for reaching such a target in terms of a train of successive short laser pulses applied at predicted time intervals. Each individual pulse imparts a kick to the molecule which orients. Transposition of such strategies to generic systems is now under investigation

  15. Superconducting currents from molecular theory

    International Nuclear Information System (INIS)

    The gauge-invariant method of London is used to solve the molecular orbital (MO) equations in a square planar slab, with one electron per site, in a perpendicular magnetic field. Pair currents appear because of the degeneracy and incomplete filling of highest occupied molecular orbital (HOMO). This type of electronic structure may alternatively result in an antiferromagnetic (AF) state of a charge density wave (CDW) state. The CDW state has alternating oxidation states which are different in two units, for example, in BaBiO3, where the valence state of Bi is alternating between +3 and +5, depending on whether the Bi6s2 electron pair is present at the site. The AF state, on the other hand, appears if only the middle valence state is stable. It is shown here that appearance of electron pair currents requires that all three oxidation states are at about the same total energy

  16. Laser Cooling of Molecular Anions

    CERN Document Server

    Yzombard, Pauline; Gerber, Sebastian; Doser, Michael; Comparat, Daniel

    2015-01-01

    We propose a scheme for laser cooling of negatively charged molecules. We briefly summarise the requirements for such laser cooling and we identify a number of potential candidates. A detailed computation study with C$\\_2^-$, the most studied molecular anion, is carried out. Simulations of 3D laser cooling in a gas phase show that this molecule could be cooled down to below 1 mK in only a few tens of milliseconds, using standard lasers. Sisyphus cooling, where no photo-detachment process is present, as well as Doppler laser cooling of trapped C$\\_2^-$, are also simulated. This cooling scheme has an impact on the study of cold molecules, molecular anions, charged particle sources and antimatter physics.

  17. Seebeck effect in molecular junctions

    Science.gov (United States)

    Zimbovskaya, Natalya A.

    2016-05-01

    Advances in the fabrication and characterization of nanoscale systems presently allow for a better understanding of their thermoelectric properties. As is known, the building blocks of thermoelectricity are the Peltier and Seebeck effects. In the present work we review results of theoretical studies of the Seebeck effect in single-molecule junctions and similar systems. The behavior of thermovoltage and thermopower in these systems is controlled by several factors including the geometry of molecular bridges, the characteristics of contacts between the bridge and the electrodes, the strength of the Coulomb interactions between electrons on the bridge, and of electron–phonon interactions. We describe the impact of these factors on the thermopower. Also, we discuss a nonlinear Seebeck effect in molecular junctions.

  18. Simulation of complex molecular systems

    International Nuclear Information System (INIS)

    The combined evolution of the electronic structure softwares and computational capabilities makes quantum molecular dynamics simulations available for increasingly complex systems, up to several hundred atoms. Among the various ab initio techniques, Density Functional Theory (DFT) is very successful due to its important computational efficiency with respect to Hartree-Fock type approaches. Its combination with empirical treatments of the weak van der Waals interactions allows the simulation of equilibrium or dynamics properties of numerous systems of interest for the nuclear and defense industry. We present 3 direct applications of quantum molecular dynamics: the determination of the structure of the complex Pu(DTPA) ion where DTPA means diethylen-triamine-penta-acid, the calculation of the equation of state and the Hugoniot curve of TATB monocrystal. (authors)

  19. Metallic, magnetic and molecular nanocontacts

    Science.gov (United States)

    Requist, Ryan; Baruselli, Pier Paolo; Smogunov, Alexander; Fabrizio, Michele; Modesti, Silvio; Tosatti, Erio

    2016-06-01

    Scanning tunnelling microscopy and break-junction experiments realize metallic and molecular nanocontacts that act as ideal one-dimensional channels between macroscopic electrodes. Emergent nanoscale phenomena typical of these systems encompass structural, mechanical, electronic, transport, and magnetic properties. This Review focuses on the theoretical explanation of some of these properties obtained with the help of first-principles methods. By tracing parallel theoretical and experimental developments from the discovery of nanowire formation and conductance quantization in gold nanowires to recent observations of emergent magnetism and Kondo correlations, we exemplify the main concepts and ingredients needed to bring together ab initio calculations and physical observations. It can be anticipated that diode, sensor, spin-valve and spin-filter functionalities relevant for spintronics and molecular electronics applications will benefit from the physical understanding thus obtained.

  20. Molecular dissociation in dilute gas

    International Nuclear Information System (INIS)

    The charge state distributions (CSD) produced during molecular dissociation are important to both Trace Element Accelerator Mass Spectrometry (TEAMS) and the ion implantation industry. The CSD of 1.3 - 1.7 MeV SiN+, SiMg+, SiMn+, and SiZn+ molecules have been measured for elements that do not form atomic negative ions (N, Mg, Mn, and Zn) using a NEC Tandem Pelletron accelerator. The molecules were produced in a Cs sputter negative ion source, accelerated, magnetically analyzed, and then passed through an N2 gas cell. The neutral and charged breakups where analyzed using an electrostatic deflector and measured with particle detectors. Equilibrium CSD were determined and comparisons made between molecular and atomic ion data. copyright 1999 American Institute of Physics

  1. Molecular imaging. Fundamentals and applications

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Jie (ed.) [Chinese Academy of Sciences, Beijing (China). Intelligent Medical Research Center

    2013-07-01

    Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

  2. Molecular imaging. Fundamentals and applications

    International Nuclear Information System (INIS)

    Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

  3. Seebeck effect in molecular junctions

    International Nuclear Information System (INIS)

    Advances in the fabrication and characterization of nanoscale systems presently allow for a better understanding of their thermoelectric properties. As is known, the building blocks of thermoelectricity are the Peltier and Seebeck effects. In the present work we review results of theoretical studies of the Seebeck effect in single-molecule junctions and similar systems. The behavior of thermovoltage and thermopower in these systems is controlled by several factors including the geometry of molecular bridges, the characteristics of contacts between the bridge and the electrodes, the strength of the Coulomb interactions between electrons on the bridge, and of electron–phonon interactions. We describe the impact of these factors on the thermopower. Also, we discuss a nonlinear Seebeck effect in molecular junctions. (topical review)

  4. Fragmentation in filamentary molecular clouds

    CERN Document Server

    Contreras, Yanett; Rathborne, Jill M; Sanhueza, Patricio

    2015-01-01

    Recent surveys of dust continuum emission at sub-mm wavelengths have shown that filamentary molecular clouds are ubiquitous along the Galactic plane. These structures are inhomogeneous, with over-densities that are sometimes associated with infrared emission and active of star formation. To investigate the connection between filaments and star formation, requires an understanding of the processes that lead to the fragmentation of filaments and a determination of the physical properties of the over-densities (clumps). In this paper, we present a multi-wavelength study of five filamentary molecular clouds, containing several clumps in different evolutionary stages of star formation. We analyse the fragmentation of the filaments and derive the physical properties of their clumps. We find that the clumps in all filaments have a characteristic spacing consistent with the prediction of the `sausage' instability theory, regardless of the complex morphology of the filaments or their evolutionary stage. We also find t...

  5. Molecular detection technologies for arboviruses

    International Nuclear Information System (INIS)

    Arthropod-borne animal viruses (arboviruses) cause significant livestock and economic losses to world agriculture. This paper discusses the current and potential impact of these viruses, as well as the current and developing molecular diagnostic tools for those emerging and re-emerging insect transmitted viruses affecting livestock and wildlife. The emphasis is on viruses for which there have been significant recent outbreaks in livestock including: bluetongue virus (BTV), epizootic hemorrhagic disease virus (EHDV), vesicular stomatitis virus (VSV), and Rift Valley fever virus (RVFV). The current readiness for rapid detection of arboviruses is fairly high, but there is a need for global harmonisation and continued evaluation due to the genetic variation of these unique pathogens. The tool chest for molecular detection contains a range of assays from low technology to high-throughput sophisticated devices. (author)

  6. Molecular-specific urokinase antibodies

    Science.gov (United States)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  7. Molecular imaging in cervical cancer.

    Science.gov (United States)

    Khan, Sairah R; Rockall, Andrea G; Barwick, Tara D

    2016-06-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID:26859085

  8. Aspectos moleculares da anemia falciforme

    OpenAIRE

    Galiza Neto Gentil Claudino de; Pitombeira Maria da Silva

    2003-01-01

    No presente artigo abordaram-se vários aspectos relacionados à natureza molecular da anemia falciforme, desordem hematológica de caráter hereditário que acomete expressivo número de indivíduos em várias regiões do mundo. As pesquisas realizadas em torno desta patologia da hemácia, ao longo de quase um século, a partir de 1910, cooperaram para a criação de um novo e importante segmento da ciência, denominado biologia molecular. A descoberta dos polimorfismos da mutação (GAT->GTG) no gene que c...

  9. Molecular Recognition within Synaptic Scaffolds

    DEFF Research Database (Denmark)

    Erlendsson, Simon

    function. At the molecular level PICK1 contains both a BAR and a PDZ domain making it quite unique. Especially the specificity and promiscuity of the PICK1 PDZ domain seems to be more complicated than normally seen for PDZ domains. Also, the ability of PICK1 to form dimeric structures via its central BAR...... by the spatial architecture of the synapse itself. In this thesis, the molecular scaffolding mechanisms of PICK1 have been investigated in both isolated and near native conditions. Our findings have significantly benefitted the general understanding of how PICK1 and PDZ domain scaffolding works. In the first...... later in evolution to accommodate increasingly diverse PDZ domain ligands. Our findings provide basis for development of new and more specific peptide inhibitors. In the second study, we utilized SAXS, NMR spectroscopy, MD simulations and various other biochemical methods, to construct a full...

  10. Molecular approaches for bacterial azoreductases

    Directory of Open Access Journals (Sweden)

    Montira Leelakriangsak

    2013-12-01

    Full Text Available Azo dyes are the dominant types of synthetic dyes, widely used in textiles, foods, leather, printing, tattooing, cosmetics, and pharmaceutical industries. Many microorganisms are able to decolorize azo dyes, and there is increasing interest in biological waste treatment methods. Bacterial azoreductases can cleave azo linkages (-N=N- in azo dyes, forming aromatic amines. This review mainly focuses on employing molecular approaches, including gene manipulation and recombinant strains, to study bacterial azoreductases. The construction of the recombinant protein by cloning and the overexpression of azoreductase is described. The mechanisms and function of bacterial azoreductases can be studied by other molecular techniques discussed in this review, such as RT-PCR, southern blot analysis, western blot analysis, zymography, and muta-genesis in order to understand bacterial azoreductase properties, function and application. In addition, understanding the regulation of azoreductase gene expression will lead to the systematic use of gene manipulation in bacterial strains for new strategies in future waste remediation technologies.

  11. Molecular deformation mechanisms in polyethylene

    CERN Document Server

    Coutry, S

    2001-01-01

    adjacent labelled stems is significantly larger when the DPE guest is a copolymer molecule. Our comparative studies on various types of polyethylene lead to the conclusion that their deformation behaviour under drawing has the same basis, with additional effects imputed to the presence of tie-molecules and branches. Three major points were identified in this thesis. The changes produced by drawing imply (1) the crystallisation of some of the amorphous polymer and the subsequent orientation of the newly formed crystals, (2) the re-orientation of the crystalline ribbons and (3) the beginning of crystallite break-up. However, additional effects were observed for the high molecular weight linear sample and the copolymer sample and were attributed, respectively, to the presence of tie-molecules and of branches. It was concluded that both the tie-molecules and the branches are restricting the molecular movement during deformation, and that the branches may be acting as 'anchors'. This work is concerned with details...

  12. Molecular tailoring of solid surfaces

    CERN Document Server

    Evenson, S A

    1997-01-01

    The overall performance of a material can be dramatically improved by tailoring its surface at the molecular level. The aim of this project was to develop a universal technique for attaching dendrimers (well-defined, nanoscale, functional polymers) and Jeffamines (high molecular weight polymer chains) to the surface of any shaped solid substrate. This desire for controlled functionalization is ultimately driven by the need to improve material compatibility in various biomedical applications. Atomic force microscopy (AFM) was used initially to study the packing and structure of Langmuir-Blodgett films on surfaces, and subsequently resulted in the first visualization of individual, spherically shaped, nanoscopic polyamidoamine dendrimers. The next goal was to develop a methodology for attaching such macromolecules to inert surfaces. Thin copolymer films were deposited onto solid substrates to produce materials with a fixed concentration of surface anhydride groups. Vapor-phase functionalization reactions were t...

  13. A molecular dawn for biogeochemistry

    Science.gov (United States)

    Zak, D.R.; Blackwood, C.B.; Waldrop, M.P.

    2006-01-01

    Biogeochemistry is at the dawn of an era in which molecular advances enable the discovery of novel microorganisms having unforeseen metabolic capabilities, revealing new insight into the underlying processes regulating elemental cycles at local to global scales. Traditionally, biogeochemical inquiry began by studying a process of interest, and then focusing downward to uncover the microorganisms and metabolic pathways mediating that process. With the ability to sequence functional genes from the environment, molecular approaches now enable the flow of inquiry in the opposite direction. Here, we argue that a focus on functional genes, the microorganisms in which they reside, and the interaction of those organisms with the broader microbial community could transform our understanding of many globally important biogeochemical processes. ?? 2006 Elsevier Ltd. All rights reserved.

  14. Molecular mimicry and multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Michael Namaka; Michael R. Mulvey; Sabina Kapoor; Leann Simms; Christine Leong; Amy Grossberndt; Michael Prouta; Emma Frost; Farid Esfahani; Andrew Gomori

    2011-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Although the exact underlying mechanism leading to myelin destruction is unknown, the molecular mimicry theory is the most commonly acknowledged elucidation of MS pathology. Although various antigens have been associated with MS induction, this review presents studies focused on key bacterial and viral antigens that lead to the development of MS. The research specific to a molecular mimicry theory of MS via each implicated agent is weak; however, collectively the reports provide credible support for this theory. Given that homologous sequences are not required to lead to antigenic cross-reactivity, it is reasonable to conclude that certain viral and bacterial antigens with 5-10 similar amino acids in sequence can lead to self destruction of similar myelin sequences. Thus, this literature review has provided insight to further the understanding of the etiology of multiple sclerosis.

  15. Symmetry breaking in molecular ferroelectrics.

    Science.gov (United States)

    Shi, Ping-Ping; Tang, Yuan-Yuan; Li, Peng-Fei; Liao, Wei-Qiang; Wang, Zhong-Xia; Ye, Qiong; Xiong, Ren-Gen

    2016-07-11

    Ferroelectrics are inseparable from symmetry breaking. Accompanying the paraelectric-to-ferroelectric phase transition, the paraelectric phase adopting one of the 32 crystallographic point groups is broken into subgroups belonging to one of the 10 ferroelectric point groups, i.e. C1, C2, C1h, C2v, C4, C4v, C3, C3v, C6 and C6v. The symmetry breaking is captured by the order parameter known as spontaneous polarization, whose switching under an external electric field results in a typical ferroelectric hysteresis loop. In addition, the responses of spontaneous polarization to other external excitations are related to a number of physical effects such as second-harmonic generation, piezoelectricity, pyroelectricity and dielectric properties. Based on these, this review summarizes recent developments in molecular ferroelectrics since 2011 and focuses on the relationship between symmetry breaking and ferroelectricity, offering ideas for exploring high-performance molecular ferroelectrics. PMID:27051889

  16. Prediction of molecular crystal structures

    CERN Document Server

    Beyer, T

    2001-01-01

    The ab initio prediction of molecular crystal structures is a scientific challenge. Reliability of first-principle prediction calculations would show a fundamental understanding of crystallisation. Crystal structure prediction is also of considerable practical importance as different crystalline arrangements of the same molecule in the solid state (polymorphs)are likely to have different physical properties. A method of crystal structure prediction based on lattice energy minimisation has been developed in this work. The choice of the intermolecular potential and of the molecular model is crucial for the results of such studies and both of these criteria have been investigated. An empirical atom-atom repulsion-dispersion potential for carboxylic acids has been derived and applied in a crystal structure prediction study of formic, benzoic and the polymorphic system of tetrolic acid. As many experimental crystal structure determinations at different temperatures are available for the polymorphic system of parac...

  17. Gastronomic botany and molecular gastronomy

    OpenAIRE

    Pérez-Urria Carril, Elena; Gómez Garay, Aranzazu; Ávalos García, Adolfo; Martín Calvarro, Luisa; Pintos López, Beatriz; Saco Sierra, M. Dolores; Martín Gómez, M. Soledad; Pérez Alonso, M. José; Puelles Gallo, María; Palá Paúl, Jesús; Cifuentes Cuencas, Blanca; Llamas Ramos, José Eugenio

    2011-01-01

    Complutense University of Madrid through the "Vicerrectorado de Calidad" develops projects to innovate and improve teaching quality. Among these projects is "Gastronomic Botany and Molecular Gastronomy" which aims to develop new materials and tools for the Virtual Campus and consequently offer new possibilities for teaching and training. Also this project organize and structure a new teaching matter for post-graduate education that will be an example of approach, relationship and cooper...

  18. Harmful molecular mechanisms in sepsis

    OpenAIRE

    Rittirsch, Daniel; Flierl, Michael A; Ward, Peter A.

    2008-01-01

    Sepsis and sepsis-associated multi-organ failure are major challenges for scientists and clinicians and are a tremendous burden for health-care systems. Despite extensive basic research and clinical studies, the pathophysiology of sepsis is still poorly understood. We are now beginning to understand that sepsis is a heterogeneous, dynamic syndrome caused by imbalances in the ‘inflammatory network’. In this Review, we highlight recent insights into the molecular interactions that occur during ...

  19. EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

    OpenAIRE

    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

    2012-01-01

    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more oppo...

  20. Molecular diagnostics and parasitic disease.

    Science.gov (United States)

    Vasoo, Shawn; Pritt, Bobbi S

    2013-09-01

    Molecular parasitology represents an emerging field in microbiology diagnostics. Although most assays use nonstandardized, laboratory-developed methods, a few commercial systems have recently become available and are slowly being introduced into larger laboratories. In addition, a few methodologies show promise for use in field settings in which parasitic infections are endemic. This article reviews the available techniques and their applications to major parasitic diseases such as malaria, leishmaniasis, and trichomoniasis. PMID:23931835