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Sample records for rev-mediated nuclear export

  1. Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

    Science.gov (United States)

    Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

    2017-02-01

    HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

  2. Nuclear Factor 90, a cellular dsRNA binding protein inhibits the HIV Rev-export function

    Directory of Open Access Journals (Sweden)

    St-Laurent Georges

    2006-11-01

    Full Text Available Abstract Background The HIV Rev protein is known to facilitate export of incompletely spliced and unspliced viral transcripts to the cytoplasm, a necessary step in virus life cycle. The Rev-mediated nucleo-cytoplasmic transport of nascent viral transcripts, dependents on interaction of Rev with the RRE RNA structural element present in the target RNAs. The C-terminal variant of dsRNA-binding nuclear protein 90 (NF90ctv has been shown to markedly attenuate viral replication in stably transduced HIV-1 target cell line. Here we examined a mechanism of interference of viral life cycle involving Rev-NF90ctv interaction. Results Since Rev:RRE complex formations depend on protein:RNA and protein:protein interactions, we investigated whether the expression of NF90ctv might interfere with Rev-mediated export of RRE-containing transcripts. When HeLa cells expressed both NF90ctv and Rev protein, we observed that NF90ctv inhibited the Rev-mediated RNA transport. In particular, three regions of NF90ctv protein are involved in blocking Rev function. Moreover, interaction of NF90ctv with the RRE RNA resulted in the expression of a reporter protein coding sequences linked to the RRE structure. Moreover, Rev influenced the subcellular localization of NF90ctv, and this process is leptomycin B sensitive. Conclusion The dsRNA binding protein, NF90ctv competes with HIV Rev function at two levels, by competitive protein:protein interaction involving Rev binding to specific domains of NF90ctv, as well as by its binding to the RRE-RNA structure. Our results are consistent with a model of Rev-mediated HIV-1 RNA export that envisions Rev-multimerization, a process interrupted by NF90ctv.

  3. 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

  4. HIV-1 pre-mRNA commitment to Rev mediated export through PSF and Matrin 3

    International Nuclear Information System (INIS)

    Kula, Anna; Gharu, Lavina; Marcello, Alessandro

    2013-01-01

    Human immunodeficiency virus gene expression and replication are regulated at several levels. Incompletely spliced viral RNAs and full-length genomic RNA contain the RRE element and are bound by the viral trans-acting protein Rev to be transported out of the nucleus. Previously we found that the nuclear matrix protein MATR3 was a cofactor of Rev-mediated RNA export. Here we show that the pleiotropic protein PSF binds viral RNA and is associated with MATR3. PSF is involved in the maintenance of a pool of RNA available for Rev activity. However, while Rev and PSF bind the viral pre-mRNA at the site of viral transcription, MATR3 interacts at a subsequent step. We propose that PSF and MATR3 define a novel pathway for RRE-containing HIV-1 RNAs that is hijacked by the viral Rev protein.

  5. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: novel insights into the regulation of Rev nuclear import.

    LENUS (Irish Health Repository)

    Gu, Lili

    2011-01-01

    The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised.

  6. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  7. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  8. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.

    LENUS (Irish Health Repository)

    Gu, Lili

    2011-03-14

    Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  9. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

    Directory of Open Access Journals (Sweden)

    Sheehy Noreen

    2011-03-01

    Full Text Available Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  10. Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

    Science.gov (United States)

    Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

    2010-03-15

    Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

    Science.gov (United States)

    Booth, David S; Cheng, Yifan; Frankel, Alan D

    2014-12-08

    The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

  12. Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

    Science.gov (United States)

    Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

    2010-05-21

    NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

  13. 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.

  14. NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

    Science.gov (United States)

    Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

    2010-11-01

    Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

  15. 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.

  16. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

    Science.gov (United States)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-07-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

    Energy Technology Data Exchange (ETDEWEB)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kondoh, Yasumitsu; Osada, Hiroyuki [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori [Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2017-07-15

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

  18. Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

    International Nuclear Information System (INIS)

    Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

    2017-01-01

    An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

  19. Identification of a nuclear export signal in the KSHV latent protein LANA2 mediating its export from the nucleus

    International Nuclear Information System (INIS)

    Munoz-Fontela, C.; Collado, M.; Rodriguez, E.; Garcia, M.A.; Alvarez-Barrientos, A.; Arroyo, J.; Nombela, C.; Rivas, C.

    2005-01-01

    LANA2 is a latent protein detected in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected B cells that inhibits p53-dependent transcriptional transactivation and apoptosis and PKR-dependent apoptosis, suggesting an important role in the transforming activity of the virus. It has been reported that LANA2 localizes into the nucleus of both KSHV-infected B cells and transiently transfected HeLa cells. In this study, we show that LANA2 is a nucleocytoplasmic shuttling protein that requires a Rev-type nuclear export signal located in the C-terminus to direct the protein to the cytoplasm, through an association with the export receptor CRM1. In addition, a functional protein kinase B (PKB)/Akt phosphorylation motif partially overlapping with the nuclear export signal was identified. Nuclear exclusion of LANA2 was negatively regulated by the phosphorylation of threonine 564 by Akt. The ability of LANA2 to shuttle between nucleus and cytoplasm has implications for the function of this viral protein

  20. Evaluating the role of CRM1-mediated export for adenovirus gene expression

    International Nuclear Information System (INIS)

    Carter, Christoph C.; Izadpanah, Reza; Bridge, Eileen

    2003-01-01

    A complex of the Adenovirus (Ad) early region 1b 55-kDa (E1b-55kDa) and early region 4 ORF6 34-kDa (E4-34kDa) proteins promotes viral late gene expression. E1b-55kDa and E4-34kDa have leucine-rich nuclear export signals (NESs) similar to that of HIV Rev. It was proposed that E1b-55kDa and/or E4-34kDa might promote the export of Ad late mRNA via their Rev-like NESs, and the transport receptor CRM1. We treated infected cells with the cytotoxin leptomycin B to inhibit CRM1-mediated export; treatment initially delays the onset of late gene expression, but this activity completely recovers as the late phase progresses. We find that the E1b-55kDa NES is not required to promote late gene expression. Previous results showed that E4-34kDa-mediated late gene expression does not require an intact NES (J. Virol. 74 (2000), 6684-6688). Our results indicate that these Ad regulatory proteins promote late gene expression without intact NESs or active CRM1

  1. Mutational definition of functional domains within the Rev homolog encoded by human endogenous retrovirus K.

    Science.gov (United States)

    Bogerd, H P; Wiegand, H L; Yang, J; Cullen, B R

    2000-10-01

    Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the approximately 25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

  2. Mining the Human Complexome Database Identifies RBM14 as an XPO1-Associated Protein Involved in HIV-1 Rev Function

    OpenAIRE

    Budhiraja, Sona; Liu, Hongbing; Couturier, Jacob; Malovannaya, Anna; Qin, Jun; Lewis, Dorothy E.; Rice, Andrew P.

    2015-01-01

    By recruiting the host protein XPO1 (CRM1), the HIV-1 Rev protein mediates the nuclear export of incompletely spliced viral transcripts. We mined data from the recently described human nuclear complexome to identify a host protein, RBM14, which associates with XPO1 and Rev and is involved in Rev function. Using a Rev-dependent p24 reporter plasmid, we found that RBM14 depletion decreased Rev activity and Rev-mediated enhancement of the cytoplasmic levels of unspliced viral transcripts. RBM14 ...

  3. 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

  4. The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export.

    Science.gov (United States)

    Brunotte, Linda; Flies, Joe; Bolte, Hardin; Reuther, Peter; Vreede, Frank; Schwemmle, Martin

    2014-07-18

    In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available Transport of messenger RNA (mRNA from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex.

  6. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  7. Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

    Directory of Open Access Journals (Sweden)

    Min-Hsuan Lin

    Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

  8. The Cellular Distribution of RanGAP1 Is Regulated by CRM1-Mediated Nuclear Export in Mammalian Cells.

    Directory of Open Access Journals (Sweden)

    Keith Cha

    Full Text Available The Ran GTPase activating protein RanGAP1 plays an essential role in nuclear transport by stimulating RanGTP hydrolysis in the cytoplasmic compartment. In mammalian cells, unmodified RanGAP1 is predominantly cytoplasmic, whereas modification by small ubiquitin-related modifier protein (SUMO targets RanGAP1 to the cytoplasmic filaments of nuclear pore complex (NPC. Although RanGAP1 contains nine putative nuclear export signals and a nuclear localization signal, little is known if RanGAP1 shuttles between the nuclear and cytoplasmic compartments and how its primary localization in the cytoplasm and at the NPC is regulated. Here we show that inhibition of CRM1-mediated nuclear export using RNAi-knockdown of CRM1 and inactivation of CRM1 by leptomycin B (LMB results in nuclear accumulation of RanGAP1. LMB treatment induced a more robust redistribution of RanGAP1 from the cytoplasm to the nucleoplasm compared to CRM1 RNAi and also uniquely triggered a decrease or loss of RanGAP1 localization at the NPC, suggesting that LMB treatment is more effective in inhibiting CRM1-mediated nuclear export of RanGAP1. Our time-course analysis of LMB treatment reveals that the NPC-associated RanGAP1 is much more slowly redistributed to the nucleoplasm than the cytoplasmic RanGAP1. Furthermore, LMB-induced nuclear accumulation of RanGAP1 is positively correlated with an increase in levels of SUMO-modified RanGAP1, suggesting that SUMOylation of RanGAP1 may mainly take place in the nucleoplasm. Lastly, we demonstrate that the nuclear localization signal at the C-terminus of RanGAP1 is required for its nuclear accumulation in cells treated with LMB. Taken together, our results elucidate that RanGAP1 is actively transported between the nuclear and cytoplasmic compartments, and that the cytoplasmic and NPC localization of RanGAP1 is dependent on CRM1-mediated nuclear export.

  9. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    International Nuclear Information System (INIS)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum; Uhm, Sang-Jun; Song, Hyuk; Kim, Nam-Hyung; Kim, Jae-Hwan

    2012-01-01

    Highlights: ► We found the putative nuclear export signal motif within human NANOG homeodomain. ► Leucine-rich residues are important for human NANOG homeodomain nuclear export. ► CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ( 125 MQELSNILNL 134 ) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-ΔNLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  10. eEF1A Mediates the Nuclear Export of SNAG-Containing Proteins via the Exportin5-Aminoacyl-tRNA Complex

    Directory of Open Access Journals (Sweden)

    José Manuel Mingot

    2013-11-01

    Full Text Available Exportin5 mediates the nuclear export of double-stranded RNAs, including pre-microRNAs, adenoviral RNAs, and tRNAs. When tRNAs are aminoacylated, the Exportin5-aminoacyl (aa-tRNA complex recruits and coexports the translation elongation factor eEF1A. Here, we show that eEF1A binds to Snail transcription factors when bound to their main target, the E-cadherin promoter, facilitating their export to the cytoplasm in association with the aa-tRNA-Exportin5 complex. Snail binds to eEF1A through the SNAG domain, a protein nuclear export signal present in several transcription factor families, and this binding is regulated by phosphorylation. Thus, we describe a nuclear role for eEF1A and provide a mechanism for protein nuclear export that attenuates the activity of SNAG-containing transcription factors.

  11. IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

    Science.gov (United States)

    Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

    2017-10-09

    Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

  12. The BRO proteins of Bombyx mori nucleopolyhedrovirus are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

    International Nuclear Information System (INIS)

    Kang, Won Kyung; Kurihara, Masaaki; Matsumoto, Shogo

    2006-01-01

    The BRO proteins of Bombyx mori nucleopolyhedrovirus (BmNPV) display a biphasic pattern of intracellular localization during infection. At early times, they reside in the nucleus but then show both cytoplasmic and nuclear localization as the infection proceeds. Therefore, we examined the possibility of nuclear export. Using inhibitors, we reveal that BmNPV BRO proteins shuttle between the nucleus and cytoplasm. Mutations on the leucine-rich region of BRO proteins resulted in nuclear accumulation of transiently expressed proteins, suggesting that this region functions as a CRM1-dependent nuclear export signal (NES). On the contrary, mutant BRO-D with an altered NES did not show nuclear accumulation in infected cells, although protein production seemed to be reduced. RT-PCR analysis showed that the lower level of protein production was due to a reduction in RNA synthesis. Taken together, our results suggest that BRO proteins are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

  13. Tap and Dbp5, but not Gag, are involved in DR-mediated nuclear export of unspliced Rous sarcoma virus RNA

    International Nuclear Information System (INIS)

    LeBlanc, Jason J.; Uddowla, Sabena; Abraham, Benjamin; Clatterbuck, Sarah; Beemon, Karen L.

    2007-01-01

    All retroviruses must circumvent cellular restrictions on the export of unspliced RNAs from the nucleus. While the unspliced RNA export pathways for HIV and Mason-Pfizer monkey virus are well characterized, that of Rous sarcoma virus (RSV) is not. We have previously reported that the RSV direct repeat (DR) elements are involved in the cytoplasmic accumulation of unspliced viral RNA. Here, using fluorescent in situ hybridization (FISH), we demonstrate that unspliced viral RNAs bearing a single point mutation (G8863C) in the DR exhibit a restricted cellular localization in and around the nucleus. In contrast, wild type unspliced viral RNA had a diffuse localization throughout the nucleus and cytoplasm. Since the RSV Gag protein has a transient localization in the nucleus, we examined the effect of Gag over-expression on a DR-mediated reporter construct. While Gag did not enhance DR-mediated nuclear export, the dominant-negative expression of two cellular export factors, Tap and Dbp5, inhibited expression of the same reporter construct. Furthermore, FISH studies using the dominant-negative Dbp5 demonstrated that unspliced wild type RSV RNA was retained within the nucleus. Taken together, these results further implicate the DR in nuclear RNA export through interactions with Tap and Dbp5

  14. Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

    International Nuclear Information System (INIS)

    Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

    2005-01-01

    The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

  15. Stable assembly of HIV-1 export complexes occurs cotranscriptionally

    DEFF Research Database (Denmark)

    Nawroth, Isabel; Mueller, Florian; Basyuk, Eugenia

    2014-01-01

    The HIV-1 Rev protein mediates export of unspliced and singly spliced viral transcripts by binding to the Rev response element (RRE) and recruiting the cellular export factor CRM1. Here, we investigated the recruitment of Rev to the transcription sites of HIV-1 reporters that splice either post......- or cotranscriptionally. In both cases, we observed that Rev localized to the transcription sites of the reporters and recruited CRM1. Rev and CRM1 remained at the reporter transcription sites when cells were treated with the splicing inhibitor Spliceostatin A (SSA), showing that the proteins associate with RNA prior...... to or during early spliceosome assembly. Fluorescence recovery after photobleaching (FRAP) revealed that Rev and CRM1 have similar kinetics as the HIV-1 RNA, indicating that Rev, CRM1, and RRE-containing RNAs are released from the site of transcription in one single export complex. These results suggest...

  16. Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export.

    Science.gov (United States)

    Larsen, Sean; Bui, Steven; Perez, Veronica; Mohammad, Adeba; Medina-Ramirez, Hilario; Newcomb, Laura L

    2014-08-28

    Influenza is a segmented negative strand RNA virus. Each RNA segment is encapsulated by influenza nucleoprotein and bound by the viral RNA dependent RNA polymerase (RdRP) to form viral ribonucleoproteins responsible for RNA synthesis in the nucleus of the host cell. Influenza transcription results in spliced mRNAs (M2 and NS2), intron-containing mRNAs (M1 and NS1), and intron-less mRNAs (HA, NA, NP, PB1, PB2, and PA), all of which undergo nuclear export into the cytoplasm for translation. Most cellular mRNA nuclear export is Nxf1-mediated, while select mRNAs utilize Crm1. Here we inhibited Nxf1 and Crm1 nuclear export prior to infection with influenza A/Udorn/307/1972(H3N2) virus and analyzed influenza intron-less mRNAs using cellular fractionation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined direct interaction between Nxf1 and influenza intron-less mRNAs using immuno purification of Nxf1 and RT-PCR of associated RNA. Inhibition of Nxf1 resulted in less influenza intron-less mRNA export into the cytoplasm for HA and NA influenza mRNAs in both human embryonic kidney cell line (293 T) and human lung adenocarcinoma epithelial cell line (A549). However, in 293 T cells no change was observed for mRNAs encoding the components of the viral ribonucleoproteins; NP, PA, PB1, and PB2, while in A549 cells, only PA, PB1, and PB2 mRNAs, encoding the RdRP, remained unaffected; NP mRNA was reduced in the cytoplasm. In A549 cells NP, NA, HA, mRNAs were found associated with Nxf1 but PA, PB1, and PB2 mRNAs were not. Crm1 inhibition also resulted in no significant difference in PA, PB1, and PB2 mRNA nuclear export. These results further confirm Nxf1-mediated nuclear export is functional during the influenza life cycle and hijacked for select influenza mRNA nuclear export. We reveal a cell type difference for Nxf1-mediated nuclear export of influenza NP mRNA, a reminder that cell type can influence molecular mechanisms. Importantly, we

  17. CRM1-mediated nuclear export is required for 26 S proteasome-dependent degradation of the TRIP-Br2 proto-oncoprotein.

    Science.gov (United States)

    Cheong, Jit Kong; Gunaratnam, Lakshman; Hsu, Stephen I-Hong

    2008-04-25

    Overexpression of the proto-oncogene TRIP-Br2 (SERTAD2) has been shown to induce E2F activity and promote tumorigenesis, whereas ablation of TRIP-Br2 arrests cell proliferation. Timely degradation of many cell cycle regulators is fundamental to the maintenance of proper cell cycle progression. Here we report novel mechanism(s) that govern the tight regulation of TRIP-Br2 levels during cell cycle progression. TRIP-Br2 was observed to be a short-lived protein in which the expression level peaks at the G(1)/S boundary. TRIP-Br2 accumulated in cells treated with 26 S proteasome inhibitors. Co-immunoprecipitation studies revealed that TRIP-Br2 forms ubiquitin conjugates. In silico analysis identified a putative leucine-rich nuclear export signal (NES) motif that overlaps with the PHD-Bromo interaction domain in the acidic C-terminal transactivation domain (TAD) of TRIP-Br2. This NES motif is highly conserved in widely divergent species and in all TRIP-Br family members. TRIP-Br2 was shown to be stabilized in G(2)/M phase cells through nuclear entrapment, either by deletion of the acidic C-terminal TAD, which includes the NES motif, or by leptomycin B-mediated inhibition of the CRM1-dependent nuclear export machinery. Mutation of leucine residue 238 of this NES motif abolished the interaction between CRM1 and TRIP-Br2, as well as the nuclear export of TRIP-Br2 and its subsequent 26 S proteasome-dependent degradation. These data suggest that CRM1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of TRIP-Br2.

  18. Physical protection of export/import and transportation of nuclear material in the Slovak Republic

    International Nuclear Information System (INIS)

    Vaclav, J

    2002-01-01

    Full text: The paper contains short overview about average amount of nuclear materials transported on the territory of the Slovak Republic in a year, and the physical protection of these nuclear materials. There are several types of transportation and export/import of nuclear materials in the SR: fresh fuel import; import of other unirradiated nuclear materials (e.g. depleted uranium, natural uranium); export of unirradiated nuclear materials (e.g. natural uranium); internal transportation of fresh fuel; internal transportation of other unirradiated nuclear materials; internal transportation of spent fuel. The main objective of the nuclear regulatory authority SR is to supervise observation of the national legislation as follows: the act no. 130 / 1998 on peaceful use of nuclear energy; UJD SR's regulation no. 186/1999 which details the physical protection of the nuclear facilities, nuclear materials, and radioactive waste (following requirements of INFCIRC 225 / Rev. 4); UJD SR's regulation no. 284 / 1999 which details conditions of nuclear material and radioactive wastes transportation. (author)

  19. Nuclear export controls

    International Nuclear Information System (INIS)

    Thorne, C.E.

    1999-01-01

    One approach to describing the multilateral nuclear export controls is to do it according to time. This led to an interesting discovery, i.e. multilateral export controls have been defined by four distinct periods, the forst two of abut five years each, the second two about twice as long. These time periods have another interesting property. The two suppliers groups, which we will discuss in detail, have alternated in dominance over nearly thirty years. After describing the historical developments, the status of the present situation in multilateral nuclear export controls is examined, with the strengths and weaknesses. The future of multilateral nuclear export controls and possible ways that might be taken are considered

  20. Exportin-5 mediates nuclear export of SRP RNA in vertebrates.

    Science.gov (United States)

    Takeiwa, Toshihiko; Taniguchi, Ichiro; Ohno, Mutsuhito

    2015-04-01

    The signal recognition particle is a ribonucleoprotein complex that is essential for the translocation of nascent proteins into the endoplasmic reticulum. It has been shown that the RNA component (SRP RNA) is exported from the nucleus by CRM1 in the budding yeast. However, how SRP RNA is exported in higher species has been elusive. Here, we show that SRP RNA does not use the CRM1 pathway in Xenopus oocytes. Instead, SRP RNA uses the same export pathway as pre-miRNA and tRNA as showed by cross-competition experiments. Consistently, the recombinant Exportin-5 protein specifically stimulated export of SRP RNA as well as of pre-miRNA and tRNA, whereas an antibody raised against Exportin-5 specifically inhibited export of the same RNA species. Moreover, biotinylated SRP RNA can pull down Exportin-5 but not CRM1 from HeLa cell nuclear extracts in a RanGTP-dependent manner. These results, taken together, strongly suggest that the principal export receptor for SRP RNA in vertebrates is Exportin-5 unlike in the budding yeast. © 2015 The Authors. Genes to Cells published by Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  1. Nuclear localization signal regulates porcine circovirus type 2 capsid protein nuclear export through phosphorylation.

    Science.gov (United States)

    Hou, Qiang; Hou, Shaohua; Chen, Qing; Jia, Hong; Xin, Ting; Jiang, Yitong; Guo, Xiaoyu; Zhu, Hongfei

    2018-02-15

    The open reading frame 2 (ORF2) of Porcine circovirus type 2 (PCV2) encodes the major Capsid (Cap) protein, which self-assembles into virus-like particle (VLP) of similar morphology to the PCV2 virion and accumulates in the nucleus through the N-terminal arginine-rich nuclear localization signal (NLS). In this study, PCV2 Cap protein and its derivates were expressed via the baculovirus expression system, and the cellular localization of the recombinant proteins were investigated using anti-Cap mAb by imaging flow cytometry. Analysis of subcellular localization of Cap protein and its variants demonstrated that NLS mediated Cap protein nuclear export as well as nuclear import, and a phosphorylation site (S17) was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the NLS domain to regulate Cap protein nuclear export. Phosphorylation of NLS regulating the PCV2 Cap protein nuclear export was also demonstrated in PK15 cells by fluorescence microscopy. Moreover, the influence of Rep and Rep' protein on Cap protein subcellular localization was investigated in PK15 cells. Phosphorylation of NLS regulating Cap protein nuclear export provides more detailed knowledge of the PCV2 viral life cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Murine Leukemia Virus Uses TREX Components for Efficient Nuclear Export of Unspliced Viral Transcripts

    Directory of Open Access Journals (Sweden)

    Toshie Sakuma

    2014-03-01

    Full Text Available Previously we reported that nuclear export of both unspliced and spliced murine leukemia virus (MLV transcripts depends on the nuclear export factor (NXF1 pathway. Although the mRNA export complex TREX, which contains Aly/REF, UAP56, and the THO complex, is involved in the NXF1-mediated nuclear export of cellular mRNAs, its contribution to the export of MLV mRNA transcripts remains poorly understood. Here, we studied the involvement of TREX components in the export of MLV transcripts. Depletion of UAP56, but not Aly/REF, reduced the level of both unspliced and spliced viral transcripts in the cytoplasm. Interestingly, depletion of THO components, including THOC5 and THOC7, affected only unspliced viral transcripts in the cytoplasm. Moreover, the RNA immunoprecipitation assay showed that only the unspliced viral transcript interacted with THOC5. These results imply that MLV requires UAP56, THOC5 and THOC7, in addition to NXF1, for nuclear export of viral transcripts. Given that naturally intronless mRNAs, but not bulk mRNAs, require THOC5 for nuclear export, it is plausible that THOC5 plays a key role in the export of unspliced MLV transcripts.

  3. Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels during Drosophila embryogenesis

    DEFF Research Database (Denmark)

    DeLotto, Robert; DeLotto, Yvonne; Steward, Ruth

    2007-01-01

    , including nuclei on the dorsal side. Nuclear export is blocked by leptomycin B, a potent inhibitor of Exportin 1 (CRM1)-mediated nuclear export. We have developed a novel in vivo assay revealing the presence of a functional leucine-rich nuclear export signal within the carboxyterminal 44 amino acids...

  4. RanBP3 influences interactions between CRM1 and its nuclear protein export substrates

    OpenAIRE

    Englmeier, Ludwig; Fornerod, Maarten; Bischoff, F. Ralf; Petosa, Carlo; Mattaj, Iain W.; Kutay, Ulrike

    2001-01-01

    We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1 family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP. However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can stabilize CRM1–export substrate interaction. Nuclear RanBP3 stimulates CRM1-dependent protein export in permeabilized cells. These data indicate that RanBP3 functions by a novel mec...

  5. Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer

    DEFF Research Database (Denmark)

    Chen, Ying; Camacho, Sandra Catalina; Silvers, Thomas R

    2017-01-01

    Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluate...

  6. Notice to exporters on products prohibited from export (nuclear material, equipment and large nuclear units)

    International Nuclear Information System (INIS)

    1988-01-01

    In order to ensure that the policy to avoid the proliferation of nuclear weapons is complied with, the French Administration applies stricter controls over the export of certain sensitive products, materials and equipment. To this effect, lists of such products, materials and equipment are published in the form of Notices to exporters and periodically revised. This Notice repeals and replaces the previous Notice published in the Official Gazette of 21 January 1986. Annex I contains the list of materials whose export is subject to nuclear non-proliferation controls. Annex II lists the equipment whose export is subject to the same controls. Annex III includes the list of large nuclear units for which an application for prior approval of export must be submitted to the Administrations concerned. (NEA) [fr

  7. Export markets for nuclear technology

    International Nuclear Information System (INIS)

    Huettl, A.J.

    1985-01-01

    By late 1984, nuclear power plants were in operation or under construction in 32 countries of the globe. An additional six countries had concrete plans for building nuclear power plants. Of these 38 countries, ten have shown that they posses the necessary know-how and the technical facilities to plan and build nuclear power plants practically on their own. Seven of these ten countries have already acted as exporters of nuclear power plants, albeit with very different degrees of market penetration. In addition, there have been a number of countries for quite some time whose industries have managed to manufacture many important nuclear power plant components. Their high level of technical development and the problems frequently encountered in export financing have made them very attractive partners of the true exporters of nuclear power plants. For the future, it must be expected that some of the countries which have so far limited their efforts to the construction of nuclear power plants at home will also develop into exporters of nuclear technology. The report contains a survey of the range of nuclear products available, a list of reactor vendors, reactor lines, and data on the economics of electricity generation in nuclear plants. It then goes on to offer detailed descriptions of the market and the demand situation. Interesting chapters are devoted to the selection criteria applied by importing countries, to financing problems, and to the influences exerted by the political environment. A realistic forecast is attempted in order to make a quantitative analysis of possible export contracts up until the year 2000. (orig.) [de

  8. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    International Nuclear Information System (INIS)

    Chen, Zhi; Liu, Shaoning; Sun, Wenbo; Chen, Lei; Yoo, Dongwan; Li, Feng; Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun; Zhou, Shun; Wu, Jiaqiang

    2016-01-01

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  9. Nuclear export signal of PRRSV NSP1α is necessary for type I IFN inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhi [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Liu, Shaoning [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Shandong Institute of Veterinary Drug Quality Inspection, Shandong Key Laboratory for Quality Safety Monitoring and Risk Assessment of Animal Products, Huaicun Street No. 68, Jinan 250722, Shandong Province (China); Sun, Wenbo; Chen, Lei [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Yoo, Dongwan [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Feng [Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007 (United States); Ren, Sufang; Guo, Lihui; Cong, Xiaoyan; Li, Jun [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); Zhou, Shun [College of marine science and engineering, Qingdao Agricultural University, Changcheng Road No. 700, Qingdao 266109 (China); Wu, Jiaqiang, E-mail: wujiaqiang2000@sina.com [Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Sangyuan Road No. 8, Jinan 250100 (China); and others

    2016-12-15

    The nonstructural protein 1α (NSP1α) of porcine reproductive and respiratory syndrome virus (PRRSV) is a nucleo-cytoplasmic protein that suppresses the production of type I interferon (IFN). In this study, we investigated the relationship between the subcellular distribution of NSP1α and its inhibition of type I IFN. NSP1α was found to contain the classical nuclear export signal (NES) and NSP1α nuclear export was CRM-1-mediated. NSP1α was shuttling between the nucleus and cytoplasm. We also showed that the nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. NSP1α was also found to interact with CBP, which implies a possible mechanism of CBP degradation by NSP1α. Taken together, our results describe a novel mechanism of PRRSV NSP1α for type I IFN inhibition and suppression of the host innate antiviral response. - Highlights: •NSP1α contains the NES and NSP1α nuclear export was CRM-1-mediated. •NSP1α was shuttling between the nucleus and cytoplasm continuously. •The nuclear export of NSP1α was necessary for its ability for type I IFN inhibition. •NSP1α interacts with CBP, which implies the mechanism of CBP degradation by NSP1α.

  10. Nuclear export controls and nuclear safeguards

    International Nuclear Information System (INIS)

    Sevini, F.

    2013-01-01

    The export control of dual use goods has developed since the early seventies to counter nuclear proliferation. The paper provides an overview of dual-use export control issues also in relation with the Additional Protocol to the Comprehensive Safeguards Agreement, which requires States to provide declarations of the export of the controlled items listed in its Annex II, derived from the Nuclear Suppliers Group Trigger list. Recommendations for improvement are proposed. On the EU level, the paper summarises the framework set by the European Council Regulation 428/2009, requiring Member States to impose control on exports, brokering and transit of dual use goods. The Regulation includes the so-called 'EU dual-use control list' integrating the lists of dual-use items defined by the international regimes and requires also the control on intangible technology transfers as foreseen by U.N. Security Council Resolution 1540. ESARDA has recently launched a new sub-Working Group on export control, which raised large interest and may evolve to a full-fledged working group. Export control may provide an opportunity of technical collaboration between ESARDA and INMM. The paper is followed by the slides of the presentation. (author)

  11. Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element

    Directory of Open Access Journals (Sweden)

    Dudley Jaquelin P

    2009-02-01

    Full Text Available Abstract Background Mouse mammary tumor virus (MMTV encodes the Rem protein, an HIV Rev-like protein that enhances nuclear export of unspliced viral RNA in rodent cells. We have shown that Rem is expressed from a doubly spliced RNA, typical of complex retroviruses. Several recent reports indicate that MMTV can infect human cells, suggesting that MMTV might interact with human retroviruses, such as human immunodeficiency virus (HIV, human T-cell leukemia virus (HTLV, and human endogenous retrovirus type K (HERV-K. In this report, we test whether the export/regulatory proteins of human complex retroviruses will increase expression from vectors containing the Rem-responsive element (RmRE. Results MMTV Rem, HIV Rev, and HTLV Rex proteins, but not HERV-K Rec, enhanced expression from an MMTV-based reporter plasmid in human T cells, and this activity was dependent on the RmRE. No RmRE-dependent reporter gene expression was detectable using Rev, Rex, or Rec in HC11 mouse mammary cells. Cell fractionation and RNA quantitation experiments suggested that the regulatory proteins did not affect RNA stability or nuclear export in the MMTV reporter system. Rem had no demonstrable activity on export elements from HIV, HTLV, or HERV-K. Similar to the Rem-specific activity in rodent cells, the RmRE-dependent functions of Rem, Rev, or Rex in human cells were inhibited by a dominant-negative truncated nucleoporin that acts in the Crm1 pathway of RNA and protein export. Conclusion These data argue that many retroviral regulatory proteins recognize similar complex RNA structures, which may depend on the presence of cell-type specific proteins. Retroviral protein activity on the RmRE appears to affect a post-export function of the reporter RNA. Our results provide additional evidence that MMTV is a complex retrovirus with the potential for viral interactions in human cells.

  12. Nuclear exports. Parliamentary control and confidentiality

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2015-01-01

    With its decision taken on 21. October 2014 (Az.: 2 BvE 5/11) the Federal Constitutional Court (BVerfG) decided during court proceedings between administrative bodies on the scope and limits of the parliamentary right of information. Even though the proceeding did not deal with nuclear exports but arm exports, foreign trade law, however, does not only designate an export licence obligation for military weapons but also for so called dual-use goods meaning goods, which can be used both for friendly as well as for military purposes. The export of these goods requires according to the so-called Dual-Use Regulation (EG) 428/2009 a licence. Annex I category 0 of the regulation (EG) 428/2009 lists a variety of nuclear materials, plants and equipment items for which this licence applies. In the same manner as arm exports, also exports of nuclear dual-use goods are being discussed in a special cabinet committee, the Federal Security Council (BSR), which shall coordinate cross-departmentally the German security and defence policy under consideration of economic interests and which categorises its results, according to the rules of procedure, as confidential. Also legally not regulated but common ''preliminary enquiries'' at the responsible Federal Ministry or rather Federal Office of Economics and Export Control by companies which plan an export and want to affirm the general approval for their export business prior to conclusion of contract take not only place for arm exports but also for nuclear dual-use goods. The decision by the Federal Constitutional Court can be applied to consultations about the authorisation of nuclear dual-use goods.

  13. A novel, mouse mammary tumor virus encoded protein with Rev-like properties

    International Nuclear Information System (INIS)

    Indik, Stanislav; Guenzburg, Walter H.; Salmons, Brian; Rouault, Francoise

    2005-01-01

    We have identified a novel, multiple spliced, subgenomic mRNA species in MMTV producing cells of different origin containing an open reading frame encoding a 39-kDa Rev-like protein, Rem (regulator of expression of MMTV). An EGFP-Rem fusion protein is shown to be predominantly in the nucleolus. Further leptomycin B inhibits the nuclear export of nonspliced MMTV transcripts, implicating Rem in nuclear export by the Crm1 pathway in MMTV. Rem is thus reminiscent of the Rec protein from the related endogenous human retrovirus, HERV-K

  14. The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta.

    Directory of Open Access Journals (Sweden)

    Keith I Pardee

    2009-02-01

    Full Text Available Heme is a ligand for the human nuclear receptors (NR REV-ERBalpha and REV-ERBbeta, which are transcriptional repressors that play important roles in circadian rhythm, lipid and glucose metabolism, and diseases such as diabetes, atherosclerosis, inflammation, and cancer. Here we show that transcription repression mediated by heme-bound REV-ERBs is reversed by the addition of nitric oxide (NO, and that the heme and NO effects are mediated by the C-terminal ligand-binding domain (LBD. A 1.9 A crystal structure of the REV-ERBbeta LBD, in complex with the oxidized Fe(III form of heme, shows that heme binds in a prototypical NR ligand-binding pocket, where the heme iron is coordinately bound by histidine 568 and cysteine 384. Under reducing conditions, spectroscopic studies of the heme-REV-ERBbeta complex reveal that the Fe(II form of the LBD transitions between penta-coordinated and hexa-coordinated structural states, neither of which possess the Cys384 bond observed in the oxidized state. In addition, the Fe(II LBD is also able to bind either NO or CO, revealing a total of at least six structural states of the protein. The binding of known co-repressors is shown to be highly dependent upon these various liganded states. REV-ERBs are thus highly dynamic receptors that are responsive not only to heme, but also to redox and gas. Taken together, these findings suggest new mechanisms for the systemic coordination of molecular clocks and metabolism. They also raise the possibility for gas-based therapies for the many disorders associated with REV-ERB biological functions.

  15. The Structural Basis of Gas-Responsive Transcription by the Human Nuclear Hormone Receptor REV-ERBβ

    Science.gov (United States)

    Pardee, Keith I; Xu, Xiaohui; Reinking, Jeff; Schuetz, Anja; Dong, Aiping; Liu, Suya; Zhang, Rongguang; Tiefenbach, Jens; Lajoie, Gilles; Plotnikov, Alexander N; Botchkarev, Alexey; Krause, Henry M; Edwards, Aled

    2009-01-01

    Heme is a ligand for the human nuclear receptors (NR) REV-ERBα and REV-ERBβ, which are transcriptional repressors that play important roles in circadian rhythm, lipid and glucose metabolism, and diseases such as diabetes, atherosclerosis, inflammation, and cancer. Here we show that transcription repression mediated by heme-bound REV-ERBs is reversed by the addition of nitric oxide (NO), and that the heme and NO effects are mediated by the C-terminal ligand-binding domain (LBD). A 1.9 Å crystal structure of the REV-ERBβ LBD, in complex with the oxidized Fe(III) form of heme, shows that heme binds in a prototypical NR ligand-binding pocket, where the heme iron is coordinately bound by histidine 568 and cysteine 384. Under reducing conditions, spectroscopic studies of the heme-REV-ERBβ complex reveal that the Fe(II) form of the LBD transitions between penta-coordinated and hexa-coordinated structural states, neither of which possess the Cys384 bond observed in the oxidized state. In addition, the Fe(II) LBD is also able to bind either NO or CO, revealing a total of at least six structural states of the protein. The binding of known co-repressors is shown to be highly dependent upon these various liganded states. REV-ERBs are thus highly dynamic receptors that are responsive not only to heme, but also to redox and gas. Taken together, these findings suggest new mechanisms for the systemic coordination of molecular clocks and metabolism. They also raise the possibility for gas-based therapies for the many disorders associated with REV-ERB biological functions. PMID:19243223

  16. Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid Protein Disrupts Host Cell Nuclear Import.

    Science.gov (United States)

    Jacobs, Susan C; Taylor, Adam; Herrero, Lara J; Mahalingam, Suresh; Fazakerley, John K

    2017-10-20

    Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export from the nucleus and a region within the N-terminal part of CHIKV capsid protein was required for active nuclear targeting. In contrast to encephalitic alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however, mutating the NES of capsid protein (∆NES) blocked host protein access to the nucleus. Interactions between capsid protein and the nucleus warrant further investigation.

  17. The export of China nuclear power

    International Nuclear Information System (INIS)

    Zhang Jian

    2012-01-01

    The article first introduces the meaning of nuclear power export, and then analyses the advantages of China nuclear industry based on the status and development of this industry. At the same time. the collection of nuclear development for the next 30 years of several nations in south-east Asia, south Asia, Middle East, Africa and South America is compiled, which could be a valuable reference for foreseeing nuclear power export market. Finally, as the situation throughout the world is considered, some suggestions are made that what else could be done for future development and export. (author)

  18. Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.

    Science.gov (United States)

    Li, Ping; Noegel, Angelika A

    2015-11-16

    Nuclear export of messenger ribonucleoproteins (mRNPs) through the nuclear pore complex (NPC) can be roughly classified into two forms: bulk and specific export, involving an nuclear RNA export factor 1 (NXF1)-dependent pathway and chromosome region maintenance 1 (CRM1)-dependent pathway, respectively. SUN proteins constitute the inner nuclear envelope component of the l I: nker of N: ucleoskeleton and C: ytoskeleton (LINC) complex. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results indicate that both SUN1 and SUN2 interact with heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. Leptomycin B treatment indicates that SUN1 functions in mammalian mRNA export involving the NXF1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complexes via a direct interaction with NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope and hands it over to Nup153. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Nuclear Import and Export of the Thyroid Hormone Receptor.

    Science.gov (United States)

    Zhang, Jibo; Roggero, Vincent R; Allison, Lizabeth A

    2018-01-01

    The thyroid hormone receptors, TRα1 and TRβ1, are members of the nuclear receptor superfamily that forms one of the most abundant classes of transcription factors in multicellular organisms. Although primarily localized to the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. The fine balance between nuclear import and export of TRs has emerged as a critical control point for modulating thyroid hormone-responsive gene expression. Mutagenesis studies have defined two nuclear localization signal (NLS) motifs that direct nuclear import of TRα1: NLS-1 in the hinge domain and NLS-2 in the N-terminal A/B domain. Three nuclear export signal (NES) motifs reside in the ligand-binding domain. A combined approach of shRNA-mediated knockdown and coimmunoprecipitation assays revealed that nuclear entry of TRα1 is facilitated by importin 7, likely through interactions with NLS-2, and importin β1 and the adapter importin α1 interacting with both NLS-1 and NLS-2. Interestingly, TRβ1 lacks NLS-2 and nuclear import depends solely on the importin α1/β1 heterodimer. Heterokaryon and fluorescence recovery after photobleaching shuttling assays identified multiple exportins that play a role in nuclear export of TRα1, including CRM1 (exportin 1), and exportins 4, 5, and 7. Even single amino acid changes in TRs dramatically alter their intracellular distribution patterns. We conclude that mutations within NLS and NES motifs affect nuclear shuttling activity, and propose that TR mislocalization contributes to the development of some types of cancer and Resistance to Thyroid Hormone syndrome. © 2018 Elsevier Inc. All rights reserved.

  20. The NPT and nuclear export controls

    International Nuclear Information System (INIS)

    Berkhout, F.

    1992-01-01

    Controls on the export of nuclear materials and technology were originally imposed in wartime and under the United States Atomic Energy Act of 1946 to restrict the supply of uranium. But there was no international agreement until the mid 1960s; before that the United States, Canada, France and the Soviet Union imposed export controls on a national basis. The Non-Proliferation Treaty, especially Articles I-IV, set out the first world wide controls on the nuclear trade. These articles are explained in the context of the relevant Committees (the Zangger Committee, the Committee on the Assurance of Supply, the National Export Committee and the Coordinating Committee for Multilateral Export Control) and Guidelines (the Nuclear Suppliers Guidelines and the International Nuclear Fuel Cycle Evaluation). Recent developments which have a bearing on nuclear trade, such as the single European market, the emergence of new supplies and the break-up of the Soviet Union, are considered. (UK)

  1. Exporting nuclear engineering and the industry's viewpoint

    International Nuclear Information System (INIS)

    Barthelt, K.

    1986-01-01

    Nuclear energy offers all possibilities to reduce the energy problems in the world which arise with the world-wide increasing population and the energy demand connected with it. The Federal Republic of Germany lives on the exports of refined technical methods which also include nuclear engineering. The exports of nuclear engineering should lead to a technology transfer with guidance and training on an equal basis between the industrial and developing countries. The preconditions of exporting nuclear-technical systems are a well-functioning domestic market and a certain support by the government, especially with regard to giving guarantees for the special exports risks of these big projects. On the other hand, exports are also needed in order to be able to continue providing high-level technology for the domestic market. (UA) [de

  2. Political implications of US nuclear-export-policy development

    International Nuclear Information System (INIS)

    Johnson-Freese, J.S.

    1981-01-01

    There has been a great deal of international debate regarding how effective strict export controls on nuclear-energy supplies are toward a non-proliferation goal. With the Carter Administration, the debate was heightened by a new, more-vigorous US nuclear-export policy, much of which was codified by the Nuclear Non-Proliferation Act of 1978 (NNPA). Because of the US position in both the international non-proliferation regime and nuclear export market, the NNPA has had far-reaching consequences. The thesis of this paper is that a nuclear-export policy that fails to consider its short-term ramifications, as the NNPA has been accused of, will be self-defeating. If the US wants a viable worldwide nuclear non-proliferation policy, it must first direct its efforts toward building a domestic non-proliferation consensus, and then worldwide, rather than first setting a highly controversial policy and expecting other nations to fall into line. This work provides a comprehensive case study of US nuclear-export policy between the years 1976 to 1980 in support of the thesis. Further, the behavior and impact of the interest groups which seem to shape US nuclear-export policies is examined, and recommendations made regarding the role of groups in nuclear policy-making and implementation. Finally, recommendations are made regarding non-proliferation policy for the future, as it relates to nuclear exports

  3. Hormone-dependent nuclear export of estradiol receptor and DNA synthesis in breast cancer cells

    Science.gov (United States)

    Lombardi, Maria; Castoria, Gabriella; Migliaccio, Antimo; Barone, Maria Vittoria; Di Stasio, Rosina; Ciociola, Alessandra; Bottero, Daniela; Yamaguchi, Hiroshi; Appella, Ettore; Auricchio, Ferdinando

    2008-01-01

    In breast cancer cells, cytoplasmic localization of the estradiol receptor α (ERα) regulates estradiol-dependent S phase entry. We identified a nuclear export sequence (NES) in ERα and show that its export is dependent on both estradiol-mediated phosphatidylinositol-3-kinase (PI3K)/AKT activation and chromosome region maintenance 1 (CRM1). A Tat peptide containing the ERα NES disrupts ERα–CRM1 interaction and prevents nuclear export of ERα- and estradiol-induced DNA synthesis. NES-ERα mutants do not exit the nucleus and inhibit estradiol-induced S phase entry; ERα-dependent transcription is normal. ERα is associated with Forkhead proteins in the nucleus, and estradiol stimulates nuclear exit of both proteins. ERα knockdown or ERα NES mutations prevent ERα and Forkhead nuclear export. A mutant of forkhead in rhabdomyosarcoma (FKHR), which cannot be phosphorylated by estradiol-activated AKT, does not associate with ERα and is trapped in the nucleus, blocking S phase entry. In conclusion, estradiol-induced AKT-dependent phosphorylation of FKHR drives its association with ERα, thereby triggering complex export from the nucleus necessary for initiation of DNA synthesis and S phase entry. PMID:18644889

  4. A Study on Improvement of Export Control law's understanding for nuclear control items' exporters in Rep. of Korea

    International Nuclear Information System (INIS)

    Lim, Dong Hyuk; Choi, Sun Do; Yang, Seung Hyo

    2011-01-01

    According to export of UAE commercial reactor and JRTR(Jordan Research and Training Reactor) in 2009, Korea's international prestige has enhanced and it has been more important for researcher in charge of export control to understand and carry out duties on export control by obeying Nuclear Suppliers Group(NSG) Guidelines. Currently, the NSG tries to prevent the proliferation of nuclear weapons by harmonising export control systems of participating countries in relation to trade with nuclear commodities and nuclear-related dual-use materials, equipment, software and technology. In addition, through the implementation of two sets of Guidelines for nuclear exports and nuclear-related exports, the NSG aims to ensure that nuclear trade for peaceful purposes does not contribute to the proliferation of nuclear weapons or other nuclear explosive devices, and that international trade and cooperation in the nuclear field is not hindered unjustly in the process. However, there is still not a little confusion of export businesses owing to lack of understanding of nuclear items in Korea. Therefore, by correctly understanding export control systems, permits and licenses, ITT and persistingly communicating with export businesses, Researchers in charge of export control are able to eliminate confusion of production businesses regarding export and establish a export control culture

  5. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1993-05-01

    On 13 December 1990 the Director General received a letter dated 10 December 1990 from the Resident Representative of Austria to the Agency in the same terms as the letter and its Annex reproduced in document INFCIRC/209/Rev.1. That document deals with communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material [ru

  6. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and other Material

    International Nuclear Information System (INIS)

    1993-06-01

    On 13 December 1990 the Director General received a letter dated 10 December 1990 from the Resident Representative of Austria to the Agency in the same terms as the letter and its Annex reproduced in document INFCIRC/209/Rev.1. That document deals with communications received from Members regarding the export of nuclear material and of certain categories of equipment and other material [es

  7. Canada's nuclear export policy

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, R W; Wonder, E F [Carleton Univ., Ottawa, Ontario (Canada)

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology.

  8. Canada's nuclear export policy

    International Nuclear Information System (INIS)

    Morrison, R.W.; Wonder, E.F.

    1978-01-01

    The factors influencing the evolution of Canada's nuclear export policy are examined. Initially, nuclear technology was exported to establish an industry in Canada and to share the technology with other countries. After 1974 an increasingly broad range of political and social factors were taken into account and safeguards became the dominant factor. The indirect impacts of the new policy fall into two groups. One consists of the effects of Canada's leadership in taking a tough stand on safeguards. The second group of effects involve the concern of other countries about access to secure energy supplies and advanced technology. (O.T.)

  9. Nuclear export criteria and controls in the United States

    International Nuclear Information System (INIS)

    Shapar, H.K.

    1979-01-01

    The paper describes the export licensing procedure and the modifications made to it under the 1978 Nuclear Non-Proliferation Act (NNPA) to achieve greater control over exports of nuclear material and facilities. Export licences from the Nuclear Regulatory Commission are now required for certain items connected with nuclear plant construction and the procedure for obtaining the views of the Executive Branch have been formalised. The President is enabled to override the denial of an export licence by the NRC. Amongst the new criteria on the export licensing procedure added to the 1954 Atomic Energy Act, the NNPA provides that the IAEA Safeguards under the Non-Proliferation Treaty are applicable to exported nuclear material or facilities, together with adequate physical protection measures. (NEA) [fr

  10. A common high standard for nuclear power plant exports: overview and analysis of the Nuclear Power Plant Exporters' Principles of Conduct

    International Nuclear Information System (INIS)

    Perkovich, George; Radzinsky, Brian

    2012-01-01

    At this time, there is no overarching global framework to regulate the development of the nuclear power industry. Laws concerning the export of nuclear technology vary across jurisdictions, and politically-binding arrangements such as the Nuclear Suppliers Group (NSG) help ensure that weapons-usable or dual-use technologies are not exported, but no single international regime or agreement manages the gamut of potential risks that may arise from the export of civilian nuclear power plants. Accordingly in 2008, the Carnegie Endowment for International Peace convened internationally-recognised experts in nuclear energy to begin a dialogue with nuclear power plant vendors about defining common criteria for the socially responsible export of nuclear power plants. The goal was to articulate a comprehensive set of principles and best practices that would raise the overall standard of practice for exports of nuclear power plants while enjoying widespread support and adherence. The outcome of this process is the Nuclear Power Plant Exporters' Principles of Conduct - an export-oriented code of conduct for nuclear power plant vendors. The Principles of Conduct help ensure that the participating companies will proceed with the sale of a new nuclear power plant only after a careful assessment of the legal, political, and technical contexts surrounding potential customers. It comprises six 'principles' that each address a major area of concern involved in the export of a nuclear power plant: safety, physical security, environmental protection and spent fuel management, systems of compensation for nuclear damage, non-proliferation and safeguards, and business ethics. The Principles of Conduct entail vendor responsibilities to apply specific standards or engage in certain practices before signing contracts and during the marketing and construction phases of a nuclear power plant export project. Conformity with the Principles of Conduct is voluntary and not-legally binding, but the

  11. Communication Received from the PermanentMission of Mexico to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-06-19

    The Director General has received a note verbale dated 15 June 2012 from the Permanent Mission of Mexico to the International Atomic Energy Agency providing information on the decision of the Government of Mexico to act in accordance with the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2.

  12. Communication Received from the Permanent Mission of Mexico to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-06-19

    The Director General has received a note verbale dated 15 June 2012 from the Permanent Mission of Mexico to the International Atomic Energy Agency providing information on the decision of the Government of Mexico to act in accordance with the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2.

  13. Communication Received from the Permanent Mission of Mexico to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2012-01-01

    The Director General has received a note verbale dated 15 June 2012 from the Permanent Mission of Mexico to the International Atomic Energy Agency providing information on the decision of the Government of Mexico to act in accordance with the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2

  14. Communication Received from the PermanentMission of Mexico to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2012-01-01

    The Director General has received a note verbale dated 15 June 2012 from the Permanent Mission of Mexico to the International Atomic Energy Agency providing information on the decision of the Government of Mexico to act in accordance with the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2

  15. Nuclear exporters cartel

    International Nuclear Information System (INIS)

    Mandelbaum, M.

    1977-01-01

    Events that have transpired in the past few years that have caused renewed concern about the spread of nuclear weapons are reviewed. Many proposals have been made recently for keeping the bomb from spreading. The author feels that the most novel and intriguing of them is the one advanced by Senator Abraham Ribicoff and Steven J. Baker; in their proposal, the world market for nuclear reactors would be divided into precisely defined shares among the industrial nations that now manufacture them for export; each exporter would be guaranteed a certain number of sales annually; and each would pledge not to sell uranium enrichment or plutonium reprocessing technology, as Germany did to Brazil. This might not halt proliferation, but it would give the world a few more years to find a solution

  16. Communications received from Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    The Director General has received notes verbales relating to the export of nuclear material, equipment and technology from the following Permanent Missions to the International Atomic Energy Agency: notes verbales dated 15 June 1994 from the Permanent Missions of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America; and a note verbale dated 10 November 1994 from the Permanent Mission of the Russian Federation. The purpose of these notes verbales is to provide further information on these Governments' nuclear export policies and practices. In the light of the wish expressed at the end of each note verbale, the analogous text of the notes verbales is attached hereto. The enclosure of these notes verbales with the amendments to the ''Guidelines for Nuclear Transfers'' contained in INFCIRC/254/Rev.1/Part 1/Mod.1 is reproduced in the Annex

  17. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  18. NESmapper: accurate prediction of leucine-rich nuclear export signals using activity-based profiles.

    Directory of Open Access Journals (Sweden)

    Shunichi Kosugi

    2014-09-01

    Full Text Available The nuclear export of proteins is regulated largely through the exportin/CRM1 pathway, which involves the specific recognition of leucine-rich nuclear export signals (NESs in the cargo proteins, and modulates nuclear-cytoplasmic protein shuttling by antagonizing the nuclear import activity mediated by importins and the nuclear import signal (NLS. Although the prediction of NESs can help to define proteins that undergo regulated nuclear export, current methods of predicting NESs, including computational tools and consensus-sequence-based searches, have limited accuracy, especially in terms of their specificity. We found that each residue within an NES largely contributes independently and additively to the entire nuclear export activity. We created activity-based profiles of all classes of NESs with a comprehensive mutational analysis in mammalian cells. The profiles highlight a number of specific activity-affecting residues not only at the conserved hydrophobic positions but also in the linker and flanking regions. We then developed a computational tool, NESmapper, to predict NESs by using profiles that had been further optimized by training and combining the amino acid properties of the NES-flanking regions. This tool successfully reduced the considerable number of false positives, and the overall prediction accuracy was higher than that of other methods, including NESsential and Wregex. This profile-based prediction strategy is a reliable way to identify functional protein motifs. NESmapper is available at http://sourceforge.net/projects/nesmapper.

  19. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Directory of Open Access Journals (Sweden)

    Beatriz M. A. Fontoura

    2013-07-01

    Full Text Available Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses.

  20. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Science.gov (United States)

    Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

    2013-01-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

  1. Nucleocytoplasmic trafficking of Nipah virus W protein involves multiple discrete interactions with the nuclear import and export machinery

    International Nuclear Information System (INIS)

    Audsley, Michelle D.; Jans, David A.; Moseley, Gregory W.

    2016-01-01

    Paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. Nevertheless, the W protein of the highly lethal bat-borne paramyxovirus Nipah virus (NiV) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (NLS) within the C-terminal domain. Here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of W. We show that the N-terminal domain interacts with importin α1 and contributes to nuclear accumulation of W, indicative of a novel N-terminal NLS. We also find that W undergoes exportin-1 mediated nuclear export, dependent on a leucine at position 174. Together, these data enable significant revision of the generally accepted model of W trafficking, with implications for understanding of the mechanisms of NiV immune evasion. - Highlights: • A new model for Nipah virus W protein nucleocytoplasmic trafficking is proposed. • Nipah W protein is shown to undergo active nuclear export via exportin-1. • Nipah W nuclear import is mediated by multiple nuclear localisation signals.

  2. Communication from the Permanent Mission of Cyprus to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2001-01-01

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of Cyprus providing information on the export policies and practices of the Government of Cyprus with respect to the export of nuclear material, equipment and technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment to the Note Verbale was issued previously as INFCIRC/254/Rev. 4/Part 1

  3. Challenges to nuclear export controls today

    International Nuclear Information System (INIS)

    Chatelus, R.; Sevini, F.; Janssens, W.; Michel, Q.

    2014-01-01

    Nuclear energy and nuclear proliferation programs are potentially inter-twinned, which is a point to be taken into account when analysing the development of civil nuclear energy, both domestically and as foreign investment. International agreements ensure that the adhering countries fulfil their obligations and do not abuse civil nuclear programs for the production of nuclear weapons. Uranium enrichment is the process currently most focused on in this respect by recent news and recent technological and commercial developments. But also the so-called reactor-based pathway, with extraction of plutonium from spent nuclear fuel by reprocessing remains in the spotlight of inspectors. Two of the main and complementary pillars on which the prevention of such diversion relies, are Strategic Export Control and International Safeguards. Strategic export control is a key barrier against nuclear proliferation. In many countries including the EU, it is set by a legal framework, envisaging implementation, enforcement and prosecution. The goods that can exported only with authorisations are those identified by the international export control regimes; primarily the Nuclear Suppliers Group in the case of nuclear items. It is complemented by nuclear safeguards measures, and especially in the past few years, by the IAEA State Level concept, which looks at the overall country's potential, including its industrial structure to derive conclusions on the absence of undeclared activities. However, the strict control of goods and knowledge is a moving target, since technological developments, globalisation and the intensifying exchange of information via the worldwide web offer increasing opportunities to proliferators to acquire sensitive items and competencies, and create bigger challenges to enforcement, calling for new responses. Research and development programmes must be directed towards supporting the adaptation of current proliferation containment systems to these new

  4. Nuclear exports and international cooperation

    International Nuclear Information System (INIS)

    McCardle, J.J.

    1981-06-01

    Canada's nuclear export policy together with its non-proliferation and safeguards policy embrace both the country's desire to promote international cooperation in the peaceful uses of nuclear energy and its effort to minimize the risk of further proliferation of nuclear weapons. This policy reflects the belief that only if Canadian parliamentary and public opinion can be convinced that Canada's nuclear exports will not contribute to nuclear proliferation will the long-term health of the country's nuclear industry be assured. Canada requires a political commitment to non-proliferation from its nuclear partners, and looks to the IAEA to administer safeguards on nuclear material of Canadian origin to guarantee that commitment. Agreements reached with its nuclear partners are in accordance with provisions of the non-proliferation treaty and include a contingency provision for fall-back safeguards if the other state should withdraw from the NPT. Provision is made for mutual agreement on reprocessing and enrichment of nuclear material. Agreements have been reached with some twenty nuclear partners, and efforts are continuing to come to new international understanding on reprocessing, enrichment, and plutonium storage

  5. Nuclear exportation and importation - the Brazilian situation

    International Nuclear Information System (INIS)

    Lavos Coimbra, G.

    1986-01-01

    The author proposes to set up a working group which should be responsible for the compilation of laws, procedures, and national policies for the nuclear importation and exportation in the supplying and receiving countries. Shared international views would simplify the flow of imports and exports between the countries. The author describes the different phases of exportation and importation of nuclear material are processed in her country, Brazil. (CW) [de

  6. The politics of fading dreams: Britain and the nuclear export business

    International Nuclear Information System (INIS)

    Boardman, R.; Grieve, M.

    1983-01-01

    The subject is discussed as follows: introduction to a chapter focused on the politics of Britain's foreign nuclear trade; export goals and the nuclear programme (discussion of Magnox, AGR, SGHWR and PWR); the pursuit of exports; nuclear exports and proliferation (reprocessing; fast reactors; plutonium; INFCE); public opinion, nuclear power and exports (interest groups); conclusions (Britain's nuclear exports and non-proliferation). (U.K.)

  7. Russian nuclear industry exports

    International Nuclear Information System (INIS)

    Gorbatchev, A.

    2016-01-01

    Rosatom is the world leader for the export of nuclear technologies. 34 reactors of Russian technology are being built or planned worldwide. Most reactors proposed by Rosatom are third generation VVER-1200 units with an electric power output of 1200 MWe. Although the nuclear island is always built by Rosatom, the remain of the plant can be subcontracted to other enterprises and European companies are sought because they would bring a european quality touch to Russian works. One of the main assets of Rosatom is to propose an integrated offer from supplying nuclear fuel to managing nuclear waste via the turnkey building of nuclear power plants. Another important asset is the financial assistance of the Russian state through state credit or the support from Russian national banks that appears to be a decisive advantage in the international competition to win markets. We have to temper the Russian export perspectives by noting that most projects are set in countries that are prone to instabilities and that the economic crisis affecting Russia has a negative impact on its financial means. (A.C.)

  8. Communication Received from the Permanent Mission of the Republic of Serbia to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2012-01-01

    The Director General has received a note verbale dated 28 September 2012 from the Permanent Mission of Serbia to the International Atomic Energy Agency providing information on the decision of the Government of Serbia to adhere to the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2 [es

  9. Communication Received from the Permanent Mission of the Republic of Serbia to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2012-01-01

    The Director General has received a note verbale dated 28 September 2012 from the Permanent Mission of Serbia to the International Atomic Energy Agency providing information on the decision of the Government of Serbia to adhere to the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2 [fr

  10. Communication Received from the Permanent Mission of the Republic of Serbia to the International Atomic Energy Agency Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology and the Guidelines for Transfers of Nuclear-related Dual-use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2012-01-01

    The Director General has received a note verbale dated 28 September 2012 from the Permanent Mission of Serbia to the International Atomic Energy Agency providing information on the decision of the Government of Serbia to adhere to the 'Guidelines for the Export of Nuclear Material, Equipment and Technology', issued as document INFCIRC/254/Rev.10/Part 1, including its Annexes, and with the 'Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Material, Software and Related Technology', issued as document INFCIRC/254/Rev.8/Part 2

  11. Study on status of nuclear export/import implementation in KAERI

    International Nuclear Information System (INIS)

    Kim, H. J.; Lee, B. D.; Lee, S. H.; Park, H. J.; So, D. S.

    2004-01-01

    As Korea is the member of ZC(Zangger Committee) and NSG(Nuclear Suppliers Group), domestic legislation reflected their guideline of nuclear export. The paper investigate the status of implementation procedures of nuclear export and import in KAERI based on domestic and international law. In addition, the paper analyzes on problem of export/import implementation system and also extract the efficient implementation system of nuclear export and import

  12. Export financing of nuclear power plants - banks experience

    International Nuclear Information System (INIS)

    Loeber

    1977-01-01

    1) Dimension and volume of the export financing of a nuclear power plant: 1.1) export orders of a new dimension; 1.2) individual loans occurring in connection with the export of a nuclear power plant: a) financial loans for maturities falling due under the export portion of the project; b) financial loans for the settlement of down- and interim payments to be made in connection with the export portion of the project; c) financial loans for the payment of local costs; d) loans for the financing of fuel elements; 2) governmental export insurance; 3) export financing in the individual industrial countries: USA, France, Great Britain, Japan (EXIMBANK), FRG. (orig./HP) [de

  13. Communication from the Permanent Mission of Australia to the International Atomic Energy Agency regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of Australia, dated 31 August 2001, providing information on the export policies and practices of the Government of Australia with respect to the export of nuclear material, equipment and technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment referenced in the Note Verbale was issued previously as INFCIRC/254/Rev. 5/Part 1

  14. B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication.

    Science.gov (United States)

    Passos-Castilho, Ana Maria; Marchand, Claude; Archambault, Denis

    2018-02-01

    The bovine immunodeficiency virus (BIV) Rev shuttling protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev proteins. Several viral proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoprotein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. US Nuclear Non-Proliferation Policy: impact on exports and nuclear industry could not be determined

    International Nuclear Information System (INIS)

    Staats, E.B.

    1980-01-01

    The Nuclear Non-Proliferation Act of 1978 established new measures to prevent the diversion to weapons use of peaceful nuclear exports. It also created a policy to confirm US reliability as a nuclear supplier. GAO did not identify any export sales lost as a result of the Act, but did find indications that nonprofileration policies can influence export sales. Based on avavailable data, GAO could not determine the impact of the Act on the competitiveness of US nuclear exports. However, US companies are at some disadvantage because importers perceive that implementation of the Act may result in delayed export licenses. The United States dominated the nuclear export market through the early 1970s. However, foreign competitors, some aided by US technology transfers, emerged to monopolize home markets and complete for third-country business. Further, the market has been depressed since 1974 and prospects for US nuclear power plant exports have dimmed greatly. However, US companies continue to view exports as important to sustain production capacity

  16. Optimizing the protein switch: altering nuclear import and export signals, and ligand binding domain

    Science.gov (United States)

    Kakar, Mudit; Davis, James R.; Kern, Steve E.; Lim, Carol S.

    2007-01-01

    Ligand regulated localization controllable protein constructs were optimized in this study. Several constructs were made from a classical nuclear export signal (HIV-rev, MAPKK, or progesterone receptor) in combination with a SV40 T-antigen type nuclear import signal. Different ligand binding domains (LBDs from glucocorticoid receptor or progesterone receptor) were also tested for their ability to impart control over localization of proteins. This study was designed to create constructs which are cytoplasmic in the absence of ligand and nuclear in the presence of ligand, and also to regulate the amount of protein translocating to the nucleus on ligand induction. The balance between the strengths of import and export signals was critical for overall localization of proteins. The amount of protein entering the nucleus was also affected by the dose of ligand (10-100nM). However, the overall import characteristics were determined by the strengths of localization signals and the inherent localization properties of the LBD used. This study established that the amount of protein present in a particular compartment can be regulated by the use of localization signals of various strengths. These optimized localization controllable protein constructs can be used to correct for diseases due to aberrant localization of proteins. PMID:17574289

  17. Nuclear export controls - Closing the gaps

    International Nuclear Information System (INIS)

    Schmidt, Fritz W.

    2005-01-01

    Concerns over a nuclear 'black market' have focused international attention on the effectiveness of nuclear export controls. IAEA Director General Mohamed ElBaradei has stated that the emergence of a multinational illicit network demonstrated the inadequacy of the present export control system, that international cooperation on export controls lay on informal arrangements that were not only not binding but also limited in membership, and that export control information was not systematically shared with the IAEA. This criticism, often heard on the political level, does not really do justice to the work of export control groups. The emergence of a multinational illicit network does not necessarily prove failures in export control systems. Criminal activities, by definition, try to circumvent existing rules and regulations, or they exploit the absence of such rules on State level. To fight such individual cases is not so much a task of regular export control systems, whose function lies primarily in establishing standards and procedures for export controls on State level, but rather the task for intelligence services and their international cooperation. The basis of the export control regime is the Nuclear Non-Proliferation Treaty (NPT). Export controls can - and do - play an important role in fostering this universality goal by demanding the implementation of internationally agreed security standards in recipient countries before export licenses are granted. Drawn from the deliberations in the NPT conferences, the current standards to be demanded as conditions of supply are the following: Safeguards, Physical Protection, National export control provisions. According to the NPT system, export controls require IAEA verification in the recipient country. In addition, export controls enable States to provide information to the IAEA on exports and imports as required by the Additional Protocol. The 2005 NPT Review Conference will be an opportunity to review developments

  18. A Study on Improvement of Export Control law's understanding for nuclear control items' exporters in Rep. of Korea

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Dong Hyuk; Choi, Sun Do; Yang, Seung Hyo [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2011-10-15

    According to export of UAE commercial reactor and JRTR(Jordan Research and Training Reactor) in 2009, Korea's international prestige has enhanced and it has been more important for researcher in charge of export control to understand and carry out duties on export control by obeying Nuclear Suppliers Group(NSG) Guidelines. Currently, the NSG tries to prevent the proliferation of nuclear weapons by harmonising export control systems of participating countries in relation to trade with nuclear commodities and nuclear-related dual-use materials, equipment, software and technology. In addition, through the implementation of two sets of Guidelines for nuclear exports and nuclear-related exports, the NSG aims to ensure that nuclear trade for peaceful purposes does not contribute to the proliferation of nuclear weapons or other nuclear explosive devices, and that international trade and cooperation in the nuclear field is not hindered unjustly in the process. However, there is still not a little confusion of export businesses owing to lack of understanding of nuclear items in Korea. Therefore, by correctly understanding export control systems, permits and licenses, ITT and persistingly communicating with export businesses, Researchers in charge of export control are able to eliminate confusion of production businesses regarding export and establish a export control culture

  19. Postage for the messenger: Designating routes for Nuclear mRNA Export

    Science.gov (United States)

    Natalizio, Barbara J.; Wente, Susan R.

    2013-01-01

    Transcription of messenger(m) RNA occurs in the nucleus, making the translocation of mRNA across the nuclear envelope (NE) boundary a critical determinant of proper gene expression and cell survival. A major mRNA export route occurs via the NXF1-dependent pathway through the nuclear pore complexes (NPCs) embedded in the NE. However, recent findings have discovered new evidence supporting the existence of multiple mechanisms for crossing the NE, including both NPC-mediated and NE budding-mediated pathways. An analysis of the trans-acting factors and cis components that define these pathways reveals shared elements as well as mechanistic differences. We review here the current understanding of the mechanisms that characterize each pathway and highlight the determinants that influence mRNA transport fate. PMID:23583578

  20. Nuclear export of human hepatitis B virus core protein and pregenomic RNA depends on the cellular NXF1-p15 machinery.

    Science.gov (United States)

    Yang, Ching-Chun; Huang, Er-Yi; Li, Hung-Cheng; Su, Pei-Yi; Shih, Chiaho

    2014-01-01

    Hepatitis B virus (HBV) core protein (HBc) can shuttle between nucleus and cytoplasm. Cytoplasm-predominant HBc is clinically associated with severe liver inflammation. Previously, we found that HBc arginine-rich domain (ARD) can associate with a host factor NXF1 (TAP) by coimmunoprecipitation. It is well known that NXF1-p15 heterodimer can serve as a major export receptor of nuclear mRNA as a ribonucleoprotein complex (RNP). In the NXF1-p15 pathway, TREX (transcription/export) complex plays an important role in coupling nuclear pre-mRNA processing with mRNA export in mammalian cells. Here, we tested the hypothesis whether HBc and HBV specific RNA can be exported via the TREX and NXF1-p15 mediated pathway. We demonstrated here that HBc can physically and specifically associate with TREX components, and the NXF1-p15 export receptor by coimmunoprecipitation. Accumulation of HBc protein in the nucleus can be induced by the interference with TREX and NXF1-p15 mediated RNA export machinery. HBV transcripts encodes a non-spliced 3.5 kb pregenomic RNA (pgRNA) which can serve as a template for reverse transcription. Cytoplasmic HBV pgRNA appeared to be reduced by siRNA treatment specific for the NXF1-p15 complex by quantitative RT-qPCR and Northern blot analyses. This result suggests that the pgRNA was also exported via the NXF1-p15 machinery. We entertain the hypothesis that HBc protein can be exported as an RNP cargo via the mRNA export pathway by hijacking the TREX and NXF1-p15 complex. In our current and previous studies, HBc is not required for pgRNA accumulation in the cytoplasm. Furthermore, HBc ARD can mediate nuclear export of a chimeric protein containing HBc ARD in a pgRNA-independent manner. Taken together, it suggests that while both pgRNA and HBc protein exports are dependent on NXF1-p15, they are using the same export machinery in a manner independent of each other.

  1. The nuclear importation and exportation - The Brazilian situation

    International Nuclear Information System (INIS)

    Coimbra, G.L.

    1985-01-01

    The panorama of Brazilian economy emphasizing the measurements adopted by Brazilian government referring to importation and exportation policy is presented. The Brazilian Nuclear Program knows the nuclear trade gives good economic perspective. In the context of importation and exportation policy the laws concerned to nuclear trade transactions, taxes, national organizations responsible by the external trade policy and their attributions are presented. (M.C.K.) [pt

  2. Exporting nuclear engineering and the government's viewpoint

    International Nuclear Information System (INIS)

    Schill, H.

    1986-01-01

    The reasons for the government's positive attitude to nuclear engineering exports are explained, especially with regard to them being a compensation of the decreasing domestic demand. The federal government considers such exports to be necessary and correct for economical and energy-political reasons. Their contribution reaches from accompanying measures to the provision of state guarantees of export financing activities. (UA) [de

  3. The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

    Science.gov (United States)

    Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

    2017-11-01

    Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

  4. Analysis and prediction of leucine-rich nuclear export signals

    DEFF Research Database (Denmark)

    La Cour, T.; Kiemer, Lars; Mølgaard, Anne

    2004-01-01

    We present a thorough analysis of nuclear export signals and a prediction server, which we have made publicly available. The machine learning prediction method is a significant improvement over the generally used consensus patterns. Nuclear export signals (NESs) are extremely important regulators...... this analysis is that the most important properties of NESs are accessibility and flexibility allowing relevant proteins to interact with the signal. Furthermore, we show that not only the known hydrophobic residues are important in defining a nuclear export signals. We employ both neural networks and hidden...

  5. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

    Science.gov (United States)

    Jackson, Brian R.; Boyne, James R.; Noerenberg, Marko; Taylor, Adam; Hautbergue, Guillaume M.; Walsh, Matthew J.; Wheat, Rachel; Blackbourn, David J.; Wilson, Stuart A.; Whitehouse, Adrian

    2011-01-01

    The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. PMID:21814512

  6. Export and import provisions for nuclear materials and power plants

    International Nuclear Information System (INIS)

    Malsch, M.G.

    1976-01-01

    The present paper deals with 1) statutory requirements for export and import licensing of nuclear reactors and fuels; 2) regulations and procedures to issuance of exportlicenses; 3) environmental impact of export licensing; 4) licensing of reactor equipment; 5) recent restrictions on imports and exports of nuclear fuels. (RW) [de

  7. Information Interaction with IAEA on Nuclear Import and Export

    International Nuclear Information System (INIS)

    Osokina, A.; Snytnikov, A.

    2015-01-01

    This paper considers organizational aspects of nuclear import and export interaction between the Russian Federation and the Agency. Requirements of nuclear import and export in Russia, information submission procedure and forms are determined in RF Government Regulation No 973 from December 15th 2000. Particularly, according to these requirements Russian licenced organizations implementing nuclear import and export submit reports about appointed transfers to State Corporation 'Rosatom'. Regulations of State Corporation 'Rosatom' entrusted gathering and processing of reporting information and interaction with IAEA to FSUE 'SCC of Rosatom'. Regulations of reporting information interaction were developed by SCC and approved by State Corporation 'Rosatom'. Russian organizations send notifications to SCC using regulation electron or paper forms. Regulations determine information security measures in reporting process. Automated nuclear import and export accounting system developed by SCC provides data entering, keeping and processing, enables to choose and submit requested information in different formats. This system is integrated with State Nuclear Material Control and Accounting System. Also submitted information is regularly compared with customs declarations data to improve reliability and consistency of information. Generalized nuclear import and export data is using by Departments of State Corporation 'Rosatom' and transmitting to Federal Environmental, Industrial and Nuclear Supervision Service of Russia in agreed forms. Summary information about international nuclear transfers is sending to IAEA according to INFCIRC/207. Reporting information is coordinating. Messaging with IAEA is realized by email using enciphering program. (author)

  8. Export of nuclear equipment and materials and the non-proliferation of nuclear weapons

    International Nuclear Information System (INIS)

    Courteix, Simone.

    1977-01-01

    The problem of the non-proliferation of nuclear weapons is one of great concern today despite the entry into force in the early '70s of the NPT. To master civilian nuclear technology implies the ability to develop nuclear explosive devices; therefore in recent years contacts have strengthened between countries exporting nuclear equipment, specially in the frame of the 'London Club' so as to ensure that their exports will not result in disseminating nuclear weapons. (NEA) [fr

  9. New U.S. nuclear export legislation

    International Nuclear Information System (INIS)

    Patermann, C.

    1978-01-01

    The new 1978 Export Control Act of the United States of America introduces a comprehensive arrangement of the criteria, responsibilities and procedures associated with nuclear exports, especially under the nonproliferation aspect. After a detailed analysis of the multitude of provisions it must be feared that, merely as a result of the high degree of formalization, bureaucratization and politicalization of these procedures, the U.S. can henceforth no longer be regarded as a reliable source of nuclear materials and facilities. An aspect received abroad with particular anguish is the fact that this unilateral aggravation of export controls was initiated after the start of the two-year INFCE program for international fuel cycle evaluation and that the new legislation forces the American government to renegotiate existing agreements on cooperation with the receiver countries under the threat of a delivery stop. (orig.) [de

  10. Assessing mRNA nuclear export in mammalian cells by microinjection.

    Science.gov (United States)

    Lee, Eliza S; Palazzo, Alexander F

    2017-08-15

    The nuclear export of mRNAs is an important yet little understood part of eukaryotic gene expression. One of the easiest methods for monitoring mRNA export in mammalian tissue culture cells is through the microinjection of DNA plasmids into the nucleus and monitoring the distribution of the transcribed product over time. Here we describe how to setup a microscope equipped with a micromanipulator used in cell microinjections, and we explain how to perform a nuclear mRNA export assay and obtain the nuclear export rate for any given mRNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    Science.gov (United States)

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. A quasi-lentiviral green fluorescent protein reporter exhibits nuclear export features of late human immunodeficiency virus type 1 transcripts

    International Nuclear Information System (INIS)

    Graf, Marcus; Ludwig, Christine; Kehlenbeck, Sylvia; Jungert, Kerstin; Wagner, Ralf

    2006-01-01

    We have previously shown that Rev-dependent expression of HIV-1 Gag from CMV immediate early promoter critically depends on the AU-rich codon bias of the gag gene. Here, we demonstrate that adaptation of the green fluorescent protein (GFP) reporter gene to HIV codon bias is sufficient to turn this hivGFP RNA into a quasi-lentiviral message following the rules of late lentiviral gene expression. Accordingly, GFP expression was significantly decreased in transfected cells strictly correlating with reduced RNA levels. In the presence of the HIV 5' major splice donor, the hivGFP RNAs were stabilized in the nucleus and efficiently exported to the cytoplasm following fusion of the 3' Rev-responsive element (RRE) and coexpression of HIV-1 Rev. This Rev-dependent translocation was specifically inhibited by leptomycin B suggesting export via the CRM1-dependent pathway used by late lentiviral transcripts. In conclusion, this quasi-lentiviral reporter system may provide a new platform for developing sensitive Rev screening assays

  13. Oil exporting countries need nuclear power

    International Nuclear Information System (INIS)

    Stauffer, T.R.

    1982-01-01

    The economic rationale for nuclear power in the oil exporting countries is analysed, with the collateral objective of defining the size of the potential market in terms of the exporting countries' economic opportunities and energy needs. The need for appropriate new institutions for licensing reactors, training personnel, and starting up plants follows directly from the size of the market and the economic incentives for the oil exporters to husband gas and oil. Gas and oil resources of the Middle Eastern countries are discussed, and future electricity needs estimated. (author)

  14. Study on the establishment of effective nuclear export system

    International Nuclear Information System (INIS)

    Kim, Byung Koo; So, Dong Sup; Baik, Dae Hyun; Kwack, Eun Ho; Shin, Jang Soo; Yoon, Wan Ki; Park, Wan Soo; Kim, Hyun Tae.

    1997-02-01

    To improve Korean nuclear export control system, the modification of the present export license procedure for the nuclear equipment and materials and the classification of control items and their related technologies are required. And it is also necessary to make a database of the original countries who have the right of prior consent. For the efficient export control of LWR items to DPRK, it is desirable to manage the export license scheme of nuclear reactor facility as a total package, and to prepare a control regime for the retransfer of nuclear reactor component such as reactor coolant pump and nuclear fuel whose technologies are not self-reliant. It is especially essential to prepare a systematic procedure for the supply of nuclear equipment and materials to DPRK in order to meet international guidelines of NSG and others through an accord on the nuclear cooperation between Republic of Korea (ROK) and DPRK. The principal elements to be included in the accord are the range of cooperation, the restriction within the peaceful uses, prior consent right in case of retransfer of important nuclear reactor components and of storage, transfer and changes of nuclear fuels, application of safeguards to the supplied Trigger list items, physical protection of nuclear material, requirement of the return of nuclear equipment and materials, and restriction right for the suspension or termination of the agreement. (author). 40 refs., 5 tabs., 8 figs

  15. Introduction to Technology Export License of Nuclear Facility

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hana; Lee, Chansuh; Shin, Donghoon [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2014-05-15

    In this regime, the Nuclear Safety and Security Commission (NSSC) has authority on final decision making. And the Korea Institute of Nuclear nonproliferation and Control (KINAC) has missions to review the classification and export licensing technically. In principle, classification and export licensing are applied and reviewed individually. However, the number of application for classification and licensing has increased geometrically in the last three years. This is largely a due to the contract that the Republic of Korea (ROK) has finalized to build the UAE Barakah Nuclear Power Plant (BNPP) and Jordan Research and Training Reactor (JRTR). This circumstance brought an administrative burden for the government and related institutes as well as stakeholders. This article introduces the law related to the 'Technology Export License of Nuclear Facility' which was developed and legislated to improve the efficiency and effectiveness of commodities classification and export licensing. This system could significantly reduce the licensing burden for transferring the technologies. However, the classification and license on this system are still requested when transferring the goods. Therefore, KINAC will continue to figure out the needs for the stakeholders and keep searching for solutions to problems inherent in the industry.

  16. Introduction to Technology Export License of Nuclear Facility

    International Nuclear Information System (INIS)

    Seo, Hana; Lee, Chansuh; Shin, Donghoon

    2014-01-01

    In this regime, the Nuclear Safety and Security Commission (NSSC) has authority on final decision making. And the Korea Institute of Nuclear nonproliferation and Control (KINAC) has missions to review the classification and export licensing technically. In principle, classification and export licensing are applied and reviewed individually. However, the number of application for classification and licensing has increased geometrically in the last three years. This is largely a due to the contract that the Republic of Korea (ROK) has finalized to build the UAE Barakah Nuclear Power Plant (BNPP) and Jordan Research and Training Reactor (JRTR). This circumstance brought an administrative burden for the government and related institutes as well as stakeholders. This article introduces the law related to the 'Technology Export License of Nuclear Facility' which was developed and legislated to improve the efficiency and effectiveness of commodities classification and export licensing. This system could significantly reduce the licensing burden for transferring the technologies. However, the classification and license on this system are still requested when transferring the goods. Therefore, KINAC will continue to figure out the needs for the stakeholders and keep searching for solutions to problems inherent in the industry

  17. Implementation of the Nuclear Export Control at KAERI

    International Nuclear Information System (INIS)

    Kim, Hyun-Jo; Lee, Byung-Doo; Lee, Sung-Ho

    2006-01-01

    Korea has joined multilateral export control regimes which include Wassenaar Arrangement(WA), Nuclear Suppliers Group(NSG), Missile Technology Control Regime(MTCR) and Australian Group(AG), and their guideline and control lists are reflected in domestic legislation. Also, Catch-all control entered into force on 1 January 2003 in Korea. The frequency of the exports of product as a result of R and D and cooperation with other countries has been increased at Korea Atomic Energy Research Institute (KAERI). Therefore, this report describes the implementation status of a nuclear export control at KAERI and points out the practical issues

  18. Korea nuclear exports: Why did the Koreans win the UAE tender? Will Korea achieve its goal of exporting 80 nuclear reactors by 2030?

    International Nuclear Information System (INIS)

    Berthelemy, Michel; Leveque, Francois

    2011-01-01

    The success of Korea in winning, in December 2009, a USD 18.6 billion nuclear tender in the United Arab Emirates (UAE) has led to a growing interest in the organization and strengths of the Korean nuclear industry. In this paper, we present the main economic and political factors that explain the success of the Korean consortium. In particular, thanks to an active national program of Nuclear Power Plant (NPP) construction, Korea has developed distinct competitive advantages in terms of low cost, high credibility and high performance. At the same time, due to the important barriers to enter into the nuclear export market in the UAE, Korea has had to sacrifice its profit margin and has benefited from a strong political support from its government through export financing. More importantly, Korea's success is also due to its alliance with Westinghouse and the support of the US diplomacy. Subsequently, we show that while Korea has recently experienced setbacks in nuclear tenders, it will most certainly try to win in the short run a second nuclear tender with another aggressive price. In the longer run, Korea could take a growing share of the international market for NPPs. However, the extent to which Korea can achieve its long term export target will depend upon its capacity to finance nuclear export through export credits and upon the development of its alliance with Westinghouse. It is important to note that this paper was written before the Fukushima nuclear disaster. The scale of the human and environmental consequences of this accident are still unknown, and will undoubtedly have short and long term consequences on nuclear safety requirements and public attitude toward nuclear energy, which will most certainly impact the outlooks for nuclear new-builds. (authors)

  19. Study on international publicity and export strategy establishment of nuclear technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Bok; Choi, C.O.; Park, K. B.; Chang, M. H.; Kim, K. K.; Yang, M. S.; Jung, I. H.; Kim, K. P.; Wu, J. S.; Jang, C. I.; Han, B. O.; Sim, J. H.; Chung, M.; Chung, J.K

    1999-05-01

    The objective of this study is to devise a proper measure for international publicity and technology export strategy. Analysed and summaries in detail are other countries nuclear policy trend and the current technology development status of Korea Standard Nuclear Plant that we developed on our own technology, design and construction technology for research reactor, System-integrated Modular Advanced Reactor of which design is in progress, Direct use of Spent PWR Fuel in CANDU Reactors, and Radioisotopes. Based on that, the measures are proposed for the export industrialization of nuclear technology and establishment of the export basis. Also the international nuclear cooperation and publicity strategy are suggested to support the technology export basis. By surveying the world nuclear status, the direction for the international cooperation and publicity is settled and the specific publicity strategy is proposed for the cooperation with IAEA and multi-countries and the establishment of the nuclear technology export basis. As part of this project, the panel on major technologies such as Korea Standard Nuclear Plant, HANARO, and System-integrated Modular Advanced Reactor was displayed successfully at the IAEA meeting, which contribute much to the publicity of our nuclear technology to the international nuclear society. (author)

  20. An evaluation of Kazakhstan nuclear export control system

    International Nuclear Information System (INIS)

    Yeligbayeva, G.; Masenov, Ch.

    2002-01-01

    A system to control the export nuclear materials and technologies is a natural part of creating a self-sustaining government. The government of Kazakhstan has made a great deal of progress in building such a system. Control of export and import of nuclear materials and technologies and dual-use materials, related to nuclear activity, became one of the important part of mechanism of Non-Proliferation conditions realization in Kazakhstan. The system of export control has developed well over the 10 years. Kazakhstan is in the midst of a long process of building a functional export control system consistent with World standards. The state system of export control currently exists in Kazakhstan on the legislative base, and is based on efficient cooperation of the KAEC with a number of competent state bodies (Ministry of Economy, Ministry of Foreign Affairs, State Customs Committee) each of them has its own specific functions, duties and rights. The export is carried out using licenses, issued by the Ministry of Economy of the RK, according to applications of certain standard which are previously agreed with the KAEC under decision of the RK Government. The KAEC, acting on the base of export control principles and observance of international obligations on non-proliferation matter, makes decisions, only after thorough evaluation of ways of export and reliability of an end-user of the commodity, to agree the application for a license. The most fully developed aspect is the licensing process. General politics of export regulation in Kazakhstan are based on normative acts and rules, which are wholly appropriate (complementary) to the managing principles of nuclear export. There exists a full legal basis for the licensing system. But the process is going, some provisions is changing: in 2000 Kazakhstan corrected the export control law and approved the national control list very similar with EU control list, in 2002 the rules of the process of licensing the export and import

  1. Contributions of individual domains to function of the HIV-1 Rev response element.

    Science.gov (United States)

    O'Carroll, Ina P; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A; Smith, Sean; Wang, Yun-Xing; Rein, Alan

    2017-08-16

    The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using SAXS and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev Response Element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is "A"-shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains, and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function. Copyright © 2017

  2. Importance of dimer formation of myocardin family members in the regulation of their nuclear export.

    Science.gov (United States)

    Hayashi, Ken'ichiro; Morita, Tsuyoshi

    2013-01-01

    Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.

  3. Exporting apocalypse: CANDU reactors and nuclear proliferation

    International Nuclear Information System (INIS)

    McKay, Paul.

    The author believes that the peaceful use of nuclear technology leads inevitably to the production of nuclear weapons, and that CANDU reactors are being bought by countries that are likely to build bombs. He states that exports of reactors and nuclear materials cannot be defended and must be stopped

  4. Legal problems concerning the export of nuclear power plants

    International Nuclear Information System (INIS)

    Pierer, Heinrich von.

    1977-01-01

    The legal problems raised by the export of nuclear power plants may be divided into three main categories: nuclear operator's liability for nuclear damage, the consequences for the supplier of the licensing requirements in the national laws of the buyer country and finally, the constraints of applying non-proliferation safeguards on export of nuclear equipment. As regards the third party liability regime in particular, the difficulties lie essentially in the insufficiency of the definition of the nuclear operator and the lack of harmonization in, or even the absence of national laws in this field. (NEA) [fr

  5. Multiple Export Mechanisms for mRNAs

    Science.gov (United States)

    Delaleau, Mildred; Borden, Katherine L. B.

    2015-01-01

    Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730

  6. Analysis of nuclear export control system and implementing international nonproliferation regime in China

    International Nuclear Information System (INIS)

    Kim, J. S.; Lee, J. S.; Ahn, J. S.; Kim, B. G.; Min, K. S.

    2000-01-01

    China's exporting behaviour of nuclear items had been disconnected from the international non-proliferation regime such as IAEA safeguards and export control related with peaceful use of nuclear energy since 1970s. Especially, China had been one of principle suppliers of nuclear facility and technologies to Pakistan and Iran which had developed nuclear weapon programs. On the other hand, according to the rapid growth of economic scale after China began to open to the world, an active program for nuclear power plant as an electricity source had established. This means that China have surfaced as a big market to Korean nuclear industries. Regarding this, the paper dealt with the nuclear export control matters, i.e. the history of nuclear export control system and analyzed on background of enforcement of U.S.-China Nuclear Cooperation Agreement that had been apolitical issue between U.S. and China. Prospects toward conforming its nuclear export policies, laws and regulations to international standards also analyzed in results

  7. Overview of nuclear export policies of major foreign supplier nations

    International Nuclear Information System (INIS)

    1977-01-01

    The United States faces increased competition from foreign nuclear suppliers, including West Germany, France, the United Kingdom, Canada, and possibly, in the near future, Japan. This general overview shows the differences and similarities in foreign nuclear supplier export requirements. It is based on summaries furnished by the Department of State covering the nuclear export policies and procedures of the major foreign supplier nations

  8. Nuclear Non-Proliferation and Export Control in the Republic of Croatia

    International Nuclear Information System (INIS)

    Valcic, I.; Prah, M.; Mikec, N.

    2006-01-01

    In accordance with its internationally accepted obligations, the Republic of Croatia is actively implementing principles of non-proliferation and export control of nuclear materials and/or equipment. The article deals with treaties, conventions, agreements and other international arrangements that are creating certain obligation for Republic of Croatia related to nuclear non-proliferation. The most important are the Treaty on the Non-proliferation of Nuclear Weapons, the Convention on the Physical Protection of Nuclear Material, the Agreement between the Republic of Croatia and the International Atomic Energy Agency for the Application of Safeguards with Protocol, the Protocol Additional to the Agreement Between the Republic of Croatia and the International Atomic Energy Agency for the Application of Safeguards, the Comprehensive Nuclear Test-Ban Treaty, the NSG Guidelines for the Export of Nuclear Material, Equipment and Technology and NSG Guidelines for Transfers of Nuclear-Related Dual-Use Equipment, Materials, Software and Related Technology. In addition the article describes a national regulative framework, the basis for conducting activities in nuclear material control, export control of dual-use items as well as non-proliferation of the weapons of mass destruction. Details are given about the Nuclear Safety Act, the Act on Liability for Nuclear Damage, the Act on Export of Dual-Use Items, the Decree on the List of Dual-Use Items, the Law on Production, Repair and Trade in Arms and Military Equipment and the Decree specifying goods subject to export and import licenses. (author)

  9. NPT, export controls and nuclear trade

    International Nuclear Information System (INIS)

    Pande, Savita

    1997-01-01

    Nuclear trade has by and large remained unhampered vis-a-vis both the NPT as well as export control regulations. The NPT rules are regarded as insufficient, the guidelines appear to contravene the spirit of cooperation in trade and development between suppliers and recipients and there is no agreement among leading suppliers themselves on what constitutes the proper conduct of trade. Export control regimes are more or less too informal to be able to be implemented. The supplier states have to invariably depend on national legislations which again vary from country to country. The only common formal basis on which action can be taken is, therefore, the NPT, its loopholes notwithstanding. The idea of transparency, and supplier-recipient dialogue continues to be a myth and will continue to be so long as these regimes remain discriminatory, so long as some nations are more powerful than others by virtue of retaining nuclear weapons and superiority in nuclear technology and trade

  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.

    2016-01-01

    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

  11. 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.

  12. U.S. nuclear non-proliferation policy: impact on exports and nuclear industry could not be determined. Report to the Congress

    International Nuclear Information System (INIS)

    1980-01-01

    The Nuclear Non-Proliferation Act of 1978 established new measures to prevent the diversion to weapons use of peaceful nuclear exports. It also created a policy to confirm U.S. reliability as a nuclear supplier. GAO did not identify any export sales lost as a result of the Act, but did find indications that nonproliferation policies can influence export sales. Based on available data, GAO could not determine the impact of the Act on the competitiveness of U.S. nuclear exports. However, U.S. companies are at some disadvantage because importers perceive that implementation of the Act may result in delayed export licenses. The United States dominated the nuclear export market through the early 1970s. However, foreign competitors, some aided by U.S. technology transfers, emerged to monopolize home markets and compete for third-country business. Further, the market has been depressed since 1974 and prospects for U.S. nuclear power plant exports have dimmed greatly. However, U.S. companies continue to view exports as important to sustain production capacity

  13. Decree of the State Office for Nuclear Safety No. 147/1997 of 17 June 1997 specifying lists of selected nuclear-related items and dual-use nuclear-related items

    International Nuclear Information System (INIS)

    1997-01-01

    The core of the Decree consists of 2 lists, viz (a) the List of Selected Items (selected nuclear-related materials, equipment and technologies) which are subject to control regimes during imports, exports and transit; and (b) the List of Dual-Use Items (dual-use nuclear-related materials, equipment and technologies) which are subject to control regimes during imports and exports. Both Lists are based on the IAEA document INFCIRC/254/Rev.2/Part 2/Mod.1. (P.A.)

  14. Nuclear technology and the export control laws

    International Nuclear Information System (INIS)

    Munroe, J.L.; Pankratz, M.C.; Hogsett, V.H.; Lundy, A.S.

    1988-01-01

    Three basic US laws regulate the export of commodities, services, and technical data. People working in nuclear fields need to know of these laws and their impact on professional endeavors. Export of technical data means the communication of any information by oral, written, or any other means to foreign nationals within or outside the US. The medium for the communication may be a model, blueprint, sketch, or any other device that can convey information. If the data relates to items on one of the control lists, a license must be sought from the appropriated federal agency. The Militarily Critical Technologies List (MCTL), though not itself a control list, plays a major role in determining what technical data will require a validated license. The US Department of Energy (DOE), through Technical Working Gorup (TWG) 11, is responsible for the Nuclear Technology chapter of the MCTL. TWG 11 also prepares the Nuclear Technology Reference Book (NTRB), a classified guide to sensitive nuclear technology

  15. NESbase version 1.0: a database of nuclear export signals

    DEFF Research Database (Denmark)

    la Cour, T.; Gupta, Ramneek; Rapacki, Krzysztof

    2003-01-01

    information of whether NES was shown to be necessary and/or sufficient for export, and whether the export was shown to be mediated by the export receptor CRM1. The compiled information was used to make a sequence logo of the Leucine-rich NESs, displaying the conservation of amino acids within a window of 25...

  16. Korean system of export control to support the commercial nuclear transfer to UAE

    International Nuclear Information System (INIS)

    Cho, Young Ho

    2011-01-01

    In December 2009, the Republic of Korea won the contract to build 4 1,400 MW nuclear power reactors worth USD 20 billion in the UAE. The states-owned KEPCO will complete the turnkey project to the UAE including design, engineering, construction, nuclear fuel, operations, maintenance and technical support. Since sensitive nuclear technologies convertible to military purpose can be spread by the transfer of commercial nuclear power plant, it is essential prerequisite to implement nuclear export control tenaciously and effectively. About twenty years have passed since the Republic of Korea introduced export control system in domestic laws and regulations. Marking a major historical milestone in 2009 by ranking among global nuclear suppliers, the Korean government made a major step forward in export control framework to support its next nuclear export goal. (orig.)

  17. A comparative study on export control systems of nuclear technology in ROK and USA

    Energy Technology Data Exchange (ETDEWEB)

    Tae, Jae Woong; Shin, Dong Hoon [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2013-10-15

    Perfect removal of transferred technology is impossible because it is impossible to find all copies of technologies such as files and documents. International community concerns about Terrorists' acquirement of nuclear technologies related to nuclear reactors, enrichment and reprocessing Facilities and heavy water production facilities, which can be used for production of nuclear weapons. Non-state actors as well as concerning countries have tried to possess nuclear technology for developing nuclear weapons. Non-state actors' activities threaten global nuclear security. Korea exported four nuclear power plants to UAE and a research reactor to Jordan. Non-state actors may try to procure nuclear equipment and technology from Korean nuclear industries. Therefore, the export control system should be enhanced for national nuclear security and safety. In this study, the export control system of Korea and the United States were compared concerning to nuclear technology. In summary, controlled activities related to nuclear technology are treated more variously and more diverse activities are controlled in the United States than In Korea. Catch-all control will lose its effectiveness without this. Related to the control of ITT (Intangible Technology Transfer), Korea and the United States are trying to amend the export control regulation. Both of them are trying to control intangible technology transfers effectively. Revised Foreign Trade Act in Korea is expected to introduce a more rigorous system of nuclear technology controls. It focuses on nationality rather than residence. The revised law may face into other problems such as dual nationals like as the United States. However, this satisfies legislative requirements for control of a deemed export. The revised law will enter into force in 2014. Accurate meanings of technology and export will be defined soon in the enforcement decree and the public notice before 2014. However, it is hard to revise the definition

  18. A comparative study on export control systems of nuclear technology in ROK and USA

    International Nuclear Information System (INIS)

    Tae, Jae Woong; Shin, Dong Hoon

    2013-01-01

    Perfect removal of transferred technology is impossible because it is impossible to find all copies of technologies such as files and documents. International community concerns about Terrorists' acquirement of nuclear technologies related to nuclear reactors, enrichment and reprocessing Facilities and heavy water production facilities, which can be used for production of nuclear weapons. Non-state actors as well as concerning countries have tried to possess nuclear technology for developing nuclear weapons. Non-state actors' activities threaten global nuclear security. Korea exported four nuclear power plants to UAE and a research reactor to Jordan. Non-state actors may try to procure nuclear equipment and technology from Korean nuclear industries. Therefore, the export control system should be enhanced for national nuclear security and safety. In this study, the export control system of Korea and the United States were compared concerning to nuclear technology. In summary, controlled activities related to nuclear technology are treated more variously and more diverse activities are controlled in the United States than In Korea. Catch-all control will lose its effectiveness without this. Related to the control of ITT (Intangible Technology Transfer), Korea and the United States are trying to amend the export control regulation. Both of them are trying to control intangible technology transfers effectively. Revised Foreign Trade Act in Korea is expected to introduce a more rigorous system of nuclear technology controls. It focuses on nationality rather than residence. The revised law may face into other problems such as dual nationals like as the United States. However, this satisfies legislative requirements for control of a deemed export. The revised law will enter into force in 2014. Accurate meanings of technology and export will be defined soon in the enforcement decree and the public notice before 2014. However, it is hard to revise the definition of export

  19. A study on the revision of nuclear safety act to build the foundation of nuclear export and import control system in Korea

    International Nuclear Information System (INIS)

    Yang, Seung Hyo; Choi, Sun Do

    2012-01-01

    Nuclear related items require export and import control beyond the multilateral export control system according to Safeguard Agreement, Additional Protocol and bilateral agreements. Besides Korea as a nuclear supplier is needed to actively cope with its export control system, which is being reinforced internationally. In regard to this trend, this study drew the revision plan of present Nuclear Safety Act to found the nuclear export and import control system in Korea by examining the related legislations and analyzing the implementation status of nuclear export and import control

  20. A study on the revision of nuclear safety act to build the foundation of nuclear export and import control system in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Seung Hyo; Choi, Sun Do [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2012-10-15

    Nuclear related items require export and import control beyond the multilateral export control system according to Safeguard Agreement, Additional Protocol and bilateral agreements. Besides Korea as a nuclear supplier is needed to actively cope with its export control system, which is being reinforced internationally. In regard to this trend, this study drew the revision plan of present Nuclear Safety Act to found the nuclear export and import control system in Korea by examining the related legislations and analyzing the implementation status of nuclear export and import control.

  1. A study on establishing export system of nuclear related equipments to the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Kim, Seung Soo; Lim, Chae Young; Kim, Hwa Sup; Min, Tae Sik [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-04-01

    In spite of the advanced status in the international nuclear society, exports of domestic nuclear industries to procurement market of the international organizations has been negligible. This study briefly explained the role and the structure of the IAEA. Then, this study surveyed the size of procurement market, major procurement items, and procurement process. This study also gave an export example to the IAEA from Korea Atomic Energy Research Institute for the ease of understanding the procurement process. Based on these surveys and analysis, this study established the goal and strategy for exports of nuclear equipments to the IAEA. Besides, this study surveyed domestic nuclear industries that have potential to export their products to the IAEA. Then, Korea Atomic Energy Research Institute, by a cooperation with Korea Atomic Industrial Forum Inc., held workshop on 'export of nuclear equipments to IAEA' in May 2001 for them. 4 refs., 1 fig., 10 tabs. (Author)

  2. Inhibiting cancer cell hallmark features through nuclear export inhibition.

    Science.gov (United States)

    Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

    2016-01-01

    Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

  3. Know-how and nuclear exports

    International Nuclear Information System (INIS)

    Luxo, A.

    1978-01-01

    The concrete content of nuclear know-how is defined, and the present position as to the exchange of know-how is discussed. The new forms which may be taken by this know-how are considered and the results which may be expected from a know-how transfer (both for the exporting and the importing countries) are related [fr

  4. Guidance and considerations for implementation of INFCIRC/225/Rev.3, the physical protection of nuclear material

    International Nuclear Information System (INIS)

    1997-09-01

    The Physical Protection of Nuclear Material, INFCIRC/225/Rev.3, provides recommendations for the physical protection of nuclear material against theft in use, storage and transport, whether national or international and whether peaceful or military, and contains provisions relating to the sabotage of nuclear material or facilities. The recommendations contained in INFCIRC/225/Rev.3 detail the elements that should be included in a State's system of physical protection. It also recognizes the adverse health and safety consequences arising from the theft of nuclear material and the sabotage of nuclear material or facilities. Most industrial and developing countries use these recommendations to some extent in the establishment and operation of their physical protection systems. Although INFCIRC/225/Rev.3 provides recommendations for protecting materials and facilities from theft or sabotage, it does not provide in-depth details for these recommendations. In June 1996, the IAEA convened a consultants meeting to consider this matter. This report is the result of continuing discussions and drafts over a period of nine months. The intent of this guidance is to provide a broader basis for relevant State organizations to prescribe appropriate requirements for the use of nuclear materials which are compatible with accepted international practice

  5. A study on establishing export system of nuclear related equipments to the IAEA

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ki Dong; Lee, Man Ki; Moon, Ki Hwan; Kim, Seung Soo; Lim, Chae Young; Kim, Hwa Sup; Min, Tae Sik [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-04-01

    In spite of the advanced status in the international nuclear society, exports of domestic nuclear industries to procurement market of the international organizations has been negligible. This study briefly explained the role and the structure of the IAEA. Then, this study surveyed the size of procurement market, major procurement items, and procurement process. This study also gave an export example to the IAEA from Korea Atomic Energy Research Institute for the ease of understanding the procurement process. Based on these surveys and analysis, this study established the goal and strategy for exports of nuclear equipments to the IAEA. Besides, this study surveyed domestic nuclear industries that have potential to export their products to the IAEA. Then, Korea Atomic Energy Research Institute, by a cooperation with Korea Atomic Industrial Forum Inc., held workshop on 'export of nuclear equipments to IAEA' in May 2001 for them. 4 refs., 1 fig., 10 tabs. (Author)

  6. Nuclear export policy of the Reagan Administration

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, J F; Donnelly, W H [Library of Congress, Washington, DC (USA)

    1983-06-01

    The Reagan Administration maintains the Carter Administration's objective of non-proliferation of nuclear weapons as being fundamental to US nuclear export policy. However, it sees the USA as having another important role to play in influencing the use of nuclear power and the trading of related goods and technologies in other countries. While the Administration believes its policies will prove beneficial to the USA, there is concern that trade considerations are being given priority over preventing the proliferation of nuclear weapons.

  7. An analysis of international situation concerning nuclear security. Focused on the revision to INFCIRC/225/Rev.5

    International Nuclear Information System (INIS)

    Inamura, Tomoaki; Tanabe, Tomoyuki

    2011-01-01

    Since the September 11 attacks in 2001, counterterrorism measures have become not just domestic issues but critical issues that need international cooperation. Various nuclear security measures are in place as part of international counterterrorism measures. This report looks at the trend of international nuclear security measures to get implications for Japan, focusing on INFCIRC/225/Rev.5, an international guideline for physical protection of nuclear materials and nuclear facilities drawn up by IAEA. The observations of this report are as follows: 1) While legally binding nuclear security measures such as multilateral treaties and United Nations Security Council Resolutions impose minimum requirements on individual countries, the approaches led by IAEA or individual countries or private associations aim at more detailed consideration or information sharing to further improve nuclear security. 2) INFCIRC/225/Rev.5 comprises new concepts such as risk-based physical protection and nuclear security culture, as well as extended range of threats such as insiders or stand-off attacks and broader scope of measures to response. Japan should consider incorporation of INFCIRC/225/Rev.5 to its national laws and regulations putting in mind that it may have heavy influence and that Japan pledged to role leadership about nuclear security to international society. (author)

  8. A biochemical framework for eIF4E-dependent mRNA export and nuclear recycling of the export machinery.

    Science.gov (United States)

    Volpon, Laurent; Culjkovic-Kraljacic, Biljana; Sohn, Hye Seon; Blanchet-Cohen, Alexis; Osborne, Michael J; Borden, Katherine L B

    2017-06-01

    The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date, over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ∼50-nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end. While eIF4E associates with the cap, an unknown factor recognizes the 4ESE element. We previously identified cofactors that functionally interacted with eIF4E in mammalian cell nuclei including the leucine-rich pentatricopeptide repeat protein LRPPRC and the export receptor CRM1/XPO1. LRPPRC simultaneously interacts with both eIF4E bound to the 5' mRNA cap and the 4ESE element in the 3' UTR. In this way, LRPPRC serves as a specificity factor to recruit 4ESE-containing RNAs within the nucleus. Further, we show that CRM1 directly binds LRPPRC likely acting as the export receptor for the LRPPRC-eIF4E-4ESE RNA complex. We also found that Importin 8, the nuclear importer for cap-free eIF4E, imports RNA-free LRPPRC, potentially providing both coordinated nuclear recycling of the export machinery and an important surveillance mechanism to prevent futile export cycles. Our studies provide the first biochemical framework for the eIF4E-dependent mRNA export pathway. © 2017 Volpon et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  9. Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats

    Science.gov (United States)

    Choi, Miyeon; Lee, Seung Hoon; Wang, Sung Eun; Ko, Seung Yeon; Song, Mihee; Choi, June-Seek; Duman, Ronald S.; Son, Hyeon

    2015-01-01

    Ketamine produces rapid antidepressant-like effects in animal assays for depression, although the molecular mechanisms underlying these behavioral actions remain incomplete. Here, we demonstrate that ketamine rapidly stimulates histone deacetylase 5 (HDAC5) phosphorylation and nuclear export in rat hippocampal neurons through calcium/calmodulin kinase II- and protein kinase D-dependent pathways. Consequently, ketamine enhanced the transcriptional activity of myocyte enhancer factor 2 (MEF2), which leads to regulation of MEF2 target genes. Transfection of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 replaced by Ala259/Ala498, HDAC5-S/A), resulted in resistance to ketamine-induced nuclear export, suppression of ketamine-mediated MEF2 transcriptional activity, and decreased expression of MEF2 target genes. Behaviorally, viral-mediated hippocampal knockdown of HDAC5 blocked or occluded the antidepressant effects of ketamine both in unstressed and stressed animals. Taken together, our results reveal a novel role of HDAC5 in the actions of ketamine and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of ketamine. PMID:26647181

  10. How the Eximbank helps US nuclear exporters

    International Nuclear Information System (INIS)

    Moore, J.L. Jr.

    1981-01-01

    The way in which the Export-Import Bank operates in support of the United States nuclear industry noting particularly its flexibility in responding to changing needs and budget constraints is described. (author)

  11. The mediating role of total quality management between entrepreneurial orientation and SMEs export performance

    Directory of Open Access Journals (Sweden)

    Muhammad Imran

    2018-06-01

    Full Text Available The purpose of this study was to investigate the mediating role of total quality management (TQM between entrepreneurial orientation (EO and SME export performance in the manufacturing sector of Pakistan. This study was originated from the fact that only a few studies have examined on how the firm’s intangible resources and capabilities such as EO and TQM drive SMEs’ export performance. Some questionnaires in Likert scale were used to collect the data and 364 usable responses were received from the owner/managers of exporting SMEs. Partial Least Squares Structural Equation Modeling (PLS-SEM was used for the data analysis. The findings reveal significant relationship between EO and TQM with SME export performance. Furthermore, this study found the complementary mediating role of TQM between EO and SME export performance of manufacturing sector of Pakistan. This study has implications for owner/managers of SMEs. The results offer a better understanding regarding EO and TQM implementation to SMEs owner / managers. Thus, owner/managers of SMEs can take better decisions for the implementation of TQM practices. Furthermore, to the best of researcher’s knowledge, this study is the first work, which examines Pakistan`s SMEs export performance in association with the TQM as the mediating factor between EO and SME export performance.

  12. German nuclear fuel exports and imports 1991

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The statistics compiled by the German Federal Office for Trade and Industry (Bundesamt fuer Wirtschaft) for the Federal Ministry for the Environment, Conservation of Nature, and Reactor Safety of imports and exports of nuclear fuels and source materials in 1991 show a major drop by 33.8% in imports and a pronounced rise by 191.5% in exports, compared to the levels in the previous year. Source material for the purposes of these statistics refers only to uranium concentrate. Quantitatively, the biggest import items are source materials, depleted uranium, and uranium enriched up to 3%. Exports of unirradiated material quantitatively comprise mainly depleted uranium, source material, and uranium enriched up to 10%. (orig.) [de

  13. Selective nuclear export of specific classes of mRNA from mammalian nuclei is promoted by GANP

    Science.gov (United States)

    Wickramasinghe, Vihandha O.; Andrews, Robert; Ellis, Peter; Langford, Cordelia; Gurdon, John B.; Stewart, Murray; Venkitaraman, Ashok R.; Laskey, Ronald A.

    2014-01-01

    The nuclear phase of the gene expression pathway culminates in the export of mature messenger RNAs (mRNAs) to the cytoplasm through nuclear pore complexes. GANP (germinal- centre associated nuclear protein) promotes the transfer of mRNAs bound to the transport factor NXF1 to nuclear pore complexes. Here, we demonstrate that GANP, subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex, promotes selective nuclear export of a specific subset of mRNAs whose transport depends on NXF1. Genome-wide gene expression profiling showed that half of the transcripts whose nuclear export was impaired following NXF1 depletion also showed reduced export when GANP was depleted. GANP-dependent transcripts were highly expressed, yet short-lived, and were highly enriched in those encoding central components of the gene expression machinery such as RNA synthesis and processing factors. After injection into Xenopus oocyte nuclei, representative GANP-dependent transcripts showed faster nuclear export kinetics than representative transcripts that were not influenced by GANP depletion. We propose that GANP promotes the nuclear export of specific classes of mRNAs that may facilitate rapid changes in gene expression. PMID:24510098

  14. Development of Export Control Comprehensive Management Model for Nuclear Power Plants and Others Projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chansuh; Seo, Hana; Choi, Sundo [Korea Institute of Nuclear Nonproliferation And Control, Daejeon (Korea, Republic of)

    2014-05-15

    It is required that there are lots of managements of care and concern if the project contains strategic items such as NPPs. The Korean nuclear industry and its related companies, such as the Korea Hydro and Nuclear Power (KHNP), are promoting greater exports of NPPs. It is likely that Korea will export more this technology to newcomer states in the future. As a result, the ROK has been improving its export control management system for NPPs. In keeping with this national effort, Korea Institute of Nuclear Nonproliferation And Control (KINAC) developed comprehensive export control management model for NPPs and other projects, in preparation for this projected growth in the industry. This model also applies to the nuclear export case of the UAE, aims to manage the project from bidding to the end of the contract. The recent Export Licensing of Nuclear Facility Technology was reflected in the Notice on Export and Import of Strategic Items in January 2014. Through this license, the large-scale project legislation framework was established. It can also minimize nonproliferation concerns of the international community through strict management. It is expected that the Korea will be able to enhance transparency and secure the nuclear use, while meeting nonproliferation purpose.

  15. Development of Export Control Comprehensive Management Model for Nuclear Power Plants and Others Projects

    International Nuclear Information System (INIS)

    Lee, Chansuh; Seo, Hana; Choi, Sundo

    2014-01-01

    It is required that there are lots of managements of care and concern if the project contains strategic items such as NPPs. The Korean nuclear industry and its related companies, such as the Korea Hydro and Nuclear Power (KHNP), are promoting greater exports of NPPs. It is likely that Korea will export more this technology to newcomer states in the future. As a result, the ROK has been improving its export control management system for NPPs. In keeping with this national effort, Korea Institute of Nuclear Nonproliferation And Control (KINAC) developed comprehensive export control management model for NPPs and other projects, in preparation for this projected growth in the industry. This model also applies to the nuclear export case of the UAE, aims to manage the project from bidding to the end of the contract. The recent Export Licensing of Nuclear Facility Technology was reflected in the Notice on Export and Import of Strategic Items in January 2014. Through this license, the large-scale project legislation framework was established. It can also minimize nonproliferation concerns of the international community through strict management. It is expected that the Korea will be able to enhance transparency and secure the nuclear use, while meeting nonproliferation purpose

  16. Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA-Helicase as for mRNA Export.

    Science.gov (United States)

    Neumann, Bettina; Wu, Haijia; Hackmann, Alexandra; Krebber, Heike

    2016-01-01

    The DEAD-box RNA-helicase Dbp5/Rat8 is known for its function in nuclear mRNA export, where it displaces the export receptor Mex67 from the mRNA at the cytoplasmic side of the nuclear pore complex (NPC). Here we show that Dbp5 is also required for the nuclear export of both pre-ribosomal subunits. Yeast temperature-sensitive dbp5 mutants accumulate both ribosomal particles in their nuclei. Furthermore, Dbp5 genetically and physically interacts with known ribosomal transport factors such as Nmd3. Similar to mRNA export we show that also for ribosomal transport Dbp5 is required at the cytoplasmic side of the NPC. However, unlike its role in mRNA export, Dbp5 does not seem to undergo its ATPase cycle for this function, as ATPase-deficient dbp5 mutants that selectively inhibit mRNA export do not affect ribosomal transport. Furthermore, mutants of GLE1, the ATPase stimulating factor of Dbp5, show no major ribosomal export defects. Consequently, while Dbp5 uses its ATPase cycle to displace the export receptor Mex67 from the translocated mRNAs, Mex67 remains bound to ribosomal subunits upon transit to the cytoplasm, where it is detectable on translating ribosomes. Therefore, we propose a model, in which Dbp5 supports ribosomal transport by capturing ribosomal subunits upon their cytoplasmic appearance at the NPC, possibly by binding export factors such as Mex67. Thus, our findings reveal that although different ribonucleoparticles, mRNAs and pre-ribosomal subunits, use shared export factors, they utilize different transport mechanisms.

  17. French nuclear industry exportations: companies and organisations, achievements and projects

    International Nuclear Information System (INIS)

    Faudon, V.; Pailler, S.; Miniere, D.; Pouget-Abadie, X.; Journes, F.; Ouali, F.; Brochard, D.; Choho, T.; Lagarde, D.; Anglaret, P.; Kottman, G.; Mockly, D.; Ouzounian, G.; Cordier, P.Y.; Prenez, J.C.; Arpino, J.M.; Jaouen, C.; Jolly, B.

    2013-01-01

    This document gathers a series of short articles in which the following players: French Nuclear Safety Authority (ASN), Electricity of France (EdF), French Alternative Energies and Atomic Energy Commission (CEA), AREVA, ALSTOM, the Association of French Nuclear Industry Exporters (AIFEN), the National Radioactive Waste Management Agency (ANDRA) and the French Society of Nuclear Energy (SFEN) present their competencies in their respective fields and their strategies and commercial offers for exports. 2 articles are dedicated to the achievements of the French nuclear industry in China and another details the cooperation between SFEN and its foreign counterparts. Another article briefly presents the EPR and ATMEA reactors. (A.C.)

  18. Nuclear export of RNA: Different sizes, shapes and functions.

    Science.gov (United States)

    Williams, Tobias; Ngo, Linh H; Wickramasinghe, Vihandha O

    2018-03-01

    Export of protein-coding and non-coding RNA molecules from the nucleus to the cytoplasm is critical for gene expression. This necessitates the continuous transport of RNA species of different size, shape and function through nuclear pore complexes via export receptors and adaptor proteins. Here, we provide an overview of the major RNA export pathways in humans, highlighting the similarities and differences between each. Its importance is underscored by the growing appreciation that deregulation of RNA export pathways is associated with human diseases like cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  19. CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization

    International Nuclear Information System (INIS)

    Neyton, Sophie; Lespinasse, Francoise; Lahaye, Francois; Staccini, Pascal; Paquis-Flucklinger, Veronique; Santucci-Darmanin, Sabine

    2007-01-01

    MSH4 and MSH5 are members of the MutS homolog family, a conserved group of proteins involved in DNA mismatch correction and homologous recombination. Although several studies have provided compelling evidences suggesting that MSH4 and MSH5 could act together in early and late stages of meiotic recombination, their precise roles are poorly understood and recent findings suggest that the human MSH4 protein may also exert a cytoplasmic function. Here we show that MSH4 is present in the cytoplasm and the nucleus of both testicular cells and transfected somatic cells. Confocal studies on transfected cells provide the first evidence that the subcellular localization of MSH4 is regulated, at least in part, by an active nuclear export pathway dependent on the exportin CRM1. We used deletion mapping and mutagenesis to define two functional nuclear export sequences within the C-terminal part of hMSH4 that mediate nuclear export through the CRM1 pathway. Our results suggest that CRM1 is also involved in MSH5 nuclear export. In addition, we demonstrate that dimerization of MSH4 and MSH5 facilitates their nuclear localization suggesting that dimerization may regulate the intracellular trafficking of these proteins. Our findings suggest that nucleocytoplasmic traffic may constitute a regulatory mechanism for MSH4 and MSH5 functions

  20. Uncapped mRNA introduced into tobacco protoplasts can be imported into the nucleus and is trapped by leptomycin B.

    Science.gov (United States)

    Stuger, Rogier; Forreiter, Christoph

    2004-08-01

    The mechanism of nuclear export of RNAs in yeast and animal cells is rapidly being uncovered, but RNA export in plants has received little attention. We introduced capped and uncapped fluorescent mRNAs into tobacco (Nicotiana plumbaginifolia) protoplasts and studied their cellular localization. Following insertion, capped transcripts were found in the cytoplasm, while uncapped messengers transiently appeared in the nucleus in about one-quarter to one-third of the cells. These mRNAs were trapped by the nuclear export-inhibiting drug leptomycin B, pointing to an export mechanism in plants similar to Rev-NES-mediated RNP export in other organisms.

  1. Export financing of nuclear power plants - banks experience

    International Nuclear Information System (INIS)

    Loeber

    1976-01-01

    Export financing of a nuclear power plant to be exported from Germany, is, in principle, provided by German commercial banks and KfW (Kreditanstalt fuer Wiederaufbau). As a rule, 50 per cent of the financing of maturities falling due under the export portion of the loan will be taken over by a banking syndicate of approximately 25 member banks, and the remaining 50 per cent would be provided by KfW. KfW and the commercial banks must grant their loans at the respective money market conditions. The banks' and KfW's loans will normally be disbursed pro rata delivery. (HP) [de

  2. The National Implementation of Nuclear Export Controls: Developing a Best Practices Model

    Energy Technology Data Exchange (ETDEWEB)

    Viski, Andrea [European University Institute, Department of Law, Badia Fiesolana, S.Domenico di Fiesole, Firenze (Italy)

    2011-12-15

    The nuclear renaissance promises significant benefits to the international community, but also raises security challenges, particularly relating to the trade of nuclear materials and equipment. The objective of this paper is to examine how supply-side non-proliferation efforts can be strengthened by developing a best practices model for national nuclear export control implementation. In order to achieve this goal, nuclear export control measures identified by the 1540 Committee will be used as a framework from which a best practices model can be formed. Such a model concentrates specifically on national legislation and enforcement measures delineated by the Committee in order to bring countries in accordance with international law. Developing a best practices model seeks to deliver an ideal process for national export control law actualization in order to encourage the peaceful development of nuclear energy and develop the infrastructure and framework for precluding nuclear proliferation.

  3. Examining the intersection between splicing, nuclear export and small RNA pathways.

    Science.gov (United States)

    Nabih, Amena; Sobotka, Julia A; Wu, Monica Z; Wedeles, Christopher J; Claycomb, Julie M

    2017-11-01

    Nuclear Argonaute/small RNA pathways in a variety of eukaryotic species are generally known to regulate gene expression via chromatin modulation and transcription attenuation in a process known as transcriptional gene silencing (TGS). However, recent data, including genetic screens, phylogenetic profiling, and molecular mechanistic studies, also point to a novel and emerging intersection between the splicing and nuclear export machinery with nuclear Argonaute/small RNA pathways in many organisms. In this review, we summarize the field's current understanding regarding the relationship between splicing, export and small RNA pathways, and consider the biological implications for coordinated regulation of transcripts by these pathways. We also address the importance and available approaches for understanding the RNA regulatory logic generated by the intersection of these particular pathways in the context of synthetic biology. The interactions between various eukaryotic RNA regulatory pathways, particularly splicing, nuclear export and small RNA pathways provide a type of combinatorial code that informs the identity ("self" versus "non-self") and dictates the fate of each transcript in a cell. Although the molecular mechanisms for how splicing and nuclear export impact small RNA pathways are not entirely clear at this early stage, the links between these pathways are widespread across eukaryotic phyla. The link between splicing, nuclear export, and small RNA pathways is emerging and establishes a new frontier for understanding the combinatorial logic of gene regulation across species that could someday be harnessed for therapeutic, biotechnology and agricultural applications. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Analysis of the influence of subcellular localization of the HIV Rev protein on Rev-dependent gene expression by multi-fluorescence live-cell imaging

    International Nuclear Information System (INIS)

    Wolff, Horst; Hadian, Kamyar; Ziegler, Manja; Weierich, Claudia; Kramer-Hammerle, Susanne; Kleinschmidt, Andrea; Erfle, Volker; Brack-Werner, Ruth

    2006-01-01

    The human immunodeficiency virus Rev protein is a post-transcriptional activator of HIV gene expression. Rev is a nucleocytoplasmic shuttle protein that displays characteristic nuclear/nucleolar subcellular localization in various cell lines. Cytoplasmic localization of Rev occurs under various conditions disrupting Rev function. The goal of this study was to investigate the relationship between localization of Rev and its functional activity in living cells. A triple-fluorescent imaging assay, called AQ-FIND, was established for automatic quantitative evaluation of nucleocytoplasmic distribution of fluorescently tagged proteins. This assay was used to screen 500 rev genes generated by error-prone PCR for Rev mutants with different localization phenotypes. Activities of the Rev mutants were determined with a second quantitative, dual-fluorescent reporter assay. In HeLa cells, the majority of nuclear Rev mutants had activities similar to wild-type Rev. The activities of Rev mutants with abnormal cytoplasmic localization ranged from moderately impaired to nonfunctional. There was no linear correlation between subcellular distribution and levels of Rev activity. In astrocytes, nuclear Rev mutants showed similar impaired activities as the cytoplasmic wild-type Rev. Our data suggest that steady-state subcellular localization is not a primary regulator of Rev activity but may change as a secondary consequence of altered Rev function. The methodologies described here have potential for studying the significance of subcellular localization for functions of other regulatory factors

  5. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

    Directory of Open Access Journals (Sweden)

    Andrea Cerutti

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS, but no nuclear export signal (NES has yet been identified.We show here that the aa(109-133 region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126 in the identified NES or in the sequence encoding the mature core aa(1-173 significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  6. Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

    Science.gov (United States)

    Cerutti, Andrea; Maillard, Patrick; Minisini, Rosalba; Vidalain, Pierre-Olivier; Roohvand, Farzin; Pecheur, Eve-Isabelle; Pirisi, Mario; Budkowska, Agata

    2011-01-01

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified.We show here that the aa(109-133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1-173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

  7. Distinct Paths for Basic Amino Acid Export in Escherichia coli: YbjE (LysO) Mediates Export of L-Lysine.

    Science.gov (United States)

    Pathania, Amit; Sardesai, Abhijit A

    2015-06-15

    In Escherichia coli, argO encodes an exporter for L-arginine (Arg) and its toxic analogue canavanine (CAN), and its transcriptional activation and repression, by Arg and L-lysine (Lys), respectively, are mediated by the regulator ArgP. Accordingly argO and argP mutants are CAN supersensitive (CAN(ss)). We report the identification of ybjE as a gene encoding a predicted inner membrane protein that mediates export of Lys, and our results confirm the previous identification with a different approach of YbjE as a Lys exporter, reported by Ueda and coworkers (T. Ueda, Y. Nakai, Y. Gunji, R. Takikawa, and Y. Joe, U.S. patents 7,629,142 B2 [December 2009] and 8,383,363 B1 [February 2013] and European patent 1,664,318 B1 [September 2009]). ybjE was isolated as a multicopy suppressor of the CAN(ss) phenotype of a strain lacking ArgO. The absence of YbjE did not confer a CAN(ss) phenotype but instead conferred hypersensitivity to the lysine antimetabolite thialysine and led to growth inhibition by the dipeptide lysylalanine, which is associated with elevated cellular Lys content. YbjE overproduction resulted in Lys excretion and syntrophic cross-feeding of a Lys auxotroph. Constitutive overexpression of argO promoted Lys cross-feeding that is indicative of a latent Lys export potential of ArgO. Arg modestly repressed ybjE transcription in an ArgR-dependent manner, and ArgR displayed Arg-sensitive binding to the ybjE promoter region in vitro. Our studies suggest that the reciprocal repression of argO and ybjE, respectively, by Lys and Arg confers the specificity for basic amino acid export by distinct paths and that such cross-repression contributes to maintenance of cytoplasmic Arg/Lys balance. We propose that YbjE be redesignated LysO. This work ascribes a lysine export function to the product of the ybjE gene of Escherichia coli, leading to a physiological scenario wherein two proteins, ArgO and YbjE, perform the task of separately exporting arginine and lysine

  8. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

    Science.gov (United States)

    Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

    2014-05-01

    In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

  9. Upgrading the safety assessment of exported nuclear power plants

    International Nuclear Information System (INIS)

    Rosen, M.

    1978-01-01

    An examination of the safety aspects of exported nuclear power plants demonstrates that additional and somewhat special considerations exist for these plants, and thus that some new approaches may be required to insure their safety. In view of the generally small regulatory staffs of importing countries, suggestions are given for measures which should be taken by the various organizations involved in the export and import of nuclear power facilities to raise the level of the very essential safety assessment. These include the upgrading of the 'export edition' of the traditionally supplied safety documentation by use of a Supplementary Information Report, written specifically for the needs of a smaller and/or less technically qualified staff, which highlights the differences that exist between the facility to be constructed and the supposedly similar reference plant of the supplier country; by improvement of supporting safety documentation to allow for adequate understanding of significant safety parameters; and by attention to the needs of smaller countries in the critical Operating Regulations (Technical Specifications for Operation). Consideration is also given to upgrading the regulatory effort and to the obligations of principal organizations involved with exported nuclear plants, including national and international, for insuring the importing countries' technical readiness and the adequacy of the regulatory effort. Special attention is directed towards the project contract as a means of implementing programmes to achieve these goals. (author)

  10. Decision support for selecting exportable nuclear technology using the analytic hierarchy process: A Korean case

    International Nuclear Information System (INIS)

    Lee, Deok Joo; Hwang, Jooho

    2010-01-01

    The Korean government plans to increase strategically focused R and D investment in some promising nuclear technology areas to create export opportunities of technology in a global nuclear market. The purpose of this paper is to present a decision support process for selecting promising nuclear technology with the perspective of exportability by using the AHP based on extensive data gathered from nuclear experts in Korea. In this study, the decision criteria for evaluating the export competitiveness of nuclear technologies were determined, and a hierarchical structure for the decision-making process was systematically developed. Subsequently relative weights of decision criteria were derived using AHP methodology and the export competitiveness of nuclear technology alternatives was quantified to prioritize them. We discuss the implications of our results with a viewpoint toward national nuclear technology policy.

  11. Nuclear export policy and regulation for non-proliferation: Federal Republic of Germany

    International Nuclear Information System (INIS)

    Boulanger, Werner.

    1978-01-01

    The nuclear export policy of the Federal Republic of Germany complies with the principle of non-proliferation of nuclear weapons. Already in 1967 the Federal Government stated in a Peace Note that no export was authorised to countries (outside Euratom) which did not comply with the IAEA Safeguards. In the bilateral agreement the Federal Republic signed with Brasil in 1975, emphasis was put on international safeguards and the control exercised on exported materials to avoid any diversion for military purposes. (NEA) [fr

  12. High-Resolution Imaging Reveals New Features of Nuclear Export of mRNA through the Nuclear Pore Complexes

    Directory of Open Access Journals (Sweden)

    Joseph M. Kelich

    2014-08-01

    Full Text Available The nuclear envelope (NE of eukaryotic cells provides a physical barrier for messenger RNA (mRNA and the associated proteins (mRNPs traveling from sites of transcription in the nucleus to locations of translation processing in the cytoplasm. Nuclear pore complexes (NPCs embedded in the NE serve as a dominant gateway for nuclear export of mRNA. However, the fundamental characterization of export dynamics of mRNPs through the NPC has been hindered by several technical limits. First, the size of NPC that is barely below the diffraction limit of conventional light microscopy requires a super-resolution microscopy imaging approach. Next, the fast transit of mRNPs through the NPC further demands a high temporal resolution by the imaging approach. Finally, the inherent three-dimensional (3D movements of mRNPs through the NPC demand the method to provide a 3D mapping of both transport kinetics and transport pathways of mRNPs. This review will highlight the recently developed super-resolution imaging techniques advanced from 1D to 3D for nuclear export of mRNPs and summarize the new features in the dynamic nuclear export process of mRNPs revealed from these technical advances.

  13. Communication received from the permanent mission of Australia on behalf of the Member States of the nuclear suppliers group

    International Nuclear Information System (INIS)

    1997-01-01

    The document reproduces the text of a letter dated 13 August 1997 received by the Director General of the IAEA from the Permanent Mission of Australia to the Agency on behalf of the Member States of the 'Nuclear Suppliers Group (NSG)'. Attached to this letter was a paper entitled 'The Nuclear Suppliers Group: Its origins, role and activities'. The purpose of the letter and the attached paper was to provide detailed background to the origins of guidelines that govern the export of items exclusively for nuclear use and the export of nuclear related dual-use items and technologies. These guidelines were published by the Agency in documents INFCIRC/254/Rev.3/Part 1 and INFCIRC/254/Rev.2/Part 2/Mod.1

  14. Nuclear safety aspects of exported replicate nuclear power plants and associated problems

    International Nuclear Information System (INIS)

    Kern, H.G.

    1978-01-01

    The standardization of the export nuclear power plant is being pursued with the concept of replication. This concept entails using another exported Nuclear Power Plant (NPP) as the base design and adapting it to a new site. The general ground rule applied to this concept is upgrading the design where necessary and duplicating the design where it is superior. Such continuous improvement will result in a standard export NPP that incorporates design features which will make it essentially acceptable for any suitable site. The advantages of replication are, therefore, boundless. However, the replication mode requires superior design control by the engineer to assure that only improvements alter the base design. With this concept, the replicating engineer is essentially assigned the responsiblity of safeguarding the standard export plant design. He is delegated the task of filtering the design such that only the conservative aspects prevail. Tight control of design changes via properly administered procedures is necessary to assure that no unforeseen compromises are made in designs which have already achieved optimization. Techniques to accomplish successful replication include, among others, the use of PCNs, system cognizant engineers, design verfication review, and the participation of all engineering disciplines in the development of the project schedule. (author)

  15. The nuclear export policy of the Reagan administration

    International Nuclear Information System (INIS)

    Pilat, J.F.; Donnelly, W.H.

    1983-01-01

    tThe Reagan Administration maintains the Carter Administration's objective of non-proliferation of nuclear weapons as being fundamental to US nuclear export policy. However, it sees the USA as having another important role to play in influencing the use of nuclear power and the trading of related goods and technologies in other countries. While the Administration believes its policies will prove beneficial to the USA, there is concern that trade considerations are being given priority over preventing the proliferation of nuclear weapons. (author)

  16. O. Nuclear energy in a food exporting country

    International Nuclear Information System (INIS)

    1976-01-01

    This report attempts to estimate the affect on agricultural exports from New Zealand which might result from the operation of nuclear power. By far the most serious of these would result from an accidental release of radioactive material, and the likely affects of such releases are considered both in the first year after an accident and in the future. Previous assessments of this type have concentrated attention on property damage and on the health hazards which might result to consumers of contaminated food in the first year or two after a release. In this report the emphasis is on exported foods to which different criteria might apply, and some very approximate estimates are made of long-term implications. To a large extent these can be described only as speculations, but they have some value as a guide. No analgous report has been found in the open literature from other countries, and this particularly includes Denmark which has much in common with New Zealand in this regard. The possible effect of routine operation of nuclear power on food exports is also briefly considered

  17. 10 CFR 110.26 - General license for the export of nuclear reactor components.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF... Denmark Finland France Germany Greece Indonesia Ireland Italy Japan Latvia Lithuania Luxembourg...

  18. 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...

  19. Role of Non-Government Organizations in strengthening Kazakstan nuclear export control

    International Nuclear Information System (INIS)

    Tazhibaeva, L.; Prokhodtseva, T.

    2002-01-01

    Non-governmental organizations (NGO) are the structures that were born by the time, the time when deep changes in our society led us to new trends in the all spheres of society development, to new decisions and, as a consequence, to new structural findings that where able to govern, to support and put into reality the new ideas the could not be inserted in the structure assemblies of the former society. All non-governmental organizations in Kazakhstan are younger than ten years old, but they already could be considered highly experienced, for intensity of their activity is rather high. The main advantages of NGOs are flexibility and independent source of ideas, basic data and policy assessment. There are several non-government organizations that are working in the field of non-proliferation and export control. Kazakhstan Nuclear Technology Safety Center (NTSC) is among them. Non-proliferation and export control is only a small part of activity that NTSC is involved in. Non-governmental organizations could be of several types: NGOs that are affiliated with university or institute, independent associations, quasi-governmental structures and various foundations. NTSC complementing efforts of Kazakhstan Atomic Energy Committee (KAEC) in the field of non-proliferation and export control. The activity of NTSC in the field of non-proliferation includes: Holding conferences, seminars and workshops; Creating databases and reports; Develop proposal for legislation; Provide specialized training; Analyze data. NTSC is involved in a number of projects devoted to non-proliferation and export control. The following projects are supported by the US Department of Energy cooperation program on nuclear export controls for Russia and the Newly Independent States: System to review Kazakhstan exports (STROKE); Computerization of historical licensing data; Export control reference materials for Kazakhstan organizations; Additional Protocol. STROKE is a technical analysis database for

  20. Germany's imports and exports of nuclear fuels in 1981

    International Nuclear Information System (INIS)

    Anon.

    1982-01-01

    The statistics of imports and exports of nuclear fuels and basic materials which is set up by the Federal Authority for trade and industry for the Ministry of the Interior shows for 1981 (without taking the basic materials into account) a slight increase by 5% on the imports' side and also a slight increase by 10,5% on the exports' side. (orig./UA) [de

  1. Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export.

    Science.gov (United States)

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun; Hopper, Anita K

    2017-11-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67-Mtr2 (TAP-p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67-Mtr2 can substitute for Los1 in los1 Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67-Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. © 2017 Chatterjee et al.; Published by Cold Spring Harbor Laboratory Press.

  2. Three-Dimensional Mapping of mRNA Export through the Nuclear Pore Complex

    Directory of Open Access Journals (Sweden)

    Steven J. Schnell

    2014-11-01

    Full Text Available The locations of transcription and translation of mRNA in eukaryotic cells are spatially separated by the nuclear envelope (NE. Plenty of nuclear pore complexes (NPCs embedded in the NE function as the major gateway for the export of transcribed mRNAs from the nucleus to the cytoplasm. Whereas the NPC, perhaps one of the largest protein complexes, provides a relatively large channel for macromolecules to selectively pass through it in inherently three-dimensional (3D movements, this channel is nonetheless below the diffraction limit of conventional light microscopy. A full understanding of the mRNA export mechanism urgently requires real-time mapping of the 3D dynamics of mRNA in the NPC of live cells with innovative imaging techniques breaking the diffraction limit of conventional light microscopy. Recently, super-resolution fluorescence microscopy and single-particle tracking (SPT techniques have been applied to the study of nuclear export of mRNA in live cells. In this review, we emphasize the necessity of 3D mapping techniques in the study of mRNA export, briefly summarize the feasibility of current 3D imaging approaches, and highlight the new features of mRNA nuclear export elucidated with a newly developed 3D imaging approach combining SPT-based super-resolution imaging and 2D-to-3D deconvolution algorithms.

  3. KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

    Science.gov (United States)

    Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

    2018-04-10

    Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

    Science.gov (United States)

    Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

    2017-07-11

    Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

  5. 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.

  6. One recommendation of nuclear power export. GDP model application to the countries which expressed nuclear power introduction and consideration

    International Nuclear Information System (INIS)

    Iida, Tekehiko

    2010-01-01

    South Korea has been excited in nuclear business after the success in the contract to build nuclear power plants in UAE. Since more than 60 countries expressed nuclear power introduction and new countries were on the rise with exporting reactor technology accumulated, new era over nuclear renaissance seems to begin. This article at first classified countries, which expressed nuclear power introduction, with an economic level of GDP per capita. Then each classified country's requirements of nuclear power introduction were taken into consideration such as economic development, consumption pattern and technology attitude. As a result recommendation of nuclear power export was proposed. Different approach to each country targeted was suggested as shown in 'nuclear power GDP model'. (T. Tanaka)

  7. 77 FR 51581 - Request for a License To Export Nuclear Grade Graphite

    Science.gov (United States)

    2012-08-24

    ... NUCLEAR REGULATORY COMMISSION Request for a License To Export Nuclear Grade Graphite Pursuant to... 27, 2012, graphite for of nuclear grade graphite to the XMAT424, 11006032. nuclear end use. graphite. Shanghai Institute of Applied Physics in China to test various types of nuclear grade graphite material in...

  8. A study on improvement of export control system for the nuclear facility

    International Nuclear Information System (INIS)

    Kim, Ok Joo; Shin, Dong Hoon; Yang, Seung Hyo

    2012-01-01

    The Republic of Korea joined Nuclear Suppliers Group(NSG) in 1995 and became a major nuclear supplier both in name and reality by contracting the Project of UAE Braka Nuclear Power Plant(BNPP) in 2009 and the Project of Jordan Research and Training Reactor(JRTR) in 2010. And ROK is currently negotiating with several countries such as Finland and Vietnam for more projects, so it is expected to obtain more orders of commercial and research reactor. At this point of time, we found that it is difficult to apply individual export licensing system as it is for the big nuclear project such as BNPP and JRTR Project. Because the nuclear project in foreign country contains transfer of thousands of items and technical documents, including a considerable number of strategic items, issuing individual licenses for all items and documents can cause the inefficiency of the project. So, an appropriate export control system which can support such a project is necessary. In this study, we focused on how to improve the export control system to guarantee not only time efficiency but careful management of strategic goods

  9. Analysis of World Nuclear Market and Strategy of Korean NPP's Competitiveness Improvement for Exportation

    International Nuclear Information System (INIS)

    Choi, Jae Young; Jeong, Yong Hoon; Roh, Seungkook; Chang, Soon Heung

    2016-01-01

    China, India and USA (nuclear adopted countries) are planning tremendous number of NPPs to meet their increasing electricity demand and Saudi Arabia, Vietnam (nuclear adopting countries) are also planning to include nuclear power in their energy mix as a long-term plan. Korea has exported 4 units of APR1400 to the UAE in December, 2009. Korea became sixth NPP supplier country and our economic feasibility and safety features were started to evaluate worldwide. Nuclear industries became a new driver of Korea’s export and nuclear industries in Korea are now expecting another NPP export to Middle-eastern countries, including UAE and Saudi Arabia, based on the first-mover’s advantage at the UAE. In 2000s, five countries (Japan, USA, France, Russia and Korea), which are able to build NPP, focused on NPP export more than domestic construction. Global trend of world nuclear market changed rapidly, especially after NPP export to the UAE. By the global trend, hegemony of nuclear market migrated from supplier country to buyer country. Nuclear companies started cooperating rather than competing. Financing to developing countries become more important. In general, one of the considerable combinations is Korea-Japan-USA alliance. Korea is in charge of EPC, Japan supports financing and deficient technology (with USA partner), and Japan-USA handles fuel supply and back-end fuel cycle based on new agreed terms of ROK-US Nuclear Cooperation Agreement. This combination was judged to best way to collaborate with global companies. Paying attention to many delayed (or potentially delayed) constructions from Russia, intercepting the construction work will be available in case of contracted countries. Korea can emphasize the short construction time, high responsiveness and mild/equal diplomatic position to the target countries

  10. HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP

    Science.gov (United States)

    Noh, Ji Heon; Kim, Kyoung Mi; Abdelmohsen, Kotb; Yoon, Je-Hyun; Panda, Amaresh C.; Munk, Rachel; Kim, Jiyoung; Curtis, Jessica; Moad, Christopher A.; Wohler, Christina M.; Indig, Fred E.; de Paula, Wilson; Dudekula, Dawood B.; De, Supriyo; Piao, Yulan; Yang, Xiaoling; Martindale, Jennifer L.; de Cabo, Rafael; Gorospe, Myriam

    2016-01-01

    Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria are poorly characterized. Using affinity RNA pull-down followed by mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich RNA sequence-binding factor 1), that associated with the nuclear DNA-encoded lncRNA RMRP and mobilized it to mitochondria. In cultured human cells, HuR bound RMRP in the nucleus and mediated its CRM1 (chromosome region maintenance 1)-dependent export to the cytosol. After RMRP was imported into mitochondria, GRSF1 bound RMRP and increased its abundance in the matrix. Loss of GRSF1 lowered the mitochondrial levels of RMRP, in turn suppressing oxygen consumption rates and modestly reducing mitochondrial DNA replication priming. Our findings indicate that RBPs HuR and GRSF1 govern the cytoplasmic and mitochondrial localization of the lncRNA RMRP, which is encoded by nuclear DNA but has key functions in mitochondria. PMID:27198227

  11. Codon optimization of the HIV-1 vpu and vif genes stabilizes their mRNA and allows for highly efficient Rev-independent expression

    International Nuclear Information System (INIS)

    Nguyen, Kim-Lien; Llano, Manuel; Akari, Hirofumi; Miyagi, Eri; Poeschla, Eric M.; Strebel, Klaus; Bour, Stephan

    2004-01-01

    Two HIV-1 accessory proteins, Vpu and Vif, are notoriously difficult to express autonomously in the absence of the viral Tat and Rev proteins. We examined whether the codon bias observed in the vpu and vif genes relative to highly expressed human genes contributes to the Rev dependence and low expression level outside the context of the viral genome. The entire vpu gene as well as the 5' half of the vif gene were codon optimized and the resulting open reading frames (ORFs) (vphu and hvif, respectively) were cloned in autonomous expression vectors under the transcriptional control of the CMV promoter. Codon optimization efficiently removed the expression block observed in the native genes and allowed high levels of Rev- and Tat-independent expression of Vpu and Vif. Most of the higher protein levels detected are accounted for by enhanced steady-state levels of the mRNA encoding the optimized species. Nuclear run-on experiments show for the first time that codon optimization has no effect on the rate of transcriptional initiation or elongation of the vphu mRNA. Instead, optimization of the vpu gene was found to stabilize the vphu mRNA in the nucleus and enhance its export to the cytoplasm. This was achieved by allowing the optimized mRNA to use a new CRM1-independent nuclear export pathway. This work provides a better understanding of the molecular mechanisms underlying the process of codon optimization and introduces novel tools to study the biological functions of the Vpu and Vif proteins independently of other viral proteins

  12. Nuclear safeguards and export controls

    International Nuclear Information System (INIS)

    Mueller, H.

    1994-01-01

    Precisely from the perspective of the two most important nonnuclear weapons states, Japan and Germany, the safeguards and arms control agendas have not been finally dealt with. Because of their central position in the nonproliferation regime as nuclear suppliers and states with large nuclear energy industries, both countries are compelled to take a leading role in pursuing future reforms. In the dialogue with the nonaligned, this leadership position is helped by their nonnuclear status. In fact, Japan and Germany have some interests in common with the nonaligned states, such as the expansion of safeguards in the nuclear weapons states. To be sure, both Japan and Germany will pursue such interests with due regard to the interests of their friends and allies. For Japan, maintaining a close relationship with the United States is as important as shaping viable relations with China. Initiatives and controversies on nuclear policy must be weighed against this interest. By the same token, Germany must take into account the dense network of relations with its allies and with Russia, in addition to the German-French friendship. This will always set limits to Germany's readiness to confront the nuclear weapons states on nuclear issues. This, however, does not mean that both countries must shut up when the P 5 speak. The nuclear weapons register and the extension of the ''erga omnes'' rule in export controls, for example, should not be relegated to the dustbin of history, just because some friendly nuclear powers don't like these ideas. (orig.)

  13. 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.

  14. Government experience in nuclear power plant export financing

    International Nuclear Information System (INIS)

    Kalbitz, K.

    1976-01-01

    Because the long-term funds at the disposal of the commercial banks were insufficient to make available the amounts required for the exportation of nuclear power plants, it was necessary to make available long-term funds of the mortgage banks. On account of the strict regulations governing the lending operations of such banks, it was, however, necessary to introduce a Federal guarantee which covers 100% of the contract value in each case. On balance, however, the Federal Government does not take over any additional risks, because recourse may be taken to the commercial banks, which are liable for all additional payments under the credit arrangement having arisen from the improvement of the guarantee in favour of the mortgage banks. This has resulted in a considerable improvement of the export financing system which, of course, is for benefit of other major export projects too. (HP) [de

  15. Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus.

    Science.gov (United States)

    Wolfisberg, Raphael; Kempf, Christoph; Ros, Carlos

    2016-06-01

    Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process. In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid

  16. Applications of the INFCIRC225/rev5 to the national physical protection regime

    International Nuclear Information System (INIS)

    Kim, Jae Gwang

    2011-01-01

    The IAEA's first effort for playing a key role in physical protection of nuclear material and facilities resulted in the publication of 'Recommendations for the physical protection of nuclear material' in 1972. These recommendations were revised by a group of experts in co-operation with the IAEA Secretariat and the revised version was published in 1975 in INFCIRC/225. The document was subsequently revised in 1977(rev.1), 1989(rev.2), in 1993(rev.3) and 1998(rev4). The Physical Protection regime in ROK has been established on the basis of INFCIRC225 rev4 since 2004 IAEA recently published The INFCIRC 225 rev5 through the 2 years expert consultations. The publication recommended 12 nuclear security fundamentals and requirements of physical protection of nuclear material and nuclear facility to the member states. This paper suggests the several applications to the national physical protection system from the 12 fundamentals and the requirements

  17. Export and import provisions for nuclear materials and power plants, from the legal point of view

    International Nuclear Information System (INIS)

    Shapar, H.K.

    1975-01-01

    This paper provides a general review of the legal bases for and the administrative procedures involved in the export and import licensing of nuclear power reactors, fuels, and other nuclear materials by the United States. The basic statutory provisions and requirements are briefly described, and the requirement of an agreement for cooperation reviewed. The regulations of the Nuclear Regulatory Commission are covered in greater detail as they apply to the export and import of power reactors, nuclear fuels, source materials and byproduct materials. The intra-governmental procedures for review of an application for an export license are described in detail. Problems encountered in the administration of the law and regulations are described and the methods of resolving them are noted. The paper concludes with a brief account of three current topics, 1) the preparation of an environmental impact statement for export programs, 2) the situation with respect to the export licensing of component parts of reactors by the U.S. Department of Commerce, and 3) the shipment of plutonium by air. (orig.) [de

  18. Nuclear Export Control Policy in Korea - Present and future

    International Nuclear Information System (INIS)

    Kim, Jongsook

    2008-01-01

    The International community has been facing with the continued challenges for possession and proliferation of WMD over the past years. In addition, it is known that the terrorist groups are interested in acquiring WMD. The black market of WMD related materials and technologies show also the one of seriousness of our challenges. A number of international treaties, agreements and initiatives to control the proliferation of weapons of N, B, C and their delivery system have been existed to deal with these challenges, but their missions are challenged greatly in recent a series of nuclear issues by Iran and North Korea. The paper reviews the current international export control status and Korea export control system and policy. It also addresses some agenda to be done as future export control policy in Korea

  19. Land use mediates riverine nitrogen export under the dominant influence of human activities

    Science.gov (United States)

    Chen, Binhui; Chang, Scott X.; Lam, Shu Kee; Erisman, Jan Willem; Gu, Baojing

    2017-09-01

    Riverine nitrogen (N) export is a crucial process that links upstream and downstream ecosystems and coastal zones. However, the driving forces of riverine N export that is closely related to water N pollution are still not well understood. In this study, we used a mass balance approach to quantify the sources of N discharge and analyzed the effect of land use composition on riverine N export, taking Zhejiang Province, China as a case study. We found that the total reactive N discharge to rivers in Zhejiang increased from 0.22 to 0.26 Tg yr-1 from 2000 to 2015. At the watershed scale, our estimate of N export agrees well with the monitored riverine N concentration in the eight major watersheds in Zhejiang. Direct discharge of domestic wastewater and effluents from wastewater treatment plants are dominant sources of riverine N export, followed by agricultural non-point sources. Although riverine N export increases with the increasing proportion of urban and agricultural land uses, we did not find any relationship between land use change and changes in riverine N export. This suggests that the dominant factor affecting riverine N export should be human activities (e.g. wastewater discharge and fertilization level), while land use only mediates riverine N export.

  20. Adducin family proteins possess different nuclear export potentials.

    Science.gov (United States)

    Liu, Chia-Mei; Hsu, Wen-Hsin; Lin, Wan-Yi; Chen, Hong-Chen

    2017-05-10

    The adducin (ADD) family proteins, namely ADD1, ADD2, and ADD3, are actin-binding proteins that play important roles in the stabilization of membrane cytoskeleton and cell-cell junctions. All the ADD proteins contain a highly conserved bipartite nuclear localization signal (NLS) at the carboxyl termini, but only ADD1 can localize to the nucleus. The reason for this discrepancy is not clear. To avoid the potential effect of cell-cell junctions on the distribution of ADD proteins, HA epitope-tagged ADD proteins and mutants were transiently expressed in NIH3T3 fibroblasts and their distribution in the cytoplasm and nucleus was examined by immunofluorescence staining. Several nuclear proteins were identified to interact with ADD1 by mass spectrometry, which were further verified by co-immunoprecipitation. In this study, we found that ADD1 was detectable both in the cytoplasm and nucleus, whereas ADD2 and ADD3 were detected only in the cytoplasm. However, ADD2 and ADD3 were partially (~40%) sequestered in the nucleus by leptomycin B, a CRM1/exportin1 inhibitor. Upon the removal of leptomycin B, ADD2 and ADD3 re-distributed to the cytoplasm. These results indicate that ADD2 and ADD3 possess functional NLS and are quickly transported to the cytoplasm upon entering the nucleus. Indeed, we found that ADD2 and ADD3 possess much higher potential to counteract the activity of the NLS derived from Simian virus 40 large T-antigen than ADD1. All the ADD proteins appear to contain multiple nuclear export signals mainly in their head and neck domains. However, except for the leucine-rich motif ( 377 FEALMRMLDWLGYRT 391 ) in the neck domain of ADD1, no other classic nuclear export signal was identified in the ADD proteins. In addition, the nuclear retention of ADD1 facilitates its interaction with RNA polymerase II and zinc-finger protein 331. Our results suggest that ADD2 and ADD3 possess functional NLS and shuttle between the cytoplasm and nucleus. The discrepancy in the

  1. Guidance and considerations for the implementation of INFCIRC/225/Rev.4, the physical protection of nuclear material and nuclear facilities

    International Nuclear Information System (INIS)

    2000-05-01

    This publication is intended to provide guidance and considerations for a State's competent authority to better understand and prescribe appropriate requirements, consistent with INFCIRC/225/Rev.4 for the protection of nuclear material and nuclear facilities which are compatible with accepted international practice. This report, together with a more detailed report, Handbook on the Physical Protection of Nuclear Material and Facilities, which addresses to the licencee or designer of physical protection systems who has specific implementation and compliance responsibilities, should be used in conjunction to each other to provide better and comprehensive guidance on physical protection

  2. Guidance and considerations for the implementation of INFCIRC/225/Rev.4, the physical protection of nuclear material and nuclear facilities

    International Nuclear Information System (INIS)

    2002-05-01

    This publication is intended to provide guidance and considerations for a State's competent authority to better understand and prescribe appropriate requirements, consistent with INFCIRC/225/Rev.4 for the protection of nuclear material and nuclear facilities which are compatible with accepted international practice. This report, together with a more detailed report, Handbook on the Physical Protection of Nuclear Material and Facilities, which addresses to the licensee or designer of physical protection systems who has specific implementation and compliance responsibilities, should be used in conjunction to each other to provide better and comprehensive guidance on physical protection

  3. Guidance and considerations for the implementation of INFCIRC/225/Rev.4, the physical protection of nuclear material and nuclear facilities; Orientaciones y sugerencias para la aplicacion del documento INFCIRC/225/Rev.4, proteccion fisica de los materiales y las instalaciones nucleares

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-05-01

    This publication is intended to provide guidance and considerations for a State's competent authority to better understand and prescribe appropriate requirements, consistent with INFCIRC/225/Rev.4 for the protection of nuclear material and nuclear facilities which are compatible with accepted international practice. This report, together with a more detailed report, Handbook on the Physical Protection of Nuclear Material and Facilities, which addresses to the licensee or designer of physical protection systems who has specific implementation and compliance responsibilities, should be used in conjunction to each other to provide better and comprehensive guidance on physical protection.

  4. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  5. Technical modifications and management innovations in exporting nuclear reactor projects

    International Nuclear Information System (INIS)

    Mao Xiaoming; Qin Xijiu; Ding Hu; Xue Zhaoqun; Wen Shengjun

    2009-01-01

    As a main channel for the foreign economic cooperation of China nuclear industry, China Zhongyuan Engineering Corporation (CZEC) has been constantly engaged in technical modifications and management innovations in its exporting nuclear reactor projects. In the implementation of heavy water research reactor contract in Algeria, CZEC had established a complete and adequate design standards system in compliance with the international standards, and made significant modifications to the reference reactor in the aspects of reactor power and reactor safety, solved quite some technical issues which-affected the reactor technical performance. The modifications and improvements enabled the technical parameters, safety features, reactor multipurpose application to attain to the advanced level in the world. In the 300 MWe PWR NPPs in Pakistan, safety features had been updated in line with upgrading regulatory requisites. The design philosophy and technology application demonstrated CZEC' s creation and innovation on basis of constant safety enhancement of nuclear power projects. Efforts had also been made by CZEC' s creation and innovation on basis of constant safety enhancement of nuclear power projects. Efforts had also been made by CZEC in promoting China made equipment items and components exportation. (authors)

  6. The RNA helicase DDX1 is involved in restricted HIV-1 Rev function in human astrocytes

    International Nuclear Information System (INIS)

    Fang Jianhua; Acheampong, Edward; Dave, Rajnish; Wang Fengxiang; Mukhtar, Muhammad; Pomerantz, Roger J.

    2005-01-01

    Productive infection by human immunodeficiency virus type I (HIV-1) in the central nervous system (CNS) involves mainly macrophages and microglial cells. A frequency of less than 10% of human astrocytes is estimated to be infectable with HIV-1. Nonetheless, this relatively low percentage of infected astrocytes, but associated with a large total number of astrocytic cells in the CNS, makes human astrocytes a critical part in the analyses of potential HIV-1 reservoirs in vivo. Investigations in astrocytic cell lines and primary human fetal astrocytes revealed that limited HIV-1 replication in these cells resulted from low-level viral entry, transcription, viral protein processing, and virion maturation. Of note, a low ratio of unspliced versus spliced HIV-1-specific RNA was also investigated, as Rev appeared to act aberrantly in astrocytes, via loss of nuclear and/or nucleolar localization and diminished Rev-mediated function. Host cellular machinery enabling Rev function has become critical for elucidation of diminished Rev activity, especially for those factors leading to RNA metabolism. We have recently identified a DEAD-box protein, DDX1, as a Rev cellular co-factor and now have explored its potential importance in astrocytes. Cells were infected with HIV-1 pseudotyped with envelope glycoproteins of amphotropic murine leukemia viruses (MLV). Semi-quantitative reverse transcriptase-polymerase chain reactions (RT-PCR) for unspliced, singly-spliced, and multiply-spliced RNA clearly showed a lower ratio of unspliced/singly-spliced over multiply-spliced HIV-1-specific RNA in human astrocytes as compared to Rev-permissive, non-glial control cells. As well, the cellular localization of Rev in astrocytes was cytoplasmically dominant as compared to that of Rev-permissive, non-glial controls. This endogenous level of DDX1 expression in astrocytes was demonstrated directly to lead to a shift of Rev sub-cellular distribution dominance from nuclear and/or nucleolar to

  7. Final report of the 2. committee of investigation of the 11. legislative period. Nuclear exports

    International Nuclear Information System (INIS)

    1990-01-01

    On the subject of 'nuclear exports' the Committee dealt with political and legal principles of the Federal Government's nuclear export policy, particularly questions concerning the Non-Proliferation Treaty, and scientific-technical cooperation of the FRG with other countries, especially Argentina, Brazil, India, and Pakistan. Individual export transactions were then investigated, followed by a general assessment of the FRG's nuclear policy. - Concerning non-proliferation policy there have been certain administrative weaknesses in converting control measures into practice. Remedy is expected from the duty of terms to report deliveries punctually and completely and subsequent supervision. - The illegal transactions with India and Pakistan require improvements in the legal instruments, in the execution of administrative measures, and in border controls. Decisive steps have been introduced. (HSCH) [de

  8. Nuclear power, nuclear exports and the non-proliferation of nuclear weapons

    International Nuclear Information System (INIS)

    Hildenbrand, G.

    1977-01-01

    Developed and developing countries alike unfortunately have no other options in replacing oil in electricity generation than to use coal or nuclear energy. As far as the supplier countries are concerned, there is no doubt that nobody is interested in adding to the proliferation of nuclear weapons. On the other hand, the future electricity requirement in the developing countries, especially the need for nuclear power plants, represents a considerable market in the medium and long term which the supplier countries cannot simply ignore because they must seek to secure their export shares in order to protect jobs at home. For the receiver countries it is a matter of principle to achieve the highest possible degree of independence in energy generation so as to be able to guarantee continuity of supply. The interest in building up national fuel cycle activities is also closely linked with the creation of jobs in the receiver countries and with the efforts of these countries to straighten out their balance of payments situation. (orig.) [de

  9. Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

    Science.gov (United States)

    Loftus, Kyle M; Cui, Heying; Coutavas, Elias; King, David S; Ceravolo, Amanda; Pereiras, Dylan; Solmaz, Sozanne R

    2017-08-03

    Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

  10. The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA export.

    Science.gov (United States)

    Kristó, Ildikó; Bajusz, Csaba; Borsos, Barbara N; Pankotai, Tibor; Dopie, Joseph; Jankovics, Ferenc; Vartiainen, Maria K; Erdélyi, Miklós; Vilmos, Péter

    2017-10-01

    Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus. The distribution of Moesin in the nucleus suggests a function in transcription and the depletion of mRNA export factors Nup98 or its interacting partner, Rae1, leads to the nuclear accumulation of Moesin, suggesting that the nuclear function of the protein is linked to mRNA export. Moesin localizes to mRNP particles through the interaction with the mRNA export factor PCID2 and knock down of Moesin leads to the accumulation of mRNA in the nucleus. Based on our results we propose that, beyond its well-known, manifold functions in the cytoplasm, the ERM protein of Drosophila is a new, functional component of the nucleus where it participates in mRNA export. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Analysis of World Nuclear Market and Strategy of Korean NPP's Competitiveness Improvement for Exportation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Young; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of); Roh, Seungkook [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Chang, Soon Heung [Handong Global University, Pohang (Korea, Republic of)

    2016-10-15

    China, India and USA (nuclear adopted countries) are planning tremendous number of NPPs to meet their increasing electricity demand and Saudi Arabia, Vietnam (nuclear adopting countries) are also planning to include nuclear power in their energy mix as a long-term plan. Korea has exported 4 units of APR1400 to the UAE in December, 2009. Korea became sixth NPP supplier country and our economic feasibility and safety features were started to evaluate worldwide. Nuclear industries became a new driver of Korea’s export and nuclear industries in Korea are now expecting another NPP export to Middle-eastern countries, including UAE and Saudi Arabia, based on the first-mover’s advantage at the UAE. In 2000s, five countries (Japan, USA, France, Russia and Korea), which are able to build NPP, focused on NPP export more than domestic construction. Global trend of world nuclear market changed rapidly, especially after NPP export to the UAE. By the global trend, hegemony of nuclear market migrated from supplier country to buyer country. Nuclear companies started cooperating rather than competing. Financing to developing countries become more important. In general, one of the considerable combinations is Korea-Japan-USA alliance. Korea is in charge of EPC, Japan supports financing and deficient technology (with USA partner), and Japan-USA handles fuel supply and back-end fuel cycle based on new agreed terms of ROK-US Nuclear Cooperation Agreement. This combination was judged to best way to collaborate with global companies. Paying attention to many delayed (or potentially delayed) constructions from Russia, intercepting the construction work will be available in case of contracted countries. Korea can emphasize the short construction time, high responsiveness and mild/equal diplomatic position to the target countries.

  12. Nuclear export and armament. New threats and peace perspectives

    International Nuclear Information System (INIS)

    Kubbig, B.W.; Mueller, H.

    1993-02-01

    The authors give a condensed analysis of safety and politico-economic dimensions regarding the further proliferation of nuclear weapons and carrier systems with which nuclear blasting charges can be transported. From the content: - Proliferation and non-proliferation: technology, economy and (international) law in a political historic survey. - Missile defense: appropriate technological answer to the political proliferation problem? -export strategies: USA and FRG in comparison, interest and policy of the European Community. - Components for an extensive proliferation strategy. (orig./HP) [de

  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. Nuclear export controls and the CTBT: Where we`ve been and challenges ahead -- Views of an engineer

    Energy Technology Data Exchange (ETDEWEB)

    Lundy, A.S.

    1998-09-01

    The paper discusses the following topics: the importance of export controls; the uniqueness of nuclear weapons and their export control requirements; ``dual-use`` controls; and recent developments in nonproliferation beyond export control. Also discussed are some non-obvious challenges which include computer modeling and visualization, and fissile material availability and instant nukes. The author concludes by asking the Nuclear Suppliers Group to consider whether there are ways to make its controls more effective.

  16. Nuclear export controls and the CTBT: Where we've been and challenges ahead - Views of an engineer

    International Nuclear Information System (INIS)

    Lundy, A.S.

    1998-01-01

    The paper discusses the following topics: the importance of export controls; the uniqueness of nuclear weapons and their export control requirements; ''dual-use'' controls; and recent developments in nonproliferation beyond export control. Also discussed are some non-obvious challenges which include computer modeling and visualization, and fissile material availability and instant nukes. The author concludes by asking the Nuclear Suppliers Group to consider whether there are ways to make its controls more effective

  17. Define rules for the exporter and importer of minerals or ores containing nuclear elements

    International Nuclear Information System (INIS)

    1969-01-01

    The present resolution establishes regulations for the exporter of minerals or ores containing associated nuclear elements, and for the importer of chemical compounds of technical purity grade, containing a quantity of fissile of fertile materials equal to the existent in the exported material

  18. Simplification of the Provisions of the Nuclear Energy Act on Imports and Exports; A Working Group Report

    International Nuclear Information System (INIS)

    2001-01-01

    The Ministry of Trade and Industry appointed a working group to map out possibilities of simplifying the provisions on imports and exports of nuclear products and to submit a proposal for the amendment of the Nuclear Energy Act in this respect. The working group should especially map out relevant international and EU norms and consider to what extent it would be possible to replace the present licensing procedure with obligations imposed on operators and/or a notification procedure. The working group should further study the possibility of combining the provisions on the control of nuclear materials, the safety of transports of nuclear and other radioactive material nuclear liability and physical protection of nuclear materials with the provisions on imports and exports. The working group did not discuss the provisions on the imports and exports of nuclear waste. The Council Regulation concerning the control of exports of dual-use items and technology, which entered into force in September 2000, and the amendment of the Regulation with a view to nuclear material adopted in January 2001 call for an amendment of the provisions of the Nuclear Energy Act concerning exports. The working group proposes that a direct reference to the EU Regulation should be included in the Nuclear Energy Decree. The definition of exports is proposed to be changed so that it corresponds to the definition in the EU Regulation. The Nuclear Energy Decree should, however, comprise provisions on applying for an authorization, on a licensing authority and on the possibility of applying for a global authorisation. The global authorisation shall replace the Intra-Community trade licence, which is proposed to be abolished. It is proposed that the Ministry of Trade and Industry should be the licensing authority. It is further proposed that provisions should be issued on a notification procedure for products falling under the scope of the Nuclear Energy Act for which no export authorisation is

  19. Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion.

    Science.gov (United States)

    Alefantis, Timothy; Flaig, Katherine E; Wigdahl, Brian; Jain, Pooja

    2007-05-01

    Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-kappaB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.

  20. Nuclear localization of Lyn tyrosine kinase mediated by inhibition of its kinase activity

    International Nuclear Information System (INIS)

    Ikeda, Kikuko; Nakayama, Yuji; Togashi, Yuuki; Obata, Yuuki; Kuga, Takahisa; Kasahara, Kousuke; Fukumoto, Yasunori; Yamaguchi, Naoto

    2008-01-01

    Src-family kinases, cytoplasmic enzymes that participate in various signaling events, are found at not only the plasma membrane but also subcellular compartments, such as the nucleus, the Golgi apparatus and late endosomes/lysosomes. Lyn, a member of the Src-family kinases, is known to play a role in DNA damage response and cell cycle control in the nucleus. However, it is still unclear how the localization of Lyn to the nucleus is regulated. Here, we investigated the mechanism of the distribution of Lyn between the cytoplasm and the nucleus in epitheloid HeLa cells and hematopoietic THP-1 cells. Lyn was definitely detected in purified nuclei by immunofluorescence and immunoblotting analyses. Nuclear accumulation of Lyn was enhanced upon treatment of cells with leptomycin B (LMB), an inhibitor of Crm1-mediated nuclear export. Moreover, Lyn mutants lacking the sites for lipid modification were highly accumulated in the nucleus upon LMB treatment. Intriguingly, inhibition of the kinase activity of Lyn by SU6656, Csk overexpression, or point mutation in the ATP-binding site induced an increase in nuclear Lyn levels. These results suggest that Lyn being imported into and rapidly exported from the nucleus preferentially accumulates in the nucleus by inhibition of the kinase activity and lipid modification

  1. Phosphorylation of zona occludens-2 by protein kinase C epsilon regulates its nuclear exportation.

    Science.gov (United States)

    Chamorro, David; Alarcón, Lourdes; Ponce, Arturo; Tapia, Rocio; González-Aguilar, Héctor; Robles-Flores, Martha; Mejía-Castillo, Teresa; Segovia, José; Bandala, Yamir; Juaristi, Eusebio; González-Mariscal, Lorenza

    2009-09-01

    Here, we have analyzed the subcellular destiny of newly synthesized tight junction protein zona occludens (ZO)-2. After transfection in sparse cells, 74% of cells exhibit ZO-2 at the nucleus, and after 18 h the value decreases to 17%. The mutation S369A located within the nuclear exportation signal 1 of ZO-2 impairs the nuclear export of the protein. Because Ser369 represents a putative protein kinase C (PKC) phosphorylation site, we tested the effect of PKC inhibition and stimulation on the nuclear export of ZO-2. Our results strongly suggest that the departure of ZO-2 from the nucleus is regulated by phosphorylation at Ser369 by novel PKCepsilon. To test the route taken by ZO-2 from synthesis to the plasma membrane, we devised a novel nuclear microinjection assay in which the nucleus served as a reservoir for anti-ZO-2 antibody. Through this assay, we demonstrate that a significant amount of newly synthesized ZO-2 goes into the nucleus and is later relocated to the plasma membrane. These results constitute novel information for understanding the mechanisms that regulate the intracellular fate of ZO-2.

  2. Export Control Guide: Loose Parts Monitoring Systems for Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Langenberg, Donald W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2012-12-01

    This report describes a typical LPMS, emphasizing its application to the RCS of a modern NPP. The report also examines the versatility of AE monitoring technology by describing several nuclear applications other than loose parts monitoring, as well as some non-nuclear applications. In addition, LPMS implementation requirements are outlined, and LPMS suppliers are identified. Finally, U.S. export controls applicable to LPMSs are discussed.

  3. Nuclear exports. Parliamentary control and confidentiality; Parlamentarische Kontrolle und Geheimhaltungsbeduerftigkeit bei Nuklearexporten. Zum Urteil des Bundesverfassungsgerichts vom 21. Oktober 2014

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2015-03-15

    With its decision taken on 21. October 2014 (Az.: 2 BvE 5/11) the Federal Constitutional Court (BVerfG) decided during court proceedings between administrative bodies on the scope and limits of the parliamentary right of information. Even though the proceeding did not deal with nuclear exports but arm exports, foreign trade law, however, does not only designate an export licence obligation for military weapons but also for so called dual-use goods meaning goods, which can be used both for friendly as well as for military purposes. The export of these goods requires according to the so-called Dual-Use Regulation (EG) 428/2009 a licence. Annex I category 0 of the regulation (EG) 428/2009 lists a variety of nuclear materials, plants and equipment items for which this licence applies. In the same manner as arm exports, also exports of nuclear dual-use goods are being discussed in a special cabinet committee, the Federal Security Council (BSR), which shall coordinate cross-departmentally the German security and defence policy under consideration of economic interests and which categorises its results, according to the rules of procedure, as confidential. Also legally not regulated but common ''preliminary enquiries'' at the responsible Federal Ministry or rather Federal Office of Economics and Export Control by companies which plan an export and want to affirm the general approval for their export business prior to conclusion of contract take not only place for arm exports but also for nuclear dual-use goods. The decision by the Federal Constitutional Court can be applied to consultations about the authorisation of nuclear dual-use goods.

  4. The HIV-1 Rev/RRE system is required for HIV-1 5' UTR cis elements to augment encapsidation of heterologous RNA into HIV-1 viral particles

    Directory of Open Access Journals (Sweden)

    Ma Hong

    2011-06-01

    Full Text Available Abstract Background The process of HIV-1 genomic RNA (gRNA encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (ψ. Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site from the 5' untranslated region (UTR. Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles. Results We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and ψ. Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons; however, the cDNA forms are episomes predominantly in the 1-LTR circle form. Conclusions Premised on encapsidation of a heterologous RNA into

  5. The new US nuclear non-proliferation and export policy

    International Nuclear Information System (INIS)

    Welck, S. von.

    1981-01-01

    The future American nuclear non-proliferation and export policy will be determined chiefly by three elements: (1) Adherence to the former objective of nuclear non-proliferation. (2) A large and varied assortment of old and new tools for implementing this goal. (3) Much more differentiation in applying these tools in the light of the reliability, with respect to non-proliferation policy, of the respective partner. Consequently, it would make little sense for the new Administration to force upon allied industrialized countries, whose nuclear technologies are at the same level as that of the United States, restrictive rules on reprocessing and breeder technology. The new measures designed to curb proliferation are especially meant to destroy motivations that could cause states to own nuclear explosives. This also applies to the removal of economic motivations. (orig.) [de

  6. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  7. Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.

    Science.gov (United States)

    Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki

    2017-06-01

    Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

  8. Mediator-dependent Nuclear Receptor Functions

    Science.gov (United States)

    Chen, Wei; Roeder, Robert

    2011-01-01

    As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

  9. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received notes verbales dated 27 August 1993 and 28 October 1993 from the Permanent Missions of Finland and Spain to the International Atomic Energy relating to the export of nuclear material, equipment and technology. The purpose of these notes verbales is to provide further information on those Governments' nuclear export policies and practices

  10. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    International Nuclear Information System (INIS)

    Kurooka, Hisanori; Sugai, Manabu; Mori, Kentaro; Yokota, Yoshifumi

    2013-01-01

    Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite

  11. A stably expressed llama single-domain intrabody targeting Rev displays broad-spectrum anti-HIV activity.

    Science.gov (United States)

    Boons, Eline; Li, Guangdi; Vanstreels, Els; Vercruysse, Thomas; Pannecouque, Christophe; Vandamme, Anne-Mieke; Daelemans, Dirk

    2014-12-01

    The HIV Rev protein mediates the transport of partially and unspliced HIV mRNA from the nucleus to the cytoplasm. Rev multimerizes on a secondary stem-loop structure present in the viral intron-containing mRNA species and recruits the cellular karyopherin CRM1 to export viral mRNAs from the nucleus to the cytoplasm. Previously we have identified a single-domain intrabody (Nb(190)), derived from a llama heavy-chain antibody, which efficiently inhibits Rev multimerization and suppresses the production of infectious virus. We recently mapped the epitope of this nanobody and demonstrated that Rev residues K20 and Y23 are crucial for interaction while residues V16, H53 and L60 are important to a lesser extent. Here, we generated cell lines stably expressing Nb(190) and assessed the capacity of these cell lines to suppress the replication of different HIV-1 subtypes. These cells stably expressing the single-domain antibody are protected from virus-induced cytopathogenic effect even in the context of high multiplicity of infection. In addition, the replication of different subtypes of group M and one strain of group O is significantly suppressed in these cell lines. Next, we analysed the natural variations of Rev amino acids in sequence samples from HIV-1 infected patients worldwide and assessed the effect of Nb(190) on the most prevalent polymorphisms occurring at the key epitope positions (K20 and Y23) in Rev. We found that Nb(190) was able to suppress the function of these Rev variants except for the K20N mutant, which was present in only 0.7% of HIV-1 sequence populations (n = 4632). Cells stably expressing the single-domain intrabody Nb(190) are protected against virus-induced cytopathogenic effect and display a selective survival advantage upon infection. In addition, Nb(190) suppresses the replication of a wide range of different HIV-1 subtypes. Large-scale sequence analysis reveals that the Nb(190) epitope positions in Rev are well conserved across major HIV-1

  12. Nuclear fuels imports and exports of the Federal Republic of Germany 1989

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    The statistics compiled by the Federal Office for the Economy (Bundesamt fuer Wirtschaft) on behalf of the German Federal Ministry for the Environment, Nature Conservation and Reactor Safety of the imports and exports of nuclear fuels and source material in 1989 show a drop in imports by 29.5% and a considerable increase in exports by 104%. For comparison, the relevant figures of the preceding year are given in brackets throughout this statistical survey. (orig.) [de

  13. 1987 nuclear fuel imports and exports of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    The statistics of imports and exports of nuclear fuels and source materials compiled by the German Federal Office for Industry (Bundesamt fuer Wirtschaft) and the Federal Ministry for the Environment, Protection of Nature, and Reactor Safety (Bundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit) shows a 29.1% increase in imports and a 16.9% decrease of exports in 1987 compared to the previous year. A major rise was experienced in imports of natural uranium, uranium enriched up to 3% and to 3-10%, and plutonium, while there was a decline in imports of depleted uranium, source materials, and more highly enriched uranium. Uranium enriched 3-10%, highly enriched uranium, and plutonium were exported in larger quantities, while only smaller quantities of depleted uranium, source materials, natural uranium, uranium enriched up to 3%, and uranium enriched 10-85% were exported. (orig.) [de

  14. Problems associated with the export of nuclear power plants

    International Nuclear Information System (INIS)

    1978-01-01

    Full text: Recent forecasts indicate that by the year 2000 there will be more than 1000 nuclear power plants operating in 50 countries and with several countries expecting to derive one-half or more of their electric generation from nuclear power plants At present only six countries are exporters of nuclear power systems, three more currently supply their own domestic markets, while the remainder are importers. It is expected that most of the importers will continue to depend to varying degrees on foreign supply, at least in the near future. If nuclear power is to offer an important benefit to the world, the achievement of this benefit will require co-operation between the supplying and receiving nations in overcoming problems which might inhibit the full development of this energy source. In addition to ensuring safety and reliability, special problem areas include financing, skilled manpower needs, adequate local industrial and engineering infrastructure, access to advanced technology, and an assured supply of nuclear fuel. The symposium had special emphasis on the problems facing many of the developing countries in the initial stages of nuclear power programmes, and was divided into three major topics nuclear safety, domestic contributions, and international aspects In the safety area, emphasis was given to the special considerations that may exist for countries that import nuclear plants. These special considerations can be due to some non-standard features of the exported reactor such as lower power ratings, dissimilar site characteristics that can effect the design, and the evolution and changes in design and safety requirements during construction. This can be complicated by differences in safety philosophy and codified standards of the various suppliers and unique construction problems in the less developed countries. Thus, the ability of the importing country to carry out the regulatory and safety function is obviously important. A number of presentations

  15. Suppression of atherosclerosis by synthetic REV-ERB agonist

    Energy Technology Data Exchange (ETDEWEB)

    Sitaula, Sadichha [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Billon, Cyrielle [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States); Kamenecka, Theodore M.; Solt, Laura A. [Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458 (United States); Burris, Thomas P., E-mail: burristp@slu.edu [Department of Pharmacological & Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104 (United States)

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  16. Canada's reactor exports

    International Nuclear Information System (INIS)

    Morrison, R.W.

    1981-01-01

    A brief sketch of the development of Canada's nuclear exports is presented and some of the factors which influence the ability to export reactors have been identified. The potential market for CANDUs is small and will develop slowly. The competition will be tough. There are few good prospects for immediate export orders in the next two or three years. Nonetheless there are reasonable opportunities for CANDU exports, especially in the mid-to-late 1980s. Such sales could be of great benefit to Canada and could do much to sustain the domestic nuclear industry. Apart from its excellent economic and technical performance, the main attraction of the CANDU seems to be the autonomy it confers on purchasing countries, the effectiveness with which the associated technology can be transferred, and the diversification it offers to countries which wish to reduce their dependence on the major industrial suppliers. Each sales opportunity is unique, and marketing strategy will have to be tailored to the customer's needs. Over the next decade, the factors susceptible to Canadian government action which are most likely to influence CANDU exports will be the political commitment of the government to those reactor exports, the performance established by the four 600 MWe CANDUs now nearing completion, the continuing successful operation of the nuclear program in Ontario, and the co-ordination of the different components of Canada's nuclear program (AECL, nuclear industry, utilities, and government) in putting forth a coherent marketing effort and following through with effective project management

  17. Review on 18th Revision of 'Notice on Export and Import of Strategic Items'

    International Nuclear Information System (INIS)

    Jeon, Jihye; Lee, Chansuh

    2014-01-01

    Nuclear Suppliers Group (NSG) has established a guideline and continued to revise it in accordance with ever-changing international situation and developing technology. The Part 1 of guideline, 'Guidelines of Nuclear Transfers' covers the Trigger List items which triggers safeguards as a condition of supply. Currently NSG has published the 12 th revised guideline (INFCIRC/254/Rev.12/Part1) in November 2013. Korean government fully reflected the guideline to its national legislation to implement in accordance with internationally agreed standard. The export control of nuclear strategic items in Korea is responsibility of Nuclear Safety and Security Commission (NSSC), which entrusted the technical review of the work to Korea Institute of Nonproliferation and Control (KINAC). The specific guidelines for the technical review are stipulated in Notice on Export and Import of Strategic Items with other strategic items usable to other Weapons of Mass Destruction. The Ministry of Trade, Industry and Energy approved the 18 th revision of Notice on Export and Import of Strategic Items on 31 January 2014 as Notice no. 2014-15, which strictly follows the NSG guideline. The 18 th revision of the notice reflects the final proposals agreed from the last Dedicated Meeting of Technical Experts (DMTE) of NSG's Consultative Group (CG) in April 2013. The 3-year-DMTE offered the 'fundamental, holistic approach to the technical review' within the international framework of NSG, rather than sporadic endeavors by individual states in the past. The 18 th version itself has meaning in that the final products of the international technical review were reflected in the Korean national legislation of nuclear export control. It addressed various changes in control text in technical, contextual, and editorial aspects. The revision is analyzed herein concentrating only on technical and semantic changes in control text

  18. The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts

    DEFF Research Database (Denmark)

    Silla, Toomas; Karadoulama, Evdoxia; Mąkosa, Dawid

    2018-01-01

    , containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1......Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci...... but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export...

  19. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  20. Import and export of small quantities of nuclear materials

    International Nuclear Information System (INIS)

    Grenier, M.

    1986-06-01

    Administrative procedures for import export of nuclear materials are specific for each country. In France regulations are reviewed for small quantities, lower threshold, in some cases, allows a simplified procedure, however thresholds are not the same in the different texts (and for one of them, concerning proliferation, is zero). It is obvious that regulations are necessary even for small quantities but national and international threshold should be harmonized [fr

  1. CD151, a novel host factor of nuclear export signaling in influenza virus infection.

    Science.gov (United States)

    Qiao, Yongkang; Yan, Yan; Tan, Kai Sen; Tan, Sheryl S L; Seet, Ju Ee; Arumugam, Thiruma Valavan; Chow, Vincent T K; Wang, De Yun; Tran, Thai

    2018-05-01

    Despite advances in our understanding of the mechanisms of influenza A virus (IAV) infection, the crucial virus-host interactions during the viral replication cycle still remain incomplete. Tetraspanin CD151 is highly expressed in the human respiratory tract, but its pathological role in IAV infection is unknown. We sought to characterize the functional role and mechanisms of action of CD151 in IAV infection of the upper and lower respiratory tracts with H1N1 and H3N2 strains. We used CD151-null mice in an in vivo model of IAV infection and clinical donor samples of in vitro-differentiated human nasal epithelial cells cultured at air-liquid interface. As compared with wild-type infected mice, CD151-null infected mice exhibited a significant reduction in virus titer and improvement in survival that is associated with pronounced host antiviral response and inflammasome activation together with accelerated lung repair. Interestingly, we show that CD151 complexes newly synthesized viral proteins with host nuclear export proteins and stabilizes microtubule complexes, which are key processes necessary for the polarized trafficking of viral progeny to the host plasma membrane for assembly. Our results provide new mechanistic insights into our understanding of IAV infection. We show that CD151 is a critical novel host factor of nuclear export signaling whereby the IAV nuclear export uses it to complement its own nuclear export proteins (a site not targeted by current therapy), making this regulation unique, and holds promise for the development of novel alternative/complementary strategies to reduce IAV severity. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Review on 18{sup th} Revision of 'Notice on Export and Import of Strategic Items'

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Jihye; Lee, Chansuh [Korea Institute of Nuclear Nonproliferation and Control, Daejeon (Korea, Republic of)

    2014-05-15

    Nuclear Suppliers Group (NSG) has established a guideline and continued to revise it in accordance with ever-changing international situation and developing technology. The Part 1 of guideline, 'Guidelines of Nuclear Transfers' covers the Trigger List items which triggers safeguards as a condition of supply. Currently NSG has published the 12{sup th} revised guideline (INFCIRC/254/Rev.12/Part1) in November 2013. Korean government fully reflected the guideline to its national legislation to implement in accordance with internationally agreed standard. The export control of nuclear strategic items in Korea is responsibility of Nuclear Safety and Security Commission (NSSC), which entrusted the technical review of the work to Korea Institute of Nonproliferation and Control (KINAC). The specific guidelines for the technical review are stipulated in Notice on Export and Import of Strategic Items with other strategic items usable to other Weapons of Mass Destruction. The Ministry of Trade, Industry and Energy approved the 18{sup th} revision of Notice on Export and Import of Strategic Items on 31 January 2014 as Notice no. 2014-15, which strictly follows the NSG guideline. The 18{sup th} revision of the notice reflects the final proposals agreed from the last Dedicated Meeting of Technical Experts (DMTE) of NSG's Consultative Group (CG) in April 2013. The 3-year-DMTE offered the 'fundamental, holistic approach to the technical review' within the international framework of NSG, rather than sporadic endeavors by individual states in the past. The 18{sup th} version itself has meaning in that the final products of the international technical review were reflected in the Korean national legislation of nuclear export control. It addressed various changes in control text in technical, contextual, and editorial aspects. The revision is analyzed herein concentrating only on technical and semantic changes in control text.

  3. A prototype system dynamic model of nuclear and radiological export controls in Central Asia and the Caucasus; enhancing the effectiveness of preventing illicit nuclear material trafficking

    International Nuclear Information System (INIS)

    Ferguston, C.D.; Ouagrham, S.B.

    2002-01-01

    An urgent need calls out for improved border security and export control systems in the Central Asian and Caucasus regions to prevent illicit nuclear and radioactive materials trafficking. Effective nuclear and radiological exports controls are essential because these regions contain numerous nuclear facilities and radioactive materials as well as lie at the crossroads between seekers and suppliers of technologies that could be employed in nuclear and radiological weapons. Porous and unprotected borders compound these concerns. Moreover, the states within these regions are struggling with forming new regulations and laws, obtaining sufficient portal monitoring equipment, training customs and border security personnel, and coordinating these activities with neighboring states. Building this infrastructure all at once can severely task any government. Thus, unsurprisingly, most of these states have inadequate export control and border security systems. To enable each state in these regions determine how to better prevent illicit nuclear and radiological materials trafficking, the authors have developed a prototype system dynamics model focused on evaluating and improving of effectiveness of export controls. System dynamics modeling, a management tool that grew out of the field of system engineering and nonlinear dynamics, uses two structures: causal loop diagrams and stock and flow diagrams. The former shows how endogenous systematic factors interact with each other to produce feedback mechanisms that results in either balancing or reinforcing loops. A classic example is a arms race, modeled as a vicious cycle or reinforcing loop. In addition to interacting with each other, causal loops influence the flow of stock, which is material concern. In the export control system dynamics model, the stock represents nuclear and radioactive materials. System dynamics modelling is an iterative process that is continually modified by user input. Therefore, export control

  4. Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

    Energy Technology Data Exchange (ETDEWEB)

    Morioka, Norimitsu, E-mail: mnori@hiroshima-u.ac.jp; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2016-01-08

    Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

  5. Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

    International Nuclear Information System (INIS)

    Morioka, Norimitsu; Tomori, Mizuki; Zhang, Fang Fang; Saeki, Munenori; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

    2016-01-01

    Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9 induction.

  6. Mapping the binding interface between an HIV-1 inhibiting intrabody and the viral protein Rev.

    Directory of Open Access Journals (Sweden)

    Thomas Vercruysse

    Full Text Available HIV-1 Rev is the key protein in the nucleocytoplasmic export and expression of the late viral mRNAs. An important aspect for its function is its ability to multimerize on these mRNAs. We have recently identified a llama single-domain antibody (Nb190 as the first inhibitor targeting the Rev multimerization function in cells. This nanobody is a potent intracellular antibody that efficiently inhibits HIV-1 viral production. In order to gain insight into the Nb190-Rev interaction interface, we performed mutational and docking studies to map the interface between the nanobody paratope and the Rev epitope. Alanine mutants of the hyper-variable domains of Nb190 and the Rev multimerization domains were evaluated in different assays measuring Nb190-Rev interaction or viral production. Seven residues within Nb190 and five Rev residues are demonstrated to be crucial for epitope recognition. These experimental data were used to perform docking experiments and map the Nb190-Rev structural interface. This Nb190-Rev interaction model can guide further studies of the Nb190 effect on HIV-1 Rev function and could serve as starting point for the rational development of smaller entities binding to the Nb190 epitope, aimed at interfering with protein-protein interactions of the Rev N-terminal domain.

  7. Four decades of living with the genie: United States nuclear export policy

    International Nuclear Information System (INIS)

    Kramish, A.

    1983-01-01

    The subject is discussed as follows: general introduction (examples of complex nature of nuclear trade); non-proliferation policy - the beginnings (early US action to control dealings with other countries); the Nuclear Non-Proliferation Act of 1978 (formulation of US policy on nuclear trade; INFCE (International Nuclear Fuel Cycle Evaluation)); the Symington and Glenn Amendments (US legislation to control trade with other countries); the Export-Import Bank Act (US legislation for the same purpose as above); the Non-Proliferation Treaty; the Reagan Policy (US present policy to support IAEA safeguards and Non-Proliferation Treaty); future prospects. (U.K.)

  8. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Science.gov (United States)

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  9. NLSdb-major update for database of nuclear localization signals and nuclear export signals.

    Science.gov (United States)

    Bernhofer, Michael; Goldberg, Tatyana; Wolf, Silvana; Ahmed, Mohamed; Zaugg, Julian; Boden, Mikael; Rost, Burkhard

    2018-01-04

    NLSdb is a database collecting nuclear export signals (NES) and nuclear localization signals (NLS) along with experimentally annotated nuclear and non-nuclear proteins. NES and NLS are short sequence motifs related to protein transport out of and into the nucleus. The updated NLSdb now contains 2253 NLS and introduces 398 NES. The potential sets of novel NES and NLS have been generated by a simple 'in silico mutagenesis' protocol. We started with motifs annotated by experiments. In step 1, we increased specificity such that no known non-nuclear protein matched the refined motif. In step 2, we increased the sensitivity trying to match several different families with a motif. We then iterated over steps 1 and 2. The final set of 2253 NLS motifs matched 35% of 8421 experimentally verified nuclear proteins (up from 21% for the previous version) and none of 18 278 non-nuclear proteins. We updated the web interface providing multiple options to search protein sequences for NES and NLS motifs, and to evaluate your own signal sequences. NLSdb can be accessed via Rostlab services at: https://rostlab.org/services/nlsdb/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Nuclear Successor States of the Soviet Union, Nuclear Weapon and Sensitive Export Status Report

    Science.gov (United States)

    1994-05-01

    international advisory group composed of: Valentin Alexandrov Ministry of Foreign Affairs, Minsk Alexander Bolsunovsky Institute of Biophysics, Krasnoyarsk Oleg...Center for Nonproliferation and Export Control, Minsk Alexander Pikayev Inst. of World Economy and Intl. Relations, Moscow Anatoly Scherba Ministry of...Bulletin of the Atomic Scientists, March/April 1994; A. Pikayev and A. Savelyev , "The USSR’s Nuclear Might: On Land, At Sea, At Air," Nezavisimaya Gazeta

  11. RRE-dependent HIV-1 Env RNA effects on Gag protein expression, assembly and release

    International Nuclear Information System (INIS)

    López, Claudia S.; Sloan, Rachel; Cylinder, Isabel; Kozak, Susan L.; Kabat, David; Barklis, Eric

    2014-01-01

    The HIV-1 Gag proteins are translated from the full-length HIV-1 viral RNA (vRNA), whereas the envelope (Env) protein is translated from incompletely spliced Env mRNAs. Nuclear export of vRNAs and Env mRNAs is mediated by the Rev accessory protein which binds to the rev-responsive element (RRE) present on these RNAs. Evidence has shown there is a direct or indirect interaction between the Gag protein, and the cytoplasmic tail (CT) of the Env protein. Our current work shows that env gene expression impacts HIV-1 Gag expression and function in two ways. At the protein level, full-length Env expression altered Gag protein expression, while Env CT-deletion proteins did not. At the RNA level, RRE-containing Env mRNA expression reduced Gag expression, processing, and virus particle release from cells. Our results support models in which Gag is influenced by the Env CT, and Env mRNAs compete with vRNAs for nuclear export. - Highlights: • At the protein level, full-length HIV-1 Env alters Gag protein expression. • HIV-1 Env RNA expression reduces Gag levels and virus release. • Env RNA effects on Gag are dependent on the RRE. • RRE-containing Env RNAs compete with vRNAs for nuclear export

  12. Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export signal

    International Nuclear Information System (INIS)

    Sato, Hiroki; Masuda, Munemitsu; Miura, Ryuichi; Yoneda, Misako; Kai, Chieko

    2006-01-01

    Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the N proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway

  13. An essential nuclear protein in trypanosomes is a component of mRNA transcription/export pathway.

    Directory of Open Access Journals (Sweden)

    Mariana Serpeloni

    Full Text Available In eukaryotic cells, different RNA species are exported from the nucleus via specialized pathways. The mRNA export machinery is highly integrated with mRNA processing, and includes a different set of nuclear transport adaptors as well as other mRNA binding proteins, RNA helicases, and NPC-associated proteins. The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, a widespread and neglected human disease which is endemic to Latin America. Gene expression in Trypanosoma has unique characteristics, such as constitutive polycistronic transcription of protein-encoding genes and mRNA processing by trans-splicing. In general, post-transcriptional events are the major points for regulation of gene expression in these parasites. However, the export pathway of mRNA from the nucleus is poorly understood. The present study investigated the function of TcSub2, which is a highly conserved protein ortholog to Sub2/ UAP56, a component of the Transcription/Export (TREX multiprotein complex connecting transcription with mRNA export in yeast/human. Similar to its orthologs, TcSub2 is a nuclear protein, localized in dispersed foci all over the nuclei -except the fibrillar center of nucleolus- and at the interface between dense and non-dense chromatin areas, proposing the association of TcSub2 with transcription/processing sites. These findings were analyzed further by BrUTP incorporation assays and confirmed that TcSub2 is physically associated with active RNA polymerase II (RNA pol II, but not RNA polymerase I (RNA pol I or Spliced Leader (SL transcription, demonstrating participation particularly in nuclear mRNA metabolism in T. cruzi. The double knockout of the TcSub2 gene is lethal in T. cruzi, suggesting it has an essential function. Alternatively, RNA interference assays were performed in Trypanosoma brucei. It allowed demonstrating that besides being an essential protein, its knockdown causes mRNA accumulation in the nucleus and

  14. The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation.

    Science.gov (United States)

    Li, Ping; Stumpf, Maria; Müller, Rolf; Eichinger, Ludwig; Glöckner, Gernot; Noegel, Angelika A

    2017-08-22

    SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.

  15. RNA Export through the NPC in Eukaryotes.

    Science.gov (United States)

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  16. Export control guide: Spent nuclear fuel reprocessing and preparation of plutonium metal

    International Nuclear Information System (INIS)

    1993-10-01

    The international Treaty on the Non-Proliferation of Nuclear Weapons, also referred to as the Non-Proliferation Treaty (NPT), states in Article III, paragraph 2(b) that open-quotes Each State Party to the Treaty undertakes not to provide . . . equipment or material especially designed or prepared for the processing, use or production of special fissionable material to any non-nuclear-weapon State for peaceful purposes, unless the source or special fissionable material shall be subject to the safeguards required by this Article.close quotes This guide was prepared to assist export control officials in the interpretation, understanding, and implementation of export laws and controls relating to the international Trigger List for irradiated nuclear fuel reprocessing equipment, components, and materials. The guide also contains information related to the production of plutonium metal. Reprocessing and its place in the nuclear fuel cycle are described briefly; the standard procedure to prepare metallic plutonium is discussed; steps used to prepare Trigger List controls are cited; descriptions of controlled items are given; and special materials of construction are noted. This is followed by a comprehensive description of especially designed or prepared equipment, materials, and components of reprocessing and plutonium metal processes and includes photographs and/or pictorial representations. The nomenclature of the Trigger List has been retained in the numbered sections of this document for clarity

  17. Competitiveness, export control and export promotion of dual-use goods. European and German balancing exercises

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2014-01-01

    The EU Commission Communication of 24 April 2014 to the Council and the European Parliament ''The review of export control policy: Ensuring Security and Competitiveness in a changing world'' as well as the increasingly number of inquiries and applications to the German Federal Government (e.g. the rejection of Hermes guarantees and state funding of nuclear export and termination of bilateral cooperation in the field of nuclear technologies) once again reason to discuss the current tension between the principle of free movement of goods, competitiveness and export promotion on the one hand and the export control on the other.

  18. Regulation of p53 tetramerization and nuclear export by ARC.

    Science.gov (United States)

    Foo, Roger S-Y; Nam, Young-Jae; Ostreicher, Marc Jason; Metzl, Mark D; Whelan, Russell S; Peng, Chang-Fu; Ashton, Anthony W; Fu, Weimin; Mani, Kartik; Chin, Suet-Feung; Provenzano, Elena; Ellis, Ian; Figg, Nichola; Pinder, Sarah; Bennett, Martin R; Caldas, Carlos; Kitsis, Richard N

    2007-12-26

    Inactivation of the transcription factor p53 is central to carcinogenesis. Yet only approximately one-half of cancers have p53 loss-of-function mutations. Here, we demonstrate a mechanism for p53 inactivation by apoptosis repressor with caspase recruitment domain (ARC), a protein induced in multiple cancer cells. The direct binding in the nucleus of ARC to the p53 tetramerization domain inhibits p53 tetramerization. This exposes a nuclear export signal in p53, triggering Crm1-dependent relocation of p53 to the cytoplasm. Knockdown of endogenous ARC in breast cancer cells results in spontaneous tetramerization of endogenous p53, accumulation of p53 in the nucleus, and activation of endogenous p53 target genes. In primary human breast cancers with nuclear ARC, p53 is almost always WT. Conversely, nearly all breast cancers with mutant p53 lack nuclear ARC. We conclude that nuclear ARC is induced in cancer cells and negatively regulates p53.

  19. Characterization of a nuclear export signal within the human T cell leukemia virus type I transactivator protein Tax.

    Science.gov (United States)

    Alefantis, Timothy; Barmak, Kate; Harhaj, Edward W; Grant, Christian; Wigdahl, Brian

    2003-06-13

    Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-kappaB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxDelta214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.

  20. Communications received from Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-04-01

    The Director General has received notes verbales to the export of nuclear material, equipment and technology from the following Permanent Missions to the International Atomic Energy Agency: notes verbales dated 1 March 1994 from the Permanent Missions of Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Hungary, Italy, Japan, the Netherlands, Poland, Portugal, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, the United States of America; and a note verbale dated 12 March 1994 from the Permanent Mission of Romania. The purpose of these notes verbales is to provide further information on these Governments' nuclear export policies and practices

  1. ENDF/B-5 Fission Products Library. Rev. 2

    International Nuclear Information System (INIS)

    Schwerer, O.; Pronyaev, V.G.; Lemmel, H.D.

    1984-07-01

    This document summarizes contents and documentation of the 1984 version of the Fission Products Nuclear Data File of the ENDF/B-5 Library (Rev. 2) maintained by the National Nuclear Data Center (NNDC) at the Brookhaven National Laboratory, USA. This file contains numerical neutron reaction data and decay data for 877 fission product nuclides. The entire file or selective retrievals from it can be obtained on magnetic tape from the IAEA Nuclear Data Section. (author)

  2. Notification to the Agency of exports and imports of nuclear material

    International Nuclear Information System (INIS)

    1991-12-01

    The document reproduces the letter dated 15 November 1991 received by the Director General of the IAEA from the Resident Representative to the Agency of the People's Republic of China, informing him that, in the interest of assisting the Agency in its safeguards activities, the Government of the People's Republic of China had decided to provide it henceforth with information on exports and imports of nuclear material

  3. Communication Received from Canada Regarding its New Nuclear Export Policy

    International Nuclear Information System (INIS)

    1977-01-01

    On 29 December 1976 the Director General received a letter dated 28 December from the Resident Representative of Canada to the Agency, informing him of a change in Canada's nuclear export policy and attaching a statement made in the Canadian House of Commons on this subject. In accordance with the request made by the Resident Representative of Canada the texts of his letter and of its attachment are reproduced below for the information of all Members.

  4. 1988 nuclear fuel imports and exports of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    The statistic of imports and exports of nuclear fuels and source materials compiled by the Federal Office for Industry on behalf of the Federal Ministry for the Environment, Nature Conservation, and Reactor Safety show a 32.3% decrease in imports and a 17.6% increase in exports in 1988 compared to the previous year. Most of the imports are made up of source materials, natural uranium, and uranium enriched up to 10%. The term 'source material' as used in these statistics refers only to uranium concentrate. A considerable increase is reported in imports of uranium enriched 3 to 10% and of plutonium. All other products have suffered major or minor decreases. (orig.)

  5. Export regulation

    International Nuclear Information System (INIS)

    Gates, D.J.

    1978-01-01

    Australia is a major uranium supplier. Uranium is exported under conditions laid down to avoid any nuclear proliferation. On 24 May 1977 the Prime Minister had stated the main elements of Australian policy: the strengthening of the system of international safeguards and the selection of importing countries. (Non-nuclear weapon states must be Contracting Parties to the NPT. Nuclear weapon states must undertake not to use Australian uranium for this purpose). Australia retains property of the uranium up to the UF 6 stage (uranium hexafluoride) in the fuel cycle; it reserves the right to stop any export if the importing country no longer complies with AIEA Safeguards. Any transfer to a third country, any irradiated fuel reprocessing, requires Australia's prior agreement. Finally, importing countries must satisfy physical protection conditions. (NEA) [fr

  6. ALS Associated Mutations in Matrin 3 Alter Protein-Protein Interactions and Impede mRNA Nuclear Export.

    Science.gov (United States)

    Boehringer, Ashley; Garcia-Mansfield, Krystine; Singh, Gurkaran; Bakkar, Nadine; Pirrotte, Patrick; Bowser, Robert

    2017-11-06

    Mutations in Matrin 3 have recently been linked to ALS, though the mechanism that induces disease in these patients is unknown. To define the protein interactome of wild-type and ALS-linked MATR3 mutations, we performed immunoprecipitation followed by mass spectrometry using NSC-34 cells expressing human wild-type or mutant Matrin 3. Gene ontology analysis identified a novel role for Matrin 3 in mRNA transport centered on proteins in the TRanscription and EXport (TREX) complex, known to function in mRNA biogenesis and nuclear export. ALS-linked mutations in Matrin 3 led to its re-distribution within the nucleus, decreased co-localization with endogenous Matrin 3 and increased co-localization with specific TREX components. Expression of disease-causing Matrin 3 mutations led to nuclear mRNA export defects of both global mRNA and more specifically the mRNA of TDP-43 and FUS. Our findings identify a potential pathogenic mechanism attributable to MATR3 mutations and further link cellular transport defects to ALS.

  7. Communication of 2 June 2009 received from the Permanent Mission of the United Kingdom regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2009-01-01

    The Director General has received a note ver bale from the Permanent Mission of the United Kingdom, dated 2 June 2009, in which it requests that the Agency circulate to all Member States a letter of 28 May 2009 from the Chairman of the Zangger Committee, Mr. Pavel Klucky, to the Director General, on behalf of the Governments of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Croatia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Kazakhstan, the Republic of Korea, Luxemburg, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom and the United States of America, concerning a number of corrections to the communication regarding the export of nuclear material and of certain categories of equipment and other material published in INFCIRC/209/Rev.2 [fr

  8. Communication of 2 June 2009 received from the Permanent Mission of the United Kingdom regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2009-01-01

    The Director General has received a note ver bale from the Permanent Mission of the United Kingdom, dated 2 June 2009, in which it requests that the Agency circulate to all Member States a letter of 28 May 2009 from the Chairman of the Zangger Committee, Mr. Pavel Klucky, to the Director General, on behalf of the Governments of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Croatia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Kazakhstan, the Republic of Korea, Luxemburg, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom and the United States of America, concerning a number of corrections to the communication regarding the export of nuclear material and of certain categories of equipment and other material published in INFCIRC/209/Rev.2 [ru

  9. Communication of 2 June 2009 received from the Permanent Mission of the United Kingdom regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2009-01-01

    The Director General has received a note ver bale from the Permanent Mission of the United Kingdom, dated 2 June 2009, in which it requests that the Agency circulate to all Member States a letter of 28 May 2009 from the Chairman of the Zangger Committee, Mr. Pavel Klucky, to the Director General, on behalf of the Governments of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Croatia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Kazakhstan, the Republic of Korea, Luxemburg, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom and the United States of America, concerning a number of corrections to the communication regarding the export of nuclear material and of certain categories of equipment and other material published in INFCIRC/209/Rev.2 [es

  10. 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.

  11. Rev1 Recruits Ung to Switch Regions and Enhances dU Glycosylation for Immunoglobulin Class Switch DNA Recombination

    Directory of Open Access Journals (Sweden)

    Hong Zan

    2012-11-01

    Full Text Available By diversifying the biological effector functions of antibodies, class switch DNA recombination (CSR plays a critical role in the maturation of the immune response. It is initiated by activation-induced cytidine deaminase (AID-mediated deoxycytosine deamination, yielding deoxyuridine (dU, and dU glycosylation by uracil DNA glycosylase (Ung in antibody switch (S region DNA. Here we showed that the translesion DNA synthesis polymerase Rev1 directly interacted with Ung and targeted in an AID-dependent and Ung-independent fashion the S regions undergoing CSR. Rev1−/− Ung+/+ B cells reduced Ung recruitment to S regions, DNA-dU glycosylation, and CSR. Together with an S region spectrum of mutations similar to that of Rev1+/+ Ung−/− B cells, this suggests that Rev1 operates in the same pathway as Ung, as emphasized by further decreased CSR in Rev1−/− Msh2−/− B cells. Rescue of CSR in Rev1−/− B cells by a catalytically inactive Rev1 mutant shows that the important role of Rev1 in CSR is mediated by Rev1’s scaffolding function, not its enzymatic function.

  12. A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei.

    Science.gov (United States)

    Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin

    2018-01-29

    Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

  13. A study on the establishment of national nuclear foreign policy with reference to nuclear export control system, strategy toward IAEA, and NPT review conferences

    International Nuclear Information System (INIS)

    Choi, Young Myung; Nam, Jang Soo; Lee, Han Myung

    1990-02-01

    The objectives of this study are follows: suggestion for i) our future nuclear development directions, ii) establishment of national export control system, iii) establishment of strategy toward IAEA, and suggestion of our standpoints toward the 4th NPT review conference. This study proposes the following; 1) It is desirable that nuclear power generation strategy is propelled under the premise of economics and proven technology. And international cooperation in connection with the nuclear fuel cycle should be reinforced. 2) It is recommened that nuclear export control system should be government-led. 3) Our country needs to make efforts in increasing the number of Korean staff in the IAEA, and to establish permanent mission which is wholly responsible for the IAEA affairs, and to construct a system which deals with nuclear foregin activities. 4) It is desirable that the basic position of our country toward the 4th NPT review conference should be : i) to urge parties to the NPT to conclude safeguards agreement with IAEA as early as possible, ii) to request nuclear suppliers to mitigate their nuclear technology for peaceful uses to nuclear developing countries, and iii) to urge nuclear weapon states to make further efforts for nuclear disarmament. (author)

  14. Deciphering mechanisms of drug sensitivity and resistance to Selective Inhibitor of Nuclear Export (SINE) compounds

    International Nuclear Information System (INIS)

    Crochiere, Marsha; Kashyap, Trinayan; Kalid, Ori; Shechter, Sharon; Klebanov, Boris; Senapedis, William; Saint-Martin, Jean-Richard; Landesman, Yosef

    2015-01-01

    Exportin 1 (XPO1) is a well-characterized nuclear export protein whose expression is up-regulated in many types of cancers and functions to transport key tumor suppressor proteins (TSPs) from the nucleus. Karyopharm Therapeutics has developed a series of small-molecule Selective Inhibitor of Nuclear Export (SINE) compounds, which have been shown to block XPO1 function both in vitro and in vivo. The drug candidate, selinexor (KPT-330), is currently in Phase-II/IIb clinical trials for treatment of both hematologic and solid tumors. The present study sought to decipher the mechanisms that render cells either sensitive or resistant to treatment with SINE compounds, represented by KPT-185, an early analogue of KPT-330. Using the human fibrosarcoma HT1080 cell line, resistance to SINE was acquired over a period of 10 months of constant incubation with increasing concentration of KPT-185. Cell viability was assayed by MTT. Immunofluorescence was used to compare nuclear export of TSPs. Fluorescence activated cell sorting (FACS), quantitative polymerase chain reaction (qPCR), and immunoblots were used to measure effects on cell cycle, gene expression, and cell death. RNA from naïve and drug treated parental and resistant cells was analyzed by Affymetrix microarrays. Treatment of HT1080 cells with gradually increasing concentrations of SINE resulted in > 100 fold decrease in sensitivity to SINE cytotoxicity. Resistant cells displayed prolonged cell cycle, reduced nuclear accumulation of TSPs, and similar changes in protein expression compared to parental cells, however the magnitude of the protein expression changes were more significant in parental cells. Microarray analyses comparing parental to resistant cells indicate that a number of key signaling pathways were altered in resistant cells including expression changes in genes involved in adhesion, apoptosis, and inflammation. While the patterns of changes in transcription following drug treatment are similar in parental

  15. Nuclear Sanctions: Section 102(b) of the Arms Export Control Act and its Application to India and Pakistan

    National Research Council Canada - National Science Library

    Grimmett, Jeanne J

    2001-01-01

    Section 102(b) of the Arms Export Control Act (AECA) requires the President to impose sanctions on any country that he has determined is a "non-nuclear-weapon state" and has received or detonated a "nuclear explosive device...

  16. Nuclear Propulsion for Space (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Corliss, William R; Schwenk, Francis C

    1971-01-01

    The operation of nuclear rockets and a description of the development of nuclear rockets in the U.S. is given. Early developments and Project Rover, Project Pluto, and the NERVA (Nuclear Engine for Rocket Vehicle Application) Program are detailed. The Nuclear Rocket Development Station facilities in Nevada are described. The possibilities and advantages of using nuclear rockets for missions beginning from an earth orbit and moving outward toward higher earth orbits, the moon, and the planets are discussed.

  17. Nuclear export and import of human hepatitis B virus capsid protein and particles.

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Li

    Full Text Available It remains unclear what determines the subcellular localization of hepatitis B virus (HBV core protein (HBc and particles. To address this fundamental issue, we have identified four distinct HBc localization signals in the arginine rich domain (ARD of HBc, using immunofluorescence confocal microscopy and fractionation/Western blot analysis. ARD consists of four tight clustering arginine-rich subdomains. ARD-I and ARD-III are associated with two co-dependent nuclear localization signals (NLS, while ARD-II and ARD-IV behave like two independent nuclear export signals (NES. This conclusion is based on five independent lines of experimental evidence: i Using an HBV replication system in hepatoma cells, we demonstrated in a double-blind manner that only the HBc of mutant ARD-II+IV, among a total of 15 ARD mutants, can predominantly localize to the nucleus. ii These results were confirmed using a chimera reporter system by placing mutant or wild type HBc trafficking signals in the heterologous context of SV40 large T antigen (LT. iii By a heterokaryon or homokaryon analysis, the fusion protein of SV40 LT-HBc ARD appeared to transport from nuclei of transfected donor cells to nuclei of recipient cells, suggesting the existence of an NES in HBc ARD. This putative NES is leptomycin B resistant. iv We demonstrated by co-immunoprecipitation that HBc ARD can physically interact with a cellular factor TAP/NXF1 (Tip-associated protein/nuclear export factor-1, which is known to be important for nuclear export of mRNA and proteins. Treatment with a TAP-specific siRNA strikingly shifted cytoplasmic HBc to nucleus, and led to a near 7-fold reduction of viral replication, and a near 10-fold reduction in HBsAg secretion. v HBc of mutant ARD-II+IV was accumulated predominantly in the nucleus in a mouse model by hydrodynamic delivery. In addition to the revised map of NLS, our results suggest that HBc could shuttle rapidly between nucleus and cytoplasm via a novel

  18. Notification to the Agency of Exports and Imports of Nuclear Material

    International Nuclear Information System (INIS)

    1984-03-01

    On 16 February 1984 the Director General received a letter dated 7 February 1984 from the Governor from France on the Agency's Board of Governors informing him that, in the interest of assisting the Agency in its safeguards activities, the Government of France had decided to provide it henceforth with information on exports and imports of nuclear material. In the light of the request made in this letter, its text is reproduced

  19. Characterisation of mouse mammary tumour virus and host related regulatory factors

    International Nuclear Information System (INIS)

    Müllner, M.

    2012-01-01

    Mouse mammary tumour virus (MMTV) is an oncogenic retrovirus that causes mammary tumours and T-cell lymphomas in mice (1,2). Although classified as a simple Betaretrovirus, MMTV was recently shown to encode an accessory protein in addition to the commonly known structural (Gag, Env) and non-structural (Pol) proteins (3,4). The regulatory protein is expressed from a doubly spliced rem-mRNA message and contains functional motifs including (i.e. a nuclear localisation signal, a nuclear export signal as well as a RNA binding domain) similar to HIV-1 Rev and Rev-like RNA export proteins of other complex retroviruses. The newly identified 39 kDa protein was demonstrated to be involved in viral RNA export and therefore termed regulator of expression of MMTV mRNA (Rem). To date, however, little is known about the binding site for Rem, the Rem responsive element (RmRE), present in the MMTV genome. Based on previous analyses, the MMTV RmRE was supposed to be located close to the 3' end of the genomic viral RNA. In order to more precisely locate RmRE and to demonstrate its proposed function, a series of MMTV full length and subgenomic molecular clones lacking different parts of the MMTV genome were constructed. After transfection into MMTV permissive cells (CrFK), viral RNA export from the nucleus was monitored by Northern blotting. By this means, a 400 nt long sequence spanning the Env-U3 region was identified to be essential for the nuclear export of unspliced MMTV RNA. These results were confirmed in a second heterologous assay showing functional interaction of Rem and RmRE. In addition, RNA export involving MMTV Rem and RmRE was demonstrated to be dependent on the cellular CRM1 protein. Detailed evaluation of the obtained results indicated that single-spliced viral env mRNA was exported only to some extent via the CRM1-mediated pathway. This suggested that MMTV exploits different RNA export strategies for transport of non-spliced and single-spliced RNA species

  20. Nuclear routing networks span between nuclear pore complexes and genomic DNA to guide nucleoplasmic trafficking of biomolecules

    Science.gov (United States)

    Malecki, Marek; Malecki, Bianca

    2012-01-01

    In health and disease, biomolecules, which are involved in gene expression, recombination, or reprogramming have to traffic through the nucleoplasm, between nuclear pore complexes (NPCs) and genomic DNA (gDNA). This trafficking is guided by the recently revealed nuclear routing networks (NRNs). In this study, we aimed to investigate, if the NRNs have established associations with the genomic DNA in situ and if the NRNs have capabilities to bind the DNA de novo. Moreover, we aimed to study further, if nucleoplasmic trafficking of the histones, rRNA, and transgenes’ vectors, between the NPCs and gDNA, is guided by the NRNs. We used Xenopus laevis oocytes as the model system. We engineered the transgenes’ DNA vectors equipped with the SV40 LTA nuclear localization signals (NLS) and/or HIV Rev nuclear export signals (NES). We purified histones, 5S rRNA, and gDNA. We rendered all these molecules superparamagnetic and fluorescent for detection with nuclear magnetic resonance (NMR), total reflection x-ray fluorescence (TXRF), energy dispersive x-ray spectroscopy (EDXS), and electron energy loss spectroscopy (EELS). The NRNs span between the NPCs and genomic DNA. They form firm bonds with the gDNA in situ. After complete digestion of the nucleic acids with the RNases and DNases, the newly added DNA - modified with the dNTP analogs, bonds firmly to the NRNs. Moreover, the NRNs guide the trafficking of the DNA transgenes’ vectors - modified with the SV40 LTA NLS, following their import into the nuclei through the NPCs. The pathway is identical to that of histones. The NRNs also guide the trafficking of the DNA transgenes’ vectors, modified with the HIV Rev NES, to the NPCs, followed by their export out of the nuclei. Ribosomal RNAs follow the same pathway. To summarize, the NRNs are the structures connecting the NPCs and the gDNA. They guide the trafficking of the biomolecules between the NPCs and the gDNA. PMID:23275893

  1. A study on strengthening measures of non-proliferation regime through the export control system of sensitive materials, equipment and technology related to nuclear activities

    International Nuclear Information System (INIS)

    Kikuchi, Masahiro; Kurosawa, Mitsuru; Komizo, Yasuyoshi

    2004-01-01

    The strengthened safeguards caused from safeguards experiences to Iraq and DPRK leads to the expansion of the IAEA's activities for verification of all nuclear activities as well as verification of nuclear material in the States. The purpose of the activities, of course, includes detection of undeclared exports and imports of specified equipment and non-nuclear material. The Additional Protocol to the agreements between States and the IAEA for the application of safeguards requires to the States to declare the exports and imports information regarding specified equipment and non-nuclear material corresponding to the export control list that is established by the nuclear suppliers group. The Additional Protocol also insists the IAEA's right to access to the location identified by the State to resolve a question related to the declarations. Recently, the IAEA detected the black market group of the sensitive materials, equipment and technologies relevant to the nuclear proliferation through the safeguards activities to Iran and Libya. International community stated deeply concerns to the indecent facts. This paper would discuss and propose the supplemental strengthening measures of non-proliferation regime by effective combination of the safeguards activities under additional protocol and the export control regime. (author)

  2. Export of radiopharmaceuticals and establishment of export base of cyclotron

    International Nuclear Information System (INIS)

    Jung, Kyungil; Kim, Youngsik

    2006-01-01

    Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

  3. Nuclear Power Plants (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Lyerly, Ray L.; Mitchell III, Walter [Southern Nuclear Engineering, Inc.

    1973-01-01

    Projected energy requirements for the future suggest that we must employ atomic energy to generate electric power or face depletion of our fossil-fuel resources—coal, oil, and gas. In short, both conservation and economic considerations will require us to use nuclear energy to generate the electricity that supports our civilization. Until we reach the time when nuclear power plants are as common as fossil-fueled or hydroelectric plants, many people will wonder how the nuclear plants work, how much they cost, where they are located, and what kinds of reactors they use. The purpose of this booklet is to answer these questions. In doing so, it will consider only central station plants, which are those that provide electric power for established utility systems.

  4. Should Australia mine and export uranium?

    International Nuclear Information System (INIS)

    Cobb, M.; Broadbent, Steve.

    1989-01-01

    In this chapter, the case for and against the mining and export of Australian uranium is discussed. For those in favour of uranium export, the nuclear energy, a source of energy which could bring a much needed boost to Australian export and employment, is being stifled by specious 'scare tactics' about the danger and misuse of uranium. It is also shown that uranium is the only feasible energy source, being cheaper, safer and cleaner when compared with other energy sources. Meanwhile, the opponents of nuclear energy, argue that uranium mining is environmentally destructive, is a danger to workers and residents health, it is bad for economy and it provides raw materials for nuclear weapons. 2 tabs

  5. Notification to the Agency of Exports and Imports of Nuclear Material

    International Nuclear Information System (INIS)

    1974-01-01

    On 11 July 1974 the Director General received letters dated 10 July from the Resident Representatives to the Agency of the Union of Soviet Socialist Republics, the United Kingdom of Great Britain and Northern Ireland and the United States of America informing him that in the interest of assisting the Agency in its safeguards activities, the Governments of these three Members had decided to provide it henceforth with information on exports and imports of nuclear material

  6. Communications received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-04-01

    The document reproduces the Note Verbale dated 8 February 1993 received by the Director General from the Permanent Mission of the Russian Federation to the International Organizations in Vienna, relating to the export of nuclear material, equipment or technology, in order to provide information on that Government's Guidelines for Nuclear Transfer

  7. Export policy and non-proliferation

    International Nuclear Information System (INIS)

    Fischer, D.A.V.

    1978-01-01

    Developing countries with a nuclear programme are about a dozen according to information obtained by IAEA. They are a group hostile to any restriction imposed on nuclear technology export and consider that such restriction is contrary to the global concept of North/South co-operation which provides for transfer of advanced technology. In particular, they object to the fact that nuclear weapon states make use of Article 4 of the NPT. Industrialised countries are required to keep a balance between a regular and stable supply system and the assurance that exported nuclear installations and materials are placed under international control according to the IAEA Safeguards. (NEA) [fr

  8. The directionality of the nuclear transport of the influenza A genome is driven by selective exposure of nuclear localization sequences on nucleoprotein

    Directory of Open Access Journals (Sweden)

    Panté Nelly

    2009-06-01

    Full Text Available Abstract Background Early in infection, the genome of the influenza A virus, consisting of eight complexes of RNA and proteins (termed viral ribonucleoproteins; vRNPs, enters the nucleus of infected cells for replication. Incoming vRNPs are imported into the nucleus of infected cells using at least two nuclear localization sequences on nucleoprotein (NP; NLS1 at the N terminus, and NLS2 in the middle of the protein. Progeny vRNP assembly occurs in the nucleus, and later in infection, these are exported from the nucleus to the cytoplasm. Nuclear-exported vRNPs are different from incoming vRNPs in that they are prevented from re-entering the nucleus. Why nuclear-exported vRNPs do not re-enter the nucleus is unknown. Results To test our hypothesis that the exposure of NLSs on the vRNP regulates the directionality of the nuclear transport of the influenza vRNPs, we immunolabeled the two NLSs of NP (NLS1 and NLS2 and analyzed their surface accessibility in cells infected with the influenza A virus. We found that the NLS1 epitope on NP was exposed throughout the infected cells, but the NLS2 epitope on NP was only exposed in the nucleus of the infected cells. Addition of the nuclear export inhibitor leptomycin B further revealed that NLS1 is no longer exposed in cytoplasmic NP and vRNPs that have already undergone nuclear export. Similar immunolabeling studies in the presence of leptomycin B and with cells transfected with the cDNA of NP revealed that the NLS1 on NP is hidden in nuclear exported-NP. Conclusion NLS1 mediates the nuclear import of newly-synthesized NP and incoming vRNPs. This NLS becomes hidden on nuclear-exported NP and nuclear-exported vRNPs. Thus the selective exposure of the NLS1 constitutes a critical mechanism to regulate the directionality of the nuclear transport of vRNPs during the influenza A viral life cycle.

  9. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

    International Nuclear Information System (INIS)

    Kumari, Gita; Mahalingam, S.

    2009-01-01

    Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

  10. Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2

    Energy Technology Data Exchange (ETDEWEB)

    Kumari, Gita [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Mahalingam, S., E-mail: mahalingam@iitm.ac.in [Laboratory of Molecular Virology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500076 (India); Department of Biotechnology, Laboratory of Molecular Virology and Cell Biology, Indian Institute of Technology-Madras, Chennai 600 036 (India)

    2009-10-01

    Ras GTPase controls the normal cell growth through binding with an array of effector molecules, such as Raf and PI3-kinase in a GTP-dependent manner. RASSF2, a member of the Ras association domain family, is known to be involved in the suppression of cell growth and is frequently down-regulated in various tumor tissues by promoter hypermethylation. In the present study, we demonstrate that RASSF2 shuttles between nucleus and cytoplasm by a signal-mediated process and its export from the nucleus is sensitive to leptomycin B. Amino acids between 240 to 260 in the C-terminus of RASSF2 harbor a functional nuclear export signal (NES), which is necessary and sufficient for efficient export of RASSF2 from the nucleus. Substitution of conserved Ile254, Val257 and Leu259 within the minimal NES impaired RASSF2 export from the nucleus. In addition, wild type but not the nuclear export defective RASSF2 mutant interacts with export receptor, CRM-1 and exported from the nucleus. Surprisingly, we observed nucleolar localization for the nuclear export defective mutant suggesting the possibility that RASSF2 may localize in different cellular compartments transiently in a cell cycle dependent manner and the observed nuclear localization for wild type protein may be due to faster export kinetics from the nucleolus. Furthermore, our data suggest that RASSF2 is specifically phosphorylated by MAPK/ERK-2 and the inhibitors of MAPK pathway impair the phosphorylation and subsequently block the export of RASSF2 from the nucleus. These data clearly suggest that ERK-2 mediated phosphorylation plays an important role in regulating the nucleo-cytoplasmic shuttling of RASSF2. Interestingly, nuclear import defective mutant of RASSF2 failed to induce cell cycle arrest at G1/S phase and apoptosis suggesting that RASSF2 regulates cell growth in a nuclear localization dependent manner. Collectively, these data provided evidence for the first time that MAPK/ERK-2 mediated phosphorylation regulates

  11. Heat-shock stress activates a novel nuclear import pathway mediated by Hikeshi

    OpenAIRE

    Imamoto, Naoko; Kose, Shingo

    2012-01-01

    Cellular stresses significantly affect nuclear transport systems. Nuclear transport pathways mediated by importin β-family members, which are active under normal conditions, are downregulated. During thermal stress, a nuclear import pathway mediated by a novel carrier, which we named Hikeshi, becomes active. Hikeshi is not a member of the importin β family and mediates the nuclear import of Hsp70s. Unlike importin β family-mediated nuclear transport, the Hikeshi-mediated nuclear import of Hsp...

  12. Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

    Science.gov (United States)

    Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

    2016-01-01

    The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

  13. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-01-01

    The document reproduces the Note Verbale dated 2 December 1992 received by the Director General from the Resident Representative of Argentina to the Agency relating to the export of nuclear material, equipment and technology in order to clarify parts of the Trigger List which is incorporated in Annex A to the Guidelines for Nuclear Transfers

  14. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1993-01-01

    The document reproduces the Note Verbale dated 2 December 1992 received by the Director General from the Resident Representative of Argentina to the Agency relating to the export of nuclear material, equipment or technology, in order to provide information on that Government's Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology

  15. HIV-1 matrix dependent membrane targeting is regulated by Gag mRNA trafficking.

    Directory of Open Access Journals (Sweden)

    Jing Jin

    Full Text Available Retroviral Gag polyproteins are necessary and sufficient for virus budding. Productive HIV-1 Gag assembly takes place at the plasma membrane. However, little is known about the mechanisms by which thousands of Gag molecules are targeted to the plasma membrane. Using a bimolecular fluorescence complementation (BiFC assay, we recently reported that the cellular sites and efficiency of HIV-1 Gag assembly depend on the precise pathway of Gag mRNA export from the nucleus, known to be mediated by Rev. Here we describe an assembly deficiency in human cells for HIV Gag whose expression depends on hepatitis B virus (HBV post-transcriptional regulatory element (PRE mediated-mRNA nuclear export. PRE-dependent HIV Gag expressed well in human cells, but assembled with slower kinetics, accumulated intracellularly, and failed to associate with a lipid raft compartment where the wild-type Rev-dependent HIV-1 Gag efficiently assembles. Surprisingly, assembly and budding of PRE-dependent HIV Gag in human cells could be rescued in trans by co-expression of Rev-dependent Gag that provides correct membrane targeting signals, or in cis by replacing HIV matrix (MA with other membrane targeting domains. Taken together, our results demonstrate deficient membrane targeting of PRE-dependent HIV-1 Gag and suggest that HIV MA function is regulated by the trafficking pathway of the encoding mRNA.

  16. Communication received from the Permanent Mission of Denmark to the Agency regarding Guidelines for the Export of Nuclear Material, Equipment and Technology; Comunicacion recibida de la Mision Permanente de Dinamarca ante el Organismo relativa a las directrices para la exportacion de materiales, equipos y tecnologia nucleares

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-01-02

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology [Spanish] El Director General ha recibido una nota verbal de la Mision Permanente de Dinamarca, de fecha 1 de diciembre de 2005, en la que se facilita informacion sobre las politicas y practicas del Gobierno de Dinamarca con respecto a la exportacion de materiales, equipos y tecnologia nucleares. Atendiendo a los deseos expresados al final de la nota verbal, se adjunta al presente documento el texto de dicha nota. El apendice a que se hace referencia en la nota verbal se publico previamente como INFCIRC/254/Rev.7/pt.1.

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

    Science.gov (United States)

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

    2016-03-01

    Nuclear export factor 1 (NXF1) exports mRNA to the cytoplasm after recruitment to mRNA by specific adaptor proteins. How and why cells use numerous different export adaptors is poorly understood. Here we critically evaluate members of the SR protein family (SRSF1-7) for their potential to act as NXF1 adaptors that couple pre-mRNA processing to mRNA export. Consistent with this proposal, >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1-7 were determined in parallel by individual-nucleotide-resolution UV cross-linking and immunoprecipitation (iCLIP). Quantitative comparisons of RNA-binding sites showed that NXF1 and SR proteins bind mRNA targets at adjacent sites, indicative of cobinding. SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Interestingly, SRSF3 and SRSF7 were shown to bind different sites in last exons and regulate 3' untranslated region length in an opposing manner. Both SRSF3 and SRSF7 promoted NXF1 recruitment to mRNA. Thus, SRSF3 and SRSF7 couple alternative splicing and polyadenylation to NXF1-mediated mRNA export, thereby controlling the cytoplasmic abundance of transcripts with alternative 3' ends. © 2016 Müller-McNicoll et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Communication received from the permanent mission of the Argentine Republic regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    On 11 May 1994, the Director General received a note verbale from the Permanent Mission of Argentina to the International Atomic Energy Agency relating to the export of nuclear material, equipment and technology. The purpose of this note verbale is to provide further information on the nuclear export policies and practices of the Government of the Argentine Republic. In the light of the wish expressed at the end of the note verbale, the text of the note verbale is annexed hereto

  19. Communication received from the permanent mission of the Argentine Republic regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1994-11-01

    On 11 May 1994, the Director General received a note verbale from the Permanent Mission of Argentina to the International Atomic Energy Agency relating to the export of nuclear material, equipment and technology. The purpose of this note verbale is to provide further information on nuclear export policies and practices of the Government of the Argentine Republic. In the light of the wish expressed at the end of the note verbale, the text of the note verbale is annexed hereto

  20. REV-ERB and ROR: therapeutic targets for treating myopathies

    Science.gov (United States)

    Welch, Ryan D.; Flaveny, Colin A.

    2017-08-01

    Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

  1. Demonstration and Dialogue: Mediation in Swedish Nuclear Waste Management

    International Nuclear Information System (INIS)

    Elam, Mark; Lidberg, Maria; Soneryd, Linda; Sundqvist, Goeran

    2009-01-01

    This report analyses mediation and mediators in Swedish nuclear waste management. Mediation is about establishing agreement and building common knowledge. It is argued that demonstrations and dialogue are the two prominent approaches to mediation in Swedish nuclear waste management. Mediation through demonstration is about showing, displaying, and pointing out a path to safe disposal for inspection. It implies a strict division between demonstrator and audience. Mediation through dialogue on the other hand, is about collective acknowledgements of uncertainty and suspensions of judgement creating room for broader discussion. In Sweden, it is the Swedish Nuclear Fuel and Waste Management Co. (SKB) that is tasked with finding a method and a site for the final disposal of the nation's nuclear waste. Two different legislative frameworks cover this process. In accordance with the Act on Nuclear Activities, SKB is required to demonstrate the safety of its planned nuclear waste management system to the government, while in respect of the Swedish Environmental Code, they are obliged to organize consultations with the public. How SKB combines these requirements is the main question under investigation in this report in relation to materials deriving from three empirical settings: 1) SKB's safety analyses, 2) SKB's public consultation activities and 3) the 'dialogue projects', initiated by other actors than SKB broadening the public arena for discussion. In conclusion, an attempt is made to characterise the long- term interplay of demonstration and dialogue in Swedish nuclear waste management

  2. Safety and exportation of nuclear power stations

    International Nuclear Information System (INIS)

    Coudray, M.; Perrais, J.P.

    1976-01-01

    Safety problems arising from exportation are especially handled through the French exportation of PWR stations. Regulations differ widely from one country to another. However, very large use of American regulations is made and frequently there is a tendency to harden such or such clause in the quotation. Industry must be ready to give satisfaction to such demands of customers. Sometimes also, it is a mere duplication of French stations which is above all looked for. In that case, it is the problem of using French regulations abroad which arises. Desirable changes in examination proceedings are analyzed together with a French regulation effort aiming to make easier the promotion of their use abroad. Finally, safety may be a factor of success for exportation attempts. It is shown how useless some outbiddings may be, but also how, on the contrary, speeding up of research and development effort towards specific safety problems in case of exportation, is to be promoted [fr

  3. Application of U.S. export controls to DOE technical exchanges: New guidelines on export control and nonproliferation

    International Nuclear Information System (INIS)

    Lisann, E.G.; Hollander, Z.; Rudolph, R.R.

    1995-01-01

    As the Department of Energy's nuclear weapon's complex shrinks, concern regarding the proliferation of nuclear weapons technology through the release of export-controlled equipment, materials and information has come to the fore. In November, 1994 Under Secretary Charles Curtis issued new guidelines on export control and nonproliferation. The new policies and procedures are designed to help Department of Energy Headquarters Offices, Operations Offices, Area Offices, laboratories and contractors implement a consistent and technologically sound policy regarding DOE transfers of unclassified equipment, materials and information that could adversely affect US nuclear nonproliferation objectives or national security. The DOE Export Control Division has developed a multi-faceted program of guidelines and training materials to sensitize DOE and DOE-contractors to their responsibilities and to teach them how to evaluate the proliferation risks of their activities

  4. Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

    Science.gov (United States)

    Mang, Géraldine M; La Spada, Francesco; Emmenegger, Yann; Chappuis, Sylvie; Ripperger, Jürgen A; Albrecht, Urs; Franken, Paul

    2016-03-01

    The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. © 2016 Associated Professional Sleep Societies, LLC.

  5. The nuclear suicide. Rev. ed.

    International Nuclear Information System (INIS)

    Gruhl, H.

    1988-01-01

    The author, one of the most consistent opponents of nuclear power, strikes a balance after the Chernobyl catastrophe. He relentlessly analyses the 'German nuclear situation', developments to be expected from risks and catastrophic events. He exposes statements offered by the owners of power plants and by politicians as attempts to play risks down, and hopes to achieve a turnabout yet. The conjunction of technical and physical arguments with a fundamental criticism of the ideology of economic growth is what distinguishes this book from other publications critical of nuclear energy. But the author does not content himself with criticism, he goes on to point out realistic measures for opting out of nuclear energy. (orig./HSCH) With 10 figs. and maps [de

  6. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.

    Science.gov (United States)

    Bedard, James E J; Purnell, Jennifer D; Ware, Stephanie M

    2007-01-15

    Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

  7. Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

    Directory of Open Access Journals (Sweden)

    Brown M Scott

    2010-12-01

    Full Text Available Abstract Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1 mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1, another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield

  8. Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα

    Science.gov (United States)

    2010-01-01

    Background Alternative processing of α-thyroid hormone receptor (TRα, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. Results The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Conclusions Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield additional insight into the

  9. Strategic plan for the development of core technologies for the Korean advanced nuclear power reactor for export

    International Nuclear Information System (INIS)

    Moon, Joo Hyun; Cho, Young Ho

    2010-01-01

    With the soaring oil price and worsening global warming, nuclear power has attracted considerable attention on a global scale and a new large market of nuclear power plants (NPPs) is expected. The Korean government aims to export up to 10 NPPs by 2012, based on the successful export of 2 NPPs to the UAE in 2009. It is also going to develop a follow-up model of the Advanced Power Reactor (APR) 1400, and join the world's NPP market under the banner of Korea's original reactor type. For this, it promulgated the strategic plan, NuTech 2012, a technology development plan intended for the early acquisition of core technologies for the Korean advanced NPP design and domestic production of the main components in NPP. This paper introduces the strategic plan of NuTech 2012. (orig.)

  10. The role of the USNRC in power reactor exports. Legal and procedural aspects

    International Nuclear Information System (INIS)

    Shapar, H.K.; Stoiber, C.R.

    1978-01-01

    I. Background on the role of NRC in nuclear export activities. The United States Nuclear Regulatory Commission, created in January 1975 to assume the licensing and regulatory responsibilities of the former Atomic Energy Commission, has final licensing authority over US nuclear reactor exports. Independent of direct Presidential control, the Commission gives great weight to Executive Branch views on national security and foreign policy issues. II. The nuclear export review process. Procedures for NRC review of nuclear export licence applications include referral to the Executive Branch for a co-ordinated expression of agency views; analysis of the record by the NRC staff; and final Commission licensing decision based on consideration of safeguards, agreements and understandings to assure that US exports will be used only for their intended peaceful purposes. III. NRC's proposed export/import licensing regulations. NRC has recently proposed to consolidate and simplify all of its export and import licensing provisions into a new Part 110 for the convenience of the public - both US and foreign. IV. Public participation in nuclear reactor export licensing. In the past two years, after formal requests by domestic and foreign interest groups, the NRC has developed procedures for direct public participation in its export licensing proceedings. V. Statutory licensing requirements. During the past two years, the NRC has refined and particularized the extremely general 'common defence and security' standard for export licences set forth in the 1954 Atomic Energy Act. Eight questions routinely posed to the Executive Branch in reviewing licence applications has given content to Commission export decisions. Recently enacted non-proliferation legislation gives congressional recognition to even more specific, mandatory nuclear export licensing criteria

  11. EXPORT STRUCTURE AT THE EXTENSIVE AND INTENSIVEMARGINS: THE CASE OF EMERGING ECONOMIES

    Directory of Open Access Journals (Sweden)

    Gulcin Elif Yucel

    2012-07-01

    Full Text Available There is a consensus that increased exports have some benefits by enablingcountries to generate more revenue. But rather than exporting more, how acountry achieves high export performance is a more important question. Recentempirical literature highlights that intensive and extensive margins have differentcontributions to the export growth. Thus, export structure across the countries andproducts differs according to the effects of these margins. Developed countrieshave lost market share in goods exports to emerging economies, especially China.In other words, the reason of this loss of market share by most advancedeconomies is the increase in exports from emerging economies. In this study, wewill focus on the export structure of Turkey-as well as Brazil, China, India,Mexico and Russia (BCIMRT as benchmark countries-by providing a detailedanalysis of which areas of goods contribute to the intensive and/or extensivemargin growth and which margin dominates. In this study, ISIC Rev.3 4-digitlevel trade data is used which is available at the United Nations Commodity TradeStatistics (COMTRADE database for 2000-2010 period. By using descriptivestatistics on BCIMRT’s exports to the world, we decompose trade into itsextensive and intensive margins and try to answer whether export has increasedmost through new partnerships or through expanding existing trade flows in theseselected emerging economies.

  12. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment or technology

    International Nuclear Information System (INIS)

    1988-11-01

    The document reproduces the text of a Note Verbale dated 20 October 1988 received by the IAEA Director General from the Permanent Mission of Spain relating to the export of nuclear material, equipment or technology

  13. Export and import. Conformity with regulations

    International Nuclear Information System (INIS)

    Shapar, M.

    1976-01-01

    Since the division of the former US Atomic Energy Commission's tasks, the regulation and control of import and export of nuclear materials and equipment has become the responsability of the Nuclear Regulatory Commission (NRC). The import and export of nuclear fuels, equipment and reactors are therefore subject to prior licensing by the Commission. This requirement aims to guarantee that such activities will not create serious hazards for defense and national safety, and that the exported products will not be diverted from their peaceful uses. The relevant applicable legal provisions are based on the Atomic Energy Act of 1954 and on the detailed regulations issued by the Commission. Under the pressure of public opinion, there is a current tendency to restrict these activities because of the hazards they present, in particular during transport, until the Commission has completed all the necessary studies. (NEA) [fr

  14. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    International Nuclear Information System (INIS)

    Jo, Hye-Ryeong; Kim, Yong-Seok; Son, Hyeon

    2016-01-01

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  15. Erythropoietin and carbamylated erythropoietin promote histone deacetylase 5 phosphorylation and nuclear export in rat hippocampal neurons

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Hye-Ryeong [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Kim, Yong-Seok [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of); Son, Hyeon, E-mail: hyeonson@hanyang.ac.kr [Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering (Korea, Republic of); Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791 (Korea, Republic of)

    2016-01-29

    Erythropoietin (EPO) produces neurotrophic effects in animal model of neurodegeneration. However, clinical use of EPO is limited due to thrombotic risk. Carbamylated EPO (cEPO), devoid of thrombotic risk, has been proposed as a novel neuroprotective and neurotrophic agent although the molecular mechanisms of cEPO remain incomplete. Here, we show a previously unidentified role of histone deacetylase 5 (HDAC5) in the actions of EPO and cEPO. EPO and cEPO regulate the HDAC5 phosphorylation at two critical sites, Ser259 and Ser498 through a protein kinase D (PKD) dependent pathway. In addition, EPO and cEPO rapidly stimulates nuclear export of HDAC5 in rat hippocampal neurons which expressing HDAC5-GFP. Consequently, EPO and cEPO enhanced the myocyte enhancer factor-2 (MEF2) target gene expression. Taken together, our results reveal that EPO and cEPO mediate MEF2 target gene expression via the regulation of HDAC5 phosphorylation at Ser259/498, and suggest that HDAC5 could be a potential mechanism contributing to the therapeutic actions of EPO and cEPO.

  16. Efficient nuclear export of p65-IkappaBalpha complexes requires 14-3-3 proteins.

    Science.gov (United States)

    Aguilera, Cristina; Fernández-Majada, Vanessa; Inglés-Esteve, Julia; Rodilla, Verónica; Bigas, Anna; Espinosa, Lluís

    2006-09-01

    IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.

  17. Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells.

    Science.gov (United States)

    Hodroj, Dana; Serhal, Kamar; Maiorano, Domenico

    2017-09-03

    The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation. In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore. Here we review recent findings related to an additional Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated during collision between transcription and replication, and upon DNA damage. Activation of a DNA damage response pathway dependent upon the ATR kinase, a major regulator of replication fork progression, stimulates translocation of the Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA double strand breaks only in proliferating cells. Overall these observations put forward Ddx19 as an important novel mediator of the crosstalk between transcription and replication.

  18. Communication from the Permanent Mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for transfers of nuclear-related dual-use equipment, materials, software and related technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-12-10

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of the Russian Federation providing information on the export policies and practices of the Government of the Russian Federation with respect to the export of nuclear-related dual-use equipment, materials, software and related technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment to the Note Verbale was issued previously as INFCIRC/2541Rev. 4/Part 2.

  19. Communication from the Permanent Mission of the Russian Federation to the International Atomic Energy Agency regarding guidelines for transfers of nuclear-related dual-use equipment, materials, software and related technology

    International Nuclear Information System (INIS)

    2001-01-01

    The Director General of the International Atomic Energy Agency has received a Note Verbale from the Permanent Mission of the Russian Federation providing information on the export policies and practices of the Government of the Russian Federation with respect to the export of nuclear-related dual-use equipment, materials, software and related technology. In the light of the wish expressed at the end of the Note Verbale, the text of the Note Verbale is attached. The attachment to the Note Verbale was issued previously as INFCIRC/2541Rev. 4/Part 2

  20. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

    Science.gov (United States)

    Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

    2014-01-01

    Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

  1. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment or technology

    International Nuclear Information System (INIS)

    1990-08-01

    The document reproduces the text of the Note Verbale dated 1 August 1990 received by the Director General of the IAEA from the Permanent Mission of Romania and relating to the export of nuclear material, equipment and technology

  2. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-01-01

    The document reproduces the text of the Note Verbale dated 18 December 1991 received by the Director General of the IAEA from the Permanent Mission of Austria and relating to the export of nuclear material, equipment and technology

  3. Communication from the Permanent Missions of Brazil and Romania to the International Atomic Energy Agency Regarding Guidelines for the Transfers of Nuclear-Related Dual-Use Equipment, Materials, Software and Related Technology

    International Nuclear Information System (INIS)

    2003-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbale from the Permanent Missions of Brazil and Romania, dated 28 February 2003, providing information on the export policies and practices of the Governments of Brazil and Romania with respect to the export of nuclear-related dual-use equipment, materials, software and related technology. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbale is attached. The attachment referenced in the Note Verbale was issued previously as INFCIRC/254/Rev.5/Part 2

  4. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    Fang Jianhua; Kubota, Satoshi; Yang Bin; Zhou Naiming; Zhang Hui; Godbout, Roseline; Pomerantz, Roger J.

    2004-01-01

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  5. [Polyadenylated RNA and mRNA export factors in extrachromosomal nuclear domains of vitellogenic oocytes of the insect Tenebrio molitor].

    Science.gov (United States)

    Bogoliubov, D S; Kiselev, A M; Shabel'nikov, S V; Parfenov, V N

    2012-01-01

    The nucleus ofvitellogenic oocytes of the yellow mealworm, Tenebrio molitor, contains a karyosphere that consists of the condensed chromatin embedded in an extrachromosomal fibrogranular material. Numerous nuclear bodies located freely in the nucleoplasm are also observed. Amongst these bodies, counterparts of nuclear speckles (= interchromatin granule clusters, IGCs) can be identified by the presence of the marker protein SC35. Microinjections of fluorescently tagged methyloligoribonucleotide probes 2'-O-Me(U)22, complementary to poly(A) tails of RNAs, revealed poly(A)+ RNA in the vast majority of IGCs. We found that all T. molitor oocyte IGCs contain heterogeneous ribonucleoprotein (hnRNP) core protein Al that localizes to IGCs in an RNA-dependent manner. The extrachromosomal material of the karyosphere and a part of nucleoplasmic IGCs also contain the adapter protein Aly that is known to provide a link between pre-mRNA splicing and mRNA export. The essential mRNA export factor/receptor NXF1 was observed to colocalize with Aly. In nucleoplasmic IGCs, NXF1 was found to localize in an RNA-dependent manner whereas it is RNA-independently located in the extrachromosomal material of the karyosphere. We believe our data suggest on a role of the nucleoplasmic IGCs in mRNA biogenesis and retention in a road to nuclear export.

  6. The implications of uranium export

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    It is argued that Australia should not enter the business of uranium mining enrichment and export because of the hazards of nuclear power and because there are practical alternatives to the development of nuclear power. (R.L.)

  7. Export and Innovation in Sub-Saharan Africa

    NARCIS (Netherlands)

    Barasa, L.; Kinyanjui, B.; Knoben, Joris; Kimuyu, P.; Vermeulen, P.A.M.

    2016-01-01

    Our study seeks to examine the bi-directional relationship between innovation and exporting in four countries in Sub-Saharan Africa. We hypothesize that there is a positive relationship between innovation and subsequent exporting, and that this relationship is mediated by market creation. We also

  8. Integration of mRNP formation and export.

    Science.gov (United States)

    Björk, Petra; Wieslander, Lars

    2017-08-01

    Expression of protein-coding genes in eukaryotes relies on the coordinated action of many sophisticated molecular machineries. Transcription produces precursor mRNAs (pre-mRNAs) and the active gene provides an environment in which the pre-mRNAs are processed, folded, and assembled into RNA-protein (RNP) complexes. The dynamic pre-mRNPs incorporate the growing transcript, proteins, and the processing machineries, as well as the specific protein marks left after processing that are essential for export and the cytoplasmic fate of the mRNPs. After release from the gene, the mRNPs move by diffusion within the interchromatin compartment, making up pools of mRNPs. Here, splicing and polyadenylation can be completed and the mRNPs recruit the major export receptor NXF1. Export competent mRNPs interact with the nuclear pore complex, leading to export, concomitant with compositional and conformational changes of the mRNPs. We summarize the integrated nuclear processes involved in the formation and export of mRNPs.

  9. Nuclear Trafficking of the Rabies Virus Interferon Antagonist P-Protein Is Regulated by an Importin-Binding Nuclear Localization Sequence in the C-Terminal Domain.

    Directory of Open Access Journals (Sweden)

    Caitlin L Rowe

    Full Text Available Rabies virus P-protein is expressed as five isoforms (P1-P5 which undergo nucleocytoplasmic trafficking important to roles in immune evasion. Although nuclear import of P3 is known to be mediated by an importin (IMP-recognised nuclear localization sequence in the N-terminal region (N-NLS, the mechanisms underlying nuclear import of other P isoforms in which the N-NLS is inactive or has been deleted have remained unresolved. Based on the previous observation that mutation of basic residues K214/R260 of the P-protein C-terminal domain (P-CTD can result in nuclear exclusion of P3, we used live cell imaging, protein interaction analysis and in vitro nuclear transport assays to examine in detail the nuclear trafficking properties of this domain. We find that the effect of mutation of K214/R260 on P3 is largely dependent on nuclear export, suggesting that nuclear exclusion of mutated P3 involves the P-CTD-localized nuclear export sequence (C-NES. However, assays using cells in which nuclear export is pharmacologically inhibited indicate that these mutations significantly inhibit P3 nuclear accumulation and, importantly, prevent nuclear accumulation of P1, suggestive of effects on NLS-mediated import activity in these isoforms. Consistent with this, molecular binding and transport assays indicate that the P-CTD mediates IMPα2/IMPβ1-dependent nuclear import by conferring direct binding to the IMPα2/IMPβ1 heterodimer, as well as to a truncated form of IMPα2 lacking the IMPβ-binding autoinhibitory domain (ΔIBB-IMPα2, and IMPβ1 alone. These properties are all dependent on K214 and R260. This provides the first evidence that P-CTD contains a genuine IMP-binding NLS, and establishes the mechanism by which P-protein isoforms other than P3 can be imported to the nucleus. These data underpin a refined model for P-protein trafficking that involves the concerted action of multiple NESs and IMP-binding NLSs, and highlight the intricate regulation of P

  10. A Study on the Export Control System at KAERI

    International Nuclear Information System (INIS)

    Kim, I. C.; Lee, B. D.; Kim, H. J.; Kim, H. S.; Jung, J. A.

    2015-01-01

    The current non-proliferation regime requires strengthening the export control from Korea to foreign countries. This means that the ministries related to export control deeply emphasize the prohibition of the illegal proliferation in the domestic society as well as international society. The principle of export control for non-proliferation of WMD is to control the transfer of the strategic items/technology to the countries which intend to develop the WMD in accordance with the multilateral agreements of the Nuclear Supply Group (NSG), Wassenaar Agreement (WA), Austrian Group (AG) and Missile Technology Control Regime (MTCR). Among them, export controls at KAERI are deeply related to the guidelines of the NSG, an international nuclear export control regime. Since the new concept of an export system was launched in Jan. 2014, KAERI needs to consider new approaches to meet the requirement of the revised domestic law and regulation. To cope with this environmental change, this paper suggests new approaches to effectively conduct the export control at KAERI

  11. A Study on the cooperation policy in multilateral nuclear control regimes and the advancing of national export control system

    International Nuclear Information System (INIS)

    Lee, Byung Wook; Oh, K. B.; Yang, M. H.; Lee, H. M.; Lee, K. S.; Ko, H. S.; Ryu, J. S.; Kim, J. S.

    2004-08-01

    This study carried out the analysis of trends of the multilateral nuclear control in four aspects. First, this study analyzes the past trends of the international nuclear non-proliferation regime, which includes the NPT, the IAEA safeguards system, the international nuclear export control regime and the physical protection of nuclear materials. Second, this study establishes the multilateral cooperation strategies for the effective cooperation in the process of strengthening the nuclear control regimes. Third, this study reviews the major agenda of nuclear control regimes and establishes national positions on each agenda. Fourth, this study also analyzes outstanding issues in nuclear control regimes and derives some factors to reflect national nuclear control system

  12. Design and construction of nuclear power plants for export. Adaptation of a reference plant from a series in a national power generating program

    International Nuclear Information System (INIS)

    Marcaillou, J.; Haond, H.

    1977-01-01

    The recent evolution of primary energy supplies places those countries having a nuclear industry in an exporting role. Exporting countries have generally developed a limited number of national reactor types and attempt to extend their manufacture with as few changes as possible. The E.D.F. in France is implementing an important PWR 900 MW program based on FRAMATOME nuclear reactors, initially conceived by WESTINGHOUSE. Such standardization poses certain problems for the importing countries. These problems and ways in which they can be solved are discussed [fr

  13. Nuclear exportin receptor CAS regulates the NPI-1-mediated nuclear import of HIV-1 Vpr.

    Directory of Open Access Journals (Sweden)

    Eri Takeda

    Full Text Available Vpr, an accessory protein of human immunodeficiency virus type 1, is a multifunctional protein that plays an important role in viral replication. We have previously shown that the region between residues 17 and 74 of Vpr (Vpr(N17C74 contained a bona fide nuclear localization signal and it is targeted Vpr(N17C74 to the nuclear envelope and then imported into the nucleus by importin α (Impα alone. The interaction between Impα and Vpr is important not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages; however, it was unclear whether full-length Vpr enters the nucleus in a manner similar to Vpr(N17C74. This study investigated the nuclear import of full-length Vpr using the three typical Impα isoforms, Rch1, Qip1 and NPI-1, and revealed that full-length Vpr is selectively imported by NPI-1, but not Rch1 and Qip1, after it makes contact with the perinuclear region in digitonin-permeabilized cells. A binding assay using the three Impα isoforms showed that Vpr bound preferentially to the ninth armadillo repeat (ARM region (which is also essential for the binding of CAS, the export receptor for Impα in all three isoforms. Comparison of biochemical binding affinities between Vpr and the Impα isoforms using surface plasmon resonance analysis demonstrated almost identical values for the binding of Vpr to the full-length isoforms and to their C-terminal domains. By contrast, the data showed that, in the presence of CAS, Vpr was released from the Vpr/NPI-1 complex but was not released from Rch1 or Qip1. Finally, the NPI-1-mediated nuclear import of Vpr was greatly reduced in semi-intact CAS knocked-down cells and was recovered by the addition of exogenous CAS. This report is the first to show the requirement for and the regulation of CAS in the functioning of the Vpr-Impα complex.

  14. Regulation of RNA-binding proteins affinity to export receptors enables the nuclear basket proteins to distinguish and retain aberrant mRNAs.

    Science.gov (United States)

    Soheilypour, M; Mofrad, M R K

    2016-11-02

    Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs. Our results show that the affinity between Tpr and RBPs is optimized to maximize the retention of aberrant mRNAs. In addition, we demonstrate how the length of mRNA affects the QC process. Since longer mRNAs spend more time in the nuclear basket to form a compact conformation and initiate their export, nuclear basket proteins could more easily capture and retain them inside the nucleus.

  15. Export Control in the AREVA Group

    International Nuclear Information System (INIS)

    Zero, S.

    2013-01-01

    After the Second World War the nuclear technology was mostly considered inappropriate for the export. It remains strictly regulated today, but the development of the civil applications urged states to facilitate the peaceful uses while establishing a strict control in the domains of the internal security and the nuclear proliferation. AREVA decided to set up an Export Control program applied to all the products and in all the countries where the group operates. AREVA can export products or make transfer of technology considered as sensitive for the non-proliferation and the risks linked to the terrorism. This sensitiveness results from the nature of the products or from the country of destination and in certain cases both of them. AREVA has set up an Export Control program and an interactive e-learning training within the Group to make exports of sensitive products, raw materials and technologies more secure. The subject is rather complex, the regulations are constantly evolving, and becoming familiar with them is necessarily a gradual process, but it must be made in-depth, hence the idea of regular training sessions. The implementation of the Export Control in the AREVA Group declines in four fundamental stages: -) Policy and procedure; -) Appointment of Export Control Officers (ECO); -) Training; and -) Audit and Self Assessment. The training program is composed by the following elements: Ethics (Value Charter) of the Group, Non-proliferation, international regulations and more particularly those that are applicable in Europe (Germany and France) and in the United States. Particular attention is devoted to the Export Control practice in China, Japan and India. (A.C.)

  16. Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cleasby, Mark E. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Millard, Susan; Leong, Gary M. [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia); Cooney, Gregory J. [Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent' s Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010 (Australia); Muscat, George E.O., E-mail: g.muscat@imb.uq.edu.au [The University of Queensland, Institute for Molecular Bioscience, St. Lucia, Qld 4072 (Australia)

    2009-10-30

    The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

  17. Communication from the Permanent Mission of Australia to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of Australia providing information on the export policies and practices of the Government of Australia with respect to the export of nuclear material, equipment and technology

  18. Communication from the Permanent Mission of Finland to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of Finland providing information on the export policies and practices of the Government of Finland with respect to the export of nuclear material, equipment and technology

  19. Communications received from members regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1993-05-01

    The document reproduces the letter dated 11 February 1993 from the Resident Representative of the Russian Federation to the Agency concerning the export of nuclear material and of certain categories of equipment and other material

  20. Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function

    DEFF Research Database (Denmark)

    Bugge, Anne Skovsø; Feng, Dan; Everett, Logan J

    2012-01-01

    of binding sites across the genome, enriched near metabolic genes. Depletion of both Rev-erbs in liver synergistically derepresses several metabolic genes as well as genes that control the positive limb of the molecular clock. Moreover, deficiency of both Rev-erbs causes marked hepatic steatosis, in contrast......-autonomous clock as well as hepatic lipid metabolism. Mouse embryonic fibroblasts were rendered arrhythmic by depletion of both Rev-erbs. In mouse livers, Rev-erbβ mRNA and protein levels oscillate with a diurnal pattern similar to that of Rev-erbα, and both Rev-erbs are recruited to a remarkably similar set...

  1. Uranium enrichment export control guide: Gaseous diffusion

    Energy Technology Data Exchange (ETDEWEB)

    1989-09-01

    This document was prepared to serve as a guide for export control officials in their interpretation, understanding, and implementation of export laws that relate to the Zangger International Trigger List for gaseous diffusion uranium enrichment process components, equipment, and materials. Particular emphasis is focused on items that are especially designed or prepared since export controls are required for these by States that are party to the International Nuclear Nonproliferation Treaty.

  2. REV-ERBalpha participates in circadian SREBP signaling and bile acid homeostasis.

    Directory of Open Access Journals (Sweden)

    Gwendal Le Martelot

    2009-09-01

    Full Text Available In mammals, many aspects of behavior and physiology, and in particular cellular metabolism, are coordinated by the circadian timing system. Molecular clocks are thought to rely on negative feedback loops in clock gene expression that engender oscillations in the accumulation of transcriptional regulatory proteins, such as the orphan receptor REV-ERBalpha. Circadian transcription factors then drive daily rhythms in the expression of clock-controlled output genes, for example genes encoding enzymes and regulators of cellular metabolism. To gain insight into clock output functions of REV-ERBalpha, we carried out genome-wide transcriptome profiling experiments with liver RNA from wild-type mice, Rev-erbalpha knock-out mice, or REV-ERBalpha overexpressing mice. On the basis of these genetic loss- and gain-of-function experiments, we concluded that REV-ERBalpha participates in the circadian modulation of sterol regulatory element-binding protein (SREBP activity, and thereby in the daily expression of SREBP target genes involved in cholesterol and lipid metabolism. This control is exerted via the cyclic transcription of Insig2, encoding a trans-membrane protein that sequesters SREBP proteins to the endoplasmic reticulum membranes and thereby interferes with the proteolytic activation of SREBPs in Golgi membranes. REV-ERBalpha also participates in the cyclic expression of cholesterol-7alpha-hydroxylase (CYP7A1, the rate-limiting enzyme in converting cholesterol to bile acids. Our findings suggest that this control acts via the stimulation of LXR nuclear receptors by cyclically produced oxysterols. In conclusion, our study suggests that rhythmic cholesterol and bile acid metabolism is not just driven by alternating feeding-fasting cycles, but also by REV-ERBalpha, a component of the circadian clockwork circuitry.

  3. Communication Received from Argentina regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1993-10-01

    The Director General has received letters dated 27 May 1993 from the Resident Representatives of Portugal and Spain to the Agency concerning the export of nuclear material and of certain categories of equipment and other material [ru

  4. Communications received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    1993-10-01

    The Director General has received letters dated 27 May 1993 from the Resident Representatives of Portugal and Spain to the Agency concerning the export of nuclear material and of certain categories of equipment and other material [es

  5. Amendment of the Ordinance on the export and transit of goods

    International Nuclear Information System (INIS)

    1989-12-01

    This Ordinance amends the Annex of the Ordinance of 7 March 1983 on the export and transit of dangerous goods which lists the nuclear items, ie nuclear reactors, equipment and materials subject to export restrictions. The Ordinance came into force on 1 January 1990 (NEA) [fr

  6. Competitiveness, export control and export promotion of dual-use goods. European and German balancing exercises; Wettbewerbsfaehigkeit, Exportkontrolle und Exportfoerderung von Dual-Use-Guetern. Europaeische und deutsche Spagatuebungen

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2014-08-15

    The EU Commission Communication of 24 April 2014 to the Council and the European Parliament ''The review of export control policy: Ensuring Security and Competitiveness in a changing world'' as well as the increasingly number of inquiries and applications to the German Federal Government (e.g. the rejection of Hermes guarantees and state funding of nuclear export and termination of bilateral cooperation in the field of nuclear technologies) once again reason to discuss the current tension between the principle of free movement of goods, competitiveness and export promotion on the one hand and the export control on the other.

  7. Communication received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear transfers

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex

  8. Communication received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear transfers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex.

  9. Communication from the Permanent Mission of Israel to the International Atomic Energy Agency regarding nuclear export controls

    International Nuclear Information System (INIS)

    2004-01-01

    The Director General of the International Atomic Energy Agency has received a letter dated 13 July 2004 from the Permanent Mission of Israel providing information on Israel's nuclear export policies and practices. As requested by the Permanent Mission, the letter and document attached to it are reproduced herein for the information of Member States

  10. France's Efforts to Promote NPP Exports and the Implications on the Role of Nuclear Regulatory Body

    International Nuclear Information System (INIS)

    Oh, Chae-Woon; Chang, Hyun-Sop; Choi, Young-Sung

    2008-01-01

    The global society facing sky-rocketing oil prices, global warming effects, and increased demand for electricity recognizes the comparative advantages of nuclear energy in terms of environmental impact and economic efficiency over the other energy sources of current use. Approximately 300 nuclear power plants (NPPs) expect to be constructed until 2030 worldwide. Accordingly, the global market size of nuclear power industry becomes scaled up to the extent of U$75 billion on the assumption that the construction of one reactor costs around U$2.5 billion. The nations in possession of advanced nuclear technology such as the U.S., France, Japan, etc not only recognized an abounding profitability in nuclear industry and anticipated nuclear renaissance but also prepared long before whatever necessary to expand their nuclear programs beyond their domestic boundaries. Amongst those nations, it seems to be France that has unfolded a remarkable array of government-led activities to export Evolutionary Pressurized Reactors (EPRs) under the cooperation of President, relevant government administration, utilities even a regulatory body. The omni-directional activities of France and its implications are presented in this paper

  11. Management of a 600 MW CANDU project to facilitate electricity export

    International Nuclear Information System (INIS)

    Gunter, G.E.

    1983-06-01

    The export of electricity from 600-MW CANDU nuclear power plants built in Canada remains feasible providing certain requirements continue to be met. The principal objective in developing nuclear power resources for export is that they must produce economically attractive electricity. A review of the experience of construction and operation of Point Lepreau Unit 1 suggests an inherent ability to reduce construction costs and shorten construction schedules so as to make electrical power output from these stations even more attractive to export customers

  12. Nuclear Trafficking of Retroviral RNAs and Gag Proteins during Late Steps of Replication

    Directory of Open Access Journals (Sweden)

    Matthew S. Stake

    2013-11-01

    Full Text Available Retroviruses exploit nuclear trafficking machinery at several distinct stages in their replication cycles. In this review, we will focus primarily on nucleocytoplasmic trafficking events that occur after the completion of reverse transcription and proviral integration. First, we will discuss nuclear export of unspliced viral RNA transcripts, which serves two essential roles: as the mRNA template for the translation of viral structural proteins and as the genome for encapsidation into virions. These full-length viral RNAs must overcome the cell’s quality control measures to leave the nucleus by co-opting host factors or encoding viral proteins to mediate nuclear export of unspliced viral RNAs. Next, we will summarize the most recent findings on the mechanisms of Gag nuclear trafficking and discuss potential roles for nuclear localization of Gag proteins in retrovirus replication.

  13. Facts on nuclear power. 4. rev. ed.

    International Nuclear Information System (INIS)

    1987-06-01

    The information booklet summarizes physical principles and other fundamental background information relating to nuclear power. The material is subdivided into various brief chapters with tables and illustrations discussing aspects such as: Basic terms and data, energy demand and supply, economics, nuclear power plants in operation, radiation protection, reactor safety, and nuclear waste management. A brief outline of the history of nuclear power in the FRG is given, and a list of addresses and literature for further reading. (UA) [de

  14. Demonstration and Dialogue: Mediation in Swedish Nuclear Waste Management. Deliverable D10

    International Nuclear Information System (INIS)

    Elam, Mark; Sundqvist, Goeran; Lidberg, Maria; Soneryd, Linda

    2008-10-01

    This report analyses mediation and mediators in Swedish nuclear waste management. Mediation is about establishing agreement and building common knowledge. It is argued that demonstrations and dialogue are the two prominent approaches to mediation in Swedish nuclear waste management. Mediation through demonstration is about showing, displaying, and pointing out a path to safe disposal for inspection. It implies a strict division between demonstrator and audience. Mediation through dialogue on the other hand, is about collective acknowledgements of uncertainty and suspensions of judgement creating room for broader discussion. In Sweden, it is the Swedish Nuclear Fuel and Waste Management Co. (SKB) that is tasked with finding a method and a site for the final disposal of the nation's nuclear waste. Two different legislative frameworks cover this process. In accordance with the Act on Nuclear Activities, SKB is required to demonstrate the safety of its planned nuclear waste management system to the government, while in respect of the Swedish Environmental Code, they are obliged to organize consultations with the public. How SKB combines these requirements is the main question under investigation in this report in relation to materials deriving from three empirical settings: 1) SKB's safety analyses, 2) SKB's public consultation activities and 3) the 'dialogue projects', initiated by other actors than SKB broadening the public arena for discussion. In conclusion, an attempt is made to characterise the long-term interplay of demonstration and dialogue in Swedish nuclear waste management

  15. Nuclear trade between developing countries

    International Nuclear Information System (INIS)

    Stahl, K.

    1990-01-01

    The analysis of nuclear south-south cooperation is based on the evaluation of official documents (the texts of laws, of contracts for nuclear cooperation treaties, safeguard treaties, official government policy speeches etc.). These data were supplemented by numerous interviews with representatives of atomic energy authorities, foreign ministries, nuclear industries, members of parliament, representatives of the nuclear energy opposition movement and military representatives in the three states and by interviews with representatives of the IAEO and OPANAL in Mexico. The study deals with each country in turn: Chapter 2 gives an overview of the Indian nuclear energy programme and India's nuclear export activity and export policy. Chapter 3 analyzes Brazil's nuclear energy policy and Brazilian export capacities, exports and export policy in the nuclear sector. Chapter 4 looks at the development of the Argentinian nuclear energy programme and the crisis in it, at Argentina's nuclear export activities and its export policy and technology transfer policy in this field. Chapter 5 analyzes separately relations between Argentina and Brazil on nuclear cooperation, since they differ considerably from the two countries' relations with other Third World countries on this topic. The appendix documents the most important contractual agreements and government policy declarations on nuclear cooperation between the two states. (orig.) [de

  16. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-07-01

    The document reproduces the text of the notes verbales dated 15 May 1992, received by the Director General from the Resident Representatives to the Agency of Australia, Austria, Belgium, Bulgaria, Canada, Czech and Slovak Federal Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, Russia Federation, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology and the Guidelines for Transfer of Nuclear-Related Dual-Use Equipment, Material and Related Technology. An Annex to these Guidelines contains the list of Nuclear-Related Dual-Use Equipment and Materials and Related Technology

  17. International legal and political issues associated with the export/import of nuclear power plants

    International Nuclear Information System (INIS)

    Manning Muntzing, L.

    1978-01-01

    The benefits of nuclear power can be achieved by most nations only through international commerce that has been shaped by political considerations and implemented through legal instruments. The end product is a structure of legal agreements designed to implement the basic political and commercial decisions that are required for any nation to enter the nuclear power arena. The IAEA Statute, the Non-Proliferation Treaty and regional nuclear agreements have reflected the international political consensus concerning nuclear power. In recent years, however, events have occurred that in all probability will result in additional international arrangements. It is expected that the increase in terrorist activities will result in greater physical protection commitments, that concern for weapons proliferation will result in further definition of sanctions, and that such troublesome issues as double labelling of materials will be discussed by the international community. In areas such as bilateral agreements between nations, commercial arrangements and export licences, this is a period of rethinking, renegotiating, and readjusting. The result is a degree of uncertainty and lack of stability that could so jeopardize the potential for nuclear transfers that the nuclear energy option may not vest. While there always will be questions and issues, it is essential to settle some of the key problems without delay so that nuclear benefits can be realized. (author)

  18. Analysis of Developed Country's Export Contract and Contract Risk and Development of Sample Contract and Guide

    International Nuclear Information System (INIS)

    Lee, D. S.; Oh, K. B.; Chung, W. S.; Lee, K. S.; Yun, S. W.; Lee, J. H.; Lee, B. W.; Kim, H. J.; Yang, M. H.

    2008-10-01

    This paper aimed at developing legal support for the non nuclear power plant industry's export. This study aids establishing government policy and promoting export of non nuclear power plant industry. This paper treated analysis of contractual risk and caution before entering into contract. To promote continuing export result, governmental and legal aids and guide will be required continuously. This study showed risks related with export contract and explained export control acts and procedures

  19. An analysis on the export license criteria for NSG control items in the US and Japan

    International Nuclear Information System (INIS)

    Choi, Young Rok

    1995-06-01

    Korea has taken steps to join the Nuclear Suppliers Group (NSG) which is a major part of the international nuclear export control regime. In this connection, it is an urgent task to build a new Korean nuclear export control system that includes NSG guidelines and control items. In addition, it is necessary to review the developed supplier countries' experience in the field of export control. The main purpose of this study is to analyze how the US and Japan have controlled the items listed in NSG part 1 and 2 guidelines. To this end, various relevant regulations of the US and Japan were studied. Among those regulations, the US Export Administration Regulation, US 10 CFR 110 and 810, and the Japan's Export Administration Order are included. Through the review process, this study identified NSG items which are controlled in the export control systems of the US and Japan. Furthermore, this study summarized and compared the export license criteria that must be satisfied before exporting each NSG item in the two countries. The export license criteria consist of permitted destinations, document requirements, and types of license. The results of this study are expected to contribute to establishing an appropriate Korean nuclear export control system and could be used as references to the practical export licensing policies of the US and Japan. 6 tabs., 13 refs., (Author) .new

  20. An analysis on the export license criteria for NSG control items in the US and Japan

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Rok [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-06-01

    Korea has taken steps to join the Nuclear Suppliers Group (NSG) which is a major part of the international nuclear export control regime. In this connection, it is an urgent task to build a new Korean nuclear export control system that includes NSG guidelines and control items. In addition, it is necessary to review the developed supplier countries` experience in the field of export control. The main purpose of this study is to analyze how the US and Japan have controlled the items listed in NSG part 1 and 2 guidelines. To this end, various relevant regulations of the US and Japan were studied. Among those regulations, the US Export Administration Regulation, US 10 CFR 110 and 810, and the Japan`s Export Administration Order are included. Through the review process, this study identified NSG items which are controlled in the export control systems of the US and Japan. Furthermore, this study summarized and compared the export license criteria that must be satisfied before exporting each NSG item in the two countries. The export license criteria consist of permitted destinations, document requirements, and types of license. The results of this study are expected to contribute to establishing an appropriate Korean nuclear export control system and could be used as references to the practical export licensing policies of the US and Japan. 6 tabs., 13 refs., (Author) .new.

  1. Communication received from the Permanent Mission of New Zealand regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1995-01-01

    The Director General has received a note verbale dated 22 December 1994 from the Permanent Mission of New Zealand to the International Atomic Energy Agency providing information on the nuclear export policies and practices of the Government of New Zealand

  2. Exports and experts:proliferation risks from the new Commonwealth

    International Nuclear Information System (INIS)

    Potter, W.C.

    1992-01-01

    Ironically, given the Cold War history and Western stereotypes about Soviet misbehavior, the long-standing experience of US-Soviet cooperation on nonproliferation may have made US policy-makers less attentive to, and less concerned about, signs of change in Soviet nuclear export policy. The breakup of the Soviet Union and the nuclear inheritance of its successor states belatedly focused Western attention on the proliferation risks posed by the disintegration of central authority. Most concern to date, however, has continued to emphasize the problems of nuclear command and control. But the nonproliferation threats associated with the unregulated export of sensitive nuclear material, technology, and equipment may be equally great, and present problems that are already real. At the same time, the new nation-building process in the Soviet successor states presents opportunities for expanding the NPT and international safeguards, containing the nuclear brain drain, promoting the cleanup of hazardous nuclear waste, enhancing international capabilities for monitoring proliferation, and building new communities of nonproliferation specialists. A rare occasion now exists for Western policy-makers to have a direct impact on the long-term nuclear export and non-proliferation behavior of the successor states to the Soviet Union. The speed and seriousness with which the West undertakes this task will largely determine how much ground, if any, will be lost from its decades-long effort to stop the proliferation of nuclear weapons

  3. Control of HIV-1 env RNA splicing and transport: investigating the role of hnRNP A1 in exon splicing silencer (ESS3a) function

    International Nuclear Information System (INIS)

    Asai, Kengo; Platt, Craig; Cochrane, Alan

    2003-01-01

    The control of HIV-1 viral RNA splicing and transport plays an important role in the successful replication of the virus. Previous studies have identified both an exon splicing enhancer (ESE) and a bipartite exon splicing silencer (ESS3a and ESS3b) within the terminal exon of HIV-1 that are involved in modulating both splicing and Rev-mediated export of viral RNA. To define the mechanism of ESS3a function, experiments were carried out to better define the cis and trans components required for ESS3a activity. Mutations throughout the 30-nt element resulted in partial loss of ESS function. Combining mutations was found to have an additive effect, suggesting the presence of multiple binding sites. Analysis of interacting factors identified hnRNP A1 as one component of the complex that modulates ESS3a activity. However, subsequent binding analyses determined that hnRNP A1 interacts with only one portion of ESS3a, suggesting the involvement of another host factor. Parallel analysis of the effect of the mutations on Rev-mediated export determined that there is not a direct correlation between the effect of the mutations on splicing and RNA transport. Consistent with this hypothesis, replacement of ESS3a with consensus hnRNP A1 binding sites was found to be insufficient to block Rev-mediated RNA export

  4. Cooperation of nuclear manpower development between Viet Nam and Korea in order to enhance establishment of infrastructure in exporting nuclear technology to Viet Nam

    International Nuclear Information System (INIS)

    Lee, E. J.; Han, K. W.; Park, J. K.; Kim, Y. T.; Nam, Y. M.; Jang, Y. H.; Yang, M. H.

    2003-08-01

    Through this project, KAERI provided OJT Programme to 3 nuclear experts of Viet Nam at the KAERI for 3 months as a cooperation of human resource development in the field of nuclear policy, nuclear safety analysis and thermo hydraulic. We could have publicity activities of S/W and H/W then achieve an advantage position of economical and technical in exporting nuclear technology to Viet Nam. Also we have provided a training course and seminar for a high-level delegation of nuclear policy decision makers, which is consisted of 5 deputy ministers and general directors of Viet Nam in Korea. Thus we could have Vietnamese who are favoring Korea. The KAERI will also prepare a data base of trained Vietnamese in Korea for the maximum utilization of them in cooperating with Viet Nam. We accomplished the cooperation of human resource development and providing program and curriculum of the nuclear education and training in Viet Nam. Furthermore, it is expected that the enhancement of nuclear technical cooperation between Viet Nam and Korea and the nuclear human resource development

  5. Cooperation of nuclear manpower development between Viet Nam and Korea in order to enhance establishment of infrastructure in exporting nuclear technology to Viet Nam

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E. J.; Han, K. W.; Park, J. K.; Kim, Y. T.; Nam, Y. M.; Jang, Y. H.; Yang, M. H

    2003-08-15

    Through this project, KAERI provided OJT Programme to 3 nuclear experts of Viet Nam at the KAERI for 3 months as a cooperation of human resource development in the field of nuclear policy, nuclear safety analysis and thermo hydraulic. We could have publicity activities of S/W and H/W then achieve an advantage position of economical and technical in exporting nuclear technology to Viet Nam. Also we have provided a training course and seminar for a high-level delegation of nuclear policy decision makers, which is consisted of 5 deputy ministers and general directors of Viet Nam in Korea. Thus we could have Vietnamese who are favoring Korea. The KAERI will also prepare a data base of trained Vietnamese in Korea for the maximum utilization of them in cooperating with Viet Nam. We accomplished the cooperation of human resource development and providing program and curriculum of the nuclear education and training in Viet Nam. Furthermore, it is expected that the enhancement of nuclear technical cooperation between Viet Nam and Korea and the nuclear human resource development.

  6. Impact of High - Performance Work Systems on Export - Oriented SMEs Performance: The Mediating Role of Human Capital Development

    Directory of Open Access Journals (Sweden)

    Zeeshan Hamid

    2017-10-01

    Full Text Available Small and medium enterprises (SMEs contribute substantially to the economic development, income generation, poverty reduction, and particularly job creation for both developed and developing economies. However, compared with large firms, SMEs face several challenges related to their performance and competitiveness. The role of human capital (HC and human resource practices (HR Practices in enhancing SMEs competitiveness and performance is vital but understudied areas. Therefore, the purpose of this study was to investigate the role of HC development between the relationship of high-performance work systems (HPWS and export-oriented SMEs performance. Quantitative strategy and cross-sectional survey method was used to collect data from 205 managerial staff through a self-administered structured questionnaire. HPWS had a significant positive impact on export-oriented SMEs performance. The findings of the study provide evidence that HC development plays a mediating role between HPWS and enterprises performance.

  7. Nuclear Energy for Desalting (Rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Urrows, Grace M.

    1967-01-01

    This booklet discusses the huge demand for fresh clean water and various ways to create it. Since 3/4 of the world is covered in salt water, many processes have been developed to desalt the salt water. Nuclear-powered desalting units are discussed extensively.

  8. The formation of nuclear export control in Azerbaijan

    International Nuclear Information System (INIS)

    Garibov, A.A.

    2003-01-01

    Full text: The controlling process of exporting and importing on Azerbaijan borders is being carried out by two state organizations. 1.Border Guard Department; 2.Azerbaijan State Customs Committee. The officers of these organizations have no enough necessary experience and knowledge dealing with the legal and illegal trafficking. There were not special educational institutions in order to train personals for both of these organizations made newly. So there's difference between the professions of the majority of the employees, that's why some of the employees follow the instructions linking to the normative documents while passing the border. When trafficking nuclear and dual-use items officially the controller and other employees should look through the list of all and know them how to behave and to make official, the characteristic parameters of the materials, and the instruction of monitoring. In order to realize all works pointed, the employees of Border Guard Department and Customs Control Check Points have to attend special courses. The employees of both organizations are frequently changed that's why studying courses are to be organized. The analysis of studying considered that will be realized shows mainly there may be two student groups. Mainly, the Institute of Radiation Problems of ANAS (Azerbaijan National Academy of Sciences) as the expert laboratory takes part in. On the borders of Azerbaijan Republic the dual-use items and equipment having the type of isotope sources being utilized in the technological process are mainly being transported. In the materials presented the results and the solution of the problems dealing with realizing the controlling expert system of nuclear materials in the existing control checkpoints due to the international standards have been given

  9. Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.

    Science.gov (United States)

    Sail, Vibhavari; Rizzo, Alessandro A; Chatterjee, Nimrat; Dash, Radha C; Ozen, Zuleyha; Walker, Graham C; Korzhnev, Dmitry M; Hadden, M Kyle

    2017-07-21

    Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate. The TLS DNA polymerase Rev1 serves as an integral scaffolding protein that mediates the assembly of the active multiprotein TLS complexes. Protein-protein interactions (PPIs) between the C-terminal domain of Rev1 (Rev1-CT) and the Rev1-interacting region (RIR) of other TLS DNA polymerases play an essential role in regulating TLS activity. To probe whether disrupting the Rev1-CT/RIR PPI is a valid approach for developing a new class of targeted anticancer agents, we designed a fluorescence polarization-based assay that was utilized in a pilot screen for small molecule inhibitors of this PPI. Two small molecule scaffolds that disrupt this interaction were identified, and secondary validation assays confirmed that compound 5 binds to Rev1-CT at the RIR interface. Finally, survival and mutagenesis assays in mouse embryonic fibroblasts and human fibrosarcoma HT1080 cells treated with cisplatin and ultraviolet light indicate that these compounds inhibit mutagenic Rev1/Polζ-dependent TLS in cells, validating the Rev1-CT/RIR PPI for future anticancer drug discovery and identifying the first small molecule inhibitors of TLS that target Rev1-CT.

  10. The Transformations of French Nuclear Export Policy (1974-1976): A Triple Double Game

    International Nuclear Information System (INIS)

    Pouponneau, Florent

    2013-01-01

    A number of problems present themselves for any scholar seeking to take into account all determinants relating to 'national' and 'international' action in the analysis of foreign policy. In the domain of the French diplomatic practices of the mid-1970's-structured around the apparent issue of nuclear exports-archival consultation and interviews reveal that the various actors involved in this policy were not necessarily playing the same national and international 'double game.' While relations between states shape what they are and do, the various effects of refraction at work at the internal level prevents one from speaking of a state taken uniformly across a space of competition

  11. Emerging nuclear suppliers in the Third World

    International Nuclear Information System (INIS)

    Stahl, K.

    1990-01-01

    The emergence of new supplier states of nuclear technology within the Third World has raised concern, if those nuclear supplier states will promote an unrestricted and uncontrolled transfer of nuclear technology to developing countries and augment the risk of nuclear weapons proliferation. The article analyses the nuclear export capacities, nuclear exports and the export policy of Argentina, Brazil and India. Argentina is considered as the most important emerging nuclear supplier state in the Third World. Nuclear exports have to be authorisized by the government in all three states and will be covered by IAEA-safeguards in the recipient country. The three states will exercise restraint in the transfer of sensitive nuclear technology. Nuclear exports of Argentina, Brazil and India so far will not augment the danger of nuclear weapons proliferation. (orig./HSCH) [de

  12. Pakistan's national legislation entitled: 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'

    International Nuclear Information System (INIS)

    2004-01-01

    The Director General has received a letter from the Permanent Mission of Pakistan, dated 4 November 2004, concerning Pakistan's national legislation entitled 'Export Control on Goods, Technologies, Material and Equipment related to Nuclear and Biological Weapons and their Delivery Systems Act, 2004'. As requested by the Permanent Mission of Pakistan, the letter and the Export Control Act of 2004, are reproduced herein for the information of the Member States

  13. The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

    International Nuclear Information System (INIS)

    Mamoor, Shahan; Onder, Zeynep; Karanam, Balasubramanyam; Kwak, Kihyuck; Bordeaux, Jennifer; Crosby, Lauren; Roden, Richard B.S.; Moroianu, Junona

    2012-01-01

    In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein—L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ( 462 LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

  14. The high risk HPV16 L2 minor capsid protein has multiple transport signals that mediate its nucleocytoplasmic traffic

    Energy Technology Data Exchange (ETDEWEB)

    Mamoor, Shahan; Onder, Zeynep [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Karanam, Balasubramanyam; Kwak, Kihyuck [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Bordeaux, Jennifer; Crosby, Lauren [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States); Roden, Richard B.S. [Department of Pathology, The Johns Hopkins University, Baltimore, MD 21231 (United States); Moroianu, Junona, E-mail: moroianu@bc.edu [Biology Department, Boston College, Chestnut Hill, MA 02467 (United States)

    2012-01-20

    In this study we examined the transport signals contributing to HPV16 L2 nucleocytoplasmic traffic using confocal microscopy analysis of enhanced green fluorescent protein-L2 (EGFP-L2) fusions expressed in HeLa cells. We confirmed that both nuclear localization signals (NLSs), the nNLS (1MRHKRSAKRTKR12) and cNLS (456RKRRKR461), previously characterized in vitro (Darshan et al., 2004), function independently in vivo. We discovered that a middle region rich in arginine residues (296SRRTGIRYSRIGNKQTLRTRS316) functions as a nuclear retention sequence (NRS), as mutagenesis of critical arginine residues within this NRS reduced the fraction of L2 in the nucleus despite the presence of both NLSs. Significantly, the infectivity of HPV16 pseudoviruses containing either RR297AA or RR297EE within the L2 NRS was strongly reduced both in HaCaT cells and in a murine challenge model. Experiments using Ratjadone A nuclear export inhibitor and mutation-localization analysis lead to the discovery of a leucine-rich nuclear export signal ({sub 462}LPYFFSDVSL) mediating 16L2 nuclear export. These data indicate that HPV16 L2 nucleocytoplasmic traffic is dependent on multiple functional transport signals.

  15. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Notes Verbales dated 1 February 2000 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Brazil, Canada, the Czech Republic, Germany, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Switzerland, Ukraine, the United Kingdom and the United States relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. The attachment to these Notes Verbales is also included

  16. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-15

    The document reproduces the text of the Notes Verbales dated 1 February 2000 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Brazil, Canada, the Czech Republic, Germany, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, the Netherlands, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Switzerland, Ukraine, the United Kingdom and the United States relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. The attachment to these Notes Verbales is also included.

  17. Communications received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1992-07-01

    The document reproduces the text of the notes verbales dated 1 June 1992, received by the Director General from the Resident Representatives to the Agency of Australia, Austria, Belgium, Bulgaria, Canada, Czech and Slovak Federal Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, japan, Luxembourg, Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment for technology. The purpose of these notes verbales is to clarify parts of the Trigger List incorporated in the Annex A to the Guidelines for Nuclear Transfer. 1 tab

  18. On The Export Control Of High Speed Imaging For Nuclear Weapons Applications

    Energy Technology Data Exchange (ETDEWEB)

    Watson, Scott Avery [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Altherr, Michael Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-09-15

    Since the Manhattan Project, the use of high-speed photography, and its cousins flash radiography1 and schieleren photography have been a technological proliferation concern. Indeed, like the supercomputer, the development of high-speed photography as we now know it essentially grew out of the nuclear weapons program at Los Alamos2,3,4. Naturally, during the course of the last 75 years the technology associated with computers and cameras has been export controlled by the United States and others to prevent both proliferation among non-P5-nations and technological parity among potential adversaries among P5 nations. Here we revisit these issues as they relate to high-speed photographic technologies and make recommendations about how future restrictions, if any, should be guided.

  19. The emerging nuclear suppliers and nonproliferation

    International Nuclear Information System (INIS)

    Potter, W.C.

    1990-01-01

    The number of states capable of exporting nuclear material, technology, equipment, and services is large and growing. Once confined primarily to states party to the Nuclear Non-Proliferation Treaty (NPT), the list of actual and potential nuclear suppliers now includes many countries that do not subscribe to the NPT or to other international nuclear export control agreements. Although international control accords---such as the Nuclear Exporters' (Zangger) Committee and the London Nuclear Suppliers Group (NSG) guidelines---do not prohibit the export of sensitive nuclear materials and equipment, they do reduce the risks of proliferation by imposing international safeguards as a condition for export. The purpose of this book---the culmination of one phase of an ongoing international research project on the emerging nuclear suppliers and nonproliferation---is to remedy, at least in part, this data deficiency

  20. Conditions applying to Australian uranium exports - safeguards obligations under NPT

    International Nuclear Information System (INIS)

    Rotsey, W.B.

    1975-08-01

    The Australian Government's expressed desire to inhibit the spread of nuclear weapons and its wish to prevent Australia's uranium exports being used for manufacture of nuclear explosives are underwritten by Australia's formal international obligations. Australia is not free to export its material without paying due regard to supra-national requirements. This paper defines two safeguards regimes, one applying to countries such as Australia which are party to the Treaty on Non-Proliferation of Nuclear Weapons (NPT), the other to those which are not parties. The application of safeguards and the role of the International Atomic Energy Agency (IAEA) are briefly explained. Australia's obligations under the NPT and those stemming from specific undertakings to the IAEA are stated. The latter require Australia to ensure that Non-Nuclear Weapons States not party to the NPT give assurances that Australian uranium will not be used for the manufacture of nuclear explosives and that they will permit verification by the IAEA. These obligations give rise to a set of minimum conditions applying to exports of Australian uranium which vary according to the NPT status of the importing countries. (author)

  1. Administrative Circulars Rev.

    CERN Multimedia

    2003-01-01

    Administrative Circular N° 19 (Rev. 3) - April 2003 Subsistence indemnity - Other expenses necessarily incurred in the course of duty travelAdministrative Circular N° 25 (Rev. 2) - April 2003 Shift work - Special provisions for the Fire and Rescue Service - These circulars have been revised. Human Resources Division Tel. 74128Copies of these circulars are available in the Divisional Secretariats. In addition, administrative and operational circulars, as well as the lists of those in force, are available for consultation on the Web at: http://humanresources.web.cern.ch/humanresources/internal/admin_services/admincirc/listadmincirc.asp

  2. Benchmark test of JENDL-3T and -3T/Rev.1

    International Nuclear Information System (INIS)

    Takano, Hideki; Kaneko, Kunio.

    1989-10-01

    The fast reactor 70-group constant set JFS-3-J3T has been generated by using the JENDL-3T nuclear data. One-dimensional 21-benchmark cores and the ZPPR-9 core were analysed with the JFS-3-J3T set. The results obtained are summarized as follows: (1) The values of keff are underestimated by 0.6% for Pu-fueled cores and overestimated by 2% for U-fueled cores. (2) The central reaction rate ratio 239 σ f φ/ 235 σ f φ is in a good agreement with the experimental value, though 238 σ c φ/ 239 σ f φ and 238 σ f φ/ 235 σ f φ are overestimated. (3) Doppler and Na-void reactivities are in a good agreement with the measured data. (4) The prediction accuracy of radial reaction rate distributions are improved in the comparison of the results obtained with the JENDL-2 data. Furthermore, the benchmark test of JENDL-3T/Rev. 1 which was revised from JENDL-3T for several important nuclides has been again performed. It was shown that JENDL-3T/Rev. 1 would predict nuclear characteristics more satisfactorily than JENDL-3T. (author)

  3. Analysis of translesion DNA synthesis activity of the human REV1-REV7 complex, which is a key player in radiation-induced mutagenesis

    International Nuclear Information System (INIS)

    Masuda, Y.; Masuda, K.; Kamiya, K.

    2003-01-01

    Full text: Ionizing radiation frequently causes oxidative DNA damage in cells. It has been suggested that functions of the REV1 and REV7 genes are induction of mutations and prevention of cell death caused by ionizing radiation. With yeast Saccharomyces cerevisiae, results from a variety of investigations have demonstrated that the REV genes play a major role in induction of mutations through replication processes which directly copy the damaged DNA template during DNA replication. However, in higher eucaryotes, functions of homologues are poorly understood and appear somewhat different from the yeast case. It has been suggested that human REV1 interacts with human REV7, this being specific to higher eucaryotes. Here we show that purified human REV1 and REV7 proteins form a heterodimer in solution, which is stable through intensive purification steps. Results from biochemical analysis of the transferase reactions of the REV1-REV7 complex demonstrated, in contrast to the case of yeast Rev3 whose polymerase activity is stimulated by assembly with yeast Rev7, that human REV7 did not influence the stability, substrate specificity or kinetic parameters of the transferase reactions of REV1 protein. A possible molecular role of the REV7 subunit may be to help assembly of the REV1 protein to a large complex containing REV3 and/or other DNA polymerases in higher eucaryotes

  4. Nuclear transport of heat shock proteins in stressed cells

    International Nuclear Information System (INIS)

    Chughtai, Zahoor Saeed

    2001-01-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or β-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-β-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single β-importin gene. With this assay I have identified Nmd5p as a β-importin required to concentrate Star-β-galactosidase in nuclei of stationary phase cells. (author)

  5. Nuclear transport of heat shock proteins in stressed cells

    Energy Technology Data Exchange (ETDEWEB)

    Chughtai, Zahoor Saeed

    2001-07-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or {beta}-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-{beta}-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single {beta}-importin gene. With this assay I have identified Nmd5p as a {beta}-importin required to concentrate Star-{beta}-galactosidase in nuclei of stationary phase cells. (author)

  6. Communication received from Argentina regarding the export of nuclear material and of certain categories of equipment and other material

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received a letter of 27 June 1995 from the Resident Representative of Argentina to the Agency concerning the export of nuclear material and of certain categories of equipment and other material. In the light of the wish expressed at the end of the letter, the text of the letter is attached hereto

  7. RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton.

    Science.gov (United States)

    Mamon, L A; Ginanova, V R; Kliver, S F; Yakimova, A O; Atsapkina, A A; Golubkova, E V

    2017-04-01

    The mutual relationship between mRNA and the cytoskeleton can be seen from two points of view. On the one hand, the cytoskeleton is necessary for mRNA trafficking and anchoring to subcellular domains. On the other hand, cytoskeletal growth and rearrangement require the translation of mRNAs that are connected to the cytoskeleton. β-actin mRNA localization may influence dynamic changes in the actin cytoskeleton. In the cytoplasm, long-lived mRNAs exist in the form of RNP (ribonucleoprotein) complexes, where they interact with RNA-binding proteins, including NXF (Nuclear eXport Factor). Dm NXF1 is an evolutionarily conserved protein in Drosophila melanogaster that has orthologs in different animals. The universal function of nxf1 genes is the nuclear export of different mRNAs in various organisms. In this mini-review, we briefly discuss the evidence demonstrating that Dm NXF1 fulfils not only universal but also specialized cytoplasmic functions. This protein is detected not only in the nucleus but also in the cytoplasm. It is a component of neuronal granules. Dm NXF1 marks nuclear division spindles during early embryogenesis and the dense body on one side of the elongated spermatid nuclei. The characteristic features of sbr mutants (sbr 10 and sbr 5 ) are impairment of chromosome segregation and spindle formation anomalies during female meiosis. sbr 12 mutant sterile males with immobile spermatozoa exhibit disturbances in the axoneme, mitochondrial derivatives and cytokinesis. These data allow us to propose that the Dm NXF1 proteins transport certain mRNAs in neurites and interact with localized mRNAs that are necessary for dynamic changes of the cytoskeleton. © 2017 Wiley Periodicals, Inc.

  8. 78 FR 60928 - Request To Amend a License To Export High-Enriched Uranium

    Science.gov (United States)

    2013-10-02

    ... NUCLEAR REGULATORY COMMISSION Request To Amend a License To Export High-Enriched Uranium Pursuant... manufacture HEU The Netherlands. National Nuclear Security Uranium uranium (17.1 targets in France... export from 9.4 kg of U-235 contained in 10.1 kg uranium to a new cumulative total of 17.1 kg of U-235...

  9. Introducing RevPASH: The Free Webtool Application

    Directory of Open Access Journals (Sweden)

    Peter Szende

    2014-10-01

    Full Text Available RevPASH (Revenue Per Available Seat Hour is an important measure that helps restaurant operators understand how efficiently each seat in a restaurant generates revenue. The RevPASH app is an easy-to-use web-tool that provides an operator with a quick way to input a few relevant numbers and calculate RevPASH.The application has the ability to compare RevPASH over different times, days, weeks, and months.

  10. Communication Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment or Technology

    International Nuclear Information System (INIS)

    1978-02-01

    The Permanent Mission of ...... presents its compliments to the Director General of the International Atomic Energy Agency and has the honour to enclose copies of three documents which have been the subject of discussion between the Government of ....... and a number of other Governments. The Government of ........ has decided that, when considering the export of nuclear material, equipment or technology, it will act in accordance with the principles contained in the attached documents

  11. Safety-reductions in cut-price nuclear power plant for export

    International Nuclear Information System (INIS)

    1985-01-01

    The report concentrates on insufficiencies and defects in safety engineering in the KWU pressurised water reactor of the 1000 MW category, which is made for export. The study was carried out in the light of the impending export of such a PWR to Egypt, but it could be applied to other potential buyer countries in many aspects. (orig.) [de

  12. Technical reports retrieval system(rev. 1) in the field of nuclear energy

    International Nuclear Information System (INIS)

    Choi, S.D.; Lee, Y.K.; Yim, S.H.

    1983-01-01

    TRRS(rev. 1), on-line Technical Reports Retrieval System, a set of computer programs, was designed and developed to provide fast and efficient access to computer-based information files. This system was foucused upon its application to the retrival of technical reports collected in KAERI, and developed not only to meet the requirements of researchers sitting at terminal but to accomodate its sufficiently general logic to other computer systems. The retrival program language is FORTRAN IV Plus. The users can search the whole files using next eleven TRRS(rev. 1) commands, HELP, SEARCH, LOOK, COMBINE, EXPAND, SELECT, REVIEW, RESTART, TYPE, PRINT, and END. The special features of this system are as follows. First, the SEARCH command can process full and truncation (truncation mark is %), and can combine such truncated terms using Boolean operators, and (*), and and-not (.). Second, COMBINE command can combine set numbers with year(s), language(s) and a substring of titles. Third, after EXPAND command, either full or truncated term, SELECT command brings same result of SEARCH command. Finally, real time response is very short, real time response is very short, usually within a second or less. (Author)

  13. Integration of renewable energies and nuclear power into North African Energy Systems: An analysis of energy import and export effects

    International Nuclear Information System (INIS)

    Supersberger, Nikolaus; Fuehrer, Laura

    2011-01-01

    The North African countries Morocco, Algeria, Tunisia, Libya and Egypt have been and are currently experiencing rapid growth in energy demand. This development confronts their political leaders with the question of how to expand or diversify their countries' generation capacities. In this context, renewable energies and nuclear power constitute options that have rarely been exploited so far in the region. This article analyzes the drawbacks and benefits of both alternatives, with a special focus on import and export dynamics. When attempting to make the strategic decision between renewables and atomic power, North African regional specifics and circumstances have to be taken into account. Hence, in a first step, the article characterizes the energy systems of the North African countries and presents scenarios for their future development. In a second step, it scrutinizes the energy challenges these states face in terms of domestic concerns and foreign affairs. Finally, a case study of Algeria is used to demonstrate how renewable energies, but not nuclear power, are able to respond to North African energy challenges. - Research highlights: → Using nuclear power would require fuel imports over the entire operation time. → Hence, energy exporters (Algeria, Libya) would become dependent on fuel imports. → Renewable energies can make North African countries less fuel import dependent. → Nuclear technologies would have to be imported over the whole life cycle of plants. → Domestic production for renewables technologies could be established after a first phase of technology imports.

  14. Project for export system construction of nuclear equipment to IAEA; survey on current market status of the nuclear related international organizations and the domestic possible suppliers

    Energy Technology Data Exchange (ETDEWEB)

    Min, T S; Cho, H K; Kim, H J [Korea Atomic Industrial Forum, Seoul (Korea)

    2001-05-01

    Republic of Korea are keeping the dynamic activities in IAEA as the 8th advanced nuclear country over the world but has occupied very low late less than 0.01% in supplying the equipments to IAEA. About 6,000 nuclear equipment suppliers are registered in IAEA Supply Roster over the world but only 3 Suppliers of our country are registered in IAEA Supply Roster. The supply of nuclear industrial products equivalent to about 100 million dollars into IAEA market will endorse not only the international authorization for our technology and products but also give contribution to activate the domestic nuclear industries in order to increase its expert. The explanation for IAEA procurement market to the 53 nuclear companies will be made on May 16, 2001, and the participants for the export of their goods will be selected. And then we will do all possible supports by the government and related organizations for them to register in IAEA Supply Roster. 21 refs. (Author)

  15. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 31 August 2001, from the Resident Representatives to the Agency of Argentina, Austria, Belarus, Belgium, Brazil, Bulgaria, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Luxembourg, Netherlands, New Zealand, Portugal, Republic of Korea, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United States and the United Kingdom, relating to the export of nuclear material, equipment and technology

  16. Export orientation and domestic electricity generation: Effects on energy efficiency innovation in select sectors

    International Nuclear Information System (INIS)

    Urpelainen, Johannes

    2011-01-01

    Why are some countries developing many energy efficiency innovations, while others are lagging behind? I argue that export orientation and electricity at low variable cost from nuclear and hydropower plants have an interactive effect on energy efficiency innovation. Export-oriented countries have strong incentives to invest in energy efficiency innovation, as they are in a position to export these technology innovations for global markets. But if inexpensive electricity is supplied in a country, the domestic demand for energy efficiency innovation is missing, and so the home market cannot serve as a springboard for international commercialization. I test this theory against international patent data on energy efficiency innovation in insulation, heating, and lighting for 22 OECD countries, 1991-2007. The statistical analysis indicates that export orientation has large positive effects on energy efficiency innovation in countries that do not rely on nuclear and hydroelectricity. - Highlights: → Export-oriented countries produce energy efficiency innovations. → Nuclear and hydropower reduce energy efficiency innovation. → Data on international patents from industrialized countries support the argument.

  17. Act of 18 December 1987 relating to the control of the export of strategic goods, services and technology

    International Nuclear Information System (INIS)

    1987-01-01

    This Act controls the export of nuclear material and equipment and sensitive nuclear technology and services. In particular, it provides for strict controls and verification of certain exports. (NEA) [fr

  18. 76 FR 36986 - Export Controls for High Performance Computers: Wassenaar Arrangement Agreement Implementation...

    Science.gov (United States)

    2011-06-24

    ... and export control standards. Croatia is a member of the Australia Group, the Nuclear Suppliers Group..., Exports, Inventions and patents, Research science and technology. 15 CFR Part 740 Administrative practice...

  19. Brucellosis vaccines: assessment of Brucella melitensis lipopolysaccharide rough mutants defective in core and O-polysaccharide synthesis and export.

    Directory of Open Access Journals (Sweden)

    David González

    Full Text Available BACKGROUND: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. METHODOLOGY/PRINCIPAL FINDINGS: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that

  20. Structural characterization of the principal mRNA-export factor Mex67–Mtr2 from Chaetomium thermophilum

    Energy Technology Data Exchange (ETDEWEB)

    Aibara, Shintaro; Valkov, Eugene; Lamers, Meindert H. [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom); Dimitrova, Lyudmila; Hurt, Ed [Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg (Germany); Stewart, Murray, E-mail: ms@mrc-lmb.cam.ac.uk [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom)

    2015-06-27

    The crystal structures of the individual domains of the Mex67–Mtr2 complex from C. thermophilum have been determined and their arrangement in solution has been studied by SAXS. Members of the Mex67–Mtr2/NXF–NXT1 family are the principal mediators of the nuclear export of mRNA. Mex67/NXF1 has a modular structure based on four domains (RRM, LRR, NTF2-like and UBA) that are thought to be present across species, although the level of sequence conservation between organisms, especially in lower eukaryotes, is low. Here, the crystal structures of these domains from the thermophilic fungus Chaetomium thermophilum are presented together with small-angle X-ray scattering (SAXS) and in vitro RNA-binding data that indicate that, not withstanding the limited sequence conservation between different NXF family members, the molecules retain similar structural and RNA-binding properties. Moreover, the resolution of crystal structures obtained with the C. thermophilum domains was often higher than that obtained previously and, when combined with solution and biochemical studies, provided insight into the structural organization, self-association and RNA-binding properties of Mex67–Mtr2 that facilitate mRNA nuclear export.

  1. Structural characterization of the principal mRNA-export factor Mex67–Mtr2 from Chaetomium thermophilum

    International Nuclear Information System (INIS)

    Aibara, Shintaro; Valkov, Eugene; Lamers, Meindert H.; Dimitrova, Lyudmila; Hurt, Ed; Stewart, Murray

    2015-01-01

    The crystal structures of the individual domains of the Mex67–Mtr2 complex from C. thermophilum have been determined and their arrangement in solution has been studied by SAXS. Members of the Mex67–Mtr2/NXF–NXT1 family are the principal mediators of the nuclear export of mRNA. Mex67/NXF1 has a modular structure based on four domains (RRM, LRR, NTF2-like and UBA) that are thought to be present across species, although the level of sequence conservation between organisms, especially in lower eukaryotes, is low. Here, the crystal structures of these domains from the thermophilic fungus Chaetomium thermophilum are presented together with small-angle X-ray scattering (SAXS) and in vitro RNA-binding data that indicate that, not withstanding the limited sequence conservation between different NXF family members, the molecules retain similar structural and RNA-binding properties. Moreover, the resolution of crystal structures obtained with the C. thermophilum domains was often higher than that obtained previously and, when combined with solution and biochemical studies, provided insight into the structural organization, self-association and RNA-binding properties of Mex67–Mtr2 that facilitate mRNA nuclear export

  2. Dynamic trafficking of STAT5 depends on an unconventional nuclear localization signal

    Science.gov (United States)

    Shin, Ha Youn; Reich, Nancy C.

    2013-01-01

    Summary Signal transducer and activator of transcription 5 (STAT5) is crucial for physiological processes that include hematopoiesis, liver metabolism and mammary gland development. However, aberrant continual activity of STAT5 has been causally linked to human leukemias and solid tumor formation. As a regulated transcription factor, precise cellular localization of STAT5 is essential. Conventional nuclear localization signals consist of short stretches of basic amino acids. In this study, we provide evidence that STAT5 nuclear import is dependent on an unconventional nuclear localization signal that functions within the conformation of an extensive coiled-coil domain. Both in vitro binding and in vivo functional assays reveal that STAT5 nuclear import is mediated by the importin-α3/β1 system independently of STAT5 activation by tyrosine phosphorylation. The integrity of the coiled-coil domain is essential for STAT5 transcriptional induction of the β-casein gene following prolactin stimulation as well as its ability to synergize with the glucocorticoid receptor. The glucocorticoid receptor accumulates in the nucleus in response to prolactin and this nuclear import is dependent on STAT5 nuclear import. STAT5 continually shuttles in and out of the nucleus and live cell imaging demonstrates that STAT5 nuclear export is mediated by both chromosome region maintenance 1 (Crm1)-dependent and Crm1-independent pathways. A Crm1-dependent nuclear export signal was identified within the STAT5 N-terminus. These findings provide insight into the fundamental mechanisms that regulate STAT5 nuclear trafficking and cooperation with the glucocorticoid receptor and provide a basis for clinical intervention of STAT5 function in disease. PMID:23704351

  3. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear-related dual-use transfers

    International Nuclear Information System (INIS)

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex

  4. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology. Nuclear-related dual-use transfers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    The Director General has received notes verbales dated 30 June 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for Transfers of Nuclear-related Dual-use Equipment, Material and related Technology. In the light of the wish expressed at the end of each note verbale, the text of the notes verbales is annexed hereto. The enclosure to these notes verbales is also reproduced in full in the Annex.

  5. 78 FR 45578 - Application For a License to Export Radioactive Waste

    Science.gov (United States)

    2013-07-29

    ... NUCLEAR REGULATORY COMMISSION Application For a License to Export Radioactive Waste Pursuant to 10..., 2013, radioactive waste authorized for disposal by the XW021, 11006101. as contaminated export will not original secondary waste exceed quantities generators, as resulting from imported in required or the...

  6. Optimized Chemical Probes for REV-ERBα

    OpenAIRE

    Trump, Ryan P.; Bresciani, Stefano; Cooper, Anthony W. J.; Tellam, James P.; Wojno, Justyna; Blaikley, John; Orband-Miller, Lisa A.; Kashatus, Jennifer A.; Dawson, Helen C.; Loudon, Andrew; Ray, David; Grant, Daniel; Farrow, Stuart N.; Willson, Timothy M.; Tomkinson, Nicholas C. O.

    2013-01-01

    REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. Potent REV-ERBα agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either IV o...

  7. Development of a Prototype for the Export Control List Management System

    International Nuclear Information System (INIS)

    Kim, GwanYoung

    2011-01-01

    The international society has concerned the possibility of a diversion with strategic items into the nuclear weapon development. So they have regulated those, and our country also has done it. Following a accomplishment of a UAE nuclear power plant export contraction in December, 2009 and a Jordan research reactor export contraction in March, 2010, thousands upon thousands of the strategic goods include the strategic technology will be supposed to transfer to UAE and Jordan. A lot of manpower in the government and the company concerned in addition to an enormous amount of time are needed so as to manage transferred items to UAE and Jordan efficiently. Accordingly, the Export Control List Management System has developed 1) to decrease the administrative time required about implementations such as the classification, the export license 2) and to plan the practical use of manpower 3) and to enhance a convenience of businesses, the government and a company concerned by the KINAC and the KOSTI. That system is scheduled to complete after June, and now a management of export items has done manually. This inconvenience can be solved by developing a prototype of the Export Control List Management System. Also an understanding of the Export Control List Management will be enhanced by doing it. A procedure of a system development and results will be presented in this paper

  8. Nuclear suicide. Rev. ed. [FRG]. Der atomare Selbstmord

    Energy Technology Data Exchange (ETDEWEB)

    Gruhl, H

    1988-01-01

    The author, one of the most consistent opponents of nuclear power, strikes a balance after the Chernobyl catastrophe. He relentlessly analyses the 'German nuclear situation', developments to be expected from risks and catastrophic events. He exposes statements offered by the owners of power plants and by politicians as attempts to play risks down, and hopes to achieve a turnabout yet. The conjunction of technical and physical arguments with a fundamental criticism of the ideology of economic growth is what distinguishes this book from other publications critical of nuclear energy. But the author does not content himself with criticism, he goes on to point out realistic measures for opting out of nuclear energy. (orig./HSCH) With 10 figs. and maps.

  9. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-24

    The document contains the text of note verbales dated 30 September 1997 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information about the Guidelines for Transfers of Nuclear-related Dual-use Equipment, material and related Technology in accordance with which the relevant Governments act.

  10. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1998-01-01

    The document contains the text of note verbales dated 30 September 1997 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. The purpose of the notes verbale is to provide further information about the Guidelines for Transfers of Nuclear-related Dual-use Equipment, material and related Technology in accordance with which the relevant Governments act

  11. Hydrologically mediated iron reduction/oxidation fluctuations and dissolved organic carbon exports in tidal wetlands

    Science.gov (United States)

    Guimond, J. A.; Seyfferth, A.; Michael, H. A.

    2017-12-01

    Salt marshes are biogeochemical hotspots where large quantities of carbon are processed and stored. High primary productivity and deposition of carbon-laden sediment enable salt marsh soils to accumulate and store organic carbon. Conversely, salt marshes can laterally export carbon from the marsh platform to the tidal channel and eventually the ocean via tidal pumping. However, carbon export studies largely focus on tidal channels, missing key physical and biogeochemical mechanisms driving the mobilization of dissolved organic carbon (DOC) within the marsh platform and limiting our understanding of and ability to predict coastal carbon dynamics. We hypothesize that iron redox dynamics mediate the mobilization/immobilization of DOC in the top 30 cm of salt marsh sediment near tidal channels. The mobilized DOC can then diffuse into the flooded surface water or be advected to tidal channels. To elucidate DOC dynamics driven by iron redox cycles, we measured porewater DOC, Fe(II), total iron, total sulfate, pH, redox potential, and electrical conductivity (EC) beside the creek, at the marsh levee, and in the marsh interior in a mid-latitude tidal salt marsh in Dover, Delaware. Samples were collected at multiple tide stages during a spring and neap tide at depths of 5-75cm. Samples were also collected from the tidal channel. Continuous Eh measurements were made using in-situ electrodes. A prior study shows that DOC and Fe(II) concentrations vary spatially across the marsh. Redox conditions near the creek are affected by tidal oscillations. High tides saturate the soil and decrease redox potential, whereas at low tide, oxygen enters the sediment and increases the Eh. This pattern is always seen in the top 7-10cm of sediment, with more constant low Eh at depth. However, during neap tides, this signal penetrates deeper. Thus, between the creek and marsh levee, hydrology mediates redox conditions. Based on porewater chemistry, if DOC mobilization can be linked to redox

  12. Nuclear Legislation in OECD and NEA Countries. Regulatory and Institutional Framework for Nuclear Activities - United States

    International Nuclear Information System (INIS)

    2015-01-01

    This country profile provide comprehensive information on the regulatory and Institutional Framework governing nuclear activities as well as a detailed review of a full range of nuclear law topics, including: mining regime; radioactive substances; nuclear installations; trade in nuclear materials and equipment; radiation protection; radioactive waste management; non-proliferation and physical protection; transport; and nuclear third party liability. The profile is complemented by reproductions of the primary legislation regulating nuclear activities in the country. Content: I. General Regulatory Regime: 1. Introduction; 2. Mining regime; 3. Radioactive substances, nuclear fuel and equipment (Special nuclear material; Source material; By-product material; Agreement state programmes); 4. Nuclear installations (Initial licensing; Operation and inspection, including nuclear safety; Operating licence renewal; Decommissioning; Emergency response); 5. Radiological protection (Protection of workers; Protection of the public); 6. Radioactive waste management (High-level waste; Low-level waste; Disposal at sea; Uranium mill tailings; Formerly Utilized Sites Remedial Action Program - FUSRAP); 7. Non-proliferation and exports (Exports of source material, special nuclear material, production or utilisation facilities and sensitive nuclear technology; Exports of components; Exports of by-product material; Exports and imports of radiation sources; Conduct resulting in the termination of exports or economic assistance; Subsequent arrangements; Technology exports; Information and restricted data); 8. Nuclear security; 9. Transport; 10. Nuclear third party liability; II. Institutional Framework: 1. Regulatory and supervisory authorities (Nuclear Regulatory Commission - NRC; Department of Energy - DOE; Department of Labor - DOL; Department of Transportation - DOT; Environmental Protection Agency - EPA); 2. Public and semi-public agencies: A. Cabinet-level departments (Department of

  13. Summary case for mining and export of Australia's uranium deposits for peaceful uses in generation of electricity

    International Nuclear Information System (INIS)

    1984-04-01

    Arguments in support of the mining and export of Australian uranium are presented. They concern economic development and export income; environmental advantages over fossil fuels; the existence of appropriate safety standards and procedures and of effective waste management procedures; and the potential, as a uranium exporter, to influence international discussions relating to safeguards. Chapters cover world statistics on nuclear power, sources of uranium, fuel cycle stages and related safety issues, environmental aspects of the fuel cycle, safeguards, high level waste management, the connection between nuclear power and nuclear weapons, and economic benefits to Australia

  14. Communications Received from Members regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material. Two Further Communications dated 26 September 1975

    International Nuclear Information System (INIS)

    1975-01-01

    On 3 October 1975 the Director General received a letter from the Resident Representative of the Netherlands to the Agency transmitting two communications dated 10 September from the Minister for Foreign Affairs of Luxembourg dealing respectively with the export of nuclear material and the export of certain categories of equipment and other material. The Resident Representative requested that all Members be informed of the contents of the two communications, and they are accordingly reproduced below

  15. Control of nuclear β-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function.

    Science.gov (United States)

    Vélez-Aguilera, Griselda; de Dios Gómez-López, Juan; Jiménez-Gutiérrez, Guadalupe E; Vásquez-Limeta, Alejandra; Laredo-Cisneros, Marco S; Gómez, Pablo; Winder, Steve J; Cisneros, Bulmaro

    2018-02-01

    β-Dystroglycan (β-DG) is a plasma membrane protein that has ability to target to the nuclear envelope (NE) to maintain nuclear architecture. Nevertheless, mechanisms controlling β-DG nuclear localization and the physiological consequences of a failure of trafficking are largely unknown. We show that β-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its transmembrane domain, by CRM1. Remarkably, NES mutations forced β-DG nuclear accumulation resulting in mislocalization and decreased levels of emerin and lamin B1 and disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and β-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are critically involved. In addition to nuclear export, the lifespan of nuclear β-DG is restricted by its nuclear proteasomal degradation. Collectively our data show that control of nuclear β-DG content by the combination of CRM1 nuclear export and nuclear proteasome pathways is physiologically relevant to preserve proper NE structure and activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding.

    Directory of Open Access Journals (Sweden)

    Yao E Wang

    2010-11-01

    Full Text Available Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4 pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS and the leucine-rich nuclear export signal (NES found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50 of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf" therapeutic against acute NiV infection.

  17. Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

    Directory of Open Access Journals (Sweden)

    Marriott Susan J

    2007-12-01

    . Ubiquitination of these residues facilitates the dissociation of Tax from sc35-containing nuclear foci, and stimulates nuclear export of Tax through the CRM1 pathway.

  18. Conceptual Design on the System Architecture of Intellectual Export Control System(IXCS)

    International Nuclear Information System (INIS)

    Jeong, Seung Ho; Yang, Seung Hyo; Tae, Jae Woong; Shin, Dong Hoon

    2013-01-01

    The commodity classification is for identifying strategic commodity, and the export license is for verifying that exports have met the requirement by the national legislation following international obligations (i. e. NSG guidelines) Since 2008, the 'Nuclear Export Promotion Service (NEPS)' System has been used as a total IT system providing various functions for exporters and reviewers. However, reviewers who make the decisions for commodity classification and export license, may have difficulties caused by ambiguity of criteria. For example, it is not sure whether a CVCS (Chemical Volume Control System) of a certain nuclear reactor plant belongs to strategic commodity or not. The NEPS is a useful system helping users save their time, but it cannot provide solutions reducing ambiguity of each classification or license case. To solve these problems and provide more efficient ways to their decisions, various intelligent IT solutions are searched and studied. A functional architecture of IXCS is defined and designed conceptually. This conceptual design will be utilized to make database specification and to find the optimized artificial algorithm for review processes

  19. Communication of 2 June 2009 received from the Permanent Mission of the United Kingdom regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material; Comunicacion de fecha 2 de junio de 2009 recibida de la Mision Permanente del Reino Unido en relacion con la exportacion de materiales nucleares y de determinadas categorias de equipo y otros materiales

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-31

    The Director General has received a note ver bale from the Permanent Mission of the United Kingdom, dated 2 June 2009, in which it requests that the Agency circulate to all Member States a letter of 28 May 2009 from the Chairman of the Zangger Committee, Mr. Pavel Klucky, to the Director General, on behalf of the Governments of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, China, Croatia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Kazakhstan, the Republic of Korea, Luxemburg, the Netherlands, Norway, Poland, Portugal, Romania, the Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom and the United States of America, concerning a number of corrections to the communication regarding the export of nuclear material and of certain categories of equipment and other material published in INFCIRC/209/Rev.2 [Spanish] El Director General ha recibido una nota verbal de la Mision Permanente del Reino Unido, de fecha 2 de junio de 2009, en la que se pide que el Organismo distribuya a todos los Estados Miembros una carta de fecha 28 de mayo de 2009 del Presidente del Comite Zangger, Sr. Pavel Klucky, en nombre de los Gobiernos de Alemania, Argentina, Australia, Austria, Belgica, Bulgaria, Canada, China, Corea (Republica de), Croacia, Dinamarca, Eslovaquia, Eslovenia, Espana, Estados Unidos de America, Federacion de Rusia, Finlandia, Francia, Grecia, Hungria, Irlanda, Italia, Japon, Kazajstan, Luxemburgo, Noruega, Paises Bajos, Polonia, Portugal, Reino Unido de Gran Bretana e Irlanda del Norte, Rumania, Sudafrica, Suecia, Suiza, Turquia y Ucrania, en relacion con varias correcciones hechas a la comunicacion referente a la exportacion de materiales nucleares y de determinadas categorias de equipo y otros materiales publicadas en el documento INFCIRC/209/Rev.2.

  20. Diagnostic nuclear medicine. 2. rev. ed.

    International Nuclear Information System (INIS)

    Schiepers, C.

    2006-01-01

    The field of nuclear medicine is undergoing rapid expansion, and is evolving into diagnostic molecular imaging. During recent years, dual-modality imaging with PET/CT has gained acceptance and this is currently the fastest-growing technique for oncological imaging applications. The glucose analogue FDG has held its place in diagnostic oncology, assessment of myocardial viability and diagnosis of neuro-degenerative disorders. Peptides have become even more important as imaging agents. The accuracy of hepatobiliary scintigraphy has been enhanced by cholecystokinin. The use of ACE inhibitors in the evaluation of renovascular hypertension has become the standard in renography. New instrumentation has led to faster scanners, and computer development to better image processing software. Automatic processing is more common, and standardization of protocols can be accomplished easily. The field of gene imaging has progressed, although routine clinical applications are not yet available. The present text, supplemented with many detailed and informative illustrations, represents an adjunct to the standard knowledge of diagnostic nuclear medicine and provides both the student and the professional with an overview of developments during the past decade. (orig.)

  1. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-02-23

    The Director General of the International Atomic Energy Agency has received Notes Verbales dated 25 October 2004 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Brazil, Canada, Cyprus, Czech Republic, Estonia, Finland, France, Greece, Hungary, Italy, Japan, Malta, Netherlands, Norway, Republic of Korea, South Africa, Spain, Sweden, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear materials, equipment and technology. The purpose of the Notes Verbales is to provide further information on those Governments' guidelines for nuclear transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to these Notes Verbales is also reproduced in full.

  2. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2005-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales dated 25 October 2004 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Brazil, Canada, Cyprus, Czech Republic, Estonia, Finland, France, Greece, Hungary, Italy, Japan, Malta, Netherlands, Norway, Republic of Korea, South Africa, Spain, Sweden, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear materials, equipment and technology. The purpose of the Notes Verbales is to provide further information on those Governments' guidelines for nuclear transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to these Notes Verbales is also reproduced in full

  3. Communications received from certain Member States regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2003-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 28 February 2003, from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Canada, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Kazakhstan, Latvia, Netherlands, Norway, Poland, Portugal, the Republic of Korea, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America, relating to the export of nuclear material, equipment and technology. The purpose of the Note Verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to the Notes Verbales is also reproduced in full

  4. Communications received from certain Member States regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-05-16

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 28 February 2003, from the Resident Representatives to the Agency of Argentina, Austria, Belgium, Bulgaria, Canada, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Kazakhstan, Latvia, Netherlands, Norway, Poland, Portugal, the Republic of Korea, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America, relating to the export of nuclear material, equipment and technology. The purpose of the Note Verbales is to provide further information on those Governments' Guidelines for Nuclear Transfers. In light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbales is attached. The attachment to the Notes Verbales is also reproduced in full.

  5. Communications received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbale, dated 31 August 2001, from the Resident Representatives to the Agency of Argentina, Austria, Belarus, Belgium, Brazil, Bulgaria, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Latvia, Luxembourg, Netherlands, New Zealand, Portugal, Republic of Korea, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United States and the United Kingdom, relating to the export of nuclear material, equipment and technology. The purpose of the Notes Verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers. In the light of the wish expressed at the end of each Note Verbale, the text of the Notes Verbale is attached. The attachment to the Notes Verbale is also reproduced in full

  6. Sustainability, innovative orientation and export performance of manufacturing SMEs: An empirical analysis of the mediating role of corporate image

    Energy Technology Data Exchange (ETDEWEB)

    Villena-Manzanares, F.; Souto-Pérez, J.E.

    2016-07-01

    The objective of this research is to empirically analyze the role played by corporate image, sustainability, and innovative orientation on export performance. Hypothesis testing was conducted with a sample of 180 manufacturing SMEs in Seville (Spain) and a structural equation system is modeled using the technique Partial Least Squares (PLS). The research model includes the following variables: corporate image, sustainability, and innovative orientation on export performance. The results show the positive effect of sustainability and innovative orientation on export performance, as well as the mediator effect of corporate image on these relationships. The results may be more general if we had used a national sample and cross cultural. The conclusions cannot be directly extrapolated to other countries. This work propose future research doing the same study with other types companies. Corporate image requires special attention, as it acts as a filter of the impacts of sustainability and innovative orientation. The creation of corporate image not only as a result of tangible items, but as a result of the actions and behavior of the company. In this research is showed that there is a high level of complexity in the management of intangibles since the intangibles influence each other, such as the influence of sustainability and innovative orientation on corporate image. Managers should focus on proper design and management of the company image, in order to compete and grow in the international area. (Author)

  7. Trust, Commitment and Competitive Advantage in SMEs Export Performance

    Directory of Open Access Journals (Sweden)

    Md Daud Ismail

    2017-04-01

    Full Text Available The entry of small businesses into international markets has intensified. However, despite the growing presence of small businesses in international markets, studies into their international behavior, particularly regarding the effect of international relationships on international outcomes, remain limited. This study investigates the cross-border relationships of Small and Medium Enterprises (SMEs by examining the effects of the dimensions of the key relationship on the competitive advantage and performance of SMEs in export markets. These dimensions include trust and commitment. Results indicate that trust is significantly related to commitment and export performance. Commitment is positively related to competitive advantage but not to export performance. Trust affects competitive advantage through commitment. The effect of commitment on export performance is mediated by competitive advantage. The methodology and results are presented. The conclusion, implications, and limitations of this study are also discussed.

  8. Mesoscale Effects on Carbon Export: A Global Perspective

    Science.gov (United States)

    Harrison, Cheryl S.; Long, Matthew C.; Lovenduski, Nicole S.; Moore, Jefferson K.

    2018-04-01

    Carbon export from the surface to the deep ocean is a primary control on global carbon budgets and is mediated by plankton that are sensitive to physical forcing. Earth system models generally do not resolve ocean mesoscale circulation (O(10-100) km), scales that strongly affect transport of nutrients and plankton. The role of mesoscale circulation in modulating export is evaluated by comparing global ocean simulations conducted at 1° and 0.1° horizontal resolution. Mesoscale resolution produces a small reduction in globally integrated export production (export production can be large (±50%), with compensating effects in different ocean basins. With mesoscale resolution, improved representation of coastal jets block off-shelf transport, leading to lower export in regions where shelf-derived nutrients fuel production. Export is further reduced in these regions by resolution of mesoscale turbulence, which restricts the spatial area of production. Maximum mixed layer depths are narrower and deeper across the Subantarctic at higher resolution, driving locally stronger nutrient entrainment and enhanced summer export production. In energetic regions with seasonal blooms, such as the Subantarctic and North Pacific, internally generated mesoscale variability drives substantial interannual variation in local export production. These results suggest that biogeochemical tracer dynamics show different sensitivities to transport biases than temperature and salinity, which should be considered in the formulation and validation of physical parameterizations. Efforts to compare estimates of export production from observations and models should account for large variability in space and time expected for regions strongly affected by mesoscale circulation.

  9. Study on Maintenance Personnel Development Plan For The Exported APR1400 Commissioning

    International Nuclear Information System (INIS)

    Cho, Sungbae; Kim, Jongdae; Jun, Hokwang; Hwang, Inok; Kang, Jaeyuel

    2012-01-01

    This paper indicates ways to develop maintenance personnel for the exported APR1400 commissioning. The exported APR1400 has not been experienced ay maintenance yet, and requirements for maintenance personnel have not been clarified yet. Based on sound maintenance experience, KEPCO Plant Service and Engineering Company (KEPCO KPS) has studied on maintenance training and career requirement to establish a development plan of the maintenance personnel for the exported nuclear power plant. By defining manpower and training requirement, and mobilization plan, we expect to secure reliability of the exported APR1400

  10. Communication received from the permanent mission of Austria regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General received a note verbale of 13 June 1996 from Permanent Mission of Austria regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material. In the light of the request expressed at the end of the note verbale, the text of the note verbale is being circulated

  11. Communication received from the permanent mission of Finland regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General received a note verbale of 8 February 1996 from Permanent Mission of Finland regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material. In the light of the request expressed at the and of the note verbale, the text of the note verbale is being circulated

  12. 78 FR 53793 - Request To Amend a License To Export Radioactive Waste

    Science.gov (United States)

    2013-08-30

    ... NUCLEAR REGULATORY COMMISSION Request To Amend a License To Export Radioactive Waste Pursuant to... total of 5,500 ``Ultimate Foreign XW012/04 radioactive tons of low- Consignee(s).'' No other 11005699 waste). level waste). changes to the existing license which authorizes the export of non-conforming...

  13. Administrative Circulars No. 12 A (Rev. 2) - "Education fees” and No. 12 B (Rev. 2) - “Education fees and language courses”

    CERN Multimedia

    2013-01-01

    Administrative Circulars No. 12 A (Rev. 2) entitled “Education fees” and No. 12 B (Rev. 2) entitled “Education fees and language courses”, approved by the Director-General following discussion at the Standing Concertation Committee meeting of 27 June 2013 and entering into force on 1 August 2013, are available on the intranet site of the Human Resources Department (see here).   Administrative Circular No. 12 A (Rev. 2) is applicable to Staff Members (except former “Local Staff Members”) recruited before 1st January 2007. Administrative Circular No. 12 B (Rev. 2) is applicable to Staff Members recruited on or after 1st January 2007, to Fellows, to Scientific Associates, to Guest Professors and to former “Local Staff” recruited before 1st January 2007. They cancel and replace Administrative Circulars No. 12 A (Rev. 1/Corr.) entitled "Education fees” and No. 12 B (Rev. 1/Corr.) entitled “Edu...

  14. Strategy of nuclear power in Korea, non-nuclear-weapon state and peaceful use of nuclear power

    International Nuclear Information System (INIS)

    Nagasaki, Takao

    2005-01-01

    The nuclear power plant started at Kori in Korea in April, 1978. Korea has carried out development of nuclear power as a national policy. The present capacity of nuclear power plants takes the sixes place in the world. It supplies 42% total power generation. The present state of nuclear power plant, nuclear fuel cycle facility, strategy of domestic production of nuclear power generation, development of next generation reactor and SMART, strategy of export in corporation with industry, government and research organization, export of nuclear power generation in Japan, nuclear power improvement project with Japan, Korea and Asia, development of nuclear power system with nuclear diffusion resistance, Hybrid Power Extraction Reactor System, radioactive waste management and construction of joint management and treatment system of spent fuel in Asia are stated. (S.Y.)

  15. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2006-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology

  16. Communications Received from Certain Member States Regarding Guidelines for the Export of Nuclear Material, Equipment and Technology

    International Nuclear Information System (INIS)

    2006-01-01

    The Director General of the International Atomic Energy Agency has received Notes Verbales, dated 1 December 2005, from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Republic of Korea, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, New Zealand, Poland, Portugal, Slovenia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, the United Kingdom of Great Britain and Northern Ireland and the United States of America, relating to the export of nuclear material, equipment and technology [es

  17. France intends to raise electricity exports

    International Nuclear Information System (INIS)

    Grotelueschen, M.; Boiteux.

    1986-01-01

    In this interview with the Chairman of the Supervisory Board of Electricite de France (EdF), the promotion of nuclear power in France, the chances on the export sector, and the structure of electric power supply are discussed and compared with the situation in West Germany. (UA) [de

  18. Quicklook overview of model changes in Melcor 2.2: Rev 6342 to Rev 9496

    Energy Technology Data Exchange (ETDEWEB)

    Humphries, Larry L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-05-01

    MELCOR 2.2 is a significant official release of the MELCOR code with many new models and model improvements. This report provides the code user with a quick review and characterization of new models added, changes to existing models, the effect of code changes during this code development cycle (rev 6342 to rev 9496), a preview of validation results with this code version. More detailed information is found in the code Subversion logs as well as the User Guide and Reference Manuals.

  19. The nuclear nineties

    International Nuclear Information System (INIS)

    Campbell, D.

    1990-01-01

    Although United States Customs recently prevented 40 krytrons, fast triggers to start a nuclear fission detonation, from being exported, other countries have been able to acquire similar items without questions being asked. Nuclear power plants have been exported to Pakistan and it is expected that this will enable Pakistan to become the world's ninth nuclear weapons state. Not all current or potential nuclear weapons states have signed and ratified the Non-Proliferation Treaty. Some nuclear plant have been built in developing countries without proper International Atomic Energy Authority Control. It would seem that there is a general indifference to nuclear proliferation by some of the western nuclear countries. (UK)

  20. Nuclear pore complex protein mediated nuclear localization of dicer protein in human cells.

    Directory of Open Access Journals (Sweden)

    Yoshinari Ando

    Full Text Available Human DICER1 protein cleaves double-stranded RNA into small sizes, a crucial step in production of single-stranded RNAs which are mediating factors of cytoplasmic RNA interference. Here, we clearly demonstrate that human DICER1 protein localizes not only to the cytoplasm but also to the nucleoplasm. We also find that human DICER1 protein associates with the NUP153 protein, one component of the nuclear pore complex. This association is detected predominantly in the cytoplasm but is also clearly distinguishable at the nuclear periphery. Additional characterization of the NUP153-DICER1 association suggests NUP153 plays a crucial role in the nuclear localization of the DICER1 protein.

  1. Nuclear Receptor Cofactors in PPARγ-Mediated Adipogenesis and Adipocyte Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Emily Powell

    2007-01-01

    Full Text Available Transcriptional cofactors are integral to the proper function and regulation of nuclear receptors. Members of the peroxisome proliferator-activated receptor (PPAR family of nuclear receptors are involved in the regulation of lipid and carbohydrate metabolism. They modulate gene transcription in response to a wide variety of ligands, a process that is mediated by transcriptional coactivators and corepressors. The mechanisms by which these cofactors mediate transcriptional regulation of nuclear receptor function are still being elucidated. The rapidly increasing array of cofactors has brought into focus the need for a clear understanding of how these cofactors interact in ligand- and cell-specific manners. This review highlights the differential effects of the assorted cofactors regulating the transcriptional action of PPARγ and summarizes the recent advances in understanding the physiological functions of corepressors and coactivators.

  2. Characterization of nuclear localization and export signals of the major tegument protein VP8 of bovine herpesvirus-1

    International Nuclear Information System (INIS)

    Zheng Chunfu; Brownlie, Robert; Babiuk, Lorne A.; Hurk, Sylvia van Drunen Littel-van den

    2004-01-01

    Bovine herpesvirus-1 (BHV-1) VP8 is found in the nucleus immediately after infection. Transient expression of VP8 fused to yellow fluorescent protein (YFP) in COS-7 cells confirmed the nuclear localization of VP8 in the absence of other viral proteins. VP8 has four putative nuclear localization signals (NLS). Deletion of pat4 ( 51 RRPR 54 ) or pat7 ( 48 PRVRRPR 54 ) NLS2 abrogated nuclear accumulation, whereas deletion of 48 PRV 50 did not, so pat4 NLS2 is critical for nuclear localization of VP8. Furthermore, NLS1 ( 11 RRPRR 15 ), pat4 NLS2, and pat7 NLS2 were all capable of transporting the majority of YFP to the nucleus. Finally, a 12-amino-acid peptide with the sequence RRPRRPRVRRPR directed all of YFP into the nucleus, suggesting that reiteration of the RRPR motif makes the nuclear localization more efficient. Heterokaryon assays demonstrated that VP8 is also capable of shuttling between the nucleus and cytoplasm of the cell. Deletion mutant analysis revealed that this property is attributed to a leucine-rich nuclear export sequence (NES) consisting of amino acids 485 LSAYLTLFVAL 495 . This leucine-rich NES caused transport of YFP to the cytoplasm. These results demonstrate that VP8 shuttles between the nucleus and cytoplasm

  3. Epistatic participation of REV1 and REV3 in the formation of UV-induced frameshift mutations in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Steinboeck, Ferdinand [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

    2006-01-29

    Mutations arising in times of cell cycle arrest may provide a selective advantage for unicellular organisms adapting to environmental changes. For multicellular organisms, however, they may pose a serious threat, in that such mutations in somatic cells contribute to carcinogenesis and ageing. The budding yeast Saccharomyces cerevisiae presents a convenient model system for studying the incidence and the mechanisms of stationary-phase mutation in a eukaryotic organism. Having studied the emergence of frameshift mutants after several days of starvation-induced cell cycle arrest, we previously reported that all (potentially error-prone) translesion synthesis (TLS) enzymes identified in S. cerevisiae did not contribute to the basal level of spontaneous stationary-phase mutations. However, we observed that an increased frequency of stationary-phase frameshift mutations, brought about by a defective nucleotide excision repair (NER) pathway or by UV irradiation, was dependent on Rev3p, the catalytic subunit of the TLS polymerase zeta (Pol {zeta}). Employing the same two conditions, we now examined the effect of deletions of the genes coding for polymerase eta (Pol {eta}) (RAD30) and Rev1p (REV1). In a NER-deficient strain background, the increased incidence of stationary-phase mutations was only moderately influenced by a lack of Pol {eta} but completely reduced to wild type level by a knockout of the REV1 gene. UV-induced stationary-phase mutations were abundant in wild type and rad30{delta} strains, but substantially reduced in a rev1{delta} as well as a rev3{delta} strain. The similarity of the rev1{delta} and the rev3{delta} phenotype and an epistatic relationship evident from experiments with a double-deficient strain suggests a participation of Rev1p and Rev3p in the same mutagenic pathway. Based on these results, we propose that the response of cell cycle-arrested cells to an excess of exo- or endogenously induced DNA damage includes a novel replication

  4. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-16

    The document contains the text of note verbales dated 17 October 1996 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. A similar note verbal dated 30 July 1997 has been received by the Director General of the IAEA from the Resident Representative to the Agency of Brazil. The purpose of the notes verbale is to provide further information on those Governments` Guidelines for Nuclear Transfers.

  5. Communication received from certain member states regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1997-01-01

    The document contains the text of note verbales dated 17 October 1996 received by the Director General of the IAEA from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, the Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Russian Federation, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, Ukraine, the United Kingdom of Great Britain and Northern Ireland, and the United States of America relating to export of nuclear material, equipment and technology. A similar note verbal dated 30 July 1997 has been received by the Director General of the IAEA from the Resident Representative to the Agency of Brazil. The purpose of the notes verbale is to provide further information on those Governments' Guidelines for Nuclear Transfers

  6. The system of nuclear material control of Kazakhstan

    International Nuclear Information System (INIS)

    Yeligbayeva, G.Zh.

    2001-01-01

    Full text: The State system for nuclear material control consists of three integral components. The efficiency of each is to guarantee the non-proliferation regime in Kazakhstan. The components are the following: accounting, export and import control and physical protection of nuclear materials. First, the implementation of the goals of accounting and control bring into force, by the organization of the system for accounting and measurement of nuclear materials to determine present quantity. Organizing the accounting for nuclear material at facilities will ensure the efficiency of accountancy and reporting information. This defines the effectiveness of the state system for the accounting for the Kazakhstan's nuclear materials. Currently, Kazakhstan's nuclear material is fully safeguarded in designated secure locations. Kazakhstan has a nuclear power plant, 4 research reactors and a fuel fabrication plant. The governmental information system for nuclear materials control consist of two level: Governmental level - KAEA collects reports from facilities and prepares the reports for International Atomic Energy Agency, keeping of supporting documents and other necessary information, a data base of export and import, a data base of nuclear material inventory. Facility level - registration and processing information from key measurement points, formation the facility's nuclear materials accounting database. All facilities have computerized systems. Currently, all facilities are safeguarded under IAEA safeguarding standards, through IAEA inspections. Annually, IAEA verifies all nuclear materials at all Kazakhstan nuclear facilities. The government reporting system discloses the existence of all nuclear material and its transfer intended for interaction through the export control system and the nuclear control accounting system. Nuclear material export is regulated by the regulations of the Nuclear Export Control Law. The standard operating procedure is the primary means for

  7. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming.

    Science.gov (United States)

    Mitani, Yasuyuki; Vagnozzi, Ronald J; Millay, Douglas P

    2017-01-01

    Knowledge regarding cellular fusion and nuclear reprogramming may aid in cell therapy strategies for skeletal muscle diseases. An issue with cell therapy approaches to restore dystrophin expression in muscular dystrophy is obtaining a sufficient quantity of cells that normally fuse with muscle. Here we conferred fusogenic activity without transdifferentiation to multiple non-muscle cell types and tested dystrophin restoration in mouse models of muscular dystrophy. We previously demonstrated that myomaker, a skeletal muscle-specific transmembrane protein necessary for myoblast fusion, is sufficient to fuse 10T 1/2 fibroblasts to myoblasts in vitro. Whether myomaker-mediated heterologous fusion is functional in vivo and whether the newly introduced nonmuscle nuclei undergoes nuclear reprogramming has not been investigated. We showed that mesenchymal stromal cells, cortical bone stem cells, and tail-tip fibroblasts fuse to skeletal muscle when they express myomaker. These cells restored dystrophin expression in a fraction of dystrophin-deficient myotubes after fusion in vitro. However, dystrophin restoration was not detected in vivo although nuclear reprogramming of the muscle-specific myosin light chain promoter did occur. Despite the lack of detectable dystrophin reprogramming by immunostaining, this study indicated that myomaker could be used in nonmuscle cells to induce fusion with muscle in vivo, thereby providing a platform to deliver therapeutic material.-Mitani, Y., Vagnozzi, R. J., Millay, D. P. In vivo myomaker-mediated heterologous fusion and nuclear reprogramming. © FASEB.

  8. 76 FR 72984 - Revised Application for a License To Export High-Enriched Uranium

    Science.gov (United States)

    2011-11-28

    ... NUCLEAR REGULATORY COMMISSION Revised Application for a License To Export High-Enriched Uranium The application for a license to export high-enriched Uranium has been revised as noted below. Notice... fabricate fuel France. Security Complex; October 18, Uranium (93.35%). uranium (174.0 elements in France...

  9. Communication from the Permanent Mission of France to the International Atomic Energy Agency regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale received by the Director General of the IAEA from the Permanent Mission of France to the IAEA providing information on the policies and practices of the Government of France with respect to the export of nuclear material, equipment and technology

  10. Communication of 12 June 2000 received from the Ministry of Foreign Affairs of the Republic of Slovenia regarding Slovenia's nuclear export policies and practices

    International Nuclear Information System (INIS)

    2000-01-01

    The document reproduces the text of the Note Verbale dated 12 June 2000 received by the Secretariat of the IAEA from the Ministry of Foreign Affairs of the Republic of Slovenia providing information on the nuclear export policies and practices of the Government of the Republic of Slovenia

  11. Communication received from the Permanent Mission of Sweden regarding the provision of certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material

    International Nuclear Information System (INIS)

    1996-01-01

    The document reproduces the text of a note verbale dated 28 June 1996 received by the Director General of IAEA from the Permanent Mission of Sweden through which the Government of Sweden provides, on a voluntary basis, certain additional information on production, inventories and international transfers of nuclear material and on exports of certain relevant equipment and non-nuclear material, in order to assist the Agency in the discharge of its safeguards responsibilities

  12. The nuclear import of RNA helicase A is mediated by importin-α3

    International Nuclear Information System (INIS)

    Aratani, Satoko; Oishi, Takayuki; Fujita, Hidetoshi; Nakazawa, Minako; Fujii, Ryouji; Imamoto, Naoko; Yoneda, Yoshihiro; Fukamizu, Akiyoshi; Nakajima, Toshihiro

    2006-01-01

    RNA helicase A (RHA), an ATPase/helicase, regulates the gene expression at various steps including transcriptional activation and RNA processing. RHA is known to shuttle between the nucleus and cytoplasm. We identified the nuclear localization signal (NLS) of RHA and analyzed the nuclear import mechanisms. The NLS of RHA (RHA-NLS) consisting of 19 amino acid residues is highly conserved through species and does not have the consensus classical NLS. In vitro nuclear import assays revealed that the nuclear import of RHA was Ran-dependent and mediated with the classical importin-α/β-dependent pathway. The binding assay indicated that the basic residues in RHA-NLS were used for interaction with importin-α. Furthermore, the nuclear import of RHA-NLS was supported by importin-α1 and preferentially importin-α3. Our results indicate that the nuclear import of RHA is mediated by the importin-α3/importin-β-dependent pathway and suggest that the specificity for importin may regulate the functions of cargo proteins

  13. Communication of 15 November 2001 Received from the People's Republic of China regarding the Export of Nuclear Material and of Certain Categories of Equipment and Other Material

    International Nuclear Information System (INIS)

    2002-01-01

    The Director General has received a letter of 15 November 2001 from the Resident Representative of the People's Republic of China concerning the export of nuclear material and of certain categories of equipment and other material

  14. Design principles of nuclear receptor signaling: how complex networking improves signal transduction

    Science.gov (United States)

    Kolodkin, Alexey N; Bruggeman, Frank J; Plant, Nick; Moné, Martijn J; Bakker, Barbara M; Campbell, Moray J; van Leeuwen, Johannes P T M; Carlberg, Carsten; Snoep, Jacky L; Westerhoff, Hans V

    2010-01-01

    The topology of nuclear receptor (NR) signaling is captured in a systems biological graphical notation. This enables us to identify a number of ‘design' aspects of the topology of these networks that might appear unnecessarily complex or even functionally paradoxical. In realistic kinetic models of increasing complexity, calculations show how these features correspond to potentially important design principles, e.g.: (i) cytosolic ‘nuclear' receptor may shuttle signal molecules to the nucleus, (ii) the active export of NRs may ensure that there is sufficient receptor protein to capture ligand at the cytoplasmic membrane, (iii) a three conveyor belts design dissipating GTP-free energy, greatly aids response, (iv) the active export of importins may prevent sequestration of NRs by importins in the nucleus and (v) the unspecific nature of the nuclear pore may ensure signal-flux robustness. In addition, the models developed are suitable for implementation in specific cases of NR-mediated signaling, to predict individual receptor functions and differential sensitivity toward physiological and pharmacological ligands. PMID:21179018

  15. 10 CFR Appendix H to Part 110 - Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under NRC Export...

    Science.gov (United States)

    2010-01-01

    ... Equipment and Components Under NRC Export Licensing Authority H Appendix H to Part 110 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Pt. 110, App. H Appendix H to Part 110—Illustrative List of Electromagnetic Enrichment Plant Equipment and Components Under...

  16. Repository Surface Design Engineering Files Report Rev 00 ICN 1

    International Nuclear Information System (INIS)

    2001-01-01

    closure; changes, if any, are indicated on appropriate tables. (8) A description of a design concept for the complete retrieval and storage of waste packages, and summary-level engineering quantities for the construction and operation of this concept, is included as Attachment I; there are no changes that impact this report. (9) The concept for a 10,000 metric tons heavy metal (MTHM) Waste Staging Facility (Attachment II) has been deleted. The addition of four spent fuel assembly (SFA) staging pools in the Waste Handling Building (WHB) is described herein. (10) Description of a design concept for an on-site Cask Maintenance Facility to provide for shipping cask repair and recertification (Attachment III) is by reference to EF Rev 03; there are no changes that impact this report. (11) Figures that have changed for the SR effort are included in Attachment IV. Unchanged figures are referenced from EF Rev 03. (12) A preliminary design concept for dry vault inventory of commercial spent nuclear fuel to support thermal blending of spent fuel assemblies in waste packages has been added as Attachment V for this supplement

  17. Communications dated 15 and 22 March 1994 received from the permanent mission of South Africa to the International Atomic Energy Agency

    International Nuclear Information System (INIS)

    1994-01-01

    The Director General received notes verbales dated 15 and 22 March 1994 from the Permanent Mission of South Africa providing information on the nuclear export policies and practices of the Government of South Africa. These notes verbales contain, in their attachments, copies of the relevant legislation and other documentation pertaining to South Africa's policy to act in accordance with the provisions of INFCIRC/254/Rev.1/Part 1 and INFCIRC/254/Rev.1/Part 1/Mod.1 and INFCIRC/254/Rev.1/Part 2 as amended. The documents are available on request from the Secretariat of the IAEA

  18. Communications of 30 November 1995 received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-19

    The Director General has received notes verbales of 30 November 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, The Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments` Guidelines for transfers of nuclear-related dual-use equipment, material and related technology.

  19. Communications of 30 November 1995 received from certain Member States regarding guidelines for the export of nuclear material, equipment and technology

    International Nuclear Information System (INIS)

    1996-01-01

    The Director General has received notes verbales of 30 November 1995 from the Resident Representatives to the Agency of Argentina, Australia, Austria, Belgium, Bulgaria, Canada, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, the Republic of Korea, Luxembourg, The Netherlands, New Zealand, Norway, Poland, Portugal, Romania, the Slovak Republic, South Africa, Spain, Sweden, Switzerland, the United Kingdom of Great Britain and Northern Ireland and the United States of America relating to the export of nuclear material, equipment and technology. The purpose of the notes verbales is to provide further information on those Governments' Guidelines for transfers of nuclear-related dual-use equipment, material and related technology

  20. Nuclear proliferation. II. Monopoly or cartel

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Increasing competition between a growing number of nations exporting nuclear technology and recent exporting of full fuel-cycle facilities raise fears of nuclear proliferation and widespread nuclear weapons. As a result of the 1973 oil crisis, industrial nations seeking a share in the international nuclear market in order to protect their economic interests must also cooperate to protect these same interests from nuclear risks. Disagreement over the form of cooperation centers on the competing exporters' tactics of undercutting safeguards and political restrictions. Monopoly was never an option for even the United States. Government intervention in the international nuclear market in the form of subsidies and financial incentives is a more practical approach than a free market. A cartel arrangement is appropriate to nuclear energy in the sense of reducing economic uncertainties, but political objections would be strong and there would be some risk of independent nuclear development. As a strategy to forestall proliferation, however, the cartel can control exports of enrichment and reprocessing facilities and make it more expensive for nations to independently develop nuclear weapons. An enlargement of safeguards arrangements by nuclear suppliers will require nations to trade some of their economic interests in order to achieve international political objectives

  1. 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.

  2. 77 FR 73054 - Application for a License To Export Radioactive Waste

    Science.gov (United States)

    2012-12-07

    ... NUCLEAR REGULATORY COMMISSION Application for a License To Export Radioactive Waste Pursuant to 10 CFR 110.70(b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear..., October 25, 2012, XW020, radioactive 1178 pounds disposal by the 11006061. waste in the (approximately...

  3. Elecnuc. Nuclear power plants in the world

    International Nuclear Information System (INIS)

    2005-01-01

    This 2005 edition of the Elecnuc booklet summarizes in tables all numerical data relative to the nuclear power plants worldwide. These data come from the PRIS database managed by the IAEA. The following aspects are reviewed: 2004 highlights; main characteristics of reactor types; map of the French nuclear power plants on 2005/01/01; worldwide status of nuclear power plants at the end of 2004; units distributed by countries; nuclear power plants connected to the grid by reactor-type group; nuclear power plants under construction on 2004; evolution of nuclear power plant capacities connected to the grid; first electric generations supplied by a nuclear unit; electrical generation from nuclear power plants by country at the end 2004; performance indicator of PWR units in France; trend of the generation indicator worldwide; 2004 load factor by owners; units connected to the grid by countries at 12/31/2004; status of licence renewal applications in USA; nuclear power plants under construction at 12/31/2004; shutdown reactors; exported nuclear capacity in net MWe; exported and national nuclear capacity connected to the grid; exported nuclear power plants under construction or order; exported and national nuclear capacity under construction or order; recycling of plutonium in LWR; Mox licence plant projects; Appendix - historical development; acronyms, glossary

  4. Nuclear medicine. 4. new rev. and enl. ed.

    International Nuclear Information System (INIS)

    Kuwert, T.; Gruenwald, F.; Haberkorn, U.; Krause, T.

    2008-01-01

    The book on nuclear medicine is devided in three chapters: fundamentals, diagnostics and therapy. The topics within these chapters are the following: 1) fundamentals: molecular imaging; radiation physics, measuring technology and quality control; dosimetry and radiation effects; radiation protection, radiopharmaceutical chemistry; immonoassays and quality control. 2) diagnostics: endocrine organs; oncology; heart, vascular system and blood vessels; brain, lungs, skelton, kidneys, gastrointestine tract; infections; hematology. 3) radiotherapy; radiosynoviorothese; palliative bone pain therapy; radioimmunotherapy; 1 31I-MIBG therapy; therapy with receptor affine peptides; specific nuclear medical therapies

  5. Cdk1 Activates Pre-Mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem cells

    Science.gov (United States)

    Baffet, Alexandre D.; Hu, Daniel J.; Vallee, Richard B.

    2015-01-01

    Summary Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells, and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2, via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell cycle regulated, and identify the trigger mechanism for apical nuclear migration in the brain. PMID:26051540

  6. The effects of nuclear war. 2. rev. enl. ed.

    International Nuclear Information System (INIS)

    Rodejohann, J.

    1982-01-01

    Possible and probable effects of a nuclear war in Europe are described on the basis of a study by the Office of Technology Assessment, US Kongress ('The effects of nuclear war', Wash. D.C. 1979). (HP) [de

  7. Export Margins, Price and Quantity of Belarus’s Export Growth

    Directory of Open Access Journals (Sweden)

    Otamurodov Shavkat

    2017-03-01

    Full Text Available This paper examines the sources of Belarus’s export growth and decomposes export growth into extensive and intensive margins. This study also aims to determine export margins for intermediate and final goods and to determine the price and quantity components of the intensive export margin. In order to achieve the desired objectives, we use two methods for decomposing export growth, the count method and the export shares method. We analyse Belarus's export growth using export data at the HS-6 digit level for the 2004-2014 period. Our results show that Belarus's exports grew mainly due to growth in the price margin during the studied period 2004-2014. However, the extensive margin was important in export growth to some extent. Comparing the growth rate across final and intermediate goods reveals that although the share of final products in Belarus’s exports is not very big (18.9% in 2014, the average annual growth in exports of final products is higher than that of intermediate goods. Our investigation also shows that Belarus produces a wide range of commodities, but the share of the most of these commodities is not large; its exports depend on a restricted range of commodities. Moreover, most of the commodities are exported to Russia and Ukraine. Our results give us reason to assume that finding new markets for their new products is one of the main challenges for developing countries wishing to increase their exports by an extensive margin. This has important implications for how policy makers promote the trade and diversification of exports.

  8. The impact of management,technology and finance on export performance : analyzing the garment industry in Bangladesh

    OpenAIRE

    Muktadir, Zahid

    2012-01-01

    Masteroppgave i økonomi og administrasjon - Universitetet i Agder 2012 Drawing on resources-base view theory and approaching from quantitative field work, this study examines the three factors influencing the export performances of Bangladeshi Readymade Garments industries: Financial resources, Technology and managerial skill. This study also investigates the role of mediating effect in the relationship between factors and export performance. Most of the previous studies about export perfo...

  9. Role of the mRNA export factor Sus1 in oxidative stress tolerance in Candida albicans.

    Science.gov (United States)

    Xiao, Chenpeng; Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Dan; Li, Mingchun

    2018-02-05

    In eukaryotes, the nuclear export of mRNAs is essential for gene expression. However, little is known about the role of mRNA nuclear export in the important fungal pathogen, Candida albicans. In this study, we identified C. albicans Sus1, a nucleus-localized protein that is required for mRNA export. Interestingly, the sus1Δ/Δ displayed hyper-sensitivity to extracellular oxidative stress, enhanced ROS accumulation and severe oxidative stress-related cell death. More strikingly, although the mutant exhibited normal activation of the expression of oxidative stress response (OSR) genes, it had attenuated activity of ROS scavenging system, which may be attributed to the defect in OSR mRNA export in this mutant. In addition, the virulence of the sus1Δ/Δ was seriously attenuated. Taken together, our findings provide evidence that the mRNA export factor Sus1 plays an important role in oxidative stress tolerance and pathogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The physical protection of nuclear material

    International Nuclear Information System (INIS)

    1993-09-01

    Technical Committee met 21-25 June 1993 to consider changes to INFCIRC/225/Rev.2. The revised document, INFCIRC/225/Rev.3, reflects the Technical Committee recommendations for changes to the text as well as other modifications determined necessary to advance the consistency of the Categorization Table in INFCIRC/225/Rev.2 with the categorization table contained in The Convention of the Physical Protection of Nuclear Material and to reflect additional improvements presented by the experts. The recommendations presented in this IAEA document reflect a broad consensus among Member States on the requirements which should be met by systems for the physical protection of nuclear materials and facilities. It is hoped that they will provide helpful guidance for Member States

  11. The physical protection of nuclear material

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    Technical Committee met 21-25 June 1993 to consider changes to INFCIRC/225/Rev.2. The revised document, INFCIRC/225/Rev.3, reflects the Technical Committee recommendations for changes to the text as well as other modifications determined necessary to advance the consistency of the Categorization Table in INFCIRC/225/Rev.2 with the categorization table contained in The Convention of the Physical Protection of Nuclear Material and to reflect additional improvements presented by the experts. The recommendations presented in this IAEA document reflect a broad consensus among Member States on the requirements which should be met by systems for the physical protection of nuclear materials and facilities. It is hoped that they will provide helpful guidance for Member States.

  12. 75 FR 74104 - Request for a License To Export Radioactive Waste

    Science.gov (United States)

    2010-11-30

    ... NUCLEAR REGULATORY COMMISSION Request for a License To Export Radioactive Waste Pursuant to 10 CFR 110.70 (b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear..., August 27, Radioactive waste Not to exceed Return to two Germany. 2010, November 3, 2010, XW018...

  13. 77 FR 14445 - Application for a License To Export Steel Forging

    Science.gov (United States)

    2012-03-09

    ... NUCLEAR REGULATORY COMMISSION Application for a License To Export Steel Forging Pursuant to 10 CFR 110.70(b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear... head steel February 7, 2012 forging. forging will be XR175 machined into the 11005983 finished vessel...

  14. Performing Free Radioactive Certificate as an Effort to Protect Import and Export Commodities in Globalization Era

    International Nuclear Information System (INIS)

    Kunto-Wiharto; Syarbaini

    2001-01-01

    Several activities such as nuclear weapon tests, nuclear fuel reprocessing and nuclear accidents have caused radioactive contamination in local, regional and global environment. In globalization and free trade era, every country will be faced to the condition with the movable commodities from and to another countries. Global contamination through import and export commodities is a problem will be found every country in the future. Therefore, performing free radioactive certification on import and export commodities must be carried out to protect a member of public and environment from radioactive contamination. (author)

  15. Expression of the clock gene Rev-erbα in the brain controls the circadian organisation of food intake and locomotor activity, but not daily variations of energy metabolism

    NARCIS (Netherlands)

    Sen, Satish; Dumont, Stéphanie; Sage-Ciocca, Dominique; Reibel, Sophie; de Goede, Paul; Kalsbeek, Andries; Challet, Etienne

    2018-01-01

    The nuclear receptor REV-ERBα is part of the molecular clock mechanism and is considered to be involved in a variety of biological processes within metabolically active peripheral tissues as well. To investigate whether Rev-erbα (also known as Nr1d1) in the brain plays a role in the daily variations

  16. Changes in export-credit for a better French commercial offer

    International Nuclear Information System (INIS)

    Crepin, A.

    2016-01-01

    Financing cost is an important part of the total cost of a nuclear power plant and as a consequence plays a role in the competitiveness of a bid. The construction of a nuclear plant require huge investments and the possibility of offering a competitive credit is an important point to win market shares. Some countries like China and Russia propose a system in which both states can act as direct lender and can propose loans with very favorable interest rates. France has recently implemented a new export-credit system in which a loan over a very long period (construction period + 18 years) guaranteed by the French Export-Credit agency (COFACE) can be obtained complementing loans from commercial banks. (A.C.)

  17. Canadian electricity exports and imports : an energy market assessment

    International Nuclear Information System (INIS)

    2003-01-01

    This energy market assessment (EMA) report focuses on recent trends in exports and imports of Canadian electricity and the associated revenue and pricing. It also outlines major developments in electricity markets in Canada and the United States in the past decade with reference to the implications of electricity trade for both consumers and the power industry. This guide comes at a time of market openings in Alberta and Ontario, and with recent increases in applications to the National Energy Board for electricity exports and international power lines. The first chapter presents an overview of current Canadian federal regulatory regime for electricity exports and restructuring of the electric power industry in Canada and the United States. The second chapter reviews electricity exports and imports from a national perspective. Provincial analyses were presented in the third chapter which also covered international interconnections, export and import trends, export and import pricing, implications for consumer prices, and factors affecting future trade. The final chapter presents some observations on each of these issues. It is noted that exports have fluctuated significantly from year to year due to specific events including the shutdown of nuclear power plants, high gas prices, and the California electricity crisis in 2000-2001. Canadian international electricity trade has continued to yield net revenues of $1 to $2 billion per year due to strong electricity export prices. The relationship between export and import prices varies from province to province. Canadian utilities have emphasized the need for more transmission to the U.S. to foster future trade and improve transmission reliability. refs., tabs., figs

  18. A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism.

    Science.gov (United States)

    Visootsat, Akasit; Payungporn, Sunchai; T-Thienprasert, Nattanan P

    2015-12-01

    Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.

  19. Panel on nuclear export and proliferation

    International Nuclear Information System (INIS)

    Kimel, W.R.

    1977-01-01

    Summaries of six panelists' remarks make the following points: one cannot suppress nuclear weapons by suppressing nuclear power; a proliferated world would be extremely dangerous; US supports IAEA safeguards; plutonium shouldn't be recycled in power reactors; and the problem of nonproliferation is a social and institutional problem, not a technological one. Viewographs showing the semantics of proliferation, ways to get nuclear weapons materials, etc. are included

  20. Identification of critical regions in human SAMHD1 required for nuclear localization and Vpx-mediated degradation.

    Science.gov (United States)

    Guo, Haoran; Wei, Wei; Wei, Zhenhong; Liu, Xianjun; Evans, Sean L; Yang, Weiming; Wang, Hong; Guo, Ying; Zhao, Ke; Zhou, Jian-Ying; Yu, Xiao-Fang

    2013-01-01

    The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1) inhibits the infection of resting CD4+ T cells and myeloid cells by human and related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by promoting its proteasome-dependent degradation through an interaction with CRL4 (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the determinants in SAMHD1 that are required for Vpx-mediated degradation have not been well characterized. SAMHD1 contains a classical nuclear localization signal (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1. Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin-β1 and other nuclear proteins. We also determined that the linker region between the SAM and HD domain and the HD domain itself is important for Vpx-mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional nuclear targeting mechanism in addition to the classical NLS. Our data indicate that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation and that association with Vpx is not sufficient for Vpx-mediated degradation of SAMHD1. Since the linker region and HD domain may be involved in SAMHD1 multimerization, our results suggest that SAMHD1 multimerization may be required for Vpx-mediation degradation.

  1. Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

    International Nuclear Information System (INIS)

    Finnen, Renee L.; Johnston, Susan M.; Neron, Casey E.; Banfield, Bruce W.

    2011-01-01

    The alphaherpesvirus serine/threonine kinase Us3 plays diverse roles in virus multiplication and modifies both nuclear and cytoplasmic substrates. We recently reported that treatment of HSV-2 Us3-transfected and HSV-2-infected cells with leptomycin B, an inhibitor of nuclear export mediated by interaction of chromosomal regional maintenance protein (CRM1) with leucine rich nuclear export signals (NESs), resulted in nuclear trapping of Us3. Here, we utilized fluorescence loss in photobleaching to monitor nuclear export of HSV-2 Us3 and confirm that this process proceeds solely via a CRM1-mediated mechanism. Analysis of deletion derivatives of HSV-2 Us3 fused to a nuclear export reporter protein implicated the involvement of NES-like sequences in nuclear export. However, nuclear trapping of HSV-2 Us3 proteins carrying mutations in these potential NESs was not observed, indicating that these sequences are not functional in the context of full-length protein. Our analyses also revealed previously unidentified regions of HSV-2 Us3 that contribute to its kinase activity.

  2. Biologic activity of the novel orally bioavailable selective inhibitor of nuclear export (SINE) KPT-335 against canine melanoma cell lines

    Science.gov (United States)

    2014-01-01

    Background Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. Results We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1 messenger RNA. Lastly, KPT-335 treatment of cell lines upregulated the expression of both protein and mRNA for the tumor suppressor proteins p53 and p21, and promoted their nuclear localization. Conclusions KPT-335 demonstrates biologic activity against canine melanoma cell lines at physiologically relevant doses, suggesting that KPT-335 may represent a viable treatment option for dogs with malignant melanoma. PMID:25022346

  3. Analysis of mutagenic DNA repair in a thermoconditional mutant of Saccharomyces cerevisiae. IV. Influence of DNA replication and excision repair on REV2 dependent UV-mutagenesis and repair

    Energy Technology Data Exchange (ETDEWEB)

    Siede, W.; Eckardt, F.

    1986-01-01

    A double mutant being thermoconditionally defective in mutation induction as well as in repair of pre-lethal UV-induced DNA damage (rev2ts) and deficient in excision repair (rad3-2) was studied in temperature-shift experiments. The influence of inhibitors of DNA replication (hydroxyurea, aphidicolin) was determined. Additionally, an analysis of the dose-response pattern of mutation induction (mutation kinetics) at several ochre alleles was carried out. It was concluded that the UV-inducible REV2 dependent mutagenic repair process is not induced in excision-deficient cells. In excision-deficient cells, REV2 dependent mutation fixation is slow and mostly post-replicative though not dependent on DNA replication. The REV2 mediated mutagenic process could be separated from the repair function.

  4. Binding and thermodynamics of REV peptide-ctDNA interaction.

    Science.gov (United States)

    Upadhyay, Santosh Kumar

    2017-03-01

    The thermodynamics of DNA-ligand binding is important as it provides useful information to understand the details of binding processes. HIV-1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV-1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV-1 were investigated using spectroscopic (UV-visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a T m of 75.5 °C, whereas the ctDNA-REV peptide complex exhibited an incremental shift in the T m by 8 °C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B→Ψ transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr-bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA-REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K-308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low ΔH values indicating that the ctDNA-REV peptide interaction is driven largely by entropy. The heat capacity change (ΔC p ) was insignificant, an unusual finding in the area of DNA-peptide interaction studies. The variation in the values obtained for ΔH, ΔS, and ΔG with temperature further suggests that ctDNA-REV peptide interaction is entropically

  5. The calculational VVER burnup Credit Benchmark No.3 results with the ENDF/B-VI rev.5 (1999)

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Gual, Maritza [Centro de Tecnologia Nuclear, La Habana (Cuba). E-mail: mrgual@ctn.isctn.edu.cu

    2000-07-01

    The purpose of this papers to present the results of CB3 phase of the VVER calculational benchmark with the recent evaluated nuclear data library ENDF/B-VI Rev.5 (1999). This results are compared with the obtained from the other participants in the calculations (Czech Republic, Finland, Hungary, Slovaquia, Spain and the United Kingdom). The phase (CB3) of the VVER calculation benchmark is similar to the Phase II-A of the OECD/NEA/INSC BUC Working Group benchmark for PWR. The cases without burnup profile (BP) were performed with the WIMS/D-4 code. The rest of the cases have been carried with DOTIII discrete ordinates code. The neutron library used was the ENDF/B-VI rev. 5 (1999). The WIMS/D-4 (69 groups) is used to collapse cross sections from the ENDF/B-VI Rev. 5 (1999) to 36 groups working library for 2-D calculations. This work also comprises the results of CB1 (obtained with ENDF/B-VI rev. 5 (1999), too) and CB3 for cases with Burnup of 30 MWd/TU and cooling time of 1 and 5 years and for case with Burnup of 40 MWd/TU and cooling time of 1 year. (author)

  6. RevManHAL: towards automatic text generation in systematic reviews.

    Science.gov (United States)

    Torres Torres, Mercedes; Adams, Clive E

    2017-02-09

    Systematic reviews are a key part of healthcare evaluation. They involve important painstaking but repetitive work. A major producer of systematic reviews, the Cochrane Collaboration, employs Review Manager (RevMan) programme-a software which assists reviewers and produces XML-structured files. This paper describes an add-on programme (RevManHAL) which helps auto-generate the abstract, results and discussion sections of RevMan-generated reviews in multiple languages. The paper also describes future developments for RevManHAL. RevManHAL was created in Java using NetBeans by a programmer working full time for 2 months. The resulting open-source programme uses editable phrase banks to envelop text/numbers from within the prepared RevMan file in formatted readable text of a chosen language. In this way, considerable parts of the review's 'abstract', 'results' and 'discussion' sections are created and a phrase added to 'acknowledgements'. RevManHAL's output needs to be checked by reviewers, but already, from our experience within the Cochrane Schizophrenia Group (200 maintained reviews, 900 reviewers), RevManHAL has saved much time which is better employed thinking about the meaning of the data rather than restating them. Many more functions will become possible as review writing becomes increasingly automated.

  7. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    Science.gov (United States)

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

  8. HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Inae; Hur, Jung; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

    2015-01-30

    Highlights: • Wnt signaling as well as β-catenin overexpression enhance HuR cytoplasmic export. • HuR overexpression promotes cytoplasmic localization of β-catenin from the perinuclear fraction. • Wnt/β-catenin-mediated transcriptional activity is repressesed by HuR. - Abstract: β-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of β-catenin is a critical step for expressing target genes. β-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/β-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the β-catenin protein in the cytoplasm. Thus, Wnt/β-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic β-catenin functions related to HuR-mediated RNA metabolism in cancer cells.

  9. HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin

    International Nuclear Information System (INIS)

    Kim, Inae; Hur, Jung; Jeong, Sunjoo

    2015-01-01

    Highlights: • Wnt signaling as well as β-catenin overexpression enhance HuR cytoplasmic export. • HuR overexpression promotes cytoplasmic localization of β-catenin from the perinuclear fraction. • Wnt/β-catenin-mediated transcriptional activity is repressesed by HuR. - Abstract: β-Catenin is the key transcriptional activator of canonical Wnt signaling in the nucleus; thus, nuclear accumulation of β-catenin is a critical step for expressing target genes. β-Catenin accumulates in the nucleus of cancer cells where it activates oncogenic target genes. Hu antigen R (HuR) is a RNA binding protein that regulates multiple post-transcriptional processes including RNA stability. Thus, cytoplasmic HuR protein may be involved in tumorigenesis by stabilizing oncogenic transcripts, but the molecular mechanism remains unclear. Here, we observed that Wnt/β-catenin signaling induced export of the HuR protein, whereas HuR overexpression promoted accumulation of the β-catenin protein in the cytoplasm. Thus, Wnt/β-catenin-mediated transcriptional activity in the nucleus was reduced by overexpressing HuR. These results suggest novel and uncharacterized cytoplasmic β-catenin functions related to HuR-mediated RNA metabolism in cancer cells

  10. NUCLEAR NONPROLIFERATION: Concerns With the U.S. International Nuclear Materials Tracking System

    National Research Council Canada - National Science Library

    Rezendes, Victor

    1996-01-01

    ...) provide data to policymakers and other government officials. The United States regulates and controls its exports of civilian-use nuclear materials through three mechanisms-agreements for cooperation, export licenses, and subsequent arrangements...

  11. Identification of a functional nuclear export signal in the green fluorescent protein asFP499

    International Nuclear Information System (INIS)

    Mustafa, Huseyin; Strasser, Bernd; Rauth, Sabine; Irving, Robert A.; Wark, Kim L.

    2006-01-01

    The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified 194 LRMEKLNI 201 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES

  12. Organizing export strategies.

    OpenAIRE

    G. Lojacono; M. Venzin

    2014-01-01

    The article unfolds as follows: after a brief introduction on the relevance of international trade and the characteristics of export strategies, we describe four distinct archetypes: export manager, centralistic export developer, export skimmer, integrated export developer.

  13. 10 CFR 40.66 - Requirements for advance notice of export shipments of natural uranium.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Requirements for advance notice of export shipments of natural uranium. 40.66 Section 40.66 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE... natural uranium. (a) Each licensee authorized to export natural uranium, other than in the form of ore or...

  14. Scenarios for Russia's natural gas exports to 2050

    International Nuclear Information System (INIS)

    Paltsev, Sergey

    2014-01-01

    Russia is an important energy supplier as it holds the world's largest natural gas reserves and it is the world's largest exporter of natural gas. Despite a recent reduction in Russia's exports to Europe, it plans to build new pipelines. We explore the long-term (up to 2050) scenarios of Russian natural gas exports to Europe and Asia using the MIT Emissions Prediction and Policy Analysis (EPPA) model, a computable general equilibrium model of the world economy. We found that over the next 20–40 years natural gas can still play a substantial role in Russian exports and there are substantial reserves to support a development of the gas-oriented energy system both in Russia and in its current and potential gas importers. Based on the considered scenarios, Russia does not need any new pipeline capacity to the EU unless it wants to diversify its export routes to supply the EU without any gas transit via Ukraine and Belarus. Asian markets are attractive to Russian gas and substantial volumes may be exported there. Relatively cheap shale gas in China may sufficiently alter the prospects of Russian gas, especially in Asian markets. In the Reference scenario, exports of natural gas grow from Russia's current 7 Tcf to 11–12 Tcf in 2030 and 13–14 Tcf in 2050. Alternative scenarios provide a wider range of projections, with a share of Russian gas exports shipped to Asian markets rising to more than 30% by 2030 and almost 50% in 2050. Europe's reliance on LNG imports increases, while it still maintains sizable imports from Russia. - Highlights: • In the Reference scenario exports of natural gas grow from Russia’s current 7 Tcf to 11–12 Tcf in 2030 and 13–14 Tcf in 2050. • In alternative scenarios a share of Russian exports to Asian markets is rising to about 30% by 2030 and 50 % in 2050. • Cheap shale gas in China can sufficiently alter Russian natural gas export. • Reduction in nuclear generation in Europe can lead to increased exports of natural gas from

  15. Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus

    International Nuclear Information System (INIS)

    Claudiani, Pamela; Riano, Elena; Errico, Alessia; Andolfi, Gennaro; Rugarli, Elena I.

    2005-01-01

    Most cases of autosomal-dominant hereditary spastic paraplegia are linked to mutations in SPG4 encoding spastin, a protein involved in microtubule dynamics and membrane trafficking. In pyramidal neurons of the motor cortex and in immortalized motor neurons, spastin is localized to the synaptic terminals and growth cones. However, in other neurons and in proliferating cells spastin is prevalently nuclear. The mechanisms that determine targeting of spastin to the nucleus or the cytoplasm are unknown. We show here that the SPG4 mRNA is able to direct synthesis of two spastin isoforms, 68 and 60 kDa, respectively, through usage of two different translational start sites. Both isoforms are imported into the nucleus, but the 68-kDa isoform contains two nuclear export signals that efficiently drive export to the cytoplasm. Nuclear export is leptomycin-B sensitive. The cytoplasmic 68-kDa spastin isoform is more abundant in the brain and the spinal cord than in other tissues. Our data indicate that spastin function is modulated through usage of alternative translational start sites and active nuclear import and export, and open new perspectives for the pathogenesis of hereditary spastic paraplegia

  16. The physical protection of nuclear material and nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-06-01

    The latest review (1993) of this document was of limited scope and resulted in changes to the text of INFCIRC/225/Rev.2 designed to make the categorization table in that document consistent with the categorization table contained in the Convention on Physical Protection of Nuclear Materials. Consequently, a comprehensive review of INFCIRC/225 has not been conducted since 1989. Consequently, a meeting of national experts was convened from 2-5 June 1998 and from 27-29 October 1998 for a thorough review of INFCIRC/225/Rev.3. The revised document reflects the recommendations of the national experts to improve the structure and clarity of the document and to take account of improved technology and current international and national practices. In particular, a chapter has been added which provides specific recommendations related to sabotage of nuclear facilities and nuclear material. As a result of this addition, the title has been changed to 'The Physical Protection of Nuclear Material and Nuclear Facilities'. The recommendations presented in this IAEA document reflect a broad consensus among Member States on the requirements which should be met by systems for the physical protection of nuclear materials and facilities. It is hoped that they will provide helpful guidance for Member States.

  17. The physical protection of nuclear material and nuclear facilities

    International Nuclear Information System (INIS)

    1999-06-01

    The latest review (1993) of this document was of limited scope and resulted in changes to the text of INFCIRC/225/Rev.2 designed to make the categorization table in that document consistent with the categorization table contained in the Convention on Physical Protection of Nuclear Materials. Consequently, a comprehensive review of INFCIRC/225 has not been conducted since 1989. Consequently, a meeting of national experts was convened from 2-5 June 1998 and from 27-29 October 1998 for a thorough review of INFCIRC/225/Rev.3. The revised document reflects the recommendations of the national experts to improve the structure and clarity of the document and to take account of improved technology and current international and national practices. In particular, a chapter has been added which provides specific recommendations related to sabotage of nuclear facilities and nuclear material. As a result of this addition, the title has been changed to 'The Physical Protection of Nuclear Material and Nuclear Facilities'. The recommendations presented in this IAEA document reflect a broad consensus among Member States on the requirements which should be met by systems for the physical protection of nuclear materials and facilities. It is hoped that they will provide helpful guidance for Member States

  18. A Human Nuclear Shuttling Protein That Interacts with Human Immunodeficiency Virus Type 1 Matrix Is Packaged into Virions

    Science.gov (United States)

    Gupta, Kalpana; Ott, David; Hope, Thomas J.; Siliciano, Robert F.; Boeke, Jef D.

    2000-01-01

    Active nuclear import of the human immunodeficiency virus type 1 (HIV-1) preintegration complex (PIC) is essential for the productive infection of nondividing cells. Nuclear import of the PIC is mediated by the HIV-1 matrix protein, which also plays several critical roles during viral entry and possibly during virion production facilitating the export of Pr55Gag and genomic RNA. Using a yeast two-hybrid screen, we identified a novel human virion-associated matrix-interacting protein (VAN) that is highly conserved in vertebrates and expressed in most human tissues. Its expression is upregulated upon activation of CD4+ T cells. VAN is efficiently incorporated into HIV-1 virions and, like matrix, shuttles between the nucleus and cytoplasm. Furthermore, overexpression of VAN significantly inhibits HIV-1 replication in tissue culture. We propose that VAN regulates matrix nuclear localization and, by extension, both nuclear import of the PIC and export of Pr55Gag and viral genomic RNA during virion production. Our data suggest that this regulatory mechanism reflects a more global process for regulation of nucleocytoplasmic transport. PMID:11090181

  19. Evaluation of vaccination strategies against infection with feline immunodeficiency virus (FIV) based on recombinant viral vectors expressing FIV Rev and OrfA

    NARCIS (Netherlands)

    Huisman, W.; Schrauwen, E.J.A.; Tijhaar, E.; Süzer, Y.; Pas, S.D.; Amerongen, van G.; Sutter, G.; Rimmelzwaan, G.F.; Osterhaus, A.D.M.E.

    2008-01-01

    In recent years it has become clear that cell-mediated immunity is playing a role in the control of lentivirus infections. In particular, cytotoxic T lymphocyte responses have been associated with improved outcome of infection, especially those directed against the regulatory proteins like Rev and

  20. Export spillovers

    DEFF Research Database (Denmark)

    Choquette, Eliane; Meinen, Philipp

    2015-01-01

    This paper studies the importance of export spillovers in a firm's decision to enter specific export markets and extends the current state of the literature by assessing different mechanisms through which they may occur, namely (i) labour movement, (ii) intra-industry spillovers and (iii) inter......-industry linkages. We do so by exploiting a unique data set covering the universe of manufacturing firms in Denmark for the period 1995–2006 which combines transaction-level export data, firm accounting data, employer–employee linked data and information from yearly input–output tables. We corroborate...... the literature on export spillovers by presenting robust evidence of destination-specific export spillovers. The results suggest that labour mobility as well as intra- and inter-industry linkages (backward linkages) are important channels for export spillovers, while presenting heterogeneous effects across firms...