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Sample records for nucleoporin p62 interacts

  1. Amyloid-like interactions within nucleoporin FG hydrogels

    NARCIS (Netherlands)

    Ader, C.; Frey, S.; Maas, W.; Schmidt, H. B.; Görlich, D.; Baldus, M.

    2010-01-01

    The 62 kDa FG repeat domain of the nucleoporin Nsp1p forms a hydrogel-based, sieve-like permeability barrier that excludes inert macromolecules but allows rapid entry of nuclear transport receptors (NTRs). We found that the N-terminal part of this domain, which is characterized by Asn-rich inter-FG

  2. Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity

    International Nuclear Information System (INIS)

    Béaslas, Olivier; Vihervaara, Terhi; Li, Jiwei; Laurila, Pirkka-Pekka; Yan, Daoguang; Olkkonen, Vesa M.

    2012-01-01

    ORP8 is an oxysterol/cholesterol binding protein anchored to the endoplasmic reticulum and the nuclear envelope, and is abundantly expressed in the macrophage. We created and characterized mouse RAW264.7 macrophages with ORP8 stably silenced using shRNA lentiviruses. A microarray transcriptome and gene ontology pathway analysis revealed significant alterations in several nuclear pathways and ones associated with centrosome and microtubule organization. ORP8 knockdown resulted in increased expression and altered subcellular distribution of an interaction partner of ORP8, nucleoporin NUP62, with an intranuclear localization aspect and association with cytoplasmic vesicular structures and lamellipodial edges of the cells. Moreover, ORP8 silenced cells displayed enhanced migration, and a more pronounced microtubule cytoskeleton than controls expressing a non-targeting shRNA. ORP8 was shown to compete with Exo70 for interaction with NUP62, and NUP62 knockdown abolished the migration enhancement of ORP8-silenced cells, suggesting that the endogenous ORP8 suppresses migration via binding to NUP62. As a conclusion, the present study reveals new, unexpected aspects of ORP8 function in macrophages not directly involving lipid metabolism, but rather associated with nuclear functions, microtubule organization, and migration capacity. -- Highlights: ► The phenotype of Raw264.7 macrophage with ORP8 silenced is characterized. ► ORP8 silencing alters mRNA levels of nuclear and microtubule/centrosome pathways. ► ORP8 silencing results in increased expression and altered distribution of NUP62. ► ORP8 silenced macrophages show enhanced migration and altered microtubule cytoskeleton. ► ORP8 competes in vitro with Exo70 for binding to NUP62.

  3. Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity

    Energy Technology Data Exchange (ETDEWEB)

    Beaslas, Olivier; Vihervaara, Terhi [Minerva Foundation Institute for Medical Research, FI-00290 Helsinki (Finland); Li, Jiwei [Department of Biology, Jinan University, Guangzhou 510632 (China); Laurila, Pirkka-Pekka [FIMM, Institute for Molecular Medicine Finland, FI-00290 Helsinki (Finland); National Institute for Health and Welfare, Public Health Genomics Unit, FI-00290 Helsinki (Finland); Yan, Daoguang [Department of Biology, Jinan University, Guangzhou 510632 (China); Olkkonen, Vesa M., E-mail: vesa.olkkonen@helsinki.fi [Minerva Foundation Institute for Medical Research, FI-00290 Helsinki (Finland); Institute of Biomedicine, Anatomy, University of Helsinki, FI-00014 (Finland)

    2012-09-10

    ORP8 is an oxysterol/cholesterol binding protein anchored to the endoplasmic reticulum and the nuclear envelope, and is abundantly expressed in the macrophage. We created and characterized mouse RAW264.7 macrophages with ORP8 stably silenced using shRNA lentiviruses. A microarray transcriptome and gene ontology pathway analysis revealed significant alterations in several nuclear pathways and ones associated with centrosome and microtubule organization. ORP8 knockdown resulted in increased expression and altered subcellular distribution of an interaction partner of ORP8, nucleoporin NUP62, with an intranuclear localization aspect and association with cytoplasmic vesicular structures and lamellipodial edges of the cells. Moreover, ORP8 silenced cells displayed enhanced migration, and a more pronounced microtubule cytoskeleton than controls expressing a non-targeting shRNA. ORP8 was shown to compete with Exo70 for interaction with NUP62, and NUP62 knockdown abolished the migration enhancement of ORP8-silenced cells, suggesting that the endogenous ORP8 suppresses migration via binding to NUP62. As a conclusion, the present study reveals new, unexpected aspects of ORP8 function in macrophages not directly involving lipid metabolism, but rather associated with nuclear functions, microtubule organization, and migration capacity. -- Highlights: Black-Right-Pointing-Pointer The phenotype of Raw264.7 macrophage with ORP8 silenced is characterized. Black-Right-Pointing-Pointer ORP8 silencing alters mRNA levels of nuclear and microtubule/centrosome pathways. Black-Right-Pointing-Pointer ORP8 silencing results in increased expression and altered distribution of NUP62. Black-Right-Pointing-Pointer ORP8 silenced macrophages show enhanced migration and altered microtubule cytoskeleton. Black-Right-Pointing-Pointer ORP8 competes in vitro with Exo70 for binding to NUP62.

  4. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    Science.gov (United States)

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-10-01

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  5. Nucleoporin 62 and Ca(2+)/calmodulin dependent kinase kinase 2 regulate androgen receptor activity in castrate resistant prostate cancer cells.

    Science.gov (United States)

    Karacosta, Loukia G; Kuroski, Laura A; Hofmann, Wilma A; Azabdaftari, Gissou; Mastri, Michalis; Gocher, Angela M; Dai, Shuhang; Hoste, Allen J; Edelman, Arthur M

    2016-02-15

    Re-activation of the transcriptional activity of the androgen receptor (AR) is an important factor mediating progression from androgen-responsive to castrate-resistant prostate cancer (CRPC). However, the mechanisms regulating AR activity in CRPC remain incompletely understood. Ca(2+) /calmodulin-dependent kinase kinase (CaMKK) 2 was previously shown to regulate AR activity in androgen-responsive prostate cancer cells. Our objective was to further explore the basis of this regulation in CRPC cells. The abundance of CaMKK2 in nuclear fractions of androgen-responsive prostate cancer and CRPC, cells were determined by subcellular fractionation and Western blotting. CaMKK2 association with nuclear pore complexes (NPCs) and nucleoporins (Nups) including Nup62, were imaged by structured illumination and super-resolution fluorescence microscopy and co-immunoprecipitation, respectively. The abundance and subcellular localization of CaMKK2 and Nup62 in human clinical specimens of prostate cancer was visualized by immunohistochemistry. The role of Nups in the growth and viability of CRPC cells was assessed by RNA interference and cell counting. The involvement of CaMKK2 and Nup62 in regulating AR transcriptional activity was addressed by RNA interference, chromatin immunoprecipitation, androgen response element reporter assay, and Western blotting. CaMKK2 was expressed at higher levels in the nuclear fraction of CPRC C4-2 cells, than in that of androgen-responsive LNCaP cells. In C4-2 cells, CaMKK2 associated with NPCs of the nuclear envelope and physically interacted with Nup62. CaMKK2 and Nup62 demonstrated pronounced, and similar increases in both expression and perinuclear/nuclear localization in human clinical specimens of advanced prostate cancer relative to normal prostate. Knockdown of Nup62, but not of Nups, 98 or 88, reduced growth and viability of C4-2 cells. Knockdown of Nup62 produced a greater reduction of the growth and viability of C4-2 cells than of non

  6. Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition.

    Science.gov (United States)

    Pérez-Garrastachu, Miguel; Arluzea, Jon; Andrade, Ricardo; Díez-Torre, Alejandro; Urtizberea, Marta; Silió, Margarita; Aréchaga, Juan

    2017-09-03

    Nucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific reports have revealed that some nucleoporins participate in nuclear processes such as transcription, replication, DNA repair and chromosome segregation. Thus, the interaction of NPCs with chromatin could modulate the distribution of chromosome territories relying on the epigenetic state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this work, histone deacetylase inhibitors (HDACi) were used to induce a hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98 are translocated from the nuclear pore toward the interior of the cell nucleus, accumulating as intranuclear nucleoporin clusters. These transitory structures are highly dynamic, and are mainly present in the population of cells arrested at the G0/G1 phase of the cell cycle. Our results indicate that the redistribution of these nucleoporins from the nuclear envelope to the nuclear interior may be implicated in the early events of cell cycle initialization, particularly during the G1 phase transition.

  7. p62 regulates CD40-mediated NFκB activation in macrophages through interaction with TRAF6

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    Seibold, Kristina; Ehrenschwender, Martin, E-mail: martin.ehrenschwender@ukr.de

    2015-08-14

    CD40 is a member of the tumor necrosis factor (TNF) receptor family. Activation-induced recruitment of adapter proteins, so-called TNF-receptor-associated factors (TRAFs) to the cytoplasmic tail of CD40 triggers signaling cascades important in the immune system, but has also been associated with excessive inflammation in diseases such as atherosclerosis and rheumatoid arthritis. Especially, pro-inflammatory nuclear factor κB (NFκB) signaling emanating from CD40-associated TRAF6 appears to be a key pathogenic driving force. Consequently, targeting the CD40-TRAF6 interaction is emerging as a promising therapeutic strategy, but the underlying molecular machinery of this signaling axis is to date poorly understood. Here, we identified the multifunctional adaptor protein p62 as a critical regulator in CD40-mediated NFκB signaling via TRAF6. CD40 activation triggered formation of a TRAF6-p62 complex. Disturbing this interaction tremendously reduced CD40-mediated NFκB signaling in macrophages, while TRAF6-independent signaling pathways remained unaffected. This highlights p62 as a potential target in hyper-inflammatory, CD40-associated pathologies. - Highlights: • CD40 activation triggers interaction of the adapter protein TRAF6 with p62. • TRAF6-p62 interaction regulates CD40-mediated NFκB signaling in macrophages. • Defective TRAF6-p62 interaction reduces CD40-mediated NFκB activation in macrophages.

  8. Nuclear distributions of NUP62 and NUP214 suggest architectural diversity and spatial patterning among nuclear pore complexes.

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    Yayoi Kinoshita

    Full Text Available The shape of nuclei in many adherent cultured cells approximates an oblate ellipsoid, with contralateral flattened surfaces facing the culture plate or the medium. Observations of cultured cell nuclei from orthogonal perspectives revealed that nucleoporin p62 (NUP62 and nucleoporin 214 (NUP214 are differentially distributed between nuclear pore complexes on the flattened surfaces and peripheral rim of the nucleus. High resolution stimulated emission depletion (STED immunofluorescence microscopy resolved individual NPCs, and suggested both heterogeneity and microheterogeneity in NUP62 and NUP214 immunolabeling among in NPC populations. Similar to nuclear domains and interphase chromosome territories, architectural diversity and spatial patterning of NPCs may be an intrinsic property of the nucleus that is linked to the functions and organization of underlying chromatin.

  9. Nuclear import of cutaneous beta genus HPV8 E7 oncoprotein is mediated by hydrophobic interactions between its zinc-binding domain and FG nucleoporins

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    Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2014-01-20

    We have previously discovered and characterized the nuclear import pathways for the E7 oncoproteins of mucosal alpha genus HPVs, type 16 and 11. Here we investigated the nuclear import of cutaneous beta genus HPV8 E7 protein using confocal microscopy after transfections of HeLa cells with EGFP-8E7 and mutant plasmids and nuclear import assays in digitonin-permeabilized HeLa cells. We determined that HPV8 E7 contains a nuclear localization signal (NLS) within its zinc-binding domain that mediates its nuclear import. Furthermore, we discovered that a mostly hydrophobic patch {sub 65}LRLFV{sub 69} within the zinc-binding domain is essential for the nuclear import and localization of HPV8 E7 via hydrophobic interactions with the FG nucleoporins Nup62 and Nup153. Substitution of the hydrophobic residues within the {sub 65}LRLFV{sub 69} patch to alanines, and not R66A mutation, disrupt the interactions between the 8E7 zinc-binding domain and Nup62 and Nup153 and consequently inhibit nuclear import of HPV8 E7. - Highlights: • HPV8 E7 has a cNLS within its zinc-binding domain that mediates its nuclear import. • Discovery of a hydrophobic patch that is critical for the nuclear import of HPV8 E7. • HPV8 E7 nuclear import is mediated by hydrophobic interactions with FG-Nups, Nup62 and Nup153.

  10. Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans.

    Science.gov (United States)

    Martino, Lisa; Morchoisne-Bolhy, Stéphanie; Cheerambathur, Dhanya K; Van Hove, Lucie; Dumont, Julien; Joly, Nicolas; Desai, Arshad; Doye, Valérie; Pintard, Lionel

    2017-10-23

    In animal cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how they coordinate their activity to trigger this event is unclear. Here, we show that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK-1) is recruited to the nuclear pore complexes, just prior to NEBD, through its Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear envelope (NE) is required for efficient NEBD. We identify the central channel nucleoporins NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62 as the critical factors anchoring PLK-1 to the NE in C. elegans. In particular, NPP-1, NPP-4, and NPP-11 primed at multiple Polo-docking sites by Cdk1 and PLK-1 itself physically interact with the PLK-1 PBD. We conclude that nucleoporins play an unanticipated regulatory role in NEBD, by recruiting PLK-1 to the NE thereby facilitating phosphorylation of critical downstream targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Aspalathin Reverts Doxorubicin-Induced Cardiotoxicity through Increased Autophagy and Decreased Expression of p53/mTOR/p62 Signaling

    Directory of Open Access Journals (Sweden)

    Rabia Johnson

    2017-09-01

    Full Text Available Doxorubicin (Dox is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53, adenosine monophosphate-activated protein kinase (AMPK, nucleoporin p62 (p62, and the mammalian target of rapamycin (mTOR are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone C-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco’s Modified Eagle’s medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2 µM Dox were co-treated with either 20 µM Dexrazozane (Dexra or 0.2 µM aspalathin (ASP daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity.

  12. Nucleoporin Nup98 mediates galectin-3 nuclear-cytoplasmic trafficking

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    Funasaka, Tatsuyoshi, E-mail: funasaka@staff.kanazawa-u.ac.jp [Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Ishikawa (Japan); Balan, Vitaly; Raz, Avraham [Department of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI (United States); Wong, Richard W., E-mail: rwong@staff.kanazawa-u.ac.jp [Laboratory of Molecular and Cellular Biology, Department of Biology, Faculty of Natural Systems, Institute of Science and Engineering, Kanazawa University, Ishikawa (Japan); Bio-AFM Frontier Research Center, Kanazawa Kanazawa University, Ishikawa (Japan)

    2013-04-26

    Highlights: •Nuclear pore protein Nup98 is a novel binding partner of galectin-3. •Nup98 transports galectin-3 into cytoplasm. •Nup98 depletion leads to galectin-3 nuclear transport and induces growth retardation. •Nup98 may involve in ß-catenin pathway through interaction with galectin-3. -- Abstract: Nucleoporin Nup98 is a component of the nuclear pore complex, and is important in transport across the nuclear pore. Many studies implicate nucleoporin in cancer progression, but no direct mechanistic studies of its effect in cancer have been reported. We show here that Nup98 specifically regulates nucleus–cytoplasm transport of galectin-3, which is a ß-galactoside-binding protein that affects adhesion, migration, and cancer progression, and controls cell growth through the ß-catenin signaling pathway in cancer cells. Nup98 interacted with galectin-3 on the nuclear membrane, and promoted galectin-3 cytoplasmic translocation whereas other nucleoporins did not show these functions. Inversely, silencing of Nup98 expression by siRNA technique localized galectin-3 to the nucleus and retarded cell growth, which was rescued by Nup98 transfection. In addition, Nup98 RNA interference significantly suppressed downstream mRNA expression in the ß-catenin pathway, such as cyclin D1 and FRA-1, while nuclear galectin-3 binds to ß-catenin to inhibit transcriptional activity. Reduced expression of ß-catenin target genes is consistent with the Nup98 reduction and the galectin-3–nucleus translocation rate. Overall, the results show Nup98’s involvement in nuclear–cytoplasm translocation of galectin-3 and ß-catenin signaling pathway in regulating cell proliferation, and the results depicted here suggest a novel therapeutic target/modality for cancers.

  13. Mutations that promote furin-independent growth of Semliki Forest virus affect p62-E1 interactions and membrane fusion

    International Nuclear Information System (INIS)

    Zhang Xinyong; Kielian, Margaret

    2004-01-01

    The enveloped alphavirus Semliki Forest virus (SFV) infects cells via a low pH-triggered membrane fusion reaction mediated by the E1 protein. E1's fusion activity is regulated by its heterodimeric interaction with a companion membrane protein E2. Mature E2 protein is generated by furin processing of the precursor p62. Processing destabilizes the heterodimer, allowing dissociation at acidic pH, E1 conformational changes, and membrane fusion. We used a furin-deficient cell line, FD11, to select for SFV mutants that show increased growth in the absence of p62 processing. We isolated and characterized 7 such pci mutants (p62 cleavage independent), which retained the parental furin cleavage site but showed significant increases in their ability to carry out membrane fusion in the p62 form. Sequence analysis of the pci mutants identified mutations primarily on the E2 protein, and suggested sites important in the interaction of p62 with E1 and the regulation of fusion

  14. A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies.

    Science.gov (United States)

    Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

    2016-04-08

    The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

  15. Purification, crystallization and preliminary X-ray analysis of a Nup107–Nup133 heterodimeric nucleoporin complex

    International Nuclear Information System (INIS)

    Boehmer, Thomas; Schwartz, Thomas U.

    2007-01-01

    A heterodimeric complex consisting of the C-terminal domains of human nucleoporins Nup107 and Nup133 was purified and crystallized and complete diffraction data sets were collected. The nuclear pore complex (NPC), the sole gateway of traffic between the nucleus and the cytoplasm, is built up from multiple copies of about 30 proteins collectively termed nucleoporins (nups). Nups are organized into distinct subcomplexes. Nup107 and Nup133 are members of the essential Nup107–160 subcomplex, a component of the central NPC architecture. A dimeric complex of the C-terminal domains of human Nup107 and Nup133 was expressed from a bicistronic vector in Escherichia coli, purified and crystallized in two different crystal forms. Crystals grown in the presence of 18–22% PEG 3350 belong to space group P2 1 2 1 2 1 and diffracted to 2.9 Å. Native and seleno-l-methionine-derivative crystals grown in the presence of 1.1 M sodium malonate belong to space group C2 and diffracted to 2.55 and 2.9 Å, respectively. Structure determination of this complex will give the first insights into the protein–protein interactions within a core module of the NPC

  16. Purification, crystallization and preliminary X-ray analysis of a Nup107–Nup133 heterodimeric nucleoporin complex

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    Boehmer, Thomas; Schwartz, Thomas U., E-mail: tus@mit.edu [Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2007-09-01

    A heterodimeric complex consisting of the C-terminal domains of human nucleoporins Nup107 and Nup133 was purified and crystallized and complete diffraction data sets were collected. The nuclear pore complex (NPC), the sole gateway of traffic between the nucleus and the cytoplasm, is built up from multiple copies of about 30 proteins collectively termed nucleoporins (nups). Nups are organized into distinct subcomplexes. Nup107 and Nup133 are members of the essential Nup107–160 subcomplex, a component of the central NPC architecture. A dimeric complex of the C-terminal domains of human Nup107 and Nup133 was expressed from a bicistronic vector in Escherichia coli, purified and crystallized in two different crystal forms. Crystals grown in the presence of 18–22% PEG 3350 belong to space group P2{sub 1}2{sub 1}2{sub 1} and diffracted to 2.9 Å. Native and seleno-l-methionine-derivative crystals grown in the presence of 1.1 M sodium malonate belong to space group C2 and diffracted to 2.55 and 2.9 Å, respectively. Structure determination of this complex will give the first insights into the protein–protein interactions within a core module of the NPC.

  17. Triage of oxidation-prone proteins by Sqstm1/p62 within the mitochondria

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    Lee, Minjung [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine and Samsung Biomedical Research Institute, Suwon-Si, Kyonggi-Do (Korea, Republic of); Shin, Jaekyoon, E-mail: jkshin@med.skku.ac.kr [Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine and Samsung Biomedical Research Institute, Suwon-Si, Kyonggi-Do (Korea, Republic of)

    2011-09-16

    Highlights: {yields} The mitochondrion contains its own protein quality control system. {yields} p62 localizes within the mitochondria and forms mega-dalton sized complexes. {yields} p62 interacts with oxidation-prone proteins and the proteins of quality control. {yields} In vitro delivery of p62 improves mitochondrial functions. {yields} p62 is implicated as a participant in mitochondrial protein quality control. -- Abstract: As the mitochondrion is vulnerable to oxidative stress, cells have evolved several strategies to maintain mitochondrial integrity, including mitochondrial protein quality control mechanisms and autophagic removal of damaged mitochondria. Involvement of an autophagy adaptor, Sqstm1/p62, in the latter process has been recently described. In the present study, we provide evidence that a portion of p62 directly localizes within the mitochondria and supports stable electron transport by forming heterogeneous protein complexes. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) of mitochondrial proteins co-purified with p62 revealed that p62 interacts with several oxidation-prone proteins, including a few components of the electron transport chain complexes, as well as multiple chaperone molecules and redox regulatory enzymes. Accordingly, p62-deficient mitochondria exhibited compromised electron transport, and the compromised function was partially restored by in vitro delivery of p62. These results suggest that p62 plays an additional role in maintaining mitochondrial integrity at the vicinity of target machineries through its function in relation to protein quality control.

  18. A mutation in the nucleoporin-107 gene causes XX gonadal dysgenesis.

    Science.gov (United States)

    Weinberg-Shukron, Ariella; Renbaum, Paul; Kalifa, Rachel; Zeligson, Sharon; Ben-Neriah, Ziva; Dreifuss, Amatzia; Abu-Rayyan, Amal; Maatuk, Noa; Fardian, Nilly; Rekler, Dina; Kanaan, Moien; Samson, Abraham O; Levy-Lahad, Ephrat; Gerlitz, Offer; Zangen, David

    2015-11-02

    Ovarian development and maintenance are poorly understood; however, diseases that affect these processes can offer insights into the underlying mechanisms. XX female gonadal dysgenesis (XX-GD) is a rare, genetically heterogeneous disorder that is characterized by underdeveloped, dysfunctional ovaries, with subsequent lack of spontaneous pubertal development, primary amenorrhea, uterine hypoplasia, and hypergonadotropic hypogonadism. Here, we report an extended consanguineous family of Palestinian origin, in which 4 females exhibited XX-GD. Using homozygosity mapping and whole-exome sequencing, we identified a recessive missense mutation in nucleoporin-107 (NUP107, c.1339G>A, p.D447N). This mutation segregated with the XX-GD phenotype and was not present in available databases or in 150 healthy ethnically matched controls. NUP107 is a component of the nuclear pore complex, and the NUP107-associated protein SEH1 is required for oogenesis in Drosophila. In Drosophila, Nup107 knockdown in somatic gonadal cells resulted in female sterility, whereas males were fully fertile. Transgenic rescue of Drosophila females bearing the Nup107D364N mutation, which corresponds to the human NUP107 (p.D447N), resulted in almost complete sterility, with a marked reduction in progeny, morphologically aberrant eggshells, and disintegrating egg chambers, indicating defective oogenesis. These results indicate a pivotal role for NUP107 in ovarian development and suggest that nucleoporin defects may play a role in milder and more common conditions such as premature ovarian failure.

  19. Nuclear import of high risk HPV16 E7 oncoprotein is mediated by its zinc-binding domain via hydrophobic interactions with Nup62

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    Eberhard, Jeremy; Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

    2013-11-15

    We previously discovered that nuclear import of high risk HPV16 E7 is mediated by a cNLS located within the zinc-binding domain via a pathway that is independent of karyopherins/importins (Angeline et al., 2003; Knapp et al., 2009). In this study we continued our characterization of the cNLS and nuclear import pathway of HPV16 E7. We find that an intact zinc-binding domain is essential for the cNLS function in mediating nuclear import of HPV16 E7. Mutagenesis of cysteine residues to alanine in each of the two CysXXCys motifs involved in zinc-binding changes the nuclear localization of the EGFP-16E7 and 2xEGFP-16E7 mutants. We further discover that a patch of hydrophobic residues, {sub 65}LRLCV{sub 69}, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. - Highlights: • An intact zinc-binding domain is essential for the nuclear localization of HPV16 E7. • Identification of a hydrophobic patch that is critical for the nuclear import of HPV16 E7. • HPV16 E7 interacts via its zinc-binding domain with the FG domain of Nup62.

  20. Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors.

    Science.gov (United States)

    Milles, Sigrid; Mercadante, Davide; Aramburu, Iker Valle; Jensen, Malene Ringkjøbing; Banterle, Niccolò; Koehler, Christine; Tyagi, Swati; Clarke, Jane; Shammas, Sarah L; Blackledge, Martin; Gräter, Frauke; Lemke, Edward A

    2015-10-22

    The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Wei-Ru Huang

    Full Text Available Avian reovirus (ARV protein p17 has been shown to regulate cell cycle and autophagy by activation of p53/PTEN pathway; nevertheless, it is still unclear how p53 and PTEN are activated by p17. Here, we report for the first time that p17 functions as a nucleoporin Tpr suppressor that leads to p53 nuclear accumulation and consequently activates p53, p21, and PTEN. The nuclear localization signal (119IAAKRGRQLD128 of p17 has been identified for Tpr binding. This study has shown that Tpr suppression occurs by p17 interacting with Tpr and by reducing the transcription level of Tpr, which together inhibit Tpr function. In addition to upregulation of PTEN by activation of p53 pathway, this study also suggests that ARV protein p17 acts as a positive regulator of PTEN. ARV p17 stabilizes PTEN by stimulating phosphorylation of cytoplasmic PTEN and by elevating Rak-PTEN association to prevent it from E3 ligase NEDD4-1 targeting. To activate PTEN, p17 is able to promote β-arrestin-mediated PTEN translocation from the cytoplasm to the plasma membrane via a Rock-1-dependent manner. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated downregulation of cyclin D1 and CDK4. Furthermore, Tpr and CDK4 knockdown increased virus production in contrast to depletion of p53, PTEN, and LC3 reducing virus yield. Taken together, our data suggest that p17-mediated Tpr suppression positively regulates p53, PTEN, and p21 and negatively regulates PI3K/AKT/mTOR and ERK signaling pathways, both of which are beneficial for virus replication.

  2. p62 modulates Akt activity via association with PKCζ in neuronal survival and differentiation

    International Nuclear Information System (INIS)

    Joung, Insil; Kim, Hak Jae; Kwon, Yunhee Kim

    2005-01-01

    p62 is a ubiquitously expressed phosphoprotein that interacts with a number of signaling molecules and a major component of neurofibrillary tangles in the brain of Alzheimer's disease patients. It has been implicated in important cellular functions such as cell proliferation and anti-apoptotic pathways. In this study, we have addressed the potential role of p62 during neuronal differentiation and survival using HiB5, a rat neuronal progenitor cell. We generated a recombinant adenovirus encoding T7-epitope tagged p62 to reliably transfer p62 cDNA into the neuronal cells. The results show that an overexpression of p62 led not only to neuronal differentiation, but also to decreased cell death induced by serum withdrawal in HiB5 cells. In this process p62-dependent Akt phosphorylation occurred via the release of Akt from PKCζ by association of p62 and PKCζ, which is known as a negative regulator of Akt activation. These findings indicate that p62 facilitates cell survival through novel signaling cascades that result in Akt activation. Furthermore, we found that p62 expression was induced during neuronal differentiation. Taken together, the data suggest p62 is a regulator of neuronal cell survival and differentiation

  3. Phosphomimetic mutation of the mitotically phosphorylated serine 1880 compromises the interaction of the transmembrane nucleoporin gp210 with the nuclear pore complex

    International Nuclear Information System (INIS)

    Onischenko, Evgeny A.; Crafoord, Ellinor; Hallberg, Einar

    2007-01-01

    The nuclear pore complexes (NPCs) reversibly disassemble and reassemble during mitosis. Disassembly of the NPC is accompanied by phosphorylation of many nucleoporins although the function of this is not clear. It was previously shown that in the transmembrane nucleoporin gp210 a single serine residue at position 1880 is specifically phosphorylated during mitosis. Using amino acid substitution combined with live cell imaging, time-lapse microscopy and FRAP, we investigated the role of serine 1880 in binding of gp210 to the NPC in vivo. An alanine substitution mutant (S1880A) was significantly more dynamic at the NPC compared to the wild-type protein, suggesting that serine 1880 is important for binding of gp210 to the NPC. Moreover a glutamate substitution (S1880E) closely mimicking phosphorylated serine specifically interfered with incorporation of gp210 into the NPC and compromised its post-mitotic recruitment to the nuclear envelope of daughter nuclei. Our findings are consistent with the idea that mitotic phosphorylation acts to dissociate gp210 from the structural elements of the NPC

  4. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.

    Directory of Open Access Journals (Sweden)

    Francesca Di Nunzio

    Full Text Available The nuclear pore complex (NPC mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.

  5. p62/Sequestosome-1 Is Indispensable for Maturation and Stabilization of Mallory-Denk Bodies.

    Directory of Open Access Journals (Sweden)

    Pooja Lahiri

    Full Text Available Mallory-Denk bodies (MDBs are hepatocytic protein aggregates found in steatohepatitis and several other chronic liver diseases as well as hepatocellular carcinoma. MDBs are mainly composed of phosphorylated keratins and stress protein p62/Sequestosome-1 (p62, which is a common component of cytoplasmic aggregates in a variety of protein aggregation diseases. In contrast to the well-established role of keratins, the role of p62 in MDB pathogenesis is still elusive. We have generated total and hepatocyte-specific p62 knockout mice, fed them with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC to induce MDBs and allowed the mice to recover from DDC intoxication on a standard diet to investigate the role of p62 in MDB formation and elimination. In the absence of p62, smaller, granular and less distinct MDBs appeared, which failed to mature to larger and compact inclusions. Moreover, p62 deficiency impaired the binding of other proteins such as NBR1 and Hsp25 to MDBs and altered the cellular defense mechanism by downregulation of Nrf2 target genes. Upon recovery from DDC intoxication on a standard diet, there was an enhanced reduction of p62-deficient MDBs, which was accompanied by a pronounced decrease in ubiquitinated proteins. Our data provide strong evidence that keratin aggregation is the initial step in MDB formation in steatohepatitis-related mouse models. Interaction of p62 with keratin aggregates then leads to maturation i.e., enlargement and stabilization of the MDBs as well as recruitment of other MDB-associated proteins.

  6. NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62.

    Science.gov (United States)

    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-07-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

  7. Two Differential Binding Mechanisms of FG-Nucleoporins and Nuclear Transport Receptors

    Directory of Open Access Journals (Sweden)

    Piau Siong Tan

    2018-03-01

    Full Text Available Summary: Phenylalanine-glycine-rich nucleoporins (FG-Nups are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex (NPC. Previous studies showed that nuclear transport receptors (NTRs were found to interact with FG-Nups by forming an “archetypal-fuzzy” complex through the rapid formation and breakage of interactions with many individual FG motifs. Here, we use single-molecule studies combined with atomistic simulations to show that, in sharp contrast, FG-Nup214 undergoes a coupled reconfiguration-binding mechanism when interacting with the export receptor CRM1. Association and dissociation rate constants are more than an order of magnitude lower than in the archetypal-fuzzy complex between FG-Nup153 and NTRs. Unexpectedly, this behavior appears not to be encoded selectively into CRM1 but rather into the FG-Nup214 sequence. The same distinct binding mechanisms are unperturbed in O-linked β-N-acetylglucosamine-modified FG-Nups. Our results have implications for differential roles of distinctly spatially distributed FG-Nup⋅NTR interactions in the cell. : Archetypal-fuzzy complexes found in most FG-Nucleoporin⋅nuclear transport receptor complexes allow fast yet specific nuclear transport. Tan et al. show that FG-Nup214, located at the periphery of the nuclear pore complex, binds to CRM1⋅RanGTP via a coupled reconfiguration-binding mechanism, which can enable different functionalities e.g., cargo release. Keywords: intrinsically disordered protein, glycosylation, FG-Nup, nuclear transport receptors, binding mechanism, single-molecule FRET, molecular dynamics simulations

  8. NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62

    Science.gov (United States)

    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-01-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus. PMID:21543505

  9. RanGTP-mediated nuclear export of karyopherin α involves its interaction with the nucleoporin Nup153

    OpenAIRE

    Moroianu, Junona; Blobel, Günter; Radu, Aurelian

    1997-01-01

    Using binding assays, we discovered an interaction between karyopherin α2 and the nucleoporin Nup153 and mapped their interacting domains. We also isolated a 15-kDa tryptic fragment of karyopherin β1, termed β1*, that contains a determinant for binding to the peptide repeat containing nucleoporin Nup98. In an in vitro assay in which export of endogenous nuclear karyopherin α from nuclei of digitonin-permeabilized cells was quantitatively monitored by indirect immunofluorescence with anti-kary...

  10. Reduced expression of AtNUP62 nucleoporin gene affects auxin response in Arabidopsis

    DEFF Research Database (Denmark)

    Boeglin, Martin; Fuglsang, Anja Thoe; Luu, Doan Trung

    2016-01-01

    seedlings and at the adult stage in stipules of cauline leaves. The atnup62-1 mutant, harbouring a T-DNA insertion in intron 5, was identified as a knock-down mutant. It displayed developmental phenotypes that suggested defects in auxin transport or responsiveness. Atnup62 mutant plantlets were found...... to be hypersensitive to auxin, at the cotyledon and root levels. The phenotype of the AtNUP62-GFP overexpressing line further supported the existence of a link between AtNUP62 and auxin signalling. Furthermore, the atnup62 mutation led to an increase in the activity of the DR5 auxin-responsive promoter, and suppressed...

  11. Lipidation of BmAtg8 is required for autophagic degradation of p62 bodies containing ubiquitinated proteins in the silkworm, Bombyx mori.

    Science.gov (United States)

    Ji, Ming-Ming; Lee, Jae Man; Mon, Hiroaki; Iiyama, Kazuhiro; Tatsuke, Tsuneyuki; Morokuma, Daisuke; Hino, Masato; Yamashita, Mami; Hirata, Kazuma; Kusakabe, Takahiro

    2017-10-01

    p62/Sequestosome-1 (p62/SQSTM1, hereafter referred to as p62) is a major adaptor that allows ubiquitinated proteins to be degraded by autophagy, and Atg8 homologs are required for p62-mediated autophagic degradation, but their relationship is still not understood in Lepidopteran insects. Here it is clearly demonstrated that the silkworm homolog of mammalian p62, Bombyx mori p62 (Bmp62), forms p62 bodies depending on its Phox and Bem1p (PB1) and ubiquitin-associated (UBA) domains. These two domains are associated with Bmp62 binding to ubiquitinated proteins to form the p62 bodies, and the UBA domain is essential for the binding, but Bmp62 still self-associates without the PB1 or UBA domain. The p62 bodies in Bombyx cells are enclosed by BmAtg9-containing membranes and degraded via autophagy. It is revealed that the interaction between the Bmp62 AIM motif and BmAtg8 is critical for the autophagic degradation of the p62 bodies. Intriguingly, we further demonstrate that lipidation of BmAtg8 is required for the Bmp62-mediated complete degradation of p62 bodies by autophagy. Our results should be useful in future studies of the autophagic mechanism in Lepidopteran insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A subset of FG-nucleoporins is necessary for efficient Msn5-mediated nuclear protein export

    Science.gov (United States)

    Finn, Erin M.; DeRoo, Elise P.; Clement, George W.; Rao, Sheila; Kruse, Sarah E.; Kokanovich, Kate M.; Belanger, Kenneth D.

    2013-01-01

    The transport of proteins between the cytoplasm and nucleus requires interactions between soluble transport receptors (karyopherins) and phenylalanine-glycine (FG) repeat domains on nuclear pore complex proteins (nucleoporins). However, the role of specific FG repeat-containing nucleoporins in nuclear protein export has not been carefully investigated. We have developed a novel kinetic assay to investigate the relative export kinetics mediated by the karyopherin Msn5/Kap142 in yeast containing specific FG-Nup mutations. Using the Msn5 substrate Crz1 as a marker for Msn5-mediated protein export, we observe that deletions of NUP100 or NUP2 result in decreased rates of Crz1 export, while nup60Δ and nup42Δ mutants do not vary significantly from wild type. The decreased Msn5 export rate in nup100Δ was confirmed using Mig1-GFP as a transport substrate. A nup100ΔGLFG mutant shows defects in nuclear export kinetics similar to a nup100Δ deletion. Removal of FG-repeats from Nsp1 also decreases export kinetics, while a loss of Nup1 FXFGs does not. To confirm that our export data reflected functional differences in protein localization, we performed Crz1 transcription activation assays using a CDRE::LacZ reporter gene that is upregulated upon increased transcription activation by Crz1 in vivo. We observe that expression from this reporter increases in nup100ΔGLFG and nsp1ΔFGΔFXFG strains that exhibit decreased Crz1 export kinetics but resembles wild-type levels in nup1ΔFXFG strains that do not exhibit export defects. These data provide evidence that the export of Msn5 is likely mediated by a specific subset of FG-Nups and that the GLFG repeat domain of Nup100 is important for Msn5-mediated nuclear protein export. PMID:23295456

  13. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

    Science.gov (United States)

    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

    2015-05-12

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

  14. The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold

    Directory of Open Access Journals (Sweden)

    Rodolfo Ciuffa

    2015-05-01

    Full Text Available The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo.

  15. Interaction of actinide ions with [NaP5W30O110]14- and [P2W18O62]6-

    International Nuclear Information System (INIS)

    Choppin, G.R.; Wall, D.E.

    2003-01-01

    Stability constants (log β 101 ) of Th 4+ , UO 2 2+ , NpO 2 + and Am 3+ with [NaP 5 W 30 O 110 ] 14- were determined by solvent extraction (μ = 0.1M NaCl) and found to be 6.18 ± 0.07, 3.80 ± 0.06, 2.98 ± 0.04, and 5.85 ± 0.05, respectively. The order of stability constants: Th 4+ > Am 3+ > UO 2 2+ > NpO 2 + is due to electrostatic repulsion between the actinyl oxygens and oxygens on the polyoxometalate surface. The order of stability constants for metal complexes with [P 2 W 18 O 62 ] 6- is Th 4+ > UO 2 2+ > Eu 3+ >NpO 2 + because the steric repulsion between actinyl oxygens and oxygens on polyoxometalate are less important. Enthalpies of complexation were measured by calorimetric titration of Th 4+ , UO 2 2+ , Nd 3+ with [NaP 5 W 30 O 110 ] 14- and [P 2 W 18 O 62 ] 6- . The results indicate that the conformation and charge distribution of the microscopic surface structures are important factors in the formation of pseudocolloids. (author)

  16. Detection of p62 on Paraffin Sections by Immunohistochemistry.

    Science.gov (United States)

    Watson, Alexander S; Soilleux, Elizabeth J

    2015-08-03

    The study of autophagy in human disease is a rapidly expanding field. Diagnostic paraffin sections of a variety of patient tissues, including bone marrow, are available to researchers-yet are unsuitable for traditional autophagy quantification methods such as western blot or electron microscopy. This protocol outlines the immunohistochemical detection of the protein p62 (sequestosome-1, encoded by the gene SQSTM1)-an indicator of autophagic degradative activity-in slide-mounted paraffin sections such as bone marrow samples cut by a trephine. The p62 protein is an autophagic cargo adaptor, capable of binding to ubiquitylated proteins as well as autophagosome membrane proteins (LC3B and GABA(A) receptor-associated protein [GABARAP] family members) and hypothesized thus to target protein aggregates for lysosomal degradation. p62 itself is degraded by autophagy, remaining at low levels when autophagy is induced, and has been shown to accumulate when autophagy is deficient. Qualitative assessment and comparison of p62 staining between healthy and disease sections or disease subtypes will help target further investigation into the potential roles for autophagy in a variety of disorders. © 2015 Cold Spring Harbor Laboratory Press.

  17. Lipopolysaccharide stimulates p62-dependent autophagy-like aggregate clearance in hepatocytes.

    Science.gov (United States)

    Chen, Christine; Deng, Meihong; Sun, Qian; Loughran, Patricia; Billiar, Timothy R; Scott, Melanie J

    2014-01-01

    Impairment of autophagy has been associated with liver injury. TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive. The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR. Autophagy-like activation was measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NF κ B transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.

  18. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death

  19. Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-09-25

    Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death.

  20. Nucleoporin Nup98 associates with Trx/MLL and NSL histone-modifying complexes and regulates Hox gene expression.

    Science.gov (United States)

    Pascual-Garcia, Pau; Jeong, Jieun; Capelson, Maya

    2014-10-23

    The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups). In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBD-R2/NSL [corrected] and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.

  1. LC3B is indispensable for selective autophagy of p62 but not basal autophagy

    International Nuclear Information System (INIS)

    Maruyama, Yoko; Sou, Yu-Shin; Kageyama, Shun; Takahashi, Takao; Ueno, Takashi; Tanaka, Keiji; Komatsu, Masaaki; Ichimura, Yoshinobu

    2014-01-01

    Highlights: • Knockdown of LC3 or GABARAP families did not affect the basal autophagy. • LC3B has a higher affinity for the autophagy-specific substrate, p62, than GABARAPs. • siRNA-mediated knockdown of LC3B, but not that of GABARAPs, resulted in significant accumulation of p62. - Abstract: Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs

  2. LC3B is indispensable for selective autophagy of p62 but not basal autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Yoko [Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Department of Pediatrics, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Sou, Yu-Shin; Kageyama, Shun [Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Takahashi, Takao [Department of Pediatrics, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Ueno, Takashi [Division of Proteomics and Biomolecular Science, Center for Biomedical Research Resources, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Tanaka, Keiji [Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan); Department of Biochemistry, School of Medicine, Niigata University, Niigata 951-8510 (Japan); Ichimura, Yoshinobu, E-mail: ichimura-ys@igakuken.or.jp [Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan)

    2014-03-28

    Highlights: • Knockdown of LC3 or GABARAP families did not affect the basal autophagy. • LC3B has a higher affinity for the autophagy-specific substrate, p62, than GABARAPs. • siRNA-mediated knockdown of LC3B, but not that of GABARAPs, resulted in significant accumulation of p62. - Abstract: Autophagy is a unique intracellular protein degradation system accompanied by autophagosome formation. Besides its important role through bulk degradation in supplying nutrients, this system has an ability to degrade certain proteins, organelles, and invading bacteria selectively to maintain cellular homeostasis. In yeasts, Atg8p plays key roles in both autophagosome formation and selective autophagy based on its membrane fusion property and interaction with autophagy adaptors/specific substrates. In contrast to the single Atg8p in yeast, mammals have 6 homologs of Atg8p comprising LC3 and GABARAP families. However, it is not clear these two families have different or similar functions. The aim of this study was to determine the separate roles of LC3 and GABARAP families in basal/constitutive and/or selective autophagy. While the combined knockdown of LC3 and GABARAP families caused a defect in long-lived protein degradation through lysosomes, knockdown of each had no effect on the degradation. Meanwhile, knockdown of LC3B but not GABARAPs resulted in significant accumulation of p62/Sqstm1, one of the selective substrate for autophagy. Our results suggest that while mammalian Atg8 homologs are functionally redundant with regard to autophagosome formation, selective autophagy is regulated by specific Atg8 homologs.

  3. Interactions involved in pH protection of the alphavirus fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Fields, Whitney; Kielian, Margaret, E-mail: margaret.kielian@einstein.yu.edu

    2015-12-15

    The alphavirus membrane protein E1 mediates low pH-triggered fusion of the viral and endosome membranes during virus entry. During virus biogenesis E1 associates as a heterodimer with the transmembrane protein p62. Late in the secretory pathway, cellular furin cleaves p62 to the mature E2 protein and a peripheral protein E3. E3 remains bound to E2 at low pH, stabilizing the heterodimer and thus protecting E1 from the acidic pH of the secretory pathway. Release of E3 at neutral pH then primes the virus for fusion during entry. Here we used site-directed mutagenesis and revertant analysis to define residues important for the interactions at the E3–E2 interface. Our data identified a key residue, E2 W235, which was required for E1 pH protection and alphavirus production. Our data also suggest additional residues on E3 and E2 that affect their interacting surfaces and thus influence the pH protection of E1 during alphavirus exit.

  4. Facilitated aggregation of FG nucleoporins under molecular crowding conditions.

    Science.gov (United States)

    Milles, Sigrid; Huy Bui, Khanh; Koehler, Christine; Eltsov, Mikhail; Beck, Martin; Lemke, Edward A

    2013-02-01

    Intrinsically disordered and phenylalanine-glycine-rich nucleoporins (FG Nups) form a crowded and selective transport conduit inside the NPC that can only be transited with the help of nuclear transport receptors (NTRs). It has been shown in vitro that FG Nups can assemble into two distinct appearances, amyloids and hydrogels. If and how these phenomena are linked and if they have a physiological role still remains unclear. Using a variety of high-resolution fluorescence and electron microscopic (EM) tools, we reveal that crowding conditions mimicking the NPC environment can accelerate the aggregation and amyloid formation speed of yeast and human FG Nups by orders of magnitude. Aggregation can be inhibited by NTRs, providing a rationale on how the cell might control amyloid formation of FG Nups. The superb spatial resolving power of EM also reveals that hydrogels are enlaced amyloid fibres, and these findings have implications for existing transport models and for NPC assembly.

  5. The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent.

    Science.gov (United States)

    Tsuji, Takahiro; Sheehy, Noreen; Gautier, Virginie W; Hayakawa, Hitoshi; Sawa, Hirofumi; Hall, William W

    2007-05-04

    HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection.

  6. Characterization of the Ala62Pro polymorphic variant of human cytochrome P450 1A1 using recombinant protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Kang, Sukmo [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of); Dong, Mi Sook [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Park, Jung-Duck [College of Medicine, Chung-Ang University, Seoul (Korea, Republic of); Park, Jinseo; Rhee, Sangkee [College of Agriculture of Life Science, Seoul National University, Seoul (Korea, Republic of); Ryu, Doug-Young, E-mail: dyryu@snu.ac.kr [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of)

    2015-06-15

    Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located. - Highlights: • Ala62 is located in α-helix A of the carcinogen-metabolizing enzyme CYP1A1. • Pro acts as an α-helix breaker. • A variant protein of CYP1A1, Ala62Pro, had lower heme content than the wild-type. • The variant of CYP1A1 had lower enzyme activities than the wild-type.

  7. Lipotoxicity induces hepatic protein inclusions through TBK1-mediated p62/SQSTM1 phosphorylation.

    Science.gov (United States)

    Cho, Chun-Seok; Park, Hwan-Woo; Ho, Allison; Semple, Ian A; Kim, Boyoung; Jang, Insook; Park, Haeli; Reilly, Shannon; Saltiel, Alan R; Lee, Jun Hee

    2017-12-18

    Obesity commonly leads to hepatic steatosis, which often provokes lipotoxic injuries to hepatocytes that cause non-alcoholic steatohepatitis (NASH). NASH in turn is associated with the accumulation of insoluble protein aggregates that are composed of ubiquitinated proteins and ubiquitin adaptor p62/sequestosome 1 (SQSTM1). The formation of p62 inclusions in hepatocytes is the critical marker that distinguishes simple fatty liver from NASH and predicts a poor prognostic outcome for subsequent liver carcinogenesis. However, the molecular mechanism by which lipotoxicity induces protein aggregation is currently unknown. Here we show that upon saturated fatty acid-induced lipotoxicity, Tank-binding protein kinase 1 (TBK1) is activated and phosphorylates p62. The TBK1-mediated p62 phosphorylation is important for lipotoxicity-induced aggregation of ubiquitinated proteins and the formation of large protein inclusions in hepatocytes. In addition, cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), upstream regulators of TBK1, are involved in the lipotoxic activation of TBK1 and subsequent p62 phosphorylation in hepatocytes. Furthermore, TBK1 inhibition prevented formation of the ubiquitin-p62 aggregates, not only in cultured hepatocytes, but also in mouse models of obesity and NASH. These results suggest that lipotoxic activation of TBK1 and subsequent p62 phosphorylation are critical steps in the NASH pathology of protein inclusion accumulation in hepatocytes. This mechanism can provide an explanation for how hypernutrition and obesity promote the development of severe liver pathologies, such as steatohepatitis and liver cancer, by facilitating the formation of p62 inclusions. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  8. Genomic organization, transcript variants and comparative analysis of the human nucleoporin 155 (NUP155) gene

    DEFF Research Database (Denmark)

    Zhang, X.; Yang, J.; Yu, J.

    2002-01-01

    Nucleoporin 155 (Nup155) is a major component of the nuclear pore complex (NPC) involved in cellular nucleo-cytoplasmic transport. We have acquired the complete sequence and interpreted the genomic organization of the Nup155 orthologos from human (Homo sapiens) and pufferfish (Fugu rubripes), which...... complementary to RNAs of the Nup155 orthologs from Fugu and mouse. Comparative analysis of the Nup155 orthologs in many species, including H. sapiens, Mus musculus, Rattus norvegicus, F. rubripes, Arabidopsis thaliana, Drosophila melanogaster, and Saccharomyces cerevisiae, has revealed two paralogs in S...

  9. SH003 suppresses breast cancer growth by accumulating p62 in autolysosomes.

    Science.gov (United States)

    Choi, Youn Kyung; Cho, Sung-Gook; Choi, Yu-Jeong; Yun, Yee Jin; Lee, Kang Min; Lee, Kangwook; Yoo, Hye-Hyun; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-10-24

    Drug markets revisits herbal medicines, as historical usages address their therapeutic efficacies with less adverse effects. Moreover, herbal medicines save both cost and time in development. SH003, a modified version of traditional herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been revealed to inhibit tumor growth and metastasis on highly metastatic breast cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is imperative for maintenance cellular homeostasis, thereby playing critical roles in cancer progression. Inhibition of autophagy by pharmacological agents induces apoptotic cell death in cancer cells, resulting in cancer treatment. In this study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive oxygen species (ROS) generation and attenuates tumor growth. SH003 induced autophagosome and autolysosome formation by inhibiting activation of STAT3- and mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins, resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of p62/SQSTM1 caused the increase of ROS, which resulted in the induction of apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could function as an important mediator for ROS generation-dependent cell death suggesting that SH003 may be useful for treating breast cancer.

  10. Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains.

    Science.gov (United States)

    Fiserova, Jindriska; Spink, Matthew; Richards, Shane A; Saunter, Christopher; Goldberg, Martin W

    2014-01-01

    Nuclear pore complexes (NPCs) mediate nucleocytoplasmic movement. The central channel contains proteins with phenylalanine-glycine (FG) repeats, or variations (GLFG, glycine-leucine-phenylalanine-glycine). These are 'intrinsically disordered' and often represent weak interaction sites that become ordered upon interaction. We investigated this possibility during nuclear transport. Using electron microscopy of S. cerevisiae, we show that NPC cytoplasmic filaments form a dome-shaped structure enclosing GLFG domains. GLFG domains extend out of this structure and are part of an 'exclusion zone' that might act as a partial barrier to entry of transport-inert proteins. The anchor domain of a GLFG nucleoporin locates exclusively to the central channel. By contrast, the localisation of the GLFG domains varied between NPCs and could be cytoplasmic, central or nucleoplasmic and could stretch up to 80 nm. These results suggest a dynamic exchange between ordered and disordered states. In contrast to diffusion through the NPC, transport cargoes passed through the exclusion zone and accumulated near the central plane. We also show that movement of cargo through the NPC is accompanied by relocation of GLFG domains, suggesting that binding, restructuring and movement of these domains could be part of the translocation mechanism.

  11. High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Iwadate, Reiko; Inoue, Jun; Tsuda, Hitoshi; Takano, Masashi; Furuya, Kenichi; Hirasawa, Akira; Aoki, Daisuke; Inazawa, Johji

    2014-01-01

    High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto High /Nuc Low ), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto High /Nuc Low subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma

  12. Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

    Science.gov (United States)

    Chao, Angel; Lin, Chiao-Yun; Chao, An-Ning; Tsai, Chia-Lung; Chen, Ming-Yu; Lee, Li-Yu; Chang, Ting-Chang; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

    2017-09-26

    Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

  13. Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.

    Science.gov (United States)

    Homma, Takujiro; Ishibashi, Daisuke; Nakagaki, Takehiro; Satoh, Katsuya; Sano, Kazunori; Atarashi, Ryuichiro; Nishida, Noriyuki

    2014-03-28

    Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrP(Sc)). In this study, we focused on the mechanism of clearance of PrP(Sc), which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrP(Sc), forming a large aggregate in the perinuclear region, hereafter referred to as PrP(Sc)-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrP(Sc) in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrP(Sc). Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.

  14. The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation.

    Science.gov (United States)

    Yokoyama, Hideki; Koch, Birgit; Walczak, Rudolf; Ciray-Duygu, Fulya; González-Sánchez, Juan Carlos; Devos, Damien P; Mattaj, Iain W; Gruss, Oliver J

    2014-01-01

    The GTP-bound form of the Ran GTPase (RanGTP), produced around chromosomes, drives nuclear envelope and nuclear pore complex (NPC) re-assembly after mitosis. The nucleoporin MEL-28/ELYS binds chromatin in a RanGTP-regulated manner and acts to seed NPC assembly. Here we show that, upon mitotic NPC disassembly, MEL-28 dissociates from chromatin and re-localizes to spindle microtubules and kinetochores. MEL-28 directly binds microtubules in a RanGTP-regulated way via its C-terminal chromatin-binding domain. Using Xenopus egg extracts, we demonstrate that MEL-28 is essential for RanGTP-dependent microtubule nucleation and spindle assembly, independent of its function in NPC assembly. Specifically, MEL-28 interacts with the γ-tubulin ring complex and recruits it to microtubule nucleation sites. Our data identify MEL-28 as a RanGTP target that functions throughout the cell cycle. Its cell cycle-dependent binding to chromatin or microtubules discriminates MEL-28 functions in interphase and mitosis, and ensures that spindle assembly occurs only after NPC breakdown.

  15. Autophagy-associated proteins BAG3 and p62 in testicular cancer.

    Science.gov (United States)

    Bartsch, Georg; Jennewein, Lukas; Harter, Patrick N; Antonietti, Patrick; Blaheta, Roman A; Kvasnicka, Hans-Michael; Kögel, Donat; Haferkamp, Axel; Mittelbronn, Michel; Mani, Jens

    2016-03-01

    Testicular germ cell tumors (TGCT) represent the most common malignant tumor group in the age group of 20 to 40-years old men. The potentially curable effect of cytotoxic therapy in TGCT is mediated mainly by the induction of apoptosis. Autophagy has been discussed as an alternative mechanism of cell death but also of treatment resistance in various types of tumors. However, in TGCT the expression and role of core autophagy-associated factors is hitherto unknown. We designed the study in order to evaluate the potential role of autophagy-associated factors in the development and progression of testicular cancers. Eighty-four patients were assessed for autophagy (BAG3, p62) and apoptosis (cleaved caspase 3) markers using immunohistochemistry (IHC) on tissue micro- arrays. In addition, western blot analyses of frozen tissue of seminoma and non-seminoma were performed. Our findings show that BAG3 was significantly upregulated in seminoma as compared to non-seminoma but not to normal testicular tissue. No significant difference of p62 expression was detected between neoplastic and normal tissue or between seminoma and non-seminoma. BAG3 and p62 showed distinct loco‑regional expression patterns in normal and neoplastic human testicular tissues. In contrast to the autophagic markers, apoptosis rate was significantly higher in testicular tumors as compared to normal testicular tissue, but not between different TGCT subtypes. The present study, for the first time, examined the expression of central autophagy proteins BAG3 and p62 in testicular cancer. Our findings imply that in general apoptosis but not autophagy induction differs between normal and neoplastic testis tissue.

  16. ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.

    Science.gov (United States)

    Linares, Juan F; Cordes, Thekla; Duran, Angeles; Reina-Campos, Miguel; Valencia, Tania; Ahn, Christopher S; Castilla, Elias A; Moscat, Jorge; Metallo, Christian M; Diaz-Meco, Maria T

    2017-12-05

    Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. ATF4 upregulation by p62 deficiency in the stroma activates glucose carbon flux through a pyruvate carboxylase-asparagine synthase cascade that results in asparagine generation as a source of nitrogen for stroma and tumor epithelial proliferation. Thus, p62 directly targets nuclear transcription factors to control metabolic reprogramming in the microenvironment and repress tumorigenesis, and identifies ATF4 as a synthetic vulnerability in p62-deficient tumor stroma. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  18. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  19. Changes in platelet functional parameters and CD62 P expression ...

    African Journals Online (AJOL)

    EB

    Objective: To investigate the changes in platelet functional parameters and CD62 P expression in liver cirrhosis as a possible .... bleeding and non-bleeding group with hepatic cirrhosis (±s). Group ... the body's coagulate function requirement.

  20. Analysis of p-bar p scattering at 31 GeV and 62 GeV by the Chou-Yang model

    International Nuclear Information System (INIS)

    Padua, A.B. de; Covolan, R.J.M.; Souza Paes, J.T. de

    1988-01-01

    The p-bar p scattering is analysed at 31 GeV and 62 GeV energies for momentum transfers in the range O 2 . The experimental (dσ/dt)p-bar p values were fitted using a pure imaginary written as a sum of exponentials, that is, a(s,t)=a(s,O) σ n i=l α i e βit . Using the parameters obtained we have calculated the absorption constant K p-bar p the form factor and the mean square radius of the p-bar matter distribuition by the Chou-Yang model. These calculations reveal a ''dip'' around -t approx.= 1.3 (GeV/c) 2 at 31 GeV and 62 GeV. (author) [pt

  1. A PYY Q62P variant linked to human obesity

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska,Anna; Collier, John Michael; Hebert, Sybil; Doelle, Heather; Dent,Robert; Pennacchio, Len A.; McPherson, Ruth

    2005-06-27

    Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysis of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.

  2. Super-resolution mapping of scaffold nucleoporins in the nuclear pore complex.

    Science.gov (United States)

    Ma, Jiong; Kelich, Joseph M; Junod, Samuel L; Yang, Weidong

    2017-04-01

    The nuclear pore complex (NPC), composed of ∼30 different nucleoporins (Nups), is one of the largest supramolecular structures in eukaryotic cells. Its octagonal ring scaffold perforates the nuclear envelope and features a unique molecular machinery that regulates nucleocytoplasmic transport. However, the precise copy number and the spatial location of each Nup in the native NPC remain obscure due to the inherent difficulty of counting and localizing proteins inside of the sub-micrometer supramolecular complex. Here, we combined super-resolution single-point edge-excitation subdiffraction (SPEED) microscopy and nanobody-specific labeling to reveal the spatial distribution of scaffold Nups within three separate layers in the native NPC with a precision of ∼3 nm. Our data reveal both the radial and axial spatial distributions for Pom121, Nup37 and Nup35 and provide evidence for their copy numbers of 8, 32 and 16, respectively, per NPC. This approach can help pave the path for mapping the entirety of Nups in native NPCs and also other structural components of macromolecular complexes. © 2017. Published by The Company of Biologists Ltd.

  3. Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes

    Science.gov (United States)

    Cauli, Alberto; Mathieu, Alessandro; Tedeschi, Valentina; Caristi, Silvana; Sorrentino, Rosa; Böckmann, Rainer A.; Fiorillo, Maria Teresa

    2012-01-01

    The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype. PMID:22403718

  4. Functional analysis of the interaction of the human immunodeficiency virus type 1 Rev nuclear export signal with its cofactors

    International Nuclear Information System (INIS)

    Kiss, A.; Li, L.; Gettemeier, T.; Venkatesh, L.K.

    2003-01-01

    Human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export of viral RNAs involves the interaction of its leucine-rich nuclear export sequence (NES) with nuclear cofactors. In yeast two-hybrid screens of a human lymph node derived cDNA expression library, we identified the human nucleoporin Nup98 as a highly specific and potent interactor of the Rev NES. Using an extensive panel of nuclear export positive and negative mutants of the functionally homologous NESs of the HIV-1 Rev, human T cell leukemia virus type 1 (HTLV-1) Rex, and equine infectious anemia virus (EIAV) Rev proteins, physiologically significant interaction of hNup98 with the various NESs was demonstrated. Missense mutations in the yeast nuclear export factor Crm1p that abrogated Rev NES interaction with the XXFG repeat-containing nucleoporin, Rab/hRIP, had minimal effects on the interaction of GLFG repeat-containing hNup98. Functional analysis of Nup98 domains required for nuclear localization demonstrated that the entire ORF was required for efficient incorporation into the nuclear envelope. A putative nuclear localization signal was identified downstream of the GLFG repeat region. Whereas overexpression of both full-length Nup98 and the amino-terminal GLFG repeat region, but not the unique carboxy-terminal region, induced significant suppression of HIV unspliced RNA export, lower levels of exogenous Nup98 expression resulted in a relatively modest increase in unspliced RNA export. These results suggest a physiological role for hNup98 in modulating Rev-dependent RNA export during HIV infection

  5. Spectra of fast protons produced in the pA → pX reaction at the angle of 62 mrad

    International Nuclear Information System (INIS)

    Barabash, L.Z.; Buklej, A.E.; Gavrilov, V.B.

    1982-01-01

    Within the framework of a program of investigations into yields of secondary particles form internal targets of an accelerator obtained were experimetnal data on inclusive production of protons in pA interactions at 62 mradn angle at initial momenta of 4.0; 6.6; 9.5 GeV/c. The data obtained on differential cross sections of proton yields are tabulated. A- and t-dependences of quasi-elastic proton scattering with nuclei are discussed. A-dependence of cross sections of inelastic quasi-free reactions both in the region of isobar production and on the left of this region within the errors is the same as for quasi-elastic peak, α approximately 0.45. This α value is markedly less than a value characteristic of the A-dependence of total cross sections

  6. Vanadium(V-Substitution Reactions of Wells–Dawson-Type Polyoxometalates: From [X2M18O62]6− (X = P, As; M = Mo, W to [X2VM17O62]7−

    Directory of Open Access Journals (Sweden)

    Tadaharu Ueda

    2015-07-01

    Full Text Available The formation processes of V(V-substituted polyoxometalates with the Wells–Dawson-type structure were studied by cyclic voltammetry and by 31P NMR and Raman spectroscopy. Generally, the vanadium-substituted heteropolytungstates, [P2VW17O62]7− and [As2VW17O62]7−, were prepared by mixing equimolar amounts of the corresponding lacunary species—[P2W17O61]10− and [As2W17O61]10−—and vanadate. According to the results of various measurements in the present study, the tungsten site in the framework of [P2W18O62]6− and [As2W18O62]6− without defect sites could be substituted with V(V to form the [P2VW17O62]7− and [As2VW17O62]7−, respectively. The order in which the reagents were mixed was observed to be the key factor for the formation of Dawson-type V(V-substituted polyoxometalates. Even when the concentration of each reagent was identical, the final products differed depending on the order of their addition to the reaction mixture. Unlike Wells–Dawson-type heteropolytungstates, the molybdenum sites in the framework of [P2Mo18O62]6− and [As2Mo18O62]6− were substituted with V(V, but formed Keggin-type [PVMo11O40]4− and [AsVMo11O40]4− instead of [P2VMo17O62]7− and [As2VMo17O62]7−, respectively, even though a variety of reaction conditions were used. The formation constant of the [PVMo11O40]4− and [AsVMo11O40]4− was hypothesized to be substantially greater than that of the [P2VMo17O62]7− and [As2VMo17O62]7−.

  7. Mechanisms involved in the p62-73 idiopeptide-modulated delay of lupus nephritis in SNF(1) mice.

    Science.gov (United States)

    Nyland, J F; Stoll, M L; Jiang, F; Feng, F; Gavalchin, J

    2012-12-01

    The F(1) progeny of the (SWR × NZB) cross develop a lupus-like disease with high serum titers of autoantibodies, and increased frequency and severity of immune complex-mediated glomerulonephritis in females. In previous work, we found that an idiotypic peptide corresponding to aa62-73 (p62-73) of the heavy chain variable region of autoantibody 540 (Id(LN)F(1)) induced the proliferation of p62-73 idiotype-reactive T cell clones. Further, monthly immunization of pre-nephritic SNF(1) female mice with p62-73 resulted in decreased nephritis and prolonged life spans. Here we show that this treatment modulated proliferative responses to Id(LN)F(1) antigen, including a reduction in the population of idiopeptide-presenting antigen-presenting cells (APCs), as early as two weeks after immunization (10 weeks of age). Th1-type cytokine production was increased at 12 weeks of age. The incidence and severity of nephritis was reduced by 14 weeks compared to controls. Clinical indicators of nephritis, specifically histological evidence of glomerulonephritis and urine protein levels, were reduced by 20 weeks. Together these data suggest that events involved in the mechanism(s) whereby p62-73 immunization delayed nephritis occurred early after immunization, and involved modulation of APCs, B and T cell populations.

  8. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

    Science.gov (United States)

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

    2014-03-01

    The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

  9. Analysis of the Varicella-Zoster Virus IE62 N-Terminal Acidic Transactivating Domain and Its Interaction with the Human Mediator Complex▿

    OpenAIRE

    Yamamoto, Shinobu; Eletsky, Alexander; Szyperski, Thomas; Hay, John; Ruyechan, William T.

    2009-01-01

    The varicella-zoster virus major transactivator, IE62, contains a potent N-terminal acidic transcriptional activation domain (TAD). Our experiments revealed that the minimal IE62 TAD encompasses amino acids (aa) 19 to 67. We showed that the minimal TAD interacts with the human Mediator complex. Site-specific mutations revealed residues throughout the minimal TAD that are important for both activation and Mediator interaction. The TAD interacts directly with aa 402 to 590 of the MED25 subunit,...

  10. Proteotoxic stress induces phosphorylation of p62/SQSTM1 by ULK1 to regulate selective autophagic clearance of protein aggregates.

    Directory of Open Access Journals (Sweden)

    Junghyun Lim

    Full Text Available Disruption of proteostasis, or protein homeostasis, is often associated with aberrant accumulation of misfolded proteins or protein aggregates. Autophagy offers protection to cells by removing toxic protein aggregates and injured organelles in response to proteotoxic stress. However, the exact mechanism whereby autophagy recognizes and degrades misfolded or aggregated proteins has yet to be elucidated. Mounting evidence demonstrates the selectivity of autophagy, which is mediated through autophagy receptor proteins (e.g. p62/SQSTM1 linking autophagy cargos and autophagosomes. Here we report that proteotoxic stress imposed by the proteasome inhibition or expression of polyglutamine expanded huntingtin (polyQ-Htt induces p62 phosphorylation at its ubiquitin-association (UBA domain that regulates its binding to ubiquitinated proteins. We find that autophagy-related kinase ULK1 phosphorylates p62 at a novel phosphorylation site S409 in UBA domain. Interestingly, phosphorylation of p62 by ULK1 does not occur upon nutrient starvation, in spite of its role in canonical autophagy signaling. ULK1 also phosphorylates S405, while S409 phosphorylation critically regulates S405 phosphorylation. We find that S409 phosphorylation destabilizes the UBA dimer interface, and increases binding affinity of p62 to ubiquitin. Furthermore, lack of S409 phosphorylation causes accumulation of p62, aberrant localization of autophagy proteins and inhibition of the clearance of ubiquitinated proteins or polyQ-Htt. Therefore, our data provide mechanistic insights into the regulation of selective autophagy by ULK1 and p62 upon proteotoxic stress. Our study suggests a potential novel drug target in developing autophagy-based therapeutics for the treatment of proteinopathies including Huntington's disease.

  11. PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-23

    p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.

  12. Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

    Science.gov (United States)

    Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

    2013-03-21

    HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

  13. Single molecule study of the intrinsically disordered FG-repeat nucleoporin 153.

    Science.gov (United States)

    Milles, Sigrid; Lemke, Edward A

    2011-10-05

    Nucleoporins (Nups), which are intrinsically disordered, form a selectivity filter inside the nuclear pore complex, taking a central role in the vital nucleocytoplasmic transport mechanism. These Nups display a complex and nonrandom amino-acid architecture of phenylalanine glycine (FG)-repeat clusters and intra-FG linkers. How such heterogeneous sequence composition relates to function and could give rise to a transport mechanism is still unclear. Here we describe a combined chemical biology and single-molecule fluorescence approach to study the large human Nup153 FG-domain. In order to obtain insights into the properties of this domain beyond the average behavior, we probed the end-to-end distance (R(E)) of several ∼50-residues long FG-repeat clusters in the context of the whole protein domain. Despite the sequence heterogeneity of these FG-clusters, we detected a reoccurring and consistent compaction from a relaxed coil behavior under denaturing conditions (R(E)/R(E,RC) = 0.99 ± 0.15 with R(E,RC) corresponding to ideal relaxed coil behavior) to a collapsed state under native conditions (R(E)/R(E,RC) = 0.79 ± 0.09). We then analyzed the properties of this protein on the supramolecular level, and determined that this human FG-domain was in fact able to form a hydrogel with physiological permeability barrier properties. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Protein Interaction Analysis Provides a Map of the Spatial and Temporal Organization of the Ciliary Gating Zone.

    Science.gov (United States)

    Takao, Daisuke; Wang, Liang; Boss, Allison; Verhey, Kristen J

    2017-08-07

    The motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium. Several protein complexes localize to the gating zone and may regulate ciliary protein composition; however, the mechanisms of ciliary gating and the dynamics of the gating components are largely unknown. Here, we used the BiFC (bimolecular fluorescence complementation) assay and report for the first time on the protein-protein interactions that occur between ciliary gating components and transiting cargoes during ciliary entry. We find that the nucleoporin Nup62 and the C termini of the nephronophthisis (NPHP) proteins NPHP4 and NPHP5 interact with the axoneme-associated kinesin-2 motor KIF17 and thus spatially map to the inner region of the ciliary gating zone. Nup62 and NPHP4 exhibit rapid turnover at the transition zone and thus define dynamic components of the gate. We find that B9D1, AHI1, and the N termini of NPHP4 and NPHP5 interact with the transmembrane protein SSTR3 and thus spatially map to the outer region of the ciliary gating zone. B9D1, AHI1, and NPHP5 exhibit little to no turnover at the transition zone and thus define components of a stable gating structure. These data provide the first comprehensive map of the molecular orientations of gating zone components along the inner-to-outer axis of the ciliary gating zone. These results advance our understanding of the functional roles of gating zone components in regulating ciliary protein composition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both

    Science.gov (United States)

    Narendra, Derek P; Kane, Lesley A; Hauser, David N; Fearnley, Ian M

    2010-01-01

    Mitochondria sustain damage with aging, and the resulting mitochondrial dysfunction has been implicated in a number of diseases including parkinson disease. We recently demonstrated that the E3 ubiquitin ligase Parkin, which is linked to recessive forms of parkinsonism, causes a dramatic increase in mitophagy and a change in mitochondrial distribution, following its translocation from the cytosol to mitochondria. Investigating how Parkin induces these changes may offer insight into the mechanisms that lead to the sequestration and elimination of damaged mitochondria. We report that following Parkin's translocation from the cytosol to mitochondria, Parkin (but not a pathogenic mutant) promotes the K63-linked polyubiquitination of mitochondrial substrate(s) and recruits the ubiquitin- and LC3-binding protein, p62/SQSTM1, to mitochondria. After its recruitment, p62/SQSTM1 mediates the aggregation of dysfunctional mitochondria through polymerization via its PB1 domain, in a manner analogous to its aggregation of polyubiquitinated proteins. Surprisingly and in contrast to what has been recently reported for ubiquitin-induced pexophagy and xenophagy, p62 appears to be dispensable for mitophagy. Similarly, mitochondrial-anchored ubiquitin is sufficient to recruit p62 and promote mitochondrial clustering, but does not promote mitophagy. Although VDAC1 (but not VDAC2) is ubiquitinated following mitochondrial depolarization, we find VDAC1 cannot fully account for the mitochondrial K63-linked ubiquitin immunoreactivity observed following depolarization, as it is also observed in VDAC1/3−/− mouse embryonic fibroblasts. Additionally, we find VDAC1 and VDAC3 are dispensable for the recruitment of p62, mitochondrial clustering and mitophagy. These results demonstrate that mitochondria are aggregated by p62, following its recruitment by Parkin in a VDAC1-independent manner. They also suggest that proteins other than p62 are likely required for mitophagy downstream of Parkin

  16. mRNA and protein dataset of autophagy markers (LC3 and p62) in several cell lines

    Science.gov (United States)

    Gómez-Sánchez, Rubén; Yakhine-Diop, Sokhna M.S.; Rodríguez-Arribas, Mario; Bravo-San Pedro, José M.; Martínez-Chacón, Guadalupe; Uribe-Carretero, Elisabet; Pinheiro de Castro, Diana C.J.; Pizarro-Estrella, Elisa; Fuentes, José M.; González-Polo, Rosa A.

    2016-01-01

    We characterized the dynamics of autophagy in vitro using four different cell systems and analyzing markers widely used in this field, i.e. LC3 (microtubule-associated protein 1 light chain 3; protein recruited from the cytosol (LC3-I) to the autophagosomal membrane where it is lipidated (LC3-II)) and p62/SQSTM1 (adaptor protein that serves as a link between LC3 and ubiquitinated substrates), (Klionsky et al., 2016) [1]. Data provided include analyses of protein levels of LC3 and p62 by Western-blotting and endogenous immunofluorescence experiments, but also p62 mRNA levels obtained by quantitative PCR (qPCR). To monitor the turnover of these autophagy markers and, thus, measure the flux of this pathway, cells were under starvation conditions and/or treated with bafilomycin A1 (Baf. A1) to block fusion of autophagosomes with lysosomes. PMID:27054171

  17. Structural and functional determinants of conserved lipid interaction domains of inward rectifying Kir6.2 channels.

    Science.gov (United States)

    Cukras, Catherine A; Jeliazkova, Iana; Nichols, Colin G

    2002-06-01

    All members of the inward rectifiier K(+) (Kir) channel family are activated by phosphoinositides and other amphiphilic lipids. To further elucidate the mechanistic basis, we examined the membrane association of Kir6.2 fragments of K(ATP) channels, and the effects of site-directed mutations of these fragments and full-length Kir6.2 on membrane association and K(ATP) channel activity, respectively. GFP-tagged Kir6.2 COOH terminus and GFP-tagged pleckstrin homology domain from phospholipase C delta1 both associate with isolated membranes, and association of each is specifically reduced by muscarinic m1 receptor-mediated phospholipid depletion. Kir COOH termini are predicted to contain multiple beta-strands and a conserved alpha-helix (residues approximately 306-311 in Kir6.2). Systematic mutagenesis of D307-F315 reveals a critical role of E308, I309, W311 and F315, consistent with residues lying on one side of a alpha-helix. Together with systematic mutation of conserved charges, the results define critical determinants of a conserved domain that underlies phospholipid interaction in Kir channels.

  18. Study of Heavy Flavours Production in pp Interactions at $\\sqrt{s}$ = 62 GeV

    CERN Multimedia

    2002-01-01

    The main purpose of experiment R422 is to study the production of Charm and Beauty particles in pp collisions at @Rs~=~62~GeV. According to a technique already used in our previous R415 experiments, the event selection is based on the detection of a prompt electron or positron as the signature for the s decay of one member of the pair of heavy-flavoured states produced in the interaction. The hadronic decay of the other member of the pair is then looked for via invariant mass studies for various possible decay channels. The electrons and positrons are identified by a system of two gas Cherenkov counters in series followed by an electromagnetic shower detector placed at 90|0 on both sides of the Split Field Magnet, while electrons/positrons originated by @p|0, and external @g conversions are rejected off-line using the information from a dE/dx chamber. The momentum of the charged particles produced in the event is measured by the Split Field Magnet spectrometer over about 75\\% of the total solid angle and some...

  19. /sup 58,60,62/Ni (. cap alpha. ,p) three--nucleon transfer reactions and. cap alpha. optical potential ambiguities

    Energy Technology Data Exchange (ETDEWEB)

    Yuanda, Wang; Xiuming, Bao; Zhiqiang, Mao; Rongfang, Yuan; Keling, Wen; Binyin, Huang; Zhifu, Wang; Shuming, Li; Jianan, Wang; Zuxun, Sun; others, and

    1985-11-01

    The differential cross sections are measured using 26.0 MeV ..cap alpha.. particle for /sup 58,62/Ni(..cap alpha.., ..cap alpha..) /sup 58,62/Ni and /sup 58,62/Ni(..cap alpha..,p) /sup 61,65/Cu reactions as well as 25.4 MeV ..cap alpha.. particle for /sup 60/Ni(..cap alpha.., ..cap alpha..)/sup 69/Ni and /sup 60/Ni(..cap alpha.., p)/sup 63/Cu reactions. Consistent calculations with optical model and ZR DWBA are made for (..cap alpha.., ..cap alpha..) and (..cap alpha.., p) reactions by using of single, two, three and four nucleon optical potential parameters. For elastic scattering due to the ..cap alpha.. optical potential ambiguities, all the above optical potential can reproduce the experimental angular distributions. However, the single, two and three nucleon potential, including the Baird's mass systematics and the Chang's energy systematics of ..cap alpha.. potentials, obviously can not provide a reasonable fitting with the (..cap alpha..,p) reaction experimental data. Only the results from the four nucleon potential is in good agreement with the (..cap alpha..,p) reaction experimental data. This reveals that in the ..cap alpha..-particle induced transfer reactions, the real depth of the ..cap alpha..-nucleus optical potential should be rather deep.

  20. Energy dependence of pi, p and pbar transverse momentum spectra for Au+Au collisions at sqrt sNN = 62.4 and 200 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, H

    2007-03-26

    We study the energy dependence of the transverse momentum (pT) spectra for charged pions, protons and anti-protons for Au+Au collisions at sqrt sNN = 62.4 and 200 GeV. Data are presented at mid-rapidity (lbar y rbar< 0.5) for 0.2< pT< 12 GeV/c. In the intermediate pT region (2< pT< 6 GeV/c), the nuclear modification factor is higher at 62.4 GeV than at 200 GeV, while at higher pT (pT> 7 GeV/c) the modification is similar for both energies. The p/pi+ and pbar/pi- ratios for central collisions at sqrt sNN = 62.4 GeV peak at pT _~;; 2 GeV/c. In the pT range where recombination is expected to dominate, the p/pi+ ratios at 62.4 GeV are larger than at 200 GeV, while the pbar/pi- ratios are smaller. For pT> 2 GeV/c, the pbar/pi- ratios at the two beam energies are independent of pT and centrality indicating that the dependence of the pbar/pi- ratio on pT does not change between 62.4 and 200 GeV. These findings challenge various models incorporating jet quenching and/or constituent quark coalescence.

  1. Analyzing power measurements in the (p,α) reaction on sup(58,60,62)Ni and 54Fe

    International Nuclear Information System (INIS)

    Katori, K.; Tagishi, Y.; Toba, Y.; Sasagase, M.; Sato, M.

    1980-01-01

    Two topics are discussed: (1) Analyzing powers for the (p, α) reactions on sup(58,60,62)Ni at E sub(p) = 22 MeV and (2) Excitation of the analog state in the 54 Fe(p, α) 51 Mn reaction at E sub(p) = 21 MeV. For the first topic, isotope (sup(58,60,62)Ni) and orbit (0f sub(7/2), 1s sub(1/2) and 0d sub(3/2)) dependences on angular distributions were compared for analyzing powers and cross sections. All the measured analyzing powers could not be reproduced within the frame work of a simple DWBA calculation. For the second topic, spin and parity of a state at 4.459 MeV in 51 Mn (the analog of the ground state of the 51 Cr nucleus) were assigned to be 7/2 - by the measurements of the analyzing power and cross section. (author)

  2. SPBP is a sulforaphane induced transcriptional coactivator of NRF2 regulating expression of the autophagy receptor p62/SQSTM1.

    Directory of Open Access Journals (Sweden)

    Sagar Ramesh Darvekar

    Full Text Available Organisms exposed to oxidative stress respond by orchestrating a stress response to prevent further damage. Intracellular levels of antioxidant agents increase, and damaged components are removed by autophagy induction. The KEAP1-NRF2 signaling pathway is the main pathway responsible for cell defense against oxidative stress and for maintaining the cellular redox balance at physiological levels. Sulforaphane, an isothiocyanate derived from cruciferous vegetables, is a potent inducer of KEAP1-NRF2 signaling and antioxidant response element driven gene expression. In this study, we show that sulforaphane enhances the expression of the transcriptional coregulator SPBP. The expression curve peaks 6-8 hours post stimulation, and parallels the sulforaphane-induced expression of NRF2 and the autophagy receptor protein p62/SQSTM1. Reporter gene assays show that SPBP stimulates the expression of p62/SQSTM1 via ARE elements in the promoter region, and siRNA mediated knock down of SPBP significantly decreases the expression of p62/SQSTM1 and the formation of p62/SQSTM1 bodies in HeLa cells. Furthermore, SPBP siRNA reduces the sulforaphane induced expression of NRF2, and the expression of the autophagy marker protein LC3B. Both these proteins contain ARE-like elements in their promoter regions. Over-expressed SPBP and NRF2 acts synergistically on the p62/SQSTM1 promoter and colocalize in nuclear speckles in HeLa cells. Collectively, these results suggest that SPBP is a coactivator of NRF2, and hence may be important for securing enhanced and sustained expression of NRF2 induced genes such as proteins involved in selective autophagy.

  3. Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of acetaminophen-induced acute liver injury in mice.

    Science.gov (United States)

    Shen, Zhenyu; Wang, Yu; Su, Zhenhui; Kou, Ruirui; Xie, Keqin; Song, Fuyong

    2018-02-25

    Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown. In the present study, the dose-response and time-course model in C57/BL6 mice were established by intraperitoneal injection of APAP. The results of serum alanine/aspartate aminotransferases (ALT/AST) and histological examination demonstrated that APAP overdose resulted in the severe liver injury. In the meantime, the levels of p62, phospho-p62 and nuclear Nrf2 were significantly increased by APAP in mice liver, suggesting an activation of p62-keap1-Nrf2 pathway. In addition, the expression of GSTA1 mRNA was increased in a dose-dependent manner, while the mRNA levels of HO-1 and GCLC were decreased with the increase of APAP dose. Our further investigation found that expression of HO-1 and GCLC peaked at 3 h∼6 h, and then were decreased gradually. Taken together, these results indicated that p62-keap1-Nrf2 antioxidant pathway was primarily activated in the early stage of APAP hepatotoxicity, which might play a protective role in the process of APAP-induced acute liver injury. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues.

    Science.gov (United States)

    Ju, L-L; Zhao, C Y; Ye, K-F; Yang, H; Zhang, J

    2016-05-01

    The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p0.05). BRCA1 expression was lower in EOC than BET (pepithelial ovarian cancer.

  5. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    Science.gov (United States)

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  6. Evaluation of the (n,p) cross sections for natural Ni and its isotopes {sup 58,60,61,62,64}Ni

    Energy Technology Data Exchange (ETDEWEB)

    Gonggui, Ma; Shiming, Wang; Kun, Zhang [Sichuan Univ., Chengdu (China). Inst. of Nuclear Science and Technology

    1996-06-01

    Nickel is a very important structure material in nuclear engineering. The neutron activation cross section of the (n,p) reaction is very important for fusion reactor from the view point of monitoring neutron field. The cross sections {sup 58,60,61,62,64}Ni(n,p){sup 58,60,61,62,64}Co were evaluated based on measured data and theoretical calculation from threshold to 20 MeV. The present evaluations agree well with the measured data of Ni isotopes. (6 figs.).

  7. Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase Pathways

    Directory of Open Access Journals (Sweden)

    Nicoletta Marchesi

    2018-01-01

    Full Text Available RNA-binding protein dysregulation and altered expression of proteins involved in the autophagy/proteasome pathway play a role in many neurodegenerative disease onset/progression, including age-related macular degeneration (AMD. HuR/ELAVL1 is a master regulator of gene expression in human physiopathology. In ARPE-19 cells exposed to the proteasomal inhibitor MG132, HuR positively affects at posttranscriptional level p62 expression, a stress response gene involved in protein aggregate clearance with a role in AMD. Here, we studied the early effects of the proautophagy AICAR + MG132 cotreatment on the HuR-p62 pathway. We treated ARPE-19 cells with Erk1/2, AMPK, p38MAPK, PKC, and JNK kinase inhibitors in the presence of AICAR + MG132 and evaluated HuR localization/phosphorylation and p62 expression. Two-hour AICAR + MG132 induces both HuR cytoplasmic translocation and threonine phosphorylation via the Erk1/2 pathway. In these conditions, p62 mRNA is loaded on polysomes and its translation in de novo protein is favored. Additionally, for the first time, we report that JNK can phosphorylate HuR, however, without modulating its localization. Our study supports HuR’s role as an upstream regulator of p62 expression in ARPE-19 cells, helps to understand better the early events in response to a proautophagy stimulus, and suggests that modulation of the autophagy-regulating kinases as potential therapeutic targets for AMD may be relevant.

  8. An interaction site of the envelope proteins of Semliki Forest virus that is preserved after proteolytic activation

    International Nuclear Information System (INIS)

    Zhang Xinyong; Kielian, Margaret

    2005-01-01

    Semliki Forest virus (SFV) membrane fusion is mediated by the viral E1 protein at acidic pH and regulated by the dimeric interaction of E1 with the E2 membrane protein. During low pH-triggered fusion, the E2/E1 heterodimer dissociates, freeing E1 to drive membrane fusion. E2 is synthesized as a precursor, p62, which is processed to mature E2 by the cellular protease furin. Both the dissociation of the p62/E1 dimer and the fusion reaction of p62 virus have a more acidic pH threshold than that of the mature E2 virus. We have previously isolated SFV mutations that allow virus growth in furin-deficient cells. Here we have used such pci mutations to compare the interactions of the p62/E1 and E2/E1 dimers. Our data suggest that there is an important p62/E1 dimer interaction site identified by an E2 R250G mutation and that this interaction is maintained after processing to the mature E2 protein

  9. Emission of circularly polarized recombination radiation from p-doped GaAs and GaAs0.62P0.38 under the impact of polarized electrons

    International Nuclear Information System (INIS)

    Fromme, B.; Baum, G.; Goeckel, D.; Raith, W.

    1989-01-01

    Circularly polarized light is emitted in radiative transitions of polarized electrons from the conduction to the valence band in GaAs or GaAs 1-x P x crystals. The degree of light polarization is directly related to the polarization of the conduction-band electrons at the instant of recombination and allows conclusions about the depolarization of electrons in the conduction band. The depolarization is caused by spin-relaxation processes. The efficiency of these processes depends on crystal type, crystal temperature, degree of doping, and kinetic energy of the electrons. Highly p-doped GaAs and GaAs 0.62 P 0.38 crystals (N A >1x10 19 atoms/cm 3 ) were bombarded with polarized electrons (initial polarization 38%), and the spectral distribution and the circular polarization of the emitted recombination radiation were measured. The initial kinetic energy of the electrons in the conduction band was varied between 5 and 1000 eV. The measurements of the spectral distribution show that the electrons are thermalized before recombination occurs, independent of their initial energy. An important thermalization process in this energy range is the excitation of crystal electrons by electron-hole pair creation. The circular polarization of the recombination radiation lies below 1% in the whole energy range. It decreases with increasing electron energy but is still of measurable magnitude at 100 eV in the case of GaAs 0.62 P 0.38 . The circular polarization is smaller for GaAs than for GaAs 0.62 P 0.38 , which we attribute to more efficient spin relaxation in GaAs

  10. Characterization of the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Nobuyoshi; Ikeda, Terumasa; Mizuki, Fumitaka [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan); Tani, Tokio, E-mail: ttani@sci.kumamoto-u.ac.jp [Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kurokami, Kumamoto 860-8555 (Japan)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer We cloned the ptr5{sup +} gene involved in nuclear mRNA export in fission yeast. Black-Right-Pointing-Pointer The ptr5{sup +} gene was found to encode nucleoporin 85 (Nup85). Black-Right-Pointing-Pointer Seh1p and Mlo3p are multi-copy suppressors for the ptr5 mutation. Black-Right-Pointing-Pointer Ptr5p/Nup85p functions in nuclear mRNA export through the mRNA export factor Rae1p. Black-Right-Pointing-Pointer Ptr5p/Nup85p interacts genetically with pre-mRNA splicing factors. -- Abstract: To analyze the mechanisms of mRNA export from the nucleus to the cytoplasm, we have isolated eleven mutants, ptr [poly(A){sup +} RNA transport] 1 to 11, which accumulate poly(A){sup +} RNA in the nucleus at a nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr5-1 mutant shows dots- or a ring-like accumulation of poly(A){sup +} RNA at the nuclear periphery after shifting to the nonpermissive temperature. We cloned the ptr5{sup +} gene and found that it encodes a component of the nuclear pore complex (NPC), nucleoporin 85 (Nup85). The ptr5-1 mutant shows no defects in protein transport, suggesting the specific involvement of Ptr5p/Nup85p in nuclear mRNA export in S. pombe. We identified Seh1p, a nucleoporin interacting with Nup85p, an mRNA-binding protein Mlo3p, and Sac3p, a component of the TREX-2 complex involved in coupling of nuclear mRNA export with transcription, as multi-copy suppressors for the ptr5-1 mutation. In addition, we found that the ptr5-1 mutation is synthetically lethal with a mutation of the mRNA export factor Rae1p, and that the double mutant exaggerates defective nuclear mRNA export, suggesting that Ptr5p/Nup85p is involved in nuclear mRNA export through Rae1p. Interestingly, the ptr5-1 mutation also showed synthetic effects with several prp pre-mRNA splicing mutations, suggesting a functional linkage between the NPCs and the splicing apparatus in the yeast nucleus.

  11. Characterization of the ptr5+ gene involved in nuclear mRNA export in fission yeast

    International Nuclear Information System (INIS)

    Watanabe, Nobuyoshi; Ikeda, Terumasa; Mizuki, Fumitaka; Tani, Tokio

    2012-01-01

    Highlights: ► We cloned the ptr5 + gene involved in nuclear mRNA export in fission yeast. ► The ptr5 + gene was found to encode nucleoporin 85 (Nup85). ► Seh1p and Mlo3p are multi-copy suppressors for the ptr5 mutation. ► Ptr5p/Nup85p functions in nuclear mRNA export through the mRNA export factor Rae1p. ► Ptr5p/Nup85p interacts genetically with pre-mRNA splicing factors. -- Abstract: To analyze the mechanisms of mRNA export from the nucleus to the cytoplasm, we have isolated eleven mutants, ptr [poly(A) + RNA transport] 1 to 11, which accumulate poly(A) + RNA in the nucleus at a nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr5–1 mutant shows dots- or a ring-like accumulation of poly(A) + RNA at the nuclear periphery after shifting to the nonpermissive temperature. We cloned the ptr5 + gene and found that it encodes a component of the nuclear pore complex (NPC), nucleoporin 85 (Nup85). The ptr5–1 mutant shows no defects in protein transport, suggesting the specific involvement of Ptr5p/Nup85p in nuclear mRNA export in S. pombe. We identified Seh1p, a nucleoporin interacting with Nup85p, an mRNA-binding protein Mlo3p, and Sac3p, a component of the TREX-2 complex involved in coupling of nuclear mRNA export with transcription, as multi-copy suppressors for the ptr5–1 mutation. In addition, we found that the ptr5–1 mutation is synthetically lethal with a mutation of the mRNA export factor Rae1p, and that the double mutant exaggerates defective nuclear mRNA export, suggesting that Ptr5p/Nup85p is involved in nuclear mRNA export through Rae1p. Interestingly, the ptr5–1 mutation also showed synthetic effects with several prp pre-mRNA splicing mutations, suggesting a functional linkage between the NPCs and the splicing apparatus in the yeast nucleus.

  12. P-matrix description of charged particles interaction

    International Nuclear Information System (INIS)

    Babenko, V.A.; Petrov, N.M.

    1992-01-01

    The paper deals with formalism of the P-matrix description of two charged particles interaction. Separation in the explicit form of the background part corresponding to the purely Coulomb interaction in the P-matrix is proposed. Expressions for the purely Coulomb P-matrix, its poles, residues and purely Coulomb P-matrix approach eigenfunctions are obtained. (author). 12 refs

  13. Study of weak interaction with p-p colliding beam

    International Nuclear Information System (INIS)

    Arafune, Jiro; Sugawara, Hirotaka

    1975-01-01

    Weak interaction in the energy range of TRISTAN project is discussed. The cross-section of production of weak boson in p-p reaction was calculated with the parton model. The observation of weak boson may be possible. The production rate of neutral weak boson was also estimated on the basis of the Weinberg model, and was almost same as that of weak boson. The method of observation of weak boson is suggested. The direct method is the observation of lepton pair due to the decay of neutral weak boson. It is expected that the spectrum of decay products (+ -) in the decay of weak boson shows a characteristic feature, and it shows the existence of weak boson. Weak interaction makes larger contribution in case of large momentum transfer than electromagnetic interaction. When the momentum transfer is larger than 60 GeV/c, the contribution of weak interaction is dominant over the others. Therefore, the experiments at high energy will give informations concerning the relations among the interactions of elementary particles. Possibility of study on the Higgs scalar meson is also discussed. (Kato, T.)

  14. Garvey-Kelson mass relations and n-p interaction

    International Nuclear Information System (INIS)

    Gao Zaochun; Meng Jie; Chen Yongshou

    2001-01-01

    Two Garvey-Kelson mass relations are found to be directly related to the n-p interaction. In the case of the same nuclear core, the neutron-proton interaction energy between two neutrons and one proton ε 2n-1p is experimentally found to be close to that between one neutron and two protons ε 1n-2p , which is equivalent to the first Garvey-Kelson mass relation. The sum of ε 2n-1p and ε 1n-2p is close to the n-p interaction energy between two neutrons and two protons ε 2n-2p , which leads to the second Garvey-Kelson mass relation. An explanation of these two n-p interaction relations is presented. It is shown that both of these mass relations hold more accurately when the core is an even-even core

  15. High spin states in 62Cu

    International Nuclear Information System (INIS)

    Tsan Ung Chan; Agard, M.; Bruandet, J.F.; Giorni, A.; Glasser, F.; Longequeue, J.P.; Morand, C.

    1977-06-01

    The 62 Cu nucleus has been studied via the reactions 60 Ni(α,pnγ), 63 Cu(p,pnγ), 52 Cr( 14 N,2p2nγ) using different in beam γ-spectroscopy techniques. The intensity of the principal γ-lines observed in different reactions leading to the 62 Cu has been compared. A brief discussion is made in terms of the independent particle model. A level scheme including levels with spin up to 9 + is proposed [fr

  16. Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1.

    Science.gov (United States)

    Moghanibashi, Mehdi; Rastgar Jazii, Ferdous; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

    2013-06-01

    Nuclear pore complex (NPC) is the only corridor for macromolecules exchange between nucleus and cytoplasm. NPC and its components, nucleoporins, play important role in the diverse physiological processes including macromolecule exchange, chromosome segregation, apoptosis and gene expression. Recent reports also suggest involvement of nucleoporins in carcinogenesis. Applying proteomics, we analyzed expression pattern of the NPC components in a newly established esophageal cancer cell line from Persia (Iran), the high-risk region for esophageal cancer. Our results indicate overexpression of Hsc70 and downregulation of subunit alpha type-3 of proteasome, calpain small subunit 1, and eIF5A-1. Among these proteins, Hsc70 and eIF5A-1 are in direct interaction with NPC and involved in the nucleocytoplasmic exchange. Hsc70 plays a critical role as a chaperone in the formation of a cargo-receptor complex in nucleocytoplasmic transport. On the other hand, it is an NPC-associated protein that binds to nucleoporins and contributes in recycling of the nucleocytoplasmic transport receptors in mammals and affects transport of proteins between nucleus and cytoplasm. The other nuclear pore interacting protein: eIF5A-1 binds to the several nucleoporins and participates in nucleocytoplasmic transport. Altered expression of Hsc70 and eIF5A-1 may cause defects in nucleocytoplasmic transport and play a role in esophageal carcinogenesis.

  17. Effective interactions in p-shell nuclei and the realistic interactions - I

    International Nuclear Information System (INIS)

    Upadhyaya, G.K.; Joshi, K.P.

    1984-04-01

    The effective interaction of Jain et al. derived from the Yale interaction by including the prominent core polarization diagrams is analyzed in terms of the interaction radial integrals and their spin tensor components. The interaction is also compared with some phenomenological effective interactions. The general features of the effective force in the 1 p shell region are discussed. (author)

  18. Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells.

    Directory of Open Access Journals (Sweden)

    Shintaro Seto

    Full Text Available Mycobacterium tuberculosis is an intracellular pathogen that can survive within phagocytic cells by inhibiting phagolysosome biogenesis. However, host cells can control the intracellular M. tuberculosis burden by the induction of autophagy. The mechanism of autophagosome formation to M. tuberculosis has been well studied in macrophages, but remains unclear in dendritic cells. We therefore characterized autophagosome formation in response to M. tuberculosis infection in dendritic cells. Autophagy marker protein LC3, autophagy adaptor protein p62/SQSTM1 (p62 and ubiquitin co-localized to M. tuberculosis in dendritic cells. Mycobacterial autophagosomes fused with lysosomes during infection, and major histcompatibility complex class II molecules (MHC II also localized to mycobacterial autophagosomes. The proteins p62 and Atg5 function in the initiation and progression of autophagosome formation to M. tuberculosis, respectively; p62 mediates ubiquitination of M. tuberculosis and Atg5 is involved in the trafficking of degradative vesicles and MHC II to mycobacterial autophagosomes. These results imply that the autophagosome formation to M. tuberculosis in dendritic cells promotes the antigen presentation of mycobacterial peptides to CD4(+ T lymphocytes via MHC II.

  19. Study of Structure-active Relationship for Inhibitors of HIV-1 Integrase LEDGF/p75 Interaction by Machine Learning Methods.

    Science.gov (United States)

    Li, Yang; Wu, Yanbin; Yan, Aixia

    2017-07-01

    HIV-1 integrase (IN) is a promising target for anti-AIDS therapy, and LEDGF/p75 is proved to enhance the HIV-1 integrase strand transfer activity in vitro. Blocking the interaction between IN and LEDGF/p75 is an effective way to inhibit HIV replication infection. In this work, 274 LEDGF/p75-IN inhibitors were collected as the dataset. Support Vector Machine (SVM), Decision Tree (DT), Function Tree (FT) and Random Forest (RF) were applied to build several computational models for predicting whether a compound is an active or weakly active LEDGF/p75-IN inhibitor. Each compound is represented by MACCS fingerprints and CORINA Symphony descriptors. The prediction accuracies for the test sets of all the models are over 70 %. The best model Model 3B built by FT obtained a prediction accuracy and a Matthews Correlation Coefficient (MCC) of 81.08 % and 0.62 on test set, respectively. We found that the hydrogen bond and hydrophobic interactions are important for the bioactivity of an inhibitor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway.

    Science.gov (United States)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP-8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76IRTFQELLF84, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Xenopus LAP2β protein knockdown affects location of lamin B and nucleoporins and has effect on assembly of cell nucleus and cell viability.

    Science.gov (United States)

    Dubińska-Magiera, Magda; Chmielewska, Magdalena; Kozioł, Katarzyna; Machowska, Magdalena; Hutchison, Christopher J; Goldberg, Martin W; Rzepecki, Ryszard

    2016-05-01

    Xenopus LAP2β protein is the single isoform expressed in XTC cells. The protein localizes on heterochromatin clusters both at the nuclear envelope and inside a cell nucleus. The majority of XLAP2β fraction neither colocalizes with TPX2 protein during interphase nor can be immunoprecipitated with XLAP2β antibody. Knockdown of the XLAP2β protein expression in XTC cells by synthetic siRNA and plasmid encoded siRNA resulted in nuclear abnormalities including changes in shape of nuclei, abnormal chromatin structure, loss of nuclear envelope, mislocalization of integral membrane proteins of INM such as lamin B2, mislocalization of nucleoporins, and cell death. Based on timing of cell death, we suggest mechanism associated with nucleus reassembly or with entry into mitosis. This confirms that Xenopus LAP2 protein is essential for the maintenance of cell nucleus integrity and the process of its reassembly after mitosis.

  2. The Interaction between Human and Organizational Capital in Strategic Human Resource Management (P.49-62)

    OpenAIRE

    Audia Junita

    2017-01-01

    Studies in strategic human resource management emphasize the contribution of human and human resource management to organizational performance achievement. Human and organizational capitals are strategic capability and mechanism to create value in an organization.This paper seeks to identify an interactive relationship between human and organizational capital in strategic human resource management theoretically, which so far, have not got adequate attention, particularly in a systemic relatio...

  3. Two Crinivirus-specific proteins of Lettuce infectious yellows virus (LIYV), P26 and P9, are self-interacting.

    Science.gov (United States)

    Stewart, Lucy R; Hwang, Min Sook; Falk, Bryce W

    2009-11-01

    Interactions of Lettuce infectious yellows virus (LIYV)-encoded proteins were tested by yeast-two-hybrid (Y2H) assays. LIYV-encoded P34, Hsp70h, P59, CP, CPm, and P26 were tested in all possible pairwise combinations. Interaction was detected only for the P26-P26 combination. P26 self-interaction domains were mapped using a series of N- and C-terminal truncations. Orthologous P26 proteins from the criniviruses Beet pseudoyellows virus (BPYV), Cucurbit yellow stunting disorder virus (CYSDV), and Lettuce chlorosis virus (LCV) were also tested, and each exhibited strong self-interaction but no interaction with orthologous proteins. Two small putative proteins encoded by LIYV RNA2, P5 and P9, were also tested for interactions with the six aforementioned LIYV proteins and each other. No interactions were detected for P5, but P9-P9 self-interaction was detected. P26- and P9-encoding genes are present in all described members of the genus Crinivirus, but are not present in other members of the family Closteroviridae. LIYV P26 has previously been demonstrated to induce a unique LIYV cytopathology, plasmalemma deposits (PLDs), but no role is yet known for P9.

  4. Multiplicity fluctuations of identified hadrons in p+p interactions at SPS energies

    CERN Document Server

    Maćkowiak-Pawłowska, Maja

    2014-01-01

    Study of energy and system size fluctuations of identified hadrons is one of the key goals of NA61/SHINE at the CERN SPS. Results may allow to discover the critical point (CP) of strongly interacting matter as well as to uncover properties of the onset of deconfinement (OD). But fluctuations exhibit numerous other sources starting from most basic ones like volume effects and conservation laws. NA49 seems to observe fluctuations related to CP in collisions of medium size nuclei at top SPS energy. However, this result will remain inconclusive until systematic data on energy and system size dependence will be available. Moreover, fluctuations in p+p as well as in Pb+Pb interactions should be better understood. In this contribution results on multiplicity fluctuations of identified hadrons in p+p interactions at the CERN SPS energies will be presented. The NA61 data will be compared with the corresponding results from central Pb+Pb collisions of NA49 in the common acceptance region of both experiments. Moreover, ...

  5. Nup358 interacts with Dishevelled and aPKC to regulate neuronal polarity

    Directory of Open Access Journals (Sweden)

    Pankhuri Vyas

    2013-10-01

    Par polarity complex, consisting of Par3, Par6, and aPKC, plays a conserved role in the establishment and maintenance of polarization in diverse cellular contexts. Recent reports suggest that Dishevelled (Dvl, a cytoplasmic mediator of Wnt signalling, interacts with atypical protein kinase C and regulates its activity during neuronal differentiation and directed cell migration. Here we show that Nup358 (also called RanBP2, a nucleoporin previously implicated in polarity during directed cell migration, interacts with Dishevelled and aPKC through its N-terminal region (BPN and regulates axon–dendrite differentiation of cultured hippocampal neurons. Depletion of endogenous Nup358 leads to generation of multiple axons, whereas overexpression of BPN abrogates the process of axon formation. Moreover, siRNA-mediated knockdown of Dvl or inhibition of aPKC by a pseudosubstrate inhibitor significantly reverses the multiple axon phenotype produced by Nup358 depletion. Collectively, these data suggest that Nup358 plays an important role in regulating neuronal polarization upstream to Dvl and aPKC.

  6. Systematics in p-n interaction vs deformation

    International Nuclear Information System (INIS)

    Singh, M.; Singh, Yuvraj; Kumar, Rajesh; Vrshney, A.K.; Gupta, K.K.

    2017-01-01

    The correlation of integrated valance p-n interaction in the onset of collectivity and deformation has been described phenomenologically in terms of N p N n scheme. L. Esser et al. presented the graphs between N p N n and deformation β and γ for some heavy nuclei

  7. Longitudinal Double Spin Asymmetry in Inclusive π0 Production at Forward Rapidities in √s=62.4 GeV Polarized p+p Collisions at RHIC

    International Nuclear Information System (INIS)

    Kazantsev, Andrey

    2007-01-01

    The gluons' Gluons spin contribution to proton spin is an important the key aspect for understanding the proton spin structure. It can be probed by the double helicity asymmetry of π0 production in polarized p+p collisions. During the longitudinally polarized proton run in 2006 PHENIX collected substantial data at √s=62.4 GeV and √s=200 GeV. In 2006 PHENIX commissioned a new electromagnetic calorimeter, the Muon Piston Calorimeter (MPC), located in the forward rapidity rapidities region. This calorimeter allows to significantly improves the PHENIX acceptance. In this report the MPC feasibility of the MPC for longitudinal double spin asymmetry studies is discussed

  8. Development of [{sup 62}Zn/{sup 62}Cu]-DOTA-rituximab as a possible novel in vivo PET generator for anti-CD20 antigen imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gholipour, Nazila [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir R.; Fazaeli, Yousef; Moradkhani, Sedigheh; Bolourinovin, Fateme [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Sabzevari, Omid [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Toxicology and Pharmacology; Khalaj, Ali [Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of). Dept. of Medical Chemistry

    2014-07-01

    In this study, zinc-62 was prepared at radiopharmaceutical grade (for {sup 62}Zn/{sup 62}Cu generator production) using {sup nat}Cu(p, xn) reaction with the production yield of 5.9 mCi/μAh at 30 MeV proton energy (radiochemical separation yield >95%, radionuclidic purity >99% and radiochemical purity >99%). In the next step, rituximab was successively labeled with [{sup 62}Zn]-ZnCl{sub 2} after conjugation with p-SCN-Bz-DOTA followed by molecular filtration and determination of the average number of DOTA conjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (>97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of [{sup 62}Zn]-DOTA-rituximab (in final formulation, and human serum) were determined 1-8 h as well as biodistribution studies in wild-type rats followed by coincidence imaging for 6 h. However, the accumulation of the radiolabeled antibody was not consistent with the former reported rituximab conjugates. [{sup 62}Zn]-labeled monoclonal antibodies and fragments can be prepared as potential in vivo PET generators for molecular imaging however, the search for application of stable zinc complexes must be continued.

  9. NA62 experiment at CERN SPS

    Directory of Open Access Journals (Sweden)

    Kozhuharov Venelin

    2014-01-01

    Full Text Available The NA62 experiment at SPS is a continuation of the long standing CERN kaon physics program. The high statistics and the unprecedent precision allow to probe the Standard Model and test the description of the strong interactions at low energy. The final results on the the lepton universality test by measuring the ratio RK = Γ(K+ → e+ν/Γ(K+ → µ+ν and the study of the K± → π±γγ decay are presented. The major goal of the NA62 experiment is to perform a measurement of the Br(K+ → π+νν̄ with a precision of 10% in two years of data taking. The detector setup together with the analysis technique is described.

  10. Role of cytochrome P450 in drug interactions

    Directory of Open Access Journals (Sweden)

    Bibi Zakia

    2008-10-01

    Full Text Available Abstract Drug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events.

  11. Influence of the p ¯ -p Nuclear Interaction on the Rate of the Low-Energy p ¯ + H μ → ( p ¯ p α + μ − Reaction

    Directory of Open Access Journals (Sweden)

    Renat A. Sultanov

    2018-04-01

    Full Text Available The influence of an additional strong p ¯ -p nuclear interaction in a three-charge-particle system with arbitrary masses is investigated. Specifically, the system of p ¯ , μ − , and p is considered in this paper, where p ¯ is an antiproton, μ − is a muon and p is a proton. A numerical computation in the framework of a detailed few-body approach is carried out for the following protonium (antiprotonic hydrogen formation three-body reaction: p ¯ + H μ ( 1 s → ( p ¯ p α + μ − . Here, H μ ( 1 s is a ground state muonic hydrogen, i.e., a bound state of p and μ − . A bound state of p and its antimatter counterpart p ¯ is a protonium atom in a quantum atomic state α , i.e., P n = ( p ¯ p α . The low-energy cross sections and rates of the P n formation reaction are computed in the framework of coupled Faddeev-Hahn-type equations. The strong p ¯ -p interaction is included in these calculations within a first order approximation. It was found, that the inclusion of the nuclear interaction results in a quite significant correction to the rate of the three-body reaction.

  12. Nuclear effects in protonium formation low-energy three-body reaction: p̄ + (pμ1s → (p̄pα + μ−: Strong p̄–p interaction in p̄ + (pμ1s

    Directory of Open Access Journals (Sweden)

    Sultanov Renat A.

    2016-01-01

    Full Text Available A three-charge-particle system (p̄, μ−, p+ with an additional matter-antimatter, i.e. p̄–p+, nuclear interaction is the subject of this work. Specifically, we carry out a few-body computation of the following protonium formation reaction: p̄ + (p+μ−1s → (p̄p+1s + μ−, where p+ is a proton, p̄ is an antiproton, μ− is a muon, and a bound state of p+ and its counterpart p̄ is a protonium atom: Pn = (p̄p+. The low-energy cross sections and rates of the Pn formation reaction are computed in the framework of a Faddeev-like equation formalism. The strong p̄–p+ interaction is approximately included in this calculation.

  13. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    Energy Technology Data Exchange (ETDEWEB)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona, E-mail: moroianu@bc.edu

    2013-08-15

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), {sub 76}IRQLQDLLL{sub 84}, within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch {sub 65}VRLVV{sub 69} within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the {sub 65}VRLVV{sub 69} sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7.

  14. Characterization of the transport signals that mediate the nucleocytoplasmic traffic of low risk HPV11 E7

    International Nuclear Information System (INIS)

    McKee, Courtney H.; Onder, Zeynep; Ashok, Aditya; Cardoso, Rebeca; Moroianu, Junona

    2013-01-01

    We previously discovered that nuclear import of low risk HPV11 E7 is mediated by its zinc-binding domain via a pathway that is independent of karyopherins/importins (Piccioli et al., 2010. Virology 407, 100–109). In this study we mapped and characterized a leucine-rich nuclear export signal (NES), 76 IRQLQDLLL 84 , within the zinc-binding domain that mediates the nuclear export of HPV11 E7 in a CRM1-dependent manner. We also identified a mostly hydrophobic patch 65 VRLVV 69 within the zinc-binding domain that mediates nuclear import of HPV11 E7 via hydrophobic interactions with the FG-repeats domain of Nup62. Substitutions of hydrophobic residues to alanine within the 65 VRLVV 69 sequence disrupt the nuclear localization of 11E7, whereas the R66A mutation has no effect. Overall the data support a model of nuclear entry of HPV11 E7 protein via hydrophobic interactions with FG nucleoporins at the nuclear pore complex. - Highlights: • HPV11 E7 has a leucine-rich nuclear export signal that mediates its nuclear export via CRM1. • HPV11 E7 interacts via its unique cNLS with the FG domain of Nup62. • Identification of a hydrophobic patch essential for nuclear localization of HPV11 E7

  15. S100A4 interacts with p53 in the nucleus and promotes p53 degradation.

    Science.gov (United States)

    Orre, L M; Panizza, E; Kaminskyy, V O; Vernet, E; Gräslund, T; Zhivotovsky, B; Lehtiö, J

    2013-12-05

    S100A4 is a small calcium-binding protein that is commonly overexpressed in a range of different tumor types, and it is widely accepted that S100A4 has an important role in the process of cancer metastasis. In vitro binding assays has shown that S100A4 interacts with the tumor suppressor protein p53, indicating that S100A4 may have additional roles in tumor development. In the present study, we show that endogenous S100A4 and p53 interact in complex samples, and that the interaction increases after inhibition of MDM2-dependent p53 degradation using Nutlin-3A. Further, using proximity ligation assay, we show that the interaction takes place in the cell nucleus. S100A4 knockdown experiments in two p53 wild-type cell lines, A549 and HeLa, resulted in stabilization of p53 protein, indicating that S100A4 is promoting p53 degradation. Finally, we demonstrate that S100A4 knockdown leads to p53-dependent cell cycle arrest and increased cisplatin-induced apoptosis. Thus, our data add a new layer to the oncogenic properties of S100A4 through its inhibition of p53-dependent processes.

  16. Search for higher twist in γp interactions

    International Nuclear Information System (INIS)

    Hoeger, K.C.

    1989-01-01

    A comparison of the experimental observations of the inclusive production of charged particles in γp interactions with 70 GeV - γ << 170 GeV and hp (h=π, K) interactions with E=80 GeV and 140 GeV is presented. (HSI)

  17. NA61/SHINE results on fluctuations and correlations in p+p and Be+Be interactions at CERN SPS energies

    CERN Document Server

    Mackowiak-Pawlowska, Maja

    2016-01-01

    The aim of the NA61/SHINE strong interaction program is to explore the phase diagram of strongly interacting matter. The main physics goals are the study of the onset of deconfinement and the search for the critical point of strongly interacting matter. These goals are pursued by performing a beam momentum (13$A$ - 158$A$ GeV/c) and system size (p+p, p+Pb, Be+Be, Ar+Sc, Xe+La) scan. This contribution presents results on transverse momentum and multiplicity fluctuations from the Be+Be and p+p energy scan. Also, results on two-particle correlations in pseudorapidity and azimuthal angle obtained in p+p interactions will be shown. The influence of conservation laws and resonance decays on multiplicity and chemical fluctuations of identified particles in p+p interactions will be discussed. Obtained results will be compared with data from other experiments and with model predictions.

  18. Effects of multiple substitution upon the P...N noncovalent interaction

    International Nuclear Information System (INIS)

    Scheiner, Steve

    2011-01-01

    Graphical abstract: The presence of one halogen opposite the N results in strong attraction between P and N. This force is little affected by identity of Y atoms, whether H or halogen. Highlights: → Strong attractive force directly between trivalent P and N atoms. → P...N force is unlike H-bonds or halogen bonds, but stronger than both. → Multiple halogenation beyond a single atom on P slightly weakens the interaction. - Abstract: The attractive noncovalent interaction of a P atom with N is derived primarily from two sources. Charge transfer from the N lone pair into the σ * antibonding orbital of a P-X bond that is turned away from the N atom combines with attractive Coulombic forces. As in the case of H-bonding, which is parallel in some ways to P...N attraction, placement of an electron-withdrawing substituent on the P atom enhances both of these components, and strengthens the overall interaction. However, in stark contrast with H-bonding, halogenation beyond monosubstitution does not lead to any further strengthening of the P...N noncovalent bond. Indeed, di and tri-substitution lead to small reductions in the interaction energy. In all cases, the geometry which contains a P...N bond is more stable than other candidate structures, some of which contain hydrogen or halogen bonds.

  19. Multi-species interactions impact the accumulation of weathered 2,2-bis (p-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE) from soil

    International Nuclear Information System (INIS)

    Kelsey, Jason W.; White, Jason C.

    2005-01-01

    The impact of interactions between the earthworms Eisenia foetida and Lumbricus terrestris and the plants Cucurbita pepo and Cucurbita maxima on the uptake of weathered p,p'-DDE from soil was determined. Although some combinations of earthworm and plant species caused significant changes in the p,p'-DDE burden in both organisms, the effects were species specific. Contaminant bioconcentration in C. pepo was increased slightly by E. foetida and by 3-fold when the plant was grown with L. terrestris. E. foetida had no effect on the contaminant BCF by C. maxima, but L. terrestris caused a 2-fold reduction in p,p'-DDE uptake by the plant. Contaminant levels in E. foetida and L. terrestris were unaffected by C. pepo. When grown with C. maxima, the concentration of p,p'-DDE decreased by approximately 4-fold and 7-fold in E. foetida and L. terrestris, respectively. The data suggest that the prediction of contaminant bioavailability should consider interactions among species. - Interactions between earthworms and plants affect both the phytoextraction and bioaccumulation of p,p'-DDE in soil

  20. Polarization of Λ hyperons produced inclusively in v p andbar v p charged current interactions

    Science.gov (United States)

    Jones, G. T.; Kennedy, B. W.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Nellen, B.; Cooper-Sarkar, A. M.; Grant, A.; Klein, H.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Barnham, K. W. J.; Clayton, E. F.; Miller, D. B.; Mobayyen, M. M.; Villalobos-Baillie, O.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K. L.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1985-03-01

    Lambda hyperons from v p andbar v p charged current interactions have been analysed for polarization. A significant polarization is observed for Λ particles in the quasi-elastic region for both types of interactions. Part of this polarization is due to the decay of highly polarized Σ(1385) resonances. The results are compared with simple predictions of the quark parton model.

  1. Encephalomyocarditis virus Leader protein hinge domain is responsible for interactions with Ran GTPase

    Energy Technology Data Exchange (ETDEWEB)

    Bacot-Davis, Valjean R., E-mail: bacotdavis@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Palmenberg, Ann C., E-mail: acpalmen@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Department of Biochemistry, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States)

    2013-08-15

    Encephalomyocarditis virus (EMCV), a Cardiovirus, initiates its polyprotein with a short 67 amino acid Leader (L) sequence. The protein acts as a unique pathogenicity factor, with anti-host activities which include the triggering of nuclear pore complex hyperphosphorylation and direct binding inhibition of the active cellular transport protein, Ran GTPase. Chemical modifications and protein mutagenesis now map the Ran binding domain to the L hinge-linker region, and in particular, to amino acids 35–40. Large deletions affecting this region were shown previously to diminish Ran binding. New point mutations, especially K35Q, D37A and W40A, preserve the intact L structure, abolish Ran binding and are deficient for nucleoporin (Nup) hyperphosphorylation. Ran itself morphs through multiple configurations, but reacts most effectively with L when in the GDP format, preferably with an empty nucleotide binding pocket. Therefore, L:Ran binding, mediated by the linker-hinge, is a required step in L-induced nuclear transport inhibition. - Highlights: • The hinge domain provides critical residues in Cardiovirus L:Ran complex formation. • Leader prefers to bind Ran in a nucleotide free, GDP-conformation. • L-induced Nup62 phosphorylation is reduced with Ran-deficient binding mutations.

  2. Targeting P-selectin glycoprotein ligand-1/P-selectin interactions as a novel therapy for metabolic syndrome.

    Science.gov (United States)

    Patel, Madhukar S; Miranda-Nieves, David; Chen, Jiaxuan; Haller, Carolyn A; Chaikof, Elliot L

    2017-05-01

    Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease. Current approaches of interfering with PSGL-1/P-selectin interactions include targeted antibodies, recombinant immunoglobulins that competitively bind P-selectin, and synthetic molecular therapies. Experimental models as well as clinical trials assessing the role of these modalities in a variety of diseases have continued to contribute to the understanding of PSGL-1/P-selectin interactions and have demonstrated the difficulty in creating clinically relevant therapeutics. Most recently, however, computational simulations have further enhanced our understanding of the structural features of PSGL-1 and related glycomimetics, which are responsible for high-affinity selectin interactions. Leveraging these insights for the design of next generation agents has thus led to development of a promising synthetic method for generating PSGL-1 glycosulfopeptide mimetics for the treatment of metabolic syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Evidence for the interaction of the regulatory protein Ki-1/57 with p53 and its interacting proteins

    International Nuclear Information System (INIS)

    Nery, Flavia C.; Rui, Edmilson; Kuniyoshi, Tais M.; Kobarg, Joerg

    2006-01-01

    Ki-1/57 is a cytoplasmic and nuclear phospho-protein of 57 kDa and interacts with the adaptor protein RACK1, the transcription factor MEF2C, and the chromatin remodeling factor CHD3, suggesting that it might be involved in the regulation of transcription. Here, we describe yeast two-hybrid studies that identified a total of 11 proteins interacting with Ki-1/57, all of which interact or are functionally associated with p53 or other members of the p53 family of proteins. We further found that Ki-1/57 is able to interact with p53 itself in the yeast two-hybrid system when the interaction was tested directly. This interaction could be confirmed by pull down assays with purified proteins in vitro and by reciprocal co-immunoprecipitation assays from the human Hodgkin analogous lymphoma cell line L540. Furthermore, we found that the phosphorylation of p53 by PKC abolishes its interaction with Ki-1/57 in vitro

  4. Interacting p- Boson model with isospin

    International Nuclear Information System (INIS)

    Chen, C.H.-T.

    A description of collective states in self-conjugate nuclei is proposed, both odd-odd and even-even, in terms of an interacting isoscalar p-boson model. Within this model, two limiting cases can be identified with the anharmonic vibrator and axial rotor limits of the classical geometrical description. (Author) [pt

  5. Low-energy Coulomb excitation of $^{62}$Fe and $^{62}$Mn following in-beam decay of $^{62}$Mn

    CERN Document Server

    Gaffney, L P; Bastin, B; Bildstein, V; Blazhev, A; Bree, N; Darby, I; De Witte, H; DiJulio, D; Diriken, J; Fedosseev, V N; Fransen, Ch; Gernhäuser, R; Gustafsson, A; Hess, H; Huyse, M; Kesteloot, N; Kröll, Th; Lutter, R; Marsh, B A; Reiter, P; Seidlitz, M; Van Duppen, P; Voulot, D; Warr, N; Wenander, F; Wimmer, K; Wrzosek-Lipska, K

    2015-01-01

    Sub-barrier Coulomb-excitation was performed on a mixed beam of $^{62}$Mn and $^{62}$Fe, following in-trap $\\beta^{-}$ decay of $^{62}$Mn at REX-ISOLDE, CERN. The trapping and charge breeding times were varied in order to alter the composition of the beam, which was measured by means of an ionisation chamber at the zero-angle position of the Miniball array. A new transition was observed at 418 keV, which has been tentatively associated to a $2^{(+)},3^{(+)}\\rightarrow1^{+}_{g.s.}$ transition. This fixes the relative positions of the $\\beta$-decaying $4^{(+)}$ and $1^{+}$ states in $^{62}$Mn for the first time. Population of the $2^{+}_{1}$ state was observed in $^{62}$Fe and the cross-section determined by normalisation to the $^{109}$Ag target excitation. Combining this Coulomb-excitation cross-section with previously measured lifetimes of the $2^{+}_{1}$ state, the spectroscopic quadrupole moment, $Q_{s}(2^{+}_{1})$, is extracted, albeit with a large uncertainty.

  6. Anti pp interactions in anti p atoms

    International Nuclear Information System (INIS)

    Poth, H.

    1975-01-01

    The x-rays of anti p atoms were recorded to trace out a strong interaction shift and width to the electromagnetic energy and the radiation width of the low-lying levels. The energy of the levels and consequently the energy of the transitions was calculated by solving numerically the Dirac equation with an electromagnetic potential, taking into account the finite size of the nucleus and the vacuum polarization. Due to the lack of sufficient data, the antiproton-nucleon interaction was not well understood at low energies. In order to separate antiproton-proton from antiproton-neutron interactions, the studies of isotope effects were proposed. (L.M.K.)

  7. Constant scattering length fits to low energy K-p interactions

    International Nuclear Information System (INIS)

    Conboy, J.E.

    1985-10-01

    The paper concerns the data on low energy K - p interactions analysed using the constant scattering length (C.S.L.) approximation. The scattering lengths are found to differ significantly from those required to fit data from previous K -1 p experiments, and these differences are discussed. The data indicate an Tspin=1 P- wave interaction, from the production angle distributions of the K-bar 0 n, Σ +- π -+ and Λπ 0 channels. However the authors have been unable to fit both the P-wave and K 0 sub(L)p data with the simple C.S.L. model. (U.K.)

  8. Forward $\\pi^{+-}$ production in p-$O_2$ and p-$N_2$ interactions at 12 GeV/c

    CERN Document Server

    Catanesi, M.G.; Edgecock, R.; Ellis, M.; Gossling, C.; Bunyatov, S.; Krasnoperov, A.; Popov, B.; Tereschenko, V.; Di Capua, E.; Vidal-Sitjes, G.; Artamonov, A.; Giani, S.; Gilardoni, S.; Gorbunov, P.; Grant, A.; Grossheim, A.; Ivanchenko, A.; Ivanchenko, V.; Kayis-Topaksu, A.; Panman, J.; Papadopoulos, I.; Tcherniaev, E.; Tsukerman, I.; Wiebusch, C.; Zucchelli, P.; Blondel, A.; Borghi, S.; Morone, M.C.; Prior, G.; Schroeter, R.; Meurer, C.; Gastaldi, U.; Mills, G.B.; Graulich, J.S.; Gregoire, G.; Bonesini, M.; Ferri, F.; Kirsanov, M.; Bagulya, A.; Grichine, V.; Polukhina, N.; Palladino, V.; Coney, L.; Schmitz, D.; Barr, G.; Bobisut, F.; Gibin, D.; Guglielmi, A.; Mezzetto, M.; Dumarchez, J.; Dore, U.; Orestano, D.; Pastore, F.; Tonazzo, A.; Tortora, L.; Booth, C.; Howlett, L.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Piperov, Stefan; Temnikov, P.; Apollonio, M.; Chimenti, P.; Giannini, G.; Burguet-Castell, J.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Martin-Albo, J.; Sorel, M.

    2008-01-01

    Measurements of double-differential charged pion production cross-sections in interactions of 12 GeV/c protons on O_2 and N_2 thin targets are presented in the kinematic range 0.5 GeV/c < p_{\\pi} < 8 GeV/c and 50 mrad < \\theta_{\\pi} < 250 mrad (in the laboratory frame) and are compared with p--C results. For p--N_2 (p--O_2) interactions the analysis is performed using 38576 (7522) reconstructed secondary pions. The analysis uses the beam instrumentation and the forward spectrometer of the HARP experiment at CERN PS. The measured cross-sections have a direct impact on the precise calculation of atmospheric neutrino fluxes and on the improved reliability of extensive air shower simulations by reducing the uncertainties of hadronic interaction models in the low energy range. In particular, the present results allow the common hypothesis that p--C data can be used to predict the p--N_2 and p--O_2 pion production cross-sections to be tested.

  9. Recent results from the NA62 experiment at CERN

    CERN Document Server

    Aliberti, Riccardo

    2016-01-01

    NA62 is a fixed target experiment located at the CERN SPS which aims to perform flavour physics studies in the charged kaon sector with an unprecedented precision. Due to the abundance of kaon decays with a po in the final state, NA62 is also a perfect environment to measure the neutral pion characteristics. NA62 collected a large sample of charged kaon decays with a highly efficient trigger for decays into electrons in 2007. We report about the measurement of the po electromagnetic transition form factor slope parameter in the time-like region. Between 2008 and 2014 the NA62 apparatus underwent an intense upgrade phase to improve the physics sensitivity of the experiment to precisely measure the Br (K+ !p+n ¯ n). NA62 took data in pilot runs in 2014 and 2015 reaching the final designed beam intensity. The quality of data acquired in view of the final measurement is presented.

  10. Role of multiparton interactions on J /ψ production in p +p collisions at LHC energies

    Science.gov (United States)

    Thakur, Dhananjaya; De, Sudipan; Sahoo, Raghunath; Dansana, Soumya

    2018-05-01

    The production mechanism of quarkonia states in hadronic collisions is still to be understood by the scientific community. In high-multiplicity p +p collisions, underlying event observables are of major interest. The multiparton interactions (MPIs) are underlying event observables, in which several interactions occur at the partonic level in a single p +p event. This leads to dependence of particle production on event multiplicity. If the MPI occurs in a harder scale, there will be a correlation between the yield of quarkonia and total charged-particle multiplicity. The ALICE experiment at the LHC in p +p collisions at √{s }=7 and 13 TeV has observed an approximate linear increase of relative J /ψ yield, (d/NJ /ψ/d y ⟨d NJ /ψ/d y ⟩ ), with relative charged-particle multiplicity density, (d/Nch/d y ⟨d Nch/d y ⟩ ). In our present work, we have performed a comprehensive study of the production of charmonia as a function of charged-particle multiplicity in p +p collisions at LHC energies using the perturbative QCD-inspired multiparton interaction model, pythia8 tune 4C, with and without the color reconnection scheme. A detailed multiplicity and energy-dependent study is performed to understand the effects of MPI on J /ψ production. The ratio of ψ (2 S ) to J /ψ is also studied as a function of charged-particle multiplicity at LHC energies.

  11. HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis

    Science.gov (United States)

    Watanabe, Yoshihisa; Tsujimura, Atsushi; Taguchi, Katsutoshi; Tanaka, Masaki

    2017-01-01

    ABSTRACT Proteostasis is important for protecting cells from harmful proteins and is mainly controlled by the HSF1 (heat shock transcription factor 1) stress response pathway. This pathway facilitates protein refolding by molecular chaperones; however, it is unclear whether it functions in autophagy or inclusion formation. The autophagy receptor SQSTM1/p62 is involved in selective autophagic clearance and inclusion formation by harmful proteins, and its phosphorylation at S349, S403, and S407 is required for binding to substrates. Here, we demonstrate that casein kinase 1 phosphorylates the SQSTM1 S349 residue when harmful proteins accumulate. Investigation of upstream factors showed that both SQSTM1 S349 and SQSTM1 S403 residues were phosphorylated in an HSF1 dependent manner. Inhibition of SQSTM1 phosphorylation suppressed inclusion formation by ubiquitinated proteins and prevented colocalization of SQSTM1 with aggregation-prone proteins. Moreover, HSF1 inhibition impaired aggregate-induced autophagosome formation and elimination of protein aggregates. Our findings indicate that HSF1 triggers SQSTM1-mediated proteostasis. PMID:27846364

  12. HSF1 stress response pathway regulates autophagy receptor SQSTM1/p62-associated proteostasis.

    Science.gov (United States)

    Watanabe, Yoshihisa; Tsujimura, Atsushi; Taguchi, Katsutoshi; Tanaka, Masaki

    2017-01-02

    Proteostasis is important for protecting cells from harmful proteins and is mainly controlled by the HSF1 (heat shock transcription factor 1) stress response pathway. This pathway facilitates protein refolding by molecular chaperones; however, it is unclear whether it functions in autophagy or inclusion formation. The autophagy receptor SQSTM1/p62 is involved in selective autophagic clearance and inclusion formation by harmful proteins, and its phosphorylation at S349, S403, and S407 is required for binding to substrates. Here, we demonstrate that casein kinase 1 phosphorylates the SQSTM1 S349 residue when harmful proteins accumulate. Investigation of upstream factors showed that both SQSTM1 S349 and SQSTM1 S403 residues were phosphorylated in an HSF1 dependent manner. Inhibition of SQSTM1 phosphorylation suppressed inclusion formation by ubiquitinated proteins and prevented colocalization of SQSTM1 with aggregation-prone proteins. Moreover, HSF1 inhibition impaired aggregate-induced autophagosome formation and elimination of protein aggregates. Our findings indicate that HSF1 triggers SQSTM1-mediated proteostasis.

  13. Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

    Science.gov (United States)

    Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

    2015-06-01

    Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

  14. Nucleon-deuteron breakup quantities calculated with separable interactions including tensor forces and P-wave interactions

    International Nuclear Information System (INIS)

    Bruinsma, J.; Wageningen, R. van

    1977-01-01

    Nucleon-deuteron breakup calculations at a nucleon bombarding energy of 22.7 MeV have been performed with separable interactions including a tensor force and P-wave interactions. Differential cross sections and a selection of polarization quantities have been computed for special regions of the phase space. The influence of a tensor force and P-wave interactions on the differential cross section is of the order of 20%. Large discrepancies between theory and experiment occur for the vector analyzing powers, both for the kinematically complete and for the incomplete situation. The calculations show that there are kinematical situations in which the differential cross sections and the tensor analyzing powers are sufficiently large to make measurements feasible. (Auth.)

  15. Single-Prolonged-Stress-Induced Changes in Autophagy-Related Proteins Beclin-1, LC3, and p62 in the Medial Prefrontal Cortex of Rats with Post-traumatic Stress Disorder.

    Science.gov (United States)

    Zheng, Shilei; Han, Fang; Shi, Yuxiu; Wen, Lili; Han, Dan

    2017-05-01

    Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis. PTSD was induced in rats by exposure to a single-prolonged stress (SPS). The Morris water maze was used to assess cognitive changes in rats from the SPS and control groups. Transmission electron microscopy (TEM) was employed to observe mPFC morphological changes. Immunohistochemistry, immunofluorescence, and Western blotting techniques were used to detect expression of Beclin-1, LC3, and p62 in the mPFC. The Morris water maze test results showed that the escape latency time was increased and that the percent time in the target quadrant was decreased in the SPS group compared with that in the control group. Numerous visible autolysosomes in mPFC neurons were observed using TEM after SPS stimulation. Compared with that in the control group, the expression of Beclin-1 and the LC3-II/I ratio significantly decreased at 1 day, then increased and peaked at 7 days, and slightly decreased at 14 days after SPS stimulation, whereas the converse was found for p62 expression. In conclusion, dysregulation of autophagic activity in the mPFC may play a crucial role in PTSD pathogenesis.

  16. 3D Structure and Interaction of p24β and p24δ Golgi Dynamics Domains: Implication for p24 Complex Formation and Cargo Transport.

    Science.gov (United States)

    Nagae, Masamichi; Hirata, Tetsuya; Morita-Matsumoto, Kana; Theiler, Romina; Fujita, Morihisa; Kinoshita, Taroh; Yamaguchi, Yoshiki

    2016-10-09

    The p24 family consists of four subfamilies (p24α, p24β, p24γ, and p24δ), and the proteins are thought to form hetero-oligomeric complexes for efficient transport of cargo proteins from the endoplasmic reticulum to the Golgi apparatus. The proteins possess a conserved luminal Golgi dynamics (GOLD) domain, whose functions are largely unknown. Here, we present structural and biochemical studies of p24β1 and p24δ1 GOLD domains. Use of GOLD domain-deleted mutants revealed that the GOLD domain of p24δ1 is required for proper p24 hetero-oligomeric complex formation and efficient transport of GPI-anchored proteins. The p24β1 and p24δ1 GOLD domains share a common β-sandwich fold with a characteristic intrasheet disulfide bond. The GOLD domain of p24δ1 crystallized as dimers, allowing the analysis of a homophilic interaction site. Surface plasmon resonance and solution NMR analyses revealed that p24β1 and p24δ1 GOLD domains interact weakly (K d = ~10 -4 M). Bi-protein titration provided interaction site maps. We propose that the heterophilic interaction of p24 GOLD domains contributes to the formation of the p24 hetero-oligomeric complex and to efficient cargo transport. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Electric Monopole Transition Strengths in 62Ni

    Science.gov (United States)

    Evitts, L. J.; Garnsworthy, A. B.; Kibédi, T.; Moukaddam, M.; Alshahrani, B.; Eriksen, T. K.; Holt, J. D.; Hota, S. S.; Lane, G. J.; Lee, B. Q.; McCormick, B. P.; Palalani, N.; Reed, M. W.; Stroberg, S. R.; Stuchbery, A. E.

    2016-09-01

    Excited states in 62Ni were populated with a (p, p') reaction using the 14UD Pelletron accelerator at the Australian National University. Electric monopole transition strengths, ρ2(E0), were measured through simultaneous detection of the internal conversion electrons and γ rays emitted from the de-excitation of populated states, using the Super-e spectrometer coupled with a germanium detector. The strength of the 02+ to 01+ transition has been measured to be 77-34+23 × 10-3 and agrees with previously reported values. Upper limits have been placed on the 03+ to 01+ and 03+ to 02+ transitions. The measured ρ2(E0) value of the 22+ to 21+ transition in 62Ni has been measured for the first time and found to be one of the largest ρ2(E0) values measured to date in nuclei heavier than Ca. The low-lying states of 62Ni have previously been classified as one- and two-phonon vibrational states based on level energies. The measured electric quadrupole transition strengths are consistent with this interpretation. However as electric monopole transitions are forbidden between states which differ by one phonon number, the simple harmonic quadrupole vibrational picture is not suffcient to explain the large ρ2(E0) value for the 22+ to 21+ transition.

  18. On the importance of personal profiles to enhance social interaction in Learning Networks

    NARCIS (Netherlands)

    Berlanga, Adriana; Bitter-Rijpkema, Marlies; Brouns, Francis; Sloep, Peter

    2008-01-01

    Berlanga, A. J., Bitter-Rijpkema, M., Brouns F., & Sloep, P.B. (2008). On the importance of personal profiles to enhance social interaction in Learning Networks. In P. Kommers (Ed.), Proceedings of Web Based Communities Conference (WEBC 2008) (pp. 55-62). July, 24-26, 2008, Amsterdam, The

  19. Alfalfa mosaic virus replicase proteins P1 and P2 interact and colocalize at the vacuolar membrane

    NARCIS (Netherlands)

    Heijden, van der M.W.; Carette, J.E.; Reinhoud, P.J.; Haegi, A.; Bol, J.F.

    2001-01-01

    Replication of Alfalfa mosaic virus (AMV) RNAs depends on the virus-encoded proteins P1 and P2. P1 contains methyltransferase- and helicase-like domains, and P2 contains a polymerase-like domain. Coimmunoprecipitation experiments revealed an interaction between in vitro translated-P1 and P2 and

  20. Revisiting final state interaction in charmless Bq→P P decays

    Science.gov (United States)

    Chua, Chun-Khiang

    2018-05-01

    Various new measurements in charmless Bu ,d ,s→P P modes, where P is a low lying pseudoscalar meson, are reported by Belle and LHCb. These include the rates of B0→π0π0, η π0, Bs→η'η', B0→K+K- and Bs0→π+π- decays. Some of these modes are highly suppressed and are among the rarest B decays. Direct C P asymmetries on various modes are constantly updated. It is well known that direct C P asymmetries and rates of suppressed modes are sensitive to final state interaction (FSI). As new measurements are reported and more data will be collected, it is interesting and timely to revisit the rescattering effects in Bu ,d ,s→P P states. We perform a χ2 analysis with all available data on C P -averaged rates and C P asymmetries in B¯u ,d ,s→P P decays. Our numerical results are compared to data and those from factorization approach. The quality of the fit is improved significantly from the factorization results in the presence of rescattering. The relations on topological amplitudes and rescattering are explored and they help to provide a better understanding of the effects of FSI. As suggested by U(3) symmetry on topological amplitudes and FSI, a vanishing exchange rescattering scenario is considered. The exchange, annihilation, u -penguin, u -penguin annihilation, and some electroweak penguin amplitudes are enhanced significantly via annihilation and total annihilation rescatterings. In particular, the u -penguin annihilation amplitude is sizably enhanced by the tree amplitude via total annihilation rescattering. These enhancements affect rates and C P asymmetries. Predictions can be checked in the near future.

  1. Charge structure of K-p interactions

    International Nuclear Information System (INIS)

    Goettgens, R.; Ransone, G.; Sixel, P.

    1981-01-01

    The charge transfer distribution, its average, dispersion and skewness are studied in K - p interactions at 110 GeV/c and lower energies. The ratio of dispersion squared to rapidity plateau height is found to be energy independent as suggested by the neutral cluster models. The short range charge correlations in rapidity are observed at all energies; at 110 GeV/c there is also evidence for a long range component. (author)

  2. Porous TiNb24O62 microspheres as high-performance anode materials for lithium-ion batteries of electric vehicles.

    Science.gov (United States)

    Yang, Chao; Deng, Shengjue; Lin, Chunfu; Lin, Shiwei; Chen, Yongjun; Li, Jianbao; Wu, Hui

    2016-11-10

    TiNb 24 O 62 is explored as a new anode material for lithium-ion batteries. Microsized TiNb 24 O 62 particles (M-TiNb 24 O 62 ) are fabricated through a simple solid-state reaction method and porous TiNb 24 O 62 microspheres (P-TiNb 24 O 62 ) are synthesized through a facile solvothermal method for the first time. TiNb 24 O 62 exhibits a Wadsley-Roth shear structure with a structural unit composed of a 3 × 4 octahedron-block and a 0.5 tetrahedron at the block-corner. P-TiNb 24 O 62 with an average sphere size of ∼2 μm is constructed by nanoparticles with an average size of ∼100 nm, forming inter-particle pores with a size of ∼8 nm and inter-sphere pores with a size of ∼55 nm. Such desirable porous microspheres are an ideal architecture for enhancing the electrochemical performances by shortening the transport distance of electrons/Li + -ions and increasing the reaction area. Consequently, P-TiNb 24 O 62 presents outstanding electrochemical performances in terms of specific capacity, rate capability and cyclic stability. The reversible capacities of P-TiNb 24 O 62 are, respectively, as large as 296, 277, 261, 245, 222, 202 and 181 mA h g -1 at 0.1, 0.5, 1, 2, 5, 10 and 20 C, which are obviously larger than those of M-TiNb 24 O 62 (258, 226, 210, 191, 166, 147 and 121 mA h g -1 ). At 10 C, the capacity of P-TiNb 24 O 62 still remains at 183 mA h g -1 over 500 cycles with a decay of only 0.02% per cycle, whereas the corresponding values of M-TiNb 24 O 62 are 119 mA h g -1 and 0.04%. These impressive results indicate that P-TiNb 24 O 62 can be a promising anode material for lithium-ion batteries of electric vehicles.

  3. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    Energy Technology Data Exchange (ETDEWEB)

    Di Nunzio, Francesca, E-mail: francesca.di-nunzio@pasteur.fr [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Fricke, Thomas [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Miccio, Annarita [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Valle-Casuso, Jose Carlos; Perez, Patricio [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States); Souque, Philippe [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Rizzi, Ermanno; Severgnini, Marco [Institute of Biomedical Technologies, CNR, Milano (Italy); Mavilio, Fulvio [University of Modena e Reggio Emilia, Centro di Medicina Rigenerativa, Modena (Italy); Genethon, Evry (France); Charneau, Pierre [Molecular Virology and Vaccinology unit, CNRS URA 3015, Department of Virology, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris (France); Diaz-Griffero, Felipe, E-mail: felipe.diaz-griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine Bronx, NY 10461 (United States)

    2013-05-25

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites.

  4. Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication

    International Nuclear Information System (INIS)

    Di Nunzio, Francesca; Fricke, Thomas; Miccio, Annarita; Valle-Casuso, Jose Carlos; Perez, Patricio; Souque, Philippe; Rizzi, Ermanno; Severgnini, Marco; Mavilio, Fulvio; Charneau, Pierre; Diaz-Griffero, Felipe

    2013-01-01

    The early steps of HIV-1 replication involve the entry of HIV-1 into the nucleus, which is characterized by viral interactions with nuclear pore components. HIV-1 developed an evolutionary strategy to usurp the nuclear pore machinery and chromatin in order to integrate and efficiently express viral genes. In the current work, we studied the role of nucleoporins 153 and 98 (Nup153 and Nup98) in infection of human Jurkat lymphocytes by HIV-1. We showed that Nup153-depleted cells exhibited a defect in nuclear import, while depletion of Nup 98 caused a slight defect in HIV integration. To explore the biochemical viral determinants for the requirement of Nup153 and Nup98 during HIV-1 infection, we tested the ability of these nucleoporins to interact with HIV-1 cores. Our findings showed that both nucleoporins bind HIV-1 cores suggesting that this interaction is important for HIV-1 nuclear import and/or integration. Distribution analysis of integration sites in Nup153-depleted cells revealed a reduced tendency of HIV-1 to integrate in intragenic sites, which in part could account for the large infectivity defect observed in Nup153-depleted cells. Our work strongly supports a role for Nup153 in HIV-1 nuclear import and integration. - Highlights: ► We studied the role of Nup98 and Nup153 in HIV-1 infection. ► Nup98 binds the HIV-1 core and is involved in HIV-1 integration. ► Nup153 binds the HIV-1 core and is involved in HIV-1 nuclear import. ► Depletion of Nup153 decreased the integration of HIV-1 in transcriptionally active sites

  5. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

  6. Investigation of the interactions of critical scale-up parameters (pH, pO2 and pCO2) on CHO batch performance and critical quality attributes.

    Science.gov (United States)

    Brunner, Matthias; Fricke, Jens; Kroll, Paul; Herwig, Christoph

    2017-02-01

    Understanding process parameter interactions and their effects on mammalian cell cultivations is an essential requirement for robust process scale-up. Furthermore, knowledge of the relationship between the process parameters and the product critical quality attributes (CQAs) is necessary to satisfy quality by design guidelines. So far, mainly the effect of single parameters on CQAs was investigated. Here, we present a comprehensive study to investigate the interactions of scale-up relevant parameters as pH, pO 2 and pCO 2 on CHO cell physiology, process performance and CQAs, which was based on design of experiments and extended product quality analytics. The study used a novel control strategy in which process parameters were decoupled from each other, and thus allowed their individual control at defined set points. Besides having identified the impact of single parameters on process performance and product quality, further significant interaction effects of process parameters on specific cell growth, specific productivity and amino acid metabolism could be derived using this method. Concerning single parameter effects, several monoclonal antibody (mAb) charge variants were affected by process pCO 2 and pH. N-glycosylation analysis showed positive correlations between mAb sialylation and high pH values as well as a relationship between high mannose variants and process pH. This study additionally revealed several interaction effects as process pH and pCO 2 interactions on mAb charge variants and N-glycosylation pattern. Hence, through our process control strategy and multivariate investigation, novel significant process parameter interactions and single effects were identified which have to be taken into account especially for process scale-up.

  7. Mutual interactions between P53 and growth factors in cancer

    NARCIS (Netherlands)

    Asschert, JGW; Vellenga, E; De Jong, S; De Vries, EGE

    1998-01-01

    The function of p53 armour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and platein-protein interactions are determined by the conformation of the protein. Thus p53 fulfils its role in cell cycle control and the onset of apoptotic

  8. CLA and CD62E expression in oral lichen planus lesions.

    Science.gov (United States)

    Werneck, Juliana Tristão; Dias, Eliane Pedra; Gonçalves, Lucio Souza; Silva Junior, Arley

    2016-03-01

    There are few reports on the migration of CLA+ T cells through E-selectin in cutaneous lichen planus, with only one study on oral lichen planus (OLP). This study aimed to analyze CLA expression and assess whether there is a correlation with E-selectin (CD62E) in OLP lesions. Biopsies were performed on 11 patients including two areas: one without clinical and histopathological features of OLP [perilesional group (PLG)] and the other with clinical and histopathological features of OLP [OLP group (OLPG)]. The specimens obtained were divided into two: One was fixed in formalin for routine analysis (H&E), and the other was frozen for CD3, CD4, CD8, CLA, and CD62E immunofluorescence markers. More CD4+ (median 1409, range 860-2519), CD8+ (median 1568, range 654-3258), and CLA+ T cells (median 958, range 453-2198) and higher CD62E expression (median 37, range 27-85) were identified in OLPG (P = 0.003; P = 0.003; P = 0.004; P = 0.003, respectively) than those in PLG. The median prevalence analysis was also significantly higher for CLA+CD8+ T cells in OLPG (OLPG = 39.4%, range 18.4-64.2; PLG = 29.4%, range 12.1-47.1) (P = 0.026). None of the correlations between CD3+ or CLA+ T cells and CD62E in OLPG and in PLG were significant. The significant presence of CLA+ T cells and E-selectin expressions in the OLPG suggests their involvement in the etiopathogenesis of OLP; however, only a weak correlation between CLA+ T cells and E-selectin was observed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Bose-Fermi U(6/2j+1) supersymmetries and high-spin anomalies

    International Nuclear Information System (INIS)

    Morrison, I.; Jarvis, P.D.

    1985-01-01

    A supersymmetric extension of the interacting boson model (IBM) is constructed to describe high-spin anomalies in both even- and odd-mass spectra of the Hg, Pt region (190<=A<=200). Supergroup chains such as U(6/2j+1)containsOsp(6/2j+1)containsO(6)xSp(2j+1)... or U(6/2j+1)containsU(5/2j+1)xU(1)containsOsp(5/2j+1)... incorporate a single j-shell fermion in addition to the usual 's' and 'd' bosons (L=0 and L=2). The orthosympletic supergroup reflects the strong pairing force in the subspace of the fermion intruder level. The model agrees favourably with experiment and microscopic calculation. (orig.)

  10. Study of ln s Physics in $\\bar{p}p$ Interactions at the Split Field Magnet

    CERN Multimedia

    2002-01-01

    This experiment uses the Split Field Magnet detector to investigate the low p^t, ``ln~s'', type of interactions that dominate the @*p cross-section. Systematic comparisons will be made to pp interactions. \\\\ \\\\ Specific areas to be studied include elastic scattering in the regions 0.05 $<$ !t! $<$ 0.8 GeV|2 and 0.8 $<$ !t! $<$ 4.0 GeV|2, and the use of a minimum bias trigger to study topological cross-sections, inclusive spectra, and two-body correlations. Some specialized triggers, run simultaneously with the high t elastic scattering trigger, are being studied. Examples are a trigger requiring Cerenkov identification in a limited region of phase space, and a trigger to select diffractively produced events.

  11. Mathematical Modeling of E6-p53 interactions in Cervical Cancer

    Science.gov (United States)

    Khattak, Faryal; Haseeb, Muhammad; Fazal, Sahar; Bhatti, A I; Ullah, Mukhtar

    2017-04-01

    Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p53 interactions was developed using mathematical laws. In-silico simulations were carried out on CellDesigner and as a test case the small molecule drug RITA was considered for its ability to rescue the functions of tumor suppressor p53 by inhibiting E6 mediated proteasomal degradation. Results: Using a computational model we scrutinized how p53 responds to RITA, and chemical reactions of this small molecule drug were incorporated to perceive the full effects. The evolved strategy allowed the p53 response and rescue of its tumor suppressor function to be delineated, RITA being found to block p53 interactions with E6 associated proteins. Conclusion: We could develop a model of E6-p53 interactions with incorporation of actions of the small molecule drug RITA. Suppression of E6 associated proteins by RITA induces accumulation of tumor suppressant p53. Using CellDesigner to encode the model ensured that it can be easily modified and extended as more data become available. This strategy should play an effective role in the development of therapies against cancer. Creative Commons Attribution License

  12. Interaction of rocuronium with human liver cytochromes P450

    OpenAIRE

    Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

    2015-01-01

    Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver micro...

  13. Quark (diquark) fragmentation in soft π-p interactions at P=40 GeV/c

    International Nuclear Information System (INIS)

    Didenko, L.A.; Grishin, V.G.; Kuznetsov, V.A.

    1984-01-01

    The quark and diquark fragmentation into π +- -, K 0 -mesons and Λ-hyperons in soft π - p-interactions at 40 GeV/c is studied. Fragmentation Dsup(πsup(+-)) (Xsub(F)) and invariant Fsup(πsup(+-)) (Xsub(F)) functions are compared with analogous data on ν(anti ν)p - interactions. It is shown that a good agreement exists in the region Xsub(F) > or approximately 0.15 for these different processes. The Xsub(E)-dependence of the quark and diquark fragmentation function for neutral kaons is similar to that in e + e - annihilation. The pickup probability of strange s(anti s) quark (lambda sub(s)) and diquark (lambda sub(qq)) relative to u(anti u) and d(anti d) quarks from the sea has been found to be equal to lambda sub(s)=0.17 and lambda sub(qq)=0.14+-0.03

  14. Crack Growth Behaviour of P92 Steel Under Creep-fatigue Interaction Conditions

    Directory of Open Access Journals (Sweden)

    JING Hong-yang

    2017-05-01

    Full Text Available Creep-fatigue interaction tests of P92 steel at 630℃ under stress-controlled were carried out, and the crack propagation behaviour of P92 steel was studied. The fracture mechanism of crack growth under creep-fatigue interaction and the transition points in a-N curves were analyzed based on the fracture morphology. The results show that the fracture of P92 steel under creep-fatigue interaction is creep ductile fracture and the (Ctavg parameter is employed to demonstrate the crack growth behaviour; in addition, the fracture morphology shows that the crack growth for P92 steel under creep-fatigue interaction is mainly caused by the nucleation and growth of the creep voids and micro-cracks. Furthermore, the transition point of a-lg(Ni/Nf curve corresponds to the turning point of initial crack growth changed into steady crack growth while the transition point of (da/dN-N curve exhibits the turning point of steady creep crack growth changed into the accelerated crack growth.

  15. Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

    International Nuclear Information System (INIS)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

  16. The nuclear pore complex protein ALADIN is anchored via NDC1 but not via POM121 and GP210 in the nuclear envelope

    Energy Technology Data Exchange (ETDEWEB)

    Kind, Barbara, E-mail: barbara.kind@uniklinikum-dresden.de [Children' s Hospital, Technical University Dresden, D-01307 Dresden (Germany); Koehler, Katrin, E-mail: katrin.koehler@uniklinikum-dresden.de [Children' s Hospital, Technical University Dresden, D-01307 Dresden (Germany); Lorenz, Mike, E-mail: mlorenz@mpi-cbg.de [Max Planck Institute of Molecular Cell Biology and Genetics, D-01307 Dresden (Germany); Huebner, Angela, E-mail: angela.huebner@uniklinikum-dresden.de [Children' s Hospital, Technical University Dresden, D-01307 Dresden (Germany)

    2009-12-11

    The nuclear pore complex (NPC) consists of {approx}30 different proteins and provides the only sites for macromolecular transport between cytoplasm and nucleus. ALADIN was discovered as a new member of the NPC. Mutations in ALADIN are known to cause triple A syndrome, a rare autosomal recessive disorder characterized by adrenal insufficiency, alacrima, and achalasia. The function and exact location of the nucleoporin ALADIN within the NPC multiprotein complex is still unclear. Using a siRNA-based approach we downregulated the three known membrane integrated nucleoporins NDC1, GP210, and POM121 in stably expressing GFP-ALADIN HeLa cells. We identified NDC1 but not GP210 and POM121 as the main anchor of ALADIN within the NPC. Solely the depletion of NDC1 caused mislocalization of ALADIN. Vice versa, the depletion of ALADIN led also to disappearance of NDC1 at the NPC. However, the downregulation of two further membrane-integral nucleoporins GP210 and POM121 had no effect on ALADIN localization. Furthermore, we could show a direct association of NDC1 and ALADIN in NPCs by fluorescence resonance energy transfer (FRET) measurements. Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. The loss of integration of ALADIN in the NPC is a main pathogenetic aspect for the development of the triple A syndrome and suggests that the interaction between ALADIN and NDC1 may be involved in the pathogenesis of the disease.

  17. WDR62 overexpression is associated with a poor prognosis in patients with lung adenocarcinoma.

    Science.gov (United States)

    Shinmura, Kazuya; Kato, Hisami; Kawanishi, Yuichi; Igarashi, Hisaki; Inoue, Yusuke; Yoshimura, Katsuhiro; Nakamura, Satoki; Fujita, Hidehiko; Funai, Kazuhito; Tanahashi, Masayuki; Niwa, Hiroshi; Ogawa, Hiroshi; Sugimura, Haruhiko

    2017-08-01

    Human WDR62, which is localized in the cytoplasm including the centrosome, is known to be responsible for primary microcephaly; however, the role of WDR62 abnormality in cancers remains largely unknown. In this study, we aimed to reveal the pathological role of WDR62 abnormality in lung adenocarcinoma (LAC). We first examined the WDR62 mRNA expression level of LAC (n = 64) using a QRT-PCR analysis and found that WDR62 mRNA transcripts were significantly overexpressed in LAC (P = 0.0432, Wilcoxon matched pairs test). An immunohistochemical analysis for LAC (n = 237) showed that WDR62 proteins were also significantly overexpressed in LAC (P overexpression have a short overall survival (P = 0.0378, log-rank test), and a multivariate analysis revealed that WDR62 overexpression was an independent predictor of a poor survival outcome among LAC patients (hazard ratio, 2.032; 95% confidence interval, 1.071-3.777; P = 0.0305). Next, we examined the functional effect of WDR62 overexpression on the lung cancer cell line H1299. WDR62-overexpressing lung cancer cells exhibited an increase in cell growth. Moreover, the concurrent overexpression of WDR62 and TPX2, a WDR62-interacting protein that is also overexpressed in LAC, induced centrosome amplification in the lung cells. Finally, we disclosed that the concurrent overexpression of WDR62 and TPX2 is common in diverse human cancers, using data from the Cancer Genome Atlas. These results suggested that WDR62 overexpression is associated with a poor prognosis in patients with LAC and leads to an increase in the malignant potential of lung cells. © 2017 Wiley Periodicals, Inc.

  18. Dynamic interaction of p220NPAT and CBP/p300 promotes S-phase entry

    International Nuclear Information System (INIS)

    Wang, Aiyan; Ikura, Tsuyoshi; Eto, Kazuhiro; Ota, Masato S.

    2004-01-01

    Cajal bodies contain cyclin E/cdk2 and the substrate p220 NPAT to regulate the transcription of histones, which is essential for cell proliferation, however, recent mouse knockout studies indicate that cyclin E and cdk2 are dispensable for these events. Because the CBP/p300 histone acetyltransferase are also known to be involved in cell proliferation, we examined the molecular and functional interactions of p220 NPAT with the CBP/p300 at the G1/S boundary as cell cycle regulators. The subnuclear localization of p220 NPAT and CBP/p300 proteins showed that their foci partially overlapped in a cell cycle dependent manner. Overexpression of p220 NPAT and CBP/p300 cooperatively enhanced G1/S transition and DNA synthesis even without cdk2 phosphorylation site. Finally, molecular alignment analysis indicated that p220 NPAT contains several potential substrate sites for CBP/p300. Overall, our findings demonstrate that p220 NPAT and CBP/p300 form a transient complex at the G1/S boundary to play cooperative roles to promote the S-phase entry

  19. 7 CFR 982.62 - Accounting.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 982.62 Section 982.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... WASHINGTON Order Regulating Handling Expenses and Assessments § 982.62 Accounting. (a) Operating reserve. The...

  20. 40 CFR 62.02 - Introduction.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Introduction. 62.02 Section 62.02 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF STATE PLANS FOR DESIGNATED FACILITIES AND POLLUTANTS General Provisions § 62.02 Introduction...

  1. The Cyclin-Dependent Kinase Ortholog pUL97 of Human Cytomegalovirus Interacts with Cyclins

    Directory of Open Access Journals (Sweden)

    Laura Graf

    2013-12-01

    Full Text Available The human cytomegalovirus (HCMV-encoded protein kinase, pUL97, is considered a cyclin-dependent kinase (CDK ortholog, due to shared structural and functional characteristics. The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. This study provides evidence of direct interaction between pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses. Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231–280. Additional co-immunoprecipitation analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners. Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. This is the first demonstration of interaction between a herpesviral CDK ortholog and cellular cyclins.

  2. Polarization of Λ hyperons produced inclusively in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Kennedy, B.W.; O'Neale, S.W.; Barnham, K.W.J.; Clayton, E.F.; Miller, D.B.; Mobayyen, M.M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K.L.; Wittek, W.

    1985-01-01

    Lambda hyperons from νp and anti np charged current interactions have been analysed for polarization. A significant polarization is observed for Λ particles in the quasi-elastic region for both types of interactions. Part of this polarization is due to the decay of highly polarized Σ(1385) resonances. The results are compared with simple predictions of the quark parton model. (orig.)

  3. Polarization of Λ hyperons produced inclusively in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Kennedy, B.W.; O'Neale, S.W.; Barnham, K.W.J.; Clayton, E.F.; Miller, D.B.; Mobayyen, M.M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1985-01-01

    Lambda hyperons from νp charged current interactions have been analysed for polarization. A significant polarization is observed for Λ particles in the quasi-elastic region for both types of interactions. Part of this polarization is due to the decay of highly polarized phi(1,385) resonances. The results are compared with simple predictions of the quark parton model. (orig.)

  4. 45 CFR 1336.62 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... NATIVE AMERICAN PROGRAMS Native Hawaiian Revolving Loan Fund Demonstration Project § 1336.62 Definitions... 45 Public Welfare 4 2010-10-01 2010-10-01 false Definitions. 1336.62 Section 1336.62 Public... for the purpose of profit. Financing statement means the document filed or recorded in country or...

  5. Movable chain jacks and winches: case study of PETROBRAS' P58/)62and ENI's Goliat

    Energy Technology Data Exchange (ETDEWEB)

    Grindheim, Reidar [Aker Pusnes AS, Arendal (Norway)

    2012-07-01

    Recently, Aker Solutions delivered a movable chain jack system to PETROBRAS's P58/P62 FPSOs and a movable windlass system to ENI's Goliat FPSO. This paper highlights the main differences between the two systems and when it is beneficial to employ movable systems. There are many parameters to consider in determining which system to use - also a traditional system involving a single winch or chain jack per mooring line may in many cases be preferred. The movable chain jack concept is designed to operate multiple mooring lines within the same cluster. A single chain jack is lifted by a skidding gantry and moved to the next mooring line and so forth. Installation and messenger chains are moved using a large sliding chain locker allowing for later offloading of the surplus chain. The movable windlass system is also designed to operate multiple mooring lines within the same cluster. However, in this case the winch is rotary and can operate via electric or hydraulic power. One of the main considerations is to move the windlass and keep the mooring lines intact without cutting them. (author)

  6. Development of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62)

    Science.gov (United States)

    Locke, Benjamin D.; Buzolitz, Johanna Soet; Lei, Pui-Wa; Boswell, James F.; McAleavey, Andrew A.; Sevig, Todd D.; Dowis, Jerome D.; Hayes, Jeffrey A.

    2011-01-01

    Few instruments have been designed specifically to address the needs of college counseling centers. This article reviews existing instruments and presents 4 studies that describe the development and psychometric properties of a new instrument, the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62). Study 1 describes the initial…

  7. Radiolabeling and biodistribution of 62Cu-dithiocarbamate

    International Nuclear Information System (INIS)

    Matsumoto, Kazuya; Fujibayashi, Yasuhisa; Yokoyama, Akira; Konishi, Junji.

    1990-01-01

    The newly developed 62 Zn/ 62 Cu generator system has made available the production of the short-lived 62 Cu (T 1/2 = 9.8 min) positron radionuclide, eluted as 62 Cu-glycine. In the search for 62 Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62 Zn/ 62 Cu generator eluate, the 62 Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62 Cu-DDC and 62 Cu-DmDC were extremely high (non-detectable 62 Cu-glycine) and both chelates were more lipophilic than 62 Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62 Cu-DDC and 62 Cu-DmDC indicated a brain accumlation of 2.8 and 5.3 times higher than 62 Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62 Cu-DDC and 62 Cu-DmDC might be due to their stable, neutral and lipophilic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62 Cu-labeled compounds using the 62 Zn/ 62 Cu generator system based on the ligand exchange reaction with 62 Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62 Cu positron radiopharmaceuticals can be recalled. (author)

  8. Charged pion production in 32 GeV/c K+p interactions

    International Nuclear Information System (INIS)

    Ajinenko, I.V.; Belokopitov, Y.A.; Chliapnikov, P.V.; Falaleev, V.P.; Fenyuk, A.B.; Gerdyukov, L.N.; Kurnosenko, A.I.; Rybin, A.M.; Wolf, E.A.; Dumont, J.J.

    1980-01-01

    Final data on topological cross sections are presented. Inclusive single particle distributions for the reactions K + p → π + -X at 32 GeV/c are discussed and compared with data at lower energies. Early scaling in the fragmentation regions is confirmed, while cross sections in the central region continue to rise with energy even faster than in pp interactions. The x- and psub(T)-dependence of the π + /π - ratio K + p interactions is discussed and a comparison of reactions K + p → π + -X and K - p → π + -X at 32 GeV/c is made in the context of constituent models. We also present transverse momentum distributions, show prominent seagull effects and study how they are influenced by resonance production. (orig.) 891 HSI/orig. 892 MKO

  9. Calumenin interacts with serum amyloid P component

    DEFF Research Database (Denmark)

    Vorum, H; Jacobsen, Christian; Honoré, Bent

    2000-01-01

    with calumenin in the presence of Ca(2+). Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin-SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate...... in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues. Udgivelsesdato: 2000-Jan-14...

  10. 12 CFR 4.62 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Definitions. 4.62 Section 4.62 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS, AVAILABILITY...; Contracting for Goods and Services § 4.62 Definitions. (a) Minority- and/or women-owned (small and large...

  11. 22 CFR 62.16 - Employment.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Employment. 62.16 Section 62.16 Foreign... § 62.16 Employment. (a) An exchange visitor may receive compensation from the sponsor or the sponsor's appropriate designee for employment when such activities are part of the exchange visitor's program. (b) An...

  12. Production of $\\Lambda$ hyperons in inelastic p+p interactions at 158 GeV/$c$

    CERN Document Server

    Aduszkiewicz, A.; Andronov, E.; Antićić, T.; Antoniou, N.; Baatar, B.; Bay, F.; Blondel, A.; Bogomilov, M.; Brandin, A.; Bravar, A.; Brzychczyk, J.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Ćirković, M.; Czopowicz, T.; Damyanova, A.; Davis, N.; Dembinski, H.; Deveaux, M.; Diakonos, F.; Di Luise, S.; Dominik, W.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Feofilov, G.A.; Fodor, Z.; Garibov, A.; Gazdzicki, M.; Golubeva, M.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Haesler, A.; Hasegawa, T.; Hervé, A.E.; Hierholzer, M.; Igolkin, S.; Ivashkin, A.; Johnson, S.R.; Kadija, K.; Kapoyannis, A.; Kaptur, E.; Kisiel, J.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalik, K.; Kowalski, S.; Koziel, M.; Krasnoperov, A.; Kuich, M.; Kurepin, A.; Larsen, D.; László, A.; Lewicki, M.; Lyubushkin, V.V.; Maćkowiak-Pawłowska, M.; Maksiak, B.; Malakhov, A.I.; Manić, D.; Marcinek, A.; Marino, A.D.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Messerly, B.; Mills, G.B.; Morozov, S.; Mrówczyński, S.; Nagai, Y.; Nakadaira, T.; Naskręt, M.; Nirkko, M.; Nishikawa, K.; Panagiotou, A.D.; Paolone, V.; Pavin, M.; Petukhov, O.; Pistillo, C.; Płaneta, R.; Popov, B.A.; Posiadała, M.; Puławski, S.; Puzović, J.; Rauch, W.; Ravonel, M.; Redij, A.; Renfordt, R.; Richter-Wąs, E.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rumberger, B.T.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Schmidt, K.; Sekiguchi, T.; Selyuzhenkov, I.; Seryakov, A.; Seyboth, P.; Sgalaberna, D.; Shibata, M.; Słodkowski, M.; Staszel, P.; Stepaniak, J.; Stefanek, G.; Ströbele, H.; Šuša, T.; Szuba, M.; Tada, M.; Taranenko, A.; Tefelski, D.; Tereshchenko, V.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberič, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Włodarczyk, Z.; Wojtaszek-Szwarc, A.; Wyszyński, O.; Zambelli, L.; Zimmerman, E.D.; Zambelli, L.; Zimmermann, E.D.

    2016-01-01

    Inclusive production of $\\Lambda$-hyperons was measured with the large acceptance NA61/SHINE spectrometer at the CERN SPS in inelastic p+p interactions at beam momentum of 158 GeVc. Spectra of transverse momentum and transverse mass as well as distributions of rapidity and x$_{_F}$ are presented. The mean multiplicity was estimated to be $0.120\\,\\pm0.006\\;(stat.)\\,\\pm 0.010\\;(sys.)$. The results are compared with previous measurements and predictions of the EPOS, UrQMD and FRITIOF models.

  13. Production of $\\Lambda$ hyperons in inelastic p+p interactions at 158 GeV/$c$

    CERN Document Server

    Aduszkiewicz, A.; Andronov, E.; Antićić, T.; Antoniou, N.; Baatar, B.; Bay, F.; Blondel, A.; Bogomilov, M.; Brandin, A.; Bravar, A.; Brzychczyk, J.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Ćirković, M.; Czopowicz, T.; Damyanova, A.; Davis, N.; Dembinski, H.; Deveaux, M.; Diakonos, F.; Di Luise, S.; Dominik, W.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Feofilov, G.A.; Fodor, Z.; Garibov, A.; Gazdzicki, M.; Golubeva, M.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Haesler, A.; Hasegawa, T.; Hervé, A.E.; Hierholzer, M.; Igolkin, S.; Ivashkin, A.; Johnson, S.R.; Kadija, K.; Kapoyannis, A.; Kaptur, E.; Kisiel, J.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalik, K.; Kowalski, S.; Koziel, M.; Krasnoperov, A.; Kuich, M.; Kurepin, A.; Larsen, D.; László, A.; Lewicki, M.; Lyubushkin, V.V.; Maćkowiak-Pawłowska, M.; Maksiak, B.; Malakhov, A.I.; Manić, D.; Marcinek, A.; Marino, A.D.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Messerly, B.; Mills, G.B.; Morozov, S.; Mrówczyński, S.; Nagai, Y.; Nakadaira, T.; Naskręt, M.; Nirkko, M.; Nishikawa, K.; Panagiotou, A.D.; Paolone, V.; Pavin, M.; Petukhov, O.; Pistillo, C.; Płaneta, R.; Popov, B.A.; Posiadała, M.; Puławski, S.; Puzović, J.; Rauch, W.; Ravonel, M.; Redij, A.; Renfordt, R.; Richter-Wąs, E.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rumberger, B.T.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Schmidt, K.; Sekiguchi, T.; Selyuzhenkov, I.; Seryakov, A.; Seyboth, P.; Sgalaberna, D.; Shibata, M.; Słodkowski, M.; Staszel, P.; Stepaniak, J.; Stefanek, G.; Ströbele, H.; Šuša, T.; Szuba, M.; Tada, M.; Taranenko, A.; Tefelski, D.; Tereshchenko, V.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberič, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Włodarczyk, Z.; Wojtaszek-Szwarc, A.; Wyszyński, O.; Zambelli, L.; Zimmerman, E.D.; Zambelli, L.; Zimmermann, E.D.

    2016-04-12

    Inclusive production of $\\Lambda$-hyperons was measured with the large acceptance NA61/SHINE spectrometer at the CERN SPS in inelastic p+p interactions at beam momentum of 158 GeVc. Spectra of transverse momentum and transverse mass as well as distributions of rapidity and x$_{_F}$ are presented. The mean multiplicity was estimated to be $0.120\\,\\pm0.006\\;(stat.)\\,\\pm 0.010\\;(sys.)$. The results are compared with previous measurements and predictions of the EPOS, UrQMD and FRITIOF models.

  14. Screening of medicinal plant phytochemicals as natural antagonists of p53-MDM2 interaction to reactivate p53 functioning.

    Science.gov (United States)

    Riaz, Muhammad; Ashfaq, Usman A; Qasim, Muhammad; Yasmeen, Erum; Ul Qamar, Muhammad T; Anwar, Farooq

    2017-10-01

    In most types of cancer, overexpression of murine double minute 2 (MDM2) often leads to inactivation of p53. The crystal structure of MDM2, with a 109-residue amino-terminal domain, reveals that MDM2 has a core hydrophobic region to which p53 binds as an amphipathic α helix. The interface depends on the steric complementarity between MDM2 and the hydrophobic region of p53. Especially, on p53's triad, amino acids Phe19, Trp23 and Leu26 bind to the MDM2 core. Results from studies suggest that the structural motif of both p53 and MDM2 can be attributed to similarities in the amphipathic α helix. Thus, in the current investigation it is hypothesized that the similarity in the structural motif might be the cause of p53 inactivation by MDM2. Hence, molecular docking and phytochemical screening approaches are appraised to inhibit the hydrophobic cleft of MDM2 and to stop p53-MDM2 interaction, resulting in reactivation of p53 activity. For this purpose, a library of 2295 phytochemicals were screened against p53-MDM2 to find potential candidates. Of these, four phytochemicals including epigallocatechin gallate, alvaradoin M, alvaradoin E and nordihydroguaiaretic acid were found to be potential inhibitors of p53-MDM2 interaction. The screened phytochemicals, derived from natural extracts, may have negligible side effects and can be explored as potent antagonists of p53-MDM2 interactions, resulting in reactivation of the normal transcription of p53.

  15. P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

    DEFF Research Database (Denmark)

    Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

    2005-01-01

    P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

  16. Interaction between S100P and the anti-allergy drug cromolyn

    International Nuclear Information System (INIS)

    Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin

    2014-01-01

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by 1 H- 15 N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex

  17. Production of Λ-hyperons in inelastic p+p interactions at 158 GeV/c

    Energy Technology Data Exchange (ETDEWEB)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M. [University of Warsaw, Warsaw (Poland); Ali, Y. [Jagiellonian University, Cracow (Poland); COMSATS Institute of Information Technology, Department of Physics, Islamabad (Pakistan); Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L. [St. Petersburg State University, St. Petersburg (Russian Federation); Anticic, T.; Kadija, K. [Ruder Boskovic Institute, Zagreb (Croatia); Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M. [University of Athens, Athens (Greece); Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D. [ETH Zuerich, Zuerich (Switzerland); Blondel, A.; Bravar, A.; Damyanova, A.; Haesler, A.; Korzenev, A.; Ravonel, M. [University of Geneva, Geneva (Switzerland); Bogomilov, M.; Kolev, D.; Tsenov, R. [University of Sofia, Faculty of Physics, Sofia (Bulgaria); Brandin, A.; Selyuzhenkov, I.; Taranenko, A. [National Research Nuclear University ' ' MEPhI' ' (Moscow Engineering Physics Institute), Moscow (Russian Federation); Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O. [Jagiellonian University, Cracow (Poland); Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Sadovsky, A. [Institute for Nuclear Research, Moscow (Russian Federation); Cirkovic, M.; Manic, D.; Puzovic, J. [University of Belgrade, Belgrade (Serbia); Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Slodkowski, M.; Tefelski, D. [Warsaw University of Technology, Warsaw (Poland); Dembinski, H.; Engel, R.; Herve, A.E.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D. [Karlsruhe Institute of Technology, Karlsruhe (Germany); Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H. [University of Frankfurt, Frankfurt (Germany); Dumarchez, J.; Robert, A. [University of Paris VI and VII, LPNHE, Paris (France); Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A. [University of Bern, Bern (Switzerland); Fodor, Z. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); University of Wroclaw, Wroclaw (Poland); Garibov, A. [National Nuclear Research Center, Baku (Azerbaijan); Gazdzicki, M. [University of Frankfurt, Frankfurt (Germany); Jan Kochanowski University in Kielce, Kielce (Poland); Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A. [University of Silesia, Katowice (Poland); Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M. [Institute for Particle and Nuclear Studies, Tsukuba (Japan); Johnson, S.R.; Marino, A.D.; Nagai, Y.; Rumberger, B.T.; Zimmerman, E.D. [University of Colorado, Boulder (United States); Kowalik, K.; Rondio, E.; Stepaniak, J. [National Centre for Nuclear Research, Warsaw (Poland); Laszlo, A.; Marton, K.; Vesztergombi, G. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); Lewicki, M.; Naskret, M.; Turko, L. [University of Wroclaw, Wroclaw (Poland); Marcinek, A. [Jagiellonian University, Cracow (Poland); University of Wroclaw, Wroclaw (Poland); Messerly, B.; Paolone, V. [University of Pittsburgh, Pittsburgh (United States); Mills, G.B. [Los Alamos National Laboratory, Los Alamos (United States); Morozov, S.; Petukhov, O. [Institute for Nuclear Research, Moscow (Russian Federation); National Research Nuclear University ' ' MEPhI' ' (Moscow Engineering Physics Institute), Moscow (Russian Federation); Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A. [Jan Kochanowski University in Kielce, Kielce (Poland); Pavin, M. [Ruder Boskovic Institute, Zagreb (Croatia); University of Paris VI and VII, LPNHE, Paris (France); Popov, B.A. [University of Paris VI and VII, LPNHE, Paris (France); Joint Institute for Nuclear Research, Dubna (Russian Federation); Rauch, W. [Fachhochschule Frankfurt, Frankfurt (Germany); Roehrich, D. [University of Bergen, Bergen (Norway); Rustamov, A. [National Nuclear Research Center, Baku (Azerbaijan); University of Frankfurt, Frankfurt (Germany); Susa, T. [Ruder Boskovic Institute, Zagreb (Croatia); Zambelli, L. [University of Paris VI and VII, LPNHE, Paris (France); Institute for Particle and Nuclear Studies, Tsukuba (Japan); Collaboration: NA61/SHINE Collaboration

    2016-04-15

    Inclusive production of Λ-hyperons was measured with the large acceptance NA61/SHINE spectrometer at the CERN SPS in inelastic p+p interactions at beam momentum of 158 GeV/c. Spectra of transverse momentum and transverse mass as well as distributions of rapidity and x{sub F} are presented. The mean multiplicity was estimated to be 0.120 ± 0.006(stat.) ± 0.010(sys.). The results are compared with previous measurements and predictions of the Epos, Urqmd and Fritiof models. (orig.)

  18. Intracellular Distribution of Capsid-Associated pUL77 of Human Cytomegalovirus and Interactions with Packaging Proteins and pUL93.

    Science.gov (United States)

    Köppen-Rung, Pánja; Dittmer, Alexandra; Bogner, Elke

    2016-07-01

    DNA packaging into procapsids is a common multistep process during viral maturation in herpesviruses. In human cytomegalovirus (HCMV), the proteins involved in this process are terminase subunits pUL56 and pUL89, which are responsible for site-specific cleavage and insertion of the DNA into the procapsid via portal protein pUL104. However, additional viral proteins are required for the DNA packaging process. We have shown previously that the plasmid that encodes capsid-associated pUL77 encodes another potential player during capsid maturation. Pulse-chase experiments revealed that pUL77 is stably expressed during HCMV infection. Time course analysis demonstrated that pUL77 is expressed in the early late part of the infectious cycle. The sequence of pUL77 was analyzed to find nuclear localization sequences (NLSs), revealing monopartite NLSm at the N terminus and bipartite NLSb in the middle of pUL77. The potential NLSs were inserted into plasmid pHM829, which encodes a chimeric protein with β-galactosidase and green fluorescent protein. In contrast to pUL56, neither NLSm nor NLSb was sufficient for nuclear import. Furthermore, we investigated by coimmunoprecipitation whether packaging proteins, as well as pUL93, the homologue protein of herpes simplex virus 1 pUL17, are interaction partners of pUL77. The interactions between pUL77 and packaging proteins, as well as pUL93, were verified. We showed that the capsid-associated pUL77 is another potential player during capsid maturation of HCMV. Protein UL77 (pUL77) is a conserved core protein of HCMV. This study demonstrates for the first time that pUL77 has early-late expression kinetics during the infectious cycle and an intrinsic potential for nuclear translocation. According to its proposed functions in stabilization of the capsid and anchoring of the encapsidated DNA during packaging, interaction with further DNA packaging proteins is required. We identified physical interactions with terminase subunits pUL56 and p

  19. Rice black-streaked dwarf virus P6 self-interacts to form punctate, viroplasm-like structures in the cytoplasm and recruits viroplasm-associated protein P9-1

    Directory of Open Access Journals (Sweden)

    Yu Jialin

    2011-01-01

    Full Text Available Abstract Background Rice black-streaked dwarf virus (RBSDV, a member of the genus Fijivirus within the family Reoviridae, can infect several graminaceous plant species including rice, maize and wheat, and is transmitted by planthoppers. Although several RBSDV proteins have been studied in detail, functions of the nonstructural protein P6 are still largely unknown. Results In the current study, we employed yeast two-hybrid assays, bimolecular fluorescence complementation and subcellular localization experiments to show that P6 can self-interact to form punctate, cytoplasmic viroplasm-like structures (VLS when expressed alone in plant cells. The region from residues 395 to 659 is necessary for P6 self-interaction, whereas two polypeptides (residues 580-620 and 615-655 are involved in the subcellular localization of P6. Furthermore, P6 strongly interacts with the viroplasm-associated protein P9-1 and recruits P9-1 to localize in VLS. The P6 395-659 region is also important for the P6-P9-1 interaction, and deleting any region of P9-1 abolishes this heterologous interaction. Conclusions RBSDV P6 protein has an intrinsic ability to self-interact and forms VLS without other RBSDV proteins or RNAs. P6 recruits P9-1 to VLS by direct protein-protein interaction. This is the first report on the functionality of RBSDV P6 protein. P6 may be involved in the process of viroplasm nucleation and virus morphogenesis.

  20. Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein.

    Science.gov (United States)

    Itagaki, Shirou; Ochiai, Akiko; Kobayashi, Masaki; Sugawara, Mitsuru; Hirano, Takeshi; Iseki, Ken

    2008-08-27

    In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.

  1. Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNase P/MRP architecture.

    Science.gov (United States)

    Aspinall, Tanya V; Gordon, James M B; Bennett, Hayley J; Karahalios, Panagiotis; Bukowski, John-Paul; Walker, Scott C; Engelke, David R; Avis, Johanna M

    2007-01-01

    Ribonuclease MRP is an endonuclease, related to RNase P, which functions in eukaryotic pre-rRNA processing. In Saccharomyces cerevisiae, RNase MRP comprises an RNA subunit and ten proteins. To improve our understanding of subunit roles and enzyme architecture, we have examined protein-protein and protein-RNA interactions in vitro, complementing existing yeast two-hybrid data. In total, 31 direct protein-protein interactions were identified, each protein interacting with at least three others. Furthermore, seven proteins self-interact, four strongly, pointing to subunit multiplicity in the holoenzyme. Six protein subunits interact directly with MRP RNA and four with pre-rRNA. A comparative analysis with existing data for the yeast and human RNase P/MRP systems enables confident identification of Pop1p, Pop4p and Rpp1p as subunits that lie at the enzyme core, with probable addition of Pop5p and Pop3p. Rmp1p is confirmed as an integral subunit, presumably associating preferentially with RNase MRP, rather than RNase P, via interactions with Snm1p and MRP RNA. Snm1p and Rmp1p may act together to assist enzyme specificity, though roles in substrate binding are also indicated for Pop4p and Pop6p. The results provide further evidence of a conserved eukaryotic RNase P/MRP architecture and provide a strong basis for studies of enzyme assembly and subunit function.

  2. Hadron production in 250 GeV/c π+p and K+p interactions

    International Nuclear Information System (INIS)

    Van Hal, P.A.

    1985-01-01

    Results on hadron production in π + p and K + p interactions at 250 GeV/c are presented from the experiment NA22 at the CERN SPS. With the present statistics we find: scaling in the fragmentation regions for both charged and neutral pions; a reasonable description of the K + p→π 0 /π + p→π 0 ratio by both the LUND M.C. and a DTU M.C. (Ranft and Ritter), agreement with these Monte Carlo's for the K + /π + population percentages in the forward hemisphere; no agreement for the seagull with the LUND M.C. and strong disagreement with the DTU M.C

  3. [Measurement and analysis of smile line of 62 Han-Chinese].

    Science.gov (United States)

    Hu, Xiu-lian; Heberer, Susanne; Nelson, Katja; Lin, Ye

    2011-11-01

    To analyze smile features in maximum lip-dynamic in Chinese. Sixty-two Han-Chinese, travelling in Germany, with a mean age of 28.5 years were enrolled and photographed. Standardized digital photos were made to measure the height of displayed maxillary gingiva, papilla and tooth during an enjoyment smile. Statistical analysis was performed using Mann-Whitney-U Test and non-parametric analysis. The mean height of tooth display for the central incisors was 10 mm, with no significant difference between the gender (P > 0.05). The mean height of gingival display was 1.3 mm and the mean papilla height was 3.4 mm. There was no significant difference between the genders (P > 0.05). 31% (19/62) of the subjects belonged to high smile line type, 50% (31/62) to medium smile line type and 19% (12/62) to low smile line type. The red esthetics is a paramount factor for Chinese men and women in the esthetic restoration. 81% of the Chinese studied showed various degree of gingival exposure from central incisor to the premolars, which defined the esthetic area for Chinese people. Papilla is a critical parameter for esthetic evaluation and treatment design. The ratio of high smile line in Chinese may be higher than that in Caucasian.

  4. Interaction between p-dihydroxyborylphenylalanine and adrenaline studied by a zone electrophoresis

    International Nuclear Information System (INIS)

    Kitaoka, Y.; Kobayashi, M.

    2000-01-01

    In order to develop a new boron carrier, we studied the interaction between p-dihydroxyborylphenylalanine (p-BPA) and adrenaline (Adre.) by a zone electrophoresis, paper chromatography, and infrared-spectroscopy. It was found that the complex of p-BPA with Adre. was stable near neutral solutions and decomposed under acidic solutions. The chemical nature of the complex was compared with those of the complexes of p-BPA with organic acids. (author)

  5. Interaction between p-dihydroxyborylphenylalanine and adrenaline studied by a zone electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Kitaoka, Y.; Kobayashi, M. [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst

    2000-10-01

    In order to develop a new boron carrier, we studied the interaction between p-dihydroxyborylphenylalanine (p-BPA) and adrenaline (Adre.) by a zone electrophoresis, paper chromatography, and infrared-spectroscopy. It was found that the complex of p-BPA with Adre. was stable near neutral solutions and decomposed under acidic solutions. The chemical nature of the complex was compared with those of the complexes of p-BPA with organic acids. (author)

  6. Electron-electron interaction in p-SiGe/Ge quantum wells

    International Nuclear Information System (INIS)

    Roessner, Benjamin; Kaenel, Hans von; Chrastina, Daniel; Isella, Giovanni; Batlogg, Bertram

    2005-01-01

    The temperature dependent magnetoresistance of high mobility p-SiGe/Ge quantum wells is studied with hole densities ranging from 1.7 to 5.9 x 10 11 cm -2 . At magnetic fields below the onset of quantum oscillations that reflect the high mobility values (up to 75000 cm 2 /Vs), we observe the clear signatures of electron-electron interaction. We compare our experiment with the theory of electron-electron interaction including the Zeeman band splitting. The observed magnetoresistance is well explained as a superposition of band structure induced positive magnetoresistance and the negative magntoresistance due to the electron-electron interaction effect

  7. Interaction between S100P and the anti-allergy drug cromolyn

    Energy Technology Data Exchange (ETDEWEB)

    Penumutchu, Srinivasa R. [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chou, Ruey-Hwang [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China)

    2014-11-21

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

  8. Analysis list: unc-62 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available unc-62 Adult,Embryo,Larvae + ce10 http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/t...arget/unc-62.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/target/unc-62.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/ce10/target/unc-62.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/unc-62....Adult.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/ce10/colo/unc-62.Embryo.tsv,http://dbarchive.bioscien...cedbc.jp/kyushu-u/ce10/colo/unc-62.Larvae.tsv http://dbarchive.biosciencedbc.jp/kyu

  9. Inner/Outer nuclear membrane fusion in nuclear pore assembly: biochemical demonstration and molecular analysis.

    Science.gov (United States)

    Fichtman, Boris; Ramos, Corinne; Rasala, Beth; Harel, Amnon; Forbes, Douglass J

    2010-12-01

    Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in double nuclear membranes, which carry out nucleocytoplasmic exchange. The mechanism of nuclear pore assembly involves a unique challenge, as it requires creation of a long-lived membrane-lined channel connecting the inner and outer nuclear membranes. This stabilized membrane channel has little evolutionary precedent. Here we mapped inner/outer nuclear membrane fusion in NPC assembly biochemically by using novel assembly intermediates and membrane fusion inhibitors. Incubation of a Xenopus in vitro nuclear assembly system at 14°C revealed an early pore intermediate where nucleoporin subunits POM121 and the Nup107-160 complex were organized in a punctate pattern on the inner nuclear membrane. With time, this intermediate progressed to diffusion channel formation and finally to complete nuclear pore assembly. Correct channel formation was blocked by the hemifusion inhibitor lysophosphatidylcholine (LPC), but not if a complementary-shaped lipid, oleic acid (OA), was simultaneously added, as determined with a novel fluorescent dextran-quenching assay. Importantly, recruitment of the bulk of FG nucleoporins, characteristic of mature nuclear pores, was not observed before diffusion channel formation and was prevented by LPC or OA, but not by LPC+OA. These results map the crucial inner/outer nuclear membrane fusion event of NPC assembly downstream of POM121/Nup107-160 complex interaction and upstream or at the time of FG nucleoporin recruitment.

  10. Influence of dietary calcium (Ca) and phosphorus (P) on phosphorus retention in chickens

    International Nuclear Information System (INIS)

    Scheideler, S.E.; Sell, J.L.

    1986-01-01

    Experiment 1 was a 3 x 3 factorial arrangement with 3 levels of dietary Ca (3.0, 3.5, and 4.0%) and 3 P feeding programs fed to laying hens for 336 days. The P programs tested were: .64% P fed continuously for 48 weeks; .64, .54, and .44% P; and .56, .49, and .39% P fed when hens were 24 to 36, 36 to 52, and 52 to 72 weeks of age, respectively. In addition to production traits, measurements of P retention were made at 34, 42, 50, 62, and 72 weeks of age. None of the production traits measured showed any dietary effects. Dietary Ca affected P retention at 50, 62, and 72 weeks of age. None of the production traits measured showed any dietary effects. Dietary Ca affected P retention at 50, 62, and 72 weeks of age. Average P retention for the experiment was 104, 148, and 178 mg/day in hens fed 3.0, 3.5, and 4.0% Ca. Dietary P affected P retention at 42 and 72 weeks, with P retention being greater in hens fed .64% P. Ca x P interactions were measured at 42, 62, and 72 weeks of age. Experiment 2 involved 2 levels of dietary Ca (.8 and 1.2%) fed to one-week-old broiler chicks for 8 days during which time 50 uCi 33 P/chick were administered. Serum, femurs, and excreta were collected 48 hours following 33 P dosing. Serum inorganic P and excreted 33 P activity were greater in chicks fed .8% Ca; whereas femur 33 P activity was greater when chicks received the 1.2% Ca diet. These data indicate increased P retention and greater bone deposition of P in chicks fed 1.2% dietary Ca. These results support those of Experiment 1 in which P retention of hens increased as dietary Ca increased

  11. Measurement of negatively charged pion spectra in inelastic p+p interactions at p{sub lab} = 20, 31, 40, 80 and 158 GeV/c

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N.; Blondel, A.; Bravar, A.; Debieux, S.; Haesler, A.; Korzenev, A.; Murphy, S.; Ravonel, M. [University of Geneva, Geneva (Switzerland); Aduszkiewicz, A.; Dominik, W.; Kielczewska, D.; Kirejczyk, M.; Matulewicz, T.; Posiadala, M.; Skrzypczak, E. [University of Warsaw, Faculty of Physics, Warsaw (Poland); Ali, Y.; Brzychczyk, J.; Majka, Z.; Marcinek, A.; Planeta, R.; Staszel, P.; Wyszynski, O. [Jagiellonian University, Cracow (Poland); Anticic, T.; Kadija, K.; Susa, T. [Rudjer Boskovic Institute, Zagreb (Croatia); Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M. [University of Athens, Athens (Greece); Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Melkumov, G.L.; Tereshchenko, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Bay, F.; Luise, S.Di; Rubbia, A.; Sgalaberna, D. [ETH, Zurich (Switzerland); Blumer, J.; Dembinski, H.; Engel, R.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M. [Karlsruhe Institute of Technology, Karlsruhe (Germany); Bogomilov, M.; Kolev, D.; Tsenov, R. [University of Sofia, Faculty of Physics, Sofia (Bulgaria); Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Marin, V.; Petukhov, O.; Sadovsky, A. [Institute for Nuclear Research, Moscow (Russian Federation); Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Maksiak, B.; Peryt, W.; Pluta, J.; Slodkowski, M. [Warsaw University of Technology, Warsaw (Poland); Drozhzhova, T.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Vechernin, V.V.; Vinogradov, L. [St. Petersburg State University, St. Petersburg (Russian Federation); Dumarchez, J.; Robert, A.; Zambelli, L. [LPNHE, University of Paris VI and VII, Paris (France); Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A. [University of Bern, Bern (Switzerland); Fodor, Z.; Fulop, A.; Kiss, T.; Laszlo, A.; Marton, K.; Palla, G.; Sipos, R.; Tolyhi, T.; Vesztergombi, G. [KFKI Research Institute for Particle and Nuclear Physics, Budapest (Hungary); Gazdzicki, M. [Jan Kochanowski University in Kielce, Kielce (Poland); University of Frankfurt, Frankfurt (Germany); Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Larsen, D.; Pulawski, S.; Schmidt, K.; Wilczek, A.; Zipper, W. [University of Silesia, Katowice (Poland); Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M. [High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki (Japan); Idczak, R.; Kovesarki, P.; Turko, L. [University of Wroclaw, Wroclaw (Poland); Jokovic, D.; Manic, D.; Puzovic, J.; Savic, M. [University of Belgrade, Belgrade (Serbia); Kleinfelder, S. [University of California, Irvine (United States); Mackowiak-Pawlowska, M.; Renfordt, R.; Rustamov, A.; Stroebele, H. [University of Frankfurt, Frankfurt (Germany); Matveev, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Institute for Nuclear Research, Moscow (Russian Federation); Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A. [Jan Kochanowski University in Kielce, Kielce (Poland); Palczewski, T.; Rondio, E.; Stepaniak, J. [National Centre for Nuclear Research, Warsaw (Poland); Paul, T.; Veberic, D. [University Nova Gorica, Laboratory of Astroparticle Physics, Nova Gorica (Slovenia); Popov, B.A. [Joint Institute for Nuclear Research, Dubna (Russian Federation); LPNHE, University of Paris VI and VII, Paris (France); Rauch, W. [Fachhochschule Frankfurt, Frankfurt (Germany); Roehrich, D. [University of Bergen, Bergen (Norway); Collaboration: NA61/SHINE Collaboration

    2014-03-15

    We present experimental results on inclusive spectra and mean multiplicities of negatively charged pions produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158 GeV/c (√(s) = 6.3, 7.7, 8.8, 12.3 and 17.3 GeV, respectively). The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN super proton synchrotron. Two-dimensional spectra are determined in terms of rapidity and transverse momentum. Their properties such as the width of rapidity distributions and the inverse slope parameter of transverse mass spectra are extracted and their collision energy dependences are presented. The results on inelastic p+p interactions are compared with the corresponding data on central Pb+Pb collisions measured by the NA49 experiment at the CERN SPS. The results presented in this paper are part of the NA61/SHINE ion program devoted to the study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter. They are required for interpretation of results on nucleus-nucleus and proton-nucleus collisions. (orig.)

  12. The NA62 GigaTracker

    CERN Document Server

    Perrin-Terrin, Mathieu

    2015-01-01

    The GigaTracker is an hybrid silicon pixel detector built for the NA62 experiment aiming at measuring the branching fraction of the ultra-rare kaon decay K + ! p + n ̄ n at the CERN SPS. The detector has to track particles in a beam with a flux reaching 1.3 MHz/mm 2 and provide single-hit timing with 200ps RMS resolution for a total material budget of less than 1.5 X 0 . The tracker comprises three 60.8mm 27mm stations installed in vacuum ( 10$^{-6}$ mbar) and cooled with liquid C 6 F 14 circulating through micro-channels etched inside few hundred of microns thick silicon plates. Each station is composed of a 200 m m thick silicon sensor readout by 2 x 5 cus- tom 100 m m thick ASIC, called TDCPix. Each chip contains 40 x 45 asynchronous pixels, each 300 m m x 300 m m and is instrumented with 100ps bin time-to-digital converters. In order to cope with the high rate, the TDCPix is equipped with four 3.2Gb/s serialisers sending out the data. We will describe the detector and the results from the 2014 NA62 ru...

  13. Electric Monopole Transition Strengths in 62Ni

    Directory of Open Access Journals (Sweden)

    Evitts L. J.

    2016-01-01

    Full Text Available Excited states in 62Ni were populated with a (p, p’ reaction using the 14UD Pelletron accelerator at the Australian National University. Electric monopole transition strengths, ρ2(E0, were measured through simultaneous detection of the internal conversion electrons and γ rays emitted from the de-excitation of populated states, using the Super-e spectrometer coupled with a germanium detector. The strength of the 02+ to 01+ transition has been measured to be 77−34+23 × 10−3 and agrees with previously reported values. Upper limits have been placed on the 03+ to 01+ and 03+ to 02+ transitions. The measured ρ2(E0 value of the 22+ to 21+ transition in 62Ni has been measured for the first time and found to be one of the largest ρ2(E0 values measured to date in nuclei heavier than Ca. The low-lying states of 62Ni have previously been classified as one- and two-phonon vibrational states based on level energies. The measured electric quadrupole transition strengths are consistent with this interpretation. However as electric monopole transitions are forbidden between states which differ by one phonon number, the simple harmonic quadrupole vibrational picture is not suffcient to explain the large ρ2(E0 value for the 22+ to 21+ transition.

  14. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    Science.gov (United States)

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. All new for NA62

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    This week sees the start of the first run of the new NA62 experiment. This will be a unique opportunity for the collaboration to test its new beam, new detectors and new data acquisition system before the physics run in 2014. Speaking to the Bulletin, the NA62 technical coordinator Ferdinand Hahn shares the many challenges that the various teams faced to be on time for beam. Ready, steady, start!   A Large Angle Veto detector (white) in place in the NA62 decay volume (blue). With components from almost all the detectors in place downstream of the decay point of the mother particles – the kaons – and of the KTAG detector that tags the kaons before they decay, NA62 is ready for its first technical run. This unique run will test all the equipment as well as the trigger and the data acquisition systems. “This year, we will have about five weeks of beam from the SPS before the long shutdown of all the CERN machines,” says Ferdinand Hahn, NA62 Technical Co-...

  16. Antihydrogen Production in $ \\bar{p} $ Z - interaction

    CERN Multimedia

    2002-01-01

    % PS210 \\\\ \\\\ The production of the antihydrogen atom $ \\bar {H}^0 \\equiv \\bar{p}e $ as the simplest atomic bound state of antimatter has been studied. Nine $ \\bar {H}^0 $ have been observed.\\\\ \\\\ The production of $ \\bar {H}^0 $ is predominantly mediated by the two-photon mechanism in the antiproton-nucleus interaction. In principle $ \\bar {H}^0 $ is well suited for investigations of fundamental CPT violation studies under different forces, however, in the present experiment we concentrated on the production of this antimatter object, since so far it never had been observed.

  17. 22 CFR 62.28 - International visitors.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false International visitors. 62.28 Section 62.28 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Specific Program Provisions § 62.28 International visitors. (a) Purpose. The international visitor category is for...

  18. Configuration interaction calculations of positron binding to Be(3P )

    International Nuclear Information System (INIS)

    Bromley, M.W.J.; Mitroy, J.

    2006-01-01

    The configuration interaction method is applied to investigate the possibility of positron binding to the metastable beryllium (1s 2 2s2p 3 P ) state. The largest calculation obtained an estimated energy that was unstable by 0.00014 Hartree with respect to the Ps + Be + (2s) lowest dissociation channel. It is likely that positron binding to parent states with non-zero angular momentum is inhibited by centrifugal barriers

  19. An Amphiphysin-Like Domain in Fus2p Is Required for Rvs161p Interaction and Cortical Localization

    Directory of Open Access Journals (Sweden)

    Richard A. Stein

    2016-02-01

    Full Text Available Cell–cell fusion fulfils essential roles in fertilization, development and tissue repair. In the budding yeast, Saccharomyces cerevisiae, fusion between two haploid cells of opposite mating type generates the diploid zygote. Fus2p is a pheromone-induced protein that regulates cell wall removal during mating. Fus2p shuttles from the nucleus to localize at the shmoo tip, bound to Rvs161p, an amphiphysin. However, Rvs161p independently binds a second amphiphysin, Rvs167p, playing an essential role in endocytosis. To understand the basis of the Fus2p–Rvs161p interaction, we analyzed Fus2p structural domains. A previously described N-terminal domain (NTD is necessary and sufficient to regulate nuclear/cytoplasmic trafficking of Fus2p. The Dbl homology domain (DBH binds GTP-bound Cdc42p; binding is required for cell fusion, but not localization. We identified an approximately 200 amino acid region of Fus2p that is both necessary and sufficient for Rvs161p binding. The Rvs161p binding domain (RBD contains three predicted alpha-helices; structural modeling suggests that the RBD adopts an amphiphysin-like structure. The RBD contains a 13-amino-acid region, conserved with Rvs161p and other amphiphysins, which is essential for binding. Mutations in the RBD, predicted to affect membrane binding, abolish cell fusion without affecting Rvs161p binding. We propose that Fus2p/Rvs161p form a novel heterodimeric amphiphysin required for cell fusion. Rvs161p binding is required but not sufficient for Fus2p localization. Mutations in the C-terminal domain (CTD of Fus2p block localization, but not Rvs161p binding, causing a significant defect in cell fusion. We conclude that the Fus2p CTD mediates an additional, Rvs161p-independent interaction at the shmoo tip.

  20. 19 CFR 210.62 - Evidentiary hearing.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Evidentiary hearing. 210.62 Section 210.62 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.62 Evidentiary hearing. An opportunity for a hearing in...

  1. A copper-methionine interaction controls the pH-dependent activation of peptidylglycine monooxygenase.

    Science.gov (United States)

    Bauman, Andrew T; Broers, Brenda A; Kline, Chelsey D; Blackburn, Ninian J

    2011-12-20

    The pH dependence of native peptidylglycine monooxygenase (PHM) and its M314H variant has been studied in detail. For wild-type (WT) PHM, the intensity of the Cu-S interaction visible in the Cu(I) extended X-ray absorption fine structure (EXAFS) data is inversely proportional to catalytic activity over the pH range of 3-8. A previous model based on more limited data was interpreted in terms of two protein conformations involving an inactive Met-on form and an active flexible Met-off form [Bauman, A. T., et al. (2006) Biochemistry 45, 11140-11150] that derived its catalytic activity from the ability to couple into vibrational modes critical for proton tunneling. The new studies comparing the WT and M314H variant have led to the evolution of this model, in which the Met-on form has been found to be derived from coordination of an additional Met residue, rather than a more rigid conformer of M314 as previously proposed. The catalytic activity of the mutant decreased by 96% because of effects on both k(cat) and K(M), but it displayed the same activity-pH profile with a maximum around pH 6. At pH 8, the reduced Cu(I) form gave spectra that could be simulated by replacement of the Cu(M) Cu-S(Met) interaction with a Cu-N/O interaction, but the data did not unambiguously assign the ligand to the imidazole side chain of H314. At pH 3.5, the EXAFS still showed the presence of a strong Cu-S interaction, establishing that the Met-on form observed at low pH in WT cannot be due to a strengthening of the Cu(M)-methionine interaction but must arise from a different Cu-S interaction. Therefore, lowering the pH causes a conformational change at one of the Cu centers that brings a new S donor residue into a favorable orientation for coordination to copper and generates an inactive form. Cys coordination is unlikely because all Cys residues in PHM are engaged in disulfide cross-links. Sequence comparison with the PHM homologues tyramine β-monooxygenase and dopamine

  2. Identification and analysis of charged hadrons in p+p interactions from NA61/SHINE experiment at CERN SPS energies

    CERN Document Server

    Pulawski, Szymon

    The phase-transition of strongly interacting matter is a very interesting phenom- ena, which still is not fully understood. Signi cant contribution to improving knowledge about properties of the onset of decon nement of strongly interact- ing matter might come from the NA61/SHINE experiment at CERN. The main goal of this xed-target experiment is to discover the critical point and study the properties of the onset of decon nement. This goal has been reached by the pre- cise measurement of the hadron production in proton-proton, proton-nucleus and nucleus-nucleus interactions in a wide range of system sizes and collision energies. The main goal of this thesis was to obtained two-dimensional spectra of positively and negatively charged pions, kaons and protons produced in p + p interactions at SPS energy range (20 ; 30 : 9 ; 40 ; 80 ; 158 GeV=c ). This studies are necessary for understanding of the onset of decon nement. For this purpose, identi cation and correction techniques dedicated...

  3. Specificity and inhibitory mechanism of andrographolide and its analogues as antiasthma agents on NF-κB p50.

    Science.gov (United States)

    Nguyen, Van Sang; Loh, Xin Yi; Wijaya, Hadhi; Wang, Jigang; Lin, Qingsong; Lam, Yulin; Wong, Wai-Shiu Fred; Mok, Yu Keung

    2015-02-27

    Andrographolide (1) is a diterpenoid lactone with an α,β-unsaturated lactone group that inhibits NF-κB DNA binding. Andrographolide reacts with the nucleophilic Cys62 of NF-κB p50 through a Michael addition at the Δ(12(13)) exocylic double bond to form a covalent adduct. Using computer docking, site-directed mutagenesis, and mass spectrometry, the noncovalent interactions between andrographolide and additional binding site residues other than Cys62 were found to be essential for the covalent incorporation of andrographolide. Furthermore, the addition reaction of andrographolide on Cys62 was highly dependent on the redox conditions and on the vicinity of nearby, positively charged Arg residues in the conserved RxxRxR motif. The reaction mechanisms of several of the analogues were determined, showing that 14-deoxy-11,12-didehydroandrographolide (8) reacts with NF-κB p50 via a novel mechanism distinct from andrographolide. The noncovalent interaction and redox environment of the binding site should be considered, in addition to the electrophilicity, when designing a covalent drug. Analogues similar in structure appear to use distinct reaction mechanisms and may have very different cytotoxicities, e.g., compound 6.

  4. 14 CFR 33.62 - Stress analysis.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Stress analysis. 33.62 Section 33.62... STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.62 Stress analysis. A stress analysis must be performed on each turbine engine showing the design safety margin of each turbine...

  5. 22 CFR 62.27 - Alien physicians.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Alien physicians. 62.27 Section 62.27 Foreign... Provisions § 62.27 Alien physicians. (a) Purpose. Pursuant to the Mutual Educational and Cultural Exchange... Foreign Medical Graduates must sponsor alien physicians who wish to pursue programs of graduate medical...

  6. 7 CFR 946.62 - Effective time.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Effective time. 946.62 Section 946.62 Agriculture... Order Regulating Handling Effective Time and Termination § 946.62 Effective time. The provisions of this subpart shall become effective at such time as the Secretary may declare above his signature attached to...

  7. 42 CFR 460.62 - Governing body.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Governing body. 460.62 Section 460.62 Public Health... Administrative Requirements § 460.62 Governing body. (a) Governing body. A PACE organization must be operating under the control of an identifiable governing body (for example, a board of directors) or a designated...

  8. Analyses on the BFS critical experiments. An analysis on the BFS-62-1 and 62-2 cores

    International Nuclear Information System (INIS)

    Sugino, Kazuteru; Shono, Akira

    2002-04-01

    In order to support the Russian excess weapons plutonium disposition, the international collaboration has been started between Japan Nuclear Cycle Development Institute (JNC) and Russian Institute of Physics and Power Engineering (IPPE). In the frame of the collaboration, JNC has carried out analyses on the BFS-62 assemblies that are constructed in the fast reactor critical experimental facility BFS-2 of IPPE. This report summarizes an experimental analysis on the BFS-62-1 and BFS-62-2 cores. The BFS-62-1 core models the present BN-600, and contains the enriched UO 2 fuel surrounded by the UO 2 blanket. The BFS-62-2 core has the same layout as the BFS-62-1 but the blanket region was replaced with stainless steel shied. For core parameter analyses, the 3-D Hexagonal-Z or XYZ geometry model was applied by not only diffusion calculation but also transport calculation. Further in terms of the utilization of the BFS experimental analysis data for the standard data base for FBR core design, consistency evaluation with JUPITER experimental analysis data has been performed using the cross-section adjustment method. As the result of analyses, good agreement was obtained between calculations and experiments for the criticality, the reaction rate ratio and reaction rate distribution in BFS-62-1. In the reaction rate distribution of BFS-62-2 calculation without cross-section adjustment produced big radial dependency of calculation over experiment value (C/E value) in the core region and overestimation in the shield region. Cross-section adjustment technique procedure improved those estimation, however alternation of cross-section of Iron, which was dominant in above improvement, compared to the cross-section error, and further investigation was required. Concerning the control rod worth of BFS-62-1, radial dependency of the C/E value was observed whether cross-section adjustment technique was applied or not, therefore comparison with results of other BFS-62 cores analyses is

  9. The tumor suppressors p33ING1 and p33ING2 interact with alien in vivo and enhance alien-mediated gene silencing.

    Science.gov (United States)

    Fegers, Inga; Kob, Robert; Eckey, Maren; Schmidt, Oliver; Goeman, Frauke; Papaioannou, Maria; Escher, Niko; von Eggeling, Ferdinand; Melle, Christian; Baniahmad, Aria

    2007-11-01

    The tumor suppressor p33ING1 is involved in DNA repair and cell cycle regulation. Furthermore, p33ING1 is a transcriptional silencer that recognizes the histone mark for trimethylated lysine 4 at histone H3. Interestingly, expression of p33ING1 and p33ING2 is able to induce premature senescence in primary human fibroblasts. The corepressor Alien is involved in gene silencing mediated by selected members of nuclear hormone receptors. In addition, Alien acts as a corepressor for E2F1, a member of the E2F cell cycle regulatory family. Furthermore, recent findings suggest that Alien is complexed with transcription factors participating in DNA repair and chromatin. Here, using a proteomic approach by surface-enhanced laser desorption ionization and mass spectrometry (SELDI-MS) combined with immunological techniques, we show that Alien interacts in vivo with the tumor suppressor p33ING1 as well as with the related tumor suppressor candidate p33ING2. The interaction of Alien with p33ING1 and p33ING2 was confirmed in vitro with GST-pull-down, suggesting a direct binding of Alien to these factors. The binding domain was mapped to a central region of Alien. Functionally, the expression of p33ING1 or p33ING2 enhances the Alien-mediated silencing, suggesting that the interaction plays a role in transcriptional regulation. Thus, the findings suggest that the identified interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network.

  10. 30 CFR 62.120 - Action level.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Action level. 62.120 Section 62.120 Mineral... OCCUPATIONAL NOISE EXPOSURE § 62.120 Action level. If during any work shift a miner's noise exposure equals or exceeds the action level the mine operator must enroll the miner in a hearing conservation program that...

  11. 30 CFR 62.160 - Hearing protectors.

    Science.gov (United States)

    2010-07-01

    ... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.160 Hearing protectors. (a) A mine operator must provide a hearing protector to a miner whose noise exposure equals or exceeds the action level under § 62.120 of this part. In addition, the mine operator must: (1) Train the miner in accordance with § 62.180 of this...

  12. Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor: EFFECT ON PKA LOCALIZATION AND P-Rex1 SIGNALING.

    Science.gov (United States)

    Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G H; Fukuhara, Shigetomo; Taylor, Susan S; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

    2016-03-18

    Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Cloning, expression and characterisation of P450-Hal1 (CYP116B62) from Halomonas sp. NCIMB 172: A self-sufficient P450 with high expression and diverse substrate scope.

    Science.gov (United States)

    Porter, Joanne L; Sabatini, Selina; Manning, Jack; Tavanti, Michele; Galman, James L; Turner, Nicholas J; Flitsch, Sabine L

    2018-06-01

    Cytochrome P450 monooxygenases are able to catalyse a range of synthetically challenging reactions ranging from hydroxylation and demethylation to sulfoxidation and epoxidation. As such they have great potential for biocatalytic applications but are underutilised due to often-poor expression, stability and solubility in recombinant bacterial hosts. The use of self-sufficient P450 s with fused haem and reductase domains has already contributed heavily to improving catalytic efficiency and simplifying an otherwise more complex multi-component system of P450 and redox partners. Herein, we present a new addition to the class VII family with the cloning, sequencing and characterisation of the self-sufficient CYP116B62 Hal1 from Halomonas sp. NCIMB 172, the genome of which has not yet been sequenced. Hal1 exhibits high levels of expression in a recombinant E. coli host and can be utilised from cell lysate or used in purified form. Hal1 favours NADPH as electron donor and displays a diverse range of activities including hydroxylation, demethylation and sulfoxidation. These properties make Hal1 suitable for future biocatalytic applications or as a template for optimisation through engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Measurement of negatively charged pion spectra in inelastic p+p interactions at $p_{lab}$ = 20, 31, 40, 80 and 158 GeV/c

    CERN Document Server

    Abgrall, N; Ali, Y; Anticic, T; Antoniou, N; Baatar, B; Bay, F; Blondel, A; Blumer, J; Bogomilov, M; Bravar, A; Brzychczyk, J; Bunyatov, S A; Busygina, O; Christakoglou, P; Czopowicz, T; Davis, N; Debieux, S; Dembinski, H; Diakonos, F; Di Luise, S; Dominik, W; Drozhzhova, T; Dumarchez, J; Dynowski, K; Engel, R; Ereditato, A; Feofilov, G A; Fodor, Z; Fulop, A; Gazdzicki, M; Golubeva, M; Grebieszkow, K; Grzeszczuk, A; Guber, F; Haesler, A; Hasegawa, T; Hierholzer, M; Idczak, R; Igolkin, S; Ivashkin, A; Jokovic, D; Kadija, K; Kapoyannis, A; Katrynska, N; Kaptur, E; Kielczewska, D; Kirejczyk, M; Kisiel, J; Kiss, T; Kleinfelder, S; Kobayashi, T; Kolesnikov, V I; Kolev, D; Kondratiev, V P; Korzenev, A; Kovesarki, P; Kowalski, S; Krasnoperov, A; Kurepin, A; Larsen, D; Laszlo, A; Lyubushkin, V V; Mackowiak-Pawlowska, M; Majka, Z; Maksiak, B; Malakhov, A I; Manic, D; Marcinek, A; Marin, V; Marton, K; Mathes, H J; Matulewicz, T; Matveev, V; Melkumov, G.L; Mrowczynski, St; Murphy, S; Nakadaira, T; Nirkko, M; Nishikawa, K; Palczewski, T; Palla, G; Panagiotou, A D; Paul, T; Pistillo, C; Peryt, W; Petukhov, O; Planeta, R; Pluta, J; Popov, B A; Posiadala, M; Pulawski, S; Puzovic, J; Rauch, W; Ravonel, M; Redij, A; Renfordt, R; Robert, A; Rohrich, D; Rondio, E; Roth, M; Rubbia, A; Rustamov, A; Rybczynski, M; Sadovsky, A; Sakashita, K; Savic, M; Schmidt, K; Sekiguchi, T; Seyboth, P; Sgalaberna, D; Shibata, M; Sipos, R; Skrzypczak, E; Slodkowski, M; Staszel, P; Stefanek, G; Stepaniak, J; Strobele, H; Susa, T; Szuba, M; Tada, M; Tereshchenko, V; Tolyhi, T; Tsenov, R; Turko, L; Ulrich, R; Unger, M; Vassiliou, M; Veberic, D; Vechernin, V V; Vesztergombi, G; Vinogradov, L; Wilczek, A; Wlodarczyk, Z; Wojtaszek-Szwarc, A; Wyszynski, O; Zambelli, L; Zipper, W

    2014-01-01

    We present experimental results on inclusive spectra and mean multiplicities of negatively charged pions produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158GeV/c ($\\sqrt{s}$ = 6.3, 7.7, 8.8, 12.3 and 17.3GeV, respectively). The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN super proton synchrotron. Two-dimensional spectra are determined in terms of rapidity and transverse momentum. Their properties such as the width of rapidity distributions and the inverse slope parameter of transverse mass spectra are extracted and their collision energy dependences are presented. The results on inelastic p+p interactions are compared with the corresponding data on central Pb+Pb collisions measured by the NA49 experiment at the CERN SPS. The results presented in this paper are part of the NA61/SHINE ion program devoted to the study of the properties of the onset of deconfinement and search for the critical point of strongly inter...

  15. 39 CFR 6.2 - Special meetings.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Special meetings. 6.2 Section 6.2 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE MEETINGS (ARTICLE VI) § 6.2 Special meetings. Consistent with the provisions of §§ 6.6 and 7.5 of these bylaws, the Chairman...

  16. 21 CFR 640.62 - Medical supervision.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Medical supervision. 640.62 Section 640.62 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.62 Medical supervision. A qualified licensed physician shall be on the...

  17. 44 CFR 6.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 6.2 Section 6.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... those concerning education, financial transactions, medical history, and criminal or employment history...

  18. 22 CFR 62.26 - Specialists.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Specialists. 62.26 Section 62.26 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Specific Program... such areas, for example, as mass media communication, environmental science, youth leadership...

  19. 15 CFR 700.62 - Directives.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Directives. 700.62 Section 700.62 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE NATIONAL SECURITY INDUSTRIAL BASE REGULATIONS DEFENSE...

  20. CCHCR1 interacts with EDC4, suggesting its localization in P-bodies

    Energy Technology Data Exchange (ETDEWEB)

    Ling, Y.H.; Wong, C.C. [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Li, K.W. [Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam (Netherlands); Chan, K.M. [School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China); Boukamp, P. [Division of Genetics of Skin Carcinogenesis, A110 German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Liu, W.K., E-mail: ken-liu@cuhk.edu.hk [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong (China)

    2014-09-10

    Coiled‐coil alpha‐helical rod protein 1 (CCHCR1) is suggested as a candidate biomarker for psoriasis for more than a decade but its function remains poorly understood because of the inconsistent findings in the literature. CCHCR1 protein is suggested to be localized in the cytoplasm, nucleus, mitochondria, or centrosome and to regulate various cellular functions, including steroidogenesis, proliferation, differentiation, and cytoskeleton organization. In this study, we attempted to find a consensus between these findings by identifying the interaction partners of CCHCR1 using co-immunoprecipiation with a stable cell line expressing EGFP-tagged CCHCR1. Out of more than 100 co-immunoprecipitants identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), the enhancer of mRNA-decapping protein 4 (EDC4), which is a processing body (P-body) component, was particularly found to be the major interacting partner of CCHCR1. Confocal imaging confirmed the localization of CCHCR1 in P-bodies and its N-terminus is required for this subcellular localization, suggesting that CCHCR1 is a novel P-body component. As P-bodies are the site for mRNA metabolism, our findings provide a molecular basis for the function of CCHCR1, any disruption of which may affect the transcriptome of the cell, and causing abnormal cell functions. - Highlights: • We identified CCHCR1 as a novel P-body component. • We identified EDC4 as the major interacting partner of CCHCR1. • N-terminus of CCHCR1 protein is required for its P-bodies localization.

  1. Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor

    Science.gov (United States)

    Chávez-Vargas, Lydia; Adame-García, Sendi Rafael; Cervantes-Villagrana, Rodolfo Daniel; Castillo-Kauil, Alejandro; Bruystens, Jessica G. H.; Fukuhara, Shigetomo; Taylor, Susan S.; Mochizuki, Naoki; Reyes-Cruz, Guadalupe; Vázquez-Prado, José

    2016-01-01

    Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA. PMID:26797121

  2. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  3. The Consequence of Drug-Drug Interactions Influencing the Interplay between P-Glycoprotein and Cytochrome P450 3a: An Ex Vivo Study with Rat Precision-Cut Intestinal Slices.

    Science.gov (United States)

    Li, Ming; de Graaf, Inge A M; Siissalo, Sanna; de Jager, Marina H; van Dam, Annie; Groothuis, Geny M M

    2016-05-01

    P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) are differentially expressed along the intestine and work coordinately to reduce the intracellular concentration of xenobiotics and the absorption of orally taken drugs. Drug-drug interactions (DDIs) based on P-gp/CYP3A interplay are of clinical importance and require preclinical investigation. We investigated the P-gp/Cyp3a interplay and related DDIs with different P-gp inhibitors in the various regions of the rat intestine ex vivo using precision-cut intestinal slices (PCIS) with quinidine (Qi), a dual substrate of P-gp and Cyp3a, as the probe. The results showed that P-gp efflux was the main factor limiting the intracellular Qi content at concentrations below 5µM, whereas both efflux and metabolism were saturated at [Qi] > 50µM. The selective P-gp inhibitors CP100356 [N-(3,4-dimethoxyphenethyl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2[1H]-yl)-6,7-dimethoxyquinazolin-2-amine] and PSC833 [valspodar, 6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-l-valine-cyclosporin A] enhanced the Qi accumulation in slices in line with the different P-gp expression in the intestinal regions and, as a result, also enhanced metabolism in the jejunum and ileum. Dual inhibitors of both P-gp and Cyp3a (verapamil and ketoconazole) increased the concentration of Qi in the jejunum and ileum, but less 3-hydroxy-quinidine was produced due to inhibition of Cyp3a. The results indicate that the P-gp/Cyp3a interplay depends on the concentration of the drug and on the intestinal region under study. Furthermore, due to the P-gp/Cyp3a interplay, DDIs can lead to remarkable changes in the intracellular concentration of both the parent drug and the metabolite, which varies among the intestinal regions and depends on the selectivity of the inhibitors, with potentially important implications for disposition and toxicity of drugs and their metabolites. Copyright © 2016 by The American Society for Pharmacology and Experimental

  4. P-MartCancer–Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets

    Energy Technology Data Exchange (ETDEWEB)

    Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Jensen, Jeffrey L.; Kobold, Markus A.; Stratton, Kelly G.; White, Amanda M.; Rodland, Karin D.

    2017-10-31

    P-MartCancer is a new interactive web-based software environment that enables biomedical and biological scientists to perform in-depth analyses of global proteomics data without requiring direct interaction with the data or with statistical software. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access to multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium (CPTAC) at the peptide, gene and protein levels. P-MartCancer is deployed using Azure technologies (http://pmart.labworks.org/cptac.html), the web-service is alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/) and many statistical functions can be utilized directly from an R package available on GitHub (https://github.com/pmartR).

  5. 22 CFR 62.77 - Reinstatement.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Reinstatement. 62.77 Section 62.77 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Student and Exchange.... (4) The Department will review the request. If approved, the Department will enter the approval in...

  6. Cadmium biosorption properties of the metal-resistant ochrobactrum cytisi Azn6.2

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Llorente, Ignacio D.; Gamane, Djamila; Lafuente, Alejandro; Dary, Mohammed; El Hamdaoui, Abdelaziz; Delgadillo, Julian; Doukkali, Bouchra; Caviedes, Miguel A.; Pajuelo, Eloisa [Departamento de Microbiologia, Facultad de Farmacia, Universidad de Sevilla, Sevilla (Spain)

    2010-02-15

    The aim of this work was to establish the conditions for using Ochrobactrum cytisi Azn6.2 as a metal biosorbent. Azn6.2 is a novel strain from the legume symbiont O. cytisi that has been isolated from nodules of Medicago polymorpha plants grown on heavy metal-polluted soils. Compared with the strain ESC1, Azn6.2 showed some biochemical differences, as well as antibiotic susceptibility, Azn6.2 was multi-resistant to heavy metals, such as Cu, Cd and Zn, and bacterial pellets were able to biosorb high amounts of Cd and Zn. As shown by scanning electron microscopy coupled to energy dispersive X-ray, most of Cd was attached to the cell surface. Optimal conditions for Cd biosorption were established, being 1 mM Cd ions in solution and 2 h of contact with the biosorbent at room temperature. At these conditions, maximal Cd loading capacity reached 32-34 mg/g. Cd desorption from bacterial pellets was achieved after washing with EDTA or, at higher efficiency, at pH 1.0. These results indicated that biosorption/desorption on O. cytisi Azn6.2 biomass should be a cost-effective method for Cd recovery from contaminated solutions. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  7. 48 CFR 9904.403-62 - Exemption. [Reserved

    Science.gov (United States)

    2010-10-01

    ....403-62 Section 9904.403-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.403-62 Exemption. [Reserved] ...

  8. A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2

    Science.gov (United States)

    Breitkopf, Susanne B.; Yang, Xuemei; Begley, Michael J.; Kulkarni, Meghana; Chiu, Yu-Hsin; Turke, Alexa B.; Lauriol, Jessica; Yuan, Min; Qi, Jie; Engelman, Jeffrey A.; Hong, Pengyu; Kontaridis, Maria I.; Cantley, Lewis C.; Perrimon, Norbert; Asara, John M.

    2016-02-01

    Using a series of immunoprecipitation (IP) - tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway.

  9. Disruption of focal adhesion kinase and p53 interaction with small molecule compound R2 reactivated p53 and blocked tumor growth

    International Nuclear Information System (INIS)

    Golubovskaya, Vita M; Ho, Baotran; Zheng, Min; Magis, Andrew; Ostrov, David; Morrison, Carl; Cance, William G

    2013-01-01

    Focal Adhesion Kinase (FAK) is a 125 kDa non-receptor kinase that plays a major role in cancer cell survival and metastasis. We performed computer modeling of the p53 peptide containing the site of interaction with FAK, predicted the peptide structure and docked it into the three-dimensional structure of the N-terminal domain of FAK involved in the complex with p53. We screened small molecule compounds that targeted the site of the FAK-p53 interaction and identified compounds (called Roslins, or R compounds) docked in silico to this site. By different assays in isogenic HCT116p53 + / + and HCT116 p53 - / - cells we identified a small molecule compound called Roslin 2 (R2) that bound FAK, disrupted the binding of FAK and p53 and decreased cancer cell viability and clonogenicity in a p53-dependent manner. In addition, dual-luciferase assays demonstrated that the R2 compound increased p53 transcriptional activity that was inhibited by FAK using p21, Mdm-2, and Bax-promoter targets. R2 also caused increased expression of p53 targets: p21, Mdm-2 and Bax proteins. Furthermore, R2 significantly decreased tumor growth, disrupted the complex of FAK and p53, and up-regulated p21 in HCT116 p53 + / + but not in HCT116 p53 - / - xenografts in vivo. In addition, R2 sensitized HCT116p53 + / + cells to doxorubicin and 5-fluorouracil. Thus, disruption of the FAK and p53 interaction with a novel small molecule reactivated p53 in cancer cells in vitro and in vivo and can be effectively used for development of FAK-p53 targeted cancer therapy approaches

  10. The K0/π- ratio and strangeness suppression in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Kennedy, O.W.; O'Neale, S.W.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Towers, S.; Shotton, P.

    1984-10-01

    Neutral kaon to negative pion production ratios from νp and anti νp charged current interactions in BEBC are presented and compared with LUND fragmentation model predictions. Good agreement is obtained with a strangeness suppression factor lambda = 0.203 +- 0.014(stat) +- 0.010(sys). No evidence is seen for an energy dependence of lambda in our kinematic region. (orig.)

  11. The K0/π- ratio and strangeness suppression in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Kennedy, O.W.; O'Neale, S.W.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Towers, S.; Shotton, P.

    1985-01-01

    Neutral kaon to negative pion production ratios from νp and anti νp charged current interactions in BEBC are presented and compared with LUND fragmentation model predictions. Good agreement is obtained with a strangeness suppression factor lambda=0.203+-0.014(stat)+-0.010(sys). No evidence is seen for an energy dependence of lambda in our kinematic region. (orig.)

  12. Footprinting analysis of interactions between the largest eukaryotic RNase P/MRP protein Pop1 and RNase P/MRP RNA components.

    Science.gov (United States)

    Fagerlund, Robert D; Perederina, Anna; Berezin, Igor; Krasilnikov, Andrey S

    2015-09-01

    Ribonuclease (RNase) P and RNase MRP are closely related catalytic ribonucleoproteins involved in the metabolism of a wide range of RNA molecules, including tRNA, rRNA, and some mRNAs. The catalytic RNA component of eukaryotic RNase P retains the core elements of the bacterial RNase P ribozyme; however, the peripheral RNA elements responsible for the stabilization of the global architecture are largely absent in the eukaryotic enzyme. At the same time, the protein makeup of eukaryotic RNase P is considerably more complex than that of the bacterial RNase P. RNase MRP, an essential and ubiquitous eukaryotic enzyme, has a structural organization resembling that of eukaryotic RNase P, and the two enzymes share most of their protein components. Here, we present the results of the analysis of interactions between the largest protein component of yeast RNases P/MRP, Pop1, and the RNA moieties of the enzymes, discuss structural implications of the results, and suggest that Pop1 plays the role of a scaffold for the stabilization of the global architecture of eukaryotic RNase P RNA, substituting for the network of RNA-RNA tertiary interactions that maintain the global RNA structure in bacterial RNase P. © 2015 Fagerlund et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  13. Nanoparticle Nucleation Is Termolecular in Metal and Involves Hydrogen: Evidence for a Kinetically Effective Nucleus of Three {Ir3H2x·P2W15Nb3O62}6- in Ir(0)n Nanoparticle Formation From [(1,5-COD)IrI·P2W15Nb3O62]8- Plus Dihydrogen.

    Science.gov (United States)

    Özkar, Saim; Finke, Richard G

    2017-04-19

    The nucleation process yielding Ir(0) ∼300 nanoparticles from (Bu 4 N) 5 Na 3 [(1,5-COD)Ir·P 2 W 15 Nb 3 O 62 ] (abbreviated hereafter as (COD)Ir·POM 8- , where POM 9- = the polyoxometalate, P 2 W 15 Nb 3 O 62 9- ) under H 2 is investigated to learn the true molecularity, and hence the associated kinetically effective nucleus (KEN), for nanoparticle formation for the first time. Recent work with this prototype transition-metal nanoparticle formation system ( J. Am. Chem. Soc. 2014 , 136 , 17601 - 17615 ) revealed that nucleation in this system is an apparent second-order in the precatalyst, A = (COD)Ir·POM 8- , not the higher order implied by classic nucleation theory and its nA ⇌ A n , "critical nucleus", A n concept. Herein, the three most reasonable more intimate mechanisms of nucleation are tested: bimolecular nucleation, termolecular nucleation, and a mechanism termed "alternative termolecular nucleation" in which 2(COD)Ir + and 1(COD)Ir·POM 8- yield the transition state of the rate-determining step of nucleation. The results obtained definitively rule out a simple bimolecular nucleation mechanism and provide evidence for the alternative termolecular mechanism with a KEN of 3, Ir 3 . All higher molecularity nucleation mechanisms were also ruled out. Further insights into the KEN and its more detailed composition involving hydrogen, {Ir 3 H 2x POM} 6- , are also obtained from the established role of H 2 in the Ir(0) ∼300 formation balanced reaction stoichiometry, from the p(H 2 ) dependence of the kinetics, and from a D 2 /H 2 kinetic isotope effect of 1.2(±0.3). Eight insights and conclusions are presented. A section covering caveats in the current work, and thus needed future studies, is also included.

  14. Unraveling Prion Protein Interactions with Aptamers and Other PrP-Binding Nucleic Acids.

    Science.gov (United States)

    Macedo, Bruno; Cordeiro, Yraima

    2017-05-17

    Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative disorders that affect humans and other mammals. The etiologic agents common to these diseases are misfolded conformations of the prion protein (PrP). The molecular mechanisms that trigger the structural conversion of the normal cellular PrP (PrP C ) into the pathogenic conformer (PrP Sc ) are still poorly understood. It is proposed that a molecular cofactor would act as a catalyst, lowering the activation energy of the conversion process, therefore favoring the transition of PrP C to PrP Sc . Several in vitro studies have described physical interactions between PrP and different classes of molecules, which might play a role in either PrP physiology or pathology. Among these molecules, nucleic acids (NAs) are highlighted as potential PrP molecular partners. In this context, the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology has proven extremely valuable to investigate PrP-NA interactions, due to its ability to select small nucleic acids, also termed aptamers, that bind PrP with high affinity and specificity. Aptamers are single-stranded DNA or RNA oligonucleotides that can be folded into a wide range of structures (from harpins to G-quadruplexes). They are selected from a nucleic acid pool containing a large number (10 14 -10 16 ) of random sequences of the same size (~20-100 bases). Aptamers stand out because of their potential ability to bind with different affinities to distinct conformations of the same protein target. Therefore, the identification of high-affinity and selective PrP ligands may aid the development of new therapies and diagnostic tools for TSEs. This review will focus on the selection of aptamers targeted against either full-length or truncated forms of PrP, discussing the implications that result from interactions of PrP with NAs, and their potential advances in the studies of prions. We will also provide a critical evaluation

  15. Interactive Influence of N and P on their uptake by four different ...

    African Journals Online (AJOL)

    The uptake kinetics of nitrogen (N) and phosphorus (P) by hydrophytes can be influenced by the interaction between N and P. In this study, Pistia stratiotes (a floating plant), Eichhornia crassipes (a floating plant), Vallisneria spiralis (a submerged plant), and Cyperus papyrus (an emergent plant) were selected to measure ...

  16. A loss-of-function mutation in the nucleoporin AtNUP160 indicates that normal auxin signalling is required for a proper ethylene response in Arabidopsis

    Science.gov (United States)

    Robles, Linda M.; Deslauriers, Stephen D.; Alvarez, Ashley A.; Larsen, Paul B.

    2012-01-01

    As part of a continuing effort to elucidate mechanisms that regulate the magnitude of ethylene signalling, an Arabidopsis mutant with an enhanced ethylene response was identified. Subsequent characterization of this loss-of-function mutant revealed severe hypocotyl shortening in the presence of saturating ethylene along with increased expression in leaves of a subset of ethylene-responsive genes. It was subsequently determined by map-based cloning that the mutant (sar1-7) represents a loss-of-function mutation in the previously described nucleoporin AtNUP160 (At1g33410, SAR1). In support of previously reported results, the sar1-7 mutant partially restored auxin responsiveness to roots of an rce1 loss-of-function mutant, indicating that AtNUP160/SAR1 is required for proper expression of factors responsible for the repression of auxin signalling. Analysis of arf7-1/sar1-7 and arf19-1/sar1-7 double mutants revealed that mutations affecting either ARF7 or ARF19 function almost fully blocked manifestation of the sar1-7-dependent ethylene hypersensitivity phenotype, suggesting that ARF7- and ARF19-mediated auxin signalling is responsible for regulating the magnitude of and/or competence for the ethylene response in Arabidopsis etiolated hypocotyls. Consistent with this, addition of auxin to ethylene-treated seedlings resulted in severe hypocotyl shortening, reminiscent of that seen for other eer (enhanced ethylene response) mutants, suggesting that auxin functions in part synergistically with ethylene to control hypocotyl elongation and other ethylene-dependent phenomena. PMID:22238449

  17. Structural effects and competition mechanisms targeting the interactions between p53 and MDM2 for cancer therapy

    Science.gov (United States)

    Liu, Shu-Xia; Geng, Yi-Zhao; Yan, Shi-Wei

    2017-06-01

    Approximately half of all human cancers show normal TP53 gene expression but aberrant overexpression of MDM2 and/or MDMX. This fact suggests a promising cancer therapeutic strategy in targeting the interactions between p53 and MDM2/MDMX. To help realize the goal of developing effective inhibitors to disrupt the p53-MDM2/MDMX interaction, we systematically investigated the structural and interaction characteristics of p53 with inhibitors of its interactions with MDM2 and MDMX from an atomistic perspective using stochastic molecular dynamics simulations. We found that some specific α helices in the structures of MDM2 and MDMX play key roles in their binding to inhibitors, and that the hydrogen bond formed by the Trp23 residue of p53 with its counterpart in MDM2 or MDMX determines the dynamic competition processes of the disruption of the MDM2-p53 interaction and replacement of p53 from the MDM2-p53 complex in vivo. The results reported in this paper are expected to provide basic information for designing functional inhibitors and realizing new strategies of cancer gene therapy.

  18. Microstates of D1–D5(-P) black holes, as interacting D-branes

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Takeshi, E-mail: morita.takeshi@shizuoka.ac.jp [Department of Physics, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan); Shiba, Shotaro, E-mail: sshiba@cc.kyoto-su.ac.jp [Maskawa Institute for Science and Culture, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan)

    2015-07-30

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P) black holes in superstring theory.

  19. Microstates of D1–D5(-P black holes, as interacting D-branes

    Directory of Open Access Journals (Sweden)

    Takeshi Morita

    2015-07-01

    Full Text Available In our previous study (Morita et al., 2014 [1], we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal. We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves. It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P black holes in superstring theory.

  20. Microstates of D1–D5(-P) black holes, as interacting D-branes

    International Nuclear Information System (INIS)

    Morita, Takeshi; Shiba, Shotaro

    2015-01-01

    In our previous study (Morita et al., 2014 [1]), we figured out that the thermodynamics of the near extremal black p-branes can be explained as the collective motions of gravitationally interacting elementary p-branes (the p-soup proposal). We test this proposal in the near-extremal D1–D5 and D1–D5-P black holes and show that their thermodynamics also can be explained in a similar fashion, i.e. via the collective motions of the interacting elementary D1-branes and D5-branes (and waves). It may imply that the microscopic origins of these intersecting black branes and the black p-brane are explained in the unified picture. We also argue the relation between the p-soup proposal and the conformal field theory calculations of the D1–D5(-P) black holes in superstring theory

  1. 7 CFR 62.205 - Conflict of interest.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Conflict of interest. 62.205 Section 62.205 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... Definitions Service § 62.205 Conflict of interest. No USDA official shall review any program documentation or...

  2. Inclusive production of π0 mesons in π+p-,K+p- and pp interactions at 250 GeV/c

    International Nuclear Information System (INIS)

    Adamus, M.A.; Azhinenko, I.V.

    1986-01-01

    Data on inclusive π 0 production in the forward hemisphere at Feynman variable (x > 0.025) in the center-of-inertia system in π + p, K + p, and pp interactions at 250 GeV/c are presented. These data are compared to the data at lower energies and interpreted in terms of quark-parton models

  3. Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

    International Nuclear Information System (INIS)

    Zhang, Hai-chang; Zhang, Fei; Wu, Bing; Han, Jing-hua; Ji, Wei; Zhou, Yan; Niu, Rui-fang

    2012-01-01

    To explore the interaction of Anxa2 with P-Glycoprotein (P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. A pair of short hairpin RNA (shRNA) targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells (P<0.05). There was a close interaction between Anxa2 and P-gp. MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in the enhanced invasiveness of MDR human breast cancer cells

  4. 46 CFR 62.35-15 - Fire safety.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Fire safety. 62.35-15 Section 62.35-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING VITAL SYSTEM AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-15 Fire safety. (a) All required fire pump...

  5. 46 CFR 62.35-10 - Flooding safety.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Flooding safety. 62.35-10 Section 62.35-10 Shipping... Requirements for Specific Types of Automated Vital Systems § 62.35-10 Flooding safety. (a) Automatic bilge.... (b) Remote controls for flooding safety equipment must remain functional under flooding conditions to...

  6. 46 CFR 503.62 - Accounting of disclosures.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Accounting of disclosures. 503.62 Section 503.62... Record of Identifiable Personal Information § 503.62 Accounting of disclosures. (a) The Secretary shall make an accounting of each disclosure of any record contained in a system of records in accordance with...

  7. 46 CFR 62.35-40 - Fuel systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Fuel systems. 62.35-40 Section 62.35-40 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING VITAL SYSTEM AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-40 Fuel systems. (a) Level alarms. Where...

  8. Configuration interaction calculations of positron binding to Be({sup 3}P )

    Energy Technology Data Exchange (ETDEWEB)

    Bromley, M.W.J. [Department of Physics, San Diego State University, San Diego, CA 92182 (United States)]. E-mail: mbromley@physics.sdsu.edu; Mitroy, J. [Faculty of Technology, Charles Darwin University, Darwin, NT 0909 (Australia)]. E-mail: jxm107@rsphysse.anu.edu.au

    2006-06-15

    The configuration interaction method is applied to investigate the possibility of positron binding to the metastable beryllium (1s{sup 2}2s2p {sup 3}P ) state. The largest calculation obtained an estimated energy that was unstable by 0.00014 Hartree with respect to the Ps + Be{sup +}(2s) lowest dissociation channel. It is likely that positron binding to parent states with non-zero angular momentum is inhibited by centrifugal barriers.

  9. Testing T-odd, p-even interactions with gamma-rays from neutron p-wave resonances

    International Nuclear Information System (INIS)

    Barabanov, A.L.

    1992-01-01

    A new method for the study of time reversal violation is described. It consists of measurements of the forward-backward asymmetry in individual gamma-ray transitions resulting from unpolarized neutron capture in p-wave resonance. An experiment with a 113 Cd target performed at the Dubna pulsed neutron source has been analyzed and a limit on the time reversal odd, parity even interaction extracted. The possibilities of experiments using the powerful pulsed neutron source at Los Alamos are considered. 23 refs.; 2 figs

  10. 22 CFR 62.32 - Summer work travel.

    Science.gov (United States)

    2010-04-01

    ...-secondary students the opportunity to work and travel in the United States for a four month period during... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Summer work travel. 62.32 Section 62.32 Foreign... Provisions § 62.32 Summer work travel. (a) Introduction. These regulations govern program participation in...

  11. 30 CFR 62.130 - Permissible exposure level.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible exposure level. 62.130 Section 62... REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.130 Permissible exposure level. (a) The mine operator must assure that no miner is exposed during any work shift to noise that exceeds the permissible exposure level. If...

  12. Synthesis and characterization of macromolecular rhodamine tethers and their interactions with P-glycoprotein.

    Science.gov (United States)

    Crawford, Lindsey; Putnam, David

    2014-08-20

    Rhodamine dyes are well-known P-glycoprotein (P-gp) substrates that have played an important role in the detection of inhibitors and other substrates of P-gp, as well as in the understanding of P-gp function. Macromolecular conjugates of rhodamines could prove useful as tethers for further probing of P-gp structure and function. Two macromolecular derivatives of rhodamine, methoxypolyethylene glycol-rhodamine6G and methoxypolyethylene glycol-rhodamine123, were synthesized through the 2'-position of rhodamine6G and rhodamine123, thoroughly characterized, and then evaluated by inhibition with verapamil for their ability to interact with P-gp and to act as efflux substrates. To put the results into context, the P-gp interactions of the new conjugates were compared to the commercially available methoxypolyethylene glycol-rhodamineB. FACS analysis confirmed that macromolecular tethers of rhodamine6G, rhodamine123, and rhodamineB were accumulated in P-gp expressing cells 5.2 ± 0.3%, 26.2 ± 4%, and 64.2 ± 6%, respectively, compared to a sensitive cell line that does not overexpress P-gp. Along with confocal imaging, the efflux analysis confirmed that the macromolecular rhodamine tethers remain P-gp substrates. These results open potential avenues for new ways to probe the function of P-gp both in vitro and in vivo.

  13. Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex.

    Science.gov (United States)

    Wu, Rentian; Wang, Jiafeng; Liang, Chun

    2012-01-01

    Regulation of DNA replication initiation is essential for the faithful inheritance of genetic information. Replication initiation is a multi-step process involving many factors including ORC, Cdt1p, Mcm2-7p and other proteins that bind to replication origins to form a pre-replicative complex (pre-RC). As a prerequisite for pre-RC assembly, Cdt1p and the Mcm2-7p heterohexameric complex accumulate in the nucleus in G1 phase in an interdependent manner in budding yeast. However, the nature of this interdependence is not clear, nor is it known whether Cdt1p is required for the assembly of the MCM complex. In this study, we provide the first evidence that Cdt1p, through its interaction with Mcm6p with the C-terminal regions of the two proteins, is crucial for the formation of the MCM complex in both the cytoplasm and nucleoplasm. We demonstrate that disruption of the interaction between Cdt1p and Mcm6p prevents the formation of the MCM complex, excludes Mcm2-7p from the nucleus, and inhibits pre-RC assembly and DNA replication. Our findings suggest a function for Cdt1p in promoting the assembly of the MCM complex and maintaining its integrity by interacting with Mcm6p.

  14. Study of $pp$ and $p\\bar{p}$ Collisions at the SFM Facility of the CERN ISR

    CERN Multimedia

    2002-01-01

    In an analysis of ``minimum bias'' data taken in experiment R415 it was shown that if this data is analysed in terms of a new energy variable E^h^a^d, obtained by correcting the ISR c.m. energy for the energy carried away by the leading protons, then there is a remarkable similarity between (pp) and (e|+e|-) interactions. The range of (e|+e|-) equivalent energies over which the data could be analysed was limited by the total c.m. energy of the colliding protons (@Rs=62~GeV). \\\\ \\\\ This experiment at the Split Field Magnet uses a momentum-selective trigger logic to collect an enriched sample of events with identified leading protons or antiprotons, covering an extended range of equivalent (e|+e|-) energies by collecting data at different~@Rs.\\\\ \\\\ A first run with proton-proton at three different @Rs (30, 44 and 62~GeV) was already performed. \\\\ \\\\ The hypothesis that the energy released by the leading protons, and not @Rs, is the important quantity when studying low p^t multiparticle production in (pp) collis...

  15. Modulating Transmembrane α-Helix Interactions through pH-Sensitive Boundary Residues.

    Science.gov (United States)

    Ng, Derek P; Deber, Charles M

    2016-08-09

    Changes in pH can alter the structure and activity of proteins and may be used by the cell to control molecular function. This coupling can also be used in non-native applications through the design of pH-sensitive biomolecules. For example, the pH (low) insertion peptide (pHLIP) can spontaneously insert into a lipid bilayer when the pH decreases. We have previously shown that the α-helicity and helix-helix interactions of the TM2 α-helix of the proteolipid protein (PLP) are sensitive to the local hydrophobicity at its C-terminus. Given that there is an ionizable residue (Glu-88) at the C-terminus of this transmembrane (TM) segment, we hypothesized that changing the ionization state of this residue through pH may alter the local hydrophobicity of the peptide enough to affect both its secondary structure and helix-helix interactions. To examine this phenomenon, we synthesized peptide analogues of the PLP TM2 α-helix (wild-type sequence (66)AFQYVIYGTASFFFLYGALLLAEGF(90)). Using circular dichroism and Förster resonance energy transfer in the membrane-mimetic detergent sodium dodecyl sulfate, we found that a decrease in pH increases both peptide α-helicity and the extent of self-association. This pH-dependent effect is due specifically to the presence of Glu-88 at the C-terminus. Additional experiments in which Phe-90 was mutated to residues of varying hydrophobicities indicated that the strength of this effect is dependent on the local hydrophobicity near Glu-88. Our results have implications for the design of TM peptide switches and improve our understanding of how membrane protein structure and activity can be regulated through local molecular environmental changes.

  16. 48 CFR 9904.402-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.402-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.402-62 Exemption. None for this Standard. ...

  17. 48 CFR 9904.407-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.407-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.407-62 Exemption. None for this Standard. ...

  18. 48 CFR 9904.404-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.404-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.404-62 Exemption. None for this Standard. ...

  19. 48 CFR 9904.406-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.406-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.406-62 Exemption. None for this Standard. ...

  20. 48 CFR 9904.401-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.401-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.401-62 Exemption. None for this Standard. ...

  1. 48 CFR 9904.405-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.405-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.405-62 Exemption. None for this Standard. ...

  2. Citrus CitNAC62 cooperates with CitWRKY1 to participate in citric acid degradation via up-regulation of CitAco3.

    Science.gov (United States)

    Li, Shao-Jia; Yin, Xue-Ren; Wang, Wen-Li; Liu, Xiao-Fen; Zhang, Bo; Chen, Kun-Song

    2017-06-15

    Citric acid is the predominant organic acid of citrus fruit. Degradation of citric acid occurs during fruit development, influencing fruit acidity. Associations of CitAco3 transcripts and citric acid degradation have been reported for citrus fruit. Here, transient overexpression of CitAco3 significantly reduced the citric acid content of citrus leaves and fruits. Using dual luciferase assays, it was shown that CitNAC62 and CitWRKY1 could transactivate the promoter of CitAco3. Subcellular localization results showed that CitWRKY1 was located in the nucleus and CitNAC62 was not. Yeast two-hybrid analysis and bimolecular fluorescence complementation (BiFC) assays indicated that the two differently located transcription factors could interact with each other. Furthermore, BiFC showed that the protein-protein interaction occurred only in the nucleus, indicating the potential mobility of CitNAC62 in plant cells. A synergistic effect on citrate content was observed between CitNAC62 and CitWRKY1. Transient overexpression of CitNAC62 or CitWRKY1 led to significantly lower citrate content in citrus fruit. The combined expression of CitNAC62 and CitWRKY1 resulted in lower citrate content compared with the expression of CitNAC62 or CitWRKY1 alone. The transcript abundance of CitAco3 was consistent with the citrate content. Thus, we propose that a complex of CitWRKY1 and CitNAC62 contributes to citric acid degradation in citrus fruit, potentially via modulation of CitAco3. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  3. Calumenin interacts with serum amyloid P component

    DEFF Research Database (Denmark)

    Vorum, H; Jacobsen, Christian; Honoré, Bent

    2000-01-01

    We recently reported the identification of human calumenin, a novel Ca(2+) binding, transformation-sensitive and secreted protein [Vorum et al. (1998) Biochim. Biophys. Acta 1386, 121-131; Vorum et al. (1999) Exp. Cell Res. 248, 473-481] belonging to the family of multiple EF-hand proteins...... with calumenin in the presence of Ca(2+). Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin-SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate...... in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues. Udgivelsesdato: 2000-Jan-14...

  4. Beam-beam interactions in p-p storage rings

    CERN Document Server

    Keil, Eberhard

    1977-01-01

    There are two lectures. The first one (sections 2 to 5) deals with the theoretical aspects of the beam-beam interaction, and the second one (sections 6 to 8) describes the results of experiments in the ISR. Section 3 describes the strength of the beam-beam interaction in terms of the linear tune shift Delta Q which has been calculated for several models. Because of the non-uniform density distribution in the beam the force results in a tune spread. This can be calculated by a perturbation method as explained in section 4. Section 5 discusses the simulation of the beam-beam interaction on a computer. Finally, section 6 reviews beam-beam phenomena observed in the CERN-ISR. These include the absence of observable beam-beam effects in unbunched beams, overlap knock-out resonances, collisions between a low-energy beam and a high-intensity stack, experiments with a nonlinear lens, and experiments with a high- beta insertion. (20 refs).

  5. 7 CFR 1216.62 - Confidential treatment.

    Science.gov (United States)

    2010-01-01

    ... this subpart or statistical data collected therefrom, which statements do not identify the information... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1216.62 Section 1216.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING...

  6. 7 CFR 1209.62 - Confidential treatment.

    Science.gov (United States)

    2010-01-01

    ... this subpart or statistical data collected therefrom, which statements do not identify the information... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1209.62 Section 1209.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING...

  7. 28 CFR 540.62 - Institutional visits.

    Science.gov (United States)

    2010-07-01

    ....62 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Contact With News Media § 540.62 Institutional visits. (a) A media representative shall make advance appointments for visits. (b) When media representatives visit the institutions...

  8. 48 CFR 9904.409-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.409-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.409-62 Exemption. This Standard shall not apply where compensation...

  9. 48 CFR 9904.408-62 - Exemption.

    Science.gov (United States)

    2010-10-01

    ... Section 9904.408-62 Federal Acquisition Regulations System COST ACCOUNTING STANDARDS BOARD, OFFICE OF FEDERAL PROCUREMENT POLICY, OFFICE OF MANAGEMENT AND BUDGET PROCUREMENT PRACTICES AND COST ACCOUNTING STANDARDS COST ACCOUNTING STANDARDS 9904.408-62 Exemption. This Standard shall not apply to contracts and...

  10. 19 CFR 10.62 - Bunker fuel oil.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Bunker fuel oil. 10.62 Section 10.62 Customs... Equipment for Vessels § 10.62 Bunker fuel oil. (a) Withdrawal under section 309, Tariff Act of 1930, as... section 309, Tariff Act of 1930, as amended (19 U.S.C. 1309), when all the bunker fuel oil in a Customs...

  11. CD62L (L-selectin) shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.

    Science.gov (United States)

    Erdoes, Gabor; Balmer, Maria L; Slack, Emma; Kocsis, Istvan; Lehmann, Lutz E; Eberle, Balthasar; Stüber, Frank; Book, Malte

    2013-01-01

    To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass. Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation. 25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p<0.001), plasma sCD62L (p ≤ 0.001). In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401). Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF

  12. CD62L (L-selectin shedding for assessment of perioperative immune sensitivity in patients undergoing cardiac surgery with cardiopulmonary bypass.

    Directory of Open Access Journals (Sweden)

    Gabor Erdoes

    Full Text Available To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA and tumor necrosis factor alpha (TNF--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA-DR, and plasma interleukin (IL-8, soluble (sCD62L, soluble (sToll-like receptor (TLR-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively. In contrast, granulocytes (p = 0.01, but not monocytes (p = 0.057 displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001 and sTLR (p = 0.004, and decreases in monocyte HLA-DR (p<0.001, plasma sCD62L (p ≤ 0.001. In contrast, ADAM17 plasma levels did not show significant differences over the observation period (p = 0.401.Monitoring granulocyte and monocyte sensitivity using the "CD62L shedding assay" in the perioperative period in cardiac surgical patients treated with the use of cardiopulmonary bypass reveals common changes in sensitivity to TLR2/6 ligands and to TNF

  13. Use of the Counseling Center Assessment of Psychological Symptoms 62 (CCAPS-62) as a Repeated Measure

    Science.gov (United States)

    Ghosh, Arpita; Rieder Bennett, Sara; Martin, Juanita K.

    2018-01-01

    The purpose of this initial, exploratory study was to examine the utility of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62) as a repeated measure tool at one university counseling center. This study investigated whether clients engaged in individual counseling changed in symptomology while in treatment and when (e.g.,…

  14. Pulse radiolysis studies of intramolecular electron transfer in model peptides and proteins. 7. Trp -> TyrO radical transformation in hen egg-white lysozyme. Effects of pH, temperature, Trp62 oxidation and inhibitor binding

    DEFF Research Database (Denmark)

    Bobrowski, K.; Holcman, J.; Poznanski, J.

    1997-01-01

    Intramolecular long-range electron transfer (LRET) in hen egg-white lysozyme (HEWL) accompanying Trp --> TyrO radical transformation was investigated in aqueous solution by pulse radiolysis as a function of pH (5.2-7.4) and temperature (283-328K). The reaction was induced by highly selective...... below its denaturation temperature. Selective oxidation by ozone of the Trp62 indole side-chain in HEWL to N'-formylkynurenine (NFKyn62-HEWL) caused a large drop in the initial yield of Trp(.) radicals, G(Trp(.))(i). This was accompanied by a relatively small decrease in k(5) but selective oxidation...

  15. 7 CFR 1218.62 - Confidential treatment.

    Science.gov (United States)

    2010-01-01

    ... of the number of persons subject to this subpart or statistical data collected therefrom, which... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1218.62 Section 1218.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING...

  16. 7 CFR 1215.62 - Confidential treatment.

    Science.gov (United States)

    2010-01-01

    ... persons subject to this part or statistical data collected therefrom, which statements do not identify the... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1215.62 Section 1215.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING...

  17. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase

    International Nuclear Information System (INIS)

    Warner, Dennis R.; Bhattacherjee, Vasker; Yin, Xiaolong; Singh, Saurabh; Mukhopadhyay, Partha; Pisano, M. Michele; Greene, Robert M.

    2004-01-01

    The transforming growth factors β control a diversity of biological processes including cellular proliferation, differentiation, apoptosis, and extracellular matrix production, and are critical effectors of embryonic patterning and development, including that of the orofacial region. TGFβ superfamily members signal through specific cell surface receptors that phosphorylate the cytoplasmic Smad proteins, resulting in their translocation to the nucleus and interaction with promoters of TGFβ-responsive genes. Subsequent alterations in transcription are cell type-specific and dependent on recruitment to the Smad/transcription factor complex of coactivators, such as CBP and p300, or corepressors, such as c-ski and SnoN. Since the affinity of Smads for DNA is generally low, additional accessory proteins that facilitate Smad/DNA binding are required, and are often cell- and tissue-specific. In order to identify novel Smad 3 binding proteins in developing orofacial tissue, a yeast two hybrid assay was employed in which the MH2 domain of Smad 3 was used to screen an expression library derived from mouse embryonic orofacial tissue. The RNA helicase, p68, was identified as a unique Smad binding protein, and the specificity of the interaction was confirmed through various in vitro and in vivo assays. Co-expression of Smad 3 and a CBP-Gal4 DNA binding domain fusion protein in a Gal4-luciferase reporter assay resulted in increased TGFβ-stimulated reporter gene transcription. Moreover, co-expression of p68 RNA helicase along with Smad 3 and CBP-Gal4 resulted in synergistic activation of Gal4-luciferase reporter expression. Collectively, these data indicate that the RNA helicase, p68, can directly interact with Smad 3 resulting in formation of a transcriptionally active ternary complex containing Smad 3, p68, and CBP. This offers a means of enhancing TGFβ-mediated cellular responses in developing orofacial tissue

  18. Sensitive detection of strong acidic condition by a novel rhodamine-based fluorescent pH chemosensor.

    Science.gov (United States)

    Tan, Jia-Lian; Yang, Ting-Ting; Liu, Yu; Zhang, Xue; Cheng, Shu-Jin; Zuo, Hua; He, Huawei

    2016-05-01

    A novel rhodamine-based fluorescent pH probe responding to extremely low pH values has been synthesized and characterized. This probe showed an excellent photophysical response to pH on the basis that the colorless spirocyclic structure under basic conditions opened to a colored and highly fluorescent form under extreme acidity. The quantitative relationship between fluorescence intensity and pH value (1.75-2.62) was consistent with the equilibrium equation pH = pKa + log[(Imax - I)/(I - Imin)]. This sensitive pH probe was also characterized with good reversibility and no interaction with interfering metal ions, and was successfully applied to image Escherichia coli under strong acidity. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Interaction of low pH cementitious concretes with groundwaters

    International Nuclear Information System (INIS)

    Garcia Calvo, Jose Luis; Alonso, Maria Cruz; Hidalgo, Ana; Fernandez Luco, Luis

    2012-01-01

    Some engineering construction concepts for high level radioactive waste underground repositories consider the use of a bentonite barrier in contact with cementitious materials with a pore fluid pH value inferior or equal to 11 (based on low-pH cements) to maintain the bentonite stability. The research on low-pH cementitious materials is mainly addressed from two different approaches, one with Calcium Silicate Cements (OPC, Ordinary Portland Cement based), the other with Calcium Aluminates Cements (CAC based). The use of these both types of cements (OPC based or CAC based) implies the use of high mineral additions contents in the binder that should significantly modify most of the concrete 'standard' properties. Taking into account the long life expected in this type of repositories, parameters related to the durability of the low-pH concretes must be analyzed. This work shows some recent studies that deal with the evaluation of the resistance of low-pH concretes to long term groundwater aggression. After a presentation of the accelerated leaching test (based on a percolation method), results are given for the characterization of the leaching solution evolution and the evaluation of the modifications generated in the solid phases. Results show that the low-pH concretes evaluated have good resistance against groundwater interaction, although an altered front can be observed from the surface in all the tested samples

  20. New results from the NA49 experiment on hadron production in p+p and p+C interactions and survey of backward hadrons in p+C collisions

    CERN Document Server

    Makariev, M

    2013-01-01

    Recent results on proton, anti-proton, neutron and charged kaon production in proton-proton and proton, anti-proton, neutron, deuteron and triton production in proton-carbon collisions at 158 GeV/c beam momentum are presented. Data samples of 4.8 million and 385 734 inelastic events in p+p and p+C, respectively, are obtained with the NA49 detector at the CERN SPS accelerator. The charged particles are identified by energy loss measurement in a system of four TPC chambers, while the neutrons are detected in a forward hadronic calorimeter. The data cover a major fraction of the phase space, ranging from 0 to 1.9 GeV in p_T and in Feynman x variable from -0.8 to 0.95 for protons, from -0.2 to 0.3 for anti-protons, from 0.1 to 0.95 for neutrons and from 0 to 0.5 for kaons. The comparison of the results on proton and neutron production in p+p interactions and deep inelastic e+p collisions at HERA reveals an independence of target fragmentation on the projectile type. Using the charged kaon data in p+p collisions a...

  1. Two-body hypercharge-exchange reactions in K-p and π+p interactions at 10 and 16 GeV/c

    International Nuclear Information System (INIS)

    Girtler, P.; Otter, G.; Sliwa, K.; Barnham, K.W.J.; Eason, R.M.; Newham, P.; Pollock, B.; Wells, J.; Mandl, F.; Markytan, M.

    1979-01-01

    Cross section values or upper limits are presented for twenty-five two-body hypercharge-exchange reactions in K - p and π + p interactions at 10 and 16 GeV/c. The 16 GeV/c results are compared with some predictions of line-reversal plus exchange-degenerate Regge poles, of SU(3) and of the additive quark model. Agreement is found in all cases. (author)

  2. Cu-62, Cu-64 and Cu-66 production with 4.2 MeV deuterons; Produccion de {sup 62} Cu y {sup 64} Cu con deuterones de 4,2 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Avila, Mario; Morales, J R; Riquelme, H O [Chile Univ., Santiago (Chile). Facultad de Ciencias. Dept. de Fisica

    1997-12-31

    Full text: The natural copper irradiation with deuterons produces the Cu-62, Cu-64 and Cu-66 radionuclides. Of two radioisotopes, those with deficiencies in neutrons, are applied in nuclear medicine diagnostic processes, mainly for the nuclear characteristic of the decay modes. The positron emitters, of short life mean Cu-62 (9.1 min, {beta}{sup +}) and Cu(12.7 h), are radionuclides applied in radio pharmacological preparation for brain, core, blood flux studies. The radiochemical process consists in the de solution of the irradiated metallic copper target, in acid medium. The result solution, can be neutralized with a base or a buffer at wished pH. Using a deuteron beam of 4,2 {+-} 0,1 MeV energy has been obtained total yields of 1,103 {+-} 0,011 {mu}Cl/{mu}Ah medium for 62 Cu and of 0,148 {+-} 0,015 {mu}Cl/{mu}Ah for 64 Cu.

  3. 22 CFR 62.3 - Sponsor eligibility.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Sponsor eligibility. 62.3 Section 62.3 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM General Provisions... visitor program are: (1) United States local, state and federal government agencies; (2) International...

  4. 7 CFR 1206.62 - Confidential treatment.

    Science.gov (United States)

    2010-01-01

    ... statements based upon the reports of the number of persons subject to this subpart or statistical data... 7 Agriculture 10 2010-01-01 2010-01-01 false Confidential treatment. 1206.62 Section 1206.62 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING...

  5. 36 CFR 62.9 - General provisions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false General provisions. 62.9 Section 62.9 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR... governments, or other interested individuals or groups to assist in administering the National Natural...

  6. Beam-beam interactions in p-p storage rings

    International Nuclear Information System (INIS)

    Keil, E.

    1977-01-01

    There are two lectures: the first part of this paper (sections 2 to 5) deals with the theoretical aspects of the beam-beam interaction, and the second part (sections 6 to 8) describe the results of experiments in the ISR. Section 3 describes the strengths of the beam-beam interaction in terms of the linear tune shift ΔQ which has been calculated for several models. Because of the non-uniform density distribution in the beam the force results in a tune spread. This can be calculated by a perturbation method as explained in section 4. Section 5 discusses the simulation of the beam-beam interaction on a computer. Finally, section 6 reviews beam-beam phenomena observed in the CERN-ISR. These include the absence of observable beam-beam effects in unbunched beams, overlap knock-out resonances, collisions between a low-energy beam and a high-intensity stack, experiments with a nonlinear lens, and experiments with a high-β insertion. Section 7 contains a few concluding remarks. (Auth.)

  7. The binary response of the GAL/MEL genetic switch of Saccharomyces cerevisiae is critically dependent on Gal80p-Gal4p interaction.

    Science.gov (United States)

    Das Adhikari, Akshay Kumar; Bhat, Paike Jayadeva

    2016-09-01

    Studies on the Saccharomyces cerevisiae GAL/MEL genetic switch have revealed that its bistability is dependent on ultrasensitivity that can be altered or abolished by disabling different combinations of nested feedback loops. In contrast, we have previously demonstrated that weakening of the interaction between Gal80p and Gal4p alone is sufficient to abolish the ultrasensitivity (Das Adhikari et al. 2014). Here, we demonstrate that altering the epistatic interaction between Gal80p and Gal4p also abolishes the bistability, and the switch response to galactose becomes graded instead of binary. However, the GAL/MEL switch of wild-type and epistatically altered strains responded in a graded fashion to melibiose. The properties of the epistatically altered strain resemble Kluyveromyces lactis, which separated from the Saccharomyces lineage 100 mya before whole-genome duplication (WGD). Based on the results reported here, we propose that epistatic interactions played a crucial role in the evolution of the fine regulation of S. cerevisiae GAL/MEL switch following WGD. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Interaction between the Cockayne syndrome B and p53 proteins: implications for aging.

    Science.gov (United States)

    Frontini, Mattia; Proietti-De-Santis, Luca

    2012-02-01

    The CSB protein plays a role in the transcription coupled repair (TCR) branch of the nucleotide excision repair pathway. CSB is very often found mutated in Cockayne syndrome, a segmental progeroid genetic disease characterized by organ degeneration and growth failure. The tumor suppressor p53 plays a pivotal role in triggering senescence and apoptosis and suppressing tumorigenesis. Although p53 is very important to avoid cancer, its excessive activity can be detrimental for the lifespan of the organism. This is why a network of positive and negative feedback loops, which most likely evolved to fine-tune the activity of this tumor suppressor, modulate its induction and activation. Accordingly, an unbalanced p53 activity gives rise to premature aging or cancer. The physical interaction between CSB and p53 proteins has been known for more than a decade but, despite several hypotheses, nobody has been able to show the functional consequences of this interaction. In this review we resume recent advances towards a more comprehensive understanding of the critical role of this interaction in modulating p53’s levels and activity, therefore helping the system find a reasonable equilibrium between the beneficial and the detrimental effects of its activity. This crosstalk re-establishes the physiological balance towards cell proliferation and survival instead of towards cell death, after stressors of a broad nature. Accordingly, cells bearing mutations in the csb gene are unable to re-establish this physiological balance and to properly respond to some stress stimuli and undergo massive apoptosis.

  9. The Arabidopsis Nuclear Pore and Nuclear Envelope

    OpenAIRE

    Meier, Iris; Brkljacic, Jelena

    2010-01-01

    The nuclear envelope is a double membrane structure that separates the eukaryotic cytoplasm from the nucleoplasm. The nuclear pores embedded in the nuclear envelope are the sole gateways for macromolecular trafficking in and out of the nucleus. The nuclear pore complexes assembled at the nuclear pores are large protein conglomerates composed of multiple units of about 30 different nucleoporins. Proteins and RNAs traffic through the nuclear pore complexes, enabled by the interacting activities...

  10. Interaction of rocuronium with human liver cytochromes P450.

    Science.gov (United States)

    Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

    2015-02-01

    Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  11. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis.

    Science.gov (United States)

    Granito, Alessandro; Muratori, Paolo; Quarneti, Chiara; Pappas, Georgios; Cicola, Ronny; Muratori, Luigi

    2012-01-01

    Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.

  12. Obliquity Variations of Habitable Zone Planets Kepler-62f and Kepler-186f

    Science.gov (United States)

    Shan, Yutong; Li, Gongjie

    2018-06-01

    Obliquity variability could play an important role in the climate and habitability of a planet. Orbital modulations caused by planetary companions and the planet’s spin axis precession due to the torque from the host star may lead to resonant interactions and cause large-amplitude obliquity variability. Here we consider the spin axis dynamics of Kepler-62f and Kepler-186f, both of which reside in the habitable zone around their host stars. Using N-body simulations and secular numerical integrations, we describe their obliquity evolution for particular realizations of the planetary systems. We then use a generalized analytic framework to characterize regions in parameter space where the obliquity is variable with large amplitude. We find that the locations of variability are fine-tuned over the planetary properties and system architecture in the lower-obliquity regimes (≲40°). As an example, assuming a rotation period of 24 hr, the obliquities of both Kepler-62f and Kepler-186f are stable below ∼40°, whereas the high-obliquity regions (60°–90°) allow moderate variabilities. However, for some other rotation periods of Kepler-62f or Kepler-186f, the lower-obliquity regions could become more variable owing to resonant interactions. Even small deviations from coplanarity (e.g., mutual inclinations ∼3°) could stir peak-to-peak obliquity variations up to ∼20°. Undetected planetary companions and/or the existence of a satellite could also destabilize the low-obliquity regions. In all cases, the high-obliquity region allows for moderate variations, and all obliquities corresponding to retrograde motion (i.e., >90°) are stable.

  13. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi

    DEFF Research Database (Denmark)

    Goddard, Amelia; Leisewitz, Andrew L; Kristensen, Annemarie Thuri

    2015-01-01

    EDTA as anticoagulant. Activated platelets and PLA formation were detected by measuring surface expression of P-selectin (CD62P) on platelets, monocytes and neutrophils. Of the Babesia-infected dogs, 29 survived and seven died. The percentage of CD62P-positive monocytes was significantly higher (P = 0.......036) in the Babesia-infected dogs (54%) than in healthy control dogs (35.3%). However, there were no significant differences between the Babesia-infected and control groups for CD62P-positive platelets (4.9% and 1.2%, respectively) and CD62P-positive neutrophils (28.3% and 17.9%, respectively). The percentage of CD62...... groups for the percentage of CD62P-positive platelets (survivors 4.8%; non-survivors 5.3%; controls 1.2%) or CD62P-positive neutrophils (survivors 31.6%; non-survivors 5.6%; controls 17.9%). In conclusion, Babesia-infected dogs, specifically dogs that survived, had a significantly increased percentage...

  14. 44 CFR 62.22 - Judicial review.

    Science.gov (United States)

    2010-10-01

    ... of process for all judicial proceedings where a claimant is suing the Administrator of FEMA pursuant... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Judicial review. 62.22... ADJUSTMENT OF CLAIMS Claims Adjustment, Claims Appeals, and Judicial Review § 62.22 Judicial review. (a) Upon...

  15. P-MartCancer-Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets.

    Science.gov (United States)

    Webb-Robertson, Bobbie-Jo M; Bramer, Lisa M; Jensen, Jeffrey L; Kobold, Markus A; Stratton, Kelly G; White, Amanda M; Rodland, Karin D

    2017-11-01

    P-MartCancer is an interactive web-based software environment that enables statistical analyses of peptide or protein data, quantitated from mass spectrometry-based global proteomics experiments, without requiring in-depth knowledge of statistical programming. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification, and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access and the capability to analyze multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium at the peptide, gene, and protein levels. P-MartCancer is deployed as a web service (https://pmart.labworks.org/cptac.html), alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/). Cancer Res; 77(21); e47-50. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. Refined study of the interaction between HIV-1 p6 late domain and ALIX

    Directory of Open Access Journals (Sweden)

    Gerlier Denis

    2008-05-01

    Full Text Available Abstract The interaction between the HIV-1 p6 late budding domain and ALIX, a class E vacuolar protein sorting factor, was explored by using the yeast two-hybrid approach. We refined the ALIX binding site of p6 as being the leucine triplet repeat sequence (Lxx4 (LYPLTSLRSLFG. Intriguingly, the deletion of the C-terminal proline-rich region of ALIX prevented detectable binding to p6. In contrast, a four-amino acid deletion in the central hinge region of p6 increased its association with ALIX as shown by its ability to bind to ALIX lacking the proline rich domain. Finally, by using a random screening approach, the minimal ALIX391–510 fragment was found to specifically interact with this p6 deletion mutant. A parallel analysis of ALIX binding to the late domain p9 from EIAV revealed that p6 and p9, which exhibit distinct ALIX binding motives, likely bind differently to ALIX. Altogether, our data support a model where the C-terminal proline-rich domain of ALIX allows the access of its binding site to p6 by alleviating a conformational constraint resulting from the presence of the central p6 hinge.

  17. Interaction between focal adhesion kinase and Crk-associated tyrosine kinase substrate p130Cas.

    Science.gov (United States)

    Polte, T R; Hanks, S K

    1995-11-07

    The focal adhesion kinase (FAK) has been implicated in integrin-mediated signaling events and in the mechanism of cell transformation by the v-Src and v-Crk oncoproteins. To gain further insight into FAK signaling pathways, we used a two-hybrid screen to identify proteins that interact with mouse FAK. The screen identified two proteins that interact with FAK via their Src homology 3 (SH3) domains: a v-Crk-associated tyrosine kinase substrate (Cas), p130Cas, and a still uncharacterized protein, FIPSH3-2, which contains an SH3 domain closely related to that of p130Cas. These SH3 domains bind to the same proline-rich region of FAK (APPKPSR) encompassing residues 711-717. The mouse p130Cas amino acid sequence was deduced from cDNA clones, revealing an overall high degree of similarity to the recently reported rat sequence. Coimmunoprecipitation experiments confirmed that p130Cas and FAK are associated in mouse fibroblasts. The stable interaction between p130Cas and FAK emerges as a likely key element in integrin-mediated signal transduction and further represents a direct molecular link between the v-Src and v-Crk oncoproteins. The Src family kinase Fyn, whose Src homology 2 (SH2) domain binds to the major FAK autophosphorylation site (tyrosine 397), was also identified in the two-hybrid screen.

  18. Insight into interaction mechanism of the inhibitor pDI5W with MDM2 based on molecular dynamics

    International Nuclear Information System (INIS)

    Chen Jianzhong; Liang Zhiqiang; Wang Wei; Liu Jinqing; Zhang Qinggang; Liu Xiaoyang

    2012-01-01

    The p53-MDM2 interaction has been an important target of drug design curing cancers. In this work, molecular dynamics (MD) simulation coupled with molecular mechanics/Poisson Boltzmann surface area method (MM-PBSA) was performed to calculate the binding free energy of peptide inhibitor pDI6W to MDM2. The results show that van der Waals energy is the dominant factor of the pDI6W— MDM2 interaction. Cross-correlation matrix calculated suggests that the main motion of the residues in MMDM2 induced by the inhibitor binding is anti-correlation motion. The calculations of residue-residue interactions between pDI6W and MDM2 not only prove that five residues Phe19', Trp22', Trp23', Leu26' and Thr27' from pDI6W can produce strong interaction with MDM2, but also show that CH-π, CH-CH and π-π interactions drive the binding of pDI6W in the hydrophobic cleft of MDM2. This study can provide theoretical helps for anti-cancer drug designs. (authors)

  19. The pH changes of artificial saliva after interaction with oral of artificial saliva after interaction with oral micropathogen

    Directory of Open Access Journals (Sweden)

    Basri A. Gani

    2012-12-01

    Full Text Available Backgorund: Saliva contains several protein elements, exocrine proteins and antibodies, such as lactoferrin, sIgA, peroxidase, albumin, polypeptides, and oligopeptides that contribute to the defense of oral mucosa and dental pellicle to prevent infection caused by oral micropathogen, such as Candida albicans, Streptococcus mutans and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans. Those micropathogens have a role to change salivary pH as an indicator of oral disease activities. Purpose: This study was aimed to analyze the changes of artificial saliva pH after interaction with S. mutans, C. albicans, and A. Actinomycetemcpmitans. Methods: The materials used in this study consist of S. mutans (ATCC 31987, C. albicans (ATCC 10231, A. actinomycetemcomitans (ATTC 702 358, and artificial saliva. To examine the pH changes of artificial saliva, those three microbiotas were cultured and incubated for 24 hours. Results: The results showed that the interactions of S. mutans, C. albicans, and A. actinomycetemcomitans in the artificial saliva can change the salivary on neutral. There were no significant difference with the control treatment salivary pH 4, 5, 6, 8, and 9 (p>0.05. Similarly, there was also no significant difference when those three microorganism interacted each other in the artificial saliva (p<0.05. Conclusion: It can be concluded that the biological activity of S. mutans, C. albicans, and A. actinomycetemcomitans in artificial saliva can change the salivary pH into neutral. It indicates that those microbiotas mutually supported and cooperated in influencing the biological cycle of the oral cavity with salivary pH as an indicator.Latar belakang: Saliva merupakan cairan eksokrin yang mengandung unsur protein dan antibodi seperti sIgA laktoferin peroksidase, albumin, polipeptida dan oligopeptida yang berperan pada pertahanan mukosa rongga mulut dan gigi guna mencegah infeksi oral mikropatogen seperti C. albicans, S. mutans, dan

  20. 16 CFR 5.62 - Hearing rights of respondent.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Hearing rights of respondent. 5.62 Section 5.62 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE STANDARDS OF CONDUCT Disciplinary Actions Concerning Postemployment Conflict of Interest § 5.62 Hearing...

  1. Interaction between 14-3-3β and PrP influences the dimerization of 14-3-3 and fibrillization of PrP106-126.

    Science.gov (United States)

    Han, Jun; Song, Qin-Qin; Sun, Peng; Zhang, Jin; Wang, Xu; Song, Juan; Li, Gong-Qi; Liu, Ying-Hui; Mei, Guo-Yong; Shi, Qi; Tian, Chan; Chen, Cao; Gao, Chen; Zhao, Bo; Dong, Xiao-Ping

    2014-02-01

    Proteins of the 14-3-3 family are universal participate in multiple cellular processes. However, their exact role in the pathogenesis of prion diseases remains unclear. In this study, we proposed that human PrP was able to form molecular complex with 14-3-3β. The domains responsible for the interactions between PrP and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within PrP and aa 1-38 within 14-3-3β. Homology modeling revealed that the key aa residues for molecular interaction were D22 and D23 in 14-3-3β as well as K110 in PrP. Mutations in these aa residues inhibited the interaction between the two proteins in vitro. Our results also showed that recombinant PrP encouraged 14-3-3β dimer formation, whereas PrP106-126 peptide inhibited it. Recombinant 14-3-3β disaggregated the mature PrP106-126 fibrils in vitro. Moreover, the PrP-14-3-3 protein complexes were observed in the brain tissues of normal and scrapie agent 263K infected hamsters. Colocalization of PrP and 14-3-3 was seen in the cytoplasm of human neuroblastoma cell line SH-SY5Y, as well as human cervical cancer cell line HeLa transiently expressing full-length human PrP. Our current data suggest the neuroprotection of PrPC and neuron damage caused by PrPSc may be associated with their functions of 14-3-3 dimerization regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions.

    Science.gov (United States)

    Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B

    2015-11-01

    Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  3. {sup 11}B-NMR spectroscopic study on the interaction of epinephrine and p-BPA

    Energy Technology Data Exchange (ETDEWEB)

    Ichihara, K.; Yoshino, K. [Shinshu Univ., Department of Chemistry, Matsumoto, Nagano (Japan)

    2000-10-01

    It is studied that p-BPA (p-bronophenylalanine) which formed complex with catechol functional group has interaction with epinephrine by {sup 11}B-NMR. Two {sup 11}B-NMR resonance signals were observed at pH 7.0. The signal at 29.6 ppm is assigned to p-BPA and at 10.8 ppm is assigned to that of complex. We can determine complex formation constants (logK') in various pH. (author)

  4. How to Build MCNP 6.2

    Energy Technology Data Exchange (ETDEWEB)

    Bull, Jeffrey S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-13

    This presentation describes how to build MCNP 6.2. MCNP®* 6.2 can be compiled on Macs, PCs, and most Linux systems. It can also be built for parallel execution using both OpenMP and Messing Passing Interface (MPI) methods. MCNP6 requires Fortran, C, and C++ compilers to build the code.

  5. Search for charm in 250 GeV/c π-p interactions

    International Nuclear Information System (INIS)

    Harris, R.; Bogert, D.; Hanft, R.

    1975-01-01

    Inclusive cross sections are found for strange particle production in π - p interactions at 250 GeV/c in a search for charmed particles using neutral particle decays in a bubble chamber. The results are preliminary, but at the present statistical level no evidence was found for charmed particle production

  6. Dimuon scaling comparison at 44 and 62 GeV

    International Nuclear Information System (INIS)

    Antreasyan, D.; Becker, U.; Bellettini, G.; Laboratory for Nuclear Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139)

    1982-01-01

    Measurements of pp→μ + μ - +X at √s = 44 and 62 GeV are compared. The data are taken under identical conditions utilizing clean proton-proton collisions from the CERN-intersecting storage rings and confirm scaling to 5%. The observed μ + μ - yield is a factor of 1.6 +- 0.2 larger than estimated from a simple parton model but is consistent with QCD. The P/sub T/ dependence of the muon pairs agrees well with expectations from QCD

  7. The importance of pKa in an analysis of the interaction of compounds with DNA.

    Science.gov (United States)

    Saha, Mouli; Nandy, Promita; Chakraborty, Mousumi; Das, Piyal; Das, Saurabh

    2018-05-01

    pK a of a compound is crucial for determining the contributions of different forms of it towards overall binding with DNA. Hence it is important to use correct pK a values in DNA interaction studies. This study takes a look at the importance of pK a values to realize binding of compounds with DNA. Since pK a of a compound determined in the presence of DNA is quite different from that determined in its absence hence, presence of different forms of a compound during interaction with DNA is different from that realized if the determination of pK a is done in normal aqueous solution in absence of DNA. Hence, calculations determining contributions of different forms of a compound interacting with DNA are affected accordingly. Two simple analogues of anthracyclines, alizarin and purpurin, were used to investigate the influence DNA has on pK a values. Indeed, they were different in presence of DNA than when determined in normal aqueous solution. pK a1 for alizarin and purpurin determined in the absence and presence of calf thymus DNA were used in equations that determine contributions of two forms (neutral and anionic) towards overall binding with DNA. The study concludes that correct pK a values, determined correctly i.e. under appropriate conditions, must be used for DNA binding experiments to evaluate contributions of individual forms. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Three cardiovirus Leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways

    Energy Technology Data Exchange (ETDEWEB)

    Ciomperlik, Jessica J. [Institute for Molecular Virology, and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI (United States); Basta, Holly A. [Department of Biology, Rocky Mountain College, Billings, MT (United States); Palmenberg, Ann C., E-mail: acpalmen@wisc.edu [Institute for Molecular Virology, and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI (United States)

    2015-10-15

    Cardiovirus infections inhibit nucleocytoplasmic trafficking by Leader protein-induced phosphorylation of Phe/Gly-containing nucleoporins (Nups). Recombinant Leader from encephalomyocarditis virus, Theiler's murine encephalomyelitis virus and Saffold virus target the same subset of Nups, including Nup62 and Nup98, but not Nup50. Reporter cell lines with fluorescence mCherry markers for M9, RS and classical SV40 import pathways, as well as the Crm1-mediated export pathway, all responded to transfection with the full panel of Leader proteins, showing consequent cessation of path-specific active import/export. For this to happen, the Nups had to be presented in the context of intact nuclear pores and exposed to cytoplasmic extracts. The Leader phosphorylation cascade was not effective against recombinant Nup proteins. The findings support a model of Leader-dependent Nup phosphorylation with the purpose of disrupting Nup-transportin interactions. - Highlights: • Nup98, but not Nup50 becomes phosphorylated by cardiovirus Leader protein-dependent mechanisms. • At least four independent nucleocytoplasmic trafficking pathways are inhibited by this process. • Nups must be presented in a nuclear pore context for Leader-directed phosphorylation. • Leader, by itself, does not cause activation of cellular kinases.

  9. Three cardiovirus Leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways

    International Nuclear Information System (INIS)

    Ciomperlik, Jessica J.; Basta, Holly A.; Palmenberg, Ann C.

    2015-01-01

    Cardiovirus infections inhibit nucleocytoplasmic trafficking by Leader protein-induced phosphorylation of Phe/Gly-containing nucleoporins (Nups). Recombinant Leader from encephalomyocarditis virus, Theiler's murine encephalomyelitis virus and Saffold virus target the same subset of Nups, including Nup62 and Nup98, but not Nup50. Reporter cell lines with fluorescence mCherry markers for M9, RS and classical SV40 import pathways, as well as the Crm1-mediated export pathway, all responded to transfection with the full panel of Leader proteins, showing consequent cessation of path-specific active import/export. For this to happen, the Nups had to be presented in the context of intact nuclear pores and exposed to cytoplasmic extracts. The Leader phosphorylation cascade was not effective against recombinant Nup proteins. The findings support a model of Leader-dependent Nup phosphorylation with the purpose of disrupting Nup-transportin interactions. - Highlights: • Nup98, but not Nup50 becomes phosphorylated by cardiovirus Leader protein-dependent mechanisms. • At least four independent nucleocytoplasmic trafficking pathways are inhibited by this process. • Nups must be presented in a nuclear pore context for Leader-directed phosphorylation. • Leader, by itself, does not cause activation of cellular kinases

  10. gigapanorama of NA 62 cavern

    CERN Multimedia

    Brice, Maximilien

    2015-01-01

    The image shows the new rare Kaon decay experiment at CERN, called NA62. The NA62 experiment is 270 metres long and includes a 120-metre-long vacuum tank, shown here, housing several of the particle detectors. (Note: the experiment axis is a straight line, the curving of the tank is an optical effect of the photo.) Kaons are particles that decay into lighter elementary particles. The kaon decay processes are mostly well known, except for some very rare decay modes. For example, NA62 is investigating a rare decay predicted by the Standard Model in which a kaon decays into one pion and two neutrinos. This process occurs only once every 10 billion decays. The understanding of such ultra-rare decays are of great importance because they test the Standard Model in energy ranges not accessible by direct measurements. They are therefore complementary to the measurements at the LHC. ultra high definition on demand (photolab@cern.ch).

  11. Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus.

    Science.gov (United States)

    Fros, Jelke J; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; van Leeuwen, Daniël M; Flipse, Jacky; Vlak, Just M; Failloux, Anna-Bella; Pijlman, Gorben P

    2015-09-17

    Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epidemic. While alphavirus replication is well understood in general, the specific function (s) of non-structural protein nsP3 remain elusive. CHIKV nsP3 modulates the mammalian stress response by preventing stress granule formation through sequestration of G3BP. In mosquitoes, nsP3 is a determinant of vector specificity, but its functional interaction with mosquito proteins is unclear. In this research we studied the domains required for localization of CHIKV nsP3 in insect cells and demonstrated its molecular interaction with Rasputin (Rin), the mosquito homologue of G3BP. The biological involvement of Rin in CHIKV infection was investigated in live Ae. albopictus mosquitoes. In insect cells, nsP3 localized as cytoplasmic granules, which was dependent on the central domain and the C-terminal variable region but independent of the N-terminal macrodomain. Ae. albopictus Rin displayed a diffuse, cytoplasmic localization, but was effectively sequestered into nsP3-granules upon nsP3 co-expression. Site-directed mutagenesis showed that the Rin-nsP3 interaction involved the NTF2-like domain of Rin and two conserved TFGD repeats in the C-terminal variable domain of nsP3. Although in vitro silencing of Rin did not impact nsP3 localization or CHIKV replication in cell culture, Rin depletion in vivo significantly decreased the CHIKV infection rate and transmissibility in Ae.albopictus. We identified the nsP3 hypervariable C-terminal domain as a critical factor for granular localization and sequestration of mosquito Rin. Our study offers novel insight into a conserved virus-mosquito interaction at the molecular level, and reveals a strong proviral role for G3BP homologue Rin in live mosquitoes

  12. 19 CFR 4.62 - Accounting for inward cargo.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Accounting for inward cargo. 4.62 Section 4.62 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Foreign Clearances § 4.62 Accounting for inward cargo...

  13. Energy dependence of identified hadron spectra and event-by-event fluctuations in p+p interactions from NA61/SHINE at the CERN SPS

    CERN Document Server

    Rybczynski, Maciej; Aduszkiewicz, A.; Ali, Y.; Anticic, T.; Antoniou, N.; Argyriades, J.; Baatar, B.; Blondel, A.; Blumer, J.; Bogomilov, M.; Bravar, A.; Brooks, W.; Brzychczyk, J.; Bubak, A.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Czopowicz, T.; Davis, N.; Debieux, S.; Dembinski, H.; Diakonos, F.; Di Luise, S.; Dominik, W.; Drozhzhova, T.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Esposito, L.S.; Feofilov, G.A.; Fodor, Z.; Ferrero, A.; Fulop, A.; Gazdzicki, M.; Golubeva, M.; Grabez, B.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Hakobyan, H.; Hasegawa, T.; Hierholzer, M.; Idczak, R.; Igolkin, S.; Ivanov, Y.; Ivashkin, A.; Jakovic, D.; Kadija, K.; Kapoyannis, A.; Katrynska, N.; Kaptur, E.; Kielczewska, D.; Kikola, D.; Kirejczyk, M.; Kisiel, J.; Kiss, T.; Kleinfelder, S.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalski, S.; Krasnoperov, A.; Kuleshov, S.; Kurepin, A.; Larsen, D.; Laszlo, A.; Lyubushkin, V.V.; Mackowiak-Pawlowska, M.; Majka, Z.; Maksiak, B.; Malakhov, A.I.; Maletic, D.; Marchionni, A.; Marcinek, A.; Marin, V.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Mrowczynski, St.; Murphy, S.; Nakadaira, T.; Nirkko, M.; Nishikawa, K.; Palczewski, T.; Palla, G.; Panagiotou, A.D.; Paul, T.; Pistillo, C.; Redij, A.; Peryt, W.; Petukhov, O.; Planeta, R.; Pluta, J.; Popov, B.A.; Posiadala, M.; Pulawski, S.; Puzovic, J.; Rauch, W.; Ravonel, M.; Renfordt, R.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Savic, M.; Sekiguchi, T.; Seyboth, P.; Shibata, M.; Sipos, M.; Skrzypczak, E.; Slodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Stroebele, H.; Susa, T.; Szuba, M.; Tada, M.; Tereshchenko, V.; Tolyhi, T.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberic, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Wlodarczyk, Z.; Wojtaszek, A.; Wyszynski, O.; Zambelli, L.; Zipper, W.

    2013-01-01

    NA61/SHINE at the CERN SPS is a fixed-target experiment pursuing a rich physics program including measurements for heavy ion, neutrino and cosmic ray physics. The main goal of the ion program is to explore the most interesting $T, mu_{B}$ region of the phase diagram of strongly interacting matter. We plan to study the properties of the onset of deconfinement and to search for the signatures of the critical point. The search is performed by varying collision energy (13A-158A GeV/c) and system size (p+p, Be+Be, Ar+Ca, Xe+La). Thanks to its large acceptance and excellent particle identification capability NA61/SHINE is well suited for performing high-precision particle production measurements as well as for studying event-by-event fluctuations in p+p, p+nucleus and nucleus+nucleus collisions. Preliminary results on p+p interactions at 20, 31, 40, 80 and 158 GeV/c are presented. They include inclusive spectra of pi+, pi-, K- and protons as a function of transverse momentum/mass and rapidity as well as event-by-ev...

  14. Q-value of the superallowed {beta} decay of {sup 62}Ga

    Energy Technology Data Exchange (ETDEWEB)

    Eronen, T. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland)]. E-mail: tommi.eronen@phys.jyu.fi; Elomaa, V. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Hager, U. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Hakala, J. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Jokinen, A. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Kankainen, A. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Moore, I. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Penttilae, H. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Rahaman, S. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Rinta-Antila, S. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Saastamoinen, A. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Sonoda, T. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Aystoe, J. [Department of Physics, P.O. Box 35 (YFL), FIN-40014 University of Jyvaeskylae (Finland); Bey, A.; Blank, B.; Canchel, G.; Dossat, C.; Giovinazzo, J.; Matea, I. [Centre d' Etudes Nucleaires de Bordeaux-Gradignan, Le Haut-Vigneau, F-33175 Gradignan cedex (France); Adimi, N. [Faculte de Physique, USTHB, BP32, El Alia, 16111 Bab Ezzouar, Alger (Algeria)

    2006-05-11

    Masses of the radioactive isotopes {sup 62}Ga, {sup 62}Zn and {sup 62}Cu have been measured at the JYFLTRAP facility with a relative precision of better than 1.8x10{sup -8}. A Q{sub EC} value of (9181.07{+-}0.54) keV for the superallowed decay of {sup 62}Ga is obtained from the measured cyclotron frequency ratios of {sup 62}Ga-{sup 62}Zn, {sup 62}Ga-{sup 62}Ni and {sup 62}Zn-{sup 62}Ni ions. The resulting Ft-value supports the validity of the conserved vector current hypothesis (CVC). The mass excess values measured were (-51986.5{+-}1.0) keV for {sup 62}Ga (-61167.9{+-}0.9) keV for {sup 62}Zn and (-62787.2{+-}0.9) keV for {sup 62}Cu.

  15. Epstein–Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus

    International Nuclear Information System (INIS)

    Changotra, Harish; Turk, Susan M.; Artigues, Antonio; Thakur, Nagendra; Gore, Mindy; Muggeridge, Martin I.; Hutt-Fletcher, Lindsey M.

    2016-01-01

    The Epstein–Barr virus glycoprotein complex gMgN has been implicated in assembly and release of fully enveloped virus, although the precise role that it plays has not been elucidated. We report here that the long predicted cytoplasmic tail of gM is not required for complex formation and that it interacts with the cellular protein p32, which has been reported to be involved in nuclear egress of human cytomegalovirus and herpes simplex virus. Although redistribution of p32 and colocalization with gM was not observed in virus infected cells, knockdown of p32 expression by siRNA or lentivirus-delivered shRNA recapitulated the phenotype of a virus lacking expression of gNgM. A proportion of virus released from cells sedimented with characteristics of virus lacking an intact envelope and there was an increase in virus trapped in nuclear condensed chromatin. The observations suggest the possibility that p32 may also be involved in nuclear egress of Epstein–Barr virus. - Highlights: • The predicted cytoplasmic tail of gM is not required to complex with gN. • Cellular p32 can interact with the predicted cytoplasmic tail of EBV gM. • Knockdown of p32 recapitulates the phenotype of virus lacking the gNgM complex.

  16. Epstein–Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus

    Energy Technology Data Exchange (ETDEWEB)

    Changotra, Harish; Turk, Susan M. [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Artigues, Antonio [Department of Biochemistry, University of Kansas Medical Center, Kansas City, KS (United States); Thakur, Nagendra; Gore, Mindy; Muggeridge, Martin I. [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Hutt-Fletcher, Lindsey M., E-mail: lhuttf@lsuhsc.edu [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2016-02-15

    The Epstein–Barr virus glycoprotein complex gMgN has been implicated in assembly and release of fully enveloped virus, although the precise role that it plays has not been elucidated. We report here that the long predicted cytoplasmic tail of gM is not required for complex formation and that it interacts with the cellular protein p32, which has been reported to be involved in nuclear egress of human cytomegalovirus and herpes simplex virus. Although redistribution of p32 and colocalization with gM was not observed in virus infected cells, knockdown of p32 expression by siRNA or lentivirus-delivered shRNA recapitulated the phenotype of a virus lacking expression of gNgM. A proportion of virus released from cells sedimented with characteristics of virus lacking an intact envelope and there was an increase in virus trapped in nuclear condensed chromatin. The observations suggest the possibility that p32 may also be involved in nuclear egress of Epstein–Barr virus. - Highlights: • The predicted cytoplasmic tail of gM is not required to complex with gN. • Cellular p32 can interact with the predicted cytoplasmic tail of EBV gM. • Knockdown of p32 recapitulates the phenotype of virus lacking the gNgM complex.

  17. Ataxia telangiectasia mutated (ATM) interacts with p400 ATPase for an efficient DNA damage response.

    Science.gov (United States)

    Smith, Rebecca J; Savoian, Matthew S; Weber, Lauren E; Park, Jeong Hyeon

    2016-11-04

    Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites. While it is understood that DNA binding transcriptional activators recruit p400 ATPase into a regulatory region of the promoter, how p400 recognises and moves to DNA double-strand break sites is far less clear. Here we investigate a possibility whether ATM serves as a shuttle to deliver p400 to break sites. Our data indicate that p400 co-immunoprecipitates with ATM independently of DNA damage state and that the N-terminal domain of p400 is vital for this interaction. Heterologous expression studies using Sf9 cells revealed that the ATM-p400 complex can be reconstituted without other mammalian bridging proteins. Overexpression of ATM-interacting p400 regions in U2OS cells induced dominant negative effects including the inhibition of both DNA damage repair and cell proliferation. Consistent with the dominant negative effect, the stable expression of an N-terminal p400 fragment showed a decrease in the association of p400 with ATM, but did not alter the association of p400 with TRRAP. Taken together, our findings suggest that a protein-protein interaction between ATM and p400 ATPase occurs independently of DNA damage and contributes to efficient DNA damage response and repair.

  18. 12 CFR 34.62 - Real estate lending standards.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Real estate lending standards. 34.62 Section 34.62 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REAL ESTATE LENDING AND APPRAISALS Real Estate Lending Standards § 34.62 Real estate lending standards. (a) Each national bank shall...

  19. Study of pH (low) insertion peptides (pHLIPs) interaction with lipid bilayer of membrane

    Science.gov (United States)

    Weerakkody, Dhammika

    The pH-dependent interactions of pHLIPsRTM (pH (Low) Insertion Peptides) with lipid bilayer of membrane provides an opportunity to study and address fundamental questions of protein folding/insertion into membrane and unfolding/exit, as well as develop novel approach to target acidic diseased tissue such as cancer, ischemic myocardium, infection and others. The main goal of the work presented here is to answer the following questions: - What is the molecular mechanism of spontaneous insertion and folding of a peptide in a lipid bilayer of membrane; - What is the molecular mechanism of unfolding and exit of a peptide from a lipid bilayer of membrane; - How polar cargo attached to a peptide's inserting end might affect the process of insertion into a lipid bilayer of membrane; How sequence variation will affect a peptide's interactions with a lipid bilayer of membrane (partitioning into bilayer at neutral and low pH; apparent pK of insertion) with the main goal to identify the best pHLIP variants for imaging and therapy of pathological states such as cancer and others. It has been demonstrated that pHLIP insertion into a membrane is associated with the protonation of Asp/Glu residues, which leads to an increase of hydrophobicity that triggers the folding and insertion of the peptide across a lipid bilayer. The insertion of the pHLIP is unidirectional and it is accompanied by the release of energy. Therefore, the energy of membrane associated-folding can be used to favor the movement of cell-impermeable polar cargo molecules across the hydrophobic membrane bilayer when they are attached to the inserting end of pHLIP. Both pH-targeting behavior and molecular translocation have been demonstrated in cultured cells and in vivo. Thus, there is an opportunity to develop a novel concept in drug delivery, which is based on the use of a monomeric, pH-sensitive peptide molecular transporter, to deliver agents that are significantly more polar than conventional drugs

  20. Interaction phenomenon to dimensionally reduced p-gBKP equation

    Science.gov (United States)

    Zhang, Runfa; Bilige, Sudao; Bai, Yuexing; Lü, Jianqing; Gao, Xiaoqing

    2018-02-01

    Based on searching the combining of quadratic function and exponential (or hyperbolic cosine) function from the Hirota bilinear form of the dimensionally reduced p-gBKP equation, eight class of interaction solutions are derived via symbolic computation with Mathematica. The submergence phenomenon, presented to illustrate the dynamical features concerning these obtained solutions, is observed by three-dimensional plots and density plots with particular choices of the involved parameters between the exponential (or hyperbolic cosine) function and the quadratic function. It is proved that the interference between the two solitary waves is inelastic.

  1. NA61/SHINE results on fluctuations and correlations in p + p and Be + Be interactions at CERN SPS energies

    Energy Technology Data Exchange (ETDEWEB)

    Mackowiak-Pawlowska, Maja

    2016-12-15

    The aim of the NA61/SHINE strong interaction program is to explore the phase diagram of strongly interacting matter. The main physics goals are the study of the onset of deconfinement and the search for the critical point of strongly interacting matter. These goals are pursued by performing a beam momentum (13A – 158A GeV/c) and system size (p+p, p+Pb, Be+Be, Ar+Sc, Xe+La) scan. This contribution presents results on transverse momentum and multiplicity fluctuations from the Be+Be and p+p energy scan. Also, results on two-particle correlations in pseudorapidity and azimuthal angle obtained in p+p interactions will be shown. The influence of conservation laws and resonance decays on multiplicity and chemical fluctuations of identified particles in p+p interactions will be discussed. Obtained results will be compared with data from other experiments and with model predictions.

  2. Comparative hepatotoxicity of 6:2 fluorotelomer carboxylic acid and 6:2 fluorotelomer sulfonic acid, two fluorinated alternatives to long-chain perfluoroalkyl acids, on adult male mice.

    Science.gov (United States)

    Sheng, Nan; Zhou, Xiujuan; Zheng, Fei; Pan, Yitao; Guo, Xuejiang; Guo, Yong; Sun, Yan; Dai, Jiayin

    2017-08-01

    Due to their structural similarities, 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and 6:2 fluorotelomer carboxylic acid (6:2 FTCA) are often used as alternatives to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), respectively. With limited health risk data and 6:2 FTSA detection in water and sludge, the toxicity of these chemicals is of growing concern. Here, adult male mice were exposed with 5 mg/kg/day of 6:2 FTCA or 6:2 FTSA for 28 days to investigate their hepatotoxicological effects. In contrast to 6:2 FTCA, 6:2 FTSA was detected at high and very high levels in serum and liver, respectively, demonstrating bioaccumulation potential and slow elimination. Furthermore, 6:2 FTSA induced liver weight increase, inflammation, and necrosis, whereas 6:2 FTCA caused no obvious liver injury, with fewer significantly altered genes detected compared with that of 6:2 FTSA (39 vs. 412). Although PFOA and PFOS commonly activate peroxisome proliferator-activated receptor α (PPARα), 6:2 FTSA induced an increase in PPARγ and related proteins, but not in lipid metabolism-related genes such as PPARα. Our results showed that 6:2 FTCA and 6:2 FTSA exhibited weak and moderate hepatotoxicity, respectively, compared with that reported for legacies PFOA and PFOS.

  3. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells

    International Nuclear Information System (INIS)

    Linxweiler, Maximilian; Greiner, Markus; Schorr, Stefan; Schäuble, Nico; Jung, Martin; Linxweiler, Johannes; Langer, Frank; Schäfers, Hans-Joachim; Cavalié, Adolfo; Zimmermann, Richard

    2013-01-01

    Tumor cells benefit from their ability to avoid apoptosis and invade other tissues. The endoplasmic reticulum (ER) membrane protein Sec62 is a key player in these processes. Sec62 is essential for cell migration and protects tumor cells against thapsigargin-induced ER stress, which are both linked to cytosolic Ca 2+ . SEC62 silencing leads to elevated cytosolic Ca 2+ and increased ER Ca 2+ leakage after thapsigargin treatment. Sec62 protein levels are significantly increased in different tumors, including prostate, lung and thyroid cancer. In lung cancer, the influence of Sec62 protein levels on patient survival was analyzed using the Kaplan-Meier method and log-rank test. To elucidate the underlying pathophysiological functions of Sec62, Ca 2+ imaging techniques, real-time cell analysis and cell migration assays were performed. The effects of treatment with the calmodulin antagonists, trifluoperazine (TFP) and ophiobolin A, on cellular Ca 2+ homeostasis, cell growth and cell migration were compared with the effects of siRNA-mediated Sec62 depletion or the expression of a mutated SEC62 variant in vitro. Using Biacore analysis we examined the Ca 2+ -sensitive interaction of Sec62 with the Sec61 complex. Sec62 overproduction significantly correlated with reduced patient survival. Therefore, Sec62 is not only a predictive marker for this type of tumor, but also an interesting therapeutic target. The present study suggests a regulatory function for Sec62 in the major Ca 2+ leakage channel in the ER, Sec61, by a direct and Ca 2+ -sensitive interaction. A Ca 2+ -binding motif in Sec62 is essential for its molecular function. Treatment of cells with calmodulin antagonists mimicked Sec62 depletion by inhibiting cell migration and rendering the cells sensitive to thapsigargin treatment. Targeting tumors that overproduce Sec62 with calmodulin antagonists in combination with targeted thapsigargin analogues may offer novel personalized therapeutic options

  4. Separation and preparation of "6"2Ni isotope

    International Nuclear Information System (INIS)

    Ren Xiuyan; Mi Yajing; Zeng Ziqiang; Li Gongliang; Tu Rui

    2014-01-01

    Micro nuclear battery is the perfect power of space craft equipment. "6"3Ni is the core operation material of the "6"3Ni battery. It can produce radioisotope "6"3Ni while high abundance "6"2Ni is irradiated in the reactor. In order to meet the requirements of the abundance and the purity, research of the separation for "6"2Ni isotope was developed. The magnetic field and beam transmission status were simulated. The improvement designs of the ion source and the collector pocket were carried out. The process flow of high abundance "6"2Ni using electromagnetic separation method was established. The experiment of "6"2Ni isotope was developed by using electromagnetism isotope separator. The results show that the enrichment of "6"2Ni isotope is more than 90%. (authors)

  5. The effect of instanton-induced interaction on P-wave meson spectra ...

    Indian Academy of Sciences (India)

    possible to reproduce the observed spectra as the tensor and spin-orbit terms of. OGEP are attractive, and hence naturally triplet states masses will be lower than the corresponding singlet states. Hence, to reproduce the full P-wave spectra it is essential to include the hyperfine interaction term of III to have a consistent. 76.

  6. Gelsolin negatively regulates the activity of tumor suppressor p53 through their physical interaction in hepatocarcinoma HepG2 cells

    International Nuclear Information System (INIS)

    An, Joo-Hee; Kim, Jung-Woong; Jang, Sang-Min; Kim, Chul-Hong; Kang, Eun-Jin; Choi, Kyung-Hee

    2011-01-01

    Highlights: → The actin binding protein Gelsolin (GSN) interacts with transcription factor p53. → GSN interacts with transactivation- and DNA binding domains of p53. → GSN represses transactivity of p53 via inhibition of nuclear translocation of p53. → GSN inhibits the p53-mediated apoptosis in hepatocarcinoma HepG2 cells. -- Abstract: As a transcription factor, p53 modulates several cellular responses including cell-cycle control, apoptosis, and differentiation. In this study, we have shown that an actin regulatory protein, gelsolin (GSN), can physically interact with p53. The nuclear localization of p53 is inhibited by GSN overexpression in hepatocarcinoma HepG2 cells. Additionally, we demonstrate that GSN negatively regulates p53-dependent transcriptional activity of a reporter construct, driven by the p21-promoter. Furthermore, p53-mediated apoptosis was repressed in GSN-transfected HepG2 cells. Taken together, these results suggest that GSN binds to p53 and this interaction leads to the inhibition of p53-induced apoptosis by anchoring of p53 in the cytoplasm in HepG2 cells.

  7. 40 CFR 62.15370 - What is yard waste?

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false What is yard waste? 62.15370 Section 62... for Small Municipal Waste Combustion Units Constructed on or Before August 30, 1999 Air Curtain Incinerators That Burn 100 Percent Yard Waste § 62.15370 What is yard waste? Yard waste is grass, grass...

  8. Two-particle correlations in azimuthal angle and pseudorapidity in inelastic p + p interactions at the CERN Super Proton Synchrotron

    International Nuclear Information System (INIS)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M.; Walewski, M.; Ali, Y.; Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Kovalenko, V.; Merzlaya, A.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L.; Anticic, T.; Kadija, K.; Susa, T.; Antoniou, N.; Christakoglou, P.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M.; Baatar, B.; Brandin, A.; Selyuzhenkov, I.; Taranenko, A.; Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D.; Blondel, A.; Bravar, A.; Damyanova, A.; Haesler, A.; Korzenev, A.; Ravonel, M.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V.; Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Sadovsky, A.; Cirkovic, M.; Knezevic, N.; Manic, D.; Puzovic, J.; Czopowicz, T.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D.; Davis, N.; Kielbowicz, M.; Ozvenchuk, V.; Rybicki, A.; Dembinski, H.; Engel, R.; Herve, A.E.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D.; Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H.; Dumarchez, J.; Robert, A.; Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A.; Fodor, Z.; Garibov, A.; Gazdzicki, M.; Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A.; Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M.; Hylen, J.; Lundberg, B.; Marchionni, A.; Rameika, R.; Zwaska, R.; Johnson, S.R.; Marino, A.D.; Nagai, Y.; Rumberger, B.T.; Zimmerman, E.D.; Kowalik, K.; Rondio, E.; Stepaniak, J.; Laszlo, A.; Marton, K.; Vesztergombi, G.; Lewicki, M.; Naskret, M.; Turko, L.; Marcinek, A.; Messerly, B.; Paolone, V.; Wickremasinghe, A.; Mills, G.B.; Morozov, S.; Petukhov, O.; Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A.; Pavin, M.; Popov, B.A.; Rauch, W.; Roehrich, D.; Rustamov, A.; Zambelli, L.

    2017-01-01

    Results on two-particle ΔηΔφ correlations in inelastic p + p interactions at 20, 31, 40, 80, and 158 GeV/c are presented. The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN Super Proton Synchrotron. The data show structures which can be attributed mainly to effects of resonance decays, momentum conservation, and quantum statistics. The results are compared with the Epos and UrQMD models. (orig.)

  9. Two-particle correlations in azimuthal angle and pseudorapidity in inelastic p + p interactions at the CERN Super Proton Synchrotron

    Energy Technology Data Exchange (ETDEWEB)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M.; Walewski, M. [University of Warsaw, Warsaw (Poland); Ali, Y. [Jagiellonian University, Cracow (Poland); COMSATS Institute of Information Technology, Islamabad (Pakistan); Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Kovalenko, V.; Merzlaya, A.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L. [St. Petersburg State University, St. Petersburg (Russian Federation); Anticic, T.; Kadija, K.; Susa, T. [Ruder Boskovic Institute, Zagreb (Croatia); Antoniou, N.; Christakoglou, P.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M. [University of Athens, Athens (Greece); Baatar, B.; Brandin, A.; Selyuzhenkov, I.; Taranenko, A. [National Research Nuclear University (Moscow Engineering Physics Institute), Moscow (Russian Federation); Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D. [ETH Zuerich, Zuerich (Switzerland); Blondel, A.; Bravar, A.; Damyanova, A.; Haesler, A.; Korzenev, A.; Ravonel, M. [University of Geneva, Geneva (Switzerland); Bogomilov, M.; Kolev, D.; Tsenov, R. [University of Sofia, Faculty of Physics, Sofia (Bulgaria); Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O. [Jagiellonian University, Cracow (Poland); Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Sadovsky, A. [Institute for Nuclear Research, Moscow (Russian Federation); Cirkovic, M.; Knezevic, N.; Manic, D.; Puzovic, J. [University of Belgrade, Belgrade (Serbia); Czopowicz, T.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D. [Warsaw University of Technology, Warsaw (Poland); Davis, N.; Kielbowicz, M.; Ozvenchuk, V.; Rybicki, A. [H. Niewodniczanski Institute of Nuclear Physics of the Polish Academy of Sciences, Krakow (Poland); Dembinski, H.; Engel, R.; Herve, A.E.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D. [Karlsruhe Institute of Technology, Karlsruhe (Germany); Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H. [University of Frankfurt, Frankfurt (Germany); Dumarchez, J.; Robert, A. [LPNHE, University of Paris VI and VII, Paris (France); Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A. [University of Bern, Bern (Switzerland); Fodor, Z. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); University of Wroclaw, Wroclaw (Poland); Garibov, A. [National Nuclear Research Center, Baku (Azerbaijan); Gazdzicki, M. [University of Frankfurt, Frankfurt (Germany); Jan Kochanowski University in Kielce, Kielce (Poland); Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A. [University of Silesia, Katowice (Poland); Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M. [Institute for Particle and Nuclear Studies, Tsukuba (Japan); Hylen, J.; Lundberg, B.; Marchionni, A.; Rameika, R.; Zwaska, R. [Fermilab, Batavia (United States); Johnson, S.R.; Marino, A.D.; Nagai, Y.; Rumberger, B.T.; Zimmerman, E.D. [University of Colorado, Boulder (United States); Kowalik, K.; Rondio, E.; Stepaniak, J. [National Centre for Nuclear Research, Warsaw (Poland); Laszlo, A.; Marton, K.; Vesztergombi, G. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); Lewicki, M.; Naskret, M.; Turko, L. [University of Wroclaw, Wroclaw (Poland); Marcinek, A. [Jagiellonian University, Cracow (Poland); University of Wroclaw, Wroclaw (Poland); Messerly, B.; Paolone, V.; Wickremasinghe, A. [University of Pittsburgh, Pittsburgh (United States); Mills, G.B. [Los Alamos National Laboratory, Los Alamos (United States); Morozov, S.; Petukhov, O. [Institute for Nuclear Research, Moscow (Russian Federation); National Research Nuclear University (Moscow Engineering Physics Institute), Moscow (Russian Federation); Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A. [Jan Kochanowski University in Kielce, Kielce (Poland); Pavin, M. [Ruder Boskovic Institute, Zagreb (Croatia); LPNHE, University of Paris VI and VII, Paris (France); Popov, B.A. [LPNHE, University of Paris VI and VII, Paris (France); Joint Institute for Nuclear Research, Dubna (Russian Federation); Rauch, W. [Fachhochschule Frankfurt, Frankfurt (Germany); Roehrich, D. [University of Bergen, Bergen (Norway); Rustamov, A. [National Nuclear Research Center, Baku (Azerbaijan); University of Frankfurt, Frankfurt (Germany); Zambelli, L. [LPNHE, University of Paris VI and VII, Paris (France); Institute for Particle and Nuclear Studies, Tsukuba (Japan)

    2017-02-15

    Results on two-particle ΔηΔφ correlations in inelastic p + p interactions at 20, 31, 40, 80, and 158 GeV/c are presented. The measurements were performed using the large acceptance NA61/SHINE hadron spectrometer at the CERN Super Proton Synchrotron. The data show structures which can be attributed mainly to effects of resonance decays, momentum conservation, and quantum statistics. The results are compared with the Epos and UrQMD models. (orig.)

  10. pH-dependent differential interacting mechanisms of sodium dodecyl sulfate with bovine serum fetuin: a biophysical insight.

    Science.gov (United States)

    Zaidi, Nida; Nusrat, Saima; Zaidi, Fatima Kamal; Khan, Rizwan H

    2014-11-20

    Sodium dodecyl sulfate (SDS)-glycoprotein interaction serves as a model for a biological membrane. To get mechanistic insight into the interaction of SDS and glycoprotein, the effect of SDS on bovine serum fetuin (BSF) was studied in subcritical micellar concentrations at pH 7.4 and pH 2 using multiple approaches. SDS interacts electrostatically with BSF through its negatively charged head groups at pH 2 and hydrophobically via its alkyl chains at pH 7.4 up to a 1:20 molar ratio of BSF to SDS. However, at higher concentrations of SDS, BSF undergoes amyloid fibril formation at pH 2, as confirmed by enhanced ThT fluorescence, β-sheet formation, and TEM microscopy, whereas BSF undergoes induction of an α-helical structure in the presence of higher SDS concentration at pH 7.4. The increase in α-helical content with increasing SDS concentrations constrains the environment around tryptophan. As a consequence, the interconversion of tryptophan conformers decreases, resulting in a decrement of the fluorescence lifetime for BSF in the presence of SDS at pH 7.4.

  11. Mucoadhesive properties and interaction with P-glycoprotein (P-gp) of thiolated-chitosans and -glycol chitosans and corresponding parent polymers: a comparative study.

    Science.gov (United States)

    Trapani, Adriana; Palazzo, Claudio; Contino, Marialessandra; Perrone, Maria Grazia; Cioffi, Nicola; Ditaranto, Nicoletta; Colabufo, Nicola Antonio; Conese, Massimo; Trapani, Giuseppe; Puglisi, Giovanni

    2014-03-10

    The aim of the present work was to compare the mucoadhesive and efflux pump P-glycoprotein (P-gp) interacting properties of chitosan (CS)- and glycolchitosan (GCS)-based thiomers and corresponding unmodified parent polymers. For this purpose, the glycol chitosan-N-acetyl-cysteine (GCS-NAC) and glycol chitosan-glutathione (GCS-GSH) thiomers were prepared under simple and mild conditions. Their mucoadhesive characteristics were studied by turbidimetric and zeta potential measurements. The P-gp interacting properties were evaluated measuring the effects of thiolated- and unmodified-polymers on the bidirectional transport (BA/AB) of rhodamine-123 across Caco-2 cells as well as in the calcein-AM and ATPase activity assays. Although all the thiomers and unmodified polymers showed optimal-excellent mucoadhesive properties, the best mucoadhesive performances have been obtained by CS and CS-based thiomers. Moreover, it was found that the pretreatment of Caco-2 cell monolayer with GCS-NAC or GCS restores Rho-123 cell entrance by inhibiting P-gp activity. Hence, GCS-NAC and GCS may constitute new biomaterials useful for improving the bioavailability of P-gp substrates.

  12. Human NTH1 physically interacts with p53 and proliferating cell nuclear antigen

    International Nuclear Information System (INIS)

    Oyama, Masaki; Wakasugi, Mitsuo; Hama, Takashi; Hashidume, Hatsuho; Iwakami, Yasutaka; Imai, Rika; Hoshino, Sanae; Morioka, Hiroshi; Ishigaki, Yasuhito; Nikaido, Osamu; Matsunaga, Tsukasa

    2004-01-01

    Thymine glycol (Tg) is one of predominant oxidative DNA lesions caused by ionizing radiation and other oxidative stresses. Human NTH1 is a bifunctional enzyme with DNA glycosylase and AP lyase activities and removes Tg as the first step of base excision repair (BER). We have searched for the factors interacting with NTH1 by using a pull-down assay and found that GST-NTH1 fusion protein precipitates proliferating cell nuclear antigen (PCNA) and p53 as well as XPG from human cell-free extracts. GST-NTH1 also bound to recombinant FLAG-tagged XPG, PCNA, and (His) 6 -tagged p53 proteins, indicating direct protein-protein interaction between those proteins. Furthermore, His-p53 and FLAG-XPG, but not PCNA, stimulated the Tg DNA glycosylase/AP lyase activity of GST-NTH1 or NTH1. These results provide an insight into the positive regulation of BER reaction and also suggest a possible linkage between BER of Tg and other cellular mechanisms

  13. The Semen pH Affects Sperm Motility and Capacitation.

    Science.gov (United States)

    Zhou, Ji; Chen, Li; Li, Jie; Li, Hongjun; Hong, Zhiwei; Xie, Min; Chen, Shengrong; Yao, Bing

    2015-01-01

    As the chemical environment of semen can have a profound effect on sperm quality, we examined the effect of pH on the motility, viability and capacitation of human sperm. The sperm in this study was collected from healthy males to avoid interference from other factors. The spermatozoa cultured in sperm nutrition solution at pH 5.2, 6.2, 7.2 and 8.2 were analyzed for sperm total motility, progressive motility (PR), hypo-osmotic swelling (HOS) rate, and sperm penetration. Our results showed that these parameters were similar in pH 7.2 and 8.2 sperm nutrition solutions, but decreased in pH 5.2 and 6.2 solutions. The HOS rate exhibited positive correlation with the sperm total motility and PR. In addition, the sperm Na(+)/K(+)-ATPase activity at different pHs was measured, and the enzyme activity was significantly lower in pH 5.2 and 6.2 media, comparing with that in pH 8.2 and pH 7.2 solutions. Using flow cytometry (FCM) and laser confocal scanning microscopy (LCSM) analysis, the intracellular Ca2(+ )concentrations of sperm cultured in sperm capacitation solution at pH 5.2, 6.2, 7.2 and 8.2 were determined. Compared with that at pH 7.2, the mean fluorescence intensity of sperm in pH 5.2 and 6.2 media decreased significantly, while that of pH 8.2 group showed no difference. Our results suggested that the declined Na(+)/K(+)-ATPase activity at acidic pHs result in decreased sperm movement and capacitation, which could be one of the mechanisms of male infertility.

  14. 27 CFR 22.62 - Change in trade name.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Change in trade name. 22.62 Section 22.62 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Original Qualification § 22.62 Change in trade name. Where there is to be a change in, or addition of, a...

  15. Collision broadening and shift of the potassium 4P-7S and 4P-5D lines by argon

    International Nuclear Information System (INIS)

    Hohimer, J.P.

    1981-01-01

    A two-step laser excitation technique has been used to investigate the collisional broadening and shift of excited-state potassium transitions. Values for the argon collisional broadening and shift constants for the potassium 4p-7s and 4p-5d transitions were determined from line shapes for argon pressures up to 100 Torr. The values of these constants (in units of 10 -9 rad s -1 atom -1 cm 3 ) are (4P/sub 1/2/-7S/sub 1/2/): γ=11.60 +- 0.07, β=-6.68 +- 0.11; (4P/sub 3/2/-7S/sub 1/2/): γ=11.49 +- 0.15, β=-6.82 +- 0.14; (4P/sub 1/2/-5D/sub 3/2/): γ=8.64 +- 0.07, β=-4.62 +- 0.04; (4P/sub 3/2/-5D/sub 3/2/): γ=8.58 +- 0.10, β=-3.49 +- 0.32; (4P/sub 3/2/-5D/sub 5/2/): γ=9.13 +- 0.10, β=-4.73 +- 0.09. These broadening and shift constants are interpreted in terms of a Lennard-Jones interaction potential

  16. Opinions of Female Juvenile Delinquents about Their Interactions in Chat Rooms

    Science.gov (United States)

    Sanger, Dixie; Long, Amie; Ritzman, Mitzi; Stofer, Keri; Davis, Candy

    2004-01-01

    The purpose of this study was to survey the opinions of 62 adolescent females residing in a correctional facility about their use of the Internet to participate in chat room conversations. Findings indicated that 54 of 62 girls (87.09%), with a mean age of 16.72 years, participated in chat room interactions. Most (n = 47) interacted in chat rooms…

  17. The short range effective interaction and the spectra of calcium isotopes in (f-p) space

    International Nuclear Information System (INIS)

    Qing-ying, Z.; Shen-wu, L.; Jian-xin, W.

    1986-01-01

    In this work, the authors use a new type of extremely short range interaction, the double delta interaction (DDI) to calculate the low-lying spectra of calcium isotopes /sup 41/Ca through /sup 48/Ca. The configuration space (f-p) includes configurations ( f/sub 7/2//sup n/ ) and ( f/sub 7/2//sup n-1/2p/sub 3/2/). The calculated energies are compared with experimental data for 75 levels. For comparison, they also use usual modified surface delta interaction (MSDI) to calculate the same spectra aforementioned. It is clear that the results calculated with DDI are better than with MSDI. Therefore, in the short-range effective interaction the addition of body delta force to the modified surface delta force may improve the agreement with experiment. The authors believe that the conclusion will not be changed if one enlarges the shell model space

  18. Interaction between 4p photoionization and 3p resonant excitation channels of krypton

    International Nuclear Information System (INIS)

    Buhr, T.; Kover, A.; Varga, D.; Muller, A.; Ricz, S.; Justus-Liebig- Universitat Giessen, Giessen; Holste, K.; Borovik, Jr.A.A.; Bernhardt, D.; Schippers, S.

    2011-01-01

    Complete text of publication follows. The angular distribution of Kr 4p photoelectrons was measured employing a linearly polarized photon beam at energies from 205 eV to 230 eV. In this range the Kr 3p→ns/md (n,m=4,5,6, etc.) resonances can be excited. The experimental anisotropy parameters (β, γ and δ) were determined for the Kr 4p shell and its fine structure components. The measurement was carried out at beamline BW3 of the DORIS III synchrotron light source at HASYLAB (Hamburg, Germany). The ESA-22D electrostatic electron spectrometer was used to analyze the emitted electrons. The spectrometer consists of a spherical and a cylindrical mirror analyzer. The spherical mirror focuses the electrons from the scattering plane to the entrance slit of the cylindrical analyzer performing the energy analysis of the electrons. (For detailed description of an ESA- 22-type electron spectrometer see Ref. [1].) The measured dipole anisotropy parameters ? of Kr 4p photoelectrons are shown in Fig. 1 as a function of photon energy. Resonance-like structure can be seen in the photon energy dependence of the dipole parameters. This structure indicates that the channel interactions are important between the 3p resonant excitation-autoionization and 4p direct photoionization processes in krypton. The natural line width of the 3p photoelectron peaks was determined from the measured spectra and it is about 0.8 eV while the experimental width of the resonance near 220 eV photon energy (3p 1/2 -1 →5s resonant excitation) is approximately 2 eV in Fig. 1. This broadening can be explained with the strong interference between the ionization and excitation channels. As before, we conclude that the angular distribution of photoelectrons is strongly influenced by the excitation processes. Acknowledgements. The authors wish to thank the DORIS III staff for providing excellent working conditions. This work was supported by the NKTH-OTKA (Grant No. K67719), and by the European Community

  19. Precision Branching Ratio Measurement for the Superallowed β+ Emitter Ga62 and Isospin-Symmetry-Breaking Corrections in A≥62 Nuclei

    Science.gov (United States)

    Hyland, B.; Svensson, C. E.; Ball, G. C.; Leslie, J. R.; Achtzehn, T.; Albers, D.; Andreoiu, C.; Bricault, P.; Churchman, R.; Cross, D.; Dombsky, M.; Finlay, P.; Garrett, P. E.; Geppert, C.; Grinyer, G. F.; Hackman, G.; Hanemaayer, V.; Lassen, J.; Lavoie, J. P.; Melconian, D.; Morton, A. C.; Pearson, C. J.; Pearson, M. R.; Phillips, A. A.; Schumaker, M. A.; Smith, M. B.; Towner, I. S.; Valiente-Dobón, J. J.; Wendt, K.; Zganjar, E. F.

    2006-09-01

    A high-precision branching ratio measurement for the superallowed β+ decay of Ga62 was performed at the Isotope Separator and Accelerator radioactive ion beam facility. Nineteen γ rays emitted following β+ decay of Ga62 were identified, establishing the dominant superallowed branching ratio to be (99.861±0.011)%. Combined with recent half-life and Q-value measurements, this branching ratio yields a superallowed ft value of 3075.6±1.4s for Ga62 decay. These results demonstrate the feasibility of high-precision superallowed branching ratio measurements in the A≥62 mass region and provide the first stringent tests of the large isospin-symmetry-breaking effects predicted for these decays.

  20. Involvement of the carboxyl-terminal region of the yeast peroxisomal half ABC transporter Pxa2p in its interaction with Pxa1p and in transporter function.

    Directory of Open Access Journals (Sweden)

    Cheng-Yi Chuang

    Full Text Available The peroxisome is a single membrane-bound organelle in eukaryotic cells involved in lipid metabolism, including β-oxidation of fatty acids. The human genetic disorder X-linked adrenoleukodystrophy (X-ALD is caused by mutations in the ABCD1 gene (encoding ALDP, a peroxisomal half ATP-binding cassette [ABC] transporter. This disease is characterized by defective peroxisomal β-oxidation and a large accumulation of very long-chain fatty acids in brain white matter, adrenal cortex, and testis. ALDP forms a homodimer proposed to be the functional transporter, whereas the peroxisomal transporter in yeast is a heterodimer comprising two half ABC transporters, Pxa1p and Pxa2p, both orthologs of human ALDP. While the carboxyl-terminal domain of ALDP is engaged in dimerization, it remains unknown whether the same region is involved in the interaction between Pxa1p and Pxa2p.Using a yeast two-hybrid assay, we found that the carboxyl-terminal region (CT of Pxa2p, but not of Pxa1p, is required for their interaction. Further analysis indicated that the central part of the CT (designated CT2 of Pxa2p was indispensable for its interaction with the carboxyl terminally truncated Pxa1_NBD. An interaction between the CT of Pxa2p and Pxa1_NBD was not detected, but could be identified in the presence of Pxa2_NBD-CT1. A single mutation of two conserved residues (aligned with X-ALD-associated mutations at the same positions in ALDP in the CT2 of the Pxa2_NBD-CT protein impaired its interaction with Pxa1_NBD or Pxa1_NBD-CT, resulting in a mutant protein that exhibited a proteinase K digestion profile different from that of the wild-type protein. Functional analysis of these mutant proteins on oleate plates indicated that they were defective in transporter function.The CT of Pxa2p is involved in its interaction with Pxa1p and in transporter function. This concept may be applied to human ALDP studies, helping to establish the pathological mechanism for CT-related X

  1. Effect of P T symmetry on nonlinear waves for three-wave interaction models in the quadratic nonlinear media

    Science.gov (United States)

    Shen, Yujia; Wen, Zichao; Yan, Zhenya; Hang, Chao

    2018-04-01

    We study the three-wave interaction that couples an electromagnetic pump wave to two frequency down-converted daughter waves in a quadratic optical crystal and P T -symmetric potentials. P T symmetric potentials are shown to modulate stably nonlinear modes in two kinds of three-wave interaction models. The first one is a spatially extended three-wave interaction system with odd gain-and-loss distribution in the channel. Modulated by the P T -symmetric single-well or multi-well Scarf-II potentials, the system is numerically shown to possess stable soliton solutions. Via adiabatical change of system parameters, numerical simulations for the excitation and evolution of nonlinear modes are also performed. The second one is a combination of P T -symmetric models which are coupled via three-wave interactions. Families of nonlinear modes are found with some particular choices of parameters. Stable and unstable nonlinear modes are shown in distinct families by means of numerical simulations. These results will be useful to further investigate nonlinear modes in three-wave interaction models.

  2. Clinical Validity of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62): Further Evaluation and Clinical Applications

    Science.gov (United States)

    McAleavey, Andrew A.; Nordberg, Samuel S.; Hayes, Jeffrey A.; Castonguay, Louis G.; Locke, Benjamin D.; Lockard, Allison J.

    2012-01-01

    Self-report instruments of psychological symptoms are increasingly used in counseling centers but rely on rigorous evaluation of their clinical validity. Three studies reported here (total N = 26,886) investigated the validity of the Counseling Center Assessment of Psychological Symptoms-62 (CCAPS-62; Locke et al., 2011) as an assessment and…

  3. Molecular dynamics simulation of S100B protein to explore ligand blockage of the interaction with p53 protein

    Science.gov (United States)

    Zhou, Zhigang; Li, Yumin

    2009-10-01

    As a tumor suppressor, p53 plays an important role in cancer suppression. The biological function of p53 as a tumor suppressor is disabled when it binds to S100B. Developing the ligands to block the S100B-p53 interaction has been proposed as one of the most important approaches to the development of anti-cancer agents. We screened a small compound library against the binding interface of S100B and p53 to identify potential compounds to interfere with the interaction. The ligand-binding effect on the S100B-p53 interaction was explored by molecular dynamics at the atomic level. The results show that the ligand bound between S100B and p53 propels the two proteins apart by about 2 Å compared to the unligated S100B-p53 complex. The binding affinity of S100B and p53 decreases by 8.5-14.6 kcal/mol after a ligand binds to the interface from the original unligated state of the S100B-p53 complex. Ligand-binding interferes with the interaction of S100B and p53. Such interference could impact the association of S100B and p53, which would free more p53 protein from the pairing with S100B and restore the biological function of p53 as a tumor suppressor. The analysis of the binding mode and ligand structural features would facilitate our effort to identify and design ligands to block S100B-p53 interaction effectively. The results from the work suggest that developing ligands targeting the interface of S100B and p53 could be a promising approach to recover the normal function of p53 as a tumor suppressor.

  4. Cytochrome P450 and P-Glycoprotein-Mediated Interactions Involving African Herbs Indicated for Common Noncommunicable Diseases

    Directory of Open Access Journals (Sweden)

    Gregory Ondieki

    2017-01-01

    Full Text Available Herbal remedies are regularly used to complement conventional therapies in the treatment of various illnesses in Africa. This may be because they are relatively cheap and easily accessible and are believed by many to be safe, cause fewer side effects, and are less likely to cause dependency. On the contrary, many herbs have been shown to alter the pharmacokinetics of coadministered allopathic medicines and can either synergize or antagonize therapeutic effects as well as altering the toxicity profiles of these drugs. Current disease burden data point towards epidemiological transitions characterised by increasing urbanization and changing lifestyles, risk factors for chronic diseases like hypertension, diabetes, and cancer which often present as multimorbidities. As a result, we highlight African herb-drug interactions (HDIs modulated via cytochrome P450 enzyme family (CYP and P-glycoprotein (P-gp and the consequences thereof in relation to antihypertensive, antidiabetic, and anticancer drugs. CYPs are enzymes which account for to up to 70% of drug metabolism while P-gp is an efflux pump that extrudes drug substrates out of cells. Consequently, regulation of the relative activity of both CYP and P-gp by African herbs influences the effective drug concentration at the site of action and modifies therapeutic outcomes.

  5. 40 CFR 62.9140 - Identification of source.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of source. 62.9140 Section 62.9140 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...] Metals, Acid Gases, Organic Compounds and Nitrogen Oxide Emissions From Existing Municipal Waste...

  6. Inclusive Λ0 production and polarization in K-p interactions

    International Nuclear Information System (INIS)

    Haupt, T.

    1985-01-01

    In this thesis a detailed analysis of inclusive production of neutral strange particles in K - p interactions at 110 GeV/c is presented. The analysis is concentrated on the Λ 0 hyperon production. About 80% of Λ 0 -s is produced in the channel K - p → Λ 0 KK-bar + anything at 110 GeV/c while at lower energies the inclusive Λ 0 production is dominated by the channel K - p → Λ 0 + pions. Next the results of the measurement of the Λ 0 polarization are presented. These results are compared with those obtained at lower energies as well as with those coming from reactions induced by non-strange projectiles. The most striking feature of the polarization is its dependence on the transverse momentum of Λ 0 , different in different channels and different hemispheres. Finally, our results are compared with predictions of models based on the quark-parton picture. 29 refs., 49 figs., 5 tabs. (author)

  7. P-glycoprotein interactions of novel psychoactive substances - stimulation of ATP consumption and transport across Caco-2 monolayers.

    Science.gov (United States)

    Meyer, Markus R; Wagmann, Lea; Schneider-Daum, Nicole; Loretz, Brigitta; de Souza Carvalho, Cristiane; Lehr, Claus-Michael; Maurer, Hans H

    2015-04-01

    In contrast to drugs for therapeutic use, there are only few data available concerning interactions between P-glycoprotein (P-gp) and drugs of abuse (DOA). In this work, interactions between structurally diverse DOA and P-gp were investigated using different strategies. First, the effect on the P-gp ATPase activity was studied by monitoring of ATP consumption after addition to recombinant, human P-gp. Second, DOA showing an increased ATP consumption were further characterized regarding their transport across filter grown Caco-2- monolayers. Analyses were performed by luminescence and liquid chromatography-mass spectrometry, respectively. Among the nine DOA initially screened, benzedrone, diclofensine, glaucine, JWH-200, MDBC, WIN-55,212-2 showed an increase of ATP consumption in the ATPase stimulation assay. In Caco-2 transport studies, Glaucine, JWH-200, mitragynine, WIN-55,212-2 could moreover be identified as non-transported substrates, but inhibitors of P-gp activity. Thus, drug-drug or drug-food interactions should be very likely for these compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Mode of Antifungal Drugs Interaction with Cytochrome P- 450

    Directory of Open Access Journals (Sweden)

    M- Mahmodian

    1991-07-01

    Full Text Available Computer was used to identify the interactions of substrates and antifungal drugs with the enzyme, Cytochrome P-450; and then Molplot.bas computer program was applied to get three dimensional figures of 5-hydroxy camphor.oxidation products of camphor analogues, and antifungal drugs.Cartesian characteristics of atoms building molecules, are taken from Buildz. for program, which can calculate X,Y,Z coordinates of atoms by Zmatrix data. The other program which can calculate X,Y,Z coordinates, using fractional characteristics, is the Coord, for program that, gives our cartesian characteristics of the atoms of molecule, then by using these data, we obtain three dimensional figures and distance between active atoms in compounds under consideration. Results show that distance between two oxygen atoms in 5-exo-hydroxy- camphor and the other compounds obtained from oxidation of camphor analogues, with the distance of two oxygen atoms in antifungal compounds under discussion are equal. Therefore, we can conclude that, the antifungal molecule also interacts with enzyme's active site, by its own sites, in a similar manner to the 5-hydroxy camphor molecule, which is:"n1. Nitrogen atom (N of Imidazole and Triazole ring in antifungal molecule with Iron atom in heam molecule belonging to Cytochrome P-450 enzyme, are coordinated."n2. The other atoms such as : 0,S or N in structure of the antifungal drug are coordinated with hydrogen atom of hydroxyl group belong ing to Tyr-96 in the structure of enzyme, forming hydrogen bonding.

  9. Multiplicity distributions of charged hadrons in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; Morrison, D.R.O.; Mobayyen, M.M.; Wainstein, S.; Borner, H.P.; Myatt, G.; Radojicic, D.; Burke, S.; Aderholz, M.; Hantke, D.; Katz, U.F.; Kern, J.; Schmitz, N.; Wittek, W.

    1991-10-01

    Using data on νp and anti νp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ∝ 20 000 events with incident ν and ∝ 10 000 events with incident anti ν. The invariant mass W of the total hadronic system ranges from 3 GeV to ∝ 14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for χ 2 /NDF. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling. (orig.)

  10. Multiplicity distributions of charged hadrons in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; Morrison, D.R.O.; Mobayyen, M.M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Katz, U.F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H.P.; Myatt, G.; Radojicic, D.; Burke, S.

    1992-01-01

    Using data on νp and anti νp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ∝20 000 events with incident ν and ∝10 000 events with incident anti ν. The invariant mass W of the total hadronic system ranges from 3 GeV to ∝14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for χ 2 /NDF. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling. (orig.)

  11. A smart pH responsive graphene/polyacrylamide complex via noncovalent interaction

    International Nuclear Information System (INIS)

    Ren Lulu; Liu Tianxi; Guo Juan; Guo Shuzhong; Wang Xiaoyan; Wang Weizhi

    2010-01-01

    We report that the graphene sheets can be stably dispersed in water by hydrophobic interaction with polyacrylamide. Most interestingly, the resultant graphene-polyacrylamide complexes show a reversible pH responsive property although polyacrylamide itself does not possess such characteristics. This method opens up novel opportunities for the potential applications of graphene in intelligent sensors, biology, medicine, nanoelectronics and other relevant areas.

  12. 22 CFR 62.21 - Short-term scholars.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Short-term scholars. 62.21 Section 62.21 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Specific... programs, confer on common problems and projects, and promote professional relationships and communications...

  13. 7 CFR 1948.62 - Environmental impact requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Environmental impact requirements. 1948.62 Section... Development Assistance Program § 1948.62 Environmental impact requirements. (a) The policies and regulations... studied for environmental impacts. (c) Boundaries shall define the area within which the environmental...

  14. 40 CFR 62.5103 - Identification of sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.5103 Section 62.5103 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS..., Frederick, Maryland. [50 FR 9628, Mar. 11, 1985] Metals, Acid Gases, Organic Compounds and Nitrogen Oxide...

  15. A Novel Protein Interaction between Nucleotide Binding Domain of Hsp70 and p53 Motif

    Directory of Open Access Journals (Sweden)

    Asita Elengoe

    2015-01-01

    Full Text Available Currently, protein interaction of Homo sapiens nucleotide binding domain (NBD of heat shock 70 kDa protein (PDB: 1HJO with p53 motif remains to be elucidated. The NBD-p53 motif complex enhances the p53 stabilization, thereby increasing the tumor suppression activity in cancer treatment. Therefore, we identified the interaction between NBD and p53 using STRING version 9.1 program. Then, we modeled the three-dimensional structure of p53 motif through homology modeling and determined the binding affinity and stability of NBD-p53 motif complex structure via molecular docking and dynamics (MD simulation. Human DNA binding domain of p53 motif (SCMGGMNR retrieved from UniProt (UniProtKB: P04637 was docked with the NBD protein, using the Autodock version 4.2 program. The binding energy and intermolecular energy for the NBD-p53 motif complex were −0.44 Kcal/mol and −9.90 Kcal/mol, respectively. Moreover, RMSD, RMSF, hydrogen bonds, salt bridge, and secondary structure analyses revealed that the NBD protein had a strong bond with p53 motif and the protein-ligand complex was stable. Thus, the current data would be highly encouraging for designing Hsp70 structure based drug in cancer therapy.

  16. Deducing T, C, and P invariance for strong interactions in topological particle theory

    International Nuclear Information System (INIS)

    Jones, C.E.

    1985-01-01

    It is shown here how the separate discrete invariances [time reversal (T), charge conjugation (C), and parity (P)] in strong interactions can be deduced as consequences of other S-matrix requirements in topological particle theory

  17. 50 CFR 300.62 - Annual management measures.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Annual management measures. 300.62 Section... REGULATIONS Pacific Halibut Fisheries § 300.62 Annual management measures. Annual management measures may be... of unloading and weighing, and sport fishing for halibut. The Assistant Administrator will publish...

  18. 40 CFR 62.1101 - Identification of sources.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Identification of sources. 62.1101 Section 62.1101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Company in San Joaquin County. (b) Simplot Company in Kings County. (c) Valley Nitrogen Products, Inc., in...

  19. Hsp12p and PAU genes are involved in ecological interactions between natural yeast strains.

    Science.gov (United States)

    Rivero, Damaríz; Berná, Luisa; Stefanini, Irene; Baruffini, Enrico; Bergerat, Agnes; Csikász-Nagy, Attila; De Filippo, Carlotta; Cavalieri, Duccio

    2015-08-01

    The coexistence of different yeasts in a single vineyard raises the question on how they communicate and why slow growers are not competed out. Genetically modified laboratory strains of Saccharomyces cerevisiae are extensively used to investigate ecological interactions, but little is known about the genes regulating cooperation and competition in ecologically relevant settings. Here, we present evidences of Hsp12p-dependent altruistic and contact-dependent competitive interactions between two natural yeast isolates. Hsp12p is released during cell death for public benefit by a fast-growing strain that also produces a killer toxin to inhibit growth of a slow grower that can enjoy the benefits of released Hsp12p. We also show that the protein Pau5p is essential in the defense against the killer effect. Our results demonstrate that the combined action of Hsp12p, Pau5p and a killer toxin is sufficient to steer a yeast community. © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. 10 CFR 430.62 - Submission of data.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Submission of data. 430.62 Section 430.62 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Certification and... data for all certification testing. Such records shall be organized and indexed in a fashion which...

  1. 22 CFR 62.8 - General program requirements.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false General program requirements. 62.8 Section 62.8 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM General... purpose of sharing the language, culture, or history of their home country with Americans, provided such...

  2. Studies of P-matrix formalism on the basis of the potential description of two-particle interaction

    International Nuclear Information System (INIS)

    Babenko, V.A.; Petrov, N.M.

    1991-01-01

    A study is made of mathematical and physical aspects of the P-matrix approach within the framework of the potential description of two particle interaction when the dynamics is based on the nonrelativistic Schroedinger equation. A dispersion formula for the P-matrix is derived correctly, different ways of its expansion by means of which it is possible to develop different methods of an approximate description of the quantities characterizing the two-particle interaction are suggested. 15 refs. (author)

  3. P450 reductase and cytochrome b5 interactions with cytochrome P450: Effects on house fly CYP6A1 catalysis

    OpenAIRE

    Murataliev, Marat B.; Guzov, Victor M.; Walker, F. Ann; Feyereisen, René

    2008-01-01

    The interactions of protein components of the xenobiotic-metabolizing cytochrome P450 system, CYP6A1, P450 reductase, and cytochrome b5 from the house fly (Musca domestica) have been characterized. CYP6A1 activity is determined by the concentration of the CYP6A1-P450 reductase complex, regardless of which protein is present in excess. Both holo- and apo-b5 stimulated CYP6A1 heptachlor epoxidase and steroid hydroxylase activities and influenced the regioselectivity of testosterone hydroxylatio...

  4. Cytochrome P450 enzyme mediated herbal drug interactions (Part 2)

    Science.gov (United States)

    Wanwimolruk, Sompon; Phopin, Kamonrat; Prachayasittikul, Virapong

    2014-01-01

    To date, a number of significant herbal drug interactions have their origins in the alteration of cytochrome P450 (CYP) activity by various phytochemicals. Among the most noteworthy are those involving St. John's wort and drugs metabolized by human CYP3A4 enzyme. This review article is the continued work from our previous article (Part 1) published in this journal (Wanwimolruk and Prachayasittikul, 2014[ref:133]). This article extends the scope of the review to six more herbs and updates information on herbal drug interactions. These include black cohosh, ginseng, grape seed extract, green tea, kava, saw palmetto and some important Chinese medicines are also presented. Even though there have been many studies to determine the effects of herbs and herbal medicines on the activity of CYP, most of them were in vitro and in animal studies. Therefore, the studies are limited in predicting the clinical relevance of herbal drug interactions. It appeared that the majority of the herbal medicines have no clear effects on most of the CYPs examined. For example, the existing clinical trial data imply that black cohosh, ginseng and saw palmetto are unlikely to affect the pharmacokinetics of conventional drugs metabolized by human CYPs. For grape seed extract and green tea, adverse herbal drug interactions are unlikely when they are concomitantly taken with prescription drugs that are CYP substrates. Although there were few clinical studies on potential CYP-mediated interactions produced by kava, present data suggest that kava supplements have the ability to inhibit CYP1A2 and CYP2E1 significantly. Therefore, caution should be taken when patients take kava with CYP1A2 or CYP2E1 substrate drugs as it may enhance their therapeutic and adverse effects. Despite the long use of traditional Chinese herbal medicines, little is known about the potential drug interactions with these herbs. Many popularly used Chinese medicines have been shown in vitro to significantly change the

  5. 16 CFR 1.62 - Ancillary court orders pending review.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Ancillary court orders pending review. 1.62 Section 1.62 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL PROCEDURES Injunctive and Condemnation Proceedings § 1.62 Ancillary court orders pending review...

  6. Cu-62, Cu-64 and Cu-66 production with 4.2 MeV deuterons

    International Nuclear Information System (INIS)

    Avila, Mario; Morales, J.R.; Riquelme, H.O.

    1996-01-01

    Full text: The natural copper irradiation with deuterons produces the Cu-62, Cu-64 and Cu-66 radionuclides. Of two radioisotopes, those with deficiencies in neutrons, are applied in nuclear medicine diagnostic processes, mainly for the nuclear characteristic of the decay modes. The positron emitters, of short life mean Cu-62 (9.1 min, β + ) and Cu(12.7 h), are radionuclides applied in radio pharmacological preparation for brain, core, blood flux studies. The radiochemical process consists in the de solution of the irradiated metallic copper target, in acid medium. The result solution, can be neutralized with a base or a buffer at wished pH. Using a deuteron beam of 4,2 ± 0,1 MeV energy has been obtained total yields of 1,103 ± 0,011 μCl/μAh medium for 62 Cu and of 0,148 ± 0,015 μCl/μAh for 64 Cu

  7. 15 CFR 990.62 - Presenting a demand.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Presenting a demand. 990.62 Section... NATURAL RESOURCE DAMAGE ASSESSMENTS Restoration Implementation Phase § 990.62 Presenting a demand. (a... demand to the responsible parties. Delivery of the demand should be made in a manner that establishes the...

  8. 22 CFR 62.41 - Change of category.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Change of category. 62.41 Section 62.41 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM Status of Exchange... that, in some cases, research skills can be substantially enhanced by doctoral study. (d) An exchange...

  9. 31 CFR 8.62 - Administrative Law Judge.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Administrative Law Judge. 8.62... BUREAU OF ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.62 Administrative Law Judge. (a) Appointment. An Administrative Law Judge, appointed as provided by 5 U.S.C. 3105, shall conduct proceedings...

  10. Characterization of Lactobacillus brevis L62 strain, highly tolerant to copper ions.

    Science.gov (United States)

    Mrvčić, Jasna; Butorac, Ana; Solić, Ema; Stanzer, Damir; Bačun-Družina, Višnja; Cindrić, Mario; Stehlik-Tomas, Vesna

    2013-01-01

    Lactic acid bacteria (LAB) as starter culture in food industry must be suitable for large-scale industrial production and possess the ability to survive in unfavorable processes and storage conditions. Approaches taken to address these problems include the selection of stress-resistant strains. In food industry, LAB are often exposed to metal ions induced stress. The interactions between LAB and metal ions are very poorly investigated. Because of that, the influence of non-toxic, toxic and antioxidant metal ions (Zn, Cu, and Mn) on growth, acid production, metal ions binding capacity of wild and adapted species of Leuconostoc mesenteroides L3, Lactobacillus brevis L62 and Lactobacillus plantarum L73 were investigated. The proteomic approach was applied to clarify how the LAB cells, especially the adapted ones, protect themselves and tolerate high concentrations of toxic metal ions. Results have shown that Zn and Mn addition into MRS medium in the investigated concentrations did not have effect on the bacterial growth and acid production, while copper ions were highly toxic, especially in static conditions. Leuc. mesenteroides L3 was the most efficient in Zn binding processes among the chosen LAB species, while L. plantarum L73 accumulated the highest concentration of Mn. L. brevis L62 was the most copper resistant species. Adaptation had a positive effect on growth and acid production of all species in the presence of copper. However, the adapted species incorporated less metal ions than the wild species. The exception was adapted L. brevis L62 that accumulated high concentration of copper ions in static conditions. The obtained results showed that L. brevis L62 is highly tolerant to copper ions, which allows its use as starter culture in fermentative processes in media with high concentration of copper ions.

  11. Test of the Zweig rule in. pi. /sup -/p interactions at 19 GeV/c

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, P L; Treille, D; Thompson, A S; Strub, R; Sonderegger, P; Palazzi-Cerrina, C; Mitaroff, W A; French, B R [European Organization for Nuclear Research, Geneva (Switzerland); Kumar, R [Glasgow Univ. (UK). Dept. of Natural Philosophy; Kenyon, I R [Birmingham Univ. (UK). Dept. of Physics

    1976-10-25

    Phi production has been observed in ..pi../sup -/p interactions at 19 GeV/c with (44+-10) events in the final state phi..pi../sup +/..pi../sup -/..pi../sup -/p and (45+-9) events in phiK/sup +/K/sup -/..pi../sup -/p. The production ratios phi..pi../sup +/..pi../sup -/..pi../sup -/p/..omega pi../sup +/..pi../sup -/..pi../sup -/p approximately 0.005 and phiK/sup +/K/sup -/..pi../sup -/p/rho/sup 0/K/sup +/K/sup -/..pi../sup -/p approximately 0.45 agree with Zweig-rule expectations.

  12. Molecular basis of Bcl-X(L-p53 interaction: insights from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Nagakumar Bharatham

    Full Text Available Bcl-X(L, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-X(L: BH3 peptide and Bcl-X(L: SN15 peptide (a peptide derived from residues S15-N29 of p53 complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-X(L and other Bcl-2 family proteins have 4 hydrophobic pockets (p1-p4, which are occupied by four systematically spaced hydrophobic residues (h1-h4 of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26 of p53 (SN15 peptide anchor into three hydrophobic pockets (p2-p4 of Bcl-X(L in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-X(L with p53.

  13. 7 CFR 1735.62 - Approval of acquisitions and mergers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Approval of acquisitions and mergers. 1735.62 Section 1735.62 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE... Mortgage Controls on Acquisitions and Mergers § 1735.62 Approval of acquisitions and mergers. (a) If a...

  14. New results from the NA49 experiment on hadron production in p+p and p+C interactions and survey of backward hadrons in p+C collisions

    Directory of Open Access Journals (Sweden)

    Makariev M.

    2013-06-01

    Full Text Available Recent results on proton, anti-proton, neutron and charged kaon production in proton-proton and proton, anti-proton, neutron, deuteron and triton production in proton-carbon collisions at 158 GeV/c beam momentum are presented. Data samples of 4.8 million and 385 734 inelastic events in p+p and p+C, respectively, are obtained with the NA49 detector at the CERN SPS accelerator. The charged particles are identified by energy loss measurement in a system of four TPC chambers, while the neutrons are detected in a forward hadronic calorimeter. The data cover a major fraction of the phase space, ranging from 0 to 1.9 GeV in pT and in Feynman x variable from -0.8 to 0.95 for protons, from -0.2 to 0.3 for anti-protons, from 0.1 to 0.95 for neutrons and from 0 to 0.5 for kaons. The comparison of the results on proton and neutron production in p+p interactions and deep inelastic e+p collisions at HERA reveals an independence of target fragmentation on the projectile type. Using the charged kaon data in p+p collisions as a reference, a new evaluation of the energy dependence of kaon production, including neutral kaons, is conducted over a range from 3 GeV to p+p− collider energies. A survey of backward production of protons and pions in p+C collisions in the range of lab angles from 10 to 180 degrees, from 0.2 to 1.2 GeV/c in lab momentum and from 1 to 400 GeV/c in projectile momentum has been performed.

  15. Combustion system optimization of a P-62 lignite boiler in ContourGlobal Maritsa East 3 with NOx-reduction and efficiency improvement

    International Nuclear Information System (INIS)

    Petkov, Ch.; Thierbach, Hans-Ulrich; Totev, T.

    2013-01-01

    Steinmueller Engineering GmbH, Gummersbach, Germany, successfully concluded in consortium with Siemens EOOD, Sofia, the combustion system modification of a P62 lignite fired boiler in TPP ContourGlobal Maritsa East 3, which was targeting mainly the reduction of the NOx emissions below 180 mg/Nm 3 at 6 % O 2 . The modification is part of an EPC contract covering the design, fabrication, installation and commissioning works needed to upgrade the boilers at the power station. The Modification concept involves optimization of PF- and Vapor distribution, replacement of the coal burners, installation of new Over-fire air (OFA) system and Side-wall air (SWA) system and minor modification of the existing control system to allow control of the OFAflow. The main results of the modification are: Reduction of the NOx emissions (at ESP exit) from approximately 390 g/Nm³ to below 180 mg/Nm³ at 6% O 2 , Efficiency increase of the furnace by reduction of the excess air ratio from 1.2 to 1.15 (at furnace outlet) and overall increase of the boiler efficiency. (authors)

  16. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1.

    Directory of Open Access Journals (Sweden)

    Xiao-Su Zhao

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC-interacting factor 1 (NIF-1, is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  17. p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

    Science.gov (United States)

    Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

  18. LS1 Report: NA62 readies for beam

    CERN Multimedia

    Katarina Anthony

    2014-01-01

    On Wednesday, 10 September, the last NA62 straw tracker chamber was lowered into position in the experiment. This feat brings almost 8 years of CERN construction and design to a close, as the tracker has gone from the drawing board to construction and installation.   The final straw tracker module is lowered into position in NA62. The NA62 straw tracker is one of a kind. As the first of its scale to be placed directly into the vacuum tank of an experiment, it will allow NA62 physicists to measure the direction and momentum of charged particles with high precision. "From the first design to the final plug-in and testing, CERN teams have been 100% involved in developing this unique tracker," says Hans Danielsson, NA62 straw project leader. "We worked in close collaboration with the Joint Institute for Nuclear Research (JINR), Russia, who helped develop the straw tracker technology and will participate in the running of the detector now that construction and installa...

  19. A surrogate p53 reporter in Drosophila reveals the interaction of eIF4E and p53

    International Nuclear Information System (INIS)

    Corujo, G.; Campagno, R.; Rivera Pomar, R.; Ferrero, P.; Lu, W.J.

    2011-01-01

    eIF4E promotes translation upon binding the mRNA 5'cap and it is required for cell proliferation. p53 is a proapoptotic protein which is activated in response to DNA damage. There is evidence that suggests that eIF4E and p53 are connected in a mechanism that regulates their function. We propose a model for that such a mechanism to explain the equilibrium between apoptosis and cell proliferation. Our data shows a correlation between the overexpression of eIF4E and the suppression of apoptosis triggered by the overexpression of p53 in Drosophila imaginal discs. We also studied a reporter transgene which expresses GFP in response to p53 activation by gamma radiation. We could confirm that this p53 surrogate works in imaginal discs as well as in embryos. This provided us a tool to quantify the effect on the GFP signal by overexpression of eIF4E to confirm how these two proteins could interact in vivo. Our results suggest that p53 and eIF4E are indeed in an equilibrium that decides if a cell shall proliferate or die. (authors)

  20. Insight into π-hole interactions containing the inorganic heterocyclic compounds S2N2/SN2P2.

    Science.gov (United States)

    Lu, Bo; Zhang, Xueying; Meng, Lingpeng; Zeng, Yanli

    2017-08-01

    Similar to σ-hole interactions, the π-hole interaction has attracted much attention in recent years. According to the positive electrostatic potentials above and below the surface of inorganic heterocyclic compounds S 2 N 2 and three SN 2 P 2 isomers (heterocyclic compounds 1-4), and the negative electrostatic potential outside the X atom of XH 3 (X = N, P, As), S 2 N 2 /SN 2 P 2 ⋯XH 3 (X = N, P, As) complexes were constructed and optimized at the MP2/aug-cc-pVTZ level. The X atom of XH 3 (X = N, P, As) is almost perpendicular to the ring of the heterocyclic compounds. The π-hole interaction energy becomes greater as the trend goes from 1⋯XH 3 to 4⋯XH 3 . These π-hole interactions are weak and belong to "closed-shell" noncovalent interactions. According to the energy decomposition analysis, of the three attractive terms, the dispersion energy contributes more than the electrostatic energy. The polarization effect also plays an important role in the formation of π-hole complexes, with the contrasting phenomena of decreasing electronic density in the π-hole region and increasing electric density outside the X atom of XH 3 (X = N, P, As). Graphical abstract Computed density difference plots for the complexes 3⋯NH 3 (a 1 ), 3⋯PH 3 (b 1 ), 3⋯AsH 3 (c 1 ) and electron density shifts for the complexes 3⋯NH 3 (a 2 ), 3⋯PH 3 (b 2 ),3⋯AsH 3 (c 2 ) on the 0.001 a.u. contour.

  1. Direct labelling of the human P2X7 receptor and identification of positive and negative cooperativity of binding.

    Science.gov (United States)

    Michel, A D; Chambers, L J; Clay, W C; Condreay, J P; Walter, D S; Chessell, I P

    2007-05-01

    The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. The P2X(7) receptor antagonist, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17), was radiolabelled with tritium and binding studies were performed using membranes prepared from U-2 OS or HEK293 cells expressing human recombinant P2X(7) receptors. Binding of [(3)H]-compound-17 was higher in membranes prepared from cells expressing P2X(7) receptors than from control cells and was inhibited by ATP suggesting labelled sites represented human P2X(7) receptors. Binding was reversible, saturable and modulated by P2X(7) receptor ligands (Brilliant Blue G, KN62, ATP, decavanadate). Furthermore, ATP potency was reduced in the presence of divalent cations or NaCl. Radioligand binding exhibited both positive and negative cooperativity. Positive cooperativity was evident from bell shaped Scatchard plots, reduction in radioligand dissociation rate by unlabelled compound-17 and enhancement of radioligand binding by KN62 and unlabelled compound-17. ATP and decavanadate inhibited binding in a negative cooperative manner as they enhanced radioligand dissociation. These data demonstrate that human P2X(7) receptors can be directly labelled and provide novel insights into receptor function. The positive cooperativity observed suggests that binding of compound-17 to one subunit in the P2X(7) receptor complex enhances subsequent binding to other P2X(7) subunits in the same complex. The negative cooperative effects of ATP suggest that ATP and compound-17 bind at separate, interacting, sites on the P2X(7) receptor.

  2. Improving multilayer films endurance by photoinduced interaction between Dawson-type polyoxometalate and diazo resin

    International Nuclear Information System (INIS)

    Zhang Jishuang; Xu Lin; Cui Yang; Cao Weixiao; Li Zhuang

    2005-01-01

    A composite multilayer film constructed of Dawson anion [P 2 Mo 18 O 62 ] 6- and diazo resin (DR) was prepared by the electrostatic layer-by-layer (LbL) self-assembly method. The film could be stabilized by the photoinduced interaction between Dawson anion and diazo resin. IR spectra and X-ray photoelectron spectra revealed the possible occurrence of partial transformation from electrostatic interaction to covalent interaction between layers of the film after irradiation by UV light. Such transformation evidently increases the endurance of the film, which was demonstrated by AFM images and etching experiments with organic solvent. This study provides a new route to stabilze the polyoxometalate-based multilayer film by virtue of the photoinduced reaction with photosensitive polymer

  3. Improving multilayer films endurance by photoinduced interaction between Dawson-type polyoxometalate and diazo resin

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jishuang [Department of Chemistry, Northeast Normal University, Renmin Street 5268, Changchun 130024 (China); Xu Lin [Department of Chemistry, Northeast Normal University, Renmin Street 5268, Changchun 130024 (China)]. E-mail: linxu@nenu.edu.cn; Cui Yang [Department of Chemistry, Northeast Normal University, Renmin Street 5268, Changchun 130024 (China); Cao Weixiao [College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Li Zhuang [Changchun Institute of Applied Chemistry, Academia Sinica, Changchun 130022 (China)

    2005-03-15

    A composite multilayer film constructed of Dawson anion [P{sub 2}Mo{sub 18}O{sub 62}]{sup 6-} and diazo resin (DR) was prepared by the electrostatic layer-by-layer (LbL) self-assembly method. The film could be stabilized by the photoinduced interaction between Dawson anion and diazo resin. IR spectra and X-ray photoelectron spectra revealed the possible occurrence of partial transformation from electrostatic interaction to covalent interaction between layers of the film after irradiation by UV light. Such transformation evidently increases the endurance of the film, which was demonstrated by AFM images and etching experiments with organic solvent. This study provides a new route to stabilze the polyoxometalate-based multilayer film by virtue of the photoinduced reaction with photosensitive polymer.

  4. Interaction between doubly-excited 4p4nln'l' resonances in KrI

    International Nuclear Information System (INIS)

    Sukhorukov, V L; Petrov, I D; Demekhin, Ph V; Schmoranzer, H; Mickat, S; Kammer, S; Schartner, K-H; Klumpp, S; Werner, L; Ehresmann, A

    2007-01-01

    Photoionization cross sections for the 4p 4 ( 3 P)5s 4 P 5/2,3/2,1/2 satellites and 4s → εl, 4p → εl main lines of Kr II were measured using the photon-induced fluorescence spectroscopy in the exciting-photon energy range between 27.80 eV and 29.44 eV with extremely narrow bandwidth (1.7 meV at 28.55 eV) of the monochromatized synchrotron radiation. The observed resonances were assigned to the 4p 4 5s( 4 P 1/2 )np and 4p 4 5s( 2 P 3/2 )np Rydberg series on the basis of the calculations including core relaxation and interaction between many resonances and many continua. The calculation shows that the resonance structure in the photoionization channels exists due to the 4p 4 ( 1 D)5s 2 D 5/2 6p 3/2 and 4p 4 ( 1 D)5s 2 D 3/2 6p 3/2,1/2 promoter states which strongly perturb the above Rydberg series

  5. 46 CFR 62.35-20 - Oil-fired main boilers.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Oil-fired main boilers. 62.35-20 Section 62.35-20... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-20 Oil-fired main boilers. (a) General. (1) All main boilers, regardless of intended mode of operation, must be provided with the...

  6. Interaction between repressor Opi1p and ER membrane protein Scs2p facilitates transit of phosphatidic acid from the ER to mitochondria and is essential for INO1 gene expression in the presence of choline.

    Science.gov (United States)

    Gaspar, Maria L; Chang, Yu-Fang; Jesch, Stephen A; Aregullin, Manuel; Henry, Susan A

    2017-11-10

    In the yeast Saccharomyces cerevisiae , the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the endoplasmic reticulum (ER) membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus, where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1 A strain devoid of Scs2p ( scs2 Δ) and a mutant, OPI1FFAT , lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism. Loss of the Opi1p-Scs2p interaction reduced INO1 expression and conferred inositol auxotrophy. Moreover, inositol depletion in strains lacking this interaction resulted in Opi1p being localized to sites of lipid droplet formation, coincident with increased synthesis of triacylglycerol. Supplementation of choline to inositol-depleted growth medium led to decreased TAG synthesis in all three strains. However, in strains lacking the Opi1p-Scs2p interaction, Opi1p remained in the nucleus, preventing expression of INO1 These data support the conclusion that a specific pool of phosphatidic acid, associated with lipid droplet formation in the perinuclear ER, is responsible for the initial rapid exit of Opi1p from the nucleus to the ER and is required for INO1 expression in the presence of choline. Moreover, the mitochondria-specific phospholipid, cardiolipin, was significantly reduced in both strains compromised for Opi1p-Scs2p interaction, indicating that this interaction is required for the transfer of phosphatidic acid from the ER to the mitochondria for cardiolipin synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Study on neutron interactions with protons and carbon nuclei at p=4.2 GeV/c

    International Nuclear Information System (INIS)

    Bekmirzaev, R.N.; Muminov, M.M.; Sultanov, M.U.; Grishina, O.V.; Dolejsi, J.; Tas, P.; Trka, Z.

    1988-01-01

    The production of neutrons with p=4.2 GeV/c in d(C 3 H 8 ) collisions and their interaction with proton and carbon nuclei are studied. The experimental material has been obtained using the 2m propane bubble chamber irradiated by deuterons with p=4.2 GeV/c per nucleon at the Dubna synchrophasotron, JINR. The data on multiplicity and momentum characteristics of secondary particles in np and nC interactions compared with the calculations on the LUND model are obtained

  8. Investigation of beam purity after in-trap decay and Coulomb excitation of $^{62}$Mn-$^{62}$Fe

    CERN Multimedia

    Clement, E; Gernhaeuser, R A; Diriken, J V J; Huyse, M L

    2008-01-01

    The in-trap decay of short lived radioactive ions is not well understood. This poses a problem for Coulomb excitation experiments at MINIBALL, where the normalization of the experiment depends strongly on observed secondary target excitation, which in turn strongly depends on the knowledge of the beam composition. For pure ISOLDE beams of short lived isotopes, the in-trap decay becomes important since a large fraction of the beam is transformed in unwanted daughter isotopes. In this proposal we intend to quantify the production of these daughter products in the REXTRAP accurately by making use of the short lived isotopes $^{61,62}$Mn and the newly installed Bragg ionization chamber at the end of the REX linear accelerator. Apart from the technical interest, the A=62 beam provides as well a good physics case, concerning the development of collectivity in neutron-rich Fe isotopes. Coulomb excitation, utilizing the standard MINIBALL setup, is proposed on both A=62 Mn and Fe. The Fe beam would be the first post-a...

  9. Long-range p-d exchange interaction in a ferromagnet-semiconductor hybrid structure

    Science.gov (United States)

    Korenev, V. L.; Salewski, M.; Akimov, I. A.; Sapega, V. F.; Langer, L.; Kalitukha, I. V.; Debus, J.; Dzhioev, R. I.; Yakovlev, D. R.; Müller, D.; Schröder, C.; Hövel, H.; Karczewski, G.; Wiater, M.; Wojtowicz, T.; Kusrayev, Yu. G.; Bayer, M.

    2016-01-01

    Hybrid structures synthesized from different materials have attracted considerable attention because they may allow not only combination of the functionalities of the individual constituents but also mutual control of their properties. To obtain such a control an interaction between the components needs to be established. For coupling the magnetic properties, an exchange interaction has to be implemented which typically depends on wavefunction overlap and is therefore short-ranged, so that it may be compromised across the hybrid interface. Here we study a hybrid structure consisting of a ferromagnetic Co layer and a semiconducting CdTe quantum well, separated by a thin (Cd, Mg)Te barrier. In contrast to the expected p-d exchange that decreases exponentially with the wavefunction overlap of quantum well holes and magnetic atoms, we find a long-ranged, robust coupling that does not vary with barrier width up to more than 30 nm. We suggest that the resulting spin polarization of acceptor-bound holes is induced by an effective p-d exchange that is mediated by elliptically polarized phonons.

  10. Perturbations in the p53/miR-34a/SIRT1 pathway in the R6/2 Huntington's disease model

    DEFF Research Database (Denmark)

    Reynolds, Regina Hertfelder; Petersen, Maria Hvidberg; Willert, Cecilie Wennemoes

    2018-01-01

    The three factors, p53, the microRNA-34 family and Sirtuin 1 (SIRT1), interact in a positive feedback loop involved in cell cycle progression, cellular senescence and apoptosis. Each factor in this triad has roles in metabolic regulation, maintenance of mitochondrial function, and regulation...... of brain-derived neurotrophic factor (BDNF). Thus, this regulatory network holds potential importance for the pathophysiology of Huntington's disease (HD), an inherited neurodegenerative disorder in which both mitochondrial dysfunction and impaired neurotrophic signalling are observed. We investigated...

  11. DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions.

    Science.gov (United States)

    Lambrughi, Matteo; De Gioia, Luca; Gervasio, Francesco Luigi; Lindorff-Larsen, Kresten; Nussinov, Ruth; Urani, Chiara; Bruschi, Maurizio; Papaleo, Elena

    2016-11-02

    Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Final State Interactions and Polarization Observables in the Reaction pp → p

    Directory of Open Access Journals (Sweden)

    Röder Matthias

    2012-12-01

    Full Text Available Due to the lack of high quality hyperon beams, final state interactions in hyperon production reactions are a compelling tool to study hyperon-nucleon interactions. The COSY-TOF experiment has recently been upgraded in order to reconstruct the pK+Λ final state with sufficient precision to determine the spin triplet pΛ scattering length with a polarized proton beam. We find an unexpected behavior of the K+ analyzing power which prevents the extraction method to be used with the available statistics. A theoretical explanation is pending. Furthermore, the polarized beam together with the self analyzing decay of the Λ allows us to determine the Λ depolarization. This is especially sensitive to K+ and π exchange in the production mechanism. Our finding verifies, to a large extent, the result from DISTO [2] that has so far been the only measurement close to the production threshold.

  13. Hard scattering in γp interactions

    International Nuclear Information System (INIS)

    Ahmed, T.; Andreev, V.; Andrieu, B.

    1992-10-01

    We report on the investigation of the final state in interactions of quasi-real photons with protons. The data were taken with the H1 detector at the HERA ep collider. Evidence for hard interactions is seen in both single particle spectra and jet formation. The data can best be described by inclusion of resolved photon processes as predicted by QCD. (orig.)

  14. Interaction of p53 with prolyl isomerases: Healthy and unhealthy relationships.

    Science.gov (United States)

    Mantovani, Fiamma; Zannini, Alessandro; Rustighi, Alessandra; Del Sal, Giannino

    2015-10-01

    The p53 protein family, comprising p53, p63 and p73, is primarily involved in preserving genome integrity and preventing tumor onset, and also affects a range of physiological processes. Signal-dependent modifications of its members and of other pathway components provide cells with a sophisticated code to transduce a variety of stress signaling into appropriate responses. TP53 mutations are highly frequent in cancer and lead to the expression of mutant p53 proteins that are endowed with oncogenic activities and sensitive to stress signaling. p53 family proteins have unique structural and functional plasticity, and here we discuss the relevance of prolyl-isomerization to actively shape these features. The anti-proliferative functions of the p53 family are carefully activated upon severe stress and this involves the interaction with prolyl-isomerases. In particular, stress-induced stabilization of p53, activation of its transcriptional control over arrest- and cell death-related target genes and of its mitochondrial apoptotic function, as well as certain p63 and p73 functions, all require phosphorylation of specific S/T-P motifs and their subsequent isomerization by the prolyl-isomerase Pin1. While these functions of p53 counteract tumorigenesis, under some circumstances their activation by prolyl-isomerases may have negative repercussions (e.g. tissue damage induced by anticancer therapies and ischemia-reperfusion, neurodegeneration). Moreover, elevated Pin1 levels in tumor cells may transduce deregulated phosphorylation signaling into activation of mutant p53 oncogenic functions. The complex repertoire of biological outcomes induced by p53 finds mechanistic explanations, at least in part, in the association between prolyl-isomerases and the p53 pathway. This article is part of a Special Issue entitled Proline-directed foldases: Cell signaling catalysts and drug targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions.

    Science.gov (United States)

    The human efflux transporter P-glycoprotein (P-gp; MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure ass...

  16. Time reversal violation in the nuclear interaction and p(pol)-/sup 3/He scattering

    Energy Technology Data Exchange (ETDEWEB)

    Simonius, M [Eidgenoessische Technische Hochschule, Zurich (Switzerland). Lab. fuer Kernphysik; Wyler, D [Carnegie-Mellon Univ., Pittsburgh, Pa. (USA). Dept. of Physics

    1977-08-08

    Using T-violating boson-exchange interactions T-violating effects in low energy p-/sup 3/He scattering are calculated. The results are below 10/sup -3/ even for full strong (not millistrong) T-violation in the nucleon-nucleon system. It is argued, that the smallness of the effects is not a particularity of the p-/sup 3/He system but a general property of low energy processes.

  17. p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200.

    Science.gov (United States)

    Morselli, Eugenia; Shen, Shensi; Ruckenstuhl, Christoph; Bauer, Maria Anna; Mariño, Guillermo; Galluzzi, Lorenzo; Criollo, Alfredo; Michaud, Mickael; Maiuri, Maria Chiara; Chano, Tokuhiro; Madeo, Frank; Kroemer, Guido

    2011-08-15

    The tumor suppressor protein p53 tonically suppresses autophagy when it is present in the cytoplasm. This effect is phylogenetically conserved from mammals to nematodes, and human p53 can inhibit autophagy in yeast, as we show here. Bioinformatic investigations of the p53 interactome in relationship to the autophagy-relevant protein network underscored the possible relevance of a direct molecular interaction between p53 and the mammalian ortholog of the essential yeast autophagy protein Atg17, namely RB1-inducible coiled-coil protein 1 (RB1CC1), also called FAK family kinase-interacting protein of 200 KDa (FIP200). Mutational analyses revealed that a single point mutation in p53 (K382R) abolished its capacity to inhibit autophagy upon transfection into p53-deficient human colon cancer or yeast cells. In conditions in which wild-type p53 co-immunoprecipitated with RB1CC1/FIP200, p53 (K382R) failed to do so, underscoring the importance of the physical interaction between these proteins for the control of autophagy. In conclusion, p53 regulates autophagy through a direct molecular interaction with RB1CC1/FIP200, a protein that is essential for the very apical step of autophagy initiation.

  18. Peculiarities of interaction of the p{sub z}-, π- electrons and the σ{sub p}-holes at the top 1–6 layers of HOPG

    Energy Technology Data Exchange (ETDEWEB)

    Dementjev, A.P., E-mail: demcarbon@yandex.ru; Ivanov, K.E.

    2017-03-31

    Graphical abstract: The formation of π-bands and σ{sub p}- holes as result of the p{sub z} → π transitions in 2–6 graphene layers HOPG. The valence band spectrum taken from Murday et al. (1981). - Abstract: The present work continues the analysis of results of Dementjev et al. (2015) in order to identify the interlayer interactions of the π-bands. Analysis of the N(E) C KVV Auger spectra of highly-ordered pyro-graphite showed the absence of the electron exchange between the π-bands in 1–6 layers. Since the π-bands are formed by the p{sub z} → π transitions, one can suggest that the π-band occupation at each graphene layer is formed by the p{sub z}-electrons of this layer. Since the p{sub z} electrons belong to the σ{sub p}-bands, the p{sub z} → π transitions in the σ{sub p}-bands in each of 2–6 graphene layers result in formation of holes H, whose concentration is equal to the concentration of electrons in the π-bands [H{sub i}] ≡ [π{sub i}]. This shows the origin of the ambipolar conductivity in graphene. The absence of the electronic interaction between the π-bands allows a suggestion that the interaction between top six graphene layers is due to the van der Waals electrostatic attractive forces. These forces promote the p{sub z} → π transitions in each of the 2–6 graphene layers and depend on the number of graphene layers above. The N(E) C KVV Auger spectra allow identification of number (1–6) of graphene layers and the π-band occupation at each of the layer. For the first time a specification of the van der Waals forces in HOPG was done.

  19. Interactions between the otitis media gene, Fbxo11, and p53 in the mouse embryonic lung.

    Science.gov (United States)

    Tateossian, Hilda; Morse, Susan; Simon, Michelle M; Dean, Charlotte H; Brown, Steve D M

    2015-12-01

    Otitis media with effusion (OME) is the most common cause of hearing loss in children, and tympanostomy (ear tube insertion) to alleviate the condition remains the commonest surgical intervention in children in the developed world. Chronic and recurrent forms of otitis media (OM) are known to have a very substantial genetic component; however, until recently, little was known of the underlying genes involved. The Jeff mouse mutant carries a mutation in the Fbxo11 gene, a member of the F-box family, and develops deafness due to a chronic proliferative OM. We previously reported that Fbxo11 is involved in the regulation of transforming growth factor beta (TGF-β) signalling by regulating the levels of phospho-Smad2 in the epithelial cells of palatal shelves, eyelids and airways of the lungs. It has been proposed that FBXO11 regulates the cell's response to TGF-β through the ubiquitination of CDT2. Additional substrates for FBXO11 have been identified, including p53. Here, we have studied both the genetic and biochemical interactions between FBXO11 and p53 in order to better understand the function of FBXO11 in epithelial development and its potential role in OM. In mice, we show that p53 (also known as Tp53) homozygous mutants and double heterozygous mutants (Jf/+ p53/+) exhibit similar epithelial developmental defects to Fbxo11 homozygotes. FBXO11 and p53 interact in the embryonic lung, and mutation in Fbxo11 prevents the interaction with p53. Both p53 and double mutants show raised levels of pSMAD2, recapitulating that seen in Fbxo11 homozygotes. Overall, our results support the conclusion that FBXO11 regulates the TGF-β pathway in the embryonic lung via cross-talk with p53. © 2015. Published by The Company of Biologists Ltd.

  20. Purinergní P2X rodina a specifické vlastnosti P2X7 podtypu

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Marie; Zemková, Hana

    2013-01-01

    Roč. 62, č. 2 (2013), s. 40-46 ISSN 1210-6313 R&D Projects: GA ČR(CZ) GPP304/12/P371 Institutional support: RVO:67985823 Keywords : extracellular ATP * purinergic P2X family * P2X7 receptor * cell proliferation and apoptosis Subject RIV: ED - Physiology

  1. Feed forward neural networks modeling for K-P interactions

    International Nuclear Information System (INIS)

    El-Bakry, M.Y.

    2003-01-01

    Artificial intelligence techniques involving neural networks became vital modeling tools where model dynamics are difficult to track with conventional techniques. The paper make use of the feed forward neural networks (FFNN) to model the charged multiplicity distribution of K-P interactions at high energies. The FFNN was trained using experimental data for the multiplicity distributions at different lab momenta. Results of the FFNN model were compared to that generated using the parton two fireball model and the experimental data. The proposed FFNN model results showed good fitting to the experimental data. The neural network model performance was also tested at non-trained space and was found to be in good agreement with the experimental data

  2. Thermodynamics of interactions between mammalian cytochromes P450 and b5.

    Science.gov (United States)

    Yablokov, Evgeny; Florinskaya, Anna; Medvedev, Alexei; Sergeev, Gennady; Strushkevich, Natallia; Luschik, Alexander; Shkel, Tatsiana; Haidukevich, Irina; Gilep, Andrei; Usanov, Sergey; Ivanov, Alexis

    2017-04-01

    Cytochromes P450 (CYPs) play an important role in the metabolism of xenobiotics and various endogenous substrates. Being a crucial component of the microsomal monooxygenase system, CYPs are involved in numerous protein-protein interactions. However, mechanisms underlying molecular interactions between components of the monooxygenase system still need better characterization. In this study thermodynamic parameters of paired interactions between mammalian CYPs and cytochromes b5 (CYB5) have been evaluated using a Surface Plasmon Resonance (SPR) based biosensor Biacore 3000. Analysis of 18 pairs of CYB5-CYP complexes formed by nine different isoforms of mammalian CYPs and two isoforms of human CYB5 has shown that thermodynamically these complexes can be subdivided into enthalpy-driven and entropy-driven groups. Formation of the enthalpy-driven complexes was observed in the case of microsomal CYPs allosterically regulated by CYB5 (CYB5A-CYP3A4, CYB5A-CYP3A5, CYB5A-CYP17A1). The entropy-driven complexes were formed when CYB5 had no effect on the CYP activity (CYB5A-CYP51A1, CYB5A-CYP1B1, CYB5B-CYP11A1). Results of this study suggest that such interactions determining protein clustering are indirectly linked to the monooxygenase functioning. Positive ΔH values typical for such interactions may be associated with displacement of the solvation shells of proteins upon clustering. CYB5-CYP complex formation accompanied by allosteric regulation of CYP activity by CYB5 is enthalpy-dependent. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Measurements of Multiparticle Correlations in d +Au Collisions at 200, 62.4, 39, and 19.6 GeV and p +Au Collisions at 200 GeV and Implications for Collective Behavior

    Science.gov (United States)

    Aidala, C.; Akiba, Y.; Alfred, M.; Andrieux, V.; Aoki, K.; Apadula, N.; Asano, H.; Ayuso, C.; Azmoun, B.; Babintsev, V.; Bagoly, A.; Bandara, N. S.; Barish, K. N.; Bathe, S.; Bazilevsky, A.; Beaumier, M.; Belmont, R.; Berdnikov, A.; Berdnikov, Y.; Blau, D. S.; Boer, M.; Bok, J. S.; Brooks, M. L.; Bryslawskyj, J.; Bumazhnov, V.; Butler, C.; Campbell, S.; Canoa Roman, V.; Cervantes, R.; Chi, C. Y.; Chiu, M.; Choi, I. J.; Choi, J. B.; Citron, Z.; Connors, M.; Cronin, N.; Csanád, M.; Csörgő, T.; Danley, T. W.; Daugherity, M. S.; David, G.; Deblasio, K.; Dehmelt, K.; Denisov, A.; Deshpande, A.; Desmond, E. J.; Dion, A.; Dixit, D.; Do, J. H.; Drees, A.; Drees, K. A.; Dumancic, M.; Durham, J. M.; Durum, A.; Elder, T.; Enokizono, A.; En'yo, H.; Esumi, S.; Fadem, B.; Fan, W.; Feege, N.; Fields, D. E.; Finger, M.; Finger, M.; Fokin, S. L.; Frantz, J. E.; Franz, A.; Frawley, A. D.; Fukuda, Y.; Gal, C.; Gallus, P.; Garg, P.; Ge, H.; Giordano, F.; Goto, Y.; Grau, N.; Greene, S. V.; Grosse Perdekamp, M.; Gunji, T.; Guragain, H.; Hachiya, T.; Haggerty, J. S.; Hahn, K. I.; Hamagaki, H.; Hamilton, H. F.; Han, S. Y.; Hanks, J.; Hasegawa, S.; Haseler, T. O. S.; He, X.; Hemmick, T. K.; Hill, J. C.; Hill, K.; Hodges, A.; Hollis, R. S.; Homma, K.; Hong, B.; Hoshino, T.; Hotvedt, N.; Huang, J.; Huang, S.; Imai, K.; Imrek, J.; Inaba, M.; Iordanova, A.; Isenhower, D.; Ito, Y.; Ivanishchev, D.; Jacak, B. V.; Jezghani, M.; Ji, Z.; Jiang, X.; Johnson, B. M.; Jorjadze, V.; Jouan, D.; Jumper, D. S.; Kang, J. H.; Kapukchyan, D.; Karthas, S.; Kawall, D.; Kazantsev, A. V.; Khachatryan, V.; Khanzadeev, A.; Kim, C.; Kim, D. J.; Kim, E.-J.; Kim, M.; Kim, M. H.; Kincses, D.; Kistenev, E.; Klatsky, J.; Kline, P.; Koblesky, T.; Kotov, D.; Kudo, S.; Kurita, K.; Kwon, Y.; Lajoie, J. G.; Lallow, E. O.; Lebedev, A.; Lee, S.; Lee, S. H.; Leitch, M. J.; Leung, Y. H.; Lewis, N. A.; Li, X.; Lim, S. H.; Liu, L. D.; Liu, M. X.; Loggins, V.-R.; Lökös, S.; Lovasz, K.; Lynch, D.; Majoros, T.; Makdisi, Y. I.; Makek, M.; Malaev, M.; Manko, V. I.; Mannel, E.; Masuda, H.; McCumber, M.; McGaughey, P. L.; McGlinchey, D.; McKinney, C.; Mendoza, M.; Metzger, W. J.; Mignerey, A. C.; Mihalik, D. E.; Milov, A.; Mishra, D. K.; Mitchell, J. T.; Mitsuka, G.; Miyasaka, S.; Mizuno, S.; Montuenga, P.; Moon, T.; Morrison, D. P.; Morrow, S. I. M.; Murakami, T.; Murata, J.; Nagai, K.; Nagashima, K.; Nagashima, T.; Nagle, J. L.; Nagy, M. I.; Nakagawa, I.; Nakagomi, H.; Nakano, K.; Nattrass, C.; Niida, T.; Nouicer, R.; Novák, T.; Novitzky, N.; Novotny, R.; Nyanin, A. S.; O'Brien, E.; Ogilvie, C. A.; Orjuela Koop, J. D.; Osborn, J. D.; Oskarsson, A.; Ottino, G. J.; Ozawa, K.; Pantuev, V.; Papavassiliou, V.; Park, J. S.; Park, S.; Pate, S. F.; Patel, M.; Peng, W.; Perepelitsa, D. V.; Perera, G. D. N.; Peressounko, D. Yu.; Perezlara, C. E.; Perry, J.; Petti, R.; Phipps, M.; Pinkenburg, C.; Pisani, R. P.; Pun, A.; Purschke, M. L.; Radzevich, P. V.; Read, K. F.; Reynolds, D.; Riabov, V.; Riabov, Y.; Richford, D.; Rinn, T.; Rolnick, S. D.; Rosati, M.; Rowan, Z.; Runchey, J.; Safonov, A. S.; Sakaguchi, T.; Sako, H.; Samsonov, V.; Sarsour, M.; Sato, K.; Sato, S.; Schaefer, B.; Schmoll, B. K.; Sedgwick, K.; Seidl, R.; Sen, A.; Seto, R.; Sexton, A.; Sharma, D.; Shein, I.; Shibata, T.-A.; Shigaki, K.; Shimomura, M.; Shioya, T.; Shukla, P.; Sickles, A.; Silva, C. L.; Silvermyr, D.; Singh, B. K.; Singh, C. P.; Singh, V.; Skoby, M. J.; Slunečka, M.; Smith, K. L.; Snowball, M.; Soltz, R. A.; Sondheim, W. E.; Sorensen, S. P.; Sourikova, I. V.; Stankus, P. W.; Stoll, S. P.; Sugitate, T.; Sukhanov, A.; Sumita, T.; Sun, J.; Syed, S.; Sziklai, J.; Takeda, A.; Tanida, K.; Tannenbaum, M. J.; Tarafdar, S.; Taranenko, A.; Tarnai, G.; Tieulent, R.; Timilsina, A.; Todoroki, T.; Tomášek, M.; Towell, C. L.; Towell, R. S.; Tserruya, I.; Ueda, Y.; Ujvari, B.; van Hecke, H. W.; Vazquez-Carson, S.; Velkovska, J.; Virius, M.; Vrba, V.; Vukman, N.; Wang, X. R.; Wang, Z.; Watanabe, Y.; Watanabe, Y. S.; Wong, C. P.; Woody, C. L.; Xu, C.; Xu, Q.; Xue, L.; Yalcin, S.; Yamaguchi, Y. L.; Yamamoto, H.; Yanovich, A.; Yin, P.; Yoo, J. H.; Yoon, I.; Yu, H.; Yushmanov, I. E.; Zajc, W. A.; Zelenski, A.; Zharko, S.; Zou, L.; Phenix Collaboration

    2018-02-01

    Recently, multiparticle-correlation measurements of relativistic p /d /He 3 +Au , p +Pb , and even p +p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d +Au collisions at √{sN N}=200 , 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p +Au collisions at √{sN N}=200 GeV . We find the four-particle cumulant to be real valued for d +Au collisions at all four energies. We also find that the four-particle cumulant in p +Au has the opposite sign as that in d +Au . Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d +Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.

  4. Neutral strange particle production in π+/K+p interactions at 250 GeV/c

    International Nuclear Information System (INIS)

    Scholten, A.J.

    1988-01-01

    This thesis in which a detailed study of K n inclusive production in K + p and π + p interactions at 250 GeV/c is presented, concentrates on neutral strange interaction products and draws some conclusions about the fate of the strange quark. In ch. 2 the experimental setup is described and in ch. 3 the series of computer programs that perform data reduction. Ch. 4 deals with the selectionn of events and neutral kaons. Also the calculations needed to correct for losses and background are described there. In ch. 5 inclusive and semi-inclusive distributions are presented and compared to data obtained in experiments at lower beam energy. In ch. 6 the data are compared with model predictions. In ch. 7 the main conclusions are summarized. (H.W.). 64 refs.; 39 refs.; 19 tabs

  5. High-resolution measurements of sup(58,60,62)Ni(p,p) scattering cross section in the proton energy range of 3.0 to 4.0 MeV

    International Nuclear Information System (INIS)

    Arai, Eiichi; Ogawa, Masao

    1976-01-01

    Differential cross sections were measured at four angles for proton scattering on sup(58,60,62)Ni at energies from 3.0 to 4.0 MeV by using a high-resolution beam from the Tokyo Institute of Technology 4 MV Van de Graaff. An overall resolution of 400 eV (FWHM) was realized using thin solid targets. (author)

  6. 40 CFR 141.62 - Maximum contaminant levels for inorganic contaminants.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Maximum contaminant levels for inorganic contaminants. 141.62 Section 141.62 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Water Regulations: Maximum Contaminant Levels and Maximum Residual Disinfectant Levels § 141.62 Maximum...

  7. Bose-Einstein correlations in αα,pp and panti p interactions

    International Nuclear Information System (INIS)

    Akesson, T.; Batley, R.; Breuker, H.; Dam, P.; Eidelman, S.; Fabjan, C.W.; Frandsen, P.; Goerlach, U.; Heck, B.; Hilke, H.J.; Jeffreys, P.; Kalinovsky, A.; Kesseler, G.; Lans, J. van der; Lindsay, J.; Markou, A.; Nielsen, B.S.; Olsen, L.H.; Rosselet, L.; Schindler, R.; Willis, W.J.; Witzeling, W.; Albrow, M.G.; Cockerill, D.; Evans, W.M.; Gibson, M.; Hiddleston, J.; McCubbin, N.A.; Williamson, J.; Benary, O.; Dagan, S.; Lissauer, D.; Oren, Y.; Boeggild, H.; Botner, O.; Dahl-Jensen, E.; Dahl-Jensen, I.; Damgaard, G.; Hansen, K.H.; Hooper, J.; Moeller, R.; Brody, H.; Frankel, S.; Frati, W.; Molzon, W.; Vella, E.; Zajc, W.A.; Burkert, V.; Rosso, E.; Rudge, A.; Carter, J.R.; Cecil, P.; Chung, S.U.; Gordon, H.; Killian, T.; Ludlam, T.; Winik, M.; Woody, C.; Cleland, W.E.; Kroeger, R.; Sullivan, M.

    1983-01-01

    Bose-Einstein correlations between pions produced in the central region of rapidity in αα, pp and panti p interactions have been studied at the ISR. The parameters r and tauc - often interpreted as the radius and depth of the π-emitting region - are found to be independent of incident particle type but to depend on the mean charged multiplicity. In high multiplicity events, the pions appear to originate from a larger space - time region. (orig.)

  8. 22 CFR 62.11 - Duties of responsible officers.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Duties of responsible officers. 62.11 Section 62.11 Foreign Relations DEPARTMENT OF STATE PUBLIC DIPLOMACY AND EXCHANGES EXCHANGE VISITOR PROGRAM... facilitate the successful completion of the exchange visitor's program. (c) Communications. Conduct the...

  9. The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export*

    Science.gov (United States)

    Port, Sarah A.; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H.

    2016-01-01

    Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A)+ RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. PMID:27613868

  10. The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export.

    Science.gov (United States)

    Port, Sarah A; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H

    2016-10-28

    Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A) + RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A) + RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Stress regulates the lymphocyte homing receptor CD62L (L-selectin Regulação do receptor de alojamento linfocitário CD62L (L-selectina pelo estresse

    Directory of Open Access Journals (Sweden)

    Gisele Gus Manfro

    2003-03-01

    Full Text Available Based on a previous study showing that panic disorder patients had increased expression of naïve phenotype lymphocytes (CD45RA+ and CD62L+, increased plasma cortisol, as well as decreased interleukin-2 (IL-2 producion, we hypothesized that changes in the percentage of expression of these lymphocyte surface molecules could be related to the substances released by the hypothalamic-pituitary-adrenal (HPA axis and possibly associated to panic disorder (cortisol, IL-2, serotonin and epinephrine. In order to study the altered expression, blood mononuclear cells of normal volunteers were stimulated with mitogen, in the presence of dexamethasone, IL-2, serotonin and epinephrin. CD62L is decreased by IL-2 in vitro. Serotonin and epinephrine did not promote changes in the expression of these surface molecules. The results of the ex vivo study are in agreement with a previous clinical study with panic patients. It could be suggested that stress is responsible for certain immunologic dysfunctions and new studies should be conducted.Baseado em estudo prévio que demonstrou que os pacientes com transtorno do pânico apresentavam aumento na porcentagem de expressão de linfócitos com fenótipo virgem (CD45RA+ e CD62L+, aumento no cortisol plasmático, assim como diminuição na produção de interleucinas, foi sugerido que as alterações na porcentagem de expressão dessas moléculas de superfície dos linfócitos poderia estar relacionada com a liberação de substâncias pelo eixo hipotálamo-hipófise-adrenal (HHA e possivelmente associada ao transtorno do pânico (cortisol, IL-2, serotonina e epinefrina. Com o objetivo de estudar essas alterações, células mononucleares do sangue periférico de voluntários normais foram estimuladas com mitógeno, na presença de dexametasona, IL-2, serotonina e epinefrina. A expressão de CD62L "in vitro" é diminuida com IL-2. Serotonina e epinefrina não promovem alterações na expressão dessas moléculas de

  12. 49 CFR 1242.62 - Clearing wrecks (account XX-51-63).

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Clearing wrecks (account XX-51-63). 1242.62 Section 1242.62 Transportation Other Regulations Relating to Transportation (Continued) SURFACE...-Transportation § 1242.62 Clearing wrecks (account XX-51-63). Separate common expenses according to specific...

  13. Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Xue-Ming Li

    2015-01-01

    Full Text Available Aim of Study: To assess the impact of glutathione S-transferase P1 (GSTP1 Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Materials and Methods: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations. Results: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR = 1.36, 95% CI = 1.01-1.84. In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR = 1.62, 95% CI: 1.13-2.31; GG vs. AG: OR = 1.49, 95% CI: 1.03-2.16; GG vs. AA + AG: OR = 1.55, 95% CI: 1.12-2.26. A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1 null genotype and GSTP1 (AG + GG mutant genotype for lung cancer risk in Chinese. Conclusion: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

  14. 22 CFR 62.20 - Professors and research scholars.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Professors and research scholars. 62.20 Section... Specific Program Provisions § 62.20 Professors and research scholars. (a) Introduction. These regulations govern Exchange Visitor Program participants in the categories of professor and research scholar, except...

  15. Detector recycling leads NA62 to new standards

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    The NA62 collaboration has just installed the first eight (out of 12) Large Angle Veto detectors for the accurate identification of photons. These subdetectors will re-use 3000 lead glass crystals with attached photomultipliers from the OPAL experiment at LEP – CERN’s former accelerator. This will give a second life to the crystals and is a great opportunity for the collaboration to save money while ensuring the required performance.   One of the LAV stations is lowered into the NA62 decay volume. The accurate identification of photons is a vital requirement of the whole NA62 physics programme. A failure in the system could lead to signals that mimic the very rare processes that the experiment is looking for, jeopardising the whole measurement. While it has not compromised on the overall performance of its detector, the NA62 collaboration has welcomed the challenge of re-using some existing equipment rather than developing new, more expensive solutions.  The tho...

  16. Liferay 6.2 user interface development

    CERN Document Server

    Chen, Xinsheng

    2013-01-01

    A step-by-step tutorial, targeting the Liferay 6.2 version. This book takes a step-by-step approach to customizing the look and feel of your website, and shows you how to build a great looking user interface as well.""Liferay 6.2 User Interface Development"" is for anyone who is interested in the Liferay Portal. It contains text that explicitly introduces you to the Liferay Portal. You will benefit most from this book if you have Java programming experience and have coded servlets or JavaServer Pages before. Experienced Liferay portal developers will also find this book useful because it expla

  17. Identification of host cell proteins which interact with herpes simplex virus type 1 tegument protein pUL37.

    Science.gov (United States)

    Kelly, Barbara J; Diefenbach, Eve; Fraefel, Cornel; Diefenbach, Russell J

    2012-01-20

    The herpes simplex virus type 1 (HSV-1) structural tegument protein pUL37, which is conserved across the Herpesviridae family, is known to be essential for secondary envelopment during the egress of viral particles. To shed light on additional roles of pUL37 during viral replication a yeast two-hybrid screen of a human brain cDNA library was undertaken. This screen identified ten host cell proteins as potential pUL37 interactors. One of the interactors, serine threonine kinase TAOK3, was subsequently confirmed to interact with pUL37 using an in vitro pulldown assay. Such host cell/pUL37 interactions provide further insights into the multifunctional role of this herpesviral tegument protein. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. RSAC 6.2 with WinRP 2.0 User Manual

    Energy Technology Data Exchange (ETDEWEB)

    Bradley Schrader

    2005-09-01

    The Radiological Safety Analysis Computer Program (RSAC-6.2) calculates the consequences of a release of radionuclides to the atmosphere. Using a personal computer, a user can generate a fission product inventory from either reactor operating history or a nuclear criticality accident. RSAC-6.2 models the effects of high-efficiency particulate air filters or other cleanup systems and calculates decay and ingrowth during transport through processes, facilities, and the environment. Doses are calculated for resuspension, inhalation, immersion, ground surface, and ingestion pathways. WinRP 2.0, a windows based overlay to RSAC-6.2, assists users in creating and running RSAC-6.2 input files. This users manual contains the mathematical models and operating instructions for RSAC-6.2 and WinRP 2.0. Instructions, screens, and examples are provided to guide the user through the functions provided by RSAC-6.2 and WinRP 2.0. These programs are designed for users who are familiar with radiological dose assessment methods.

  19. Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export.

    Science.gov (United States)

    Krebber, H; Taura, T; Lee, M S; Silver, P A

    1999-08-01

    Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear.

  20. 7 CFR 62.204 - Authority to request service.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Authority to request service. 62.204 Section 62.204 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards... prove his/her financial interest in the product or service at the discretion of the Deputy Administrator. ...

  1. 14 CFR 298.62 - Reporting of financial data.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Reporting of financial data. 298.62 Section... PROCEEDINGS) ECONOMIC REGULATIONS EXEMPTIONS FOR AIR TAXI AND COMMUTER AIR CARRIER OPERATIONS Reporting Requirements § 298.62 Reporting of financial data. (a) Each commuter air carrier and each small certificated...

  2. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS iv: magnesium modulation at pH 7.20

    Directory of Open Access Journals (Sweden)

    Ali Akbar Moosavi-Movahedi

    2016-03-01

    Full Text Available We investigate the interaction of Mg2+ (0–2.30 mM and sodium n-dodecyl sulfate (SDS with hemoglobins (Hbs A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS and proteases (5.0 mM SDS. Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg2+]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg2+] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.

  3. 30 CFR 18.62 - Tests to determine explosion-proof characteristics.

    Science.gov (United States)

    2010-07-01

    ... characteristics. 18.62 Section 18.62 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Inspections and Tests § 18.62 Tests to determine explosion-proof characteristics. (a) In testing for explosion-proof characteristics of an enclosure, it shall be filled and surrounded with various explosive mixtures...

  4. Elliptic flow of electrons from heavy-flavor hadron decays in Au + Au collisions at √{sN N}=200 , 62.4, and 39 GeV

    Science.gov (United States)

    Adamczyk, L.; Adkins, J. K.; Agakishiev, G.; Aggarwal, M. M.; Ahammed, Z.; Ajitanand, N. N.; Alekseev, I.; Anderson, D. M.; Aoyama, R.; Aparin, A.; Arkhipkin, D.; Aschenauer, E. C.; Ashraf, M. U.; Attri, A.; Averichev, G. S.; Bai, X.; Bairathi, V.; Behera, A.; Bellwied, R.; Bhasin, A.; Bhati, A. K.; Bhattarai, P.; Bielcik, J.; Bielcikova, J.; Bland, L. C.; Bordyuzhin, I. G.; Bouchet, J.; Brandenburg, J. D.; Brandin, A. V.; Brown, D.; Bunzarov, I.; Butterworth, J.; Caines, H.; Calderón de la Barca Sánchez, M.; Campbell, J. M.; Cebra, D.; Chakaberia, I.; Chaloupka, P.; Chang, Z.; Chankova-Bunzarova, N.; Chatterjee, A.; Chattopadhyay, S.; Chen, X.; Chen, J. H.; Chen, X.; Cheng, J.; Cherney, M.; Christie, W.; Contin, G.; Crawford, H. J.; Das, S.; De Silva, L. C.; Debbe, R. R.; Dedovich, T. G.; Deng, J.; Derevschikov, A. A.; Didenko, L.; Dilks, C.; Dong, X.; Drachenberg, J. L.; Draper, J. E.; Dunkelberger, L. E.; Dunlop, J. C.; Efimov, L. G.; Elsey, N.; Engelage, J.; Eppley, G.; Esha, R.; Esumi, S.; Evdokimov, O.; Ewigleben, J.; Eyser, O.; Fatemi, R.; Fazio, S.; Federic, P.; Federicova, P.; Fedorisin, J.; Feng, Z.; Filip, P.; Finch, E.; Fisyak, Y.; Flores, C. E.; Fulek, L.; Gagliardi, C. A.; Garand, D.; Geurts, F.; Gibson, A.; Girard, M.; Grosnick, D.; Gunarathne, D. S.; Guo, Y.; Gupta, S.; Gupta, A.; Guryn, W.; Hamad, A. I.; Hamed, A.; Harlenderova, A.; Harris, J. W.; He, L.; Heppelmann, S.; Heppelmann, S.; Hirsch, A.; Hoffmann, G. W.; Horvat, S.; Huang, H. Z.; Huang, X.; Huang, B.; Huang, T.; Humanic, T. J.; Huo, P.; Igo, G.; Jacobs, W. W.; Jentsch, A.; Jia, J.; Jiang, K.; Jowzaee, S.; Judd, E. G.; Kabana, S.; Kalinkin, D.; Kang, K.; Kauder, K.; Ke, H. W.; Keane, D.; Kechechyan, A.; Khan, Z.; Kikoła, D. P.; Kisel, I.; Kisiel, A.; Kochenda, L.; Kocmanek, M.; Kollegger, T.; Kosarzewski, L. K.; Kraishan, A. F.; Kravtsov, P.; Krueger, K.; Kulathunga, N.; Kumar, L.; Kvapil, J.; Kwasizur, J. H.; Lacey, R.; Landgraf, J. M.; Landry, K. D.; Lauret, J.; Lebedev, A.; Lednicky, R.; Lee, J. H.; Li, X.; Li, C.; Li, Y.; Li, W.; Lidrych, J.; Lin, T.; Lisa, M. A.; Liu, P.; Liu, Y.; Liu, F.; Liu, H.; Ljubicic, T.; Llope, W. J.; Lomnitz, M.; Longacre, R. S.; Luo, X.; Luo, S.; Ma, Y. G.; Ma, L.; Ma, R.; Ma, G. L.; Magdy, N.; Majka, R.; Mallick, D.; Margetis, S.; Markert, C.; Matis, H. S.; Meehan, K.; Mei, J. C.; Miller, Z. W.; Minaev, N. G.; Mioduszewski, S.; Mishra, D.; Mizuno, S.; Mohanty, B.; Mondal, M. M.; Morozov, D. A.; Mustafa, M. K.; Nasim, Md.; Nayak, T. K.; Nelson, J. M.; Nie, M.; Nigmatkulov, G.; Niida, T.; Nogach, L. V.; Nonaka, T.; Nurushev, S. B.; Odyniec, G.; Ogawa, A.; Oh, K.; Okorokov, V. A.; Olvitt, D.; Page, B. S.; Pak, R.; Pandit, Y.; Panebratsev, Y.; Pawlik, B.; Pei, H.; Perkins, C.; Pile, P.; Pluta, J.; Poniatowska, K.; Porter, J.; Posik, M.; Poskanzer, A. M.; Pruthi, N. K.; Przybycien, M.; Putschke, J.; Qiu, H.; Quintero, A.; Ramachandran, S.; Ray, R. L.; Reed, R.; Rehbein, M. J.; Ritter, H. G.; Roberts, J. B.; Rogachevskiy, O. V.; Romero, J. L.; Roth, J. D.; Ruan, L.; Rusnak, J.; Rusnakova, O.; Sahoo, N. R.; Sahu, P. K.; Salur, S.; Sandweiss, J.; Saur, M.; Schambach, J.; Schmah, A. M.; Schmidke, W. B.; Schmitz, N.; Schweid, B. R.; Seger, J.; Sergeeva, M.; Seyboth, P.; Shah, N.; Shahaliev, E.; Shanmuganathan, P. V.; Shao, M.; Sharma, M. K.; Sharma, A.; Shen, W. Q.; Shi, Z.; Shi, S. S.; Shou, Q. Y.; Sichtermann, E. P.; Sikora, R.; Simko, M.; Singha, S.; Skoby, M. J.; Smirnov, N.; Smirnov, D.; Solyst, W.; Song, L.; Sorensen, P.; Spinka, H. M.; Srivastava, B.; Stanislaus, T. D. S.; Stock, R.; Strikhanov, M.; Stringfellow, B.; Sugiura, T.; Sumbera, M.; Summa, B.; Sun, Y.; Sun, X. M.; Sun, X.; Surrow, B.; Svirida, D. N.; Tang, A. H.; Tang, Z.; Taranenko, A.; Tarnowsky, T.; Tawfik, A.; Thäder, J.; Thomas, J. H.; Timmins, A. R.; Tlusty, D.; Todoroki, T.; Tokarev, M.; Trentalange, S.; Tribble, R. E.; Tribedy, P.; Tripathy, S. K.; Trzeciak, B. A.; Tsai, O. D.; Ullrich, T.; Underwood, D. G.; Upsal, I.; Van Buren, G.; van Nieuwenhuizen, G.; Vasiliev, A. N.; Videbæk, F.; Vokal, S.; Voloshin, S. A.; Vossen, A.; Wang, G.; Wang, Y.; Wang, F.; Wang, Y.; Webb, J. C.; Webb, G.; Wen, L.; Westfall, G. D.; Wieman, H.; Wissink, S. W.; Witt, R.; Wu, Y.; Xiao, Z. G.; Xie, W.; Xie, G.; Xu, J.; Xu, N.; Xu, Q. H.; Xu, W.; Xu, Y. F.; Xu, Z.; Yang, Y.; Yang, Q.; Yang, C.; Yang, S.; Ye, Z.; Ye, Z.; Yi, L.; Yip, K.; Yoo, I.-K.; Yu, N.; Zbroszczyk, H.; Zha, W.; Zhang, Z.; Zhang, X. P.; Zhang, J. B.; Zhang, S.; Zhang, J.; Zhang, Y.; Zhang, J.; Zhang, S.; Zhao, J.; Zhong, C.; Zhou, L.; Zhou, C.; Zhu, X.; Zhu, Z.; Zyzak, M.; STAR Collaboration

    2017-03-01

    We present measurements of elliptic flow (v2) of electrons from the decays of heavy-flavor hadrons (eHF) by the STAR experiment. For Au+Au collisions at √{sN N}=200 GeV we report v2, for transverse momentum (pT) between 0.2 and 7 GeV /c , using three methods: the event plane method (v2{EP } ), two-particle correlations (v2{2 } ), and four-particle correlations (v2{4 } ). For Au+Au collisions at √{sN N}=62.4 and 39 GeV we report v2{2 } for pT<2 GeV /c . v2{2 } and v2{4 } are nonzero at low and intermediate pT at 200 GeV, and v2{2 } is consistent with zero at low pT at other energies. The v2{2 } at the two lower beam energies is systematically lower than at √{sN N}=200 GeV for pT<1 GeV /c . This difference may suggest that charm quarks interact less strongly with the surrounding nuclear matter at those two lower energies compared to √{sN N}=200 GeV.

  5. Interaction of GABAA receptors with purinergic P2X2 receptors

    International Nuclear Information System (INIS)

    Shrivastava, A.

    2010-01-01

    GABA A Rs in the spinal cord are evolving as an important target for drug development against pain. Purinergic P2X 2 Rs are also expressed in spinal cord neurons and are known to cross-talk with GABA A Rs. Here we investigated a possible 'dynamic' interaction between GABA A Rs and P2X 2 Rs using co-immunoprecipitation and FRET studies in HEK cells along with co-localization and single particle tracking studies in spinal cord neurons. Our results suggest that a significant proportion of P2X 2 Rs forms a transient complex with GABA A Rs inside the cell, thus stabilizing these receptors and using them for co-trafficking to the cell surface. P2X 2 Rs and GABA A Rs are then co-inserted into the cell membrane and are primarily located extra-synaptically. Furthermore, agonist induced activation of P2X 2 Rs results in disassembly of the receptor complex and destabilization of GABA A Rs whereas P2X 2 Rs are stabilized and form larger clusters. Antagonist-induced blocking of P2XRs results in co-stabilization of this receptor complex at the cell surface. These results suggest a novel mechanism where association of P2XRs with other receptors could be used for specific targeting to the neuronal membrane, thus providing an extrasynaptic receptor reserve that could regulate the excitability of neurons. We further conclude that blocking the excitatory activity of excessively released ATP under diseased state by P2XR antagonists could simultaneously enhance synaptic inhibition mediated by GABA A Rs.(author) (author) [de

  6. DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair.

    Science.gov (United States)

    Serrano, M A; Li, Z; Dangeti, M; Musich, P R; Patrick, S; Roginskaya, M; Cartwright, B; Zou, Y

    2013-05-09

    Homologous recombination (HR) and nonhomologous end joining (NHEJ) are two distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-dependent protein kinase (DNA-PK), the core component of NHEJ, partnering with DNA-damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR), regulates HR repair of DSBs. The regulation was accomplished through modulation of the p53 and replication protein A (RPA) interaction. We show that upon DNA damage, p53 and RPA were freed from a p53-RPA complex by simultaneous phosphorylations of RPA at the N-terminus of RPA32 subunit by DNA-PK and of p53 at Ser37 and Ser46 in a Chk1/Chk2-independent manner by ATR and ATM, respectively. Neither the phosphorylation of RPA nor of p53 alone could dissociate p53 and RPA. Furthermore, disruption of the release significantly compromised HR repair of DSBs. Our results reveal a mechanism for the crosstalk between HR repair and NHEJ through the co-regulation of p53-RPA interaction by DNA-PK, ATM and ATR.

  7. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xue, E-mail: lixue@imm.ac.cn; Hu, Jinping, E-mail: hujp@imm.ac.cn; Wang, Baolian, E-mail: wangbaolian@imm.ac.cn; Sheng, Li, E-mail: shengli@imm.ac.cn; Liu, Zhihao, E-mail: liuzhihao@imm.ac.cn; Yang, Shuang, E-mail: yangsh@imm.ac.cn; Li, Yan, E-mail: yanli@imm.ac.cn

    2014-03-01

    Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F{sub 1} [20(S)-GF{sub 1}] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC{sub 50} = 9.42 μM), followed by 18β-GA (IC{sub 50} = 21.78 μM), 20(S)-GF{sub 1} (IC{sub 50} = 76.08 μM) and DAG (IC{sub 50} = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K{sub m} and V{sub max} values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF{sub 1} exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC{sub 0−t} and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF{sub 1} and Rh{sub 1} at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18

  8. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

    International Nuclear Information System (INIS)

    Li, Xue; Hu, Jinping; Wang, Baolian; Sheng, Li; Liu, Zhihao; Yang, Shuang; Li, Yan

    2014-01-01

    Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F 1 [20(S)-GF 1 ] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC 50 = 9.42 μM), followed by 18β-GA (IC 50 = 21.78 μM), 20(S)-GF 1 (IC 50 = 76.08 μM) and DAG (IC 50 = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K m and V max values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF 1 exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC 0−t and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF 1 and Rh 1 at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18β-GA, DAG, and 20(S)-GF 1 significantly inhibited P-gp in vitro

  9. 30 CFR 62.140 - Dual hearing protection level.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Dual hearing protection level. 62.140 Section... HEALTH REGULATIONS OCCUPATIONAL NOISE EXPOSURE § 62.140 Dual hearing protection level. If during any work shift a miner's noise exposure exceeds the dual hearing protection level, the mine operator must, in...

  10. 25 CFR 175.62 - Utility actions pending the appeal process.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Utility actions pending the appeal process. 175.62 Section 175.62 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN ELECTRIC POWER UTILITIES Appeals § 175.62 Utility actions pending the appeal process. Pending an appeal, utility...

  11. 30 CFR 206.62 - Does MMS protect information I provide?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Does MMS protect information I provide? 206.62 Section 206.62 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT PRODUCT VALUATION Indian Oil § 206.62 Does MMS protect information I provide? The MMS will keep...

  12. Two-particle inclusive and semi-inclusive rapidity distributions of π+-mesons in K-p interactions at 32 GeV/c

    International Nuclear Information System (INIS)

    Bumazhnov, V.A.; Babintsev, V.V.; Bogolyubskij, M.Yu.

    1983-01-01

    The inclusive and semiinclusive invariant differential cross sections of pair π +- mesons for different charged states in K - p-interactions at 32 GeV/c a K - p-interactions at 32 GeV/c are presented as functions of rapidity. Inclusive and semiinclusive pΩduction cross sections of pai pair π +- mesons are determined. The obtained experimental distributions are compared with predictions of quark recombination model

  13. Anti p-nucleus interaction

    International Nuclear Information System (INIS)

    Peng, J.C.

    1986-05-01

    Status and future prospects of antiproton-nucleus scattering experiments are presented. These scattering experiments were conducted at antiproton beam momentums of 300 and 600 MeV/c on target nuclei of 6 Li, 12 C, 16 O, 18 O, 40 Ca, 48 Ca, and 208 Pb. Antiproton-proton reactions investigated antiproton-nucleus bound or resonant states in antiproton reactions with d, 6 Li, 12 C, 63 Cu, and 209 Bi. Inelastic scattering experiments investigated the spin-isospin dependence of the NN interactions. 19 refs., 1 fig., 1 tab

  14. Systematical investigation of in vitro interaction of InP/ZnS quantum dots with human serum albumin by multispectroscopic approach.

    Science.gov (United States)

    Huang, Shan; Qiu, Hangna; Liu, Yi; Huang, Chusheng; Sheng, Jiarong; Cui, Jianguo; Su, Wei; Xiao, Qi

    2016-12-01

    Cadmium-free quantum dots (QDs) have attracted great attention in biological and biomedical applications due to their less content of toxic metals, but their potential toxicity investigations on molecular biology level are rarely involved. Since few studies have addressed whether InP/ZnS QDs could bind and alter the structure and function of human serum albumin (HSA), in vitro interaction between InP/ZnS QDs and HSA was systematically characterized by multispectroscopic approaches. InP/ZnS QDs could quench the intrinsic fluorescence of HSA via static mode. The binding site of InP/ZnS QDs was mainly located at subdomain IIA of HSA. Some thermodynamic parameters suggested that InP/ZnS QDs interacted with HSA mainly through electrostatic interactions. As further revealed by three-dimensional spectrometry, FT-IR spectrometry and circular dichroism technique, InP/ZnS QDs caused more global and local conformational change of HSA than CdSe/ZnS QDs, which illustrated the stronger binding interaction and higher potential toxicity of InP/ZnS QDs on biological function of HSA. Our results offer insights into the in vitro binding mechanism of InP/ZnS QDs with HSA and provide important information for possible toxicity risk of these cadmium-free QDs to human health. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Momentum and angular characteristics of diffractional and nondiffractional π-p interactions at 40 GeV/c

    International Nuclear Information System (INIS)

    Grishin, V.G.; Kerachev, P.P.; Tsivtsivadze, Eh.T.

    1976-01-01

    The πsup(+-)-meson and γ-quantum distribution on the longitudinal rapidities and transversal momenta in diffractional and nondiffractional interactions at p=40 GeV/c are presented. The topological cross sections and the dependence of the average multiplicity of π 0 -mesons on the number of secondary charged particles in the diffraction interactions have been determined

  16. X-ray diffraction studies on merohedrally twinned Δ1–62NtNBCe1-A crystals of the sodium/bicarbonate cotransporter

    International Nuclear Information System (INIS)

    Gill, Harindarpal S.; Dutcher, Lauren; Boron, Walter F.; Patel, Samir; Guay-Woodford, Lisa M.

    2013-01-01

    A truncated mutant missing the first 62 residues of the N-terminal, cytoplasmic domain of the sodium-bicarbonate NBCe1-A cotransporter crystallizes in space group P3 1 with pseudo-P3 1 21 symmetry and a hemihedral twin fraction of 33.0%. Twinned fractions and twin-pair statistics over binned resolutions confirm that the calculated twin fraction is associated with hemihedral twinning and not to non-crystallographic symmetry. NBCe1-A membrane-embedded macromolecules that cotransport sodium and bicarbonate ions across the bilayer serve to maintain acid–base homeostasis throughout the body. Defects result in a number of renal and eye disorders, including type-II renal tubular acidosis and cataracts. Here, crystals of a human truncated mutant of the cytoplasmic N-terminal domain of NBCe1 (Δ1–62NtNBCe1-A) are reported that diffract X-rays to 2.4 Å resolution. The crystal symmetry of Δ1–62NtNBCe1-A is of space group P3 1 with pseudo-P3 1 21 symmetry and it has a hemihedral twin fraction of 33.0%. The crystals may provide insight into the pathogenic processes observed in a subset of patients with truncating and point mutations in the gene encoding NBCe1

  17. 7 CFR 62.300 - Fees and other costs for service.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Fees and other costs for service. 62.300 Section 62...) Quality Systems Verification Programs Definitions Charges for Service § 62.300 Fees and other costs for service. Fees and other charges will be levied based on the following provisions: (a) Fees for service...

  18. MCNP Version 6.2 Release Notes

    Energy Technology Data Exchange (ETDEWEB)

    Werner, Christopher John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bull, Jeffrey S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Solomon, C. J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Brown, Forrest B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McKinney, Gregg Walter [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rising, Michael Evan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dixon, David A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Martz, Roger Lee [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hughes, Henry G. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cox, Lawrence James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zukaitis, Anthony J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Armstrong, J. C. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Forster, Robert Arthur [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Casswell, Laura [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2018-02-05

    Monte Carlo N-Particle or MCNP® is a general-purpose Monte Carlo radiation-transport code designed to track many particle types over broad ranges of energies. This MCNP Version 6.2 follows the MCNP6.1.1 beta version and has been released in order to provide the radiation transport community with the latest feature developments and bug fixes for MCNP. Since the last release of MCNP major work has been conducted to improve the code base, add features, and provide tools to facilitate ease of use of MCNP version 6.2 as well as the analysis of results. These release notes serve as a general guide for the new/improved physics, source, data, tallies, unstructured mesh, code enhancements and tools. For more detailed information on each of the topics, please refer to the appropriate references or the user manual which can be found at http://mcnp.lanl.gov. This release of MCNP version 6.2 contains 39 new features in addition to 172 bug fixes and code enhancements. There are still some 33 known issues the user should familiarize themselves with (see Appendix).

  19. Multiplicities of secondary hadrons produced in #betta#p and anti #betta#p charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1983-02-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in #betta#p and anti #betta# interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e + e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above approx.=7 GeV and local charge compensation within an event. (orig.)

  20. Analysis of the structure of events by the method of rapidity intervals in K-p interactions at 32 GeV/c and pp interactions at 69 GeV/c

    International Nuclear Information System (INIS)

    Babintsev, V.V.; Bumazhnov, V.A.; Kruglov, N.A.; Moiseev, A.M.; Proskuryakov, A.S.; Smirnova, L.N.; Ukhanov, M.N.

    1981-01-01

    We present an analysis of the structure of distributions in the magnitude r/sup n//sub m/ of rapidity intervals containing m charged particles in events with n charged particles in K - p interactions at 32 GeV/c and pp interactions at 69 GeV/c. It is found that all distributions correspond to a smooth curve with a single maximum. A comparison is made between the shape of the experimental distributions for K - p interactions and the shape of the distributions for generated events corresponding to the multi-Regge model

  1. Synthesis, Characterization and Inhibition Effects of Vanadium Substituted Dawson-type Heteropoly Acids(Mo, P)

    Institute of Scientific and Technical Information of China (English)

    YIN Yan-bing; YANG Yu-lin; FAN Rui-qing; ZHU Yang-qing; SUN Ji-ru

    2011-01-01

    Four new vanadium substituted Dawson-type heteropoly acids H7[P2Mo17VO62]·39H2O(1),H8[P2Mo16V2O62]·41H2O(2), H9[P2Mo15V3O62]·51H2O(3) and H8[P2Mo14V4O62H2]·45H2O(4) were prepared respectively. Their structures were determined by IR and ICP. The inhibition effects of vanadium substituted Dawson-type heteropoly acids(Mo, P) on free radical polymerization of methyl methacrylate(MMA) were investigated by dilatometry. The results show that the rate of the polymerization of MMA decreases and the inhibition effects of the four heteropoly acids reach the inhibitor performance of hydroquinone at a certain ratio.

  2. Solar wind interaction with comet 67P: Impacts of corotating interaction regions

    Science.gov (United States)

    Edberg, N. J. T.; Eriksson, A. I.; Odelstad, E.; Vigren, E.; Andrews, D. J.; Johansson, F.; Burch, J. L.; Carr, C. M.; Cupido, E.; Glassmeier, K.-H.; Goldstein, R.; Halekas, J. S.; Henri, P.; Koenders, C.; Mandt, K.; Mokashi, P.; Nemeth, Z.; Nilsson, H.; Ramstad, R.; Richter, I.; Wieser, G. Stenberg

    2016-02-01

    We present observations from the Rosetta Plasma Consortium of the effects of stormy solar wind on comet 67P/Churyumov-Gerasimenko. Four corotating interaction regions (CIRs), where the first event has possibly merged with a coronal mass ejection, are traced from Earth via Mars (using Mars Express and Mars Atmosphere and Volatile EvolutioN mission) to comet 67P from October to December 2014. When the comet is 3.1-2.7 AU from the Sun and the neutral outgassing rate ˜1025-1026 s-1, the CIRs significantly influence the cometary plasma environment at altitudes down to 10-30 km. The ionospheric low-energy (˜5 eV) plasma density increases significantly in all events, by a factor of >2 in events 1 and 2 but less in events 3 and 4. The spacecraft potential drops below -20 V upon impact when the flux of electrons increases. The increased density is likely caused by compression of the plasma environment, increased particle impact ionization, and possibly charge exchange processes and acceleration of mass-loaded plasma back to the comet ionosphere. During all events, the fluxes of suprathermal (˜10-100 eV) electrons increase significantly, suggesting that the heating mechanism of these electrons is coupled to the solar wind energy input. At impact the magnetic field strength in the coma increases by a factor of 2-5 as more interplanetary magnetic field piles up around the comet. During two CIR impact events, we observe possible plasma boundaries forming, or moving past Rosetta, as the strong solar wind compresses the cometary plasma environment. We also discuss the possibility of seeing some signatures of the ionospheric response to tail disconnection events.

  3. Preparation, distribution, stability and tumor imaging properties of [62Zn] Bleomycin complex in normal and tumor-bearing mice

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Fateh, B.; Ghergherehchi, M.; Karimian, A.; Matloobi, M.; Moradkhani, S.; Kamalidehghan, M.; Tabeie, F.

    2003-01-01

    Backgrounds: Bleomycin (BLM) has been labeled with radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [ 62 Zn] zinc chloride for oncologic PET studies. Materials and methods: The complex was obtained at the P H=2 normal saline at 90 d eg C in 60 min. Radio-TLC showed on overall radiochemical yield of 95-97% (radiochemical purity>97%). Stability of complex was checked in vitro in mice and human plasma/urine. Results: Preliminary in vitro studies performed to determined complex stability and distribution of [ 62 Zn] BLM in normal and fibrosarcoma tumors in mice according to bio-distribution/imaging studies. Conclusion: [ 62 Zn] BLM can be used in PET oncology studies due to its suitable physico-chemical propertied as a diagnostic complex behavior in higher animals

  4. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  5. pH dependence of steroid hormone-organic matter interactions at environmental concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Neale, Peta A. [School of Engineering and Electronics, University of Edinburgh, Edinburgh, EH9 3JL (United Kingdom)], E-mail: p.neale@ed.ac.uk; Escher, Beate I. [Swiss Federal Institute of Aquatic Science and Technology (Eawag), 8600, Duebendorf (Switzerland); Schaefer, Andrea I. [School of Engineering and Electronics, University of Edinburgh, Edinburgh, EH9 3JL (United Kingdom)

    2009-01-15

    The interaction of estradiol, estrone, progesterone and testosterone with environmentally relevant concentrations of Aldrich humic acid, alginic acid and tannic acid was studied using solid-phase microextraction (SPME). Since bulk organic matter and certain hormones such as estradiol and estrone contain dissociable functional groups, the effect of pH on sorption was investigated as this will influence their fate and bioavailability. For humic acid and tannic acid, sorption was strongest at acidic pH when the bulk organic matter was in a non-dissociated form and decreased when they became partially negatively charged. At acidic and neutral pH the strength of partitioning was influenced by hormone functional groups content, with the strongest sorption observed for progesterone and estrone. At alkaline pH conditions, when the bulk organics were dissociated, sorption decreased considerably (up to a factor of 14), although the non-dissociated hormones testosterone and progesterone indicated greater sorption to humic acid at pH 10 compared to the partially deprotonated estradiol and estrone. This study demonstrates that SPME can be used to assess organic matter sorption behaviour of a selected range of micropollutants and at environmentally relevant organic matter concentrations.

  6. Recent results and prospects from NA62

    Directory of Open Access Journals (Sweden)

    Bizzeti Andrea

    2016-01-01

    K+ → π+ vv̄ is a theoretically very clean decay where indirect effects of new physics may be detectable. The NA62 apparatus has been significantly upgraded between 2008 and 2014 in order to measure the branching ratio of this decay with 10% precision. The NA62 experiment took data with the new setup in pilot runs in 2014 and 2015, reaching the design beam intensity. Results of first data quality studies in view of the 2016-2017 physics runs are presented.

  7. Hydrogen interaction with radiation defects in p-type silicon

    CERN Document Server

    Feklisova, O V; Yakimov, E B; Weber, J

    2001-01-01

    Hydrogen interaction with radiation defects in p-type silicon has been investigated by deep-level non-stationary spectroscopy. Hydrogen is introduced into the high-energy electron-irradiated crystals under chemical etching in acid solutions at room temperature followed by the reverse-bias annealing at 380 K. It is observed that passivation of the irradiation-induced defects is accompanied by formation of novel electrically active defects with hydrogen-related profiles. Effect of hydrogen on the electrical activity of the C sub s C sub i complexes is shown for the first time. Based on the spatial distribution and passivation kinetics, possible nature of the novel complexes is analyzed. The radii for hydrogen capture by vacancies, K-centers, C sub s C sub i centers and the novel complexes are determined

  8. Energy spectra in $p$-shell $\\Lambda$ hypernuclei and $^{19}_{\\Lambda}\\textrm{F}$ and spin-dependent $\\Lambda N$ interactions

    OpenAIRE

    Kanada-En'yo, Yoshiko; Isaka, Masahiro; Motoba, Toshio

    2018-01-01

    Energy spectra of $0s$-orbit $\\Lambda$ states in $p$-shell $\\Lambda$ hypernuclei ($^{A}_\\Lambda Z$) and those in $^{19}_{\\Lambda}\\textrm{F}$ are studied with the microscopic cluster model and antisymmetrized molecular dynamics using the $G$-matrix effective $\\Lambda N$ ($\\Lambda NG$) interactions. Spin-dependent terms of the ESC08a version of the $\\Lambda NG$ interactions are tested and phenomenologically tuned to reproduce observed energy spectra in $p$-shell $^{A}_\\Lambda Z$. Spin-dependent...

  9. Mediator MED23 regulates basal transcription in vivo via an interaction with P-TEFb.

    Science.gov (United States)

    Wang, Wei; Yao, Xiao; Huang, Yan; Hu, Xiangming; Liu, Runzhong; Hou, Dongming; Chen, Ruichuan; Wang, Gang

    2013-01-01

    The Mediator is a multi-subunit complex that transduces regulatory information from transcription regulators to the RNA polymerase II apparatus. Growing evidence suggests that Mediator plays roles in multiple stages of eukaryotic transcription, including elongation. However, the detailed mechanism by which Mediator regulates elongation remains elusive. In this study, we demonstrate that Mediator MED23 subunit controls a basal level of transcription by recruiting elongation factor P-TEFb, via an interaction with its CDK9 subunit. The mRNA level of Egr1, a MED23-controlled model gene, is reduced 4-5 fold in Med23 (-/-) ES cells under an unstimulated condition, but Med23-deficiency does not alter the occupancies of RNAP II, GTFs, Mediator complex, or activator ELK1 at the Egr1 promoter. Instead, Med23 depletion results in a significant decrease in P-TEFb and RNAP II (Ser2P) binding at the coding region, but no changes for several other elongation regulators, such as DSIF and NELF. ChIP-seq revealed that Med23-deficiency partially reduced the P-TEFb occupancy at a set of MED23-regulated gene promoters. Further, we demonstrate that MED23 interacts with CDK9 in vivo and in vitro. Collectively, these results provide the mechanistic insight into how Mediator promotes RNAP II into transcription elongation.

  10. Functional Characterization of Cotton GaMYB62L, a Novel R2R3 TF in Transgenic Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Hamama Islam Butt

    Full Text Available Drought stress can trigger the production of ABA in plants, in response to adverse conditions, which induces the transcript of stress-related marker genes. The R2R3 MYB TFs are implicated in regulation of various plants developmental, metabolic and multiple environmental stress responses. Here, a R2R3-MYB cloned gene, GaMYB62L, was transformed in Arabidopsis and was functionally characterized. The GaMYB62L protein contains two SANT domains with a conserved R2R3 imperfect repeats. The GaMYB62L cDNA is 1,017 bp with a CDS of 879, encodes a 292-residue polypeptide with MW of 38.78 kD and a pI value of 8.91. Overexpressed GaMYB62L transgenic Arabidopsis have increased proline and chlorophyll content, superior seed germination rate under salt and osmotic stress, less water loss rate with reduced stomatal apertures, high drought avoidance as compared to WT on water deprivation and also significant plant survival rates at low temperature. In addition, overexpressed GaMYB62L lines were more sensitive to ABA mediated germination and root elongation assay. Moreover, ABA induced GaMYB62L overexpression, enhanced the expression of ABA stress related marker genes like RD22, COR15A, ADH1, and RD29A. Together, overexpression of GaMYB62L suggested having developed better drought, salt and cold tolerance in transgenic Arabidopsis and thus presented it as a prospective candidate gene to achieve better abiotic stress tolerance in cotton crop.

  11. A study of the ''young'' states of particles in p-, d-, and α-nuclei interactions

    International Nuclear Information System (INIS)

    Sarycheva, L.I.

    1977-01-01

    Experimental data on leading particle generation in p-, d- and α-nuclei interactions are compared with calculations within the framework of a simple classical model of scattering. Data show that deuterons and α-particles in inelastic interactions retain their individuality in some case, even after loosing from 10 to 30% of their energy and scattering on considerable angles. Comparison between the experimental data and the calculations made in terms of simplified model shows, that there exists a sufficiently high probability for 8.4 GeV/c deuterons and 16.8 GeV/c α-particles to undergo more than one interaction in the same nuclei

  12. Hyperon-nucleon interaction and the 2.13 GeV strange dibaryonic system in the P-matrix approach

    International Nuclear Information System (INIS)

    Kerbikov, B.O.; Bakker, B.L.G.; Daling, R.

    1988-01-01

    A description is presented of the low-energy YN (Y = Λ, Σ) interactions within the Jaffe-Low P-matrix formalism. Analysing the enhancement of the Λp invariant mass near the Σ + n threshold we conclude that it should be identified as a P-matrix partner of the deuteron and not as a six-quark dibaryon resonance. (orig.)

  13. Quantitative and microscopic assessment of compatible and incompatible interactions between chickpea cultivars and Fusarium oxysporum f. sp. ciceris races.

    Science.gov (United States)

    Jiménez-Fernández, Daniel; Landa, Blanca B; Kang, Seogchan; Jiménez-Díaz, Rafael M; Navas-Cortés, Juan A

    2013-01-01

    Fusarium wilt caused by Fusarium oxysporum f. sp. ciceris, a main threat to global chickpea production, is managed mainly by resistant cultivars whose efficiency is curtailed by Fusarium oxysporum f. sp. ciceris races. We characterized compatible and incompatible interactions by assessing the spatial-temporal pattern of infection and colonization of chickpea cvs. P-2245, JG-62 and WR-315 by Fusarium oxysporum f. sp. ciceris races 0 and 5 labeled with ZsGreen fluorescent protein using confocal laser scanning microscopy. The two races colonized the host root surface in both interactions with preferential colonization of the root apex and subapical root zone. In compatible interactions, the pathogen grew intercellularly in the root cortex, reached the xylem, and progressed upwards in the stem xylem, being the rate and intensity of stem colonization directly related with the degree of compatibility among Fusarium oxysporum f. sp. ciceris races and chickpea cultivars. In incompatible interactions, race 0 invaded and colonized 'JG-62' xylem vessels of root and stem but in 'WR-315', it remained in the intercellular spaces of the root cortex failing to reach the xylem, whereas race 5 progressed up to the hypocotyl. However, all incompatible interactions were asymptomatic. The differential patterns of colonization of chickpea cultivars by Fusarium oxysporum f. sp. ciceris races may be related to the operation of multiple resistance mechanisms.

  14. Quantitative and microscopic assessment of compatible and incompatible interactions between chickpea cultivars and Fusarium oxysporum f. sp. ciceris races.

    Directory of Open Access Journals (Sweden)

    Daniel Jiménez-Fernández

    Full Text Available BACKGROUND: Fusarium wilt caused by Fusarium oxysporum f. sp. ciceris, a main threat to global chickpea production, is managed mainly by resistant cultivars whose efficiency is curtailed by Fusarium oxysporum f. sp. ciceris races. METHODOLOGY: We characterized compatible and incompatible interactions by assessing the spatial-temporal pattern of infection and colonization of chickpea cvs. P-2245, JG-62 and WR-315 by Fusarium oxysporum f. sp. ciceris races 0 and 5 labeled with ZsGreen fluorescent protein using confocal laser scanning microscopy. FINDINGS: The two races colonized the host root surface in both interactions with preferential colonization of the root apex and subapical root zone. In compatible interactions, the pathogen grew intercellularly in the root cortex, reached the xylem, and progressed upwards in the stem xylem, being the rate and intensity of stem colonization directly related with the degree of compatibility among Fusarium oxysporum f. sp. ciceris races and chickpea cultivars. In incompatible interactions, race 0 invaded and colonized 'JG-62' xylem vessels of root and stem but in 'WR-315', it remained in the intercellular spaces of the root cortex failing to reach the xylem, whereas race 5 progressed up to the hypocotyl. However, all incompatible interactions were asymptomatic. CONCLUSIONS: The differential patterns of colonization of chickpea cultivars by Fusarium oxysporum f. sp. ciceris races may be related to the operation of multiple resistance mechanisms.

  15. On the dependance of the ''normalized multiplicity'' of particles produced in proton-nucleus interactions on the primary energy

    International Nuclear Information System (INIS)

    Babecki, J.

    1975-01-01

    The mean ''normalized multiplicities'' of particles produced in p-nucleus interactions: with the leading particles (R 1 ) and without them (R 2 ) were calculated from the emulsion data. The independence of R 2 of the primary energy E 0 were stated in very wide interval of E 0 from 6.2 to thousands of GeV. R 2 is approximately equal to the mean number of collisions of the primary particle in the nucleus. (author)

  16. STS-62 Space Shuttle mission report

    Science.gov (United States)

    Fricke, Robert W., Jr.

    1994-01-01

    The STS-62 Space Shuttle Program Mission Report summarizes the Payload activities as well as the Orbiter, External Tank (ET), Solid Rocket Booster (SRB), Redesigned Solid Rocket Motor (RSRM), and the Space Shuttle main engine (SSHE) systems performance during the sixty-first flight of the Space Shuttle Program and sixteenth flight of the Orbiter vehicle Columbia (OV-102). In addition to the Orbiter, the flight vehicle consisted of an ET designated as ET-62; three SSME's which were designated as serial numbers 2031, 2109, and 2029 in positions 1, 2, and 3, respectively; and two SRB's which were designated BI-064. The RSRM's that were installed in each SRB were designated as 360L036A (lightweight) for the left SRB, and 36OWO36B (welterweight) for the right SRB. This STS-62 Space Shuttle Program Mission Report fulfills the Space Shuttle Program requirement as documented in NSTS 07700, Volume 8, Appendix E. That document requires that each major organizational element supporting the Program report the results of its hardware evaluation and mission performance plus identify all related in-flight anomalies. The primary objectives of the STS-62 mission were to perform the operations of the United States Microgravity Payload-2 (USMP-2) and the Office of Aeronautics and Space Technology-2 (OAST-2) payload. The secondary objectives of this flight were to perform the operations of the Dexterous End Effector (DEE), the Shuttle Solar Backscatter Ultraviolet/A (SSBUV/A), the Limited Duration Space Environment Candidate Material Exposure (LDCE), the Advanced Protein Crystal Growth (APCG), the Physiological Systems Experiments (PSE), the Commercial Protein Crystal Growth (CPCG), the Commercial Generic Bioprocessing Apparatus (CGBA), the Middeck Zero-Gravity Dynamics Experiment (MODE), the Bioreactor Demonstration System (BDS), the Air Force Maui Optical Site Calibration Test (AMOS), and the Auroral Photography Experiment (APE-B).

  17. The Effect of Orbital Configuration on the Possible Climates and Habitability of Kepler-62f.

    Science.gov (United States)

    Shields, Aomawa L; Barnes, Rory; Agol, Eric; Charnay, Benjamin; Bitz, Cecilia; Meadows, Victoria S

    2016-06-01

    As lower-mass stars often host multiple rocky planets, gravitational interactions among planets can have significant effects on climate and habitability over long timescales. Here we explore a specific case, Kepler-62f (Borucki et al., 2013 ), a potentially habitable planet in a five-planet system with a K2V host star. N-body integrations reveal the stable range of initial eccentricities for Kepler-62f is 0.00 ≤ e ≤ 0.32, absent the effect of additional, undetected planets. We simulate the tidal evolution of Kepler-62f in this range and find that, for certain assumptions, the planet can be locked in a synchronous rotation state. Simulations using the 3-D Laboratoire de Météorologie Dynamique (LMD) Generic global climate model (GCM) indicate that the surface habitability of this planet is sensitive to orbital configuration. With 3 bar of CO2 in its atmosphere, we find that Kepler-62f would only be warm enough for surface liquid water at the upper limit of this eccentricity range, providing it has a high planetary obliquity (between 60° and 90°). A climate similar to that of modern-day Earth is possible for the entire range of stable eccentricities if atmospheric CO2 is increased to 5 bar levels. In a low-CO2 case (Earth-like levels), simulations with version 4 of the Community Climate System Model (CCSM4) GCM and LMD Generic GCM indicate that increases in planetary obliquity and orbital eccentricity coupled with an orbital configuration that places the summer solstice at or near pericenter permit regions of the planet with above-freezing surface temperatures. This may melt ice sheets formed during colder seasons. If Kepler-62f is synchronously rotating and has an ocean, CO2 levels above 3 bar would be required to distribute enough heat to the nightside of the planet to avoid atmospheric freeze-out and permit a large enough region of open water at the planet's substellar point to remain stable. Overall, we find multiple plausible combinations of

  18. Neutron-to-proton ratios in pA and π+-A interactions

    International Nuclear Information System (INIS)

    Bayukov, Yu.D.; Degtyarenko, P.V.; Druzhinin, B.L.

    1983-01-01

    Measurements of neutron and proton yields at 120 deg have been carried out in 7.5 GeV/c pA and in 1.4 GeV/c and 5.0 GeV/c π +- A interactions. The ratios of secondary neutrons to protons are considered in detail. The ratios depend on kinetic energy of secondary nucleons and this dependence is more pronounced for heavy nuclei. Dependence of this ratios on the incident particle charge and the asymmetry resulting from a different number of protons and neutrons in the nucleus are discussed

  19. Charge transfer and rapidity gap analysis in p(π+)n interactions at 195 GeV/c

    International Nuclear Information System (INIS)

    Eisenberg, Y.; Haber, B.; Hochmann, D.; Karshon, U.; Ronat, E.E.; Shapira, A.; Yekutieli, G.

    1980-01-01

    We present charge transfer probabilities between CM hemispheres in pn and π + n interactions at 195 GeV/c. The relative probabilities for charge exchanges ΔQ > 1 as a function of rapidity gap length, r, are given. Both results are compared with those of π - p interactions at 200 GeV/c. The average of r, viz. , is given as a function of the gap number and of ΔQ for various multiplicities, and the reduced average gap lengths /ysub(max) for pn interactions are compared with data at a lower energy. (orig.)

  20. Anti-restenotic effect of copper-62 liquid-filled balloon in porcine coronary arteries: novel use of a short half-life positron emitter

    International Nuclear Information System (INIS)

    Chan, Rosanna C.; Lacy, Jeffrey L.; Bhargava, Balram; Collins, Sara D.; Cates, Pamela; Cottin, Yves; Kollum, Marc; Yang, Nathan; Haynes, Neal G.; Martin, Christopher S.; Nayak, Nisha; Vodovotz, Yoram; Kim, Han-Soo; Waksman, Ron

    2000-01-01

    Purpose: To determine the efficacy of the use of copper-62, a positron emitter with a half-life of 9.7 minutes, as an intracoronary brachytherapy (IRBT) source in the prevention of neointima formation (NF) following overstretch balloon injury (BI) in the porcine model. Methods and Materials: Sixteen swine were treated after BI to their left anterior descending (LAD), left circumflex (LCX), and/or right coronary artery (RCA). Twelve of the injured arteries received placebo and 10 received 25 Gy, delivered to 0.5 mm from the surface of the treatment balloon filled with liquid 62 Cu. Dosimetry was based on Monte Carlo calculations. Two weeks after treatment, the animals were sacrificed, and the treated coronaries were perfusion-fixed and stained. Intimal area (IA) and medial fracture length (FL) were analyzed by computer-aided histomorphometry. Results: The ( 62 Zn/ 62 Cu) generator, together with a rapid concentration process, was successful in delivering the short-lived 62 Cu at the high concentration required for intravascular brachytherapy (IVBT). The fracture length in the two groups was similar (2.10 ± 0.57; 2.02 ± 0.77; p = NS). Arteries studied showed significant reduction in NF (IA: 0.23 ± 0.47 mm 2 vs. 1.08 ± 0.57 mm 2 ; p 62 Cu as an IVBT source is safe and feasible. All 16 swine tolerated the treatment well with no radiation-induced side effects or symptoms throughout the 2-week period. The isotope delivered the dose necessary to inhibit NF in the porcine coronary BI model

  1. Inclusive gamma production in π-p interactions at 5 GeV/C

    International Nuclear Information System (INIS)

    Amaglobeli, N.S.; Salukvadze, R.G.; Chiladze, B.G.; Shoshiashvili, Sh.S.; Subinsky, J.; Rumyantsev, V.S.; Budagov, Yu.A.; Vinogradov, V.B.; Volodko, A.G.; Dzhelepov, V.P.; Lomakin, Yu.F.

    1975-01-01

    The results of the experimental study of the inclusive reaction π - p→ γ + ... at 5 GeV/c are reported. The behaviour of the invariant inclusive cross section for γ-guanta in the central and the fragmentation regions has been investigated. The conclusion can be made from the comparison of results with data obtained at higher energies that gamma production in π - p interactions shows the scaling properties already at 5 GeV

  2. Novel recurrent neural network for modelling biological networks: oscillatory p53 interaction dynamics.

    Science.gov (United States)

    Ling, Hong; Samarasinghe, Sandhya; Kulasiri, Don

    2013-12-01

    Understanding the control of cellular networks consisting of gene and protein interactions and their emergent properties is a central activity of Systems Biology research. For this, continuous, discrete, hybrid, and stochastic methods have been proposed. Currently, the most common approach to modelling accurate temporal dynamics of networks is ordinary differential equations (ODE). However, critical limitations of ODE models are difficulty in kinetic parameter estimation and numerical solution of a large number of equations, making them more suited to smaller systems. In this article, we introduce a novel recurrent artificial neural network (RNN) that addresses above limitations and produces a continuous model that easily estimates parameters from data, can handle a large number of molecular interactions and quantifies temporal dynamics and emergent systems properties. This RNN is based on a system of ODEs representing molecular interactions in a signalling network. Each neuron represents concentration change of one molecule represented by an ODE. Weights of the RNN correspond to kinetic parameters in the system and can be adjusted incrementally during network training. The method is applied to the p53-Mdm2 oscillation system - a crucial component of the DNA damage response pathways activated by a damage signal. Simulation results indicate that the proposed RNN can successfully represent the behaviour of the p53-Mdm2 oscillation system and solve the parameter estimation problem with high accuracy. Furthermore, we presented a modified form of the RNN that estimates parameters and captures systems dynamics from sparse data collected over relatively large time steps. We also investigate the robustness of the p53-Mdm2 system using the trained RNN under various levels of parameter perturbation to gain a greater understanding of the control of the p53-Mdm2 system. Its outcomes on robustness are consistent with the current biological knowledge of this system. As more

  3. The interaction between epiphytic algae, a parasitic fungus and Sphagnum as affected by N. and P.

    NARCIS (Netherlands)

    Limpens, J.; Jeffrey, T.A.G.; Baar, J.; Berendse, F.; Zijlstra, J.D.

    2003-01-01

    We report the effects of fertilisation with N and P on the infection of Sphagnum by its fungal parasite Lyophyllum palustre, the expansion of epiphytic algae and the interaction between the latter two from 1998 to 2001. We added 40 kg N ha(-1) yr(-1) or 3 kg P ha(-1) yr(-1) in a full factorial

  4. Inclusive ϱ0 production in overlineνμp charged current interactions

    Science.gov (United States)

    Grässler, H.; Lanske, D.; Schulte, R.; Jones, G. T.; Kennedy, B. W.; Middleton, R. P.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Hoffmann, E.; Nellen, B.; Saarikko, H.; Klein, H.; Mittendorfer, J.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Barnham, K. W. J.; Clayton, E. F.; Hamisi, F.; Miller, D. B.; Mobayyen, M. M.; Aderholz, M.; Deck, L.; Schmitz, N.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Aachen-Birmingham-Bonn-CERN-Imperial College-München (MPI)-Oxford Collaboration

    1986-07-01

    Inclusive ϱ0 production has been studied in antineutrino-proton charged current interactions, using a sample of 3340 events obtained in BEBC filled with hydrogen and exposed to the CERN wideband antineutrino beam. An average multiplicity of 0.11 ± 0.02 ϱ0 per event at a mean hadronic mass W of 4.2 GeV is observed. The ϱ0 production characteristics are determined as functions of pT, xF, and z. The ratio ϱ 0/"π 0" is found to be low at small z values consistent with centrally produced pions coming mainly from resonances. At large z values this ratio approaches 0.45 ± 0.15 which is compatible with a vector/pseudoscalar meson direct production ratio of one. The results are compared with those obtained from neutrino-proton interactions in the same experimental set-up.

  5. An investigation of the reaction mechanism for resonance neutron capture in 54Fe and 62Ni

    International Nuclear Information System (INIS)

    Mason, J.P.

    1986-01-01

    The gamma-ray spectra produced following neutron capture in the low energy resonances of 54 Fe and 62 Ni have been observed, using the Harwell 136 MeV electron linear accelerator facility, HELIOS, as a source of pulsed neutrons. The work indicated that, for s-wave capture in the mass region A approx. 55, single particle effects may only be apparent if the size of the valence component is about an order of magnitude larger than the compound nuclear component, and that this may limit the importance of such effects to a few nuclides. In addition, some information was obtained on the radiative decay of p-wave resonances of 54 Fe and 62 Ni. (author)

  6. 28 CFR 51.62 - Enforcement by the Attorney General.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Enforcement by the Attorney General. 51.62 Section 51.62 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR THE... Attorney General. (a) The Attorney General is authorized to bring civil actions for appropriate relief...

  7. Tuning interionic interaction by rationally controlling solution pH for highly selective colorimetric sensing of arginine.

    Science.gov (United States)

    Qian, Qin; Hao, Jie; Ma, Wenjie; Yu, Ping; Mao, Lanqun

    2016-04-01

    Direct selective sensing of arginine in central nervous systems remains very essential to understanding of the molecular basis of some physiological events. This study presents the first demonstration on a simple yet effective method for arginine sensing with gold nanoparticles (Au-NPs) as the signal readout. The rationale for the method is based on the pH-dependent feature of the interionic interaction between cysteine and arginine. At pH 6.0, cysteine can only interact with arginine through the ion-pair interaction and such interaction can lead to the changes in both the solution color and UV-vis spectrum of the cysteine-protected Au-NPs upon the addition of arginine. These changes are further developed into an analytical strategy for effective sensing of arginine by rationally controlling the pH values of Au-NP dispersions with the ratio of the absorbance at 650 nm (A 650) to that at 520 nm (A 520) (A 650/A 520) as a parameter for analysis. The method is responsive to arginine without the interference from other species in the cerebral system; under the optimized conditions, the A 650/A 520 values are linear with the concentration of arginine within a concentration range from 0.80 to 64 μM, yet remain unchanged with the addition of other kinds of amino acids or the species in the central nervous system into the Au-NPs dispersion containing cysteine. The method demonstrated here is reliable and robust and could thus be used for detection of the increase of arginine in central nervous systems.

  8. Study of the nuclear spin-orbit interaction by performing the transfer reaction 36S(d,p)37S and 34Si(d,p)35Si

    International Nuclear Information System (INIS)

    Burgunder, G.

    2011-12-01

    The spin-orbit interaction depends on the spin orientation of the nucleons with respect to their angular momenta as well as on the derivative of the nuclear density. Even though this density dependence is used in all mean field model, it has never been tested yet due to the lack of data. We propose an original method to test this density dependence by comparing a bubble nucleus ( 34 Si) to a normal nucleus ( 36 S). The 34 Si exhibits a central density which is depleted by a factor of two which induces a non-zero central density derivative and should change the strength of the spin orbit interaction for the inner orbits such as the p orbits (L=1). By performing (d,p) transfer reactions with 36 S and 34 Si beams, the p(3/2) and p(1/2) spin orbit splitting can be inferred for these nuclei. Depending on the models, the spin-orbit splitting varies from 7% (VlowK interaction) up to 70% (Relativistic mean field approach). Beams of 36 S and 34 Si, produced at the LISE spectrometer at 20 A.MeV, were impinged onto a CD 2 target. Tracking the beam particles was achieved using 2 xy beam tracking gas detectors. Protons emitted were detected by 4 multi-segmented Si detectors (MUST2) placed at backwards angles. Gammas issued from the excited states decay were detected in the 4 EXOGAM segmented Germanium detectors. Transfer like nuclei were identified with an ionization chamber and a plastic detector. The excitation energy spectra of the 37 S and 35 Si are determined up to about 7 MeV. Spectroscopic factors and energies of p and f states are derived for the first time in 35 Si. The two nuclei show strong similarity for the f spin-orbit partners, whereas the p(3/2) - p(1/2) energy gap is reduced by 55%. (author)

  9. + → +̅: first result from NA62 experiment

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    The decay + → +̅, with a very precisely predicted branching ratio of less than 10−10, is one of the best candidates to reveal indirect effects of new physics at the highest mass scales. The NA62 experiment at CERN SPS is designed to measure the branching ratio of the + → +̅ with a decay- in-flight technique, novel for this channel. NA62 took data in 2016, 2017 and another year run is scheduled in 2018. Statistics collected in 2016 allows NA62 to reach the Standard Model sensitivity for + → +̅, entering the domain of 10−10 single event sensitivity and showing the proof of principle of the experiment. The preliminary result on + → +̅ from the analysis of the 2016 data set is presented and prospects for future reviewed.

  10. Design, Synthesis and Evaluation of 2,5-Diketopiperazines as Inhibitors of the MDM2-p53 Interaction.

    Directory of Open Access Journals (Sweden)

    Mariell Pettersson

    Full Text Available The transcription factor p53 is the main tumour suppressor in cells and many cancer types have p53 mutations resulting in a loss of its function. In tumours that retain wild-type p53 function, p53 activity is down-regulated by MDM2 (human murine double minute 2 via a direct protein-protein interaction. We have designed and synthesised two series of 2,5-diketopiperazines as inhibitors of the MDM2-p53 interaction. The first set was designed to directly mimic the α-helical region of the p53 peptide, containing key residues in the i, i+4 and i+7 positions of a natural α-helix. Conformational analysis indicated that 1,3,6-trisubstituted 2,5-diketopiperazines were able to place substituents in the same spatial orientation as an α-helix template. The key step of the synthesis involved the cyclisation of substituted dipeptides. The other set of tetrasubstituted 2,5-diketopiperazines were designed based on structure-based docking studies and the Ugi multicomponent reaction was used for the synthesis. This latter set comprised the most potent inhibitors which displayed micromolar IC50-values in a biochemical fluorescence polarisation assay.

  11. 7 CFR 250.62 - Summer Food Service Program (SFSP).

    Science.gov (United States)

    2010-01-01

    ....62 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE... Program (NSLP) and Other Child Nutrition Programs § 250.62 Summer Food Service Program (SFSP). (a... eligible for donated food support, in accordance with 7 CFR part 225. (c) Distribution of donated foods to...

  12. 50 CFR 20.62 - Importation of birds of another.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Importation of birds of another. 20.62... WILDLIFE AND PLANTS (CONTINUED) MIGRATORY BIRD HUNTING Importations § 20.62 Importation of birds of another. No person shall import migratory game birds belonging to another person. ...

  13. 36 CFR 62.1 - Purpose

    Science.gov (United States)

    2010-07-01

    ... Landmarks Program focuses attention on areas of exceptional natural value to the nation as a whole rather... United States, enhances the scientific and educational values of preserved areas, strengthens public... LANDMARKS PROGRAM § 62.1 Purpose The procedures in this part set forth the processes and criteria for the...

  14. Centrality Dependence of Charged Hadron Transverse Momentum Spectra in Au+Au Collisions from √(sNN)=62.4 to 200 GeV

    Science.gov (United States)

    Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Halliwell, C.; Hamblen, J.; Hauer, M.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Hołyński, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kulinich, P.; Kuo, C. M.; Lin, W. T.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Reed, C.; Roland, C.; Roland, G.; Sagerer, J.; Seals, H.; Sedykh, I.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S.; Sukhanov, A.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Wenger, E.; Wolfs, F. L.; Wosiek, B.; Woźniak, K.; Wysłouch, B.

    2005-03-01

    We have measured transverse momentum distributions of charged hadrons produced in Au+Au collisions at √(sNN)=62.4 GeV. The spectra are presented for transverse momenta 0.25<pT<4.5 GeV/c, in a pseudorapidity range of 0.2<η<1.4. The nuclear modification factor RAA is calculated relative to p+p data at the same collision energy as a function of collision centrality. For 2<pT<4.5 GeV/c, RAA is found to be significantly larger than in Au+Au collisions at √(sNN)= 130 and 200 GeV. In contrast to the large change in RAA, we observe a very similar centrality evolution of the pT spectra at √(sNN)=62.4 and 200 GeV. The dynamical origin of this surprising factorization of energy and centrality dependence of particle production in heavy-ion collisions remains to be understood.

  15. Study of quasiexclusive neutral meson production in pN interactions at E{sub p} = 70 GeV in the deep fragmentation region

    Energy Technology Data Exchange (ETDEWEB)

    Golovkin, S.V.; Kozhevnikov, A.P.; Kubarovsky, V.P. [Institute for High Energy Physics (IHEP), Protvino (Russian Federation)] [and others; SPHINX Collaboration (IHEP-ITEP)

    1997-11-01

    Quasiexclusive neutral meson production in pN-interactions is studied in experiments with the SPHINX facility operating in a proton beam from the IHEP accelerator (E{sub p}=70 GeV). The cross sections and the parameters of the differential distributions for {pi}{sup 0}, {omega}, {eta} and K{sup 0} production in the deep fragmentation region (x{sub F}>0.79/0.86) are presented. The results show that such proton quasiexclusive reactions with baryon exchange may be promising in searches for exotic mesons. (orig.) 20 refs.

  16. Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast.

    Science.gov (United States)

    Banerjee, Subhrajit; Kane, Patricia M

    2017-09-15

    Luminal pH and phosphoinositide content are fundamental features of organelle identity. Vacuolar H + -ATPases (V-ATPases) drive organelle acidification in all eukaryotes, and membrane-bound a-subunit isoforms of the V-ATPase are implicated in organelle-specific targeting and regulation. Earlier work demonstrated that the endolysosomal lipid PI(3,5)P 2 activates V-ATPases containing the vacuolar a-subunit isoform in Saccharomyces cerevisiae Here we demonstrate that PI(4)P, the predominant Golgi phosphatidylinositol (PI) species, directly interacts with the cytosolic amino terminal (NT) domain of the yeast Golgi V-ATPase a-isoform Stv1. Lysine-84 of Stv1NT is essential for interaction with PI(4)P in vitro and in vivo, and interaction with PI(4)P is required for efficient localization of Stv1-containing V-ATPases. The cytosolic NT domain of the human V-ATPase a2 isoform specifically interacts with PI(4)P in vitro, consistent with its Golgi localization and function. We propose that NT domains of V o a-subunit isoforms interact specifically with PI lipids in their organelles of residence. These interactions can transmit organelle-specific targeting or regulation information to V-ATPases. © 2017 Banerjee and Kane. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  17. Novel archaeal plasmid pAH1 and its interactions with the lipothrixvirus AFV1

    DEFF Research Database (Denmark)

    Basta, Tamara; Smyth, John; Forterre, Patrick

    2009-01-01

    . Although nucleotide sequence comparisons revealed extensive intergenomic exchange during the evolution of archaeal conjugative plasmids, pAH1 was shown to be stably maintained suggesting that the host system is suitable for studying plasmid-virus interactions. AFV1 infection and propagation leads to a loss...... of the circular form of pAH1 and this effect correlates positively with the increase in the intracellular quantity of AFV1 DNA. We infer that the virus inhibits plasmid replication since no pAH1 degradation was observed. This mechanism of archaeal viral inhibition of plasmid propagation is not observed...... in bacteria where relevant bacteriophages either are dependent on a conjugative plasmid for successful infection or are excluded by a resident plasmid....

  18. Water-rock interactions and the pH stability of groundwater from Yucca Mountain, Nevada

    International Nuclear Information System (INIS)

    Ebinger, M.H.

    1992-01-01

    Titrations of acidic solutions in waters from the tuff and carbonate aquifers at Yucca Mountain were simulated using the geochemical codes PHREEQE and EQ3/6. The simulations tested pH stability of the waters in the presence of different minerals and in their absence. Two acidic solutions, 10 -4 HCl and 10 -4 M UO 2 (NO 3 ) 2 , were titrated in to the water. Little pH and/or compositional change resulted in the groundwater when the HCl solution was titrated, but significant pH and CO 2 fugacity changes were observed when UO 2 (NO 3 ) 2 was titrated. Water interactions with alkali feldspar, quartz or cristobalite, and Ca-smectite buffered the pH and compositional changes in the carbonate water and decreased the magnitude of pH and compositional changes when small volumes of UO 2 (NO 3 ) 2 added to the tuffaceous waters

  19. Charm hadron properties in 360 GeV/c π-p-interactions

    International Nuclear Information System (INIS)

    Aguilar-Benitez, M.; Colino, N.; Ladron de Guevara, P.; Willmott, C.; Allison, W.W.M.; Colwill, S.; Lyons, L.; Wright, P.; Bailly, J.L.; Baland, J.F.; Grard, F.; Kesteman, J.; Pilette, P.; Banerjee, S.; Ganguli, S.; Malhotra, P.K.; Shankar, K.; Subramanian, A.; Bartl, W.; Epp, B.; Hrubec, J.; Pernicka, M.; Rohringer, H.; Begalli, M.; Otter, G.; Ransone, G.; Schulte, R.; Struczinski, W.; Belliere, P.; Defoix, C.; Dolbeau, J.; Laloum, M.; Bettini, A.; Checchia, P.; Cresti, M.; De-Angelis, A.; Gasparini, U.; Mazzucato, M.; Pinori, C.; Ventura, L.; Zotto, P.L.; Zumerle, G.; Billy, L. de; Briand, H.; Dumarchez, J.; Nguyen, H.K.; Touboul, M.C.; Bizarri, R.; Capua, E. di; Falciano, S.; Gentile, S.; Marel, G.; Marzano, F.; Piredda, G.; Zanello, L.; Borreani, G.; Garbellini, L.; Marchetto, F.; Rinaudo, G.; Brun, R.; Fernandez, C.; Goshaw, A.; Gurtu, A.; Hernandez, J.J.; Herve, A.; Iori, M.; Leutz, H.; Montanet, L.; Neuhofer, G.; Nowak, H.; Poppleton, A.; Powell, B.; Reucroft, S.; Richardson, J.; Schouten, M.; Bugg, W.M.; Handler, T.; Hart, E.L.; Caso, C.; Contri, R.; Fontanelli, F.; Monge, R.; Squarcia, S.; Trevisan, U.; Castelli, E.; Poropat, P.; Sessa, M.; Troncon, C.; Chliapnikov, P.; Fisyak, Yu.; Kistenev, E.; Kniazev, V.; Stopchenko, V.; Uvarov, V.; Vlasov, E.; Yarba, V.; Crennel, D.; Fisher, C.; Hughes, P.; MacDermott, M.; Dimarco, R.; Plano, R.; Stamer, P.; Fry, J.R.; Houlden, M.A.; Mason, P.; Patel, G.D.; Roberts, K.; Hamatsu, R.; Iga, Y.; Kita, I.; Kitamura, S.; Oshima, N.; Tsurugai, T.; Yamagata, T.; Haupt, L.; Hellman, S.; Holmgren, S.O.; Johanson, E.; Nilsson, S.; Sellden, B.; Huss, D.; Jegham, E.; Michalon, A.; Michalon-Mentzer, M.E.; Voltolini, C.; Lemonne, J.; Vilain, P.; Vonck, B.; Wickens, J.

    1986-01-01

    A study of the properties of charm particles produced in 360 GeV/c π - p interactions is reported. The experiment was performed using the high resolution hydrogen bubble chamber LEBC in association with the European Hybrid Spectrometer at the CERN SPS. Details of the exposure and operation of the spectrometer are given and the methods used to extract the charm data are presented. The essential physics results on the decay properties (lifetime, branching ratios) as well as on the hadroproduction properties (cross sections for D, anti D, F, Λsub(c), Dsup(*), correlations between charm particles) are given. (orig.)

  20. The Influence of Ca2+ and pH on the Interaction between PAHs and Molybdenite Edges

    Directory of Open Access Journals (Sweden)

    He Wan

    2017-06-01

    Full Text Available Nonpolar hydrocarbon oils are widely used as collectors for floating molybdenite. However, they can only adsorb on molybdenite faces and not on molybdenite edges, resulting in limited molybdenite recovery, especially in processed water containing a high amounts of Ca2+. In this study, the influence of Ca2+ and pH on the adsorption of polycyclic aromatic hydrocarbons (PAHs, as part of composite collection on molybdenite edges, was studied. It was found that PAHs could only adsorb on molybdenite edges in the presence of Ca2+. Ca2+ reacted with molybdenite edges to form CaMoO4 precipitates. Then, CaMoO4 precipitates interacted with PAHs to form a structure of π–cation–π by (1 the cation–π interaction, (2 the π–π interaction and (3 the electrostatic interaction. It was also found that CaMoO4 precipitates on molybdenite edges promoted the adsorption of PAHs. The more the CaMoO4 precipitates, the easier the PAHs adsorption occurred. As a result, the high amount of Ca2+and low pH enhanced the adsorption of PAHs on molybdenite edges. This study provides insights into reducing the deleterious effect of Ca2+ on fine molybdenite flotation.

  1. Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Jian Gong

    2016-10-01

    Full Text Available Genome-wide association studies (GWAS have identified many genetic susceptibility loci for colorectal cancer (CRC. However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO. Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10-8; permuted p-value 3.51x10-8 region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74-0.91]; P = 2.1×10-4 and TT genotypes (OR,0.62 [95% CI, 0.51-0.75]; P = 1.3×10-6 but not associated among those with the CC genotype (p = 0.059. No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

  2. p15PAF is an intrinsically disordered protein with nonrandom structural preferences at sites of interaction with other proteins.

    Science.gov (United States)

    De Biasio, Alfredo; Ibáñez de Opakua, Alain; Cordeiro, Tiago N; Villate, Maider; Merino, Nekane; Sibille, Nathalie; Lelli, Moreno; Diercks, Tammo; Bernadó, Pau; Blanco, Francisco J

    2014-02-18

    We present to our knowledge the first structural characterization of the proliferating-cell-nuclear-antigen-associated factor p15(PAF), showing that it is monomeric and intrinsically disordered in solution but has nonrandom conformational preferences at sites of protein-protein interactions. p15(PAF) is a 12 kDa nuclear protein that acts as a regulator of DNA repair during DNA replication. The p15(PAF) gene is overexpressed in several types of human cancer. The nearly complete NMR backbone assignment of p15(PAF) allowed us to measure 86 N-H(N) residual dipolar couplings. Our residual dipolar coupling analysis reveals nonrandom conformational preferences in distinct regions, including the proliferating-cell-nuclear-antigen-interacting protein motif (PIP-box) and the KEN-box (recognized by the ubiquitin ligase that targets p15(PAF) for degradation). In accordance with these findings, analysis of the (15)N R2 relaxation rates shows a relatively reduced mobility for the residues in these regions. The agreement between the experimental small angle x-ray scattering curve of p15(PAF) and that computed from a statistical coil ensemble corrected for the presence of local secondary structural elements further validates our structural model for p15(PAF). The coincidence of these transiently structured regions with protein-protein interaction and posttranslational modification sites suggests a possible role for these structures as molecular recognition elements for p15(PAF). Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Fluorescent derivatives of nucleotides. Metal ion interactions and pH dependency.

    Science.gov (United States)

    Vanderkooi, J M; Weiss, C J; Woodrow, G V

    1979-02-01

    The fluorescence parameters of ethenoadenosine derivatives are influenced by metal cations and pH, as summarized here. The pH profile of ethenoadenosine determined by fluorescence intensity gives a normal titration curve and is not affected by ionic strength. In contrast, the pH titration curves of etheno-ATP, etheno ADP, and etheno AMP depend upon ionic strength. At high ionic strength normal curves are obtained, whereas at low ionic strength anomalies are obtained; this suggests that the phosphates can interact with the ring, possibly by hydrogen binding to the ring nitrogens. The room temperature fluorescence of ethenoadenosine occurs from the base form, although excitation of either the acid or base forms can contribute to the emission. This result can be explained if the excited state pK is lower than the ground state pK, and if deprotonation occurs within the time scale of the excited state. At low pH values the fluorescence lifetime of the base form is dependent upon the buffer concentration, indicating that the reverse reaction, protonation, occurs. The affinity constants for the binding of metals to the ethenoadenosine phosphates resemble those for the corresponding adenosine phosphates. Ni(II) and Co(II) are more effective than Mn(II) in quenching the fluorescence of ethenoadenosine phosphates; this result is predicted by Förster's theory for energy transfer based upon the overlap between donor emission spectrum and acceptor absorption spectrum. The diamagnetic ions Mg(II), Ca(II), and Zn(II) do not appear to affect the fluorescence of the ethenoadenosine phosphates directly, but rather to affect the conformation of the molecule, thereby affecting the quantum yield.

  4. NA62: Hidden Sector Physics

    CERN Document Server

    Cesarotti, Carissa Joyce

    2016-01-01

    Modern experimental physics is often probing for new physics by either finding deviations from predictions on extremely precise measurements, or by looking for a new signal that cannot be explained with existing models. The NA62 experiment at CERN does the former by measuring the ultra-rare decay $K^+ \\rightarrow \\pi^+ \

  5. Easy H5Peasy: Interactive Teaching with H5P Technology (workshop)

    OpenAIRE

    Aizpurua, Michelle De

    2017-01-01

    This 90 minute workshop was for the Heartbeat of Teaching symposium, part of the Educational Designer's Making a Difference series for Monash University. Hosted by the Faculty of Medicine, Nursing and Health Sciences. Abstract: Using new technologies in teaching can be intimidating. New programs have steep learning curves and it can be hard to know where to start. H5P however is a quick and easy way to develop interactive activities for online environments, such as Moodle, or for us...

  6. 19 CFR 12.62 - Enforcement; duties of Customs officers.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Enforcement; duties of Customs officers. 12.62 Section 12.62 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY...; duties of Customs officers. (a) In accordance with the authority contained in sections 10 and 12 of the...

  7. 19 CFR 181.62 - Commercial samples of negligible value.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Commercial samples of negligible value. 181.62... Returned After Repair or Alteration § 181.62 Commercial samples of negligible value. (a) General. Commercial samples of negligible value imported from Canada or Mexico may qualify for duty-free entry under...

  8. Resonance production in π-p interactions at 100 GeV/c. Technical report No. 77-039

    International Nuclear Information System (INIS)

    Svrcek, F.C.

    1976-11-01

    A bubble chamber-wide-gap optical spark chamber experiment has been performed in order to make use of precision momentum measurements (delta p/p less than 0.25) in studying the π - p interaction at 100 GeV/c. These measurements were used to study phenomenological characteristics of and resonance production in the π - p interaction. Peyrou plots and single particle inclusive distributions in rapidity, Feynman x, and transverse momentum for π + , π - , and p production were used to point out the incident particle and leading proton effects. Factorization of the differential cross section was tested, indicating a slight preference for the variables (rapidity, transverse momentum). Two-particle rapidity correlations as a function of rapidity gap for like and unlike charge pion pairs were investigated inclusively, where short range correlation behavior was noted, and semi-inclusively, where a suggestion that clusters may consist of one positive particle and one negative particle was seen. A search for the production of known resonances was conducted in the following effective mass distributions: (pπ +- ), (π + π - ), (π + π - π +- ), (π + π - π + π - ), (K +- π -+ ), and (K + K - ). The Δ ++ (1236) was seen in the (pπ + ) channel, and substantial rho 0 (770) was seen in the (π + π - ) spectrum. Differential cross sections in center of mass rapidity and transverse momentum for the rho 0 indicated the dominance of production in the central and forward rapidity regions and production comparable to that for pions at p 2 /sub T/ greater than 0.5 (GeV/c) 2 . No other resonances were observed

  9. Using PyMOL to Explore the Effects of pH on Noncovalent Interactions between Immunoglobulin G and Protein A: A Guided-Inquiry Biochemistry Activity.

    Science.gov (United States)

    Roche Allred, Zahilyn D; Tai, Heeyoung; Bretz, Stacey Lowery; Page, Richard C

    2017-11-01

    Students' understandings of foundational concepts such as noncovalent interactions, pH and pK a are crucial for success in undergraduate biochemistry courses. We developed a guided-inquiry activity to aid students in making connections between noncovalent interactions and pH/pK a . Students explore these concepts by examining the primary and tertiary structures of immunoglobulin G (IgG) and Protein A. Students use PyMOL, an open source molecular visualization application, to (1) identify hydrogen bonds and salt bridges between and within the proteins at physiological pH and (2) apply their knowledge of pH/pK a to association rate constant data for these proteins at pH 4 and pH 11. The laboratory activity was implemented within a one semester biochemistry laboratory for students majoring in allied health disciplines, engineering, and biological sciences. Several extensions for more advanced students are discussed. Students' overall performance highlighted their ability to successfully complete tasks such as labeling and identifying noncovalent interactions and revealed difficulties with analyzing noncovalent interactions under varying pH/pK a conditions. Students' evaluations after completing the activity indicated they felt challenged but also recognized the potential of the activity to help them gain meaningful understanding of the connections between noncovalent interactions, pH, pK a , and protein structure. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):528-536, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

  10. 32 CFR 644.62 - Title evidence.

    Science.gov (United States)

    2010-07-01

    ... HANDBOOK Acquisition Procurement of Title Evidence, Title Clearance, and Closings § 644.62 Title evidence... and their charter to issue the same. They must also be financially sound and be willing and able to...

  11. 40 CFR 82.62 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... Containing or Manufactured With Class II Substances § 82.62 Definitions. For purposes of this subpart... to subpart A. Class II Substance means any substance designated as class II in 40 CFR part 82.... Hydrochlorofluorocarbon means any substance listed as class II in 40 CFR part 82, appendix B to subpart A. Initial...

  12. Energy dependence of the ratio of isovector effective interaction strengths |JστJτ| from 0° (p,n) cross sections

    Science.gov (United States)

    Taddeucci, T. N.; Rapaport, J.; Bainum, D. E.; Goodman, C. D.; Foster, C. C.; Gaarde, C.; Larsen, J.; Goulding, C. A.; Horen, D. J.; Masterson, T.; Sugarbaker, E.

    1982-02-01

    Information concerning the ratio of the isovector effective interaction strengths |JστJτ| may be obtained from the ratio of (p,n) Gamow-Teller and isobaric analog state 0° differential cross sections. We have examined 0° (p,n) data for the energy range 5-200 MeV and find that for energies larger than 50 MeV and for targets with A=7-42 the product of the interaction-strength and distortion-factor ratios |JστJτ|(NστNτ)12 appears to be mass independent and linear as a function of bombarding energy. NUCLEAR REACTIONS 7Li, 13, 14C, 26Mg, 37Cl, 41Ca(p,n), measured σ(θ=0°), GT, IAS transitions, Ep=60-200 MeV. Deduced energy dependence, interaction strength ratio |JστJτ|.

  13. Histone deacetylase 3 represses p15INK4b and p21WAF1/cip1 transcription by interacting with Sp1

    International Nuclear Information System (INIS)

    Huang Weifeng; Tan Dapeng; Wang Xiuli; Han Songyan; Tan Jiang; Zhao Yanmei; Lu Jun; Huang Baiqu

    2006-01-01

    Histone deacetylase 3 (HDAC3) has been implicated to play roles in governing cell proliferation. Here we demonstrated that the overexpression of HDAC3 repressed transcription of p15 INK4b and p21 WAF1/cip1 genes in 293T cells, and that the recruitment of HDAC3 to the promoter regions of these genes was critical to this repression. We also showed that HDAC3 repressed GAL4-Sp1 transcriptional activity, and that Sp1 was co-immunoprecipitated with FLAG-tagged HDAC3. We conclude that HDAC3 can repress p15 INK4b and p21 WAF1/cip1 transcription by interacting with Sp1. Furthermore, knockdown of HDAC3 by RNAi up-regulated the transcriptional expression of p15 INK4b , but not that of p21 WAF1/cip1 , implicating the different roles of HDAC3 in repression of p15 INK4b and p21 WAF1/cip1 transcription. Data from this study indicate that the inhibition of p15 INK4b and p21 WAF1/cip1 may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis

  14. Computer and internet use in vascular outpatients--ready for interactive applications?

    Science.gov (United States)

    Richter, J G; Schneider, M; Klein-Weigel, P

    2009-11-01

    Exploring patients' computer and internet use, their expectations and attitudes is mandatory for successful introduction of interactive online health-care applications in Angiology. We included 165 outpatients suffering from peripheral arterial disease (PAD; n = 62) and chronic venous and / or lymphatic disease (CVLD; n = 103) in a cross-sectional-study. Patients answered a paper-based questionnaire. Patients were predominantly female (54.5%). 142 (86.1%) reported regular computer use for 9.7 +/- 5.8 years and 134 (81.2 %) used the internet for 6.2 +/- 3.6 years. CVLD-patients and internet-user were younger and higher educated, resulting in a significant difference in computer and internet use between the disease groups (p internet users without significant differences between the groups. The topics retrieved from the internet covered a wide spectrum and searches for health information were mentioned by 41.2 %. Although confidence in the internet (3.3 +/- 1.1 on a 1-6 Likert scale) and reliability in information retrieved from the internet (3.1 +/- 1.1) were relatively low, health-related issues were of high actual and future interest. 42.8% of the patients were even interested in interactive applications like health educational programs, 37.4% in self-reported assessments and outcome questionnaires and 26.9% in chatforums; 50% demanded access to their medical data on an Internetserver. Compared to older participants those internet more often for shopping, chatting, and e-mailing, but not for health information retrieval and interactive applications. Computers are commonly used and the internet has been adopted as an important source of information by patients suffering from PAD and CVLD. Besides, the internet offers great potentials and new opportunities for interactive disease (self-)management in angiology. To increase confidence and reliability in the medium a careful introduction and evaluation of these new online applications is mandatory.

  15. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    Directory of Open Access Journals (Sweden)

    Lin CL

    2015-07-01

    Full Text Available Ching-Lung Lin,1 Sheue-Er Wang,2 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Soeurs de Saint Paul de Chartres Medical Corporate Body, Taoyuan City, 3Brion Research Institute of Taiwan, New Taipei City, Taiwan Abstract: Cardiac failure is often observed in aging patients with Huntington’s disease (HD. However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01. Cardiac expressions of superoxide dismutase 2 (SOD2 and B-cell lymphoma 2 (Bcl-2 in aging R6/2 HD mice were significantly lower than their WT (P<0.01, but cardiac expressions of tumor necrosis factor alpha (TNF-α, neurotrophin-3 (3-NT, 4-hydroxynonenal (4-HNE, Bcl-2-associated X protein (Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05. Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05. Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01, but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly

  16. Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions.

    Science.gov (United States)

    Ismail, Hanafy M; O'Neill, Paul M; Hong, David W; Finn, Robert D; Henderson, Colin J; Wright, Aaron T; Cravatt, Benjamin F; Hemingway, Janet; Paine, Mark J I

    2013-12-03

    Pyrethroid insecticides are used to control diseases spread by arthropods. We have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism. The probes were screened against pyrethroid-metabolizing and nonmetabolizing mosquito P450s, as well as rodent microsomes, to measure labeling specificity, plus cytochrome P450 oxidoreductase and b5 knockout mouse livers to validate P450 activation and establish the role for b5 in probe activation. Using PyABPs, we were able to profile active enzymes in rat liver microsomes and identify pyrethroid-metabolizing enzymes in the target tissue. These included P450s as well as related detoxification enzymes, notably UDP-glucuronosyltransferases, suggesting a network of associated pyrethroid-metabolizing enzymes, or "pyrethrome." Considering the central role P450s play in metabolizing insecticides, we anticipate that PyABPs will aid in the identification and profiling of P450s associated with insecticide pharmacology in a wide range of species, improving understanding of P450-insecticide interactions and aiding the development of unique tools for disease control.

  17. Unitary Pole Approximation For 16O S12state And 40ca P32state When Coulomb Interaction Is Included

    Directory of Open Access Journals (Sweden)

    A. Acharya

    2015-08-01

    Full Text Available Abstract The form factor of a separable interaction between a pair of particles is an important input in a three body calculation for a transfer reaction. The three body equations of Alt Grassberger and Sandhas have been solved for a system of three particles viz.p n and 16Oand p n and 40Ca when coulomb interaction is included between the particle pairs. The input in this calculation i.e. the two body t-matrices representing the interaction between the pairs of particles is taken to be of a separable form conforming to the bound state of the pair. The form factors of the total interaction between the particle pairs are constructed using the prescription of Ueta and Bund.

  18. Nuclear-transparency effect in the interaction of 6.2 GeV/c negative ions and neon nuclei

    International Nuclear Information System (INIS)

    Kiselevich, I.L.; Mikhailichenko, V.I.; Panitkin, S.Yu.; Ponosov, A.K.; Sergeev, F.M.; Tel'nov, M.Yu.

    1993-01-01

    The inelastic reaction of pions with neon nuclei π - + Ne → nπ - + mπ + + kp + X (n,m,k≥1) has been studied. The initial momentum was 6.2 GeV/c. It is found that in the region of variation of the Feynman variable X F > 0 there is a correlation between the longitudinal and mean transverse momenta of the secondary particles that resembles the so-called seagull effect in πN collisions. The correlation is absent for values X F 1 this correlation disappears. The two results are in mutual agreement and indicate the existence of a region of the nucleus where its action on the secondary-particle flux is attenuated. 6 refs., 3 figs

  19. 12 CFR 792.62 - Requests for accounting for disclosures.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Requests for accounting for disclosures. 792.62... § 792.62 Requests for accounting for disclosures. At the time of the request for access or correction or at any other time, an individual may request an accounting of disclosures made of the individual's...

  20. 22 CFR 62.31 - Au pairs.

    Science.gov (United States)

    2010-04-01

    ... requirements set forth at § 62.10 sponsors shall: (1) Inform all host families of the philosophy, rules, and... Department of State any incidents involving or alleging a crime of moral turpitude or violence. (m) Reporting...