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Sample records for adaptor molecule grb2

  1. Crystal structure of the mammalian Grb2 adaptor.

    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

  2. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia

    Gillis, LC; Berry, DM; Minden, MD; McGlade, CJ; Barber, DL

    2016-01-01

    Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (B-ALL), are driven by the oncogenic BCR-ABL fusion protein. Animal modeling experiments utilizing retroviral transduction and subsequent bone marrow transplantation have demonstrated that BCR-ABL generates both myeloid and lymphoid disease in mice receiving whole bone marrow transduced with BCR-ABL. Y177 of BCR-ABL is critical to the development of myeloid disease, and phosphorylation of Y177 has been shown to induce GRB2 binding to BCR-ABL, followed by activation of the Ras and phosphoinositide 3 kinase signaling pathways. We show that the GRB2-related adapter protein, GADS, also associates with BCR-ABL, specifically through Y177 and demonstrate that BCR-ABL-driven lymphoid disease requires Gads. BCR-ABL transduction of Gads(−/−) bone marrow results in short latency myeloid disease within 3–4 weeks of transplant, while wild-type mice succumb to both a longer latency lymphoid and myeloid diseases. We report that GADS mediates a unique BCR-ABL complex with SLP-76 in BCR-ABL-positive cell lines and B-ALL patient samples. These data suggest that GADS mediates lymphoid disease downstream of BCR-ABL through the recruitment of specific signaling intermediates. PMID:23399893

  3. Association between receptor protein-tyrosine phosphatase RPTPalpha and the Grb2 adaptor. Dual Src homology (SH) 2/SH3 domain requirement and functional consequences

    Su, J; Yang, L T; Sap, J

    1996-01-01

    binding site in RPTPalpha was studied further by expression of wild type or mutant RPTPalpha proteins in PC12 cells. In these cells, wild type RPTPalpha interferes with acidic fibroblast growth factor-induced neurite outgrowth; this effect requires both the catalytic activity and the Grb2 binding Tyr798...

  4. The adaptor molecule CARD9 is essential for tuberculosis control

    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...

  5. Short-hairpin RNA-mediated stable silencing of Grb2 impairs cell growth and DNA synthesis

    Grb2 is an SH2-SH3 protein adaptor responsible for linking growth factor receptors with intracellular signaling cascades. To study the role of Grb2 in cell growth, we have generated a new COS7 cell line (COS7shGrb2), based on RNAi technology, as null mutations in mammalian Grb2 genes are lethal in early development. This novel cell line continuously expresses a short hairpin RNA that targets endogenous Grb2. Stable COS7shGrb2 cells had the shGrb2 integrated into the genomic DNA and carried on SiL construct (made refractory to the shRNA-mediated interference), but not with an SH2-deficient mutant (R86K). Thus, a viable knock-down and rescue protocol has demonstrated that Grb2 is crucial for cell proliferation

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

    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

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

    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

  8. Grb2 Is Important for T Cell Development, Th Cell Differentiation, and Induction of Experimental Autoimmune Encephalomyelitis.

    Radtke, Daniel; Lacher, Sonja M; Szumilas, Nadine; Sandrock, Lena; Ackermann, Jochen; Nitschke, Lars; Zinser, Elisabeth

    2016-04-01

    The small adaptor protein growth factor receptor-bound protein 2 (Grb2) modulates and integrates signals from receptors on cellular surfaces in inner signaling pathways. In murine T cells, Grb2 is crucial for amplification of TCR signaling. T cell-specific Grb2(fl/fl) Lckcre(tg) Grb2-deficient mice show reduced T cell numbers due to impaired negative and positive selection. In this study, we found that T cell numbers in Grb2(fl/fl) CD4cre(tg) mice were normal in the thymus and were only slightly affected in the periphery. Ex vivo analysis of CD4(+) Th cell populations revealed an increased amount of Th1 cells within the CD4(+) population of Grb2(fl/fl) CD4cre(tg) mice. Additionally, Grb2-deficient T cells showed a greater potential to differentiate into Th17 cells in vitro. To test whether these changes in Th cell differentiation potential rendered Grb2(fl/fl) CD4cre(tg) mice more prone to inflammatory diseases, we used the murine Th1 cell- and Th17 cell-driven model of experimental autoimmune encephalomyelitis (EAE). In contrast to our expectations, Grb2(fl/fl) CD4cre(tg) mice developed a milder form of EAE. The impaired EAE disease can be explained by the reduced proliferation rate of Grb2-deficient CD4(+) T cells upon stimulation with IL-2 or upon activation by allogeneic dendritic cells, because the activation of T cells by dendritic cells and the subsequent T cell proliferation are known to be crucial factors for the induction of EAE. In summary, Grb2-deficient T cells show defects in T cell development, increased Th1 and Th17 cell differentiation capacities, and impaired proliferation after activation by dendritic cells, which likely reduce the clinical symptoms of EAE. PMID:26921310

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

    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.

  10. Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)

    Huebner, K; Kastury, K; Druck, T;

    1994-01-01

    Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding...... "adapter" proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human...... hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ...

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

    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

  12. 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.

    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.

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

    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

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

    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

  15. Preliminary crystallographic characterization of the Grb2 SH2 domain in complex with a FAK-derived phosphotyrosyl peptide

    Crystals of the Grb2 SH2 domain in complex with a phosphotyrosyl peptide corresponding to residues 921–930 of focal adhesion kinase (FAK) have been obtained using the sitting-drop vapour-diffusion technique. Data have been collected to 2.49 Å resolution. Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein with a single SH2 domain that specifically binds to focal adhesion kinase (FAK) when residue Tyr925 of FAK is phosphorylated. The Grb2–FAK interaction is associated with cellular integrin-activated signal transduction events leading to the activation of the Ras-MAPK pathway. Crystals of the Grb2 SH2 domain in complex with a phosphopeptide corresponding to residues 921–930 of FAK have been obtained using the sitting-drop vapour-diffusion technique. The crystals belonged to space group P3121, with unit-cell parameters a = b = 102.7, c = 127.6 Å, α = β = 90.0, γ = 120.0°. A diffraction data set was collected from a flash-cooled crystal at 100 K to 2.49 Å resolution using synchrotron radiation. Structure determination by molecular replacement and analysis of the detailed structure of the complex are currently in progress

  16. Structural and biophysical investigation of the interaction of a mutant Grb2 SH2 domain (W121G) with its cognate phosphopeptide.

    Papaioannou, Danai; Geibel, Sebastian; Kunze, Micha B A; Kay, Christopher W M; Waksman, Gabriel

    2016-03-01

    The adaptor protein Grb2 is a key element of mitogenetically important signaling pathways. With its SH2 domain it binds to upstream targets while its SH3 domains bind to downstream proteins thereby relaying signals from the cell membranes to the nucleus. The Grb2 SH2 domain binds to its targets by recognizing a phosphotyrosine (pY) in a pYxNx peptide motif, requiring an Asn at the +2 position C-terminal to the pY with the residue either side of this Asn being hydrophobic. Structural analysis of the Grb2 SH2 domain in complex with its cognate peptide has shown that the peptide adopts a unique β-turn conformation, unlike the extended conformation that phosphopeptides adopt when bound to other SH2 domains. TrpEF1 (W121) is believed to force the peptide into this unusual conformation conferring this unique specificity to the Grb2 SH2 domain. Using X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and isothermal titration calorimetry (ITC), we describe here a series of experiments that explore the role of TrpEF1 in determining the specificity of the Grb2 SH2 domain. Our results demonstrate that the ligand does not adopt a pre-organized structure before binding to the SH2 domain, rather it is the interaction between the two that imposes the hairpin loop to the peptide. Furthermore, we find that the peptide adopts a similar structure when bound to both the wild-type Grb2 SH2 domain and a TrpEF1Gly mutant. This suggests that TrpEF1 is not the determining factor for the conformation of the phosphopeptide. PMID:26645482

  17. Purification, stabilization, and crystallization of a modular protein: Grb2.

    Guilloteau, J P; Fromage, N; Ries-Kautt, M; Reboul, S; Bocquet, D; Dubois, H; Faucher, D; Colonna, C; Ducruix, A; Becquart, J

    1996-05-01

    We report here the purification and the crystallization of the modular protein Grb2. The protein was expressed as a fusion with glutathione-S-transferase and purified by affinity chromatography on glutathione agarose. It was apparent from reverse phase chromatography that the purified protein was conformationally unstable. Instability was overcome by the addition of 100 mM arginine to the buffers. Because Grb2 appeared to be extremely sensitive to oxidation, crystallization experiments were performed with a dialysis button technique involving daily addition of fresh DTT to the reservoirs. The presence of 8 to 14% glycerol was necessary to obtain monocrystals. These results are discussed in relation with the modular nature of Grb2. PMID:8727323

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

    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

  19. Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer.

    Timsah, Z; Ahmed, Z; Ivan, C; Berrout, J; Gagea, M; Zhou, Y; Pena, G N A; Hu, X; Vallien, C; Kingsley, C V; Lu, Y; Hancock, J F; Liu, J; Gladden, A B; Mills, G B; Lopez-Berestein, G; Hung, M-C; Sood, A K; Bogdanov, M; Ladbury, J E

    2016-04-28

    In the absence of extracellular stimulation the adaptor protein growth factor receptor-bound protein (Grb2) and the phospholipase Plcγ1 compete for the same binding site on fibroblast growth factor receptor 2 (FGFR2). Reducing cellular Grb2 results in upregulation of Plcγ1 and depletion of the phospholipid PI(4,5)P2. The functional consequences of this event on signaling pathways are unknown. We show that the decrease in PI(4,5)P2 level under non-stimulated conditions inhibits PTEN activity leading to the aberrant activation of the oncoprotein Akt. This results in excessive cell proliferation and tumor progression in a xenograft mouse model. As well as defining a novel mechanism of Akt phosphorylation with important therapeutic consequences, we also demonstrate that differential expression levels of FGFR2, Plcγ1 and Grb2 correlate with patient survival. Oncogenesis through fluctuation in the expression levels of these proteins negates extracellular stimulation or mutation and defines them as novel prognostic markers in ovarian cancer. PMID:26212011

  20. Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.

    Shounak Baksi

    Full Text Available Growth factor receptor protein binding protein 2 (Grb2 is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt, a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease (HD. We observed an elevated expression of Grb2 in neuronal cells in animal and cell models of HD. Grb2 overexpression was predominantly regulated by the transcription factor Forkhead Box D3 (Foxd3. Exogenous expression of Grb2 also reduced aggregation of mutant Htt in Neuro2A cells. Grb2 is also known to interact with Htt, depending on epidermal growth factor receptor (EGFR activation. Grb2- mutant Htt interaction in the contrary, took place in vesicular structures, independent of EGFR activation that eventually merged with autophagosomes and activated the autophagy machinery helping in autophagosome and lysosome fusion. Grb2, with its emerging dual role, holds promise for a survival mechanism for HD.

  1. A high-content imaging workflow to study Grb2 signaling complexes by expression cloning.

    Freeman, Jamie; Kriston-Vizi, Janos; Seed, Brian; Ketteler, Robin

    2012-01-01

    Signal transduction by growth factor receptors is essential for cells to maintain proliferation and differentiation and requires tight control. Signal transduction is initiated by binding of an external ligand to a transmembrane receptor and activation of downstream signaling cascades. A key regulator of mitogenic signaling is Grb2, a modular protein composed of an internal SH2 (Src Homology 2) domain flanked by two SH3 domains that lacks enzymatic activity. Grb2 is constitutively associated with the GTPase Son-Of-Sevenless (SOS) via its N-terminal SH3 domain. The SH2 domain of Grb2 binds to growth factor receptors at phosphorylated tyrosine residues thus coupling receptor activation to the SOS-Ras-MAP kinase signaling cascade. In addition, other roles for Grb2 as a positive or negative regulator of signaling and receptor endocytosis have been described. The modular composition of Grb2 suggests that it can dock to a variety of receptors and transduce signals along a multitude of different pathways(1-3). Described here is a simple microscopy assay that monitors recruitment of Grb2 to the plasma membrane. It is adapted from an assay that measures changes in sub-cellular localization of green-fluorescent protein (GFP)-tagged Grb2 in response to a stimulus(4-6). Plasma membrane receptors that bind Grb2 such as activated Epidermal Growth Factor Receptor (EGFR) recruit GFP-Grb2 to the plasma membrane upon cDNA expression and subsequently relocate to endosomal compartments in the cell. In order to identify in vivo protein complexes of Grb2, this technique can be used to perform a genome-wide high-content screen based on changes in Grb2 sub-cellular localization. The preparation of cDNA expression clones, transfection and image acquisition are described in detail below. Compared to other genomic methods used to identify protein interaction partners, such as yeast-two-hybrid, this technique allows the visualization of protein complexes in mammalian cells at the sub

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

    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

  3. *611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 [OMIM

    Full Text Available FIELD NO 611540 FIELD TI 611540 SH3-DOMAIN GRB2-LIKE (ENDOPHILIN)-INTERACTING PROTEIN 1; SGIP1 F ... differential-display PCR of hypothalamic RNA from lean ... and obese Psammomys obesus (Israeli sand rats), a ... nhibition of Sgip1 hypothalamic expression in both lean ... P. obesus and Sprague-Dawley rats caused a signifi ...

  4. Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2

    VanderKuur, J; Allevato, G; Billestrup, Nils;

    1995-01-01

    Growth hormone (GH) has been shown to stimulate the mitogen-activated protein (MAP) kinases designated ERKs (extracellular signal regulated kinases) 1 and 2. One pathway by which ERKs 1 and 2 are activated by tyrosine kinases involves the Src homology (SH)-2 containing proteins SHC and Grb2. To...... phosphorylation of 66-, 52-, and 46-kDa SHC proteins in 3T3-F442A fibroblasts. GH also promoted binding of GHR and JAK2 to the SH2 domain of 46/52-kDa SHC protein fused to glutathione S-transferase (GST). Constitutively phosphorylated JAK2, from COS-7 cells transiently transfected with murine JAK2 cDNA, bound to...

  5. The fifth adaptor protein complex.

    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...

  6. The Fifth Adaptor Protein Complex

    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...

  7. The fifth adaptor protein complex.

    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.

  8. Inhibition of Grb2-mediated activation of MAPK signal transduction suppresses NOR1/CB1954-induced cytotoxicity in the HepG2 cell line.

    Gui, Rong; Li, Dengqing; Qi, Guannan; Suhad, Ali; Nie, Xinmin

    2012-09-01

    The nitroreductase oxidored-nitro domain containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyngeal carcinoma (NPC). We have previously demonstrated that NOR1 overexpression is capable of converting the monofunctional alkylating agent 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) into a toxic form by reducing the 4-nitro group of CB1954. Toxic CB1954 is able to enhance cell killing in the NPC cell line CNE1; however, the underlying mechanisms remain unknown. Using cDNA microarrays and quantitative real-time PCR, we previously discovered that NOR1 increases the expression of growth factor receptor-bound protein 2 (Grb2) mRNA by 4.8-fold in the human hepatocellular carcinoma cell line HepG2. In the present study, we revealed that NOR1 increased Grb2 protein expression by 3-fold in HepG2 cells. Additionally, we demonstrated that NOR1 enhanced CB1954-induced cell killing in HepG2 cells, and cell cytotoxicity was inhibited with the tyrosine kinase inhibitor genistein, or by stable transfection of Grb2 small hairpin RNA (shRNA) pU6(+27)-shGrb2 to silence the expression of Grb2. Western blot analysis revealed that Grb2 downregulation may reduce the activity of the mitogen-activated protein kinase (MAPK). Inhibiting the activation of MAPK using the methyl ethyl ketone (MEK) inhibtor PD98059 suppressed CB1954-induced cell killing. These results suggested that the NOR1 gene enhances CB1954-mediated cell cytotoxicity through the upregulation of Grb2 expression and the activation of MAPK signal transduction in the HepG2 cell line. PMID:23741254

  9. Grb2 Is a Negative Modulator of the Intrinsic Ras-GEF Activity of hSos1

    Zarich, Natasha; Oliva, José Luis; Martínez, Natalia; Jorge, Rocío; Ballester, Alicia; Gutiérrez-Eisman, Silvia; García-Vargas, Susana; Rojas, José M

    2006-01-01

    hSos1 is a Ras guanine-nucleotide exchange factor. It was suggested that the carboxyl-terminal region of hSos1 down-regulates hSos1 functionality and that the intrinsic guanine-nucleotide exchange activity of this protein may be different before and after stimulation of tyrosine kinase receptors. Using different myristoylated hSos1 full-length and carboxyl-terminal truncated mutants, we show that Grb2 function accounts not only for recruitment of hSos1 to the plasma membrane but also for modu...

  10. α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction.

    Gingras, Jacinthe; Gawor, Marta; Bernadzki, Krzysztof M; Grady, R Mark; Hallock, Peter; Glass, David J; Sanes, Joshua R; Proszynski, Tomasz J

    2016-03-01

    Neuromuscular junctions (NMJs), the synapses made by motor neurons on muscle fibers, form during embryonic development but undergo substantial remodeling postnatally. Several lines of evidence suggest that α-dystrobrevin, a component of the dystrophin-associated glycoprotein complex (DGC), is a crucial regulator of the remodeling process and that tyrosine phosphorylation of one isoform, α-dystrobrevin-1, is required for its function at synapses. We identified a functionally important phosphorylation site on α-dystrobrevin-1, generated phosphorylation-specific antibodies to it and used them to demonstrate dramatic increases in phosphorylation during the remodeling period, as well as in nerve-dependent regulation in adults. We then identified proteins that bind to this site in a phosphorylation-dependent manner and others that bind to α-dystrobrevin-1 in a phosphorylation-independent manner. They include multiple members of the DGC, as well as α-catulin, liprin-α1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, α-catulin (phosphorylation independent) and Grb2 (phosphorylation dependent) are localized to NMJs in vivo, and that they are required for proper organization of neurotransmitter receptors on myotubes. PMID:26769899

  11. Expression pattern of FGFR2, Grb2 and Plcγ1 acts as a novel prognostic marker of recurrence recurrence-free survival in lung adenocarcinoma

    Timsah, Zahra; Berrout, Jonathan; Suraokar, Milind; Behrens, Carmen; Song, Juhee; Lee, J Jack; Ivan, Cristina; Gagea, Mihai; Shires, Michael; Hu, Xin; Vallien, Courtney; Kingsley, Charles V; Wistuba, IgnacioI; Ladbury, John E

    2015-01-01

    Lung adenocarcinoma is characterized by complex biology involving alterations at the genomic and protein expression levels. FGFR2 mutation and/or amplification are key drivers of disease progression and drug resistance in lung adenocarcinoma patients. These genetic alterations drive oncogenic downstream signalling due to the deregulated activity of the receptor. We have previously reported that wild type FGFR2 provides a binding site for which two proteins, Grb2 and Plcγ1, compete in a concentration-dependent manner. Metastasis and invasion ensue when Plcγ1 prevails on the receptor giving rise to oncogenic outcome in the absence of gene mutation/deletion. The effect of this signalling mechanism on FGFR2-driven lung adenocarcinoma has not previously been considered. In this study we show that fluctuation in the combinatorial expression levels of FGFR2, Grb2 and Plcγ1 modulates cell invasive properties, tumor formation and is linked to recurrence-free survival in 150 lung adenocarcinoma patients. High levels of expression of FGFR2 and Plcγ1 in a low background of Grb2 significantly correlates with poor prognosis. On the other hand, low levels of expression of FGFR2 and Plcγ1 in a high background of Grb2 correlates with favourable prognosis. This study defines the expression pattern of FGFR2, Plcγ1 and Grb2 as a novel prognostic marker in human lung adenocarcinoma. Thus, consideration of the Grb2 and Plcγ1-mediated mechanism of FGFR2 regulation will enhance the therapeutic targeting of aberrant FGFR2 activity to provide the much-needed improvement to the treatment regimen of this high mortality disease. PMID:26693065

  12. Mapping the X(+1) binding site of the Grb2-SH2 domain with alpha,alpha-disubstituted cyclic alpha-amino acids.

    García-Echeverría, C; Gay, B; Rahuel, J; Furet, P

    1999-10-18

    A series of phosphopeptides containing alpha,alpha-disubstituted cyclic alpha-amino acids (Ac(n)c, 3 activity as antagonists of the Grb2-SH2 domain has been determined in competitive binding assays. The SAR data obtained have been interpreted by using models constructed from the X-ray structure of the ligand-bound Grb2-SH2 domain. The used of alpha,alpha-disubstituted cyclic alpha-amino acids to map the binding pockets of proteins expands the classical alanine scan concept and takes advantage of the known conformational preferences of these amino acids. PMID:10571147

  13. PAG - a multipurpose transmembrane adaptor protein

    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

  14. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    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

  15. Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes

    Stork, B.; Engelke, M.; Frey, J.; Hořejší, Václav; Hamm-Baarke, A.; Schraven, B.; Kurosaki, T.; Wienands, J.

    2004-01-01

    Roč. 21, č. 5 (2004), s. 681-691. ISSN 1074-7613 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : NTAL * Grb2 * lymphocyte Subject RIV: EC - Immunology Impact factor: 15.448, year: 2004

  16. Adaptor protein complexes and intracellular transport

    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...

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

    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

  18. Grb2-associated binder 1 polymorphism was associated with the risk of Helicobactor pylori infection and gastric atrophy

    Yasuyuki Goto, Takafumi Ando, Kazuko Nishio, Sayo Kawai, Yoshiko Ishida, Mariko Naito, Hidemi Goto, Nobuyuki Hamajima

    2007-01-01

    Full Text Available Background: Various single nucleotide polymorphisms (SNPs have explained the association between Helicobacter pylori (H. pylori and gastric atrophy and cancer. This study investigated the associations of Grb2 associated binder 1 (Gab1 polymorphism and the combination of PTPN11 gene encoding src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2 and Gab1 gene with gastric cancer and gastric atrophy among H. pylori seropositive subjects. Methods: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345 was examined for 454 Japanese health checkup examinees (126 males and 328 females aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients (134 males and 68 females aged 33 to 94 with pathologically confirmed diagnosis of gastric adenocarcinoma. Results: The decreased OR of the Gab1 A/A for H. pylori seropositivity was 0.25 (95% confidence interval (CI: 0.08-0.71. Among seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was significant (OR=1.95, 95% CI: 1.12 -3.40. Seropositive individuals with PTPN11 G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with significance (OR=3.49, 95% CI: 1.54-7.90 relative to PTPN11 G/A+A/A and Gab1 G/G, the lowest risk combination, as a reference. However, the gene-gene interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41-4.66. Compared to gastric cancer case, the Gab1 did not influence the step of atrophy/metaplasia-gastric cancer sequence. Conclusions: This study represents that the Gab1 polymorphism was associated with the low risk of H. pylori infection and the high risk of gastric atrophy among seropositive healthy controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were associated with the greatest risk of gastric atrophy. These findings require confirmation in much larger studies.

  19. Application of Azide-Alkyne Cycloaddition “Click Chemistry” for the Synthesis of Grb2 SH2 Domain-Binding Macrocycles

    Choi, Won Jun; Shi, Zhen-Dan; Worthy, Karen M.; Bindu, Lakshman; Karki, Rajeshri G.; Nicklaus, Marc C.; Fisher, Robert J.; Burke, Terrence R

    2006-01-01

    Copper (I) promoted [3+2] Huisgen cycloaddition of azides with terminal alkynes was used to prepare triazole-containing macrocycles based on the Grb2 SH2 domain-binding motif, “Pmp-Ac6 c-Asn”, where Pmp and Ac6 c stand for 4-phosphonomethylphenylalanine and 1-aminocyclohexanecarboxylic acid, respectively. When cycloaddition reactions were conducted at 1 mM substrate concentrations cyclization of monomeric units occurred. At 2 mM substrate concentrations the predominant products were macrocycl...

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

    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...

  1. Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain

    The three-dimensional structure of the N-terminal SH3 domain (residues 583-660) of murine Vav, which contains a tetra-proline sequence (Pro 607-Pro 610), was determined by NMR. The solution structure of the SH3 domain shows a typical SH3 fold, but it exists in two conformations due to cis-trans isomerization at the Gly614-Pro615 bond. The NMR structure of the P615G mutant, where Pro615 is replaced by glycine, reveals that the tetra-proline region is inserted into the RT-loop and binds to its own SH3 structure. The C-terminal SH3 domain of Grb2 specifically binds to the trans form of the N-terminal SH3 domain of Vav. The surface of Vav N-terminal SH3 which binds to Grb2 C-terminal SH3 was elucidated by chemical shift mapping experiments using NMR. The surface does not involve the tetra-proline region but involves the region comprising the n-src loop, the N-terminal and the C-terminal regions. This surface is located opposite to the tetra-proline containing region, consistent with that of our previous mutagenesis studies

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

    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.

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

    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.

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

    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...

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

    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-...

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

    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

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

    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.

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

    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.

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

    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.

  10. Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways

    Gesang, Luobu; Dan, Zeng; Gusang, Lamu

    2016-01-01

    The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.

  11. Autologous antibody to src-homology 3-domain GRB2-like 1 specifically increases in the sera of patients with low-grade gliomas

    Matsutani Tomoo

    2012-10-01

    Full Text Available Abstract Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9 L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1 was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas.

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

    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…

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

    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

  14. The effects of rehabilitative training on neural function and the expression of glial fibrillary acidic protein and ionized calcium binding adaptor molecule-1 after traumatic brain injury%康复训练对脑损伤后大鼠神经功能及胶原纤维酸性蛋白和离子钙接头分子表达的影响

    刘苏; 沈光宇; 吴勤峰; 张志军; 郭爱松; 李欣嫄; 邹玉婷

    2012-01-01

    目的 研究康复功能训练对大鼠脑损伤神经功能恢复及损伤边缘皮质胶原纤维酸性蛋白(GFAP)和离子钙接头分子(Iba-1)表达的影响.方法 SD大鼠131只,按随机数字表法选取30只为假手术组,其余101只制作脑损伤模型.剔除制模未达标大鼠11只,余90只按随机数字表法分为康复训练组、制动组和自由活动组,每组30只大鼠.康复训练组于术后第4天开始每天给予平衡、旋转、行走等功能训练,每项15min,共训练45min,每周6d;制动组置于网状笼内固定;自由活动组和假手术组置于普通笼内饲养.在术后第3天及术后1、2、3和4周对上述4组分别进行神经和运动功能评估,观察其恢复状况;同时采用免疫荧光染色观察损伤区边缘皮质GFAP和Iba-1的表达.结果 康复训练组术后2、3和4周在功能评估方面优于制动组和自由活动组(P<0.05);术后4周自由活动组较制动组的神经运动功能也有所恢复(P<0.05).脑损伤术后2、3和4周康复训练组GFAP阳性细胞灰度值和术后3、4周康复训练组Iba-1阳性细胞平均灰度值均明显低于制动组和自由活动组(P<0.01).结论 康复功能训练可促进大鼠脑损伤的神经功能恢复,其机制可能与损伤区边缘皮质星形胶质细胞和小胶质细胞的活化数目减少有关.%Objective To study the effectsof rehabilitative training on neural function and the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) in rats after traumatic brain injury.Methods A left hemisphere traumatic brain injury model was established in ninety Sprague-Dawley rats.They were then randomly divided into a rehabilitation training group,an immobilization group and a free-running group,with 30 rats in each group.Another thirty rats received sham injury as the shamoperated group.Beginning 4 days post-operation the rats of the rehabilitation training group were given

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

    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.

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

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

    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...

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

    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.

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

    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...

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

    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.

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

    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.

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

    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.

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

    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

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

    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

  5. 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.

    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

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

    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

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

    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

  8. Synapse formation is regulated by the signaling adaptor GIT1

    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...

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

    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

  10. 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

    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.

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

    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

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

    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.

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

    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...

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

    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

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

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

    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...

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

    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...

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

    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...

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

    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...

  20. Biochemical and Structural Studies on the Adaptor Protein p130Cas

    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...

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

    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.

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

    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

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

    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...

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

    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

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

    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

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

    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

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

    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

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

    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...

  9. Photoisomerisable molecules

    Peris Fajarnes, Eduardo Víctor; Mata Martínez, José Antonio; Márquez Linares, Francisco Manuel; Sabater Picot, María José

    2005-01-01

    [EN] The invention relates to a molecule comprising at least one carbon-carbon double bond which is substituted by at least one cyclopentadienyl-metal-cyclopentadienyl complex, having the cis/trans isomerisation property, in a reversible manner in response to the absorption of light. Preferably, the rest of the molecule comprises a dendrimer of any generation, advantageously of the polypropylenimine octaamine type. The inventive molecule can be used as a molecular switch and in various differ...

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

    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

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

    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.

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

    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.

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

    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

  14. Enumerating molecules.

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

    2004-04-01

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

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

    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

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

    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.

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

    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

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

    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

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

    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.

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

    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.

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

    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...

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

    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

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

    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

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

    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.

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

    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...

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

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

    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

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

    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.

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

    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

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

    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

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

    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

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

    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

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

    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

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

    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.

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

    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

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

    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

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

    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...

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

    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...

  3. 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

    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

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

    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.

  5. One-way membrane trafficking of SOS in receptor-triggered Ras activation.

    Christensen, Sune M; Tu, Hsiung-Lin; Jun, Jesse E; Alvarez, Steven; Triplet, Meredith G; Iwig, Jeffrey S; Yadav, Kamlesh K; Bar-Sagi, Dafna; Roose, Jeroen P; Groves, Jay T

    2016-09-01

    SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is thought to be initiated predominantly by membrane recruitment of SOS via the adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics. However, SOS has multiple protein and lipid interactions that provide linkage to the membrane. In reconstituted-membrane experiments, these Grb2-independent interactions were sufficient to retain human SOS on the membrane for many minutes, during which a single SOS molecule could processively activate thousands of Ras molecules. These observations raised questions concerning how receptors maintain control of SOS in cells and how membrane-recruited SOS is ultimately released. We addressed these questions in quantitative assays of reconstituted SOS-deficient chicken B-cell signaling systems combined with single-molecule measurements in supported membranes. These studies revealed an essentially one-way trafficking process in which membrane-recruited SOS remains trapped on the membrane and continuously activates Ras until being actively removed via endocytosis. PMID:27501536

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

    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

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

    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

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

    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...

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

    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

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

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

    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.

  12. Origins and Early Evolution of the tRNA Molecule

    Koji Tamura

    2015-12-01

    Full Text Available Modern transfer RNAs (tRNAs are composed of ~76 nucleotides and play an important role as “adaptor” molecules that mediate the translation of information from messenger RNAs (mRNAs. Many studies suggest that the contemporary full-length tRNA was formed by the ligation of half-sized hairpin-like RNAs. A minihelix (a coaxial stack of the acceptor stem on the T-stem of tRNA can function both in aminoacylation by aminoacyl tRNA synthetases and in peptide bond formation on the ribosome, indicating that it may be a vestige of the ancestral tRNA. The universal CCA-3′ terminus of tRNA is also a typical characteristic of the molecule. “Why CCA?” is the fundamental unanswered question, but several findings give a comprehensive picture of its origin. Here, the origins and early evolution of tRNA are discussed in terms of various perspectives, including nucleotide ligation, chiral selectivity of amino acids, genetic code evolution, and the organization of the ribosomal peptidyl transferase center (PTC. The proto-tRNA molecules may have evolved not only as adaptors but also as contributors to the composition of the ribosome.

  13. 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

    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

  14. A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation.

    Chen, Bill B; Coon, Tiffany A; Glasser, Jennifer R; McVerry, Bryan J; Zhao, Jing; Zhao, Yutong; Zou, Chunbin; Ellis, Bryon; Sciurba, Frank C; Zhang, Yingze; Mallampalli, Rama K

    2013-05-01

    Uncontrolled activation of tumor necrosis factor receptor-associated factor (TRAF) proteins may result in profound tissue injury by linking surface signals to cytokine release. Here we show that a ubiquitin E3 ligase component, Fbxo3, potently stimulates cytokine secretion from human inflammatory cells by destabilizing a sentinel TRAF inhibitor, Fbxl2. Fbxo3 and TRAF protein in circulation positively correlated with cytokine responses in subjects with sepsis, and we identified a polymorphism in human Fbxo3, with one variant being hypofunctional. A small-molecule inhibitor targeting Fbxo3 was sufficient to lessen severity of cytokine-driven inflammation in several mouse disease models. These studies identified a pathway of innate immunity that may be useful to detect subjects with altered immune responses during critical illness or provide a basis for therapeutic intervention targeting TRAF protein abundance. PMID:23542741

  15. CD molecules 2005: human cell differentiation molecules

    Zola, H.; Swart, B.; Nicholson, I.; Aasted, B.; Bensussan, A.; Boumsell, L.; Buckley, C.; Clark, G.; Drbal, Karel; Engel, P.; Hart, D.; Hořejší, Václav; Isacke, C.; Macardle, P.; Malavasi, F.; Mason, D.; Olive, D.; Saalmüller, A.; Schlossman, S.F.; Schwartz-Albiez, R.; Simmons, P.; Tedder, T.F.; Uguccioni, M.; Warren, H.

    2005-01-01

    Roč. 106, č. 9 (2005), s. 3123-3126. ISSN 0006-4971 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD molecules * leukocyte antigen Subject RIV: EC - Immunology Impact factor: 10.131, year: 2005

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

    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

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

    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...

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

    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 ...

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

    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

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

    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.

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

    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

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

    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

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

    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

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

    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

  5. Formation of Ultracold Molecules

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

    2016-01-28

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

  6. Trapping molecules on chips

    Santambrogio, Gabriele

    2015-01-01

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

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

    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

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

    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

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

    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

  10. Electron correlation in molecules

    Wilson, S

    2007-01-01

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

  11. 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

    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

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

    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...

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

    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 ...

  14. Electron-molecule collisions

    Takayanagi, Kazuo

    1984-01-01

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

  15. Single molecules and nanotechnology

    Vogel, Horst

    2007-01-01

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

  16. Optothermal Molecule Trap

    Duhr, Stefan; Braun, Dieter

    2006-01-01

    Thermophoresis moves molecules along temperature gradients, typically from hot to cold. We superpose fluid flow with thermophoretic molecule flow under well defined microfluidic conditions, imaged by fluorescence microscopy. DNA is trapped and accumulated 16-fold in regions where both flows move in opposite directions. Strong 800-fold accumulation is expected, however with slow trapping kinetics. The experiment is equally described by a three-dimensional and one-dimensional analytical model. ...

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

    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

  18. Towards single molecule switches.

    Zhang, Jia Lin; Zhong, Jian Qiang; Lin, Jia Dan; Hu, Wen Ping; Wu, Kai; Xu, Guo Qin; Wee, Andrew T S; Chen, Wei

    2015-05-21

    The concept of using single molecules as key building blocks for logic gates, diodes and transistors to perform basic functions of digital electronic devices at the molecular scale has been explored over the past decades. However, in addition to mimicking the basic functions of current silicon devices, molecules often possess unique properties that have no parallel in conventional materials and promise new hybrid devices with novel functions that cannot be achieved with equivalent solid-state devices. The most appealing example is the molecular switch. Over the past decade, molecular switches on surfaces have been intensely investigated. A variety of external stimuli such as light, electric field, temperature, tunneling electrons and even chemical stimulus have been used to activate these molecular switches between bistable or even multiple states by manipulating molecular conformations, dipole orientations, spin states, charge states and even chemical bond formation. The switching event can occur either on surfaces or in break junctions. The aim of this review is to highlight recent advances in molecular switches triggered by various external stimuli, as investigated by low-temperature scanning tunneling microscopy (LT-STM) and the break junction technique. We begin by presenting the molecular switches triggered by various external stimuli that do not provide single molecule selectivity, referred to as non-selective switching. Special focus is then given to selective single molecule switching realized using the LT-STM tip on surfaces. Single molecule switches operated by different mechanisms are reviewed and discussed. Finally, molecular switches embedded in self-assembled monolayers (SAMs) and single molecule junctions are addressed. PMID:25757483

  19. Physical activation of molecules

    A brief review of processes of physical activation of molecules on the basis of phenomena of electronic and vibrational excitation, electron polarization is presented. Consideration is given to activation by electron impact, photo-, magneto- and mechanoactivation, as well as to radiation activation, proceeding under the effect of high-power radiations (102-107 eV). The character of disturbance of molecules, participating in chemical reactions, under the effect of different types of ionizing radiation (α-particles, electrons, γ-quanta etc.) is discussed

  20. Prebiologically Important Interstellar Molecules

    Kuan, Y.-J.; Huang, H.-C.; Charnley, S. B.; Tseng, W.-L.; Snyder, L. E.; Ehrenfreund, P.; Kisiel, Z.; Thorwirth, S.; Bohn, R. K.; Wilson, T. L.

    2004-06-01

    Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.

  1. Atoms, Molecules, and Compounds

    Manning, Phillip

    2007-01-01

    Explores the atoms that govern chemical processes. This book shows how the interactions between simple substances such as salt and water are crucial to life on Earth and how those interactions are predestined by the atoms that make up the molecules.

  2. Exotic helium molecules

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range 4He2(23S1-23P0) molecule, or a 4He2(23S1-23S1) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 ± 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range 4He2(23S1-23S1) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime τ = (1.4 ± 0.3) μs is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  3. OMG: Open Molecule Generator

    Peironcely Julio E

    2012-09-01

    Full Text Available Abstract Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG, which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.

  4. Bacterial invasion reconstructed molecule by molecule

    Werner, James H [Los Alamos National Laboratory

    2009-01-01

    We propose to visualize the initial stages of bacterial infection of a human host cell with unmatched spatial and temporal resolution. This work will develop a new capability for the laboratory (super-resolution optical imaging), will test unresolved scientific hypotheses regarding host-pathogen interaction dynamics, and leverages state of the art 3D molecular tracking instrumentation developed recently by our group. There is much to be gained by applying new single molecule tools to the important and familiar problem of pathogen entry into a host cell. For example, conventional fluorescence microscopy has identified key host receptors, such as CD44 and {alpha}5{beta}1 integrin, that aggregate near the site of Salmonella typhimurium infection of human cells. However, due to the small size of the bacteria ({approx} 2 {micro}m) and the diffraction of the emitted light, one just sees a fluorescent 'blob' of host receptors that aggregate at the site of attachment, making it difficult to determine the exact number of receptors present or whether there is any particular spatial arrangement of the receptors that facilitates bacterial adhesion/entry. Using newly developed single molecule based super-resolution imaging methods, we will visualize how host receptors are directed to the site of pathogen adhesion and whether host receptors adopt a specific spatial arrangement for successful infection. Furthermore, we will employ our 3D molecular tracking methods to follow the injection of virulence proteins, or effectors, into the host cell by the pathogen Type III secretion system (TTSS). We expect these studies to provide mechanistic insights into the early events of pathogen infection that have here-to-fore been technically beyond our reach. Our Research Goals are: Goal 1--Construct a super-resolution fluorescence microscope and use this new capability to image the spatial distribution of different host receptors (e.g. CD44, as {alpha}5{beta}1 integrin) at the

  5. Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways

    Pandey, A; Fernandez, M M; Steen, H;

    2000-01-01

    molecule containing a Src homology 3 domain as well as an immunoreceptor tyrosine-based activation motif (ITAM). This molecule is 55% identical to a previously isolated molecule designated signal transducing adaptor molecule (STAM) that was identified as an interleukin (IL)-2-induced phosphoprotein and is...... therefore designated STAM2. Tyrosine phosphorylation of STAM2 is induced by growth factors such as epidermal growth factor and platelet-derived growth factor as well as by cytokines like IL-3. Several of the deletion mutants tested except the one containing only the amino-terminal region underwent tyrosine...... phosphorylation upon growth factor stimulation, implying that STAM2 is phosphorylated on several tyrosine residues. STAM2 is downstream of the Jak family of kinases since coexpression of STAM2 with Jak1 or Jak2 but not an unrelated Tec family kinase, Etk, resulted in its tyrosine phosphorylation. In contrast to...

  6. Molecules without electrons

    Electrons are the glue that holds the atoms in molecules together. Without them the positive charges of nuclei would repel each other, and the world would be a much simpler place. But in the quest to gain control over matter at a fundamental level, physicists in Russia and Canada have come up with a way of binding charged nuclei without any electrons. Instead the researchers use intense laser light. (U.K.)

  7. Atoms, molecules & elements

    Graybill, George

    2007-01-01

    Young scientists will be thrilled to explore the invisible world of atoms, molecules and elements. Our resource provides ready-to-use information and activities for remedial students using simplified language and vocabulary. Students will label each part of the atom, learn what compounds are, and explore the patterns in the periodic table of elements to find calcium (Ca), chlorine (Cl), and helium (He) through hands-on activities.

  8. Single Molecule Mechanochemistry

    Li, Shaowei; Zhang, Yanxing; Ho, Wilson; Wu, Ruqian; Ruqian Wu, Yanxing Zhang Team; Wilson Ho, Shaowei Li Team

    Mechanical forces can be used to trigger chemical reactions through bending and stretching of chemical bonds. Using the reciprocating movement of the tip of a scanning tunneling microscope (STM), mechanical energy can be provided to a single molecule sandwiched between the tip and substrate. When the mechanical pulse center was moved to the outer ring feature of a CO molecule, the reaction rate was significantly increased compared with bare Cu surface and over Au atoms. First, DFT calculations show that the presence of CO makes the Cu cavity more attractive toward H2 Second, H2 prefers the horizontal adsorption geometry in the Cu-Cu and Au-Cu cavities and no hybridization occurs between the antibonding states of H2 and states of Cu atoms. While H2 loses electrons from its bonding state in all three cavities, the filling of its anti-bonding state only occurs in the CO-Cu cavity. Both make the CO-Cu cavity much more effectively to chop the H2 molecule. Work was supported by the National Science Foundation Center for Chemical Innovation on Chemistry at the Space-Time Limit (CaSTL) under Grant No. CHE-1414466.

  9. Photonic Molecule Lasers Revisited

    Gagnon, Denis; Dumont, Joey; Déziel, Jean-Luc; Dubé, Louis J.

    2014-05-01

    Photonic molecules (PMs) formed by coupling two or more optical resonators are ideal candidates for the fabrication of integrated microlasers, photonic molecule lasers. Whereas most calculations on PM lasers have been based on cold-cavity (passive) modes, i.e. quasi-bound states, a recently formulated steady-state ab initio laser theory (SALT) offers the possibility to take into account the spectral properties of the underlying gain transition, its position and linewidth, as well as incorporating an arbitrary pump profile. We will combine two theoretical approaches to characterize the lasing properties of PM lasers: for two-dimensional systems, the generalized Lorenz-Mie theory will obtain the resonant modes of the coupled molecules in an active medium described by SALT. Not only is then the theoretical description more complete, the use of an active medium provides additional parameters to control, engineer and harness the lasing properties of PM lasers for ultra-low threshold and directional single-mode emission. We will extend our recent study and present new results for a number of promising geometries. The authors acknowledge financial support from NSERC (Canada) and the CERC in Photonic Innovations of Y. Messaddeq.

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

    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.

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

    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.

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

    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

  13. Watching single molecules dance

    Mehta, Amit Dinesh

    Molecular motors convert chemical energy, from ATP hydrolysis or ion flow, into mechanical motion. A variety of increasingly precise mechanical probes have been developed to monitor and perturb these motors at the single molecule level. Several outstanding questions can be best approached at the single molecule level. These include: how far does a motor progress per energy quanta consumed? how does its reaction cycle respond to load? how many productive catalytic cycles can it undergo per diffusional encounter with its track? and what is the mechanical stiffness of a single molecule connection? A dual beam optical trap, in conjunction with in vitro ensemble motility assays, has been used to characterize two members of the myosin superfamily: muscle myosin II and chick brain myosin V. Both move the helical polymer actin, but myosin II acts in large ensembles to drive muscle contraction or cytokinesis, while myosin V acts in small numbers to transport vesicles. An optical trapping apparatus was rendered sufficiently precise to identify a myosin working stroke with 1nm or so, barring systematic errors such as those perhaps due to random protein orientations. This and other light microscopic motility assays were used to characterize myosin V: unlike myosin II this vesicle transport protein moves through many increments of travel while remaining strongly bound to a single actin filament. The step size, stall force, and travel distance of myosin V reveal a remarkably efficient motor capable of moving along a helical track for over a micrometer without significantly spiraling around it. Such properties are fully consistent with the putative role of an organelle transport motor, present in small numbers to maintain movement over long ranges relative to cellular size scales. The contrast between myosin II and myosin V resembles that between a human running on the moon and one walking on earth, where the former allows for faster motion when in larger ensembles but for less

  14. Ultra-cold molecule production.

    Ramirez-Serrano, Jamie; Chandler, David W.; Strecker, Kevin; Rahn, Larry A.

    2005-12-01

    The production of Ultra-cold molecules is a goal of many laboratories through out the world. Here we are pursuing a unique technique that utilizes the kinematics of atomic and molecular collisions to achieve the goal of producing substantial numbers of sub Kelvin molecules confined in a trap. Here a trap is defined as an apparatus that spatially localizes, in a known location in the laboratory, a sample of molecules whose temperature is below one degree absolute Kelvin. Further, the storage time for the molecules must be sufficient to measure and possibly further cool the molecules. We utilize a technique unique to Sandia to form cold molecules from near mass degenerate collisions between atoms and molecules. This report describes the progress we have made using this novel technique and the further progress towards trapping molecules we have cooled.

  15. Magnetic field modification of ultracold molecule-molecule collisions

    Tscherbul, T. V.; Suleimanov, Yu. V.; Aquilanti, V.; Krems, R.V.

    2008-01-01

    We present an accurate quantum mechanical study of molecule-molecule collisions in the presence of a magnetic field. The work focusses on the analysis of elastic scattering and spin relaxation in collisions of O2(3Sigma_g) molecules at cold (~0.1 K) and ultracold (~10^{-6} K) temperatures. Our calculations show that magnetic spin relaxation in molecule-molecule collisions is extremely efficient except at magnetic fields below 1 mT. The rate constant for spin relaxation at T=0.1 K and a magnet...

  16. Passing Current through Touching Molecules

    Schull, G.; Frederiksen, Thomas; Brandbyge, Mads;

    2009-01-01

    The charge flow from a single C-60 molecule to another one has been probed. The conformation and electronic states of both molecules on the contacting electrodes have been characterized using a cryogenic scanning tunneling microscope. While the contact conductance of a single molecule between two...

  17. Efficient single molecule detection and single molecule photochemistry

    Affleck, R.L.; Ambrose, W.P.; Goodwin, P.M. [Los Alamos National Lab., NM (United States)] [and others

    1996-12-31

    Single molecule detection efficiencies greater than 90% in flowing sample streams can be attained by confining the sample to the center of the excitation laser beam and photobleaching the reagent stream immediately before it enters the detection flow cell. Photolysis of single molecules of B-Phycoerythrin dissolved in aqueous solution is observed as an abrupt cessation of the fluorescence from these molecules as they flow through {approximately}40 pl probe volume. An analysis of the survival times of individual molecules in the laser beams yields the photodestruction quantum yield of the molecule. Photon pair correlation measurements of the fluorescence detected from single B-PE molecules demonstrate that the molecule fluoresces from only one bilin chromophore at a time.

  18. Photochemistry of biological molecules

    Earlier studies of the photodamage induced by 254nm irradiation of linear alanine peptides in the solid state have been supplemented by an investigation into the gaseous photoproducts from the cyclic dipeptide, 3,6-dimethyl-2,5-diketopiperazine. The trans and cis isomers have been prepared and the photoproducts compared with those from the DL-mixture. The conformation of the molecule did influence the yield of gaseous products. CO was produced by peptide bond rupture with concomitant release of hydrogen. C02 was also produced. The use of N- and C-deuterated analogues together with relevant crystallographic and EPR data has enabled a detailed study of the mechanism of photodegradation to be made, from which it was concluded that the methyl protons are not inert but rather are the major source of the hydrogen observed on photolysis. (author)

  19. Forces in molecules.

    Hernández-Trujillo, Jesús; Cortés-Guzmán, Fernando; Fang, De-Chai; Bader, Richard F W

    2007-01-01

    Chemistry is determined by the electrostatic forces acting within a collection of nuclei and electrons. The attraction of the nuclei for the electrons is the only attractive force in a molecule and is the force responsible for the bonding between atoms. This is the attractive force acting on the electrons in the Ehrenfest force and on the nuclei in the Feynman force, one that is countered by the repulsion between the electrons in the former and by the repulsion between the nuclei in the latter. The virial theorem relates these forces to the energy changes resulting from interactions between atoms. All bonding, as signified by the presence of a bond path, has a common origin in terms of the mechanics determined by the Ehrenfest, Feynman and virial theorems. This paper is concerned in particular with the mechanics of interaction encountered in what are classically described as 'nonbonded interactions'--are atoms that 'touch' bonded or repelling one another? PMID:17328425

  20. Lanthanide single molecule magnets

    Tang, Jinkui

    2015-01-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs, and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures – an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and...

  1. Lanthanide single molecule magnets

    Tang, Jinkui; Zhang, Peng [Chinese Academy of Sciences, Changchun (China). Changchun Inst. of Applied Chemistry

    2015-10-01

    This book begins by providing basic information on single-molecule magnets (SMMs), covering the magnetism of lanthanide, the characterization and relaxation dynamics of SMMs and advanced means of studying lanthanide SMMs. It then systematically introduces lanthanide SMMs ranging from mononuclear and dinuclear to polynuclear complexes, classifying them and highlighting those SMMs with high barrier and blocking temperatures - an approach that provides some very valuable indicators for the structural features needed to optimize the contribution of an Ising type spin to a molecular magnet. The final chapter presents some of the newest developments in the lanthanide SMM field, such as the design of multifunctional and stimuli-responsive magnetic materials as well as the anchoring and organization of the SMMs on surfaces. In addition, the crystal structure and magnetic data are clearly presented with a wealth of illustrations in each chapter, helping newcomers and experts alike to better grasp ongoing trends and explore new directions.

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

    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

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

    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.

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

    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

  5. Reactions of oriented molecules.

    Brooks, P R

    1976-07-01

    Beams of oriented molecules have been used to directly study geometrical requirements in chemical reactions. These studies have shown that reactivity is much greater in some orientations than others and demonstrated the existence of steric effects. For some reactions portions of the orientation results are in good accord with traditional views of steric hindrance, but for others it is clear that our chemical intuition needs recalibrating. Indeed, the information gained from simultaneously orienting the reactants and observing the scattering angle of the products may lead to new insights about the detailed mechanism of certain reactions. Further work must be done to extend the scope and detail of the studies described here. More detailed information is needed on the CH(3)I reaction and the CF(3)I reaction. The effects of alkyl groups of various sizes and alkali metals of various sizes are of interest. In addition, reactions where a long-lived complex is formed should be studied to see if orientation is important. Finally, it would be of interest to apply the technique to the sort of reactions that led to our interest in the first place: the S(N)2 displacements in alkyl halides where the fascinating Walden inversion occurs. PMID:17793988

  6. Molecule-based magnets

    J V Yakhmi

    2009-06-01

    The conventional magnetic materials used in current technology, such as, Fe, Fe2O3, Cr2O3, SmCo5, Nd2Fe14B etc are all atom-based, and their preparation/processing require high temperature routes. Employing self-assembly methods, it is possible to engineer a bulk molecular material with long-range magnetic order, mainly because one can play with the weak intermolecular interactions. Since the first successful synthesis of molecular magnets in 1986, a large variety of them have been synthesized, which can be categorized on the basis of the chemical nature of the magnetic units involved: organic-, metal-based systems, heterobimetallic assemblies, or mixed organic–inorganic systems. The design of molecule-based magnets has also been extended to the design of poly-functional molecular magnets, such as those exhibiting second-order optical nonlinearity, liquid crystallinity, or chirality simultaneously with long-range magnetic order. Solubility, low density and biocompatibility are attractive features of molecular magnets. Being weakly coloured, unlike their opaque classical magnet ‘cousins’ listed above, possibilities of photomagnetic switching exist. Persistent efforts also continue to design the ever-elusive polymer magnets towards applications in industry. While providing a brief overview of the field of molecular magnetism, this article highlights some recent developments in it, with emphasis on a few studies from the author’s own lab.

  7. Tunnelling of a molecule

    A quantum-mechanical description of tunnelling is presented for a one-dimensional system with internal oscillator degrees of freedom. The 'charged diatomic molecule' is frustrated on encountering a barrier potential by its centre of charge not being coincident with its centre of mass, resulting in transitions amongst internal states. In an adiabatic limit, the tunnelling of semiclassical coherent-like oscillator states is shown to exhibit the Hartman and Bueuttiker-Landauer times tH and tBL, with the time dependence of the coherent state parameter for the tunnelled state given by α(t) = α e-iω(t+Δt) , Δt = tH - itBL. A perturbation formalism is developed, whereby the exact transfer matrix can be expanded to any desired accuracy in a suitable limit. An 'intrinsic' time, based on the oscillator transition rate during tunnelling, transmission or reflection, is introduced. In simple situations the resulting intrinsic tunnelling time is shown to vanish to lowest order. In the general case a particular (nonzero) parametrisation is inferred, and its properties discussed in comparison with the literature on tunnelling times for both wavepackets and internal clocks. Copyright (1998) CSIRO Australia

  8. Organic Molecules in Meteorites

    Martins, Zita

    2015-08-01

    Carbonaceous meteorites are primitive samples from the asteroid belt, containing 3-5wt% organic carbon. The exogenous delivery of organic matter by carbonaceous meteorites may have contributed to the organic inventory of the early Earth. The majority (>70%) of the meteoritic organic material consist of insoluble organic matter (IOM) [1]. The remaining meteoritic organic material (Haber-Bosch type gas-grain reactions after the meteorite parent body cooled to lower temperatures [13, 14].The analysis of the abundances and distribution of the organic molecules present in meteorites helps to determine the physical and chemical conditions of the early solar system, and the prebiotic organic compounds available on the early Earth.[1] Cody and Alexander (2005) GCA 69, 1085. [2] Cronin and Chang (1993) in: The Chemistry of Life’s Origin. pp. 209-258. [3] Martins and Sephton (2009) in: Amino acids, peptides and proteins in organic chemistry. pp. 1-42. [4] Martins (2011) Elements 7, 35. [5] Botta et al. (2007) MAPS 42, 81. [6] Martins et al. (2015) MAPS, in press. [7] Cooper and Cronin (1995) GCA 59, 1003. [8] Glavin et al. (2006) MAPS. 41, 889. [9] Glavin et al. (2011) MAPS 45, 1948. [10] Elsila et al. (2005) GCA 5, 1349. [11] Glavin and Dworkin (2009) PNAS 106, 5487. [12] Pizzarello et al. (2003) GCA 67, 1589. [13] Chan et al. (2012) MAPS. 47, 1502. [14] Burton et al. (2011) MAPS 46, 1703.

  9. Thread bonds in molecules

    Ivlev, B

    2015-01-01

    Unusual chemical bonds are proposed. Each bond is almost covalent but is characterized by the thread of a small radius $\\sim 0.6\\times 10^{-11}$cm, between two nuclei in a molecule. The main electron density is concentrated outside the thread as in a covalent bond. The thread is formed by the electron wave function which has a tendency to be singular on it. The singularity along the thread is cut off by electron "vibrations" due to the interaction with zero point electromagnetic oscillations. The electron energy has its typical value of (1-10)eV. Due to the small tread radius the uncertainty of the electron momentum inside the thread is large resulting in a large electron kinetic energy $\\sim 1 MeV$. This energy is compensated by formation of a potential well due to the reduction of the energy of electromagnetic zero point oscillations. This is similar to formation of a negative van der Waals potential. Thread bonds are stable and cannot be created or destructed in chemical or optical processes.

  10. 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

    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...

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

    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.

  12. Strongly interacting ultracold polar molecules

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  13. Strongly interacting ultracold polar molecules

    Gadway, Bryce

    2016-01-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  14. Molecules Best Paper Award 2012

    Derek J. McPhee

    2012-02-01

    Full Text Available Molecules starts to institute the “Best Paper” award to recognize these outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the first “Molecules Best Paper Award” for 2012. Nominations were selected by the editor-in-chief and selected editorial board members from all the papers published in 2008. [...

  15. Molecules Best Paper Award 2014

    Derek J. McPhee

    2014-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2014. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2010. Reviews and research papers were evaluated separately.

  16. Molecules Best Paper Award 2013

    Derek J. McPhee

    2013-02-01

    Full Text Available Molecules has started to institute a "Best Paper" award to recognize the most outstanding papers in the area of natural products, medicinal chemistry and molecular diversity published in Molecules. We are pleased to announce the second "Molecules Best Paper Award" for 2013. Candidates were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2009.

  17. Recoiling DNA Molecule: Simulation & Experiment

    Neto, Jose Coelho; Dickman, Ronald; Mesquita, O. N.

    2002-01-01

    Single molecule DNA experiments often generate data from force versus extension measurements involving the tethering of a microsphere to one end of a single DNA molecule while the other is attached to a substrate. We show that the persistence length of single DNA molecules can also be measured based on the recoil dynamics of these DNA-microsphere complexes if appropriate corrections are made to the friction coefficient of the microsphere in the vicinity of the substrate. Comparison between co...

  18. Labelled molecules, modern research implements

    Details of the synthesis of carbon 14- and tritium-labelled molecules are examined. Although the methods used are those of classical organic chemistry the preparation of carbon 14-labelled molecules differs in some respects, most noticeably in the use of 14CO2 which requires very special handling techniques. For the tritium labelling of organic molecules the methods are somewhat different, very often involving exchange reactions. The following are described in turn: the so-called Wilzbach exchange method; exchange by catalysis in solution; catalytic hydrogenation with tritium; reductions with borotritides. Some applications of labelled molecules in organic chemistry, biochemistry and pharmacology are listed

  19. STM investigation of surfactant molecules

    2002-01-01

    Adsorption and self-organization of sodium alkyl sulfonates (STS and SHS) have been studied on HOPG by using the in situ scanning tunneling microscopy (STM). Both SHS and STS molecules adsorb on the HOPG surface and form long-range well-ordered monolayers. The neighboring molecules in different rows form a "head to head" configuration. In the high-resolution images of STS and SHS molecules, one end of the molecules shows bright spots which are attributed to the SO3- groups.

  20. Molecules Best Paper Award 2015

    Derek J. McPhee

    2015-01-01

    Full Text Available Molecules instituted some years ago a “Best Paper” award to recognize the most outstanding papers in the area of organic synthesis, natural products, medicinal chemistry and molecular diversity published each year in Molecules. We are pleased to announce the third “Molecules Best Paper Award” for 2015. The winners were chosen by the Editor-in-Chief and selected editorial board members from among all the papers published in 2011. Reviews and research papers were evaluated separately. We are pleased to announce that the following eight papers have won the Molecules Best Paper Award for 2015:[...

  1. Aromatic molecules as spintronic devices

    In this paper, we study the spin-dependent electron transport through aromatic molecular chains attached to two semi-infinite leads. We model this system taking into account different geometrical configurations which are all characterized by a tight binding Hamiltonian. Based on the Green's function approach with a Landauer formalism, we find spin-dependent transport in short aromatic molecules by applying external magnetic fields. Additionally, we find that the magnetoresistance of aromatic molecules can reach different values, which are dependent on the variations in the applied magnetic field, length of the molecules, and the interactions between the contacts and the aromatic molecule

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

    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.

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

    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

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

    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

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

    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.

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

    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

  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.

    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*

    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.

    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

    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. Single-molecule magnet engineering

    Pedersen, Kasper Steen; Bendix, Jesper; Clérac, Rodolphe

    2014-01-01

    to delicately tune, for instance, the properties of molecules that behave as "magnets", the so-called single-molecule magnets (SMMs). Although many interesting SMMs have been prepared by a more or less serendipitous approach, the assembly of predesigned, isolatable molecular entities into higher nuclearity...

  12. Small-Molecule Stabilization of the 14-3-3/Gab2 Protein-Protein Interaction (PPI) Interface.

    Bier, David; Bartel, Maria; Sies, Katharina; Halbach, Sebastian; Higuchi, Yusuke; Haranosono, Yu; Brummer, Tilman; Kato, Nobuo; Ottmann, Christian

    2016-04-19

    Small-molecule modulation of protein-protein interactions (PPIs) is one of the most promising new areas in drug discovery. In the vast majority of cases only inhibition or disruption of PPIs is realized, whereas the complementary strategy of targeted stabilization of PPIs is clearly under-represented. Here, we report the example of a semi-synthetic natural product derivative--ISIR-005--that stabilizes the cancer-relevant interaction of the adaptor protein 14-3-3 and Gab2. The crystal structure of ISIR-005 in complex with 14-3-3 and the binding motif of Gab2 comprising two phosphorylation sites (Gab2pS210pT391) showed how the stabilizing molecule binds to the rim-of-the-interface of the protein complex. Only in the direct vicinity of 14-3-3/Gab2pT391 site is a pre-formed pocket occupied by ISIR-005; binding of the Gab2pS210 motif to 14-3-3 does not create an interface pocket suitable for the molecule. Accordingly, ISIR-005 only stabilizes the binding of the Gab2pT391 but not the Gab2pS210 site. This study represents structural and biochemical proof of the druggability of the 14-3-3/Gab2 PPI interface with important implications for the development of PPI stabilizers. PMID:26644359

  13. When water molecules meet air

    Hsie, Cho-Shuen; Campen, R. Kramer; Verde, Ana Vila; Bolhuis, Peter; Nienhuys, Han-Kwang; Bonn, Mischa

    2012-01-01

    About 70% of our planet is covered in water. Most of that water exists as water in the bulk – the neighbors of water molecules are other water molecules – and only a small fraction of molecules are at the air-water interface. Despite the small relative abundance of interfacial water, it is of the utmost importance: it governs the chemistry involving the surface of oceans and seawater aerosols, or the small water droplets forming clouds. Reactions at the air-water interface are directly releva...

  14. Quantum transport through aromatic molecules

    In this paper, we study the electronic transport properties through aromatic molecules connected to two semi-infinite leads. The molecules are in different geometrical configurations including arrays. Using a nearest neighbor tight-binding approach, the transport properties are analyzed into a Green's function technique within a real-space renormalization scheme. We calculate the transmission probability and the Current-Voltage characteristics as a function of a molecule-leads coupling parameter. Our results show different transport regimes for these systems, exhibiting metal-semiconductor-insulator transitions and the possibility to employ them in molecular devices

  15. 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.

    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

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

    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

  17. Theoretical Investigations Regarding Single Molecules

    Pedersen, Kim Georg Lind

    interfere destructively or constructively. Destructive interference effects in electron transport could potentially improve thermo-electrics, organic logic circuits and energy harvesting. We have investigated destructive interference in off-resonant transport through organic molecules, and have found a set...

  18. Polar molecule dominated electrorheological effect

    Lu Kun-Quan; Shen Rong; Wang Xue-Zhao; Sun Gang; Wen Wei-Jia; Liu Ji-Xing

    2006-01-01

    The yield stress of our newly developed electrorheological (ER) fluids consisting of dielectric nano-particles suspended in silicone oil reaches hundreds of kPa, which is orders of magnitude higher than that of conventional ones. We found that the polar molecules adsorbed on the particles play a decisive role in such new ER fluids. To explain this polar molecule dominated ER (PM-ER) effect a model is proposed based on the interaction of polar molecule-charge between the particles, where the local electric field is significantly enhanced and results in the polar molecules aligning in the direction of the electric field. The model can well explain the giant ER effect and a near-linear dependence of the yield stress on the electric field. The main effective factors for achieving high-performance PM-ER fluids are discussed. The PM-ER fluids with the yield stress higher than one MPa can be expected.

  19. Nuclear molecules with three clusters

    Full text: Recently, in the cold fusion of 252 Cf, indications where found for the existence of nuclear molecules with three clusters. The system identified is 96 Sr + 10 Be + 146 Ba. In the first half of the talk the geometric model for three-cluster molecules is resumed and calculations done are presented. Problems and restrictions of the geometric model will be discussed. In the second half an Ansatz for an algebraic model for nuclear molecules is given. In a first step we restrict to two clusters only, which might have an application to standard two-cluster molecules. A Hamiltonian is proposed. The mapping to a geometric potential is described, which is fitted to the calculation of internuclear potentials using double-folding techniques. (Author)

  20. Single-Molecule DNA Analysis

    Efcavitch, J. William; Thompson, John F.

    2010-07-01

    The ability to detect single molecules of DNA or RNA has led to an extremely rich area of exploration of the single most important biomolecule in nature. In cases in which the nucleic acid molecules are tethered to a solid support, confined to a channel, or simply allowed to diffuse into a detection volume, novel techniques have been developed to manipulate the DNA and to examine properties such as structural dynamics and protein-DNA interactions. Beyond the analysis of the properties of nucleic acids themselves, single-molecule detection has enabled dramatic improvements in the throughput of DNA sequencing and holds promise for continuing progress. Both optical and nonoptical detection methods that use surfaces, nanopores, and zero-mode waveguides have been attempted, and one optically based instrument is already commercially available. The breadth of literature related to single-molecule DNA analysis is vast; this review focuses on a survey of efforts in molecular dynamics and nucleic acid sequencing.

  1. Absorption characteristics of bacteriorhodopsin molecules

    H K T Kumar; K Appaji Gowda

    2000-03-01

    The bacteriorhodopsin molecule absorbs light and undergoes a series of structural transformation following a well-defined photocycle. The complex photocycle is transformed to an equivalent level diagram by considering the lifetime of the intermediate states. Assuming that only and states are appreciably populated at any instant of time, the level diagram is further simplified to two-level system. Based on the rate equations for two-level system, an analytic expression for the absorption coefficient of bacteriorhodopsin molecule is derived. It is applied to study the behaviour of absorption coefficient of bacteriorhodopsin film in the visible wavelength region of 514 nm. The dependence of absorption coefficient of bacteriorhodopsin film on the thickness of the film, total number density of active molecules and initial number density of molecules in -state is presented in the graphical form.

  2. Ultracold molecules and ultracold chemistry

    Softley, Tim; Bell, Martin

    2009-01-01

    Abstract The recent development of a range of new methods for producing samples of gas phase molecules that are translationally cold (T < 1 K) or ultracold (T < 1 mK) is driving efforts to study reactive and inelastic collisional processes in these temperature regimes. In this review article the new methods for cold/ultracold molecule production are reviewed in the context of their potential or current use in collisional studies and progress in the application of these methods i...

  3. Raman Optical Activity Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    Jovan Jose, K V; Raghavachari, Krishnan

    2016-02-01

    We present an efficient method for the calculation of the Raman optical activity (ROA) spectra for large molecules through the molecules-in-molecules (MIM) fragment-based method. The relevant higher energy derivatives from smaller fragments are used to build the property tensors of the parent molecule to enable the extension of the MIM method for evaluating ROA spectra (MIM-ROA). Two factors were found to be particularly important in yielding accurate results. First, the link-atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, yielding a mathematically rigorous method. Second, the long-range interactions between fragments are taken into account by using a less computationally expensive lower level of theory. The performance of the MIM-ROA model is calibrated on the enantiomeric pairs of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and ROA intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-ROA method is employed to predict the ROA spectra of d-maltose, α-D-cyclodextrin, and cryptophane-A, yielding spectra in excellent agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-ROA model for exploring ROA spectra of large molecules. PMID:26760444

  4. Vibrational Circular Dichroism Spectra for Large Molecules through Molecules-in-Molecules Fragment-Based Approach.

    Jose, K V Jovan; Beckett, Daniel; Raghavachari, Krishnan

    2015-09-01

    We present the first implementation of the vibrational circular dichroism (VCD) spectrum of large molecules through the Molecules-in-Molecules (MIM) fragment-based method. An efficient projection of the relevant higher energy derivatives from smaller fragments to the parent molecule enables the extension of the MIM method for the evaluation of VCD spectra (MIM-VCD). The overlapping primary subsystems in this work are constructed from interacting fragments using a number-based scheme and the dangling bonds are saturated with link hydrogen atoms. Independent fragment calculations are performed to evaluate the energies, Hessian matrix, atomic polar tensor (APT), and the atomic axial tensor (AAT). Subsequently, the link atom tensor components are projected back onto the corresponding host and supporting atoms through the Jacobian projection method, as in the ONIOM approach. In the two-layer model, the long-range interactions between fragments are accounted for using a less computationally intensive lower level of theory. The performance of the MIM model is calibrated on the d- and l-enantiomers of 10 carbohydrate benchmark molecules, with strong intramolecular interactions. The vibrational frequencies and VCD intensities are accurately reproduced relative to the full, unfragmented, results for these systems. In addition, the MIM-VCD method is employed to predict the VCD spectra of perhydrotriphenylene and cryptophane-A, yielding spectra in agreement with experiment. The accuracy and performance of the benchmark systems validate the MIM-VCD model for exploring vibrational circular dichroism spectra of large molecules. PMID:26575919

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

    Ertl Peter

    2012-07-01

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

  6. Electron Collisions with Large Molecules

    McKoy, Vincent

    2006-10-01

    In recent years, interest in electron-molecule collisions has increasingly shifted to large molecules. Applications within the semiconductor industry, for example, require electron collision data for molecules such as perfluorocyclobutane, while almost all biological applications involve macromolecules such as DNA. A significant development in recent years has been the realization that slow electrons can directly damage DNA. This discovery has spurred studies of low-energy collisions with the constituents of DNA, including the bases, deoxyribose, the phosphate, and larger moieties assembled from them. In semiconductor applications, a key goal is development of electron cross section sets for plasma chemistry modeling, while biological studies are largely focused on understanding the role of localized resonances in inducing DNA strand breaks. Accurate calculations of low-energy electron collisions with polyatomic molecules are computationally demanding because of the low symmetry and inherent many-electron nature of the problem; moreover, the computational requirements scale rapidly with the size of the molecule. To pursue such studies, we have adapted our computational procedure, known as the Schwinger multichannel method, to run efficiently on highly parallel computers. In this talk, we will present some of our recent results for fluorocarbon etchants used in the semiconductor industry and for constituents of DNA and RNA. In collaboration with Carl Winstead, California Institute of Technology.

  7. Laser spectroscopy of cold molecules

    Borri, Simone

    2016-01-01

    This paper reviews the recent results in high-resolution spectroscopy on cold molecules. Laser spectroscopy of cold molecules addresses issues of symmetry violation, like in the search for the electric dipole moment of the electron and the studies on energy differences in enantiomers of chiral species; tries to improve the precision to which fundamental physical constants are known and tests for their possible variation in time and space; tests quantum electrodynamics, and searches for a fifth force. Further, we briefly review the recent technological progresses in the fields of cold molecules and mid-infrared lasers, which are the tools that mainly set the limits for the resolution that is currently attainable in the measurements.

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

    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

  9. Technetium-aspirin molecule complexes

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author)

  10. Phase structure of soliton molecules

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E-fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained

  11. Phase structure of soliton molecules

    Hause, A.; Hartwig, H.; Seifert, B.; Stolz, H.; Böhm, M.; Mitschke, F.

    2007-06-01

    Temporal optical soliton molecules were recently demonstrated; they potentially allow further increase of data rates in optical telecommunication. Their binding mechanism relies on the internal phases, but these have not been experimentally accessible so far. Conventional frequency-resolved optical gating techniques are not suited for measurement of their phase profile: Their algorithms fail to converge due to zeros both in their temporal and their spectral profile. We show that the VAMPIRE (very advanced method of phase and intensity retrieval of E -fields) method performs reliably. With VAMPIRE the phase profile of soliton molecules has been measured, and further insight into the mechanism is obtained.

  12. Orbital molecules in electronic materials

    Attfield, J. Paul, E-mail: j.p.attfield@ed.ac.uk [Centre for Science at Extreme Conditions and School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JZ (United Kingdom)

    2015-04-01

    Orbital molecules are made up of coupled orbital states on several metal ions within an orbitally ordered (and sometimes also charge-ordered) solid such as a transition metal oxide. Spin-singlet dimers are known in many materials, but recent discoveries of more exotic species such as 18-electron heptamers in AlV{sub 2}O{sub 4} and magnetic 3-atom trimerons in magnetite (Fe{sub 3}O{sub 4}) have shown that orbital molecules constitute a general new class of quantum electronic states in solids.

  13. Recoiling DNA Molecule Simulation & Experiment

    Neto, J C; Mesquita, O N; Neto, Jose Coelho; Dickman, Ronald

    2002-01-01

    Many recent experiments with single DNA molecules are based on force versus extension measurements and involve tethering a microsphere to one of its extremities and the other to a microscope coverglass. In this work we show that similar results can also be obtained by studying the recoil dynamics of the tethered microspheres. Computer simulations of the corresponding Langevin equation indicate which assumptions are required for a reliable analysis of the experimental recoil curves. We have measured the persistence length A of single naked DNA molecules and DNA-Ethidium Bromide complexes using this approach.

  14. Teaching lasers to control molecules

    We simulate a method to teach a laser pulse sequences to excite specified molecular states. We use a learning procedure to direct the production of pulses based on ''fitness'' information provided by a laboratory measurement device. Over a series of pulses the algorithm learns an optimal sequence. The experimental apparatus, which consists of a laser, a sample of molecules and a measurement device, acts as an analog computer that solves Schroedinger's equation n/Iexactly, in real time. We simulate an apparatus that learns to excite specified rotational states in a diatomic molecule

  15. Exotic helium molecules; Molecules exotiques d'helium

    Portier, M

    2007-12-15

    We study the photo-association of an ultracold cloud of magnetically trapped helium atoms: pairs of colliding atoms interact with one or two laser fields to produce a purely long range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}P{sub 0}) molecule, or a {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) long range molecule. Light shifts in one photon photo-association spectra are measured and studied as a function of the laser polarization and intensity, and the vibrational state of the excited molecule. They result from the light-induced coupling between the excited molecule, and bound and scattering states of the interaction between two metastable atoms. Their analysis leads to the determination of the scattering length a = (7.2 {+-} 0.6) ruling collisions between spin polarized atoms. The two photon photo-association spectra show evidence of the production of polarized, long-range {sup 4}He{sub 2}(2{sup 3}S{sub 1}-2{sup 3}S{sub 1}) molecules. They are said to be exotic as they are made of two metastable atoms, each one carrying a enough energy to ionize the other. The corresponding lineshapes are calculated and decomposed in sums and products of Breit-Wigner and Fano profiles associated to one and two photon processes. The experimental spectra are fit, and an intrinsic lifetime {tau} = (1.4 {+-} 0.3) {mu}s is deduced. It is checked whether this lifetime could be limited by spin-dipole induced Penning autoionization. This interpretation requires that there is a quasi-bound state close to the dissociation threshold in the singlet interaction potential between metastable helium atoms for the theory to match the experiment. (author)

  16. Multiphoton dissociation of polyatomic molecules

    The dynamics of infrared multiphoton excitation and dissociation of SF6 was investigated under collision free conditions by a crossed laser-molecular beam method. In order to understand the excitation mechanism and to elucidate the requirements of laser intensity and energy fluence, a series of experiments were carried out to measure the dissociation yield dependences on energy fluence, vibrational temperature of SF6, the pulse duration of the CO2 laser and the frequency in both one and two laser experiments. Translational energy distributions of the SF5 dissociation product measured by time of flight and angular distributions and the dissociation lifetime of excited SF6 as inferred from the observation of secondary dissociation of SF5 into SF4 and F during the laser pulse suggest that the dynamics of dissociation of excited molecules is dominated by complete energy randomization and rapid intramolecular energy transfer on a nanosecond timescale, and can be adequately described by RRKM theory. An improved phenomenological model including the initial intensity dependent excitation, a rate equation describing the absorption and stimulated emission of single photons, and the unimolecular dissociation of excited molecules is constructed based on available experimental results. The model shows that the energy fluence of the laser determines the excitation of molecules in the quasi-continuum and the excess energy with which molecules dissociate after the laser pulse. The role played by the laser intensity in multiphoton dissociation is more significant than just that of overcoming the intensity dependent absorption in the lowest levels. 63 references

  17. Tunneling Ionization of Diatomic Molecules

    Svensmark, Jens Søren Sieg

    2016-01-01

    of tunneling ionizaion of molecules is presented and the results of numerical calculations are shown. One perhaps surprising result is, that the frequently used Born-Oppenheimer approximation breaks down for weak fields when describing tunneling ionization. An analytic theory applicable in the weak...

  18. Monitoring Molecules: Insights and Progress

    Wightman, R Mark

    2014-01-01

    In August, 2014, neuroscientists and physical scientists gathered together on the campus of the University of California, Los Angeles to discuss how to monitor molecules in neuroscience. This field has seen significant growth since its inception in the 1970s. Here, the advances in this field are documented, including its advance into understanding the actions that specific neurotransmitters mediate during behavior.

  19. Azobenzene-functionalized cascade molecules

    Archut, A.; Vogtle, F.; De Cola, L.;

    1998-01-01

    Cascade molecules bearing up to 32 azobenzene groups in the periphery have been prepared from poly(propylene imine) dendrimers and N-hydroxysuccinimide esters. The dendritic azobenzene species show similar isomerization properties as the corresponding azobenzene monomers. The all-E azobenzene den...

  20. Engineering crystals of dendritic molecules.

    Lukin, Oleg; Schubert, Dirk; Müller, Claudia M; Schweizer, W Bernd; Gramlich, Volker; Schneider, Julian; Dolgonos, Grygoriy; Shivanyuk, Alexander

    2009-07-01

    A detailed single-crystal X-ray study of conformationally flexible sulfonimide-based dendritic molecules with systematically varied molecular architectures was undertaken. Thirteen crystal structures reported in this work include 9 structures of the second-generation dendritic sulfonimides decorated with different aryl groups, 2 compounds bearing branches of both second and first generation, and 2 representatives of the first generation. Analysis of the packing patterns of 9 compounds bearing second-generation branches shows that despite their lack of strong directive functional groups there is a repeatedly reproduced intermolecular interaction mode consisting in an anchor-type packing of complementary second-generation branches of neighbouring molecules. The observed interaction tolerates a wide range of substituents in meta- and para-positions of the peripheral arylsulfonyl rings. Quantum chemical calculations of the molecule-molecule interaction energies agree at the qualitative level with the packing preferences found in the crystalline state. The calculations can therefore be used as a tool to rationalize and predict molecular structures with commensurate and non-commensurate branches for programming of different packing modes in crystal. PMID:19549870

  1. Nucleic Acids as Information Molecules.

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  2. Quantum interferometry with complex molecules

    Arndt, Markus; Hornberger, Klaus

    2009-01-01

    This chapter reviews recent experiments on matter wave interferometry with large molecules. Starting from an elementary introduction to matter wave physics we discuss far-field diffraction and near-field interferometry with thermally excited many-body systems. We describe the constraints imposed by decoherence and dephasing effects, and present an outlook to the future challenges in macromolecule and cluster interferometry.

  3. Molecule-by-Molecule Writing Using a Focused Electron Beam

    Van Dorp, Willem F.; Zhang, Xiaoyan; Feringa, Ben L.; Hansen, Thomas Willum; Wagner, Jakob Birkedal; De Hosson, Jeff Th. M.

    2012-01-01

    The resolution of lithography techniques needs to be extended beyond their current limits to continue the trend of miniaturization and enable new applications. But what is the ultimate spatial resolution? It is known that single atoms can be imaged with a highly focused electron beam. Can single...... atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor on...... graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated...

  4. Ballonet String Model of Molecules

    Gavril NIAC

    2008-06-01

    Full Text Available Strings of ballonets, modelling rows of orbitals, are assembled to molecule models by crossing them properly. The ballonets at the ends of the strings of 2, 3, 4 or 5 spheres represent bonding orbitals of hydrogen with other elements like C, N or O (the proton being inside the sphere, as well as nonbonding orbitals. The ballonets between them are modelling bonding orbitals among elements other than hydrogen - except the double bond in diborane, the atomic cores laying at the junction of two or more spheres.Advantages of elastic sphere models range from self-adjusting bond angles to resistance when closing cycles like cyclopropane or modeling double bonds.Examples comprise alkanes, including platonic hydrocarbons, ethene, acetylene, and some inorganic molecules.

  5. Electrochemical detection of single molecules.

    Fan, F R; Bard, A J

    1995-02-10

    The electrochemical behavior of a single molecule can be observed by trapping a small volume of a dilute solution of the electroactive species between an ultramicroelectrode tip with a diameter of approximately 15 nanometers and a conductive substrate. A scanning electrochemical microscope was used to adjust the tip-substrate distance ( approximately 10 nanometers), and the oxidation of [(trimethylammonio)methyl] ferrocene (Cp(2)FeTMA(+)) to Cp(2)FeTMA(2+) was carried out. The response was stochastic, and anodic current peaks were observed as the molecule moved into and out of the electrode-substrate gap. Similar experiments were performed with a solution containing two redox species, ferrocene carboxylate (Cp(2)FeCOO(-)) and Os(bpy)(3)(2+) (bpy is 2,2'-bipyridyl). PMID:17813918

  6. Observing electron motion in molecules

    We study analytically the possibility for monitoring electron motion in a molecule using two ultrashort laser pulses. The first prepares a coherent superposition of two electronic molecular states whereas the second (attosecond pulse) photoionizes the molecule. We show that interesting information about electron dynamics can be obtained from measurement of the photoelectron spectra as a function of the time delay between two pulses. In particular, asymmetries in photoelectron angular distribution provide a simple signature of the electron motion within the initial time-dependent coherently coupled two molecular states. Both asymmetries and electron spectra show very strong two-centre interference patterns. We illustrate these effects using as an example a dissociating hydrogen molecular ion probed by the attosecond pulses

  7. Nano trap for polar molecules

    A new ac/dc monopole trap for neutral polar particles, introduced and explored by Blümel (2011 Phys. Rev. A 83 045402 and 2011 Eur. Phys. J. D 64 85–101), is significantly advanced in several directions. (1) Previously shown to work only for polar classical particles and polar macro-molecules, the trap is shown to work for polar diatomic molecules. (2) A homogeneous electric field, optionally switched on for improved stability in the angular direction, leads to stable trapping in higher order stability regions of the Mathieu equation. (3) Based on the Floquet formalism, analytical and numerical calculations are presented that show that the trap is quantum mechanically stable. (4) Definition and derivation of a quantum pseudo-potential allow a qualitative understanding of the quantum trapping mechanism. (5) It is shown that the proposed ac/dc trap may be realized experimentally using currently available scanning tunnelling microscopy technology. (paper)

  8. Laser tunneling from aligned molecules

    Smeenk, C T L; Sokolov, A V; Spanner, M; Lee, K F; Staudte, A; Villeneuve, D M; Corkum, P B

    2013-01-01

    We study multi-photon ionization from N_2, O_2 and benzene using circularly polarized light. By examining molecular frame photo-electron angular distributions, we illustrate how multi-photon ionization acts a momentum-selective probe of the local electron density in the Dyson orbitals for these molecules. We find good agreement with calculations based on a tunneling model and including saturation effects.

  9. Metagenomic small molecule discovery methods

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- bas...

  10. Bioactive molecules from sea hares.

    Kamiya, H; Sakai, R; Jimbo, M

    2006-01-01

    Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and "shell-less" snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the "Aplysianin A family," although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an alpha-amino group of the substrate with

  11. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo;

    2012-01-01

    -surface are possibly crucial in these contexts. We here investigated internalization and subsequent recycling or degradation of ADAM12 as a potentially important regulatory mechanism. Our results show that ADAM12 is constitutively internalized primarily via the clathrin-dependent pathway and is subsequently......ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell...... detected in both early and recycling endosomes. The protease activity of ADAM12 does not influence this internalization mechanism. Analysis of essential elements for internalization established that proline-rich regions in the cytoplasmic domain of ADAM12, previously shown to interact with Src-homology 3...

  12. Simple molecules as complex systems.

    Furtenbacher, Tibor; Arendás, Péter; Mellau, Georg; Császár, Attila G

    2014-01-01

    For individual molecules quantum mechanics (QM) offers a simple, natural and elegant way to build large-scale complex networks: quantized energy levels are the nodes, allowed transitions among the levels are the links, and transition intensities supply the weights. QM networks are intrinsic properties of molecules and they are characterized experimentally via spectroscopy; thus, realizations of QM networks are called spectroscopic networks (SN). As demonstrated for the rovibrational states of H2(16)O, the molecule governing the greenhouse effect on earth through hundreds of millions of its spectroscopic transitions (links), both the measured and first-principles computed one-photon absorption SNs containing experimentally accessible transitions appear to have heavy-tailed degree distributions. The proposed novel view of high-resolution spectroscopy and the observed degree distributions have important implications: appearance of a core of highly interconnected hubs among the nodes, a generally disassortative connection preference, considerable robustness and error tolerance, and an "ultra-small-world" property. The network-theoretical view of spectroscopy offers a data reduction facility via a minimum-weight spanning tree approach, which can assist high-resolution spectroscopists to improve the efficiency of the assignment of their measured spectra. PMID:24722221

  13. Functional molecules in electronic circuits.

    Weibel, Nicolas; Grunder, Sergio; Mayor, Marcel

    2007-08-01

    Molecular electronics is a fascinating field of research contributing to both fundamental science and future technological achievements. A promising starting point for molecular devices is to mimic existing electronic functions to investigate the potential of molecules to enrich and complement existing electronic strategies. Molecules designed and synthesized to be integrated into electronic circuits and to perform an electronic function are presented in this article. The focus is set in particular on rectification and switching based on molecular devices, since the control over these two parameters enables the assembly of memory units, likely the most interesting and economic application of molecular based electronics. Both historical and contemporary solutions to molecular rectification are discussed, although not exhaustively. Several examples of integrated molecular switches that respond to light are presented. Molecular switches responding to an electrochemical signal are also discussed. Finally, supramolecular and molecular systems with intuitive application potential as memory units due to their hysteretic switching are highlighted. Although a particularly attractive feature of molecular electronics is its close cooperation with neighbouring disciplines, this article is written from the point of view of a chemist. Although the focus here is largely on molecular considerations, innovative contributions from physics, electro engineering, nanotechnology and other scientific disciplines are equally important. However, the ability of the chemist to correlate function with structure, to design and to provide tailor-made functional molecules is central to molecular electronics. PMID:17637951

  14. Water molecules orientation in surface layer

    Klingo, V. V.

    2000-08-01

    The water molecules orientation has been investigated theoretically in the water surface layer. The surface molecule orientation is determined by the direction of a molecule dipole moment in relation to outward normal to the water surface. Entropy expressions of the superficial molecules in statistical meaning and from thermodynamical approach to a liquid surface tension have been found. The molecules share directed opposite to the outward normal that is hydrogen protons inside is equal 51.6%. 48.4% water molecules are directed along to surface outward normal that is by oxygen inside. A potential jump at the water surface layer amounts about 0.2 volts.

  15. The neural cell adhesion molecule

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  16. The molecule-metal interface

    Koch, Norbert; Wee, Andrew Thye Shen

    2013-01-01

    Reviewing recent progress in the fundamental understanding of the molecule-metal interface, this useful addition to the literature focuses on experimental studies and introduces the latest analytical techniques as applied to this interface.The first part covers basic theory and initial principle studies, while the second part introduces readers to photoemission, STM, and synchrotron techniques to examine the atomic structure of the interfaces. The third part presents photoelectron spectroscopy, high-resolution UV photoelectron spectroscopy and electron spin resonance to study the electroni

  17. Dissociation Energies of Diatomic Molecules

    FAN Qun-Chao; SUN Wei-Guo

    2008-01-01

    Molecular dissociation energies of 10 electronic states of alkali molecules of KH, 7LID, 7LiH, 6LiH, NaK, NaLi and NaRb are studied using the highest three accurate vibrational energies of each electronic state, and an improved parameter-free analytical formula which is obtained starting from the LeRoy-Bernstein vibrational energy expression near the dissociation limit. The results show that as long as the highest three vibrational energies are accurate, the current analytical formula will give accurate theoretical dissociation energies Detheory, which are in excellent agreement with the experimental dissociation energies Dexpte.

  18. XUV ionization of aligned molecules

    Kelkensberg, F.; Siu, W.; Gademann, G. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Rouzee, A.; Vrakking, M. J. J. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Max-Born-Institut, Max-Born Strasse 2A, D-12489 Berlin (Germany); Johnsson, P. [FOM Institute AMOLF, Science Park 104, NL-1098 XG Amsterdam (Netherlands); Department of Physics, Lund University, Post Office Box 118, SE-221 00 Lund (Sweden); Lucchini, M. [Department of Physics, Politecnico di Milano, Istituto di Fotonica e Nanotecnologie CNR-IFN, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Lucchese, R. R. [Department of Chemistry, Texas A and M University, College Station, Texas 77843-3255 (United States)

    2011-11-15

    New extreme-ultraviolet (XUV) light sources such as high-order-harmonic generation (HHG) and free-electron lasers (FELs), combined with laser-induced alignment techniques, enable novel methods for making molecular movies based on measuring molecular frame photoelectron angular distributions. Experiments are presented where CO{sub 2} molecules were impulsively aligned using a near-infrared laser and ionized using femtosecond XUV pulses obtained by HHG. Measured electron angular distributions reveal contributions from four orbitals and the onset of the influence of the molecular structure.

  19. Hydrophobic Porous Material Adsorbs Small Organic Molecules

    Sharma, Pramod K.; Hickey, Gregory S.

    1994-01-01

    Composite molecular-sieve material has pore structure designed specifically for preferential adsorption of organic molecules for sizes ranging from 3 to 6 angstrom. Design based on principle that contaminant molecules become strongly bound to surface of adsorbent when size of contaminant molecules is nearly same as that of pores in adsorbent. Material used to remove small organic contaminant molecules from vacuum systems or from enclosed gaseous environments like closed-loop life-support systems.

  20. Electric dipole moment of diatomic molecules

    The calculation of the electric dipole moment of diatomic molecules by the Variational Cellular Method is presented, discussed and compared with the semiempirical CNDO/2 method. The molecule HF is taken as example. It is also shown that the value of the electric dipole moment by the VCM improves considerably when the electronegativity of the atoms of the molecule is taken into account. (Author)

  1. Ultrafast electron diffraction from aligned molecules

    Centurion, Martin [Univ. of Nebraska, Lincoln, NE (United States)

    2015-08-17

    The aim of this project was to record time-resolved electron diffraction patterns of aligned molecules and to reconstruct the 3D molecular structure. The molecules are aligned non-adiabatically using a femtosecond laser pulse. A femtosecond electron pulse then records a diffraction pattern while the molecules are aligned. The diffraction patterns are then be processed to obtain the molecular structure.

  2. Optoelectronics of Molecules and Polymers

    Moliton, André

    2006-01-01

    Optoelectronic devices are being developed at an extraordinary rate. Organic light emitting diodes, photovoltaic devices and electro-optical modulators are pivotal to the future of displays, photosensors and solar cells, and communication technologies. This book details the theories underlying the relevant mechanisms in organic materials and covers, at a basic level, how the organic components are made. The first part of this book introduces the fundamental theories used to detail ordered solids and localised energy levels. The methods used to determine energy levels in perfectly ordered molecular and macromolecular systems are discussed, making sure that the effects of quasi-particles are not missed. The function of excitons and their transfer between two molecules are studied, and the problems associated with interfaces and charge injection into resistive media are presented. The second part details technological aspects such as the fabrication of devices based on organic materials by dry etching. The princ...

  3. Photoluminescence of a Plasmonic Molecule.

    Huang, Da; Byers, Chad P; Wang, Lin-Yung; Hoggard, Anneli; Hoener, Ben; Dominguez-Medina, Sergio; Chen, Sishan; Chang, Wei-Shun; Landes, Christy F; Link, Stephan

    2015-07-28

    Photoluminescent Au nanoparticles are appealing for biosensing and bioimaging applications because of their non-photobleaching and non-photoblinking emission. The mechanism of one-photon photoluminescence from plasmonic nanostructures is still heavily debated though. Here, we report on the one-photon photoluminescence of strongly coupled 50 nm Au nanosphere dimers, the simplest plasmonic molecule. We observe emission from coupled plasmonic modes as revealed by single-particle photoluminescence spectra in comparison to correlated dark-field scattering spectroscopy. The photoluminescence quantum yield of the dimers is found to be surprisingly similar to the constituent monomers, suggesting that the increased local electric field of the dimer plays a minor role, in contradiction to several proposed mechanisms. Aided by electromagnetic simulations of scattering and absorption spectra, we conclude that our data are instead consistent with a multistep mechanism that involves the emission due to radiative decay of surface plasmons generated from excited electron-hole pairs following interband absorption. PMID:26165983

  4. Photonic molecules and spectral engineering

    Boriskina, Svetlana V

    2012-01-01

    This chapter reviews the fundamental optical properties and applications of pho-tonic molecules (PMs) - photonic structures formed by electromagnetic coupling of two or more optical microcavities (photonic atoms). Controllable interaction between light and matter in photonic atoms can be further modified and en-hanced by the manipulation of their mutual coupling. Mechanical and optical tunability of PMs not only adds new functionalities to microcavity-based optical components but also paves the way for their use as testbeds for the exploration of novel physical regimes in atomic physics and quantum optics. Theoretical studies carried on for over a decade yielded novel PM designs that make possible lowering thresholds of semiconductor microlasers, producing directional light emission, achieving optically-induced transparency, and enhancing sensitivity of microcavity-based bio-, stress- and rotation-sensors. Recent advances in material science and nano-fabrication techniques make possible the realization of opt...

  5. Diamond Molecules Found in Petroleum

    Carlson, R. M. K.; Dahl, J. E. P.; Liu, S. G.; Olmstead, M. M.; Buerki, P. R.; Gat, R.

    We recently reported [1,2] the discovery and isolation of new members of the hydrogen-terminated diamond series, ˜1 to ˜2 nm sized higher diamondoids from petroleum. Crystallographic studies [1,2] revealed a wealth of diamond molecules that are nanometer-sized rods, helices, discs, pyramids, etc. Highly rigid, well-defined, readily derivatizable structures make them valuable molecular building blocks for nanotechnology. We now produce certain higher diamondoids in gram quantities. Although more stable than graphite particles of comparable size, higher diamondoids are extraordinarily difficult to synthesize. Attempts to synthesize them were abandoned in the 1980's. We examined extracts of diamond-containing materials synthesized by CO2 laser-induced gas-phase synthesis [3] and commercial CVD in an attempt to detect diamantane to undecamantane. However, high-sensitivity GCMS detected no diamondoids in these materials.

  6. Anti-cancer Lead Molecule

    Sagar, Sunil

    2014-04-17

    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  7. Symmetries in nuclei and molecules

    Recent progress in two different fronts is reported. First, the concept of bisection of a harmonic oscillator or hydrogen atom, used in the past in establishing the connection between U(3) and O(4), is generalized into multisection (trisection, tetra section, etc.). It is then shown that all symmetries of the N-dimensional anisotropic harmonic oscillator with rational ratios of frequencies (RHO), some of which are underlying the structure of superdeformed and hyperdeformed nuclei, can be obtained from the U(N) symmetry of the corresponding isotropic oscillator with the appropriate combination of multisections. Furthermore, it is seen that bisections of the N-dimensional hydrogen atom, which possesses an O(N+1) symmetry, lead to the U(N) symmetry, so that further multisections of the hydrogen atom lead to the symmetries of the N-dim RHO. The opposite is in general not true, i.e. multisections of U(N) do not lead to O(N+1) symmetries, the only exception being the occurrence of O(4) after the bisection of U(3). Second, it is shown that there is evidence that the recently observed in superdeformed nuclear bands δ I=4 bifurcation is also occurring in normal deformed bands of actinides and rare earths, in hyperdeformed nuclear bands, as well as in rotational bands of diatomic molecules. In addition there is evidence that a δ I=8 bifurcation, of the same order of magnitude as the δ I=4 one, is observed in superdeformed nuclear bands and rotational bands of diatomic molecules. (author)

  8. Stability of small exotic molecules

    Complete text of publication follows. Three and four unit-charge particles with different masses may form bound states depending on the mass ratios. The aim of this work is to find out how many particles of unit charges can be put together to form bound states. We explore the possibility of the formation of stable N = 5,6...-particle systems of unit charges. We use a variational approach, in which the trial function is constructed out of generalised Gaussians whose parameters are determined by stochastic sampling. For few-body bound states this method has been shown to produce accurate results. First we made calculations for the five-body system (m+, m-, m+, m-, M+) with 0 ≤ σ ≤ ∞, where σ = m/M. We found that the binding energy of the system is larger than the nearest threshold for 0 ≤ σ ≤ 1.81, so the system in this region of mass ratio is bound. In the case of the system (m+, m-, m-, M+, M+) we cannot find a bound state for σ = 0. For 1 ≤ σ ≤ ∞, however, the system is bound. By decreasing σ from σ = 1, the binding energy is reduced, and around σ = 0.4 the system dissociates into (m-, m-, M+, M+) plus m+. Some six-body systems are under study, and cases have been found both for the existence and non-existence of bound states. From this study we can learn, e.g. that an H2 molecule cannot bind a positron and the positronium molecule can bind a proton, but it cannot bind an electron, unless we make the extra electron non-identical with the others. By comparing systems formed by identical and non-identical particles, we can point out the role of the Pauli principle in reducing the binding energy. (author)

  9. Spin polarization effect of Ni2 molecule

    Yan Shi-Ying; Zhu Zheng-He

    2008-01-01

    The density functional theory (DFT) method (b3p86) of Gaussian 03 is used to optimize the structure of the Ni2 molecule. The result shows that the ground state for the Ni2 molecule is a 5-multiple state, symbolizing a spin polarization effect existing in the Ni2 molecule, a transition metal molecule, but no spin pollution is found because the wavefunction of the ground state does not mingle with wavefunctions of higher-energy states. So the ground state for Ni2 molecule, which is a 5-multiple state, is indicative of spin polarization effect of the Ni2 molecule, that is, there exist 4 parallel spin electrons in Ni2 molecule. The number of non-conjugated electrons is greatest. These electrons occupy different spatial orbitals so that the energy of the Ni2 molecule is minimized. It can be concluded that the effect of parallel spin in the Ni2 molecule is larger than that of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters of the ground state and other states of the Ni2 molecule are derived. The dissociation energy De for the ground state of the Ni2 molecule is 1.835 eV, equilibrium bond length Re is 0.2243 nm, vibration frequency ωe is 262.35 cm-1. Its force constants f2, f3 and f4 are 1.1901 aJ.nm-2, 5.8723 aJ.nm-3, and 21.2505 aJ.nm-4 respectively. The other spectroscopic data for the ground state of the Ni2 molecule ωexe, Be and αe are 1.6315cm-1, 0.1141 cm-1, and 8.0145×10-4 cm-1 respectively.

  10. Spin polarization effect for Cr2 molecule

    Yan Shi-Ying

    2008-01-01

    Density functional theory (DFT) (B3P86) of Ganssian 03 has been used to optimize the structure of the Cr2 molecule, a transition metal element molecule. The result shows that the ground state for the Cr2 molecule is a 13-multiple state, indicating that there exists a spin polarization effect in the Cr2 molecule. Meanwhile, we have not found any spin pollution because the wave function of the ground state does not mingle with wave functions of higher-energy states. So the ground state for Cr2 molecule being a 13-multiple state is indicative of spin polarization effect of the Cr2 molecule among transition metal elements, that is, there are 12 parallel spin electrons in the Cr2 molecule. The number of non-conjugated electrons is greatest. These electrons occupy different spatial orbitals so that the energy of the Cr2 molecule is minimized. It can be concluded that the effect of parallel spin in the Cr2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition,the Murrell-Sorbie potential functions with the parameters for the ground state and other states of the Cr2 molecule are derived. The dissociation energy De for the ground state of the Cr2 molecule is 0.1034eV, equilibrium bond length Re is 0.3396nm, and vibration frequency ωe is 73.81cm-1. Its force constants f2, f3 and f4 are 0.0835, -0.2831 and 0.3535 aJ·nm-4 respectively. The other spectroscopic data for the ground state of the Cr2 molecule ωeχe, Be and αe are 1.2105, 0.0562 and 7.2938 × 10-4cm-1 respectively.

  11. Coordination programming of photofunctional molecules.

    Sakamoto, Ryota; Kusaka, Shinpei; Hayashi, Mikihiro; Nishikawa, Michihiro; Nishihara, Hiroshi

    2013-01-01

    Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET) initiated by the metal-to-ligand charge transfer (MLCT) transition of the Cu(I) state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinato)zinc(II) complexes. Conventional homoleptic bis(dipyrrinato)zinc(II) complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynyl)fumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics. PMID:23563859

  12. Coordination Programming of Photofunctional Molecules

    Hiroshi Nishihara

    2013-04-01

    Full Text Available Our recent achievements relating to photofunctional molecules are addressed. Section 1 discloses a new concept of photoisomerization. Pyridylpyrimidine-copper complexes undergo a ring inversion that can be modulated by the redox state of the copper center. In combination with an intermolecular photoelectron transfer (PET initiated by the metal-to-ligand charge transfer (MLCT transition of the Cu(I state, we realize photonic regulation of the ring inversion. Section 2 reports on the first examples of heteroleptic bis(dipyrrinatozinc(II complexes. Conventional homoleptic bis(dipyrrinatozinc(II complexes suffered from low fluorescence quantum yields, whereas the heteroleptic ones feature bright fluorescence even in polar solvents. Section 3 describes our new findings on Pechmann dye, which was first synthesized in 1882. New synthetic procedures for Pechmann dye using dimethyl bis(arylethynylfumarate as a starting material gives rise to its new structural isomer. We also demonstrate potentiality of a donor-acceptor-donor type of Pechmann dye in organic electronics.

  13. Single Molecule Studies of Chromatin

    Jeans, C; Thelen, M P; Noy, A

    2006-02-06

    In eukaryotic cells, DNA is packaged as chromatin, a highly ordered structure formed through the wrapping of the DNA around histone proteins, and further packed through interactions with a number of other proteins. In order for processes such as DNA replication, DNA repair, and transcription to occur, the structure of chromatin must be remodeled such that the necessary enzymes can access the DNA. A number of remodeling enzymes have been described, but our understanding of the remodeling process is hindered by a lack of knowledge of the fine structure of chromatin, and how this structure is modulated in the living cell. We have carried out single molecule experiments using atomic force microscopy (AFM) to study the packaging arrangements in chromatin from a variety of cell types. Comparison of the structures observed reveals differences which can be explained in terms of the cell type and its transcriptional activity. During the course of this project, sample preparation and AFM techniques were developed and optimized. Several opportunities for follow-up work are outlined which could provide further insight into the dynamic structural rearrangements of chromatin.

  14. Single-molecule stochastic resonance

    Hayashi, K; Manosas, M; Huguet, J M; Ritort, F; 10.1103/PhysRevX.2.031012

    2012-01-01

    Stochastic resonance (SR) is a well known phenomenon in dynamical systems. It consists of the amplification and optimization of the response of a system assisted by stochastic noise. Here we carry out the first experimental study of SR in single DNA hairpins which exhibit cooperatively folding/unfolding transitions under the action of an applied oscillating mechanical force with optical tweezers. By varying the frequency of the force oscillation, we investigated the folding/unfolding kinetics of DNA hairpins in a periodically driven bistable free-energy potential. We measured several SR quantifiers under varied conditions of the experimental setup such as trap stiffness and length of the molecular handles used for single-molecule manipulation. We find that the signal-to-noise ratio (SNR) of the spectral density of measured fluctuations in molecular extension of the DNA hairpins is a good quantifier of the SR. The frequency dependence of the SNR exhibits a peak at a frequency value given by the resonance match...

  15. NMR of dielectrically oriented molecules

    General information on experimental aspects of EFNMR is given. It is shown that the complete 14N quadrupole tensor (qct) of pyridine and pyrimidine in the liquid state is accessible to EFNMR. Information obtained about 17O qct in liquid nitromethane, is compared with results from other techniques. The 33S qct in liquid sulfolane is investigated. The EFNMR results, combined with those from spin-lattice relaxation time measurements and from Hartree-Fock-Slater MO calculations, allowed the complete assignment of the 33S qct. The quadrupole coupling of both 10B and 11B in a carborane compound is investigated and, together with the results of spin-lattice relaxation time measurements, detailed information about the assignment of the boron qct's could be derived. EFNMR studies of apolar molecules are described. A limitation in EFNMR is the inhomogeneity (delta B) of the magnetic field, which is introduced by the use of non-spinning sample cells. A way out is the detection of zero quantum transitions, their widths being independent of delta B. The results and prospectives of this approach are shown for the simple three spin 1/2 system of acrylonitrile in which the small dipolar proton-proton couplings could be revealed via zero quantum transitions. (Auth.)

  16. NMR studies of oriented molecules

    Sinton, S.W.

    1981-11-01

    Deuterium and proton magnetic resonance are used in experiments on a number of compounds which either form liquid crystal mesophases themselves or are dissolved in a liquid crystal solvent. Proton multiple quantum NMR is used to simplify complicated spectra. The theory of nonselective multiple quantum NMR is briefly reviewed. Benzene dissolved in a liquid crystal are used to demonstrate several outcomes of the theory. Experimental studies include proton and deuterium single quantum (..delta..M = +-1) and proton multiple quantum spectra of several molecules which contain the biphenyl moiety. 4-Cyano-4'-n-pentyl-d/sub 11/-biphenyl (5CB-d/sub 11/) is studied as a pure compound in the nematic phase. The obtained chain order parameters and dipolar couplings agree closely with previous results. Models for the effective symmetry of the biphenyl group in 5CB-d/sub 11/ are tested against the experimental spectra. The dihedral angle, defined by the planes containing the rings of the biphenyl group, is found to be 30 +- 2/sup 0/ for 5DB-d/sub 11/. Experiments are also described for 4,4'-d/sub 2/-biphenyl, 4,4' - dibromo-biphenyl, and unsubstituted biphenyl.

  17. Observation of pendular butterfly Rydberg molecules

    Niederprüm, Thomas; Eichert, Tanita; Lippe, Carsten; Pérez-Ríos, Jesús; Greene, Chris H; Ott, Herwig

    2016-01-01

    Obtaining full control over the internal and external quantum states of molecules is the central goal of ultracold chemistry and allows for the study of coherent molecular dynamics, collisions and tests of fundamental laws of physics. When the molecules additionally have a permanent electric dipole moment, the study of dipolar quantum gases and spin-systems with long-range interactions as well as applications in quantum information processing are possible. Rydberg molecules constitute a class of exotic molecules, which are bound by the interaction between the Rydberg electron and the ground state atom. They exhibit extreme bond lengths of hundreds of Bohr radii and giant permanent dipole moments in the kilo-Debye range. A special type with exceptional properties are the so-called butterfly molecules, whose electron density resembles the shape of a butterfly. Here, we report on the photoassociation of butterfly Rydberg molecules and their orientation in a weak electric field. Starting from a Bose-Einstein cond...

  18. Rotational Cooling of Trapped Polyatomic Molecules.

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G U; Rempe, Gerhard; Zeppenfeld, Martin

    2015-12-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH_{3}F) by optically pumping the population of 16 M sublevels in the rotational states J=3, 4, 5 and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (≈30  mK) and nearly pure state ensemble of about 10^{6} molecules. Our scheme is extendable to larger sets of initial states, other final states, and a variety of molecule species, thus paving the way for internal-state control of ever-larger molecules. PMID:26684114

  19. Rotational cooling of trapped polyatomic molecules

    Glöckner, Rosa; Englert, Barbara G U; Rempe, Gerhard; Zeppenfeld, Martin

    2015-01-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH3F) by optically pumping the population of 16 M-sublevels in the rotational states J=3,4,5, and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby generating a translationally cold (~30mK) and nearly pure state ensemble of about 10^6 molecules. Our scheme is extendable to larger sets of initial states, other final states and a variety of molecule species, thus paving the way for internal-state control of ever larger molecules.

  20. Broadband single-molecule excitation spectroscopy

    Piatkowski, Lukasz; Gellings, Esther; van Hulst, Niek F.

    2016-01-01

    Over the past 25 years, single-molecule spectroscopy has developed into a widely used tool in multiple disciplines of science. The diversity of routinely recorded emission spectra does underpin the strength of the single-molecule approach in resolving the heterogeneity and dynamics, otherwise hidden in the ensemble. In early cryogenic studies single molecules were identified by their distinct excitation spectra, yet measuring excitation spectra at room temperature remains challenging. Here we present a broadband Fourier approach that allows rapid recording of excitation spectra of individual molecules under ambient conditions and that is robust against blinking and bleaching. Applying the method we show that the excitation spectra of individual molecules exhibit an extreme distribution of solvatochromic shifts and distinct spectral shapes. Importantly, we demonstrate that the sensitivity and speed of the broadband technique is comparable to that of emission spectroscopy putting both techniques side-by-side in single-molecule spectroscopy.

  1. Laser cooling of a diatomic molecule

    Shuman, E S; DeMille, D

    2011-01-01

    It has been roughly three decades since laser cooling techniques produced ultracold atoms, leading to rapid advances in a vast array of fields. Unfortunately laser cooling has not yet been extended to molecules because of their complex internal structure. However, this complexity makes molecules potentially useful for many applications. For example, heteronuclear molecules possess permanent electric dipole moments which lead to long-range, tunable, anisotropic dipole-dipole interactions. The combination of the dipole-dipole interaction and the precise control over molecular degrees of freedom possible at ultracold temperatures make ultracold molecules attractive candidates for use in quantum simulation of condensed matter systems and quantum computation. Also ultracold molecules may provide unique opportunities for studying chemical dynamics and for tests of fundamental symmetries. Here we experimentally demonstrate laser cooling of the molecule strontium monofluoride (SrF). Using an optical cycling scheme re...

  2. Dynamics of a linear magnetic "microswimmer molecule"

    Babel, Sonja; Löwen, Hartmut; Menzel, Andreas M.

    2015-01-01

    In analogy to nanoscopic molecules that are composed of individual atoms, we consider an active "microswimmer molecule". It is built up from three individual magnetic colloidal microswimmers that are connected by harmonic springs and hydrodynamically interact with each other. In the ground state, they form a linear straight molecule. We analyze the relaxation dynamics for perturbations of this straight configuration. As a central result, with increasing self-propulsion, we observe an oscillat...

  3. Making "Operations" inside a Single Molecule

    2005-01-01

    @@ Free and delicate manipulation of single molecules has long been expected by scientists so as to realize specific functions. In the 1990s, the laboratory led by Prof. Wison Ho from the University of California was successful in inducing chemical reactions at the single molecule level with scanning tunneling microscopy (STM), revealing the extensive potentials of "single molecule operation." However, until recently, researchers have failed to utilize the reaction to give rise to special physical properties.

  4. Scanning tunneling microscopy of biological molecules

    Scanning Tunnelling Microscopy (STM) has been used to image a number of biological molecules including thrombospondin and glycoprotein 88 (GP88). In this paper, STM images which clearly resolve the morphology of these molecules are presented. Ultimately, it is hoped that STM will provide information about the interaction between these molecules after overcoming problems associated with sample preparation and reproducibility of results which are discussed. 4 refs., 2 figs

  5. Charge correlations in polaron hopping through molecules

    Schmidt, Benjamin B.; Hettler, Matthias H.; Schön, Gerd

    2009-01-01

    In many organic molecules the strong coupling of excess charges to vibrational modes leads to the formation of polarons, i.e., a localized state of a charge carrier and a molecular deformation. Incoherent hopping of polarons along the molecule is the dominant mechanism of transport at room temperature. We study the far-from-equilibrium situation where, due to the applied bias, the induced number of charge carriers on the molecule is high enough such that charge correlations become relevant. W...

  6. RNA Reactions One Molecule at a Time

    Tinoco, Ignacio; Chen, Gang; Qu, Xiaohui

    2010-01-01

    Much of the dynamics information is lost in bulk measurements because of the population averaging. Single-molecule methods measure one molecule at a time; they provide knowledge not obtainable by other means. In this article, we review the application of the two most widely used single-molecule methods—fluorescence resonance energy transfer (FRET) and force versus extension measurements—to several RNA reactions. First, we discuss folding/unfolding studies on a hairpin ribozyme that revealed m...

  7. Single-molecule recognition imaging microscopy

    Stroh, C.; Wang, H.; Bash, R.; B Ashcroft; Nelson, J.; Gruber, H; Lohr, D.; Lindsay, S M; Hinterdorfer, P.

    2004-01-01

    Atomic force microscopy is a powerful and widely used imaging technique that can visualize single molecules and follow processes at the single-molecule level both in air and in solution. For maximum usefulness in biological applications, atomic force microscopy needs to be able to identify specific types of molecules in an image, much as fluorescent tags do for optical microscopy. The results presented here demonstrate that the highly specific antibody–antigen interaction can be used to gener...

  8. Ultracold polar molecules near quantum degeneracy

    Ospelkaus, S.; Ni, K.-K.; de Miranda, M. H. G.; Neyenhuis, B.; Wang, D; Kotochigova, S.; Julienne, P. S.; Jin, D. S.; J. Ye

    2008-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar $^{40}$K-$^{87}$Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute...

  9. Production and Trapping of Ultracold Polar Molecules

    David, DeMille [Yale Univ., New Haven, CT (United States)

    2015-04-21

    We report a set of experiments aimed at the production and trapping of ultracold polar molecules. We begin with samples of laser-cooled and trapped Rb and Cs atoms, and bind them together to form polar RbCs molecules. The binding is accomplished via photoassociation, which uses a laser to catalyze the sticking process. We report results from investigation of a new pathway for photoassociation that can produce molecules in their absolute ground state of vibrational and rotational motion. We also report preliminary observations of collisions between these ground-state molecules and co-trapped atoms.

  10. Single-molecule pulling: phenomenology and interpretation

    Franco, Ignacio; Schatz, George C

    2012-01-01

    Single-molecule pulling techniques have emerged as versatile tools for probing the noncovalent forces holding together the secondary and tertiary structure of macromolecules. They also constitute a way to study at the single-molecule level processes that are familiar from our macroscopic thermodynamic experience. In this Chapter, we summarize the essential phenomenology that is typically observed during single-molecule pulling, provide a general statistical mechanical framework for the interpretation of the equilibrium force spectroscopy and illustrate how to simulate single-molecule pulling experiments using molecular dynamics.

  11. Electron-molecule interactions and their applications

    Christophorou, L G

    1984-01-01

    Electron-Molecule Interactions and Their Applications, Volume 2 provides a balanced and comprehensive account of electron-molecule interactions in dilute and dense gases and liquid media. This book consists of six chapters. Chapter 1 deals with electron transfer reactions, while Chapter 2 discusses electron-molecular positive-ion recombination. The electron motion in high-pressure gases and electron-molecule interactions from single- to multiple-collision conditions is deliberated in Chapter 3. In Chapter 4, knowledge on electron-molecule interactions in gases is linked to that on similar proc

  12. Circularly Polarized Luminescence from Simple Organic Molecules.

    Sánchez-Carnerero, Esther M; Agarrabeitia, Antonia R; Moreno, Florencio; Maroto, Beatriz L; Muller, Gilles; Ortiz, María J; de la Moya, Santiago

    2015-09-21

    This article aims to show the identity of "circularly polarized luminescent active simple organic molecules" as a new concept in organic chemistry due to the potential interest of these molecules, as availed by the exponentially growing number of research articles related to them. In particular, it describes and highlights the interest and difficulty in developing chiral simple (small and non-aggregated) organic molecules able to emit left- or right-circularly polarized light efficiently, the efforts realized up to now to reach this challenging objective, and the most significant milestones achieved to date. General guidelines for the preparation of these interesting molecules are also presented. PMID:26136234

  13. Reactive scattering of halogen molecules

    A study of the endoergic, bimolecular reactions of F2 with I2, ICl, and HI in a crossed molecular beam experiment is described. The trihalogens IIF, ClIF, and HIF were directly observed as the products of these reactions. At high collision energies a second reactive channel producing IF becomes important. Product angular and velocity distributions show that this IF does not result from a four-center exchange reaction. Measured threshold energies for the formation of IIF, ClIF, and HIF yield lower bounds to the stabilities of these molecules, with respect to the separated atoms, of 69, 81, and 96 kcal/mole, respectively. Analysis of product center-of-mass angular distributions indicates that a slightly nonlinear approach is most effective in bringing about reaction to form the stable triatomic radical. Also described is a crossed molecular beam study of the Cl + Br2 → BrCl + Br reaction at collision energies from 6.8 to 17.7 kcal/mole. The results indicate that this reaction has the characteristics of an exoergic reaction on an attractive potential energy surface with early energy release. Reagent translational energy is very efficiently channeled into product internal energy. At high collision energy the reaction appears to approach the spectator stripping limit. Finally, a series of computer programs which can be used to carry out the requisite data analysis for crossed molecular beam reactive scattering experiments are described. These programs recover the reactive scattering center-of-mass flux distribution from the measured angular and velocity distributions of the products

  14. Submillimeter Spectroscopy of Hydride Molecules

    Phillips, T. G.

    1998-05-01

    Simple hydride molecules are of great importance in astrophysics and astrochemistry. Physically they dominate the cooling of dense, warm phases of the ISM, such as the cores and disks of YSOs. Chemically they are often stable end points of chemical reactions, or may represent important intermediate stages of the reaction chains, which can be used to test the validity of the process. Through the efforts of astronomers, physicists, chemists, and laboratory spectroscopists we have an approximate knowledge of the abundance of some of the important species, but a great deal of new effort will be required to achieve the comprehensive and accurate data set needed to determine the energy balance and firmly establish the chemical pathways. Due to the low moment of inertia, the hydrides rotate rapidly and so have their fundamental spectral lines in the submillimeter. Depending on the cloud geometry and temperature profile they may be observed in emission or absorption. Species such as HCl, HF, OH, CH, CH(+) , NH_2, NH_3, H_2O, H_2S, H_3O(+) and even H_3(+) have been detected, but this is just a fraction of the available set. Also, most deduced abundances are not nearly sufficiently well known to draw definitive conclusions about the chemical processes. For example, the most important coolant for many regions, H_2O, has a possible range of deduced abundance of a factor of 1000. The very low submillimeter opacity at the South Pole site will be a significant factor in providing a new capabilty for interstellar hydride spectroscopy. The new species and lines made available in this way will be discussed.

  15. Spin polarization effect for Fe2 molecule

    Yan Shi-Ying; Zhu Zheng-He

    2006-01-01

    This paper uses the density functional theory (DFT)(B3p86) of Gaussian03 to optimize the structure of Fe2 molecule. The result shows that the ground state for Fe2 molecule is a 9-multiple state, which shows spin polarization effect of Fe2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, that the ground state for Fe2 molecule is a 9-multiple state is indicative of the spin polarization effect of Fe2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of the Fe2 molecule is minimized. It can be concluded that the effect of parallel spin of the Fe2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and other states of Fe2 molecule are derived. Dissociation energy De for the ground state of Fe2 molecule is 2.8586ev, equilibrium bond length Re is 0.2124nm, vibration frequency ωe is 336.38 cm-1. Its force constants f2, f3, and f4 are 1.8615aJ·nm-2, -8.6704a J·nm-3, 29.1676aJ·nm-4 respectively. The other spectroscopic data for the ground state of Fe2 moleculeωeχe, Be, αe are 1.5461 cm-1, 0.1339 cm-1, 7.3428×10-4 cm-1 respectively.

  16. Spin polarization effect for Tc2 molecule

    Yan Shi-Ying; Zhu Zheng-He

    2004-01-01

    Density functional method (DFT) (B3p86) of Gaussian98 has been used to optimize the structure of the Tc2 molecule. The result shows that the ground state for Tc2 molecule is an 11-multiple state and its electronic configuration is 11∑- g, which shows the spin polarization effect of Tc2 molecule of a transition metal element for the first time.Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions of higher energy states. So, that the ground state for Tc2 molecule is an 11-multiple state is indicative of the spin polarization effect of Tc2 molecule of a transition metal element: that is, there exist 10 parallel spin electrons. The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of Tc2 molecule is minimized. It can be concluded that the effect of parallel spin of the Tc2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization.In addition, the Murrell-Sorbie potential functions with the parameters for the ground state 11∑- g and other states of Tc2 molecule are derived. Dissociation energy De for the ground state of Tc2 molecule is 2.266eV, equilibrium bond length Re is 0.2841nm, vibration frequency ωe is 178.52cm-1. Its force constants f2, f3, and f4 are 0.9200aJ.nm-2,-3.5700aJ.nm-3, 11.2748aJ.nm-4 respectively. The other spectroscopic data for the ground state of Tc2 molecule ωexe,Be, αe are 0.5523cm- 1, 0.0426cm- 1, 1.6331 × 10-4cm- 1 respectively.

  17. Molecule-oriented programming in Java

    Bergstra, J.A.

    2002-01-01

    Molecule-oriented programming is introduced as a programming style carrying some perspective for Java. A sequence of examples is provided. Supporting the development of the molecule-oriented programming style several matters are introduced and developed: profile classes allowing the representation o

  18. Controlled contact to a C-60 molecule

    Neel, N.; Kröger, J.; Limot, L.; Frederiksen, Thomas; Brandbyge, Mads

    2007-01-01

    The tip of a low-temperature scanning tunneling microscope is approached towards a C-60 molecule adsorbed at a pentagon-hexagon bond on Cu(100) to form a tip-molecule contact. The conductance rapidly increases to approximate to 0.25 conductance quanta in the transition region from tunneling to...

  19. Infrared emission from electronically excited biacetyl molecules

    Drent, E.; Kommandeur, J.

    1971-01-01

    The infrared emission of electronically excited biacetyl molecules in the gas phase at low pressure was observed. Some experimental details are given, and it is shown that the emission derives from biacetyl molecules in their triplet state. The emission is dependent on the wavelength of excitation.

  20. Single molecule fluorescence detection on functionalized surfaces

    Full text: The immobilization of organic molecules on surfaces is important for various applications in nanolithography and also essential in novel detectors for matter wave interferometry. We use fluorescence imaging up to the single molecule level to study the suppression of long-range surface diffusion of ZnTPP on pyridine functionalized surfaces. (author)

  1. Small azomethine molecules and their use in photovoltaic devices

    Dingemans, T.J.; Petrus, M.L.

    2015-01-01

    The present invention is in the field of a small azomethine molecule having photovoltaic characteristics, a method of synthesizing said molecule, use of said molecule in a photovoltaic device, a solar cell comprising said molecule, and a film comprising said molecule. The present molecules may find

  2. Spin polarization effect for Co2 molecule

    Yan Shi-Ying; Bao Wen-Sheng

    2007-01-01

    The density functional theory (DFT)(b3p86) of Gaussian 03 has been used to optimize the structure of the Co2molecule, a transition metal element molecule. The result shows that the ground state for the Co2 molecule is a 7-multiple state, indicating a spin polarization effect in the Co2 molecule. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state is not mingled with wavefunctions of higher-energy states. So for the ground state of Co2 molecule to be a 7-multiple state is the indicative of spin polarization effect of the Co2molecule, that is, there exist 6 parallel spin electrons in a Co2 molecule. The number of non-conjugated electrons is the greatest. These electrons occupy different spacial orbitals so that the energy of the Co2 molecule is minimized. It can be concluded that the effect of parallel spin in the Co2 molecule is larger than the effect of the conjugated molecule,which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state and the other states of the Co2 molecule are derived. The dissociation energy De for the ground state of Co2 molecule is 4.0489eV, equilibrium bond length Re is 0.2061 nm, and vibration frequency 11.2222 aJ.nm-4respectively(1 a.J=10-18 J). The other spectroscopic data for the ground state of Co2 molecule ωexe,Be, and αe are 0.7202 cm-1, 0.1347 cm-1, and 2.9120× 10-1 cm-1 respectively. And ωexe is the non-syntonic part of frequency, Be is the rotational constant, αe is revised constant of rotational constant for non-rigid part of Co2 molecule.

  3. The symmetry of single-molecule conduction.

    Solomon, Gemma C; Gagliardi, Alessio; Pecchia, Alessandro; Frauenheim, Thomas; Di Carlo, Aldo; Reimers, Jeffrey R; Hush, Noel S

    2006-11-14

    We introduce the conductance point group which defines the symmetry of single-molecule conduction within the nonequilibrium Green's function formalism. It is shown, either rigorously or to within a very good approximation, to correspond to a molecular-conductance point group defined purely in terms of the properties of the conducting molecule. This enables single-molecule conductivity to be described in terms of key qualitative chemical descriptors that are independent of the nature of the molecule-conductor interfaces. We apply this to demonstrate how symmetry controls the conduction through 1,4-benzenedithiol chemisorbed to gold electrodes as an example system, listing also the molecular-conductance point groups for a range of molecules commonly used in molecular electronics research. PMID:17115774

  4. Chemical principles of single-molecule electronics

    Su, Timothy A.; Neupane, Madhav; Steigerwald, Michael L.; Venkataraman, Latha; Nuckolls, Colin

    2016-03-01

    The field of single-molecule electronics harnesses expertise from engineering, physics and chemistry to realize circuit elements at the limit of miniaturization; it is a subfield of nanoelectronics in which the electronic components are single molecules. In this Review, we survey the field from a chemical perspective and discuss the structure-property relationships of the three components that form a single-molecule junction: the anchor, the electrode and the molecular bridge. The spatial orientation and electronic coupling between each component profoundly affect the conductance properties and functions of the single-molecule device. We describe the design principles of the anchor group, the influence of the electronic configuration of the electrode and the effect of manipulating the structure of the molecular backbone and of its substituent groups. We discuss single-molecule conductance switches as well as the phenomenon of quantum interference and then trace their fundamental roots back to chemical principles.

  5. Small-molecule-dependent split aptamer ligation.

    Sharma, Ashwani K; Heemstra, Jennifer M

    2011-08-17

    Here we describe the first use of small-molecule binding to direct a chemical reaction between two nucleic acid strands. The reported reaction is a ligation between two fragments of a DNA split aptamer using strain-promoted azide-alkyne cycloaddition. Utilizing the split aptamer for cocaine, we demonstrate small-molecule-dependent ligation that is dose-dependent over a wide range of cocaine concentrations and is compatible with complex biological fluids such as human blood serum. Moreover, studies of split aptamer ligation at varying salt concentrations and using structurally similar analogues of cocaine have revealed new insight into the assembly and small-molecule binding properties of the cocaine split aptamer. The ability to translate the presence of a small-molecule target into the output of DNA ligation is anticipated to enable the development of new, broadly applicable small-molecule detection assays. PMID:21761903

  6. Extracting Models in Single Molecule Experiments

    Presse, Steve

    2013-03-01

    Single molecule experiments can now monitor the journey of a protein from its assembly near a ribosome to its proteolytic demise. Ideally all single molecule data should be self-explanatory. However data originating from single molecule experiments is particularly challenging to interpret on account of fluctuations and noise at such small scales. Realistically, basic understanding comes from models carefully extracted from the noisy data. Statistical mechanics, and maximum entropy in particular, provide a powerful framework for accomplishing this task in a principled fashion. Here I will discuss our work in extracting conformational memory from single molecule force spectroscopy experiments on large biomolecules. One clear advantage of this method is that we let the data tend towards the correct model, we do not fit the data. I will show that the dynamical model of the single molecule dynamics which emerges from this analysis is often more textured and complex than could otherwise come from fitting the data to a pre-conceived model.

  7. The Homology Relation between Molecules: a Revival of an Old Way for Classification of Molecules

    Dobrowolski, Jan Cz.

    2009-01-01

    The homology (homolo) relation between molecules was introduced. This relation is a generalization of an old idea of series of homologous compounds. The homolo relation operates on a molecule by removing all the structural fragments that are identical with a certain selected fragment. As a result a multiset of fragments is produced. It was shown that the homolo relation is an equivalence relation in a set of molecules. Thus, by choosing various reference fragments, the molecules can be classi...

  8. Novel Applications of Buffer-Gas Cooling to Cold Atoms, Diatomic Molecules, and Large Molecules

    Drayna, Garrett Korda

    2016-01-01

    Cold gases of atoms and molecules provide a system for the exploration of a diverse set of physical phenomena. For example, cold gasses of magnetically and electrically polar atoms and molecules are ideal systems for quantum simulation and quantum computation experiments, and cold gasses of large polar molecules allow for novel spectroscopic techniques. Buffer-gas cooling is a robust and widely applicable method for cooling atoms and molecules to temperatures of approximately 1 Kelvin. In thi...

  9. 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

    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...

  10. High Harmonic Generation from Rotationally Excited Molecules

    Lock, Robynne M.

    2011-12-01

    High harmonic generation (HHG) is understood through a three-step model. A strong laser field ionizes an atom or molecule. The free electron propagates in the laser field and may recombine with the atom or molecule leading to the generation of extreme ultraviolet or soft x-ray light at odd harmonics of the fundamental. Since the wavelength of the recombining electron is on the order of internuclear distances in molecules, HHG acts as a probe of molecular structure and dynamics. Conversely, control of the molecules leads to control of the properties (intensity, phase, and polarization) of the harmonic emission. Rotationally exciting molecules provides field-free molecular alignment at time intervals corresponding to fractions of the rotational period of the molecule. Alignment is necessary for understanding how the harmonic emission depends on molecular structure and alignment. Additionally, HHG acts as a probe of the rotational wavepackets. This thesis reports three experiments on HHG from rotationally excited molecules. Before we can use HHG as a probe of complex molecular dynamics or control harmonic properties through molecules, the harmonic emission from aligned, linear molecules must first be understood. To that end, the first experiment measures the intensity and phase of harmonics generated from N 2O and N2 near times of strong alignment revealing interferences during recombination. The second experiment demonstrates HHG as a sensitive probe of rotational wavepacket dynamics in CO2 and N2O, revealing new revival features not detected by any other probe. The final experiment focuses on understanding and controlling the polarization state of the harmonic emission. Generating elliptically polarized harmonics would be very useful for probing molecular and materials systems. We observe an elliptical dichroism in polarization-resolved measurements of the harmonic emission from aligned N2 and CO2 molecules, revealing evidence for electron-hole dynamics between the

  11. Search for complex organic molecules in space

    Ohishi, Masatoshi

    2016-07-01

    It was 1969 when the first organic molecule in space, H2CO, was discovered. Since then many organic molecules were discovered by using the NRAO 11 m (upgraded later to 12 m), Nobeyama 45 m, IRAM 30 m, and other highly sensitive radio telescopes as a result of close collaboration between radio astronomers and microwave spectroscopists. It is noteworthy that many famous organic molecules such as CH3OH, C2H5OH, (CH3)2O and CH3NH2 were detected by 1975. Organic molecules were found in so-called hot cores where molecules were thought to form on cold dust surfaces and then to evaporate by the UV photons emitted from the central star. These days organic molecules are known to exist not only in hot cores but in hot corinos (a warm, compact molecular clump found in the inner envelope of a class 0 protostar) and even protoplanetary disks. As was described above, major organic molecules were known since 1970s. It was very natural that astronomers considered a relationship between organic molecules in space and the origin of life. Several astronomers challenged to detect glycine and other prebiotic molecules without success. ALMA is expected to detect such important materials to further consider the gexogenous deliveryh hypothesis. In this paper I summarize the history in searching for complex organic molecules together with difficulties in observing very weak signals from larger species. The awfully long list of references at the end of this article may be the most useful part for readers who want to feel the exciting discovery stories.

  12. Spin polarization effect for Mn2 molecule

    Yan Shi-Ying; Xu Guo-Liang

    2007-01-01

    The density functional theory method (DFT) (b3p86) of Gaussian 03 has been used to optimize the structure of the Mn2 molecule.The result shows that the ground state of the Mn2 molecule is an 11-multiple state,indicating a spin polarization effect in the Mn2 molecule,a transition metal element molecule.Meanwhile,we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions of higher-energy states.So the ground state for Mn2 molecule being of an 11-multiple state is the indicative of spin polarization effect of the Mn2 molecule among those in the transition metal elements:that is,there are 10 parallel spin electrons in a Mn2 molecule.The number of non-conjugated electrons is the greatest.These electrons occupy different spacious orbitals so that the energy of the Mn2 molecule is minimized.It can be concluded that the effect of parallel spin in the Mn2 molecule is larger than the effect of the conjugated molecule,which is obviously related to the effect of electron d delocalization.In addition,the Murrell-Sorbie potential functions with the parameters for the ground state and other states of the Mn2 molecule are derived.The dissociation energy De for the ground state of the Mn2 molecule is 1.4477eV,equilibrium bond length Re is 0.2506 nm,vibration frequency ωe is 211.51 cm-1.Its force constants,f2,f3,and f4 are 0.7240 aJ·nm-2,-3.35574 aJ·nm-3,11.4813 aJ·nm-4 respectively. The other spectroscopic data for the ground state of the Mn2 molecule ωeχe,Be,αe are 1.5301 cm-1,0.0978 cm-1,7.7825×10-4 cm-1 respectively.

  13. 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.

    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

  14. Tuning the Magnetic Anisotropy of Single Molecules.

    Heinrich, Benjamin W; Braun, Lukas; Pascual, Jose I; Franke, Katharina J

    2015-06-10

    The magnetism of single atoms and molecules is governed by the atomic scale environment. In general, the reduced symmetry of the surrounding splits the d states and aligns the magnetic moment along certain favorable directions. Here, we show that we can reversibly modify the magnetocrystalline anisotropy by manipulating the environment of single iron(II) porphyrin molecules adsorbed on Pb(111) with the tip of a scanning tunneling microscope. When we decrease the tip-molecule distance, we first observe a small increase followed by an exponential decrease of the axial anisotropy on the molecules. This is in contrast to the monotonous increase observed earlier for the same molecule with an additional axial Cl ligand ( Nat. Phys. 2013 , 9 , 765 ). We ascribe the changes in the anisotropy of both species to a deformation of the molecules in the presence of the attractive force of the tip, which leads to a change in the d level alignment. These experiments demonstrate the feasibility of a precise tuning of the magnetic anisotropy of an individual molecule by mechanical control. PMID:25942560

  15. Molecules-in-Molecules: An Extrapolated Fragment-Based Approach for Accurate Calculations on Large Molecules and Materials.

    Mayhall, Nicholas J; Raghavachari, Krishnan

    2011-05-10

    We present a new extrapolated fragment-based approach, termed molecules-in-molecules (MIM), for accurate energy calculations on large molecules. In this method, we use a multilevel partitioning approach coupled with electronic structure studies at multiple levels of theory to provide a hierarchical strategy for systematically improving the computed results. In particular, we use a generalized hybrid energy expression, similar in spirit to that in the popular ONIOM methodology, that can be combined easily with any fragmentation procedure. In the current work, we explore a MIM scheme which first partitions a molecule into nonoverlapping fragments and then recombines the interacting fragments to form overlapping subsystems. By including all interactions with a cheaper level of theory, the MIM approach is shown to significantly reduce the errors arising from a single level fragmentation procedure. We report the implementation of energies and gradients and the initial assessment of the MIM method using both biological and materials systems as test cases. PMID:26610128

  16. Single molecule microscopy and spectroscopy: concluding remarks.

    van Hulst, Niek F

    2015-01-01

    Chemistry is all about molecules: control, synthesis, interaction and reaction of molecules. All too easily on a blackboard, one draws molecules, their structures and dynamics, to create an insightful picture. The dream is to see these molecules in reality. This is exactly what "Single Molecule Detection" provides: a look at molecules in action at ambient conditions; a breakthrough technology in chemistry, physics and biology. Within the realms of the Royal Society of Chemistry, the Faraday Discussion on "Single Molecule Microscopy and Spectroscopy" was a very appropriate topic for presentation, deliberation and debate. Undoubtedly, the Faraday Discussions have a splendid reputation in stimulating scientific debates along the traditions set by Michael Faraday. Interestingly, back in the 1830's, Faraday himself pursued an experiment that led to the idea that atoms in a compound were joined by an electrical component. He placed two opposite electrodes in a solution of water containing a dissolved compound, and observed that one of the elements of the compound accumulated on one electrode, while the other was deposited on the opposite electrode. Although Faraday was deeply opposed to atomism, he had to recognize that electrical forces were responsible for the joining of atoms. Probably a direct view on the atoms or molecules in his experiment would have convinced him. As such, Michael Faraday might have liked the gathering at Burlington House in September 2015 (). Surely, with the questioning eyes of his bust on the 1st floor corridor, the non-believer Michael Faraday has incited each passer-by to enter into discussion and search for deeper answers at the level of single molecules. In these concluding remarks, highlights of the presented papers and discussions are summarized, complemented by a conclusion on future perspectives. PMID:26606461

  17. Understanding Polymer Properties through Imaging of Molecules.

    Sheiko, Sergei

    2008-03-01

    The unique advantage of Scanning Probe Microscopy (SPM) is that it allows imaging of flexible polymer molecules, whose overall size and local curvature are below the optical resolution limit. The role of molecular visualization has grown to be especially profound with the synthesis of complex macromolecules whose structure is difficult to confirm using conventional techniques such as NMR and light scattering. This is especially true for molecules that are branched, heterogeneous, and polydisperse. Here, SPM images provide unambiguous proof of the molecular architecture along with accurate analysis of size, conformation, and ordering of molecules on surfaces. The unique advantage of SPM is that one obtains molecular dimensions in direct space. This offers more opportunities for statistical analysis including fractionation of molecules by size, branching topology, and chemical composition as well as sorting out the irrelevant species. Unlike molecular characterization of static molecules, it remains challenging to study molecules as they move and react on surfaces. We will discuss pioneering AFM studies of flowing monolayers one molecule at a time. Through use of AFM, the flow process was monitored over a broad range of length scales from the millimeter long precursor film all the way down to the movements of individual molecules within the film. Molecular imaging enabled independent measurements both the driving and frictional forces that control spreading rate. In these studies, one also discovered a new type of flow instability in polymer monolayers caused by flow-induced conformational transitions. Recently, molecular imaging has been successfully used to monitor adsorption-induced degradation of branched molecules. These experiments open an entirely new perspective in chemistry wherein the chemical bonds can be mechanically activated upon the physical contact of a macromolecule with a substrate. This research directly impacts coatings, lubrication, heterogeneous

  18. Imaging Cold Molecules on a Chip

    Marx, S; Abel, M J; Zehentbauer, T; Meijer, G; Santambrogio, G

    2013-01-01

    We present the integrated imaging of cold molecules in a microchip environment. The on-chip de- tection is based on REMPI, which is quantum-state-selective and generally applicable. We demon- strate and characterize time-resolved spatial imaging and subsequently use it to analyze the effect of a phase-space manipulation sequence aimed at compressing the velocity distribution of a molec- ular ensemble with a view to future high-resolution spectroscopic studies. The realization of such on-chip measurements adds the final fundamental component to the molecule chip, offering a new and promising route for investigating cold molecules.

  19. The MHC molecules of nonmammalian vertebrates

    Kaufman, J; Skjoedt, K; Salomonsen, J

    1990-01-01

    encoding polymorphic class I and class II molecules) and evidence for polymorphic class I and class II molecules in reptiles. However, many details differ from the mammals, and it is not clear whether these reflect historical accident or selection for different lifestyles or environment. For example, the...... ontogeny and the consequences for the immune system and survival of the animals. These animals also differ markedly in the level of MHC polymorphism. Another difference from mammals is the presence of previously uncharacterized molecules. In Xenopus and reptiles, there are two populations of class I alpha...

  20. Rotational cooling of trapped polyatomic molecules

    Glöckner, Rosa; Prehn, Alexander; Englert, Barbara G. U.; Rempe, Gerhard; Zeppenfeld, Martin

    2015-01-01

    Controlling the internal degrees of freedom is a key challenge for applications of cold and ultracold molecules. Here, we demonstrate rotational-state cooling of trapped methyl fluoride molecules (CH3F) by optically pumping the population of 16 M-sublevels in the rotational states J=3,4,5, and 6 into a single level. By combining rotational-state cooling with motional cooling, we increase the relative number of molecules in the state J=4, K=3, M=4 from a few percent to over 70%, thereby genera...

  1. Aligning molecules with intense nonresonant laser fields

    Larsen, J.J.; Safvan, C.P.; Sakai, H.;

    1999-01-01

    Molecules in a seeded supersonic beam are aligned by the interaction between an intense nonresonant linearly polarized laser field and the molecular polarizability. We demonstrate the general applicability of the scheme by aligning I2, ICl, CS2, CH3I, and C6H5I molecules. The alignment is probed by...... mass selective two dimensional imaging of the photofragment ions produced by femtosecond laser pulses. Calculations on the degree of alignment of I2 are in good agreement with the experiments. We discuss some future applications of laser aligned molecules....

  2. Tunable optical absorption in silicene molecules

    Mokkath, Junais Habeeb

    2016-07-13

    Two-dimensional materials with a tunable band gap that covers a wide range of the solar spectrum hold great promise for sunlight harvesting. For this reason, we investigate the structural, electronic, and optical properties of silicene molecules using time dependent density functional theory. We address the influence of the molecular size, buckling, and charge state as well as that of a dielectric environment. Unlike planar graphene molecules, silicene molecules prefer to form low-buckled structures with strong visible to ultraviolet optical response. We also identify molecular plasmons.

  3. Handbook of single-molecule electronics

    Moth-Poulsen, Kasper

    2015-01-01

    Single-molecule electronics has evolved as a vibrant research field during the last two decades. The vision is to be able to create electronic components at the highest level of miniaturization-the single molecule. This book compiles and details cutting-edge research with contributions from chemists, physicists, theoreticians, and engineers. It covers all aspects of single-molecule electronics, from the theory through experimental realizations and the chemical synthesis of molecular components to the implementation of molecular components in future integrated circuits. This book describes in d

  4. Single Molecule Biophysics Experiments and Theory

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

    2011-01-01

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

  5. Non-sequential double ionization of molecules

    Prauzner-Bechcicki, J S; Eckhardt, B; Zakrzewski, J; Prauzner-Bechcicki, Jakub S.; Sacha, Krzysztof; Eckhardt, Bruno; Zakrzewski, Jakub

    2004-01-01

    Double ionization of diatomic molecules by short linearly polarized laser pulses is analyzed. We consider the final stage of the ionization process, that is the decay of a highly excited two electron molecule, which is formed after re-scattering. The saddles of the effective adiabatic potential energy close to which simultaneous escape of electrons takes place are identified. Numerical simulations of the ionization of molecules show that the process can be dominated by either sequential or non-sequential events. In order to increase the ratio of non-sequential to sequential ionizations very short laser pulses should be applied.

  6. A Classification Scheme For Toroidal Molecules

    Berger, J; Berger, Jorge; Avron, Joseph E.

    1995-01-01

    We construct a class of periodic tilings of the plane, which corresponds to toroidal arrangements of trivalent atoms, with pentagonal, hexagonal and heptagonal rings. Each tiling is characterized by a set of four integers and determines a toroidal molecule. The tiling rules are motivated by geometric considerations and the tiling patterns are rich enough to describe a wide class of toroidal carbon molecules, with a broad range of shapes and numbers of atoms. The molecular dimensions are simply related to the integers that determine the tiling. The configurational energy and the delocalisation energy of several molecules obtained in this way were computed for Tersoff and H\\"uckel models. The results indicate that many of these molecules are not strained, and may be expected to be stable. We studied the influence of size on the H\\"{u}ckel spectrum: it bears both similarities and differences as compared with the case of tubules.

  7. Molecular junctions: Single-molecule contacts exposed

    Nichols, Richard J.; Higgins, Simon J.

    2015-05-01

    Using a scanning tunnelling microscopy-based method it is now possible to get an atomistic-level description of the most probable binding and contact configuration for single-molecule electrical junctions.

  8. Synaptic Cell Adhesion Molecules in Alzheimer's Disease

    Leshchyns'ka, Iryna

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder associated with the loss of synapses between neurons in the brain. Synaptic cell adhesion molecules are cell surface glycoproteins which are expressed at the synaptic plasma membranes of neurons. These proteins play key roles in formation and maintenance of synapses and regulation of synaptic plasticity. Genetic studies and biochemical analysis of the human brain tissue, cerebrospinal fluid, and sera from AD patients indicate that levels and function of synaptic cell adhesion molecules are affected in AD. Synaptic cell adhesion molecules interact with Aβ, a peptide accumulating in AD brains, which affects their expression and synaptic localization. Synaptic cell adhesion molecules also regulate the production of Aβ via interaction with the key enzymes involved in Aβ formation. Aβ-dependent changes in synaptic adhesion affect the function and integrity of synapses suggesting that alterations in synaptic adhesion play key roles in the disruption of neuronal networks in AD. PMID:27242933

  9. Models, mysteries, and magic of molecules

    Boeyens, Jan CA

    2007-01-01

    Molecules have for a long time been of central importance in chemistry as the basis on which all new products and materials have been designed, developed and interpreted. Since the discovery and characterization of active biomolecules, biology has also been transformed into a molecular science. With the new developments of molecular devices, single-molecule spectroscopy, time-resolved x-ray diffraction and the study of mass-selected clusters in molecular beams, materials science and electronics may move in the same direction. The understanding of molecules and the dynamics of their transition between isolated and assembled states rests on three pillars: structure, activity and function. Enormous progress has been made in the experimental study of molecules by diffraction and spectroscopic analysis, directed at all three of the basic aspects. In the process molecular scientists have developed efficient working models in terms of which to design and interpret their experiments. A vital feature of such models is...

  10. Stochastic Models of Molecule Formation on Dust

    Charnley, Steven; Wirstroem, Eva

    2011-01-01

    We will present new theoretical models for the formation of molecules on dust. The growth of ice mantles and their layered structure is accounted for and compared directly to observations through simulation of the expected ice absorption spectra

  11. The evolution of polymorphic compatibility molecules

    Boer, R.J. de

    1995-01-01

    Several primitive colonial organisms distinguish self from nonself by means of polymorphic compatibility molecules bearing similarity to the major histocompatibility complex (MHC). The evolution of such polymorphisms is generally explained in terms of resistance to parasites. Ignoring parasites, I d

  12. Novel electrostatic trap for cold polar molecules

    Xu Xue-Yan; Ma Hui; Yin Jian-Ping

    2007-01-01

    We propose a novel scheme in which cold polar molecules are trapped by an electrostatic field generated by the combination of a pair of parallel transparent electrodes (i.e., two infinite transparent plates) and a ring electrode (i.e., a ring wire). The spatial distributions of the electrostatic fields from the above charged wire and the charged plates and the corresponding Stark potentials for cold CO molecules are calculated; the dependences of the trap centre position on the geometric parameters of the electrode are analysed. We also discuss the loading process of cold molecules from a cold molecular beam into our trap. This study shows that the proposed scheme is not only simple and convenient to trap, manipulate and control cold polar molecules in weak-field-seeking states, but also provides an opportunity to study cold collisions and collective quantum effects in a variety of cold molecular systems, etc.

  13. Global warming and SF6 molecule

    Gajević Jelena

    2006-01-01

    Full Text Available In this paper the basic SF6 molecule physical characteristics are given concerning its influence on global warming and green house effect. Absorption and relaxation characteristics of this molecule have been investigated within the frame of nonlinear molecule – strong laser field interaction in different gas mixtures. All experiments have been performed on a different gas mixture pressures to analyze and investigate relaxation and energy transfer characteristics of absorbing molecules and non-absorbing collision partners. To show the SF6 absorption and relaxation and energy transfer capability comparison between SF6 and C2H4 was given using the same experimental conditions and argon as a buffer gas. All measurement points and their calculated values presented in this paper have been obtained using the infrared-pulsed photoacoustics technique adopted for atmospheric and subatmospheric pressures.

  14. Sisyphus Cooling of Electrically Trapped Polyatomic Molecules

    Zeppenfeld, M; Glöckner, R; Prehn, A; Mielenz, M; Sommer, C; van Buuren, L D; Motsch, M; Rempe, G

    2012-01-01

    The rich internal structure and long-range dipole-dipole interactions establish polar molecules as unique instruments for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where a plethora of effects is predicted in many-body physics, quantum information science, ultracold chemistry, and physics beyond the standard model. These objectives have inspired the development of a wide range of methods to produce cold molecular ensembles. However, cooling polyatomic molecules to ultracold temperatures has until now seemed intractable. Here we report on the experimental realization of opto-electrical cooling, a paradigm-changing cooling and accumulation method for polar molecules. Its key attribute is the removal of a large fraction of a molecule's kinetic energy in each step of the cooling cycle via a Sisyphus effect, allowing cooling with only few dissipative decay processes. We demonstrate its potential by reducing the temperature of about 10^6 ...

  15. Single-Molecule Studies in Live Cells

    Yu, Ji

    2016-05-01

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

  16. Electron-impact-induced tryptophan molecule fragmentation

    In our investigation, we have studied the interactions of low-energy (<70 eV) electrons with tryptophan molecule belonging to the essential amino acids in order to probe the intrinsic properties of the molecule and trace its change(s) under the electron impact. The fragmentation of a gas-phase tryptophan molecule by low-energy electrons was studied both experimentally and theoretically. Various positively charged fragments were observed and analyzed. A special attention was paid to the energy characteristics of the ionic fragment yield. The geometrical parameters of the initial molecule rearrangement were also analyzed. The fragmentation observed was due to either a simple bond cleavage or more complex reactions involving molecular rearrangements

  17. Polyatomic molecules under intense femtosecond laser irradiation.

    Konar, Arkaprabha; Shu, Yinan; Lozovoy, Vadim V; Jackson, James E; Levine, Benjamin G; Dantus, Marcos

    2014-12-11

    Interaction of intense laser pulses with atoms and molecules is at the forefront of atomic, molecular, and optical physics. It is the gateway to powerful new tools that include above threshold ionization, high harmonic generation, electron diffraction, molecular tomography, and attosecond pulse generation. Intense laser pulses are ideal for probing and manipulating chemical bonding. Though the behavior of atoms in strong fields has been well studied, molecules under intense fields are not as well understood and current models have failed in certain important aspects. Molecules, as opposed to atoms, present confounding possibilities of nuclear and electronic motion upon excitation. The dynamics and fragmentation patterns in response to the laser field are structure sensitive; therefore, a molecule cannot simply be treated as a "bag of atoms" during field induced ionization. In this article we present a set of experiments and theoretical calculations exploring the behavior of a large collection of aryl alkyl ketones when irradiated with intense femtosecond pulses. Specifically, we consider to what extent molecules retain their molecular identity and properties under strong laser fields. Using time-of-flight mass spectrometry in conjunction with pump-probe techniques we study the dynamical behavior of these molecules, monitoring ion yield modulation caused by intramolecular motions post ionization. The set of molecules studied is further divided into smaller sets, sorted by type and position of functional groups. The pump-probe time-delay scans show that among positional isomers the variations in relative energies, which amount to only a few hundred millielectronvolts, influence the dynamical behavior of the molecules despite their having experienced such high fields (V/Å). High level ab initio quantum chemical calculations were performed to predict molecular dynamics along with single and multiphoton resonances in the neutral and ionic states. We propose the

  18. Spin polarization effect for Os2 molecule

    Xie An-Dong; Yan Shi-Ying; Zhu Zheng-He; Fu Yi-Bei

    2005-01-01

    Density functional Theory (DFT) (B3p86) of Gaussian03 has been used to optimize the structure of Os2 molecule.The result shows that the ground state for Os2 molecule is 9-multiple state and its electronic configuration is 9∑+g,which shows spin polarization effect of Os2 molecule of transition metal elements for the first time. Meanwhile, we have not found any spin pollution because the wavefunction of the ground state does not mingle with wavefunctions with higher energy states. So, the fact that the ground state for Os2 molecule is a 9-multiple state is indicative of spin polarization effect of Os2 molecule of transition metal elements. That is, there exist 8 parallel spin electrons.The non-conjugated electron is greatest in number. These electrons occupy different spacious tracks, so that the energy of Os2 molecule is minimized. It can be concluded that the effect of parallel spin of Os2 molecule is larger than the effect of the conjugated molecule, which is obviously related to the effect of electron d delocalization. In addition, the Murrell-Sorbie potential functions with the parameters for the ground state 9∑+g and other states of Os2 molecule are derived. Dissociation energy De for the ground state of Os2 molecule is 3.3971eV, equilibrium bond length Re is 0.2403nm, vibration frequency ωe is 235.32cm-1. Its force constants f2, f3, and f4 are 3.1032×102aJ.nm-2,-14.3425×103aJ.nm-3 and 50.5792×104aJ.nm-4 respectively. The other spectroscopic data for the ground state of Os2 molecule ωeχe, Be and αe are 0.4277cm-1, 0.0307cm-1 and 0.6491× 10-4cm-1 respectively.

  19. The coordination chemistry of saturated molecules

    Bercaw, John E.; Labinger, Jay A.

    2007-01-01

    Our understanding of bonding in transition metal complexes, as well as our ability to use that understanding in the synthesis and application of new species, has evolved over the last 100 years; and in some sense this special feature on the coordination chemistry of saturated molecules may be considered to represent its culmination. The nature of complexes between transition metal ions and neutral molecules such as ammonia was first correctly described by Werner around the beginning of the 20...

  20. Single Molecule Applications of Quantum Dots

    Rasmussen, Thomas Elmelund; Jauffred, Liselotte; Brewer, Jonathan R.;

    2013-01-01

    tracking single lipids in lipid bilayers, 4) two-photon fluorescence correlation spectroscopy of QDs and 5) optical trapping and excitation of single QDs. In all of these applications, the focus is on the single particle sensitivity level of QDs. The high applicability of QDs in live cell imaging...... experiments held together with the prospects in localization microscopy and single molecule manipulation experiments gave QDs a promising future in single molecule research....

  1. Dissociation of ultracold molecules with Feshbach resonances

    Dürr, Stephan; Volz, Thomas; Rempe, Gerhard

    2004-01-01

    Ultracold molecules are associated from an atomic Bose-Einstein condensate by ramping a magnetic field across a Feshbach resonance. The reverse ramp dissociates the molecules. The kinetic energy released in the dissociation process is used to measure the widths of 4 Feshbach resonances in 87Rb. This method to determine the width works remarkably well for narrow resonances even in the presence of significant magnetic-field noise. In addition, a quasi-mono-energetic atomic wave is created by ju...

  2. Properties of molecules in tunnel junctions

    Yeriskin, Irene

    2013-01-01

    Molecular tunnel junctions involve studying the behaviour of a single molecule sandwiched between metal leads. When a molecule makes contact with electrodes, it becomes open to the environment which can heavily influence its properties, such as electronegativity and electron transport. While the most common computational approaches remain to be single particle approximations, in this thesis it is shown that a more explicit treatment of electron interactions can be required. By studying an ope...

  3. Small Molecule Subgraph Detector (SMSD) toolkit

    Rahman Syed; Bashton Matthew; Holliday Gemma L; Schrader Rainer; Thornton Janet M

    2009-01-01

    Abstract Background Finding one small molecule (query) in a large target library is a challenging task in computational chemistry. Although several heuristic approaches are available using fragment-based chemical similarity searches, they fail to identify exact atom-bond equivalence between the query and target molecules and thus cannot be applied to complex chemical similarity searches, such as searching a complete or partial metabolic pathway. In this paper we present a new Maximum Common S...

  4. Biological mechanisms, one molecule at a time

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these tw...

  5. The Escape Rate of a Molecule

    Knauf, Andreas, E-mail: knauf@mi.uni-erlangen.de; Krapf, Markus [Universitaet Erlangen-Nuernberg, Department Mathematik (Germany)

    2010-06-15

    We show existence and give an implicit formula for the escape rate of the n-centre problem of celestial mechanics for high energies. Furthermore we give precise computable estimates of this rate. This exponential decay rate plays an important role especially in semiclassical scattering theory of n-atomic molecules. Our result shows that the diameter of a molecule is measurable in a (classical) high-energy scattering experiment.

  6. Vibrational spectroscopy of polar molecules with superradiance

    Lin, Guin-Dar; Yelin, Susanne F.

    2013-07-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy of high optical-depth samples. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to speed-up of decay processes. We compare our calculation to recent work and find very good agreement, suggesting that superradiant effects need to be taken into account in a wide variety of ultracold molecule experiments, including vibrational and rotational states.

  7. Electron affinities of atoms, molecules, and radicals

    We review briefly but comprehensively the theoretical, semiempirical and experimental methods employed to determine electron affinities (EAs) of atoms, molecules and radicals, and summarize the EA data obtained by these methods. The detailed processes underlying the principles of the experimental methods are discussed very briefly. It is, nonetheless, instructive to recapitulate the definition of EA and those of the related quantities, namely, the vertical detachment energy, VDE, and the vertical attachment energy, VAE. The EA of an atom is defined as the difference in total energy between the ground state of the neutral atom (plus the electron at rest at infinity) and its negative ion. The EA of a molecule is defined as the difference in energy between the neutral molecule plus an electron at rest at infinity and the molecular negative ion when both, the neutral molecules and the negative ion, are in their ground electronic, vibrational and rotational states. The VDE is defined as the minimum energy required to eject the electron from the negative ion (in its ground electronic and nuclear state) without changing the internuclear separation; since the vertical transition may leave the neutral molecule in an excited vibrational/rotational state, the VDE, although the same as the EA for atoms is, in general, different (larger than), from the EA for molecules. Similarly, the VAE is defined as the difference in energy between the neutral molecule in its ground electronic, vibrational and rotational states plus an electron at rest at infinity and the molecular negative ion formed by addition of an electron to the neutral molecule without allowing a change in the intermolecular separation of the constituent nuclei; it is a quantity appropriate to those cases where the lowest negative ion state lies above the ground states of the neutral species and is less or equal to EA

  8. Do triatomic molecules echo atomic periodicity?

    Hefferlin, R., E-mail: hefferln@southern.edu; Barrow, J. [Southern Adventist University, PO Box 370, Collegedale, Tennessee 37315 (United States)

    2015-03-30

    Demonstrations of periodicity among triatomic-molecular spectroscopic constants underscore the role of the periodic law as a foundation of chemistry. The objective of this work is to prepare for another test using vibration frequencies ν{sub 1} of free, ground-state, main-group triatomic molecules. Using data from four data bases and from computation, we have collected ν{sub 1} data for molecules formed from second period atoms.

  9. Single-molecule dynamics at variable temperatures

    Zondervan, Rob

    2006-01-01

    Single-molecule optics has evolved from a specialized variety of optical spectroscopy at low temperatures into a versatile tool to address questions in physics, chemistry, biology, and materials science. In this thesis, the potential of single-molecule (and ensemble) optical microscopy at variable temperatures is demonstrated: Electron transfer has been identified as a crucial step in the photodynamics of organic fluorophores, and long-term memory effects have been discovered in the relaxatio...

  10. Interfacial energies of systems of chiral molecules

    Braides, Andrea; Garroni, Andrea; Palombaro, Mariapia

    2016-01-01

    We consider a simple model for the assembly of chiral molecules in two dimensions driven by maximization of the contact area. We derive a macroscopic model described by a parameter taking nine possible values corresponding to the possible minimal microscopic patterns and modulated phases of the chiral molecules. We describe the overall behaviour by means of an interaction energy of perimeter type between such phases. This energy is a crystalline perimeter energy, highlighting preferred direct...

  11. Hadronic molecules in the heavy baryon spectrum

    We study possible baryon molecules in the non-strange heavy baryon spectrum. We include configurations with a heavy-meson and a light baryon. We find several structures, in particular we can understand the Λc(2940) as a D*N molecule with JP = 3/2− quantum numbers. We also find D(*)Δ candidates for the recently discovered Xc(3250) resonance

  12. Modelling water molecules inside cyclic peptide nanotubes

    Tiangtrong, Prangsai; Thamwattana, Ngamta; Baowan, Duangkamon

    2016-03-01

    Cyclic peptide nanotubes occur during the self-assembly process of cyclic peptides. Due to the ease of synthesis and ability to control the properties of outer surface and inner diameter by manipulating the functional side chains and the number of amino acids, cyclic peptide nanotubes have attracted much interest from many research areas. A potential application of peptide nanotubes is their use as artificial transmembrane channels for transporting ions, biomolecules and waters into cells. Here, we use the Lennard-Jones potential and a continuum approach to study the interaction of a water molecule in a cyclo[(- D-Ala- L-Ala)_4-] peptide nanotube. Assuming that each unit of a nanotube comprises an inner and an outer tube and that a water molecule is made up of a sphere of two hydrogen atoms uniformly distributed over its surface and a single oxygen atom at the centre, we determine analytically the interaction energy of the water molecule and the peptide nanotube. Using this energy, we find that, independent of the number of peptide units, the water molecule will be accepted inside the nanotube. Once inside the nanotube, we show that a water molecule prefers to be off-axis, closer to the surface of the inner nanotube. Furthermore, our study of two water molecules inside the peptide nanotube supports the finding that water molecules form an array of a 1-2-1-2 file inside peptide nanotubes. The theoretical study presented here can facilitate thorough understanding of the behaviour of water molecules inside peptide nanotubes for applications, such as artificial transmembrane channels.

  13. Bipolar Conductance Switching of Single Anthradithiophene Molecules.

    Borca, Bogdana; Schendel, Verena; Pétuya, Rémi; Pentegov, Ivan; Michnowicz, Tomasz; Kraft, Ulrike; Klauk, Hagen; Arnau, Andrés; Wahl, Peter; Schlickum, Uta; Kern, Klaus

    2015-12-22

    Single molecular switches are basic device elements in organic electronics. The pentacene analogue anthradithiophene (ADT) shows a fully reversible binary switching between different adsorption conformations on a metallic surface accompanied by a charge transfer. These transitions are activated locally in single molecules in a low-temperature scanning tunneling microscope . The switching induces changes between bistable orbital structures and energy level alignment at the interface. The most stable geometry, the "off" state, which all molecules adopt upon evaporation, corresponds to a short adsorption distance at which the electronic interactions of the acene rings bend the central part of the molecule toward the surface accompanied by a significant charge transfer from the metallic surface to the ADT molecules. This leads to a shift of the lowest unoccupied molecular orbital down to the Fermi level (EF). In the "on" state the molecule has a flat geometry at a larger distance from the surface; consequently the interaction is weaker, resulting in a negligible charge transfer with an orbital structure resembling the highest occupied molecular orbital when imaged close to EF. The potential barrier between these two states can be overcome reversibly by injecting charge carriers locally into individual molecules. Voltage-controlled current traces show a hysteresis characteristic of a bipolar switching behavior. The interpretation is supported by first-principles calculations. PMID:26580569

  14. Auxin biology revealed by small molecules.

    Ma, Qian; Robert, Stéphanie

    2014-05-01

    The plant hormone auxin regulates virtually every aspect of plant growth and development and unraveling its molecular and cellular modes of action is fundamental for plant biology research. Chemical genomics is the use of small molecules to modify protein functions. This approach currently rises as a powerful technology for basic research. Small compounds with auxin-like activities or affecting auxin-mediated biological processes have been widely used in auxin research. They can serve as a tool complementary to genetic and genomic methods, facilitating the identification of an array of components modulating auxin metabolism, transport and signaling. The employment of high-throughput screening technologies combined with informatics-based chemical design and organic chemical synthesis has since yielded many novel small molecules with more instantaneous, precise and specific functionalities. By applying those small molecules, novel molecular targets can be isolated to further understand and dissect auxin-related pathways and networks that otherwise are too complex to be elucidated only by gene-based methods. Here, we will review examples of recently characterized molecules used in auxin research, highlight the strategies of unraveling the mechanisms of these small molecules and discuss future perspectives of small molecule applications in auxin biology. PMID:24252105

  15. Self-Assemblies of novel molecules, VECAR

    Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

    2015-03-01

    VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

  16. Dissociation and Decay of Ultra-cold Sodium Molecules

    Mukaiyama, T.; Abo-Shaeer, J. R.; Xu, K.; Chin, J. K.; Ketterle, W.

    2003-01-01

    The dissociation of ultracold molecules is studied by ramping an external magnetic field through a Feshbach resonance. The observed dissociation energy shows non-linear dependence on the ramp speed and directly yields the strength of the atom-molecule coupling. In addition, inelastic molecule-molecule and molecule-atom collisions are characterized.

  17. Spin polarization effect for molecule Ta2

    Xie An-Dong

    2006-01-01

    Density functional theory (DFT) (B3p86) has been used to optimize the structure of the molecule Taa- The result shows that the ground state of molecule Ta,2 is a 7- multiple state and its electronic configuration is 7∑+u which shows the spin polarization effect for molecule Ta2 of transition metal elements for the first time. Meanwhile, spin pollution has not been found because the wavefunction of the ground state does not mix with those of higher states. So, the fact that the ground state of molecule Ta2 is a 7-multiple state indicates a spin polarization effect of molecule Ta2 of the transition metal elements, i.e. there exist 6 parallel spin electrons and the non-conjugated electrons are greatest in number. These electrons occupy different space orbitals so that the energy of molecule Ta2 is minimized. It can be concluded that the effect of parallel spin of the molecule Ta2 is larger than the effect of the conjugated molecule, which is obviously related to the effect of d-electron delocalization. In addition, the Murrell-Sorbie potential functions with parameters for the ground state 7∑+u and other states of the molecule Ta2 are derived. The dissociation energy De, equilibrium bond length Re and vibration frequency ωe for the ground state of molecule Ta2 are 4.5513eV, 0.2433nm and 173.06cm-1, respectively. Its force constants f2,f3 and f4 are 1.5965×l02aJ·nm-2,-6.4722×l03aJ·nm-3 and 29.4851×04aJ·nm-4, respectively. Other spectroscopic data ωe χe, Be and αe for the ground state of Ta2 are 0.2078cm-1, 0.0315cm-1 and 0.7858×104 cm-1, respectively.

  18. Quantifying molecule-surface interactions using AFM-based single-molecule manipulation

    Tautz, F. S.; Wagner, C.; Temirov, R.; Fournier, N.; Green, M.; Esat, T.; Leinen, P.; Groetsch, A.; Ruiz, V. G.; Tkatchenko, A.; Li, C.; Muellen, K.; Rohlfing, M.

    2015-03-01

    Scanning probe microscopy plays an important role in the investigation of molecular adsorption. Promising, is the possibility to probe the molecule-surface interaction while tuning its strength through AFM tip-induced single-molecule manipulation. Here, we outline a strategy to achieve quantitative understanding of such manipulation experiments. The example of qPlus sensor based PTCDA molecule lifting experiments is used to demonstrate how different aspects of the molecule-surface interaction, namely the short-range adsorption potential, the asymptotic van der Waals potential, local chemical bonds which are the source of the surface corrugation, and molecule-molecule interactions can be measured with SPM and interpreted by the help of force-field simulations.

  19. Image Analysis of Defocused Single-molecule Images for Three-dimensional Molecule Orientation Studies

    Patra, D; Gregor, I.; Enderlein, J.

    2004-01-01

    An efficient algorithm for pattern matching has been developed based on least-squares analysis of fitting a discrete set of master patterns against measured images. This algorithm has been applied to determine three-dimensional molecule orientations in defocused single-molecule images. The developed algorithm exploits the excellent agreement between electrodynamic calculations of single-molecule emission and experimentally measured images. The procedure is found to be reliable and simple and ...

  20. Clusters of mobile molecules in supercooled water

    Giovambattista, Nicolas; Buldyrev, Sergey V.; Stanley, H. Eugene; Starr, Francis W.

    2005-07-01

    We study the spatially heterogeneous dynamics in water via molecular dynamics simulations using the extended simple point charge potential. We identify clusters formed by mobile molecules and study their properties. We find that these clusters grow in size and become more compact as temperature decreases. We analyze the probability density function of cluster size, and we study the cluster correlation length. We find that clusters appear to be characterized by a fractal dimension consistent with that of lattice animals. We relate the cluster size and correlation length to the configurational entropy, Sconf . We find that these quantities depend weakly on 1/Sconf . In particular, the linearity found between the cluster mass n* and 1/Sconf suggests that n* may be interpreted as the mass of the cooperatively rearranging regions that form the basis of the Adam-Gibbs approach to the dynamics of supercooled liquids. We study the motion of molecules within a cluster, and find that each molecule preferentially follows a neighboring molecule in the same cluster. Based on this finding we hypothesize that stringlike cooperative motion may be a general mechanism for molecular rearrangement of complex, as well as simple liquids. By mapping each equilibrium configuration onto its corresponding local potential energy minimum or inherent structure (IS), we are able to compare the mobile molecule clusters in the equilibrium system with the molecules forming the clusters identified in the transitions between IS. We find that (i) mobile molecule clusters obtained by comparing different system configurations and (ii) clusters obtained by comparing the corresponding IS are completely different for short time scales, but are the same on the longer time scales of diffusive motion.

  1. Electromechanical Properties of Single Molecule Devices

    Bruot, Christopher

    Understanding the interplay between the electrical and mechanical properties of single molecules is of fundamental importance for molecular electronics. The sensitivity of charge transport to mechanical fluctuations is a key problem in developing long lasting molecular devices. Furthermore, harnessing this response to mechanical perturbation, molecular devices which can be mechanically gated can be developed. This thesis demonstrates three examples of the unique electromechanical properties of single molecules. First, the electromechanical properties of 1,4-benzenedithiol molecular junctions are investigate. Counterintuitively, the conductance of this molecule is found to increase by more than an order of magnitude when stretched. This conductance increase is found to be reversible when the molecular junction is compressed. The current-voltage, conductance-voltage and inelastic electron tunneling spectroscopy characteristics are used to attribute the conductance increase to a strain-induced shift in the frontier molecular orbital relative to the electrode Fermi level, leading to resonant enhancement in the conductance. Next, the effect of stretching-induced structural changes on charge transport in DNA molecules is studied. The conductance of single DNA molecules with lengths varying from 6 to 26 base pairs is measured and found to follow a hopping transport mechanism. The conductance of DNA molecules is highly sensitive to mechanical stretching, showing an abrupt decrease in conductance at surprisingly short stretching distances, with weak dependence on DNA length. This abrupt conductance decrease is attributed to force-induced breaking of hydrogen bonds in the base pairs at the end of the DNA sequence. Finally, the effect of small mechanical modulation of the base separation on DNA conductance is investigated. The sensitivity of conductance to mechanical modulation is studied for molecules of different sequence and length. Sequences with purine-purine stacking

  2. Mining for Molecules in the Milky Way

    2008-06-01

    Scientists are using the giant Robert C. Byrd Green Bank Telescope (GBT) to go prospecting in a rich molecular cloud in our Milky Way Galaxy. They seek to discover new, complex molecules in interstellar space that may be precursors to life. The GBT and Molecules The Robert C. Byrd Green Bank Telescope and some molecules it has discovered. CREDIT: Bill Saxton, NRAO/AUI/NSF "Clouds like this one are the raw material for new stars and planets. We know that complex chemistry builds prebiotic molecules in such clouds long before the stars and planets are formed. There is a good chance that some of these interstellar molecules may find their way to the surface of young planets such as the early Earth, and provide a head start for the chemistry of life. For the first time, we now have the capability to make a very thorough and methodical search to find all the chemicals in the clouds," said Anthony Remijan, of the National Radio Astronomy Observatory (NRAO). In the past three years, Remijan and his colleagues have used the GBT to discover ten new interstellar molecules, a feat unequalled in such a short time by any other team or telescope. The scientists discovered those molecules by looking specifically for them. However, they now are changing their strategy and casting a wide net designed to find whatever molecules are present, without knowing in advance what they'll find. In addition, they are making their data available freely to other scientists, in hopes of speeding the discovery process. The research team presented its plan to the American Astronomical Society's meeting in St. Louis, MO. As molecules rotate and vibrate, they emit radio waves at specific frequencies. Each molecule has a unique pattern of such frequencies, called spectral lines, that constitutes a "fingerprint" identifying that molecule. Laboratory tests can determine the pattern of spectral lines that identifies a specific molecule. Most past discoveries came from identifying a molecule's pattern in

  3. Conduction mechanisms and stability of single molecule nanoparticle/molecule/nanoparticle junctions

    Nanoparticle/molecule/nanoparticle dimer assemblies have been successfully trapped by dielectrophoresis across nanogap electrodes, enabling temperature dependent charge transport measurements through an oligomeric phenylene ethynylene molecule, and transition from direct tunnelling to Fowler-Nordheim tunnelling is observed at ∼1.5 V. Samples formed by dielectrophoresis show better contact stability than those formed by receding meniscus. The junction shows stable operation over several weeks in a vacuum, but current increases with time upon exposure to air, possibly due to the adsorbed water molecules near the molecule/gold nanoparticle contacts

  4. The reaction dynamics of alkali dimer molecules and electronically excited alkali atoms with simple molecules

    Hou, H [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1995-12-01

    This dissertation presents the results from the crossed molecular beam studies on the dynamics of bimolecular collisions in the gas phase. The primary subjects include the interactions of alkali dimer molecules with simple molecules, and the inelastic scattering of electronically excited alkali atoms with O2. The reaction of the sodium dimers with oxygen molecules is described in Chapter 2. Two reaction pathways were observed for this four-center molecule-molecule reaction, i.e. the formations of NaO2 + Na and NaO + NaO. NaO2 products exhibit a very anisotropic angular distribution, indicating a direct spectator stripping mechanism for this reaction channel. The NaO formation follows the bond breaking of O2, which is likely a result of a charge transfer from Na2 to the excited state orbital of O2-. The scattering of sodium dimers from ammonium and methanol produced novel molecules, NaNH3 and Na(CH3OH), respectively. These experimental observations, as well as the discussions on the reaction dynamics and the chemical bonding within these molecules, will be presented in Chapter 3. The lower limits for the bond dissociation energies of these molecules are also obtained. Finally, Chapter 4 describes the energy transfer between oxygen molecules and electronically excited sodium atoms.

  5. Single-Molecule Electronics with Cross- Conjugated Molecules: Quantum Interference, IETS and Non-Equilibrium "Temperatures"

    Jørgensen, Jacob Lykkebo

    , which is characterised by destructive quantum interference. The molecules are cross-conjugated, which means that the two parts of the molecules are conjugated to a third part, but not to each other. This gives rise to an anti-resonance in the trans- mission. In the low bias and low temperature regime......, the electrons can tunnel in- elastically from the left to the right electrode. This is the process behind inelastic electron tunnelling spectroscopy (IETS), which is a single-molecule spectroscopic method, where the vibrational ngerprint of a molecule is di- rectly observed by the tunnelling current...

  6. Preparation and manipulation of molecules for fundamental physics tests

    Tarbutt, M. R.; Hudson, J. J.; Sauer, B. E.; Hinds, E. A.

    2008-01-01

    This paper is a chapter from an upcoming book on cold molecule physics. In it we describe techniques for the preparation and manipulation of cold molecules. We further describe techniques for applying said cold molecules to tests of fundamental physics.

  7. 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

    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.

  8. 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

    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.

  9. Quantum Computer Using Coupled Quantum Dot Molecules

    Wu, N J; Natori, A; Yasunaga, H; Wu*, Nan-Jian

    1999-01-01

    We propose a method for implementation of a quantum computer using artificial molecules. The artificial molecule consists of two coupled quantum dots stacked along z direction and one single electron. One-qubit and two-qubit gates are constructed by one molecule and two coupled molecules, respectively.The ground state and the first excited state of the molecule are used to encode the |0> and |1> states of a qubit. The qubit is manipulated by a resonant electromagnetic wave that is applied directly to the qubit through a microstrip line. The coupling between two qubits in a quantum controlled NOT gate is switched on (off) by floating (grounding) the metal film electrodes. We study the operations of the gates by using a box-shaped quantum dot model and numerically solving a time-dependent Schridinger equation, and demonstrate that the quantum gates can perform the quantum computation. The operating speed of the gates is about one operation per 4ps. The reading operation of the output of the quantum computer can...

  10. Ultracold polar molecules near quantum degeneracy.

    Ospelkaus, S; Ni, K K; de Miranda, M H G; Neyenhuis, B; Wang, D; Kotochigova, S; Julienne, P S; Jin, D S; Ye, J

    2009-01-01

    We report the creation and characterization of a near quantum-degenerate gas of polar 40K-87Rb molecules in their absolute rovibrational ground state. Starting from weakly bound heteronuclear KRb Feshbach molecules, we implement precise control of the molecular electronic, vibrational, and rotational degrees of freedom with phase-coherent laser fields. In particular, we coherently transfer these weakly bound molecules across a 125 THz frequency gap in a single step into the absolute rovibrational ground state of the electronic ground potential. Phase coherence between lasers involved in the transfer process is ensured by referencing the lasers to two single components of a phase-stabilized optical frequency comb. Using these methods, we prepare a dense gas of 4 x 10(4) polar molecules at a temperature below 400 nK. This fermionic molecular ensemble is close to quantum degeneracy and can be characterized by a degeneracy parameter of T/T(F) = 3. We have measured the molecular polarizability in an optical dipole trap where the trap lifetime gives clues to interesting decay mechanisms. Given the large measured dipole moment of the KRb molecules of 0.5 Debye, the study of quantum degenerate molecular gases interacting via strong dipolar interactions is now within experimental reach. PACS numbers: 37.10.Mn, 37.10.Pq. PMID:20151553

  11. Difference Raman spectroscopy of DNA molecules

    In this paper the micro-Raman spectra of calf DNA for different points of DNA sample have been recorded. The Raman spectra were made with help of difference Raman spectroscopy technique. Raman spectra were recorded with high spatial resolution from different points of the wet and dry samples in different spectral range (100÷4000cm−1) using two lasers: argon (514.5 nm) and helium -neon (632.8 nm). The significant differences in the Raman spectra for dry and wet DNA and for different points of DNA molecules were observed. The obtained data on difference Raman scattering spectra of DNA molecules may be used for identification of DNA types and for analysis of genetic information associated with the molecular structure of this molecule

  12. Complex Molecule Formation in Grain Mantles

    Hall, P

    2010-01-01

    Context: Complex molecules such as ethanol and dimethyl ether have been observed in a number of hot molecular cores and hot corinos. Attempts to model the molecular formation process using gas phase only models have so far been unsuccessful. Aims : To demonstrate that grain surface processing is a viable mechanism for complex molecule formation in these environments. Methods: A variable environment parameter computer model has been constructed which includes both gas and surface chemistry. This is used to investigate a variety of cloud collapse scenarios. Results: Comparison between model results and observation shows that by combining grain surface processing with gas phase chemistry complex molecules can be produced in observed abundances in a number of core and corino scenarios. Differences in abundances are due to the initial atomic and molecular composition of the core/corino and varying collapse timescales. Conclusions: Grain surface processing, combined with variation of physical conditions, can be reg...

  13. Collision data involving hydro-carbon molecules

    Hydro-carbon molecules are abundantly produced when graphites are used as internal wall materials of hydrogen plasmas and strongly influence properties of low temperature plasmas near the edges as well as those of high temperature plasmas at the center. In this report, following simple description of the production mechanisms of hydro-carbon molecules under the interactions between graphite and hydrogen plasma, the present status of collision data for hydro-carbon molecules by electron impact is discussed and the relevant data are summarized in a series of figures and tables. It should also be noted that, in addition to fusion plasmas, these hydrocarbon data compiled here are quite useful in other applications such as plasma chemistry and material processing. (author)

  14. Watching single protein molecules in action

    Heiðarsson, Pétur Orri

    . This knowledge-gap is partly due to our inability to unveil the details of folding mechanisms that can be buried in the ensemble-averaged output of traditional bulk methods. Single-molecule techniques have provided a perspective beyond the ensemble average and enable studying the folding trajectories...... of protein molecules in unprecedented detail. These methods can, in principle, detect rare folding or misfolding events, and ultimately lead to a reconstruction of the free energy landscape. In this thesis, the folding mechanism of both single- and double-domain proteins is unraveled using single......-molecule optical tweezers. We first focused on the mechanical properties and unfolding pathway of the four-helix acyl-CoA binding protein (ACBP). Contrary to previous studies which have shown protein native states to be brittle, we observed extraordinary compliance for ACBP along two orthogonal pulling axis, with...

  15. Sample preparation for single molecule localization microscopy.

    Allen, John R; Ross, Stephen T; Davidson, Michael W

    2013-11-21

    Single molecule localization-based optical nanoscopy was introduced in 2006, surpassing traditional diffraction-limited resolutions by an order of magnitude. Seven years later, this superresolution technique is continuing to follow a trend of increasing popularity and pervasiveness, with the proof-of-concept work long finished and commercial implementations now available. However one important aspect that tends to become lost in translation is the importance of proper sample preparation, with very few resources addressing the considerations that must be made when preparing samples for imaging with single molecule level sensitivity. Presented here is a an in-depth analysis of all aspects of sample preparation for single molecule superresolution, including both live and fixed cell preparation, choice of fluorophore, fixation and staining techniques, and imaging buffer considerations. PMID:24084850

  16. Organization of Lipid Molecules within Biomembranes

    M. Benhamou

    2008-01-01

    Full Text Available In this review, we report on the organization of lipid molecules forming biomembranes. More precisely, the question is how these amphiphiles phase separate under a change of a suitable parameter, like temperature, pressure or membrane environment. The mixture may undergo a lateral or transversal phase separations. This essentially depends on two principal factors, which are the structure (length of hydrocarbon chains of lipid molecules and the curvature asymmetry of membranes. When the former dominates, a lateral separation is then expected. In contrary, for those biomembranes of high curvature asymmetry, a vertical separation is rather observed. We examine the problem from a static (phase diagrams and kinetics (relaxation in time point of view. Finally, the discussion is also extended to the phase separation between lipid molecules and cholesterol in biomembranes (formation of rafts, between phospholipids and grafted polymers on liposomes, or between surfactant and its co-surfactant in bilayer systems.

  17. Photodissociation and excitation of interstellar molecules

    Apart from a rather long introduction containing some elementary astrophysics, quantum chemistry and spectroscopy and an incomplete, historical review of molecular observations, this thesis is divided into three sections. In part A, a rigorous quantum chemical and dynamical study is made of the photodissociation processes in the OH and HCl molecules. In part B, the cross sections obtained in part A are used in various astrophysical problems such as the study of the abundances of the OH and HCl molecules in interstellar clouds, the use of the OH abundance as a measure of the cosmic ray ionization rate, the lifetime of the OH radical in comets and the abundance of OH in the solar photosphere. Part C discusses the excitation of the C2 molecule under interstellar conditions, its use as a diagnostic probe of the temperature, density and strength of the radiation field in interstellar clouds. Quadrupole moments and oscillator strengths are analyzed. (Auth.)

  18. Single-molecule studies using magnetic traps.

    Lionnet, Timothée; Allemand, Jean-François; Revyakin, Andrey; Strick, Terence R; Saleh, Omar A; Bensimon, David; Croquette, Vincent

    2012-01-01

    In recent years, techniques have been developed to study and manipulate single molecules of DNA and other biopolymers. In one such technique, the magnetic trap, a single DNA molecule is bound at one end to a glass surface and at the other to a magnetic microbead. Small magnets, whose position and rotation can be controlled, pull on and rotate the microbead. This provides a simple method to stretch and twist the molecule. The system allows one to apply and measure forces ranging from 10(-3) to >100 pN. In contrast to other techniques, the force measurement is absolute and does not require calibration of the sensor. In this article, we describe the principle of the magnetic trap, as well as its use in the measurement of the elastic properties of DNA and the study of DNA-protein interactions. PMID:22194259

  19. Protein Scaffolding for Small Molecule Catalysts

    Baker, David [Univ. of Washington, Seattle, WA (United States)

    2014-09-14

    We aim to design hybrid catalysts for energy production and storage that combine the high specificity, affinity, and tunability of proteins with the potent chemical reactivities of small organometallic molecules. The widely used Rosetta and RosettaDesign methodologies will be extended to model novel protein / small molecule catalysts in which one or many small molecule active centers are supported and coordinated by protein scaffolding. The promise of such hybrid molecular systems will be demonstrated with the nickel-phosphine hydrogenase of DuBois et. al.We will enhance the hydrogenase activity of the catalyst by designing protein scaffolds that incorporate proton relays and systematically modulate the local environment of the catalyticcenter. In collaboration with DuBois and Shaw, the designs will be experimentally synthesized and characterized.

  20. Single Molecule Sensitive FRET in Attoliter Droplets

    Milas, Peker; Gamari, Ben D; Goldner, Lori S

    2013-01-01

    Single molecular-pair fluorescence resonance energy transfer (spFRET) has become an cross-disciplinary tool for understanding molecular folding and interactions. While providing detailed information about the individual members of a molecular ensemble, this technique is always limited by fluorophore brightness and stability. In the case of diffusing molecules, the experiment is further limited by the number of photons that can be collected during the time it takes for a molecule to diffuse across the detection volume. To maximize the number of photons it is common to either increase the detection volume at the expense of increased background, or increase the diffusion time by adding glycerol or sucrose to increase viscosity. Here we demonstrate that FRET from attoliter volume (100 nm radius) aqueous droplets in perfluorinated oil has significantly higher signal-to-noise and a much wider dynamic range than FRET from molecules diffusing in solution. However, our measurements also reveal a droplet environment th...

  1. Multiphoton processes in isolated atoms and molecules

    The theory of coherent excitation of a multilevel quantum mechanical system is developed. Damping of the system is taken into account by the use of a density matrix formalism. General properties of the wave function and/or the density matrix are discussed. The physical implications for the behavior of the system are described, together with possible applications of the formalism, including the infrared multiphoton excitation of molecules, and optical pumping in alkali atoms. Experimental results are presented on the infrared multiphoton dissociation of molecules, followed by a discussion of the general features of this process. The experimental results were obtained using a crossed laser and molecular beam method, and the emphasis is on determining the properties of the dissociating molecule and the dissociation products. The dissociation process is shown to be described very well by the standard statistical theory (RRKM theory) of unimolecular reactions, a brief presentation of which is also included

  2. Observational astrochemistry: The quest for interstellar molecules

    Guélin M.

    2012-01-01

    Full Text Available Over 160 molecular species, not counting isotopologues, have been identified in circumstellar envelopes and interstellar clouds. These species have revealed a wealth of familiar, as much as exotic molecules and in complex organic (and silicon compounds, that was fully unexpected in view of the harshness of surrounding conditions: vanishingly low densities, extreme temperatures and intense embedding UV radiation. They illustrate the diversity of astrochemistry and show robust prebiotic molecules may be. In this lecture, we review the quest for interstellar molecules and show how tributary it is from theoretical ideas and technology developments. A. A. Penzias, who discovered interstellar CO and the 2.7 K Cosmic Background radiation, used to joke that astronomical research is easy: the great questions have largely been formulated; one only has to wait until technological progress makes it possible to answer.

  3. High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients.

    Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

    2015-08-01

    Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. PMID:26126624

  4. High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients

    Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

    2015-01-01

    Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. PMID:26126624

  5. A Nonvolatile Plasmonic Switch Employing Photochromic Molecules

    We demonstrate a surface plasmon-polariton (SPP) waveguide all-optical switch that combines the unique physical properties of small molecules and metallic (plasmonic) nanostructures. The switch consists of a pair of gratings defined in an aluminum film coated with a 65 nm thick layer of photochromic (PC) molecules. The first grating couples a signal beam consisting of free space photons to SPPs that interact effectively with the PC molecules. These molecules can reversibly be switched between transparent and absorbing states using a free space optical pump. In the transparent (signal 'on') state, the SPPs freely propagate through the molecular layer, and in the absorbing (signal 'off') state, the SPPs are strongly attenuated. The second grating serves to decouple the SPPs back into a free space optical beam, enabling measurement of the modulated signal with a far-field detector. In a preliminary study, the switching behavior of the PC molecules themselves was confirmed and quantified by surface plasmon resonance spectroscopy. The excellent (16%) overlap of the SPP mode profile with the thin layer of switching molecules enabled efficient switching with power densities of ∼6.0 mW/cm2 in 1.5 (micro)m x 8 (micro) m devices, resulting in plasmonic switching powers of 0.72 nW per device. Calculations further showed that modulation depths in access of 20 dB can easily be attained in optimized designs. The quantitative experimental and theoretical analysis of the nonvolatile switching behavior in this letter guides the design of future nanoscale optically or electrically pumped optical switches.

  6. Small Molecule Subgraph Detector (SMSD toolkit

    Rahman Syed

    2009-08-01

    Full Text Available Abstract Background Finding one small molecule (query in a large target library is a challenging task in computational chemistry. Although several heuristic approaches are available using fragment-based chemical similarity searches, they fail to identify exact atom-bond equivalence between the query and target molecules and thus cannot be applied to complex chemical similarity searches, such as searching a complete or partial metabolic pathway. In this paper we present a new Maximum Common Subgraph (MCS tool: SMSD (Small Molecule Subgraph Detector to overcome the issues with current heuristic approaches to small molecule similarity searches. The MCS search implemented in SMSD incorporates chemical knowledge (atom type match with bond sensitive and insensitive information while searching molecular similarity. We also propose a novel method by which solutions obtained by each MCS run can be ranked using chemical filters such as stereochemistry, bond energy, etc. Results In order to benchmark and test the tool, we performed a 50,000 pair-wise comparison between KEGG ligands and PDB HET Group atoms. In both cases the SMSD was shown to be more efficient than the widely used MCS module implemented in the Chemistry Development Kit (CDK in generating MCS solutions from our test cases. Conclusion Presently this tool can be applied to various areas of bioinformatics and chemo-informatics for finding exhaustive MCS matches. For example, it can be used to analyse metabolic networks by mapping the atoms between reactants and products involved in reactions. It can also be used to detect the MCS/substructure searches in small molecules reported by metabolome experiments, as well as in the screening of drug-like compounds with similar substructures. Thus, we present a robust tool that can be used for multiple applications, including the discovery of new drug molecules. This tool is freely available on http://www.ebi.ac.uk/thornton-srv/software/SMSD/

  7. A toy model for a diatomic molecule

    Hecker Denschlag, Johannes

    2016-08-01

    We introduce a toy model for a diatomic molecule which is based on coupling electronic and nuclear spins to a rigid rotor. Despite its simplicity, the model can be used scientifically to analyze and understand complex molecular hyperfine spectra. In addition, the model has educational value as a number of fundamental symmetries and conservation laws of the molecule can be studied. Because of its simple structure, the model can be readily implemented as a computer program with comparatively short computing times on the order of a few seconds.

  8. Relativistic Scott correction for atoms and molecules

    Solovej, Jan Philip; Sørensen, Thomas Østergaard; Spitzer, Wolfgang Ludwig

    2010-01-01

    We prove the first correction to the leading Thomas-Fermi energy for the ground state energy of atoms and molecules in a model where the kinetic energy of the electrons is treated relativistically. The leading Thomas-Fermi energy, established in [25], as well as the correction given here, are of...... semiclassical nature. Our result on atoms and molecules is proved from a general semiclassical estimate for relativistic operators with potentials with Coulomb-like singularities. This semiclassical estimate is obtained using the coherent state calculus introduced in [36]. The paper contains a unified treatment...

  9. Allosteric small-molecule kinase inhibitors

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of various human diseases, especially cancers. While the majority of approved and developed preclinical small-molecule inhibitors are characterized as type I or type II inhibitors that target the ATP......-binding pocket of kinases, the remarkable sequential and structural similarity among ATP pockets renders the selective inhibition of kinases a daunting challenge. Therefore, targeting allosteric pockets of kinases outside the highly conversed ATP pocket has been proposed as a promising alternative to overcome...

  10. Chemical activation of molecules during coordination

    Activation processes of N2, O2, NO molecules in transition metal complexes and electron reconstructions of coordination sphere of compounds, related with it, were considered on tha basis of single-parameter approximation of vibronic activation theory. A special attention is paid to CO molecule activation in carbonyl complexes of transition metals (V, Nb, Mo, W, Tc, Re, Ru and others) and lanthanides. The effect of metal oxidation degree, the nature of metal and ligand, complex structure on chemical activation processes is analyzed

  11. Organic- and molecule-based magnets

    Joel S Miller

    2006-07-01

    The discovery of organic- and molecule-based magnets has led to design and synthesis of several families with magnetic ordering temperatures as high as ∼ 125° C. Examples of soft and hard magnets with coercivities as high as 27 kOe have also been reported. Examples from our laboratory of organic-based magnets using the tetracya- noethylene radical anion, [TCNE]$^{\\bullet -}$, are discussed. In addition, several molecule-based magnets based on Prussian Blue structured materials as well as dicyanamide are discussed.

  12. Collisional Transitions in Interstellar Asymmetric Top Molecules

    Chandra, Suresh

    2012-07-01

    For the study of a molecule in interstellar space or in circumstellar envelopes of an evolved star, one has to deal with a multi-level system in the molecule. These levels are connected through radiative as well as collisional transitions. The NLTE effects in a molecule come in the picture only when collisional transitions are present. Computation of collisional rates is quite cumbersome task. Besides emission and absorption, two anomalous phenomena: (i) MASER action and (ii) Anomalous absorption (Absorption against the CMB) are shown by some molecules in interstellar space. Both of these phenomena are good examples of NLTE prevailing in the interstellar space and circumstellar envelopes of evolved stars. In the present talk, we shall discuss about the collisional transitions between rotational levels in a molecule. The collisional rate coefficients for the rotational transition J τ → J' τ' at the kinetic temperature T, averaged over the Maxwellian distribution are C(J τ → J' τ'|T) = \\Big(\\frac{8 k T}{π μ}\\Big)^{1/2} \\Big(\\frac{1}{k T}\\Big)^2 \\int_0^\\infty σ (J τ → J' τ'|E) E {e}^{-E/kT} {d} E where μ is the reduced mass of the system and the cross section σ(J τ → J' τ'|E) for the transition is \\begin{eqnarray} σ (J τ → J' τ'|E) = \\sum_{L M M'} S(J, τ, J', τ'|L, M, M') q(L, M, M'|E) The q(L, M, M'|E) are the parameters which can be obtained from the software MOLSCAT. The spectroscopic coefficients, S ( J, τ, J', τ'|L, M, M'), depend on the wave-functions of the molecules and on the angular momentum coupling factors: S(J, τ, J', τ'|L, M, M') = \\sum_{p, p', q, q'} g^p_{J τ} g^q_{J τ} g^{p'}_{J' τ'} g^{q'}_{J' τ'} \\big \\big Here, \\big represents the Clebsch-Gorden coefficient. The g-coefficients can be obtained from laboratory analysis of the molecule and the parameters q(L, M, M'|E) can be obtained with the help of the software MOLSCAT for a known interaction potential. As an example, we shall discuss collisional

  13. Single-molecule electrophoresis. Final report

    Castro, A.; Shera, E.B.

    1996-05-22

    A novel method for the detection and identification of single molecules in solution has been devised, computer-simulated, and experimentally achieved. The technique involves the determination of electrophoretic velocities by measuring the time required by individual molecules to travel a fixed distance between two laser beams. Computer simulations of the process were performed beforehand in order to estimate the experimental feasibility of the method, and to determine the optimum values for the various experimental parameters. Examples of the use of the technique for the ultrasensitive detection and identification of rhodamine-6G, a mixture of DNA restriction fragments, and a mixture of proteins in aqueous solution are presented.

  14. Vibrational spectroscopy of polar molecules with superradiance

    Lin, Guin-Dar

    2013-01-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy when a high optical-depth (OD) sample is studied. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to the speed-up of decay process. We compare our calculation to recent work [Deiglmayr et al., Eur. Phys. J. D 65, 99 (2011)] and find very good agreement, suggesting that superradiant effects need to be included in a wide variety of ultracold molecule setups including vibrational and rotational states.

  15. Matter-wave interferometer for large molecules

    Brezger, B; Uttenthaler, S; Petschinka, J; Arndt, M; Zeilinger, Anton

    2002-01-01

    We demonstrate a near-field Talbot-Lau interferometer for C-70 fullerene molecules. Such interferometers are particularly suitable for larger masses. Using three free-standing gold gratings of one micrometer period and a transversally incoherent but velocity-selected molecular beam, we achieve an interference fringe visibility of 40 % with high count rate. Both the high visibility and its velocity dependence are in good agreement with a quantum simulation that takes into account the van der Waals interaction of the molecules with the gratings and are in striking contrast to a classical moire model.

  16. Photoassociative production of ultracold heteronuclear ytterbium molecules

    Borkowski, Mateusz; Ciurylo, Roman [Instytut Fizyki, Uniwersytet Mikolaja Kopernika, ul. Grudziadzka 5/7, PL-87-100 Torun (Poland); Julienne, Paul S. [Joint Quantum Institute, National Institute of Standards and Technology and the University of Maryland, 100 Bureau Drive, Stop 8423, Gaithersburg, Maryland 20899-8423 (United States); Yamazaki, Rekishu; Takahashi, Yoshiro [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); CREST, JST, 4-1-8 Honcho Kawaguchi, Saitama 332-0012 (Japan); Hara, Hideaki; Taie, Shintaro; Sugawa, Seiji; Takasu, Yosuke [Department of Physics, Graduate School of Science, Kyoto University, Kyoto 606-8502 (Japan); Enomoto, Katsunari [Department of Physics, University of Toyama, Toyama 930-8555 (Japan)

    2011-09-15

    We report observations of photoassociation (PA) spectra near the intercombination line in isotopic mixtures of ultracold ytterbium gases. Several heteronuclear bound states have been found for the excited {sup 170}Yb{sup 174}Yb and {sup 174}Yb{sup 176}Yb molecules. We develop a single-channel mass-scaled interaction model for the excited state molecule which well reproduces the measured bound state energies. This is an important step toward optical control of interactions in mixtures of ultracold ytterbium gases using heteronuclear optical Feshbach resonances. The model developed is applicable in collisions of other similar systems, such as cadmium and mercury.

  17. Extracellular Molecules Involved in Cancer Cell Invasion

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  18. Scanning probe microscopy characterisation of immobilised enzyme molecules on a biosensor surface: visualisation of individual molecules

    JOE G. SHAPTER

    2004-02-01

    Full Text Available Scanning probe microscopy techniques were used to study immobilised enzyme molecules of glucose oxidase (GOD on a biosensor surface. The study was carried out in order to optimise atomic force microscopy (AFM imaging and reveal the molecular resolution of individual GOD molecules. Chemically modified AFM tips and the light tapping mode were found to be the optimal conditions for imaging soft biomolecules such as GOD. The information obtained from the AFM images included spatial distribution and organization of the enzyme molecules on the surface, surface coverage and shape, size and orientation of individual molecules. Two typical shapes of GOD molecules were found, spherical and butterfly, which are in accordance with the shapes obtained from scanning tunnelling microscopy (STM images. Using a model of the orientation of the GOD molecules on the surface, these shapes are assigned to the enzyme standing and lying on the surface. After AFM tip deconvolution, the size of the spherical shaped GOD molecules was found to be 12 ± 2.1 nm in diameter, whereas the butterfly shapes were 16.5 ± 3.3 nm ´10.2 ± 2.5 nm. Corresponding STM images showed smaller lateral dimensions of 10 ± 1 nm ´ 6 ± 1 nm and 6.5 ± 1 nm ´ 5 ± 1 nm. The disagreement between these two techniques is attributed to the deformation of the GOD molecules caused by the tapping process.

  19. Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

    Max Greenfeld

    Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

  20. Making More-Complex Molecules Using Superthermal Atom/Molecule Collisions

    Shortt, Brian; Chutjian, Ara; Orient, Otto

    2008-01-01

    A method of making more-complex molecules from simpler ones has emerged as a by-product of an experimental study in outer-space atom/surface collision physics. The subject of the study was the formation of CO2 molecules as a result of impingement of O atoms at controlled kinetic energies upon cold surfaces onto which CO molecules had been adsorbed. In this study, the O/CO system served as a laboratory model, not only for the formation of CO2 but also for the formation of other compounds through impingement of rapidly moving atoms upon molecules adsorbed on such cold interstellar surfaces as those of dust grains or comets. By contributing to the formation of increasingly complex molecules, including organic ones, this study and related other studies may eventually contribute to understanding of the origins of life.

  1. Long-lived dipolar molecules and Feshbach molecules in a 3D optical lattice

    Chotia, Amodsen; Moses, Steven A; Yan, Bo; Covey, Jacob P; Foss-Feig, Michael; Rey, Ana Maria; Jin, Deborah S; Ye, Jun

    2011-01-01

    We have realized long-lived ground-state polar molecules in a 3D optical lattice, with a lifetime of up to 25 s, which is limited only by off-resonant scattering of the trapping light. Starting from a 2D optical lattice, we observe that the lifetime increases dramatically as a small lattice potential is added along the tube-shaped lattice traps. The 3D optical lattice also dramatically increases the lifetime for weakly bound Feshbach molecules. For a pure gas of Feshbach molecules, we observe a lifetime of >20 s in a 3D optical lattice; this represents a 100-fold improvement over previous results. This lifetime is also limited by off-resonant scattering, the rate of which is related to the size of the Feshbach molecule. Individually trapped Feshbach molecules in the 3D lattice can be converted to pairs of K and Rb atoms and back with nearly 100% efficiency.

  2. Self and directed assembly: people and molecules.

    James, Tony D

    2016-01-01

    Self-assembly and directed-assembly are two very important aspects of supramolecular chemistry. As a young postgraduate student working in Canada with Tom Fyles my introduction to Supramolecular Chemistry was through the self-assembly of phospholipid membranes to form vesicles for which we were developing unimolecular and self-assembling transporter molecules. The next stage of my development as a scientist was in Japan with Seiji Shinkai where in a "Eureka" moment, the boronic acid templating unit (directed-assembly) of Wulff was combined with photoinduced electron transfer systems pioneered by De Silva. The result was a turn-on fluorescence sensor for saccharides; this simple result has continued to fuel my research to the present day. Throughout my career as well as assembling molecules, I have enjoyed bringing together researchers in order to develop collaborative networks. This is where molecules meet people resulting in assemblies worth more than the individual "molecule" or "researcher". My role in developing networks with Japan was rewarded by the award of a Daiwa-Adrian Prize in 2013 and I was recently rewarded for developing networks with China with an Inaugural CASE Prize in 2015. PMID:27340435

  3. Progress in Computational Electron-Molecule Collisions

    Rescigno, Tn

    1997-10-01

    The past few years have witnessed tremendous progress in the development of sophisticated ab initio methods for treating collisions of slow electrons with isolated small molecules. Researchers in this area have benefited greatly from advances in computer technology; indeed, the advent of parallel computers has made it possible to carry out calculations at a level of sophistication inconceivable a decade ago. But bigger and faster computers are only part of the picture. Even with today's computers, the practical need to study electron collisions with the kinds of complex molecules and fragments encountered in real-world plasma processing environments is taxing present methods beyond their current capabilities. Since extrapolation of existing methods to handle increasingly larger targets will ultimately fail as it would require computational resources beyond any imagined, continued progress must also be linked to new theoretical developments. Some of the techniques recently introduced to address these problems will be discussed and illustrated with examples of electron-molecule collision calculations we have carried out on some fairly complex target gases encountered in processing plasmas. Electron-molecule scattering continues to pose many formidable theoretical and computational challenges. I will touch on some of the outstanding open questions.

  4. Uranium-mediated activation of small molecules.

    Arnold, Polly L

    2011-08-28

    Molecular complexes of uranium are capable of activating a range of industrially and economically important small molecules such as CO, CO(2), and N(2); new and often unexpected reactions provide insight into an element that needs to be well-understood if future clean-energy solutions are to involve nuclear power. PMID:21614341

  5. Photoelectron spectroscopy of heavy atoms and molecules

    The importance of relativistic interactions in the photoionization of heavy atoms and molecules has been investigated by the technique of photoelectron spectroscopy. In particular, experiments are reported which illustrate the effects of the spin-orbit interaction in the neutral ground state, final ionic states and continuum states of the photoionization target

  6. Comprehensive Map of Molecules Implicated in Obesity.

    Jaisri Jagannadham

    Full Text Available Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome.

  7. Comprehensive Map of Molecules Implicated in Obesity.

    Jagannadham, Jaisri; Jaiswal, Hitesh Kumar; Agrawal, Stuti; Rawal, Kamal

    2016-01-01

    Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome. PMID:26886906

  8. Orbits in the H2O molecule

    Efstathiou, K; Contopoulos, G

    2001-01-01

    We study the forms of the orbits in a symmetric configuration of a realistic model of the H2O molecule with particular emphasis on the periodic orbits. We use an appropriate Poincare surface of section (PSS) and study the distribution of the orbits on this PSS for various energies. We find both orde

  9. Chiral Sensitivity in Electron-Molecule Interactions

    Dreiling, Joan

    2015-09-01

    All molecular forms of life possess a chiral asymmetry, with amino acids and sugars found respectively in L- and D-enantiomers only. The primordial origin of this enantiomeric excess is unknown. One possible explanation is given by the Vester- Ulbricht hypothesis, which suggests that left-handed electrons present in beta-radiation, produced by parity-violating weak decays, interacted with biological precursors and preferentially destroyed one of the two enantiomers. Experimental tests of this idea have thus far yielded inconclusive results. We show direct evidence for chirally-dependent bond breaking through a dissociative electron attachment (DEA) reaction when spin-polarized electrons are incident on gas-phase chiral molecules. This provides unambiguous evidence for a well-defined, chirally-sensitive destructive molecular process and, as such, circumstantial evidence for the Vester-Ulbricht hypothesis. I will also present the results of our systematic study of the DEA asymmetry for different chiral halocamphor molecules. Three halocamphor molecules were investigated: 3-bromocamphor (C10H15BrO), 3-iodocamphor(C10H15IO), and 10-iodocamphor. The DEA asymmetries collected for bromocamphor and iodocamphor are qualitatively different, suggesting that the atomic number of the heaviest atom in the molecule plays a crucial role in the asymmetric interactions. The DEA asymmetry data for 3- and 10-iodocamphor have the same qualitative behavior, but the 10-iodocamphor asymmetry is about twice as large at the lowest energies investigated, so the location of the heavy atom in the camphor molecule also affects the asymmetries. This work was performed at the University of Nebraska-Lincoln. This project is funded by NSF Grant PHY-1206067.

  10. Electron attachment to the SF6 molecule

    Smirnov, B. M.; Kosarim, A. V.

    2015-09-01

    Various models for transition between electron and nuclear subsystems are compared in the case of electron attachment to the SF6 molecule. Experimental data, including the cross section of electron attachment to this molecule as a function of the electron energy and vibrational temperature, the rate constants of this process in swarm experiments, and the rates of the chemionization process involving Rydberg atoms and the SF6 molecule, are collected and treated. Based on the data and on the resonant character of electron capture into an autodetachment ion state in accordance with the Breit-Wigner formula, we find that intersection of the molecule and negative ion electron terms proceeds above the potential well bottom of the molecule with the barrier height 0.05-0.1 eV, and the transition between these electron terms has both the tunnel and abovebarrier character. The limit of small electron energies e for the electron attachment cross section at room vibrational temperature takes place at ɛ ≪ 2 meV, while in the range 2 meV ≪ ɛ ≪ 80 meV, the cross section is inversely proportional to ɛ. In considering the attachment process as a result of the interaction between the electron and vibrational degrees of freedom, we find the coupling factor f between them to be f = aT at low vibrational temperatures T with a ≈ 3 × 10-4 K-1. The coupling factor is independent of the temperature at T > 400 K.

  11. Molecules for Fluorescence Detection of Specific Chemicals

    Fedor, Steve

    2008-01-01

    A family of fluorescent dye molecules has been developed for use in on-off fluorescence detection of specific chemicals. By themselves, these molecules do not fluoresce. However, when exposed to certain chemical analytes in liquid or vapor forms, they do fluoresce (see figure). These compounds are amenable to fixation on or in a variety of substrates for use in fluorescence-based detection devices: they can be chemically modified to anchor them to porous or non-porous solid supports or can be incorporated into polymer films. Potential applications for these compounds include detection of chemical warfare agents, sensing of acidity or alkalinity, and fluorescent tagging of proteins in pharmaceutical research and development. These molecules could also be exploited for use as two-photon materials for photodynamic therapy in the treatment of certain cancers and other diseases. A molecule in this family consists of a fluorescent core (such as an anthracene or pyrene) attached to two end groups that, when the dye is excited by absorption of light, transfer an electron to the core, thereby quenching the fluorescence. The end groups can be engineered so that they react chemically with certain analytes. Upon reaction, electrons on the end groups are no longer available for transfer to the core and, consequently, the fluorescence from the core is no longer quenched. The chemoselectivity of these molecules can be changed by changing the end groups. For example, aniline end groups afford a capability for sensing acids or acid halides (including those contained in chemical warfare agents). Pyridine or bipyridyl end groups would enable sensing of metal ions. Other chemicals that can be selectively detected through suitable choice of end groups include glucose and proteins. Moreover, the fluorescent cores can be changed to alter light-absorption and -emission characteristics: anthracene cores fluoresce at wavelengths around 500 nm, whereas perylene cores absorb and emit at

  12. Prebiotic molecules and interstellar grain clumps

    It is stated that interstellar molecules detected by radioastronomical techniques in galactic clouds cover a wide range of types and complexities. Amongst the heaviest recently discovered is cyanodiacetylene. There have also been earlier detections of precursors to the simplest amino-acid, glycine and probably detections of polyoxymethylene polymers and co-polymers. A possible identification of organic molecules of even greater complexity is here discussed, together with implications for the commencement of biological activity. The large departures from thermodynamic equilibrium in the interstellar medium and the co-existence of solid grains, molecules, radicals, ions, and uv photons provide conditions that are ideal for production of 'exotic' molecular species. The effect of clumping of dust grains is discussed. The possible spectral identification of highly complex organic species in the interstellar medium is also discussed and reference is made to a property common to a wide class of such molecules, that is, an absorption band centered at 2,200 A. It is tempting to identify this feature with the well-known 2,200 A band of the interstellar extinction curve. It is thought that it may be tentatively concluded that the data so far obtained could be interpreted as independent new chemical evidence of the existence of composite grain clumps in the interstellar medium and in carbonaceous chondrites, and that these grain clumps probably include a significant mass fraction of highly complex organic pre-biotic molecules that could have led to the start and dispersal of biological activity on the Earth and elsewhere in the Galaxy. Processes of natural selection probably also played an important part, particularly in the production of self-replicable peptide chains. The problem of protection of pre-biotic material against external disruptive agencies, such as u/v light, is also discussed. (U.K.)

  13. Handbook of Single-Molecule Biophysics

    Hinterdorfer, Peter

    2009-01-01

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

  14. Is the focus on "molecules" obsolete?

    Whitesides, George M

    2013-01-01

    The technologies developed in analytical chemistry have defined in spectacular detail the properties of molecules. The field now faces enormously important and interesting problems of which molecules are only a part: for example, understanding the nature of life; helping to manage megacities, oceans, and atmospheres; and making health care (especially diagnostics) affordable and relevant. The emergence of these problems involving molecular systems raises the issue of how (and what) analytical chemistry should teach. Historically, it has been essential to chemistry in teaching the science of measurement. As complicated analytical techniques proliferate, it must consider how to balance teaching the uses of sophisticated devices and the fundamentals of analysis and measurement. This review (by an admiring but nonanalytical chemist) sketches the essential role of analytical methods--especially simple ones made up on the spot--in guiding research in new fields, with examples from self-assembled monolayers, soft lithography, paper diagnostics, and self-assembly; and suggests issues in teaching. PMID:23772657

  15. Is the Focus on ``Molecules'' Obsolete?

    Whitesides, George M.

    2013-06-01

    The technologies developed in analytical chemistry have defined in spectacular detail the properties of molecules. The field now faces enormously important and interesting problems of which molecules are only a part: for example, understanding the nature of life; helping to manage megacities, oceans, and atmospheres; and making health care (especially diagnostics) affordable and relevant. The emergence of these problems involving molecular systems raises the issue of how (and what) analytical chemistry should teach. Historically, it has been essential to chemistry in teaching the science of measurement. As complicated analytical techniques proliferate, it must consider how to balance teaching the uses of sophisticated devices and the fundamentals of analysis and measurement. This review (by an admiring but nonanalytical chemist) sketches the essential role of analytical methods—especially simple ones made up on the spot—in guiding research in new fields, with examples from self-assembled monolayers, soft lithography, paper diagnostics, and self-assembly; and suggests issues in teaching.

  16. Exploring $X(5568)$ as a meson molecule

    Agaev, S S; Sundu, H

    2016-01-01

    The parameters, i.e. the mass and decay constant of the exotic $X_b(5568)$ state newly observed by D0 Collaboration, as well as the decay width of the process $X_b \\to B_s^{0}\\pi^{+}$ are explored using $B\\overline{K}$ molecule assumption on its structure. Computational methods employed here encompass QCD two-point and light-cone sum rules, latter being considered in the soft-meson approximation. The obtained results are compared with the data of the D0 Collaboration, as well as with the predictions of the diquark-antidiquark model. This comparison strengthens the diquark-antidiquark picture for the $X_b(5568)$ state rather than a meson molecule structure.

  17. Imaging Genetic Molecules At Atomic Resolution

    Coles, L. Stephen

    1993-01-01

    Proposed method of imaging informational polymeric biological molecules at atomic resolution enables determination of sequences of component monomers about 10 to the 3rd power to 10 to the 4th power times as fast as conventional methods do. Accelerates research on genetic structures of animals and plants. Also contributes significantly to imaging processes like scanning electron microscopy (SEM), atomic-force microscopy (AFM), and scanning tunneling microscopy (STM) in cases in which necessary to locate or identify small specimens on relatively large backgrounds and subtract background images to obtain images of specimens in isolation. V-grooves on silicon wafer laid out in square pattern, intersections of which marked to identify coordinates. Specimen molecules held in grooves for reproducible positioning and scanning by AFM or STM.

  18. Photochemical dynamics of surface oriented molecules

    The period 8/01/91-7/31/92 is the first year of a new project titled ''Photochemical Dynamics of Surface Oriented Molecules'', initiated with DOE Support. The main objective of this project is to understand the dynamics of elementary chemical reactions by studying photochemical dynamics of surface-oriented molecules. In addition, the mechanisms of photon-surface interactions need to be elucidated. The strategy is to carry out experiments to measure the translational energy distribution, as a function of the angle from the surface normal, of the photoproducts by time-of-flight (TOF) technique by varying the photon wavelength, intensity, polarization, and pulse duration. By choosing adsorbates with different bonding configuration, the effects of adsorbate orientation on surface photochemical dynamics can be studied

  19. - Fourier Transform Infrared Spectroscopy of Small - Molecules

    Li, G.; Bernath, P. F.

    2011-06-01

    A series of small boron-containing molecules were synthesized in the gas phase using a tube furnace. High-resolution spectra of these species were recorded in either emission or absorption in the mid-infrared region using a Bruker IFS-125HR spectrometer. Our observations contain vibration-rotation bands of BO, the V1 and V3 bands of HBO, the V1 and V3 bands of HBS, the V1 band of FBO, and the V1 band of HBF2. The vibrational bands of HOBO, BF2OH and other boron-containing molecules may also be present. Ab initio calculations were performed at the MRCI level to assist in the vibrational assignments. Preliminary assignments of the spectra for these species will be reported.

  20. Interstellar molecules - Formation in solar nebulae

    Anders, E.

    1973-01-01

    Herbig's (1970) hypothesis that solar nebulae might be the principal source of interstellar grains and molecules is investigated. The investigation includes the determination of physical and chemical conditions in the early solar system. The production of organic compounds in the solar nebula is studied, and the compounds in meteorites are compared with those obtained in Miller-Urey and Fischer-Tropsch-type (FTT) reactions, taking into consideration aliphatic hydrocarbons, aromatic hydrocarbons, purines, pyrimidines, amino acids, porphyrins, and aspects of carbon-isotope fractionation. It is found that FTT reactions account reasonably well for all well-established features of organic matter in meteorites investigated. The distribution of compounds produced by FTT reactions is compared with the distribution of interstellar molecules. Biological implications of the results are considered.

  1. Chirally-sensitive electron-molecule interactions

    Dreiling, J. M.; Gay, T. J.

    2015-09-01

    All molecular forms of life have chemically-specific handedness. However, the origin of these asymmetries is not understood. A possible explanation was suggested by Vester and Ulbricht immediately following the discovery of parity violation in 1957: chiral beta radiation in cosmic rays may have preferentially destroyed one enantiomeric form of various biological precursors. In the experiments reported here, we observed chiral specificity in two electron- molecule interactions: quasi-elastic scattering and dissociative electron attachment. Using low- energy longitudinally spin-polarized (chiral) electrons as substitutes for beta rays, we found that chiral bromocamphor molecules exhibited both a transmission and dissociative electron attachment rate that depended on their handedness for a given direction of incident electron spin. Consequently, these results, especially those with dissociative electron attachment, connect the universal chiral asymmetry of the weak force with a molecular breakup process, thereby demonstrating the viability of the Vester-Ulbricht hypothesis.

  2. Photoassociative Excitation Spectroscopy of Excimer Molecules

    Jones, Ronald Blake

    Laser excitation spectroscopy of transitions having dissociative ground states was explored as a tool for the study of excimer molecules. Since the repulsive nature of the ground state constrains collision pairs to large internuclear transitions, bound >=ts free excitation spectra contain more structure than the bound to free fluorescence spectra for the same molecules, therefore containing more information about the potential surfaces. Unique properties of the photoassociative excitation spectroscopy technique are described which allow the dependence of the dipole transition moment on the internuclear separation (mu (R)) to be extracted in a very direct manner. Excitation spectra are presented for the B >=ts X transitions of KrF and XeI for the wavelength (lambda) interval 206 nm KrI are given. This work required the development of a tunable VUV source, which is described.

  3. Modelling proton transfer in water molecule chains

    Korzhimanov, Artem; Shutova, Tatiana; Samuelsson, Goran

    2011-01-01

    The process of protons transport in molecular water chains is of fundamental interest for many biological systems. Although many features of such systems can be analyzed using large-scale computational modeling, other features are better understood in terms of simplified model problems. Here we have tested, analytically and numerically, a model describing the classical proton hopping process in molecular water chains. In order to capture the main features of the proton hopping process in such molecular chains, we use a simplified model for our analysis. In particular, our discrete model describes a 1D chain of water molecules situated in an external protein channel structure, and each water molecule is allowed to oscillate around its equilibrium point in this system, while the protons are allowed to move along the line of neighboring oxygen atoms. The occurrence and properties of nonlinear solitary transport structures, allowing for much faster proton transport, are discussed, and the possible implications of...

  4. Photoluminescence of a quantum-dot molecule

    The coherent coupling of quantum dots is a sensitive indicator of the energy and phase relaxation processes taking place in the nanostructure components. We formulate a theory of low-temperature, stationary photoluminescence from a quantum-dot molecule composed of two spherical quantum dots whose electronic subsystems are resonantly coupled via the Coulomb interaction. We show that the coupling leads to the hybridization of the first excited states of the quantum dots, manifesting itself as a pair of photoluminescence peaks with intensities and spectral positions strongly dependent on the geometric, material, and relaxation parameters of the quantum-dot molecule. These parameters are explicitly contained in the analytical expression for the photoluminescence differential cross section derived in the paper. The developed theory and expression obtained are essential in interpreting and analyzing spectroscopic data on the secondary emission of coherently coupled quantum systems

  5. Atomic Rydberg Reservoirs for Polar Molecules

    Zhao, Bo; Pupillo, Guido; Zoller, Peter

    2011-01-01

    We discuss laser dressed dipolar and Van der Waals interactions between atoms and polar molecules, so that a cold atomic gas with laser admixed Rydberg levels acts as a designed reservoir for both elastic and inelastic collisional processes. The elastic scattering channel is characterized by large elastic scattering cross sections and repulsive shields to protect from close encounter collisions. In addition, we discuss a dissipative (inelastic) collision where a spontaneously emitted photon carries away (kinetic) energy of the collision partners, thus providing a significant energy loss in a single collision. This leads to the scenario of rapid thermalization and cooling of a molecule in the mK down to the \\mu K regime by cold atoms.

  6. Artifacts in single-molecule localization microscopy.

    Burgert, Anne; Letschert, Sebastian; Doose, Sören; Sauer, Markus

    2015-08-01

    Single-molecule localization microscopy provides subdiffraction resolution images with virtually molecular resolution. Through the availability of commercial instruments and open-source reconstruction software, achieving super resolution is now public domain. However, despite its conceptual simplicity, localization microscopy remains prone to user errors. Using direct stochastic optical reconstruction microscopy, we investigate the impact of irradiation intensity, label density and photoswitching behavior on the distribution of membrane proteins in reconstructed super-resolution images. We demonstrate that high emitter densities in combination with inappropriate photoswitching rates give rise to the appearance of artificial membrane clusters. Especially, two-dimensional imaging of intrinsically three-dimensional membrane structures like microvilli, filopodia, overlapping membranes and vesicles with high local emitter densities is prone to generate artifacts. To judge the quality and reliability of super-resolution images, the single-molecule movies recorded to reconstruct the images have to be carefully investigated especially when investigating membrane organization and cluster analysis. PMID:26138928

  7. Vibrational and coherence dynamics of molecules

    Zhang, Zhedong

    2015-01-01

    We {\\it analytically} investigate the population and coherence dynamics and relaxations in the vibrational energy transport in molecules. The corresponding two time scales $t_1$ and $t_2$ are explored. Coherence-population entanglement is found to considerably promote the time scale $t_2$ for dephasing and the amplitude of coherence. This is attributed to the suppression of the environment-induced drift force by coherence. Moreover the population imbalance (magnetization) is shown to be significantly amplified with the coherence-population entanglement. Contrary to the previous studies, we exactly elucidate a coherent process by showing $t_1molecules dissolved in D$_2$O. Finally we explore the coherence effect on the heat current at the macroscopic level.

  8. Multichannel quantum defect theory for ro-vibrational transitions in ultracold molecule-molecule collisions

    Hazra, Jisha; Ruzic, Brandon P.; Balakrishnan, N.; Bohn, John L.

    2014-01-01

    Multichannel quantum defect theory (MQDT) has been widely applied to resonant and non-resonant scattering in a variety of atomic collision processes. In recent years, the method has been applied to cold collisions with considerable success, and it has proven to be a computationally viable alternative to full-close coupling (CC) calculations when spin, hyperfine and external field effects are included. In this paper, we describe a hybrid approach for molecule-molecule scattering that includes ...

  9. Femtosecond dynamics of molecules and clusters

    Baumert, Thomas,; Thalweiser, Rainer; Weiss, V.; Wiedenmann, Ernst; Gerber, Gustav

    1994-01-01

    The real-time dynamics of multiphoton ionization and fragmentation of molecules - Na_2 , Na_3 - and clusters - Na_n, Hg_n - has been studied in molecular beam experiments employing ion and electron spectroscopy together with femtosecond pump-probe techniques. Experiments with Na_2 and Na_3 reveal unexpected features of the dynamics of the absorption of several photons as seen in the one- and three dimensional vibrational wave packet motion in different potential surfaces and...

  10. Excitonic molecules in type-II superlattices

    Tsuchiya, T.; Katayama, S.; Ando, T.

    1998-01-01

    Excitonic molecules in GaAs/AlAs type-II superlattices are numerically investigated. In spite of large difference of electronic structures between type-II and type-I superlattices, variational calculations show that the configuration of particles is similar to that in type-I superlattices. This is because the layer width is smaller than the extent of excitonic wavefunctions in the direction parallel to the layers in the present superlattices.

  11. Isatin, a versatile molecule: studies in Brazil

    Silva, Barbara, E-mail: barbara.iq@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2013-05-15

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

  12. Field-free orientation of molecules

    Machholm, Mette; Henriksen, Niels Engholm

    2001-01-01

    The excitation of angular motion, in particular, the creation of a wave packet in the angular degrees of freedom via short-pulse, off-resonant excitation with respect to rotational transitions, was examined. The key result was that field-free time-dependent orientation for a molecule like LiH can...... be generated after the turn-off of a state-of-the-art electromagnetic half-cycle pulse....

  13. Rotations and Vibrations of trinuclear molecules

    A model describing the rotations and vibrations of trinuclear molecules is presented. The treatment is made in the spirit of Bohr-Mottelson collective model of nucleus. The two-body interactions between the composing clusters are calculated assuming the density independent M3Y forces, supplemented by a phenomenological repulsive component. Under simplifying assumptions, such as linear chain quasi-equilibrium configuration and freezing of the contact point between the light cluster and the heavy clusters, analytical solutions are available. (authors)

  14. Development of proneurogenic, neuroprotective small molecules

    MacMillan, Karen S.; Naidoo, Jacinth; Liang, Jue; Melito, Lisa; Williams, Noelle S.; Morlock, Lorraine; Huntington, Paula J.; Estill, Sandi Jo; Longgood, Jamie; Becker, Ginger L.; McKnight, Steven L.; Pieper, Andrew A.; De Brabander, Jef K.; Ready, Joseph M.

    2011-01-01

    Degeneration of the hippocampus is associated with Alzheimer’s disease, and occurs very early in the progression of the disease. Current options for treating the cognitive symptoms associated with Alzheimer’s are inadequate, giving urgency to the search for novel therapeutic strategies. Pharmacologic agents that safely enhance hippocampal neurogenesis may provide new therapeutic approaches. We discovered the first synthetic molecule, named P7C3, which protects newborn neurons from apopotic ce...

  15. Small Molecule Library Synthesis Using Segmented Flow

    Thompson, Christina M.; Djuric, Stevan W.; Cross, Jeffrey L.; Irini Akritopoulou-Zanze; Poole, Jennifer L.

    2011-01-01

    Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing l...

  16. Femtosecond Photodissociation of Molecules Facilitated by Noise

    Singh, Kamal P.; Kenfack, Anatole; Rost, Jan M

    2007-01-01

    We investigate the dynamics of diatomic molecules subjected to both a femtosecond mid-infrared laser pulse and Gaussian white noise. The stochastic Schr\\"odinger equation with a Morse potential is used to describe the molecular vibrations under noise and the laser pulse. For weak laser intensity, well below the dissociation threshold, it is shown that one can find an optimum amount of noise that leads to a dramatic enhancement of the dissociation probability. The enhancement landscape which i...

  17. Colloquium: Quantum interference of clusters and molecules

    Hornberger, Klaus; Gerlich, Stefan; Haslinger, Philipp; Nimmrichter, Stefan; Arndt, Markus

    2011-01-01

    We review recent progress and future prospects of matter wave interferometry with complex organic molecules and inorganic clusters. Three variants of a near-field interference effect, based on diffraction by material nanostructures, at optical phase gratings, and at ionizing laser fields are considered. We discuss the theoretical concepts underlying these experiments and the experimental challenges. This includes optimizing interferometer designs as well as understanding the role of decoheren...

  18. Stepwise oscillatory circuits of a DNA molecule

    Xu, Kunming

    2009-01-01

    A DNA molecule is characterized by a stepwise oscillatory circuit where every base pair is a capacitor, every phosphate bridge is an inductance, and every deoxyribose is a charge router. The circuitry accounts for DNA conductivity through both short and long distances in good agreement with experimental evidence that has led to the identification of the so-called super-exchange and multiple-step hopping mechanisms. However, in contrast to the haphazard hopping and super-exchanging events, the...

  19. Single molecules as whispering galleries for electrons

    Reecht, G.; Bulou, H.; Schull, G.; Scheurer, F.

    2016-04-01

    Whispering gallery modes, well-known for acoustic and optical waves, have been shown recently for electrons in molecules on surfaces. The existence of such waves opens new possibilities for nanoelectronic devices. Here we propose a simple analytical textbook model which allows the main characteristic features of such electronic waves to be understood. The model is illustrated by two- and three-dimensional experimental situations.

  20. Imaging Cold Molecules on a Chip

    Marx, S.; Adu Smith, D.; Abel, M.; Zehentbauer, T.; Meijer, G.J.M.; Santambrogio, G.

    2013-01-01

    We present the integrated imaging of cold molecules in a microchip environment. The on-chip detection is based on resonance-enhanced multiphoton ionization, which is quantum state selective and generally applicable. We demonstrate and characterize time-resolved spatial imaging and subsequently use it to analyze the effect of a phase-space manipulation sequence aimed at compressing the velocity distribution of a molecular ensemble with a view to future high-resolution spectroscopic studies. Th...

  1. Bringing Molecules Back into Molecular Evolution

    Wilke, Claus O.

    2012-01-01

    Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models a...

  2. TBD Resistence mechanisms and small molecules

    Corneila Zumbrunn

    2015-01-01

    The bacterial topoisomerases Gyrase and Topoisomerase IV are well validated targets in antibiotic research and discovery. Fluoroquinolones (eg. Ciprofloxacin) are potent inhibitors of these targets and are an important weapon in the battle against infections. Unfortunately their utility has lately been limited due to emerging resistance. Over the last years several companies have discovered molecules that inhibit topoisomerases by a novel mode of action and are therefore devoid of cross-resis...

  3. Sisyphus Cooling of Electrically Trapped Polyatomic Molecules

    Zeppenfeld, M.; Englert, B. G. U.; Glöckner, R.; Prehn, A; Mielenz, M; Sommer, C.; van Buuren, L. D.; Motsch, M.; Rempe, G.

    2012-01-01

    The rich internal structure and long-range dipole-dipole interactions establish polar molecules as unique instruments for quantum-controlled applications and fundamental investigations. Their potential fully unfolds at ultracold temperatures, where a plethora of effects is predicted in many-body physics, quantum information science, ultracold chemistry, and physics beyond the standard model. These objectives have inspired the development of a wide range of methods to produce cold molecular en...

  4. Vibrational spectroscopy of polar molecules with superradiance

    Lin, Guin-Dar; Yelin, Susanne F.

    2013-01-01

    We investigate cooperative phenomena and superradiance for vibrational transitions in polar molecule spectroscopy when a high optical-depth (OD) sample is studied. Such cooperativity comes from the build-up of inter-particle coherence through dipole-dipole interactions and leads to the speed-up of decay process. We compare our calculation to recent work [Deiglmayr et al., Eur. Phys. J. D 65, 99 (2011)] and find very good agreement, suggesting that superradiant effects need to be included in a...

  5. Caspr2 : possible synaptogenic cell adhesion molecule

    Do, Trinh Thuy

    2011-01-01

    Synapses are crucial for communication among neurons in the central nervous system. Contactin-associated protein- like 2 (Caspr2) is a neuronal protein that is a member of the neurexin superfamily and is found in the juxtaparanodal regions of myelinated axons. Caspr2 has also been found in synapses and therefore is also thought to function as a cell adhesion molecule. As such, it should also induce synaptogenesis in vitro similar to the interaction between neurexins (located presynaptically) ...

  6. Small Talk: Children's Everyday `Molecule' Ideas

    Jakab, Cheryl

    2013-08-01

    This paper reports on 6-11-year-old children's `sayings and doings' (Harré 2002) as they explore molecule artefacts in dialectical-interactive teaching interviews (Fleer, Cultural Studies of Science Education 3:781-786, 2008; Hedegaard et al. 2008). This sociocultural study was designed to explore children's everyday awareness of and meaning-making with cultural molecular artefacts. Our everyday world is populated with an ever increasing range of molecular or nanoworld words, symbols, images, and games. What do children today say about these artefacts that are used to represent molecular world entities? What are the material and social resources that can influence a child's everyday and developing scientific ideas about `molecules'? How do children interact with these cognitive tools when given expert assistance? What meaning-making is afforded when children are socially and materially assisted in using molecular tools in early chemical and nanoworld thinking? Tool-dependent discursive studies show that provision of cultural artefacts can assist and direct developmental thinking across many domains of science (Schoultz et al., Human Development 44:103-118, 2001; Siegal 2008). Young children's use of molecular artefacts as cognitive tools has not received much attention to date (Jakab 2009a, b). This study shows 6-11-year-old children expressing everyday ideas of molecular artefacts and raising their own questions about the artefacts. They are seen beginning to domesticate (Erneling 2010) the words, symbols, and images to their own purposes when given the opportunity to interact with such artefacts in supported activity. Discursive analysis supports the notion that using `molecules' as cultural tools can help young children to begin `putting on molecular spectacles' (Kind 2004). Playing with an interactive game (ICT) is shown to be particularly helpful in assisting children's early meaning-making with representations of molecules, atoms, and their chemical symbols.

  7. Circular Intensity Differential Scattering of chiral molecules

    Bustamante, C.J.

    1980-12-01

    In this thesis a theory of the Circular Intensity Differential Scattering (CIDS) of chiral molecules as modelled by a helix oriented with respect to the direction of incidence of light is presented. It is shown that a necessary condition for the existence of CIDS is the presence of an asymmetric polarizability in the scatterer. The polarizability of the scatterer is assumed generally complex, so that both refractive and absorptive phenomena are taken into account.

  8. Matter-wave interferometer for large molecules

    Brezger, B.; Hackermüller, L.; Uttenthaler, S.; Petschinka, J.; Arndt, M.; Zeilinger, A.

    2002-01-01

    We demonstrate a near-field Talbot-Lau interferometer for C-70 fullerene molecules. Such interferometers are particularly suitable for larger masses. Using three free-standing gold gratings of one micrometer period and a transversally incoherent but velocity-selected molecular beam, we achieve an interference fringe visibility of 40 % with high count rate. Both the high visibility and its velocity dependence are in good agreement with a quantum simulation that takes into account the van der W...

  9. Dipole-Dipole coupled double Rydberg molecules

    Kiffner, Martin; Park, Hyunwook; Li, Wenhui; Gallagher, Tom F.

    2012-01-01

    We show that the dipole-dipole interaction between two Rydberg atoms can give rise to long range molecules. The binding potential arises from two states that converge to different separated atom asymptotes. These states interact weakly at large distances, but start to repel each other strongly as the van der Waals interaction turns into a resonant dipole-dipole interaction with decreasing separation between the atoms. This mechanism leads to the formation of an attractive well for one of the ...

  10. Electron correlation in molecules and condensed phases

    March, N H

    1996-01-01

    This reference describes the latest research on correlation effects in the multicenter problems of atoms, molecules, and solids The author utilizes first- and second-order matrices, including the important observable electron density rho(r), and the Green function for discussing quantum computer simulations With its focus on concepts and theories, this volume will benefit experimental physicists, materials scientists, and physical and inorganic chemists as well as graduate students

  11. Single Molecule Data Analysis: An Introduction

    Tavakoli, Meysam; Li, Chun-Biu; Komatsuzaki, Tamiki; Pressé, Steve

    2016-01-01

    We review methods of data analysis for biophysical data with a special emphasis on single molecule applications. Our review is intended for anyone, from student to established researcher. For someone just getting started, we focus on exposing the logic, strength and limitations of each method and cite, as appropriate, the relevant literature for implementation details. We review traditional frequentist and Bayesian parametric approaches to data analysis and subsequently extend our discussion to recent non-parametric and information theoretic methods.

  12. Electrical transport through individual DNA molecules

    Li, Xin-Qi; Yan, YiJing

    2001-01-01

    A theoretical study is presented to quantitatively analyze the transport experiment through individual DNA molecules reported recently by Porath {\\it et al.} [Nature {\\bf 403}, 635 (2000)]. A variety of valuable quantities are identified by contacting the theoretical model with the measured data. The partially decoherent nature on the GC pairs of DNA is elaborated in contrast to the completely incoherent hopping mechanism discussed in the context of charge transfer experiments.

  13. Motors and Adaptors : Transport Regulation within Neurons

    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...

  14. Transmembrane adaptor proteins: organizers of immunoreceptor signalling

    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

  15. Electron attachment to the phthalide molecule

    Asfandiarov, N. L. [Institute of Molecule and Crystal Physics, Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya 151, 450075 Ufa (Russian Federation); Bashkir State Pedagogical University, Oktyabrskoy Revolutsii St., 3a, 450000 Ufa (Russian Federation); Pshenichnyuk, S. A. [Institute of Molecule and Crystal Physics, Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya 151, 450075 Ufa (Russian Federation); St.-Petersburg State University, Uljanovskaja, 1, 198504 St.-Petersburg (Russian Federation); Vorob’ev, A. S.; Nafikova, E. P. [Institute of Molecule and Crystal Physics, Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya 151, 450075 Ufa (Russian Federation); Lachinov, A. N. [Bashkir State Pedagogical University, Oktyabrskoy Revolutsii St., 3a, 450000 Ufa (Russian Federation); Kraikin, V. A. [Institute of Organic Chemistry, Ufa Research Centre, Russian Academy of Sciences, Prospect Oktyabrya 59, 450075 Ufa (Russian Federation); Modelli, A. [Dipartimento di Chimica “G. Ciamician,” Universitá di Bologna, Via Selmi 2, 40126 Bologna (Italy); Centro Interdipartimentale di Ricerca in Scienze Ambientali (CIRSA), Universitá di Bologna, Via S. Alberto 163, 48123 Ravenna (Italy)

    2015-05-07

    Phthalide, the simplest chain of conductive polymer thin film, was investigated by means of Electron Transmission Spectroscopy, Negative Ion Mass Spectrometry, and density functional theory quantum chemistry. It has been found that formation of gas-phase long-lived molecular anions of phthalide around 0.7 eV takes place through cleavage of a C–O bond of the pentacyclic ring of the parent molecular anion to give a vibrationally excited (electronically more stable) open-ring molecular anion. The energy of the transition state for ring opening of the parent negative ion is calculated to be 0.65 eV above the neutral ground state of the molecule. The energy (2.64 eV) evaluated for the corresponding transition state in the neutral molecule is much higher, so that the process of electron detachment from the anion must lead to a neutral molecule with its initial pentacyclic structure. The average lifetime of the molecular negative ions formed at an electron energy of 0.75 eV and 80 °C is measured to be about 100 μs. The known switching effect of thin phthalide films could stem from the presence of a similar open/closed transition state also in the polymer.

  16. Quantum Optics of Ultra-Cold Molecules

    Meiser, D.; Miyakawa, T.; Uys, H.; Meystre, P.

    Quantum optics has been a major driving force behind the rapid experimental developments that have led from the first laser cooling schemes to the Bose-Einstein condensation (BEC) of dilute atomic and molecular gases. Not only has it provided experimentalists with the necessary tools to create ultra-cold atomic systems, but it has also provided theorists with a formalism and framework to describe them: many effects now being studied in quantum-degenerate atomic and molecular systems find a very natural explanation in a quantum optics picture. This article briefly reviews three such examples that find their direct inspiration in the trailblazing work carried out over the years by Herbert Walther, one of the true giants of that field. Specifically, we use an analogy with the micromaser to analyze ultra-cold molecules in a double-well potential; study the formation and dissociation dynamics of molecules using the passage time statistics familiar from superradiance and superfluorescence studies; and show how molecules can be used to probe higher-order correlations in ultra-cold atomic gases, in particular bunching and antibunching.

  17. Small molecule-guided thermoresponsive supramolecular assemblies

    Rancatore, Benjamin J.

    2012-10-23

    Small organic molecules with strong intermolecular interactions have a wide range of desirable optical and electronic properties and rich phase behaviors. Incorporating them into block copolymer (BCP)-based supramolecules opens new routes to generate functional responsive materials. Using oligothiophene- containing supramolecules, we present systematic studies of critical thermodynamic parameters and kinetic pathway that govern the coassemblies of BCP and strongly interacting small molecules. A number of potentially useful morphologies for optoelectronic materials, including a nanoscopic network of oligothiophene and nanoscopic crystalline lamellae, were obtained by varying the assembly pathway. Hierarchical coassemblies of oligothiophene and BCP, rather than macrophase separation, can be obtained. Crystallization of the oligothiophene not only induces chain stretching of the BCP block the oligothiophene is hydrogen bonded to but also changes the conformation of the other BCP coil block. This leads to an over 70% change in the BCP periodicity (e.g., from 31 to 53 nm) as the oligothiophene changes from a melt to a crystalline state, which provides access to a large BCP periodicity using fairly low molecular weight BCP. The present studies have demonstrated the experimental feasibility of generating thermoresponsive materials that convert heat into mechanical energy. Incorporating strongly interacting small molecules into BCP supramolecules effectively increases the BCP periodicity and may also open new opportunities to tailor their optical properties without the need for high molecular weight BCP. © 2012 American Chemical Society.

  18. J-factors of short DNA molecules.

    Zoli, Marco

    2016-06-01

    The propensity of short DNA sequences to convert to the circular form is studied by a mesoscopic Hamiltonian method which incorporates both the bending of the molecule axis and the intrinsic twist of the DNA strands. The base pair fluctuations with respect to the helix diameter are treated as path trajectories in the imaginary time path integral formalism. The partition function for the sub-ensemble of closed molecules is computed by imposing chain end boundary conditions both on the radial fluctuations and on the angular degrees of freedom. The cyclization probability, the J-factor, proves to be highly sensitive to the stacking potential, mostly to its nonlinear parameters. We find that the J-factor generally decreases by reducing the sequence length (N) and, more significantly, below N = 100 base pairs. However, even for very small molecules, the J-factors remain sizeable in line with recent experimental indications. Large bending angles between adjacent base pairs and anharmonic stacking appear as the causes of the helix flexibility at short length scales. PMID:27276942

  19. Single-Molecule Imaging of Cellular Signaling

    De Keijzer, Sandra; Snaar-Jagalska, B. Ewa; Spaink, Herman P.; Schmidt, Thomas

    Single-molecule microscopy is an emerging technique to understand the function of a protein in the context of its natural environment. In our laboratory this technique has been used to study the dynamics of signal transduction in vivo. A multitude of signal transduction cascades are initiated by interactions between proteins in the plasma membrane. These cascades start by binding a ligand to its receptor, thereby activating downstream signaling pathways which finally result in complex cellular responses. To fully understand these processes it is important to study the initial steps of the signaling cascades. Standard biological assays mostly call for overexpression of the proteins and high concentrations of ligand. This sets severe limits to the interpretation of, for instance, the time-course of the observations, given the large temporal spread caused by the diffusion-limited binding processes. Methods and limitations of single-molecule microscopy for the study of cell signaling are discussed on the example of the chemotactic signaling of the slime-mold Dictyostelium discoideum. Single-molecule studies, as reviewed in this chapter, appear to be one of the essential methodologies for the full spatiotemporal clarification of cellular signaling, one of the ultimate goals in cell biology.

  20. Driving Organic Molecule Crystalliztion with Surface Reconstructions

    Bickel, Jessica; Trovato, Gianfranco

    This work examines how surface reconstructions can drive crystallization of organic molecules via self-assembly. Organic electronic molecules have low conductivities compared to inorganic materials, but crystallizing these polymers increases their conductivity. This project uses surface reconstructions with periodically repeating topographies to drive the crystallization process. The samples are grown by placing a drop of a dilute PEDOT solution on the clean Si(001)-(2x1) or Si(111)-(7x7) surface reconstruction and heating the surface up to both evaporate the solvent and promote diffusion of the polymer to the thermodynamically defined lowest energy position. The resulting samples are characterized by scanning tunneling microscopy (STM) with respect to their crystallinity and electronic properties. Of particular interest is whether there is a preferential location for the PEDOT molecule to adsorb and whether there are any conformational changes upon adsorption that modify the HOMO-LUMO gap. This work is being done in a new pan-style RHK-STM enclosed in a glovebox at Cleveland State University. The glovebox has O2 and H2O levels of less than 1ppm. This allows for sample preparation and imaging in a controlled environment that is free from contamination.

  1. Stark quantum beat spectroscopy of polyatomic molecules

    We derive analytical expressions for Stark quantum beat signals of polyatomic molecules and discuss them with regard to molecular and geometrical parameters. The general treatment is specified for near prolate asymmetric rotor molecules and a method for determining rotational constants and all components of the dipole moment of electronically excited polyatomic molecules is presented. The method is tested and illustrated for the vibrationless S1 state of deuterated propynal (HCtriple bondCCDO, Cs symmetry) and its lowest frequency non-totally symmetric state 121. The results of the vibrationless state are compared with structural data reported in the literature. For the 121 state we obtain A=1.5004(43) cm-1, B=0.16131(34) cm-1, C=0.14623(34) cm-1, and the components of the electric dipole moment in the molecular plane μa=-0.88(2) D, μb=1.03(2) D. Furthermore, it is shown that the modulation depth of Stark quantum beat signals can be utilized to quantify the contribution of the individual components of the transition moment to the total emission. (orig.)

  2. Rescattering photoelectron spectroscopy of small molecules

    Highlights: • We extracted DCSs of electron scattering from ions using electron spectroscopy. • Detail of the extraction procedure of DCS from the experiment is presented. • Experimentally extracted DCSs are compared with ab initio calculations. • Factorization model of rescattering is confirmed for molecules experimentally. - Abstract: We have measured angle-resolved rescattering photoelectron spectra of three small molecules (O2, CO2, and C2H4) using intense near-infrared laser pulses at several laser intensities. Based on the factorization formula for rescattering processes, we have extracted, from the electron spectra, the field-free differential cross sections of elastic electron scattering by the molecular ions. The detail of the extraction procedure is described. The experimentally extracted differential cross sections are compared with theoretical calculations of the field-free differential cross sections. Fairly good agreement between the experimentally extracted and theoretically calculated DCSs for wide range of the collision momentum indicates the validity of the present extraction procedure for the molecules

  3. Single- and multiphoton ionization processes in molecules

    This dissertation is theoretical in nature and can be separated into two main areas: (1) single- and multiphoton ionization studies of a novel photoelectron effect, and (2) single-photon ionization studies of simple clusters as models for adsorbate photoemission. The first area centers on the phenomenon of circular dichroism in photoelectron angular distributions (CDAD). CDAD is shown to exist from oriented linear molecules, adsorbed atoms, and aligned atoms and molecules in the gas phase. The calculations presented here are the first to demonstrate the experimental feasability of CDAD studies. CDAD is shown to be a measureable effect which exists because the photoelectron collection direction can break the symmetry of these otherwise highly symmetric systems. As a direct results of the work presented here, CDAD has now been observed experimentally. Coupled with resonantly enhanced multiphoton ionization (REMPI), CDAD is shown to be a powerful probe of unknown alignment in gas phase atomic and molecular samples. The second area of research focuses on the simple oriented molecules NiCO and NiN2 as models for the corresponding adsorbate systems. These simple models provide insight into features observed in the experimental angle-resolved photoemission spectra

  4. Designing a small molecule erythropoietin mimetic.

    Guarnieri, Frank

    2015-01-01

    Erythropoietin (EPO) is a protein made by the kidneys in response to low red blood cell count that is secreted into the bloodstream and binds to a receptor on hematopoietic stem cells in the bone marrow inducing them to become new red blood cells. EPO made with recombinant DNA technology was brought to market in the 1980s to treat anemia caused by kidney disease and cancer chemotherapy. Because EPO infusion was able to replace blood transfusions in many cases, it rapidly became a multibillion dollar per year drug and as the first biologic created with recombinant technology it launched the biotech industry. For many years intense research was focused on creating a small molecule orally available EPO mimetic. The Robert Wood Johnson (RWJ) group seemed to definitively establish that only large peptides with a minimum of 60 residues could replace EPO, as anything less was not a full agonist. An intense study of the published work led me to hypothesize that the size of the mimetic is not the real issue, but the symmetry making and breaking of the EPO receptor induced by the ligand is the key to activating the stem cells. This analysis meant that residues in the binding site of the receptor deemed absolutely essential for ligand binding and activation from mutagenesis experiments, were probably not really that important. My fundamental hypotheses were: (a) the symmetric state of the homodimeric receptor is the most stable state and thus must be the off-state, (b) a highly localized binding site exists at a pivot point where the two halves of the receptor meet, (c) small molecules can be created that have high potency for this site that will be competitive with EPO and thus can displace the protein-protein interaction, (d) small symmetric molecules will stabilize the symmetric off-state of the receptor, and (e) a key asymmetry in the small molecule will stabilize a mirror image asymmetry in the receptor resulting in the stabilization of the on-state and proliferation of

  5. Heavy Exotic Molecules with Charm and Bottom

    Liu, Yizhuang

    2016-01-01

    We revisit the formation of pion-mediated heavy-light exotic molecules with both charm and bottom and their chiral partners under the general strictures of both heavy-quark and chiral symmetry. The chiral exotic partners with good parity formed using the $(0^+, 1^+)$ multiplet are about twice more bound than their primary exotic partners formed using the $(0^-,1^-)$ multiplet. The chiral couplings across the multiplets $(0^\\pm, 1^\\pm)$ cause the chiral exotic partners to unbind, and the primary exotic molecules to be about twice more bound, for $J\\leq 1$. Our multi-channel coupling results show that only the charm isosinglet exotic molecules with $J^{PC}=1^{++}$ binds, which we identify as the reported neutral $X(3872)$. Also, the bottom isotriplet exotic with $J^{PC}=1^{+-}$ binds, which we identify as a mixture of the reported charged exotics $Z^+_b(10610)$ and $Z^+_b(10650)$. The bound isosinglet with $J^{PC}=1^{++}$ is suggested as a possible neutral $X_b(10532)$ not yet reported.

  6. [Aerodynamic focusing of particles and heavy molecules

    By accelerating a gas containing suspended particles or large molecules through a converging nozzle, the suspended species may be focused and therefore used to write fine lines on a surface. Our objective was to study the limits on how narrow this focal region could be as a function of particle size. We find that, for monodisperse particles with masses mp some 3.6 x 105 times larger than the molecular mass m of the carrier gas (diameters above some 100 angstrom), there is no fundamental obstacle to directly write submicron features. However, this conclusion has been verified experimentally only with particles larger than 0.1 μm. Experimental, theoretical and numerical studies on the defocusing role of Brownian motion for very small particles or heavy molecules have shown that high resolution (purely aerodynamic) focusing is impossible with volatile molecules whose masses are typically smaller than 1000 Dalton. For these, the minimal focal diameter after optimization appears to be 5√(m/mp) times the nozzle diameter dn. But combinations of focused lasers and aerodynamic focusing appear as promising for direct writing with molecular precursors. Theoretical and numerical schemes capable of predicting the evolution of the focusing beam, including Brownian motion effects, have been developed, although further numerical work would be desirable. 11 refs

  7. Biomedical applications of single molecule detection

    Kelso, D. M.

    1997-05-01

    The search for increased sensitivity of bio-analytical techniques has recently shifted from signal generation to detection. While enzyme amplifiers and chemiluminescent reporters developed by chemists over the last two decades gradually moved detection limits to the attomol level, it has taken engineers only a few years to reach single- molecule sensitivity with the development of new instrumentation. A number of different approaches have successfully achieved single-molecule fluorescence detection including confocal and near-field scanning optical microscopy, photon-counting cameras, fluorescence- correlation and time-gated spectroscopy. They detect labels immobilized on substrates, diffusing in solution and flowing in electro-osmotic and hydrodynamically focused streams. Biotechnology has created numerous application s for single- molecule detection. In research labs, it can dramatically increase the rate of DNA sequencing, screen libraries for products of directed evolution, and characterize compounds in drug discovery programs. In medical diagnostics, ultra- sensitive detection technologies can be used for genetic screening, detection of infectious diseases, or multi- analyte profiles. It can be applied to immunoassays as well as DNA or RNA hybridization assays.

  8. Electron attachment to the phthalide molecule

    Phthalide, the simplest chain of conductive polymer thin film, was investigated by means of Electron Transmission Spectroscopy, Negative Ion Mass Spectrometry, and density functional theory quantum chemistry. It has been found that formation of gas-phase long-lived molecular anions of phthalide around 0.7 eV takes place through cleavage of a C–O bond of the pentacyclic ring of the parent molecular anion to give a vibrationally excited (electronically more stable) open-ring molecular anion. The energy of the transition state for ring opening of the parent negative ion is calculated to be 0.65 eV above the neutral ground state of the molecule. The energy (2.64 eV) evaluated for the corresponding transition state in the neutral molecule is much higher, so that the process of electron detachment from the anion must lead to a neutral molecule with its initial pentacyclic structure. The average lifetime of the molecular negative ions formed at an electron energy of 0.75 eV and 80 °C is measured to be about 100 μs. The known switching effect of thin phthalide films could stem from the presence of a similar open/closed transition state also in the polymer

  9. The origin of large molecules in primordial autocatalytic reaction networks

    Giri, Varun

    2011-01-01

    Large molecules such as proteins and nucleic acids are crucial for life, yet their primordial origin remains a major puzzle. The production of large molecules, as we know it today, requires good catalysts, and the only good catalysts we know that can accomplish this task consist of large molecules. Thus the origin of large molecules is a chicken and egg problem in chemistry. Here we present a mechanism, based on autocatalytic sets (ACSs), that is a possible solution to this problem. We discuss a mathematical model describing the population dynamics of molecules in a stylized but prebiotically plausible chemistry. Large molecules can be produced in this chemistry by the coalescing of smaller ones, with the smallest molecules, the `food set', being buffered. Some of the reactions can be catalyzed by molecules within the chemistry with varying catalytic strengths. Normally the concentrations of large molecules in such a scenario are very small, diminishing exponentially with their size. ACSs, if present in the c...

  10. Single Molecule Studies on Dynamics in Liquid Crystals

    Daniela Täuber

    2013-09-01

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

  11. Oligomer Molecules for Efficient Organic Photovoltaics.

    Lin, Yuze; Zhan, Xiaowei

    2016-02-16

    Solar cells, a renewable, clean energy technology that efficiently converts sunlight into electricity, are a promising long-term solution for energy and environmental problems caused by a mass of production and the use of fossil fuels. Solution-processed organic solar cells (OSCs) have attracted much attention in the past few years because of several advantages, including easy fabrication, low cost, lightweight, and flexibility. Now, OSCs exhibit power conversion efficiencies (PCEs) of over 10%. In the early stage of OSCs, vapor-deposited organic dye materials were first used in bilayer heterojunction devices in the 1980s, and then, solution-processed polymers were introduced in bulk heterojunction (BHJ) devices. Relative to polymers, vapor-deposited small molecules offer potential advantages, such as a defined molecular structure, definite molecular weight, easy purification, mass-scale production, and good batch-to-batch reproducibility. However, the limited solubility and high crystallinity of vapor-deposited small molecules are unfavorable for use in solution-processed BHJ OSCs. Conversely, polymers have good solution-processing and film-forming properties and are easily processed into flexible devices, whereas their polydispersity of molecular weights and difficulty in purification results in batch to batch variation, which may hamper performance reproducibility and commercialization. Oligomer molecules (OMs) are monodisperse big molecules with intermediate molecular weights (generally in the thousands), and their sizes are between those of small molecules (generally with molecular weights 10000). OMs not only overcome shortcomings of both vapor-deposited small molecules and solution-processed polymers, but also combine their advantages, such as defined molecular structure, definite molecular weight, easy purification, mass-scale production, good batch-to-batch reproducibility, good solution processability, and film-forming properties. Therefore, OMs are a

  12. Energy distribution in dissociations of polyatomic molecules

    In this thesis studies are reported of fragmentation processes in polyatomic molecules. In order to find out which dessocaciation reactions take place, how they are brought about by the internal energy of the reactant, and to investigate the structure of the dissociating 'transition state', the fragment mass and the corresponding kinetic energy release (KER) are determined by differential translational spectroscopy using a position and time sensitive two-particle coincidence detector. The results are interpreted using the statistical theory of unimolecular dissociation. It turns out that the standard assumptions of the theory, especially in calculating KER-distributions, are not realistic in all molecules considered. Dissociation is induced by the neutralization with alkali metal vapour. In ch. 2 the experimental method and the analysis of the data (dissociation pathways, branching ratios and ε-d-distributions) are introduced and exemplified by measurements of cyclohexane, which represents the upper limit in precursor and fragment mass accessible in the apparatus. In ch. 3 a study is reported of the molecules methylchloride (CH3Cl) and the acetylradical (CH3CO). In spite of their similar geometric structures, completely different dissociation mechanisms have been found. Methylchloride dissociates via a repulsive state; acetyl radicals show energy scrambling. The energy distribution from dissociating acetyl exemplifies dynamical effects in the dissociation. In ch. 4 an investigation of a number of prototype hydrocarbons is presented. The dissociation pathways of several small linear alkanes indicate that neutralization takes place to unknown repulsive potentials, of which the position and steepness are determined from the kinetic energy release. (author). 118 refs.; 40 figs.; 5 tabs

  13. Raman scattering mediated by neighboring molecules

    Williams, Mathew D.; Bradshaw, David S.; Andrews, David L.

    2016-05-01

    Raman scattering is most commonly associated with a change in vibrational state within individual molecules, the corresponding frequency shift in the scattered light affording a key way of identifying material structures. In theories where both matter and light are treated quantum mechanically, the fundamental scattering process is represented as the concurrent annihilation of a photon from one radiation mode and creation of another in a different mode. Developing this quantum electrodynamical formulation, the focus of the present work is on the spectroscopic consequences of electrodynamic coupling between neighboring molecules or other kinds of optical center. To encompass these nanoscale interactions, through which the molecular states evolve under the dual influence of the input light and local fields, this work identifies and determines two major mechanisms for each of which different selection rules apply. The constituent optical centers are considered to be chemically different and held in a fixed orientation with respect to each other, either as two components of a larger molecule or a molecular assembly that can undergo free rotation in a fluid medium or as parts of a larger, solid material. The two centers are considered to be separated beyond wavefunction overlap but close enough together to fall within an optical near-field limit, which leads to high inverse power dependences on their local separation. In this investigation, individual centers undergo a Stokes transition, whilst each neighbor of a different species remains in its original electronic and vibrational state. Analogous principles are applicable for the anti-Stokes case. The analysis concludes by considering the experimental consequences of applying this spectroscopic interpretation to fluid media; explicitly, the selection rules and the impact of pressure on the radiant intensity of this process.

  14. A New Interstellar Cyclic Molecule, Ethylene Oxide

    Dickens, J. E.; Irvine, W. M.; Ohishi, M.; Ikeda, M.; Ishikawa, S.; Nummelin, A.; Hjalmarson, A.

    1997-12-01

    Ethylene oxide (c-C2H4O) is only the fourth known ring molecule identified in the interstellar medium, detected in the Galactic Center cloud SgrB2(N) by Dickens et al. (1997). It is the higher energy isomer of both the more familiar interstellar species acetaldehyde (CH3CHO) and the as yet undetected molecule vinyl alcohol (CH2CHOH). Dickens et al. (1997) reported a c-C2H4O molecular column density about an order of magnitude less than that reported for CH3CHO in SgrB2(N). This is a factor of 200 larger than the predictions of the new standard gas phase chemistry model of Lee, Bettens, and Herbst (1996), suggesting that the formation of c-C2H4O may be related to molecular formation on interstellar grains. We present observations of the c-C2H4O to CH3CHO abundance ratio in 5 additional molecular clouds. The data were taken in October 1997 with the Swedish-European Submillimeter Telescope in Chile. The confirmation of ethylene oxide in molecular clouds provides an appealing scenario for the first link in the chain of reactions leading to the origin of life, since it has been suggested as a possible pathway to the formation of the related cyclic molecule oxiranecarbonitrile (c-C3H3NO; cf., Dickens et al. 1996), a precursor to the synthesis of sugar phosphates which comprise the backbone of our molecular genetic structure. References: Dickens, J.E., Irvine, W.M., Ohishi, M., Ikeda, M., Ishikawa, S., Nummelin, A., and Hjalmarson, A. 1997, Astrophys. J., 489 (in press). Dickens, J.E. et al. 1996, Orig. Life Evol. Biosphere, 26, 97. Lee, H.-H., Bettens, R.P.A., and Herbst, E. 1996, Astron. Astrophys. Supp., 119, 111.

  15. Transport properties of individual C60-molecules

    Géranton, G.; Seiler, C.; Bagrets, A.; Venkataraman, L.; Evers, F.

    2012-01-01

    Electrical and thermal transport properties of C60 molecules are investigated with density-functional-theory based calculations. These calculations suggest that the optimum contact geometry for an electrode terminated with a single-Au atom is through binding to one or two C-atoms of C60 with a tendency to promote the sp2-hybridization into an sp3-type one. Transport in these junctions is primarily through an unoccupied molecular orbital that is partly hybridized with the Au, which results in ...

  16. Humidity Effects on Conductivity of DNA Molecules

    YAN Xun-Ling; DONG Rui-Xin; LIN Qing-De

    2006-01-01

    We present a model related to the humidity to describe the conductivity of homogeneous DNA molecule,where the hydration of phosphate group and bases are taken into account. The calculated results show the oscillation feature of dⅠ/dⅤ-Ⅴ curves and the semiconductor behavior of DNA. With the relative humidity increasing, the voltage gap becomes narrow and the maximum of conductance increases nonlinearly. The conductivity of DNA approaches to stabilization when the relative humidity reaches a certain value. These results are in agreement with experimental measurements.

  17. Tunnel magnetoresistance of an organic molecule junction

    Coherent spin-dependent electronic transport is investigated in a molecular junction based on oligophenylene attached to two the semi-infinite ferromagnetic (FM) electrodes with finite cross sections. The work is based on the tight-binding Hamiltonian model and within the framework of a non-equilibrium Green's function (NEGF) technique. It is shown that tunnel magnetoresistance (TMR) of molecular junction can be large (over 60 %) by adjusting the related parameters, and depends on: (i) the applied voltages and (ii) the length of oligophenylele molecule.

  18. Molecular-beam spectroscopy of interhalogen molecules

    A molecular-beam electric-resonance spectrometer employing a supersonic nozzle source has been used to obtain hyperfine spectra of 79Br35Cl. Analyses of these spectra and of microwave spectra published by other authors have yielded new values for the electric dipole moment and for the nuclear quadrupole coupling constants in this molecule. The new constants are significantly different from the currently accepted values. Van der Waals clusters containing chlorine monofluoride have been studied under various expansion conditions by the molecular-beam electric-deflection method. The structural possibilities indicated by the results are discussed, and cluster geometries are proposed

  19. Chiral control of electron transmission through molecules.

    Skourtis, Spiros S; Beratan, David N; Naaman, Ron; Nitzan, Abraham; Waldeck, David H

    2008-12-01

    Electron transmission through chiral molecules induced by circularly polarized light can be very different for mirror-image structures, a peculiar fact given that the electronic energy spectra of the systems are identical. We propose that this asymmetry--as large as 10% for resonant transport--arises from different dynamical responses of the mirrored structures to coherent excitation. This behavior is described in the context of a general novel phenomenon of current transfer (transfer of charge with its momentum information) and accounts for the observed asymmetry and its dependence on structure. PMID:19113598

  20. Inorganic Nanoparticles Conjugated with Biofunctional Molecules

    J.H.Choy

    2007-01-01

    1 Results We have attempted to conjugate inorganic nanoparticles with biofunctional molecules.Recently we were quite successful in demonstrating that a two-dimensional inorganic compound like layered double hydroxide (LDH),and natural and synthetic clays can be used as gene or drug delivery carriers1-4.To the best of our knowledge,such inorganic vectors are completely new and different from conventionally developed ones such as viruses and cationic liposomes,those which are limited in certain cases of ap...

  1. Heavy Meson Molecules in Effective Field Theory

    AlFiky, Mohammad T.; Gabbiani, Fabrizio; Petrov, Alexey A.

    2006-01-01

    We consider the implications from the possibility that the recently observed state X(3872) is a meson-antimeson molecule. We write an effective Lagrangian consistent with the heavy-quark and chiral symmetries needed to describe X(3872). We explore the consequences of the assumption that X(3872) is a molecular bound state of D^{*0} and anti-D^0 mesons for the existence of bound states in the D^0-anti-D^0 and D^{*0}-anti-D^{*0}.

  2. Optical spectroscopy of ultra cold molecules

    Supersonic free jets of helium expanded from 100 atm into a vacuum of 10-2 torr permit the cooling of molecules seeded into the flow. There are a relatively large number of two-body collisions and a relatively small number of three body collisions in these expansions. Those processes which are easily accomplished by two body collisions such as translational and rotational energy exchange substantially equilibrate with the carrier gas temperature. Those processes that are not easily accomplished by two body collisions or require three body collisions such as vibrational-translational energy exchange or condensation will not equilibrate with the carrier gas temperature. (Auth.)

  3. Collective effects in Single Molecule Magnets

    Subedi, Pradeep

    Single molecule magnets (SMMs), such as Mn12-acetate, are composed of transition metal ions and consists of identical molecules with large ground-state spin (S = 10) and a strong uniaxial anisotropy (65 K). Below about 3 K, Mn12-acetate exhibits magnetic hysteresis with steps at specific values of longitudinal magnetic field due to resonant quantum tunneling between spin up and down projections along the easy axis. The intermolecular exchange interactions between spins on molecules are quite small and spins are considered to be independent and non-interacting. However, the molecules do interact with each other both through magnetic dipolar interactions and through the lattice (e.g. phonons). I have investigated collective effects in SMMs due to these intermolecular interactions. In the thesis I will present experiments that explored magnetic ordering due to magnetic dipole interactions in Mn12-acetate and Mn12-acetate-MeOH. I will also present exper- iments on the onset of magnetic de agration in Mn12-acetate due to a thermal instability. The magnetic ordering studies involved investigating the effect of transverse fields on the susceptibility of single crystals of Mn12-acetate and Mn12-acetate- MeOH. Transverse fields increase quantum spin uctuations that suppress long- range order. However, the suppression of the Curie temperature by transverse fields in Mn12-acetate is far more rapid than predicted by the Transverse-Field Ising Ferromagnetic Model (TFIFM) and instead agrees with the predictions of the Random-Field Ising Ferromagnet Model. It appears that solvent disorder in Mn12-acetate gives rise to a distribution of random-fields that further suppress long-range order. Subsequent studies on Mn12-acetate-MeOH, with the same spin and similar lattice constants but without solvent disorder as Mn12-acetate, agrees with the TFIFM. The magnetic de agration studies involved studying the instability that leads to the ignition of magnetic deflagration in a thermally

  4. Small-Molecule Target Engagement in Cells.

    Schürmann, Marc; Janning, Petra; Ziegler, Slava; Waldmann, Herbert

    2016-04-21

    Monitoring how, when, and where small molecules engage their targets inside living cells is a critical step in chemical biology and pharmacological research, because it enables compound efficacy and confirmation of mode of action to be assessed. In this mini-review we summarize the currently available methodologies to detect and prove direct target engagement in cells and offer a critical view of their key advantages and disadvantages. As the interest of the field shifts toward discovery and validation of high-quality agents, we expect that efforts to develop and refine these types of methodologies will also intensify in the near future. PMID:27049669

  5. Bringing molecules back into molecular evolution.

    Claus O Wilke

    Full Text Available Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events.

  6. Photonic molecules formed by coupled hybrid resonators

    Peng, Bo; Zhu, Jiangang; Yang, Lan; 10.1364/OL.37.003435

    2013-01-01

    We describe a method that enables free-standing whispering-gallery-mode microresonators, and report spectral tuning of photonic molecules formed by coupled free and on-chip resonators with different geometries and materials. We study direct coupling via evanescent fields of free silica microtoroids and microspheres with on-chip polymer coated silica microtoroids. We demonstrate thermal tuning of resonance modes to achieve maximal spectral overlap, mode splitting induced by direct coupling, and the effects of distance between the resonators on the splitting spectra.

  7. Gaseous Electronics Tables, Atoms, and Molecules

    Raju, Gorur Govinda

    2011-01-01

    With the constant emergence of new research and application possibilities, gaseous electronics is more important than ever in disciplines including engineering (electrical, power, mechanical, electronics, and environmental), physics, and electronics. The first resource of its kind, Gaseous Electronics: Tables, Atoms, and Molecules fulfills the author's vision of a stand-alone reference to condense 100 years of research on electron-neutral collision data into one easily searchable volume. It presents most--if not all--of the properly classified experimental results that scientists, researchers,

  8. The (e,2e) reaction in molecules

    The aplication of the (e,2e) technique is discussed in the framework of (e,2e) on molecular hydrogen. It is shown that the technique is sufficiently sensitive to distinguish between simple wavefunctions and those containing configuration interactions. By comparing the data on H2 and D2 is shown that the Born-Oppenheimer approximation is confirmed to an accuracy of about 3 per cent. The data is also used to contrast other methods of determining electron momentum distributions in molecules. Data on methane, carbon monoxide and molecular nitrogen is also presented. (author)

  9. Single cell analysis of signaling molecules

    Klepárník, Karel; Luksch, Jaroslav; Adamová, Eva; Potáčová, Anna; Matalová, E.; Foret, František

    Grupo VLS Print Solution, 2014 - (Guzman, N.; Taveres, M.). s. 49-49 [International Symposium on Electro- and Liquid Phase-Separation Techniques /21./ and Latin-American Symposium on Biotechnology, Biomedical, Biopharmaceutical, and Industrial Applications of Capillary Electrophoresis and Microchip Technology /21./. 04.10.2014-08.10.2014, Natal] R&D Projects: GA ČR(CZ) GA14-28254S Institutional support: RVO:68081715 ; RVO:67985904 Keywords : single cell analysis * signaling molecules * caspase Subject RIV: CB - Analytical Chemistry, Separation

  10. Aging-From molecules to populations

    Sander, Miriam; Avlund, Kirsten; Lauritzen, Martin;

    2008-01-01

    The mean age of the human population is steadily increasing in many areas around the globe, a phenomenon with large social, political, economic and biological/medical implications. Inevitably, this phenomenon is stimulating great interest in understanding and potentially modulating the process of......-From Molecules to Populations. The following questions about human aging were discussed at the workshop: What is the limit of human life expectancy? What are the key indicators of human aging? What are the key drivers of human aging? Which genes have the greatest impact on human aging? How similar is aging...

  11. Inelastic Collisions and Chemical Reactions of Molecules at Ultracold Temperatures

    Quéméner, Goulven; Balakrishnan, Naduvalath; Dalgarno, Alexander

    2010-01-01

    This paper summarizes the recent theoretical works on inelastic collisions and chemical reactions at cold and ultracold temperatures involving neutral or ionic systems of atoms and molecules. Tables of zero-temperature rate constants of various molecules are provided.

  12. Formation of Ultracold NaRb Feshbach Molecules

    Wang, Fudong; Li, Xiaoke; Zhu, Bing; Chen, Jun; Wang, Dajun

    2015-01-01

    We report the creation of ultracold bosonic $^{23}$Na$^{87}$Rb Feshbach molecules via magneto-association. By ramping the magnetic field across an interspecies Feshbach resonance, at least 4000 molecules can be produced out of the near degenerate ultracold mixture. Fast loss due to inelastic atom-molecule collisions is observed, which limits the pure molecule number, after residual atoms removal, to 1700. The pure molecule sample can live for 21.8(8) ms in the optical trap, long enough for future molecular spectroscopy studies toward coherently transferring to the singlet ro-vibrational ground state, where these molecules are stable against chemical reaction and have a permanent electric dipole moment of 3.3 Debye. We have also measured the Feshbach molecule's binding energy near the Feshbach resonance by the oscillating magnetic field method and found these molecules have a large closed-channel fraction.

  13. Recent advances in developing small molecules targeting RNA.

    Guan, Lirui; Disney, Matthew D

    2012-01-20

    RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void. PMID:22185671

  14. Controlling single-molecule junction conductance by molecular interactions

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

    2015-01-01

    For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact ...

  15. Can STM be used to image molecules on surfaces?

    Ramos, Marta M. D.

    1993-01-01

    The STM's ability to image adsorbates depends on the probability that the electronic states localized on the adsorbed molecule contribute to the tunnelling current. When the STM images are dominated by the substrate, any interpretation in terms of the actual positions of the atoms within the molecule is controversial. A criterion is presented for deciding whether an STM observation is of the adsorbed molecule directly or of the indirect effect of the molecule on the current from the substrate...

  16. Medical diagnostics using designed molecules with sense and logic

    Cardona, Mario; Farrugia, Kristina; David C. Magri

    2013-01-01

    Luminescent molecules responsive to cations, anions and even small molecules can be designed with the appropriate selectivity and sensitivity for monitoring physiological and pathological levels of analytes. We highlight some recent examples of designed molecules that can sense for a specific analyte or a combination of analytes in blood and in living cells. Furthermore, we demonstrate how molecules can be designed with built-in algorithms according to principles of Boolean logic to perform i...

  17. Quantum Effects at Low Energy Atom-Molecule Interface

    Deb, B.; Rakshit, A.; Hazra, J.; Chakraborty, D.

    2013-01-01

    Quantum interference effects in inter-conversion between cold atoms and diatomic molecules are analysed. Within the framework of Fano's theory, continuum-bound anisotropic dressed state formalism of atom-molecule quantum dynamics is presented. This formalism is applicable in photo- and magneto-associative strong-coupling regimes. The significance of Fano effect in ultracold atom-molecule transitions is discussed. Quantum effects at low energy atom-molecule interface are important for explorin...

  18. Axion Dark Matter Detection with Cold Molecules

    Graham, Peter W

    2011-01-01

    Current techniques cannot detect axion dark matter over much of its parameter space, particularly in the theoretically well-motivated region where the axion decay constant f_a lies near the GUT and Planck scales. We suggest a novel experimental method to search for QCD axion dark matter in this region. The axion field oscillates at a frequency equal to its mass when it is a component of dark matter. These oscillations induce time varying CP-odd nuclear moments, such as electric dipole and Schiff moments. The coupling between internal atomic fields and these nuclear moments gives rise to time varying shifts to atomic energy levels. These effects can be enhanced by using elements with large Schiff moments such as the light Actinides, and states with large spontaneous parity violation, such as molecules in a background electric field. The energy level shift in such a molecule can be ~ 10^-24 eV or larger. While challenging, this energy shift may be observable in a molecular clock configuration with technology pr...

  19. Sisyphus Laser Cooling of a Polyatomic Molecule

    Kozyryev, Ivan; Matsuda, Kyle; Augenbraun, Benjamin L; Anderegg, Loic; Sedlack, Alexander P; Doyle, John M

    2016-01-01

    We perform magnetically-assisted Sisyphus laser cooling of the triatomic free radical strontium monohydroxide (SrOH). This is achieved with principal optical cycling in the rotationally closed $P\\left(N"=1\\right)$ branch of either the $\\tilde{X}^{2}\\Sigma^{+}\\left(000\\right)\\leftrightarrow\\tilde{A}^{2}\\Pi_{1/2}\\left(000\\right)$ or the $\\tilde{X}^{2}\\Sigma^{+}\\left(000\\right)\\leftrightarrow\\tilde{B}^{2}\\Sigma^{+}\\left(000\\right)$ vibronic transitions. Molecules lost into the excited vibrational states during the cooling process are repumped back through the $\\tilde{B}\\left(000\\right)$ state for both the $\\left(100\\right)$ level of the Sr-O stretching mode and the $\\left(02^{0}0\\right)$ level of the bending mode. The transverse temperature of a SrOH molecular beam is reduced in one dimension by two orders of magnitude to $\\sim700\\ {\\rm \\mu K}$. This approach opens a path towards creating a variety of ultracold polyatomic molecules, including much larger ones, by means of direct laser cooling.

  20. Toroidal nanotraps for cold polar molecules

    Salhi, Marouane; Passian, Ali; Siopsis, George

    2015-09-01

    Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, and polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.