WorldWideScience

Sample records for nuclear localization signal-dependent

  1. The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features

    NARCIS (Netherlands)

    Gronwald, Carsten; Vegh, Vladimir; Hollmann, Markus W.; Hahnenkamp, Anke; Garaj, Vladimir; Hahnenkamp, Klaus

    2012-01-01

    Development of postoperative hyperalgesia depends on N-methyl-D-aspartate (NMDA) receptor activation. Local anesthetics protect against those hyperalgesic pain states and inhibit NMDA receptor activation. To outline what structural features of local anesthetics are responsible for NMDA receptor

  2. Extracellular signal-dependent nuclear import of STAT3 is mediated by various importin αs

    International Nuclear Information System (INIS)

    Ushijima, Ryosuke; Sakaguchi, Naoko; Kano, Arihiro; Maruyama, Atsushi; Miyamoto, Yoichi; Sekimoto, Toshihiro; Yoneda, Yoshihiro; Ogino, Kenji; Tachibana, Taro

    2005-01-01

    The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. STAT3 is activated by cytokines and growth factors via the phosphorylation of a tyrosine residue, dimerization, and subsequent nuclear translocation. However, the mechanism of its nuclear translocation is unclear. A study of the cytokine-stimulated import of STAT3 into the nucleus is reported herein. An oncostatin M (OSM)-dependent nuclear import assay system was first established in living cells. Using this system, we demonstrated that the microinjection of the importin α5/NPI-1 mutant, an anti-importin β antibody, and the RanQ69L mutant inhibited the nuclear import of STAT3. Second, we showed that tyrosine-phosphorylated STAT3 associates, not only with importin α5/NPI-1 but also with other importin αs, as a result of OSM stimulation, as evidenced by a solution binding assay. These findings suggest that the extracellular signal-dependent nuclear transport of STAT3 is mediated by various importin αs, importin β, and Ran

  3. The local community and the nuclear waste

    International Nuclear Information System (INIS)

    Lidskog, R.

    1998-01-01

    In this book social and political scientists discuss different aspects of the selection of a site for disposal of the Swedish nuclear waste. Special attention is given to the preliminary studies that have been performed at a few localities. The authors study the chain of events after a community is proposed for a site study. What powers are set in motion? How do different groups act in order to support or stop the study? Which is the role played by political parties, local environmentalist movements, media and experts? Why is there a forceful opposition in one community and not in another? Why does one local government invite the nuclear waste company to perform the study, while another refuses? The role of the local government has become crucial, since the nuclear waste company have chosen to perform studies only in municipalities that show a positive interest

  4. Localization of nuclear power plant technology

    International Nuclear Information System (INIS)

    Stiteler, F.Z.; Rudek, T.G.

    1998-01-01

    Asia, and particularly China, has an enormous need for power and must deal with the practicalities of building large base load units. In China, as in other countries, there are limitations on the use of large quantities of fossil fuel. This raises the possibility of turning to nuclear power to satisfy their energy needs. Other issues tend to point to the nuclear option for these growing economies, including economic considerations, environmental concerns, energy independence and raising the technological capabilities of the country. When a country embarks on a nuclear power program with the intention of localizing the technology, a long-term commitment is necessary to achieve this objective. Localization of nuclear technology is not a new phenomenon. The nature of the industry from the early beginnings has always involved transfer of technology when a new country initiated a nuclear power construction program. In fact, most previous experiences with this localization process involved heavy governmental, political and financial support to drive the success of the program. Because of this strong governmental support, only the receiving nation's companies were generally allowed to participate in the local business operations of the technology recipient. What is new and different today is the retreat from heavy financial support by the receiving country's government. This change has created a strong emphasis on cost-effectiveness in the technology transfer process and opportunities for foreign companies to participate in local business activities. ABB is a world-wide company with two parent companies that have been very active over many years in establishing cost-justified local operations throughout the world. Today, ABB has become the largest electrical engineering company in the world with respected local operations in nearly every country. Lessons learned by ABB in their world-wide localization initiatives are being applied to the challenge of cost

  5. Yeast proteins that recognize nuclear localization sequences

    OpenAIRE

    1989-01-01

    A variety of peptides can mediate the localization of proteins to the nucleus. We have identified yeast proteins of 70 and 59 kD that bind to nuclear localization peptides of SV-40 T antigen, Xenopus nucleoplasmin, and the yeast proteins Ga14 and histone H2B. These proteins are assayed by the binding of peptide-albumin conjugates to proteins immobilized on nitrocellulose filters. These binding proteins fractionate with nuclei and are extractable with salt but not detergent. Radiolabeled pepti...

  6. Nuclear technologies for local energy systems

    International Nuclear Information System (INIS)

    McDonnell, F.N.; Lynch, G.F.

    1990-03-01

    If nuclear energy is to realize its full potential as a safe and cost-effective alternative to fossil fuels, applications beyond those that are currently being serviced by large, central nuclear power stations must be identified and appropriate reactors developed. The Canadian program on reactor systems for local energy supply is at the forefront of these developments. This program emphasizes design simplicity, low power density and fuel rating, reliance on natural processes, passive systems, and reduced reliance on operator action. The first product, the SLOWPOKE Energy System, is a 10 MW heat source specifically designed to provide hot water to satisfy the needs of local heating systems for building complexes, institutions and municipal district heating systems. A demonstration heating reactor has been constructed at the Whiteshell Nuclear Research Establishment in Manitoba and has been undergoing an extensive test program since first operation in 1987 July. Based on the knowledge learned from the design, construction, licensing and operational testing of this facility, the design of the 10 MW commercial-size unit is well advanced, and Atomic Energy of Canada Limited is prepared to commit the construction of the first commercial unit. Although the technical demonstration of the concept is important, it is recognized that another crucial element is the public and regulatory acceptance of small nuclear systems in urban areas. The decision by a community to commit the construction of a SLOWPOKE Energy System brings to a sharp focus the current public apprehension about nuclear technologies

  7. Exploring Localization in Nuclear Spin Chains

    Science.gov (United States)

    Wei, Ken Xuan; Ramanathan, Chandrasekhar; Cappellaro, Paola

    2018-02-01

    Characterizing out-of-equilibrium many-body dynamics is a complex but crucial task for quantum applications and understanding fundamental phenomena. A central question is the role of localization in quenching thermalization in many-body systems and whether such localization survives in the presence of interactions. Probing this question in real systems necessitates the development of an experimentally measurable metric that can distinguish between different types of localization. While it is known that the localized phase of interacting systems [many-body localization (MBL)] exhibits a long-time logarithmic growth in entanglement entropy that distinguishes it from the noninteracting case of Anderson localization (AL), entanglement entropy is difficult to measure experimentally. Here, we present a novel correlation metric, capable of distinguishing MBL from AL in high-temperature spin systems. We demonstrate the use of this metric to detect localization in a natural solid-state spin system using nuclear magnetic resonance (NMR). We engineer the natural Hamiltonian to controllably introduce disorder and interactions, and observe the emergence of localization. In particular, while our correlation metric saturates for AL, it slowly keeps increasing for MBL, demonstrating analogous features to entanglement entropy, as we show in simulations. Our results show that our NMR techniques, akin to measuring out-of-time correlations, are well suited for studying localization in spin systems.

  8. Local economic impact of nuclear power

    International Nuclear Information System (INIS)

    Shurcliff, A.W.

    1977-01-01

    The local economic impact of nuclear installations is examined and the conclusion reached that much of the subsequent area growth may be coincidental to the facility. Nuclear siting criteria favor proximity to a regional power grid, abundant water for cooling, and extensive vacant land with a major access road. These criteria coincide with the characteristics of commuter suburbs, centers for retirement, and recreation areas. Clustering of nuclear units introduces an extraordinary level of new construction, office requirements, and capital. Economic changes will occur at the start and completion of the construction stage and at the time of decommissioning the facility. Past experiences are detailed in terms of employment, payroll, housing, public services, and procurement. When construction is completed, employment falls to a relatively low level. Proximity to the plant offers no advantage in terms of local power rates. While nuclear facilities do not preclude other development in the area, there are restrictions on access, regulatory agencies may reject absorbing the cost of public use as a business expense in the rate structure, and security measures may constrain public use. There is pressure for tax equalization laws to compensate communities for the loss of potential property tax revenues. Some agencies (e.g., the Tennessee Valley Authority) make in-lieu-of-tax payments, while some plants have produced tax benefits large enough to effect significant public improvements. 8 references

  9. Unattended nuclear systems for local energy supply

    International Nuclear Information System (INIS)

    Lynch, G.F.; Bancroft, A.R.; Hilborn, J.W.; McDougall, D.S.; Ohta, M.M.

    1988-02-01

    This paper describes recent developments in a small nuclear heat and electricity production system - the SLOWPOKE Energy System - that make it possible to locate the system close to the load, and that could have a major impact on local energy supply. The most important unique features arising from these developments are walk-away safety and the ability to operate in an unattended mode. Walk-away safety means that radiological protection is provided by intrinsic characteristics and does not depend on either engineered safety systems or operator intervention. This, in our view, is essential to public acceptance. The capability for unattended operation results from self-regulation; however, the performance can be remotely monitored. The SLOWPOKE Energy System consists of a water-filled pool, operating at atmospheric pressure, which cools and moderates a beryllium-reflected thermal reactor that is fuelled with 100 to 400 kg of low-enriched uranium. The pool water also provides shielding from radioactive materials trapped in the fuel. Heat is drawn from the pool and transferred either to a building hot-water distribution system or to an organic liquid which is converted to vapour to drive a turbine-generator unit. Heating loads between 2 qnd 10 MWt, and electrical loads up to 1 MWe can be satisfied. SLOWPOKE is a dramatic departure from conventional nuclear power reactors. Its nuclear heat source is intrinsically simple, having only one moving part: a solid neutron absorber which is slowly withdrawn from the reactor to balance the fuel burnup. Its power is self-regulated and excessive heat production cannot occur, even for the most severe combinations of system failure. Cooling of the fuel is assured by natural physical processes that do not depend on mechanical components such as pumps. These intrinsic characteristics assure public safety and ultra high reliability

  10. Unattended nuclear systems for local energy supply

    International Nuclear Information System (INIS)

    Lynch, G.F.; Bancroft, A.R.; Hilborn, J.W.; McDougall, D.S.; Ohta, M.M.

    1986-10-01

    This paper describes recent developments in a small nuclear heat and electricity production system - the SLOWPOKE energy system - that make it possible to locate the system close to the load, and that could have a major impact on local energy supply. The most important unique features arising from these developments are walk-away safety and the ability to operate in an unattended mode. Walk-away safety means that radiological protection is provided by intrinsic characteristics and does not depend on either engineered safety systems or operator intervention. This, in our view, is essential to public acceptance. The capability for unattended operation results from self-regulation, however the performance can be remotely monitored. The SLOWPOKE energy system consists of a water-filled pool, operating at atmospheric pressure, which cools and moderates a beryllium-reflected thermal reactor that is fuelled with 100 to 400 kg of low enriched uranium. The pool water also provides shielding from radioactive materials trapped in the fuel. Heat is drawn from the pool and transferred either to a building hot-water distribution system or to an organic liquid which is converted to vapour to drive a turbine-generator unit. Heating loads between 2 and 10 MWt, and electrical loads up to 1 MWe can be satisfied. SLOWPOKE is a dramatic departure from conventional nuclear power reactors. Its nuclear heat source is intrinsically simple, having only one moving part: a solid neutron absorber which is slowly withdrawn from the reactor to balance the fuel burnup. Its power is self-regulated and excessive heat production cannot occur, even for the most severe combinations of system failure. Cooling of the fuel is assured by natural physical processes that do not depend on mechanical components such as pumps. These intrinsic characteristics assure public safety and ultra high reliability. (author)

  11. Local competence building and public information in European nuclear territories

    International Nuclear Information System (INIS)

    Martell, Meritxell; Vila D'Abadal, Maria

    2010-01-01

    Opinion polls and case study analysis show that there is a strong public demand for more participation in decision-making processes relating to the environment and nuclear issues specifically (IGNA, 2007; EC DG TREN 2008). In this regard, the implementation of transparency and participation at local level in municipalities hosting nuclear facilities is being claimed by local representatives over Europe. The pilot project 'Local Competence Building and Public Information in European Nuclear Territories' (2007-2008) was promoted by the Group of European Municipalities with Nuclear Facilities (GMF) and partly financed by the Directorate General for Energy and Transport (DG TREN). The project aims at supporting the European Commission (EC) in the process of harmonising national practices in the field of governance in nuclear territories. The objectives of this pilot project were two-fold: firstly, to identify local good practices at European level with regards to governance in the nuclear field and, secondly, to provide a methodological framework to recommend good practices and establish a set of indicators. The results of the project are briefly explained under the five dimensions of local governance on nuclear matters: access to environmental information, participation, access to justice, competence building and local development. Firstly, access to information on nuclear issues is broadly acknowledged by local representatives to be of relevant importance in increasing public knowledge on nuclear issues, especially on nuclear safety and radiation protection. Secondly, most local representatives feel that the current participatory level on nuclear issues in municipalities is too low and they would appreciate a greater involvement of local communities in decision-making processes on nuclear issues through local commissions or other mechanisms. Thirdly, according to local authorities, access to justice should be provided not only for the public but also for themselves

  12. Practical signal-dependent noise parameter estimation from a single noisy image.

    Science.gov (United States)

    Liu, Xinhao; Tanaka, Masayuki; Okutomi, Masatoshi

    2014-10-01

    The additive white Gaussian noise is widely assumed in many image processing algorithms. However, in the real world, the noise from actual cameras is better modeled as signal-dependent noise (SDN). In this paper, we focus on the SDN model and propose an algorithm to automatically estimate its parameters from a single noisy image. The proposed algorithm identifies the noise level function of signal-dependent noise assuming the generalized signal-dependent noise model and is also applicable to the Poisson-Gaussian noise model. The accuracy is achieved by improved estimation of local mean and local noise variance from the selected low-rank patches. We evaluate the proposed algorithm with both synthetic and real noisy images. Experiments demonstrate that the proposed estimation algorithm outperforms the state-of-the-art methods.

  13. New nuclear plant development - balancing localization with competitiveness

    International Nuclear Information System (INIS)

    Caplan, M.; Thompson, T.S.

    2014-01-01

    Nuclear power plants are large infrastructure projects that require government support and approval. This paper will highlight and contrast the larger, mostly government-desired, nuclear program localization objectives with the more utility-specific requirements for successful project implementation. Governments are concerned about sustainable industrial development, particularly manufacturing, and job creation while utilities are focused on delivering reliable electricity to consumers at the lowest cost. Numerous countries emphasize local content as a key requirement when procuring a station. For countries like China and Korea that have large programs, their strategy has been to localize to the point of having their own indigenous design. However, developing a workable localization strategy that truly benefits the local economy for others including existing nuclear markets like Canada, the UK, South Africa and Brazil as well as in newly developing markets such as Vietnam and Malaysia is more challenging. These countries may not look to indigenize a new design, rather they would localize elements of the nuclear program that best fit their strengths. The paper will discuss the issues related to developing successful localization and industrialization strategies in a changing nuclear world. (author)

  14. New nuclear plant development - balancing localization with competitiveness

    Energy Technology Data Exchange (ETDEWEB)

    Caplan, M.; Thompson, T.S. [MZ Consulting Inc., ON (Canada)

    2014-07-01

    Nuclear power plants are large infrastructure projects that require government support and approval. This paper will highlight and contrast the larger, mostly government-desired, nuclear program localization objectives with the more utility-specific requirements for successful project implementation. Governments are concerned about sustainable industrial development, particularly manufacturing, and job creation while utilities are focused on delivering reliable electricity to consumers at the lowest cost. Numerous countries emphasize local content as a key requirement when procuring a station. For countries like China and Korea that have large programs, their strategy has been to localize to the point of having their own indigenous design. However, developing a workable localization strategy that truly benefits the local economy for others including existing nuclear markets like Canada, the UK, South Africa and Brazil as well as in newly developing markets such as Vietnam and Malaysia is more challenging. These countries may not look to indigenize a new design, rather they would localize elements of the nuclear program that best fit their strengths. The paper will discuss the issues related to developing successful localization and industrialization strategies in a changing nuclear world. (author)

  15. Understanding local residents of Korea using nuclear effective safety

    International Nuclear Information System (INIS)

    Chung, Yun Hyung; Lee, Gey Hwi; Hah, Yeonhee; Kim, Beom Jun

    2010-01-01

    The risk perception gap between experts and lay people is based on the use of different concept on risk. It is getting increasingly important for nuclear practitioners to understand the lay people's subjective perception on nuclear safety. We proposed the nuclear effective safety index (NESI) which is based on data of the public survey of local inhabitants. We extracted the four factors for effective safety indicators; communication, trust, plant emergency response capability, and personal emergency coping skills. The latest NESI was 41.54, which was increased from 38.22 but still low. The three-year data of NESI showed the differences between genders and between sites as well as trend. The survey of antecedents of effective safety showed some meaningful events and profound differences between plant employees and local inhabitants. The NESI can be utilized as useful communication tool between the local inhabitants and nuclear practitioners. (authors)

  16. Spatial localization in nuclear magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Keevil, Stephen F

    2006-01-01

    The ability to select a discrete region within the body for signal acquisition is a fundamental requirement of in vivo NMR spectroscopy. Ideally, it should be possible to tailor the selected volume to coincide exactly with the lesion or tissue of interest, without loss of signal from within this volume or contamination with extraneous signals. Many techniques have been developed over the past 25 years employing a combination of RF coil properties, static magnetic field gradients and pulse sequence design in an attempt to meet these goals. This review presents a comprehensive survey of these techniques, their various advantages and disadvantages, and implications for clinical applications. Particular emphasis is placed on the reliability of the techniques in terms of signal loss, contamination and the effect of nuclear relaxation and J-coupling. The survey includes techniques based on RF coil and pulse design alone, those using static magnetic field gradients, and magnetic resonance spectroscopic imaging. Although there is an emphasis on techniques currently in widespread use (PRESS, STEAM, ISIS and MRSI), the review also includes earlier techniques, in order to provide historical context, and techniques that are promising for future use in clinical and biomedical applications. (topical review)

  17. Src nuclear localization and its prognostic relevance in human osteosarcoma.

    Science.gov (United States)

    Urciuoli, Enrica; Coletta, Ilenia; Rizzuto, Emanuele; De Vito, Rita; Petrini, Stefania; D'Oria, Valentina; Pezzullo, Marco; Milano, Giuseppe Maria; Cozza, Raffaele; Locatelli, Franco; Peruzzi, Barbara

    2018-02-01

    Osteosarcoma is the most common malignant bone tumor in children and young adults. The identification of proteins which exhibit different subcellular localization in low- versus high-risk osteosarcoma can be instrumental to obtain prognostic information and to develop innovative therapeutic strategies. Beside the well-characterized membrane and cytoplasmic localization of Src protein, this study evaluated the prognostic relevance of its so-far unknown nuclear compartmentalization. We analyzed the subcellular distribution of total and activated (pY418) Src in a tissue microarray including 60 osteosarcoma samples. Immunohistochemical analyses revealed a variable pattern of Src expression and localization, ranging from negative to high-stained nuclei combined with a substantial cytoplasmic staining for total and activated forms. The analysis of Kaplan-Meier survival curves in relationship to the diverse permutations of cytoplasmic and nuclear staining suggested a correlation between Src subcellular localization and the overall survival (OS) of osteosarcoma patients. In order to explain this different subcellular localization, normal osteoblasts and three osteosarcoma cell lines were used to investigate the molecular mechanism. Once confirmed a variable Src localization also in these cell lines, we demonstrated a correlation between the N-myristoyltransferase enzymes expression and activity and the Src nuclear content. In conclusion, these results described a so-far unknown Src nuclear localization in osteosarcoma cells, suggesting that the combined detection of nuclear and cytoplasmic Src levels can be used as a prognostic marker for osteosarcoma patient survival. A correlation between the N-myristoyltransferase enzymes and the Src subcellular localization was described as well. © 2017 Wiley Periodicals, Inc.

  18. Initial operations in local nuclear emergency response headquarter

    International Nuclear Information System (INIS)

    2012-06-01

    As a result of the Fukushima nuclear accident due to the Great East Japan Earthquake and the tsunami that occurred thereafter, local nuclear emergency response headquarters (local headquarters) was set up at off-site center (OFC). However, several obstacles such as the collapse of means of communication resulting from severed communication lines, food and fuel shortage resulting from stagnant physical distribution, and increasing radiation dose around the center significantly restricted originally intended operation of local headquarters. In such severe situation, the personnel gathered at the OFC from the government, local public bodies and electric companies from March 11 to 15 acted without sufficient food, sleep or rest and did all they could against successively occurring unexpected challenges by using limited means of communication. However, issues requiring further consideration were activities of each functional group, location of OFC and the functions of equipment, machines and materials and reflecting the consideration results into future protective measures and revision of the manual for nuclear emergency response were greatly important. This report described investigated results on initial operations in local headquarters such as situation of activities conducted by local headquarters and operations at functional groups. (T. Tanaka)

  19. The ANCLI White Paper on Local Governance of Nuclear Sites

    International Nuclear Information System (INIS)

    Delalonde, Jean-Claude; Demet, Michel; Gadbois, Serge; Heriard Dubreuil, Gilles

    2006-01-01

    The 1981 circular, 'Information Commissions attached to Power Stations', was an important regulatory step, which enabled local communities to come together to discuss nuclear issues with the site operators and official inspectorates. However the Local Information Commissions (CLI), have encountered numerous obstacles, both practical and legislative, in fulfilling their role as information providers and, particularly, as monitors. It is now acknowledged in France both by members of commissions at local level and by public authorities that CLI would benefit from a more statutory role in the decision-making process as well as from a specific legal statute associated with independent resources. The forthcoming Nuclear Safety and Transparency Bill should establish a new legal and institutional framework for local commissions. The National Association of CLI (ANCLI) gathers and represents the CLI at national level. In Spring 2005, in the perspective of the Nuclear Safety and Transparency bill, the ANCLI initiated a participatory process involving about 30 delegates from a dozen CLI (elected representatives, NGOs, local experts) in order to raise a common expertise and make recommendations on this new legal statute, on the basis of their own return of experience. The White Paper is structured around four main subject areas: Structure and status of CLIs, local powers; - Role of CLIs and ANCLI in the national and international decision-making process; Local communities' access to specialist expertise; and Waste management. The CLIs reaffirm their local powers and ability to best assure the continued monitoring of nuclear sites and any other nuclear issues in their area. In particular, this local authority allows them to balance different risks as well as political and economic decisions which have a bearing on their region's future. It implies a certain autonomy on the part of CLIs in the exercise of their scrutiny functions, evaluating all the factors impacting both on the

  20. Regulation of Nuclear Localization of Signaling Proteins by Cytokinin

    Energy Technology Data Exchange (ETDEWEB)

    Kieber, J.J.

    2010-05-01

    Cytokinins are a class of mitogenic plant hormones that play an important role in most aspects of plant development, including shoot and root growth, vascular and photomorphogenic development and leaf senescence. A model for cytokinin perception and signaling has emerged that is similar to bacterial two-component phosphorelays. In this model, binding of cytokinin to the extracellular domain of the Arabidopsis histidine kinase (AHKs) receptors induces autophosphorylation within the intracellular histidine-kinase domain. The phosphoryl group is subsequently transferred to cytosolic Arabidopsis histidine phosphotransfer proteins (AHPs), which have been suggested to translocate to the nucleus in response to cytokinin treatment, where they then transfer the phosphoryl group to nuclear-localized response regulators (Type-A and Type-B ARRs). We examined the effects of cytokinin on AHP subcellular localization in Arabidopsis and, contrary to expectations, the AHPs maintained a constant nuclear/cytosolic distribution following cytokinin treatment. Furthermore, mutation of the conserved phosphoacceptor histidine residue of the AHP, as well as disruption of multiple cytokinin signaling elements, did not affect the subcellular localization of the AHP proteins. Finally, we present data indicating that AHPs maintain a nuclear/cytosolic distribution by balancing active transport into and out of the nucleus. Our findings suggest that the current models indicating relocalization of AHP protein into the nucleus in response to cytokinin are incorrect. Rather, AHPs actively maintain a consistent nuclear/cytosolic distribution regardless of the status of the cytokinin response pathway.

  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. Nuclear materials transportation workshops: USDOE outreach to local governments

    International Nuclear Information System (INIS)

    1987-01-01

    To provide direct outreach to local governments, the Transportation Management Division of the United States Department of Energy asked the Urban Consortium and its Energy Task Force to assemble representatives for two workshops focusing on the transport of nuclear materials. The first session, for jurisdictions east of the Mississippi River, was held in New Orleans on May 5--6, 1988; the second was conducted on June 6--7, 1988 in Denver for jurisdictions to the west. Twenty local government professionals with management or operational responsibility for hazardous materials transportation within their jurisdictions were selected to attend each workshop. The discussions identified five major areas of concern to local government professionals; coordination; training; information resources; marking and placarding; and responder resources. Integrated federal, state, and local levels of government emerged as a priority coordination issue along with the need for expanded availability of training and training resources for first-reponders

  3. An N-terminal nuclear localization sequence but not the calmodulin-binding domain mediates nuclear localization of nucleomorphin, a protein that regulates nuclear number in Dictyostelium

    International Nuclear Information System (INIS)

    Myre, Michael A.; O'Day, Danton H.

    2005-01-01

    Nucleomorphin is a novel nuclear calmodulin (CaM)-binding protein (CaMBP) containing an extensive DEED (glu/asp repeat) domain that regulates nuclear number. GFP-constructs of the 38 kDa NumA1 isoform localize as intranuclear patches adjacent to the inner nuclear membrane. The translocation of CaMBPs into nuclei has previously been shown by others to be mediated by both classic nuclear localization sequences (NLSs) and CaM-binding domains (CaMBDs). Here we show that NumA1 possesses a CaMBD ( 171 EDVSRFIKGKLLQKQQKIYKDLERF 195 ) containing both calcium-dependent-binding motifs and an IQ-like motif for calcium-independent binding. GFP-constructs containing only NumA1 residues 1-129, lacking the DEED and CaMBDs, still localized as patches at the internal periphery of nuclei thus ruling out a direct role for the CaMBD in nuclear import. These constructs contained the amino acid residues 48 KKSYQDPEIIAHSRPRK 64 that include both a putative bipartite and classical NLS. GFP-bipartite NLS constructs localized uniformly within nuclei but not as patches. As with previous work, removal of the DEED domain resulted in highly multinucleate cells. However as shown here, multinuclearity only occurred when the NLS was present allowing the protein to enter nuclei. Site-directed mutation analysis in which the NLS was changed to 48 EF 49 abolished the stability of the GFP fusion at the protein but not RNA level preventing subcellular analyses. Cells transfected with the 48 EF 49 construct exhibited slowed growth when compared to parental AX3 cells and other GFP-NumA1 deletion mutants. In addition to identifying an NLS that is sufficient for nuclear translocation of nucleomorphin and ruling out CaM-binding in this event, this work shows that the nuclear localization of NumA1 is crucial to its ability to regulate nuclear number in Dictyostelium

  4. Incorporating signal-dependent noise for hyperspectral target detection

    Science.gov (United States)

    Morman, Christopher J.; Meola, Joseph

    2015-05-01

    The majority of hyperspectral target detection algorithms are developed from statistical data models employing stationary background statistics or white Gaussian noise models. Stationary background models are inaccurate as a result of two separate physical processes. First, varying background classes often exist in the imagery that possess different clutter statistics. Many algorithms can account for this variability through the use of subspaces or clustering techniques. The second physical process, which is often ignored, is a signal-dependent sensor noise term. For photon counting sensors that are often used in hyperspectral imaging systems, sensor noise increases as the measured signal level increases as a result of Poisson random processes. This work investigates the impact of this sensor noise on target detection performance. A linear noise model is developed describing sensor noise variance as a linear function of signal level. The linear noise model is then incorporated for detection of targets using data collected at Wright Patterson Air Force Base.

  5. Nuclear waste information in supplements of local newspapers

    International Nuclear Information System (INIS)

    Ryhaenen, Veijo

    1995-01-01

    Full text: The utility Teollisuuden Voima Oy (TVO) is conducting site investigations in Finland to select a final disposal site for spent nuclear fuel. Site selection studies, including deep drillings and other field investigations, have been carried out in different parts of the country since 1987. Now there are three areas in which detailed studies are continued. The programme aims at site selection in the year 2000. Before the construction of the final disposal facility can be started around the year 2010 a precondition in the Finnish legislation is that the council of the local municipality accepts the facility. Hence, an essential task is to distribute information of the studies and of the principles of final disposal to the local decision-makers and public. Information work has an important role already now in order to make people familiar with the long-term project and to build confidence on the safety of final disposal. TVO's information programme includes several types of actions to different target groups, such as press conferences, contact group meetings, open houses, exhibitions, lectures to different groups, visits to the drilling sites and to the existing nuclear waste facilities as well as use of various written material. In January 1994 a new method was applied in the distribution of TVO's written information directly to local public. Four-page supplements were prepared to the local newspapers to inform public of the stage of the site investigations and other topical issues. After that, new supplements have been published in six months intervals. Own supplements have been made for different municipalities in which the candidate areas are situated. The form of the supplement is same as that of the newspaper. As a matter of fact, TVO's information forms a special advertising section in a single issue of a newspaper. The topics handled in the supplements are for example present status of the local bedrock studies, other topical information of TVO

  6. Local environment of zirconium in nuclear gels studied by XAS

    International Nuclear Information System (INIS)

    Pelegrin, E.; Ildefonse, Ph.; Calas, G.; Ricol, St.; Flank, A.M.

    1997-01-01

    During lixiviation experiments, nuclear gels are formed and heavy metals are retained. In order to understand this retardation mechanisms, we performed an analysis of the local environment of Zr in parent glasses and derived alteration gels both at the Zr-L II,III , and Zr-K edges. Calibration of the method was conducted through the analysis of model compounds with known coordination number (CN): catapleite Na 2 ZrSi 3 O 9 ,2H 2 O (CN=6), baddeleyite ZrO 2 (CN=7) and zircon SiZrO 4 (CN=8). Nuclear glasses (R7T7, and a simplified nuclear glass V 1) and gels obtained at 90 deg C, with leaching times from 7 to 12 months and with solution renewal. were also investigated (GR7T7R and GV1). Zr-L II,III XANES spectra evidenced that zirconium is 6-fold coordinated in R7T7 and V1 nuclear glasses. For GR7T7R and GV1 gels, Zr local environment is significantly changed, and a mixture of CN (6 and 7J has been evidenced. Quantitative structural results were derived from EXAFS analysis at Zr-K edge. In parent glasses, derived Zr-O distance is 2.10±0.01 10 -10 m, and is in the range Zr-O distances for octahedral coordination in model compounds. In both gels studied, Zr-O distances increase significantly up to 2.15 ±0.01 10 -10 m. This distance is close to that known in baddeleyite (2,158 10 -10 m). A better understanding of the Zr retention mechanism has to be made by studying the second neighbors contributions. (authors)

  7. INTERNATIONAL TECHNOLOGY TRANSFER AND LOCALIZATION: SUCCESS STORIES IN NUCLEAR BRANCH

    Directory of Open Access Journals (Sweden)

    Yulia V. Chernyakhovskaya

    2016-01-01

    Full Text Available countries are considering nuclear power industry development [2, p. 3; 3, p. 3; 4]. For newcomer-countries it is of great importance to stimulate the national industry through NPP projects implementation based on technology transfer and localization (TTL. The study and systematization of world experience is useful in purpose to elaborate the national industry development programs. Objectives. The aim of article is to determine success factors of TTL; tasks: 1 to study TTL international experience in the fi eld of nuclear power technologies; 2 on the ground of the world practice to analyze preconditions, contents, stages, arrangement modes, formats and results of TTL. Methods. The following methods are utilized in the study: analysis and synthesis including problem-chronological, cause and eff ect and logical analysis and historical-diachronic method (method of periodization. Results. The following conclusions presented below have been made on the basis of the three cases study related to nuclear industry development using TTL (France, South Korea and China. Conclusions. The TTL success factors includes: Government support that provides long-term governmental development plan of nuclear power and industry for nuclear power based on TTL, and an appropriate international cooperation (under favorable conditions of “NPP buyers market”; Complex approach to implementation of the national TTL program and NPP construction projects: signing of NPP construction contracts with vendors stipulating technology transfer; NPP designing and constructing should be performed jointly with training and transferring of technical documentation and software. Technology transfer cooperation should be implemented through the licenses agreements and setting up joint ventures; Public acceptance and support.

  8. Restoration of mammographic images in the presence of signal-dependent noise

    Science.gov (United States)

    Aghdasi, Farzin; Ward, Rabab K.; Palcic, Branko

    1993-07-01

    We developed and implemented two locally adaptive image smoothing filters to improve the signal to noise ratio of digitized mammogram images. The application of these smoothing filters in conjunction with the deconvolution of the images results in better visualization of image details. Previous efforts in restoration of digitized mammograms have assumed a stationary image with uncorrelated white Gaussian noise. In this work we considered a more realistic case of a non-stationary image model and signal-dependent noise of photonic and film-grain origins. Both the camera blur and the MTF of the screen-film combination were considered. The camera noise may be minimized through averaging and background subtraction. The signal-dependent nature of the radiographic noise was modelled by a linear shift-invariant system and the relative strengths of various noise sources were compared. The deconvolution filter was designed to respond to the particular form of the noise in the system based on the Minimum Mean Squared Error (MMSE) criteria. Of the two smoothing filters the Bayesian estimator was found to outperform the adaptive Wiener filter. Filters were implemented in a real time processing environment using our mammographic image acquisition and analysis system.

  9. Early localization of NPA58, a rat nuclear pore-associated protein

    Indian Academy of Sciences (India)

    We have studied the mitotic reassembly of the nuclear envelope, using antibodies to nuclear marker proteins and NPA58 in F-111 rat fibroblast cells. In earlier studies we have proposed that NPA58, a 58 kDa rat nuclear protein, is involved in nuclear protein import. In this report, NPA58 is shown to be localized on the ...

  10. Local policies around nuclear power plants in France

    International Nuclear Information System (INIS)

    Joffroy, D.

    2000-01-01

    Faced by the oil crisis, in 1973, France accelerated its program of building NPPs. The priority objective has been achieved: the rate of energy self sufficiency of France is almost 50%. The price of electricity is among the most stable and lowest in Europe. Nuclear energy is at the same time a good choice for environment meaning no emission of harmful gasses. In 1998, 57 PWR NPPs were in operation. Super Phenix fast-breeder (in Creys Malville) was shut down in 1998 by government decision. In order to achieve the public acceptance of nuclear power government has built in the following measures: tax provisions, land planning and employment based measures. Obligations imposed to the communities in France were concerned with security, information, health and safety issues. The municipalities with NPPs are still confronted with some problems as public acceptance, changes in local life, pressure of ecological political groups, security and health problems, preparation of crisis management, unemployment after the construction of the plant was finished, closure due to political decision, economic problems after the exploitation cycle is over, permanent control of the legislator. Respective associations were created to resolve these problems and avoid situations such as those arisen in Creys Malville

  11. Image restoration by Wiener filtering in the presence of signal-dependent noise.

    Science.gov (United States)

    Kondo, K; Ichioka, Y; Suzuki, T

    1977-09-01

    An optimum filter to restore the degraded image due to blurring and the signal-dependent noise is obtained on the basis of the theory of Wiener filtering. Computer simulations of image restoration using signal-dependent noise models are carried out. It becomes clear that the optimum filter, which makes use of a priori information on the signal-dependent nature of the noise and the spectral density of the signal and the noise showing significant spatial correlation, is potentially advantageous.

  12. Nuclear localization of Annexin A7 during murine brain development

    Directory of Open Access Journals (Sweden)

    Noegel Angelika A

    2005-04-01

    Full Text Available Abstract Background Annexin A7 is a member of the annexin protein family, which is characterized by its ability to interact with phospholipids in the presence of Ca2+-ions and which is thought to function in Ca2+-homeostasis. Results from mutant mice showed altered Ca2+-wave propagation in astrocytes. As the appearance and distribution of Annexin A7 during brain development has not been investigated so far, we focused on the distribution of Annexin A7 protein during mouse embryogenesis in the developing central nervous system and in the adult mouse brain. Results Annexin A7 is expressed in cells of the developing brain where a change in its subcellular localization from cytoplasm to nucleus was observed. In the adult CNS, the subcellular distribution of Annexin A7 depends on the cell type. By immunohistochemistry analysis Annexin A7 was detected in the cytosol of undifferentiated cells at embryonic days E5–E8. At E11–E15 the protein is still present in the cytosol of cells predominantly located in the ventricular germinative zone surrounding the lateral ventricle. Later on, at embryonic day E16, Annexin A7 in cells of the intermediate and marginal zone of the neopallium translocates to the nucleus. Neuronal cells of all areas in the adult brain present Annexin A7 in the nucleus, whereas glial fibrillary acidic protein (GFAP-positive astrocytes exhibit both, a cytoplasmic and nuclear staining. The presence of nuclear Annexin A7 was confirmed by extraction of the nucleoplasm from isolated nuclei obtained from neuronal and astroglial cell lines. Conclusion We have demonstrated a translocation of Annexin A7 to nuclei of cells in early murine brain development and the presence of Annexin A7 in nuclei of neuronal cells in the adult animal. The role of Annexin A7 in nuclei of differentiating and mature neuronal cells remains elusive.

  13. 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

  14. Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A

    Energy Technology Data Exchange (ETDEWEB)

    Bateman, Nicholas W. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Shoji, Yutaka [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI (United States); Conrads, Kelly A.; Stroop, Kevin D. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); Hamilton, Chad A. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Walter Reed National Military Medical Center, 8901 Wisconsin Ave, MD, Bethesda, 20889 (United States); Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda 20814, MD (United States); Darcy, Kathleen M. [Women' s Health Integrated Research Center at Inova Health System, Gynecologic Cancer Center of Excellence, Annandale 22003, VA (United States); The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda 20889, MD (United States); Maxwell, George L. [Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, VA 22042 (United States); Risinger, John I. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids 49503, MI (United States); and others

    2016-01-01

    AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors. - Highlights: • We have identified a bipartite nuclear localization sequence (NLS) in ARID1A. • Confirmation of the NLS was performed using GFP constructs. • NLS mutant ARID1A exhibits greater stability than wild-type ARID1A.

  15. Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation.

    Science.gov (United States)

    Johansson, Bente Berg; Fjeld, Karianne; Solheim, Marie Holm; Shirakawa, Jun; Zhang, Enming; Keindl, Magdalena; Hu, Jiang; Lindqvist, Andreas; Døskeland, Anne; Mellgren, Gunnar; Flatmark, Torgeir; Njølstad, Pål Rasmus; Kulkarni, Rohit N; Wierup, Nils; Aukrust, Ingvild; Bjørkhaug, Lise

    2017-10-15

    The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ( 30 LKKVMRR 36 ) in the human enzyme. Substituting the residues KK 31,32 and RR 35,36 with AA led to a loss of its nuclear localization in transfected cells. Furthermore, our data indicates that SUMOylation of glucokinase modulates its nuclear import, while high glucose concentrations do not significantly alter the enzyme nuclear/cytosolic ratio. Thus, for the first time, we provide data in support of a nuclear import of glucokinase mediated by a redundant mechanism, involving a nuclear localization signal, and which is modulated by its SUMOylation. These findings add new knowledge to the functional role of glucokinase in the pancreatic beta-cell. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Local people's understanding of risk from civil nuclear power in the Chinese context.

    Science.gov (United States)

    Fang, Xiang

    2014-04-01

    This paper analyses how people understand civil nuclear risk in the local context in China. The findings of the paper are based on six months of fieldwork research on a potential inland nuclear power project in Dapu townland in 2007 and 2008. Understanding varies greatly depending on local context, with economic, geographic and social factors influencing the way people view risks and benefits. I argue that when local people do not have enough 'scientific knowledge' to understand risk from nuclear power, they can still use their experience of everyday life to reflect rationally on the risks and benefits that they face. I conclude that when local people trust in nuclear technology and 'the government', and are unaware of nuclear risk it is partly because of their over-dependence on institutions and experts. However, despite their lack of agency, local people rationally calculate risk and benefit in accordance with their social identity and geographical location.

  17. On the global and local nuclear stopping in mass asymmetric nuclear collisions using density-dependent symmetry energy

    Science.gov (United States)

    Amandeep, K.; Suneel, K.

    2017-09-01

    The present theoretical calculations have been performed within the framework of IQMD model to study a particular set of mass symmetric and asymmetric reactions (keeping total mass fixed) over a wide range of incident energies and colliding geometries. It has been observed that global as well as local nuclear stopping is influenced by the mass asymmetry of the reaction strongly. Influence of density-dependent symmetry energy has been observed in local nuclear stopping. Global stopping decreases with the increase in colliding geometry. Effect of colliding geometry on nuclear stopping is more at higher energies.

  18. Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear localization.

    Science.gov (United States)

    Nevzorov, Ilja; Sidorenko, Ekaterina; Wang, Weihuan; Zhao, Hongxia; Vartiainen, Maria K

    2018-02-01

    Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by its interaction with the endoplasmic reticulum, and phosphoinositide binding is specifically required for nuclear import, but not nuclear retention, of Myo1C. Our results therefore demonstrate, for the first time, that membrane association and binding to nuclear partners is sufficient to drive nuclear localization of also soluble proteins, opening new perspectives to evolution of cellular protein sorting mechanisms. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  19. Planning experience and prospects of local participation in implementation of nuclear power in Bangladesh

    International Nuclear Information System (INIS)

    Rahman, M.A.; Islam, A.B.M.N.; Quaiyum, M.A.; Hasnat, K.A.; Hossain, M.

    1983-01-01

    The paper summarizes the overall experience of Bangladesh in planning for the introduction of its nuclear power programme. The basis for selection of the type of contract for the first nuclear power project of the country is explained. The paper then analyses the prospect of local participation in the construction of the first nuclear power station by detailing the local capabilities in fields such as civil works, civil works materials supply, electrical/mechanical supplies, mechanical fabrication/erection, transportation, etc. After analysing the domestic infrastructure, the problem areas are identified and measures necessary to improve the degree of local participation are described. (author)

  20. To put nuclear technical expertise at the service of local authorities

    International Nuclear Information System (INIS)

    Laffin, R.; Domeneghetti, B.

    2016-01-01

    The MARN (Mission of support for the management of the nuclear risk) was founded in 1995 to assure the interface between the actors of the nuclear world (nuclear power plant operators, ASN and IRSN) and official bodies at the national scale (ministry of interior) or local scale (prefecture). The MARN takes part in the definition of the crisis exercises and is in charge of organizing the simulation of the media pressure during the exercise. The MARN can also intervene in a real nuclear crisis and its work consists in putting into perspective the technical appreciations and recommendations of nuclear experts and to translate them into operational options for the Prefect. (A.C.)

  1. IGFBP-3 nuclear localization predicts human prostate cancer recurrence.

    Science.gov (United States)

    Seligson, David B; Yu, Hong; Tze, Sheila; Said, Jonathan; Pantuck, Allan J; Cohen, Pinchas; Lee, Kuk-Wha

    2013-02-01

    Insulin-like growth factor binding protein-3 (IGFBP-3) is a pro-apoptotic, anti-metastasic, and anti-angiogenic protein. Low serum IGFBP-3 has been associated with risk of more aggressive prostate cancer (PCa). We investigated the impact of nuclear and cytoplasmic IGFBP-3 protein expression levels in PCa by examining their in situ expression across a wide spectrum of primary tumors by immunohistochemical analysis of tissue microarrays. Immunohistochemistry was performed on PCa microarrays constructed from 226 hormone naïve patients who underwent radical prostatectomy. Both cytoplasmic and nuclear IGFBP-3 expressions were scored in a semi-quantitative fashion using an integrated measure of intensity and positivity. The distribution of IGFBP-3 protein expression was examined across the spectrum of epithelial tissues, and its association with standard clinicopathological covariates and tumor recurrence was examined. There was a broad range of IGFBP-3 staining across all histologies examined. Tumor had higher IGFBP-3 cytoplasmic and nuclear staining than benign histologies. For IGFBP-3 nuclear staining, PCa was significantly different than benign prostatic hyperplasia, normal prostate, and prostate intraepithelial neoplasia. As both a continuous and dichotomized variable, higher nuclear IGFBP-3 expression had statistically significant associations with PCa recurrence. The cytoplasmic staining had no significance in any patient subgroup. In patients with low-grade cancer, IGFBP-3 nuclear positivity was a better predictor of recurrence than baseline PSA, tumor margin status, TNM tumor stage, or presence of capsular invasion. High nuclear IGFBP-3 is amongst the strongest predictors of cancer recurrence in patients with low-grade prostate cancers and may therefore play an important role in risk stratification.

  2. Characterization of a nuclear localization signal in the foot-and-mouth disease virus polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Aparicio, Maria Teresa; Rosas, Maria Flora [Centro de Biología Molecular, “Severo Ochoa” (CSIC-UAM), Cantoblanco 28049, Madrid (Spain); Sobrino, Francisco, E-mail: fsobrino@cbm.uam.es [Centro de Biología Molecular, “Severo Ochoa” (CSIC-UAM), Cantoblanco 28049, Madrid (Spain); Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid (Spain)

    2013-09-15

    We have experimentally tested whether the MRKTKLAPT sequence in FMDV 3D protein (residues 16 to 24) can act as a nuclear localization signal (NLS). Mutants with substitutions in two basic residues within this sequence, K18E and K20E, were generated. A decreased nuclear localization was observed in transiently expressed 3D and its precursor 3CD, suggesting a role of K18 and K20 in nuclear targeting. Fusion of MRKTKLAPT to the green fluorescence protein (GFP) increased the nuclear localization of GFP, which was not observed when GFP was fused to the 3D mutated sequences. These results indicate that the sequence MRKTKLAPT can be functionally considered as a NLS. When introduced in a FMDV full length RNA replacements K18E and K20E led to production of revertant viruses that replaced the acidic residues introduced (E) by K, suggesting that the presence of lysins at positions 18 and 20 of 3D is essential for virus multiplication. - Highlights: • The FMDV 3D polymerase contains a nuclear localization signal. • Replacements K18E and K20E decrease nuclear localization of 3D and its precursor 3CD. • Fusion of the MRKTKLAPT 3D motif to GFP increases the nuclear localization of GFP. • Replacements K18E and K20E abolish the ability of MRKTKLAPT to relocate GFP. • RNAs harboring replacements K18E and K20E lead to recovery of revertant FMDVs.

  3. Identification of the nuclear localization signal of human immunodeficiency virus type 2 Vpx

    International Nuclear Information System (INIS)

    Belshan, Michael; Ratner, Lee

    2003-01-01

    The Vpx protein of human immunodeficiency virus type 2 (HIV-2) is a viral accessory protein related to, but distinct from, the Vpr protein of HIV-1. Vpx is packaged into virions and, as a component of the viral preintegration complex (PIC), Vpx is required for efficient virus replication in nondividing cells. Therefore, the localization of Vpx in cells is dynamic and dependent upon discrete domains of the protein. Expressed in the absence of other viral proteins, Vpx localizes to the nucleus of cells. However, if expressed with the Gag protein of HIV-2, Vpx localizes to the plasma membrane of cells. To further understand the regulation of Vpx localization, we fused regions of Vpx to β-galactosidase to identify regions of the protein sufficient to mediate nuclear localization. The minimal transferable region of Vpx that conferred nuclear localization in these assays was aa 65 to 72. Alanine substitution of K 68 and R 70 in a GFP-Vpx construct abolished nuclear localization, suggesting that the basic residues in this region are important for nuclear import. Analysis of the membrane transport of several GFP-Vpx alanine mutants demonstrated that while separable, the domains of Vpx required for nuclear localization are not distinct from the domains required for membrane transport. The results of heterokaryon shuttling assays indicated that Vpx is not a shuttling protein; however, HIV-2 Vpr did shuttle similar to HIV-1 Vpr

  4. Construction of a nuclear power station in one's locality: attitudes and salience

    NARCIS (Netherlands)

    van der Pligt, J.; Eiser, J.R.; Spears, R.

    1986-01-01

    Examined the attitudes toward the building of a nuclear power station in one's locality by surveying 290 residents (mean age 47.5 yrs) of 3 small rural communities that were listed as possible locations for a new nuclear power station. Results show that a large majority of Ss opposed the building of

  5. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Eizuru, Yoshito [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.

  6. Localization of Manufacturing Capabilities in Setting Up Nuclear Power Plants

    International Nuclear Information System (INIS)

    Chadda, Sushil Kumar

    2011-01-01

    Nuclear renaissance is now imminent and is inevitable in view of rapidly increasing global warming concerns. A steep shift towards environmentally benign sources of energy remains an unavoidable choice as continents are warming up pushing seas into human habitation and disturbing global ecology. Accordingly, Indian government in its integrated energy policy document has planned for raising nuclear power capacity to generate 63 GWe by 2030. This envisages estimated investments of US$22 billion in the next 15 to 20 years. Setting up of nuclear energy generation capacity, however, remains a painstakingly slow process primarily due to complex, multidisciplinary efforts required to crank up a reactor. A robust supply chain remains key to expediting this process. In the light of this, it is critically important to ensure supply-chain for materials and components and putting in place cost effective project management to complete the projects on time and within the budgets. In this context, the participation of industries and their preparedness to meet the challenges are necessary. This would also require investments towards up gradation of manufacturing technology, training of manpower and mobilization of resources at the construction site. The industry would also need to enhance detailing and design engineering capabilities for the plants. It is only when such capabilities have been brought up that the possibilities of time-bound setting up of nuclear plants can be realized. In this paper, various issues with regard to project cost, regulatory and licensing, technology and gestation period etc for new build plants relevant to manufacturing industry are discussed. The plans for enhancing manufacturing capabilities for the critical path items of the project schedule with viable business, ensuring returns to stakeholders and financing and investment cycle are brought out. The various steps and initiatives being taken by Bharat Forge Ltd, the flagship company of Kalyani

  7. Finding synergy between local competitiveness and global sustainability to provide a future to nuclear energy

    International Nuclear Information System (INIS)

    Van Den Durpel, Luc; Yacout, Abdellatif; Wade, Dave

    2008-01-01

    The world's future energy needs will require a mix of energy conversion technologies matched to the local energy market needs while also responding to both local and global socio-political concerns, e.g. energy security, environmental impact, safety and non-proliferation. There is growing recognition worldwide that nuclear energy should not only be part of the solution but maybe as well play a larger share in future's energy supply. The sustainability of future nuclear energy systems is hereby important and a variety of studies have already shown that sustainability of nuclear energy from a resource perspective is achievable via the nuclear fuel cycle though where economic sustainability is essentially defined by the nuclear power plants. The main challenge in deploying sustainable nuclear energy systems will be to find synergies between this local competitiveness of nuclear power plants and the global resource sustainability defined via the nuclear fuel cycle. Both may go hand-in-hand in the long-term but may need government guidance in starting the transition towards such future sustainable nuclear energy systems. (authors)

  8. ERK5 and cell proliferation: nuclear localization is what matters

    Directory of Open Access Journals (Sweden)

    Nestor Gomez

    2016-09-01

    Full Text Available ERK5, the last MAP kinase family member discovered, is activated by the upstream kinase MEK5 in response to growth factors and stress stimulation. MEK5-ERK5 pathway has been associated to different cellular processes, playing a crucial role in cell proliferation in normal and cancer cells by mechanisms that are both dependent and independent of its kinase activity. Thus, nuclear ERK5 activates transcription factors by either direct phosphorylation or acting as co-activator thanks to a unique transcriptional activation TAD domain located at its C-terminal tail. Consequently, ERK5 has been proposed as an interesting target to tackle different cancers, and either inhibitors of ERK5 activity or silencing the protein have shown antiproliferative activity in cancer cells and to block tumour growth in animal models. Here, we review the different mechanisms involved in ERK5 nuclear translocation and their consequences. Inactive ERK5 resides in the cytosol, forming a complex with Hsp90-Cdc37 superchaperone. In a canonical mechanism, MEK5-dependent activation results in ERK5 C-terminal autophosphorylation, Hsp90 dissociation and nuclear translocation. This mechanism integrates signals such as growth factors and stresses that activate the MEK5-ERK5 pathway. Importantly, two other mechanisms, MEK5-independent, have been recently described. These mechanisms allow nuclear shuttling of kinase-inactive forms of ERK5. Although lacking kinase activity, these forms activate transcription by interacting with transcription factors through the TAD domain. Both mechanisms also require Hsp90 dissociation previous to nuclear translocation. One mechanism involves phosphorylation of the C-terminal tail of ERK5 by kinases that are activated during mitosis, such as Cyclin-dependent kinase-1. The second mechanism involves overexpression of chaperone Cdc37, an oncogene that is overexpressed in cancers such as prostate adenocarcinoma, where it collaborates with ERK5 to promote

  9. Dual localized mitochondrial and nuclear proteins as gene expression regulators in plants?

    Directory of Open Access Journals (Sweden)

    Philippe eGiegé

    2012-09-01

    Full Text Available Mitochondria heavily depend on the coordinated expression of both mitochondrial and nuclear genomes because some of their most significant activities are held by multi-subunit complexes composed of both mitochondrial and nuclear encoded proteins. Thus, precise communication and signaling pathways are believed to exist between the two compartments. Proteins dual localized to both mitochondria and the nucleus make excellent candidates for a potential involvement in the envisaged communication. Here, we review the identified instances of dual localized nucleo-mitochondrial proteins with an emphasis on plant proteins and discuss their functions, which are seemingly mostly related to gene expression regulation. We discuss whether dual localization could be achieved by dual targeting and / or by re-localization and try to apprehend the signals required for the respective processes. Finally, we propose that in some instances, dual localized mitochondrial and nuclear proteins might act as retrograde signaling molecules for mitochondrial biogenesis.

  10. Immunofluorescent localization of the proteins of nuclear ribonucleoprotein complexes

    OpenAIRE

    1980-01-01

    Antibodies were raised in chickens against heterogeneous nuclear RNA (hnRNA)-binding proteins from 30S ribonucleoprotein (RNP) complexes of mouse Taper hepatoma ascites cell nuclei. The antibody preparations were characterized for immunological specificity and purity by double- diffusion gels, binding to specific bands in SDS polyacrylamide gels, and crossed immunoelectrophoresis. Antibodies raised against either whole 30S RNP complexes or purified RNP core proteins had a strong selective aff...

  11. Nup98 Localizes to Both Nuclear and Cytoplasmic Sides of the Nuclear Pore and Binds to Two Distinct Nucleoporin Subcomplexes

    Science.gov (United States)

    Griffis, Eric R.; Xu, Songli; Powers, Maureen A.

    2003-01-01

    The vertebrate nuclear pore is an enormous structure that spans the double membrane of the nuclear envelope. In yeast, most nucleoporins are found symmetrically on both the nuclear and cytoplasmic sides of the structure. However, in vertebrates most nucleoporins have been localized exclusively to one side of the nuclear pore. Herein, we show, by immunofluorescence and immunoelectron microscopy, that Nup98 is found on both sides of the pore complex. Additionally, we find that the pore-targeting domain of Nup98 interacts directly with the cytoplasmic nucleoporin Nup88, a component of the Nup214, Nup88, Nup62 subcomplex. Nup98 was previously described to interact with the nuclear-oriented Nup160, 133, 107, 96 complex through direct binding to Nup96. Interestingly, the same site within Nup98 is involved in binding to both Nup88 and Nup96. Autoproteolytic cleavage of the Nup98 C terminus is required for both of these binding interactions. When cleavage is blocked by a point mutation, a minimal eight amino acids downstream of the cleavage site is sufficient to prevent most binding to either Nup96 or Nup88. Thus, Nup98 interacts with both faces of the nuclear pore, a localization in keeping with its previously described nucleocytoplasmic shuttling activity. PMID:12589057

  12. Characterization of a novel tripartite nuclear localization sequence in the EGFR family.

    Science.gov (United States)

    Hsu, Sheng-Chieh; Hung, Mien-Chie

    2007-04-06

    Aberrant expression of epidermal growth factor receptor (EGFR) is present in many human tumors. Several reports have shown that EGFR is translocated into the nucleus during liver regeneration and in several types of cells and tissues such as placenta and thyroid. Nuclear EGFR is associated with transcription, DNA synthesis, and DNA repair activity and serves as a prognostic marker in breast carcinoma and oropharyngeal squamous cell cancer. However, the nuclear localization sequence (NLS) of EGFR has not been extensively examined. In this study, we have shown that the juxtamembrane region of EGFR harbors a putative NLS with three clusters of basic amino acids (RRRHIVRKRTLRR (amino acids 645-657)) that mediates the nuclear localization of EGFR. We found that this newly characterized tripartite NLS is conserved among the EGFR family members (EGFR, ErbB2, ErbB3, and ErbB4) and is able to move each to the nucleus. Further, this tripartite NLS could also mediate the nuclear localization of other known cytoplasmic proteins such as pyruvate kinase. We have demonstrated that mutating one of the three basic amino acid clusters (R or K --> A) leads to significant impairment of the nuclear localization of EGFR and that of a green fluorescent protein-pyruvate kinase-NLS reporter protein. Our results show that this tripartite NLS is distinct from the traditional mono- and bipartite NLS and reveal a mechanism that could account for the nuclear localization of membrane receptors.

  13. Local opposition to the construction of a nuclear power station: differential salience of impacts

    NARCIS (Netherlands)

    Eiser, J.R.; van der Pligt, J.; Spears, R.

    1988-01-01

    Surveyed attitudes among 290 residents of 3 villages in southwest England toward proposals to build a nuclear power station nearby. Ss were grouped according to being neutral or in favor of a new power station either locally or elsewhere (Group PN), against one locally but neutral or pro elsewhere

  14. To the non-local theory of cold nuclear fusion.

    Science.gov (United States)

    Alexeev, Boris V

    2014-10-01

    In this paper, we revisit the cold fusion (CF) phenomenon using the generalized Bolzmann kinetics theory which can represent the non-local physics of this CF phenomenon. This approach can identify the conditions when the CF can take place as the soliton creation under the influence of the intensive sound waves. The vast mathematical modelling leads to affirmation that all parts of soliton move with the same velocity and with the small internal change of the pressure. The zone of the high density is shaped on the soliton's front. It means that the regime of the 'acoustic CF' could be realized from the position of the non-local hydrodynamics.

  15. Nuclear microprobe local characterization of YBaCuO superconductors

    Science.gov (United States)

    Berger, P.; Berthier, B.; Revel, G.; Trocellier, P.

    1995-09-01

    Stoichiometric local characterizations of YBaCuO oxides have been performed using a 1.4 MeV deuteron microbeam. A beam with a size of 10 × 15 μm 2 allows the observation of variations of x = 0.2 in sintered YBa 2Cu 3O 7-x. Local variations of oxygen stoichiometry in a melt-textured sample, correlated with the microstructure, have been observed. In spite of the degradation of the sample under the beam, oxygen measurements seem to remain significant for doses above 10 18 ions/cm 2.

  16. Efficient and dynamic nuclear localization of green fluorescent protein via RNA binding.

    Science.gov (United States)

    Kitamura, Akira; Nakayama, Yusaku; Kinjo, Masataka

    2015-07-31

    Classical nuclear localization signal (NLS) sequences have been used for artificial localization of green fluorescent protein (GFP) in the nucleus as a positioning marker or for measurement of the nuclear-cytoplasmic shuttling rate in living cells. However, the detailed mechanism of nuclear retention of GFP-NLS remains unclear. Here, we show that a candidate mechanism for the strong nuclear retention of GFP-NLS is via the RNA-binding ability of the NLS sequence. GFP tagged with a classical NLS derived from Simian virus 40 (GFP-NLS(SV40)) localized not only in the nucleoplasm, but also to the nucleolus, the nuclear subdomain in which ribosome biogenesis takes place. GFP-NLS(SV40) in the nucleolus was mobile, and intriguingly, the diffusion coefficient, which indicates the speed of diffusing molecules, was 1.5-fold slower than in the nucleoplasm. Fluorescence correlation spectroscopy (FCS) analysis showed that GFP-NLS(SV40) formed oligomers via RNA binding, the estimated molecular weight of which was larger than the limit for passive nuclear export into the cytoplasm. These findings suggest that the nuclear localization of GFP-NLS(SV40) likely results from oligomerization mediated via RNA binding. The analytical technique used here can be applied for elucidating the details of other nuclear localization mechanisms, including those of several types of nuclear proteins. In addition, GFP-NLS(SV40) can be used as an excellent marker for studying both the nucleoplasm and nucleolus in living cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Signal dependence of inter-pixel capacitance in hybridized HgCdTe H2RG arrays for use in James Webb space telescope's NIRcam

    Science.gov (United States)

    Donlon, Kevan; Ninkov, Zoran; Baum, Stefi

    2016-08-01

    Interpixel capacitance (IPC) is a deterministic electronic coupling by which signal generated in one pixel is measured in neighboring pixels. Examination of dark frames from test NIRcam arrays corroborates earlier results and simulations illustrating a signal dependent coupling. When the signal on an individual pixel is larger, the fractional coupling to nearest neighbors is lesser than when the signal is lower. Frames from test arrays indicate a drop in average coupling from approximately 1.0% at low signals down to approximately 0.65% at high signals depending on the particular array in question. The photometric ramifications for this non-uniformity are not fully understood. This non-uniformity intro-duces a non-linearity in the current mathematical model for IPC coupling. IPC coupling has been mathematically formalized as convolution by a blur kernel. Signal dependence requires that the blur kernel be locally defined as a function of signal intensity. Through application of a signal dependent coupling kernel, the IPC coupling can be modeled computationally. This method allows for simultaneous knowledge of the intrinsic parameters of the image scene, the result of applying a constant IPC, and the result of a signal dependent IPC. In the age of sub-pixel precision in astronomy these effects must be properly understood and accounted for in order for the data to accurately represent the object of observation. Implementation of this method is done through python scripted processing of images. The introduction of IPC into simulated frames is accomplished through convolution of the image with a blur kernel whose parameters are themselves locally defined functions of the image. These techniques can be used to enhance the data processing pipeline for NIRcam.

  18. Reflections on the development of local suppliers for the Argentine nuclear industry

    International Nuclear Information System (INIS)

    Quilici, Domingo F.

    2008-01-01

    Argentina has given recently a new start to its nuclear power activities. Looking for background and experiences that can be useful under the new reality, the paper is a survey of the past development of local suppliers for the national nuclear industry. Based on the intention to answer the questions: Why so early it was decided to build a nuclear power plant? Why it was decided to buy it under a turnkey basis rather than developing an indigenous design? and what was the meaning of the 'opening of the technology package' at that time?, the paper describes the actions that led to the purchase of the Atucha I, Embalse and Atucha II nuclear power plants and how these decisions were implemented in order to maximize local participation and the technology transfer. It also analyzes the influence of the Argentine Nuclear Plan of the late seventies on the development of endogenous technology and describes the facts that helped to preserve until now the technological nuclear capabilities of the country in spite of the stopping of the Atucha II construction, and to create positive expectations regarding the revival of the local industry as a supplier of nuclear goods and services. (author) [es

  19. Monitoring device for local power distribution in nuclear reactor

    International Nuclear Information System (INIS)

    Uematsu, Hitoshi

    1989-01-01

    The object of the present invention is to provide a local power monitoring device of more excellent instant response and higher speed operation than usual. That is, counted values from each of reactor core present status data detector, movable type neutron flux detector and fixed type neutron flux detector are inputted to a data sampler. A neutron flux distribution calculation device calculates the neutron flux distribution in the reactor core for the inputs of the calculated values from the reactor core present status data detector based on previously incorporated physical models. The optimum neutron flux distribution calculation device is inputted with each of the calculated values from the movable neutron detector and the fixed neutron detector and signals of the incore neutron flux distribution from the data sampler described above. Then, the device compensates the neutron flux distribution in accordance with the change of the control rod positions from the calculation point of time of the incore neutron flux distribution. Then, the power distribution is calculated by using the compensated neutron flux distribution . Accordingly, it is possible to obtain a local power distribution monitor of more excellent rapid response and high speed operation than usual. (I.S.)

  20. The Political Styles of Local Anti-Nuclear Waste Movements in Finland

    International Nuclear Information System (INIS)

    Kojo, Matti

    2001-01-01

    This paper aims to analyse the political styles of local anti-nuclear waste movements in Finland. The main focus is on the tension between the environmental impact assessment process (EIA) and the activity of local opposing groups. According to the EIA Act the purpose of the EIA process is to provide information and opportunities for citizens to participate in planning. It therefore aims to enhance the transparency of the decision-making process. The Finnish nuclear waste company, Posiva Oy, made great efforts locally to create opportunities for participation, but was much criticised by local activists. My questions are the following: How did these local movements participate in Posiva's EIA process? What kind of local differences were there in participating and how can these differences be explained? And finally; what did the EIA process mean to the political styles of movements? EIA meant a temporary change in political style on local level. Firstly; because it brought science into local politics very clearly. Secondly EIA with the Nuclear Energy Act framed decision-making with a timetable, which Posiva emphasised when local groups wanted to make a decision immediately. Thirdly EIA enabled the problem to be defined according to local needs but on the other hand plan level EIA separated nuclear waste issue from the use of nuclear power. Fourthly dialogue in the EIA process favoured rational discourse. Although local views were heard, the process did try to teach the people how to speak with the decision-making system, in the system's language. Thus the purpose of EIA was to make the local discussion controllable. All the local groups, the Romuvaara, Kivetty and Loviisa Movements and the Friends of the Earth in Pori region, took part in EIA dialogue but the reactions were different. The Romuvaara Movement was very active in participating and succeeded in exploiting EIA locally whereas the Loviisa Movement tried to displace the whole process. The Loviisa Movement

  1. The Political Styles of Local Anti-Nuclear Waste Movements in Finland

    Energy Technology Data Exchange (ETDEWEB)

    Kojo, Matti [Univ. of Tampere (Finland). Dept. of Political Science and International Relations

    2001-07-01

    This paper aims to analyse the political styles of local anti-nuclear waste movements in Finland. The main focus is on the tension between the environmental impact assessment process (EIA) and the activity of local opposing groups. According to the EIA Act the purpose of the EIA process is to provide information and opportunities for citizens to participate in planning. It therefore aims to enhance the transparency of the decision-making process. The Finnish nuclear waste company, Posiva Oy, made great efforts locally to create opportunities for participation, but was much criticised by local activists. My questions are the following: How did these local movements participate in Posiva's EIA process? What kind of local differences were there in participating and how can these differences be explained? And finally; what did the EIA process mean to the political styles of movements? EIA meant a temporary change in political style on local level. Firstly; because it brought science into local politics very clearly. Secondly EIA with the Nuclear Energy Act framed decision-making with a timetable, which Posiva emphasised when local groups wanted to make a decision immediately. Thirdly EIA enabled the problem to be defined according to local needs but on the other hand plan level EIA separated nuclear waste issue from the use of nuclear power. Fourthly dialogue in the EIA process favoured rational discourse. Although local views were heard, the process did try to teach the people how to speak with the decision-making system, in the system's language. Thus the purpose of EIA was to make the local discussion controllable. All the local groups, the Romuvaara, Kivetty and Loviisa Movements and the Friends of the Earth in Pori region, took part in EIA dialogue but the reactions were different. The Romuvaara Movement was very active in participating and succeeded in exploiting EIA locally whereas the Loviisa Movement tried to displace the whole process. The Loviisa

  2. Nuclear localization of DMP1 proteins suggests a role in intracellular signaling

    Energy Technology Data Exchange (ETDEWEB)

    Siyam, Arwa [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Department of Endodontology, Kornberg School of Dentistry, Temple University, 3223 North Broad Street, Philadelphia, PA 19140-5007 (United States); Wang, Suzhen; Qin, Chunlin; Mues, Gabriele [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Stevens, Roy [Department of Endodontology, Kornberg School of Dentistry, Temple University, 3223 North Broad Street, Philadelphia, PA 19140-5007 (United States); D' Souza, Rena N. [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Lu, Yongbo, E-mail: ylu@bcd.tamhsc.edu [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nuclear localization of DMP1 in various cell lines. Black-Right-Pointing-Pointer Non-synchronized cells show either nuclear or cytoplasmic localization of DMP1. Black-Right-Pointing-Pointer Nuclear DMP1 is restricted to the nucleoplasm but absent in the nucleolus. -- Abstract: Dentin matrix protein 1 (DMP1) is highly expressed in odontoblasts and osteoblasts/osteocytes and plays an essential role in tooth and bone mineralization and phosphate homeostasis. It is debatable whether DMP1, in addition to its function in the extracellular matrix, can enter the nucleus and function as a transcription factor. To better understand its function, we examined the nuclear localization of endogenous and exogenous DMP1 in C3H10T1/2 mesenchymal cells, MC3T3-E1 preosteoblast cells and 17IIA11 odontoblast-like cells. RT-PCR analyses showed the expression of endogenous Dmp1 in all three cell lines, while Western-blot analysis detected a major DMP1 protein band corresponding to the 57 kDa C-terminal fragment generated by proteolytic processing of the secreted full-length DMP1. Immunofluorescent staining demonstrated that non-synchronized cells presented two subpopulations with either nuclear or cytoplasmic localization of endogenous DMP1. In addition, cells transfected with a construct expressing HA-tagged full-length DMP1 also showed either nuclear or cytoplasmic localization of the exogenous DMP1 when examined with an antibody against the HA tag. Furthermore, nuclear DMP1 was restricted to the nucleoplasm but was absent in the nucleolus. In conclusion, these findings suggest that, apart from its role as a constituent of dentin and bone matrix, DMP1 might play a regulatory role in the nucleus.

  3. 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

  4. Nuclear medicine imaging of locally advanced laryngeal and hypopharyngeal cancer

    Science.gov (United States)

    Medvedeva, A.; Chernov, V.; Zeltchan, R.; Sinilkin, I.; Bragina, O.; Chijevskaya, S.; Choynzonov, E.; Goldberg, A.

    2017-09-01

    The diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. A total of 40 patients with histologically verified laryngeal and hypopharyngeal cancer and 20 patients with benign laryngeal lesions were included into the study. Submucosal injections of 99mTc-MIBI and 99mTc-Alotech were made around the tumor. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-MIBI. Sentinel lymph nodes (SLNs) were detected in 26 patients. In 18 hours after the injection of 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17%) of the 12 patients. Twenty eight SLNs were detected by SPECT and 31 SLNs were identified using the intraoperative gamma probe. The percentage of 99mTc-Alotech in the SLN was 5-10% of the radioactivity in the injection site by SPECT and 18-33% by intraoperative gamma probe detection. Thus, SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specificity and accuracy of this technique were 95%, 80% and 92%, respectively. The use of 99mTc-Alotech for the detection of SLNs in patients with laryngeal/hypopharyngeal cancer is characterized by 92.8% sensitivity.

  5. The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization.

    Science.gov (United States)

    Korge, Sandra; Maier, Bert; Brüning, Franziska; Ehrhardt, Lea; Korte, Thomas; Mann, Matthias; Herrmann, Andreas; Robles, Maria S; Kramer, Achim

    2018-01-01

    Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics. Among them was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose knockdown and knockout led to short circadian periods. TNPO1 was found in endogenous clock protein complexes and particularly binds to PER1 regulating its (but not PER2's) nuclear localization. While PER1 is also transported to the nucleus by the classical, Importin β-mediated pathway, TNPO1 depletion slowed down PER1 nuclear import rate as revealed by fluorescence recovery after photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated nuclear import may constitute a novel input pathway of how cellular redox state signals to the clock, since redox stress increases binding of TNPO1 to PER1 and decreases its nuclear localization. Together, our RNAi screen knocking down import carriers (but also export carriers) results in short and long circadian periods indicating that the regulatory pathways that control the timing of clock protein subcellular localization are far more complex than previously assumed. TNPO1 is one of the novel players essential for normal circadian periods and potentially for redox regulation of the clock.

  6. Baculovirus LEF-11 nuclear localization signal is important for viral DNA replication.

    Science.gov (United States)

    Chen, Tingting; Dong, Zhanqi; Hu, Nan; Hu, Zhigang; Dong, Feifan; Jiang, Yaming; Li, Jun; Chen, Peng; Lu, Cheng; Pan, Minhui

    2017-06-15

    Baculovirus LEF-11 is a small nuclear protein that is involved in viral late gene transcription and DNA replication. However, the characteristics of its nuclear localization signal and its impact on viral DNA replication are unknown. In the present study, systemic bioinformatics analysis showed that the baculovirus LEF-11 contains monopartite and bipartite classical nuclear localization signal sequences (cNLSs), which were also detected in a few alphabaculovirus species. Localization of representative LEF-11 proteins of four baculovirus genera indicated that the nuclear localization characteristics of baculovirus LEF-11 coincided with the predicted results. Moreover, Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 could be transported into the nucleus during viral infection in the absence of a cNLSs. Further investigations demonstrated that the NLS of BmNPV LEF-11 is important for viral DNA replication. The findings of the present study indicate that the characteristics of the baculovirus LEF-11 protein and the NLS is essential to virus DNA replication and nuclear transport mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Development of Necessary Technology for localizing of Nuclear Safety Grade I and C System

    International Nuclear Information System (INIS)

    Kwon, Kee Choon; Jang, Tong Il; Kim, Jung Tack

    2010-08-01

    Through KNICS and Nu-Tech 2012, a MMIS(Man-Machine Interface System) package for nuclear plants was localized and is expected to be applied to SUN 1,2 plants. This study is aimed to support the application of the MMIS package including the following technologies that meet strengthened regulation requirements and enhanced utility's performance requirements to nuclear plants. - Dedication to safety-grade computers and real time operating systems - The broadband communication network for safety information - Application of the automatic test for safety systems - Application of programmable logic controllers to nuclear plants - Development strategy for an integrated SW development tool for control device

  8. Local nuclear slope and curvature in high energy pp and pp-bar elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Desgrolard, P. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire; Kontros, J.; Lengyel, A.I. [Inst. of Electron Physics, Uzhgorod (Ukraine); Martynov, E.S. [National Academy of Sciences of Ukraine, Kiev (Ukraine). Bogolyubov Inst. for Theoretical Physics

    1997-05-01

    The local nuclear slope is reconstructed from the experimental angular distributions with a procedure that uses overlapping t-bins, for an energy that ranges from the ISR to the Sp-bar pS and the Tevatron. Predictions of several models of (p-bar,p) elastic scattering at high energy are tested. Only a model with two-components Pomeron and Odderon gives a satisfactory agreement with the (non fitted) slope data. The extreme sensitivity of the local nuclear curvature with the choice for a Pomeron model is emphasized. (author). 30 refs.

  9. Infrared-microwave double resonance: signal dependence on microwave radiation strength

    NARCIS (Netherlands)

    Vreede, J.P.M. de; Dijkerman, H.A.

    1980-01-01

    The influence of MW radiation on the magnitude of double resonance signals is studied in the case of steady-state 3-level IR-MW double resonance, using IR or MW radiation as probe field. The measurements reveal a strong signal dependence on the microwave power level. Changes in the absorption factor

  10. Framing the national nuclear legacy at the local level: Implications for the future of federal facilities

    International Nuclear Information System (INIS)

    Morrone, Michele; Basta, Tania B.; Somerville, Jennifer

    2012-01-01

    There are several major federal nuclear facilities located in small towns and rural areas of the United States. While many of these facilities were developed in the 1950s to support national defense, in the 1960s and 1970s, some of these shifted their mission to focus on national energy infrastructure. Now, many of these facilities are in a clean-up phase, and local communities are becoming increasingly engaged in influencing decisions about the future of the sites. Communicating with the public in rural communities is challenging when it involves a complicated environmental issue that could have widespread economic impacts. The local media reflect public understanding, so getting a sense of how these media frame issues can be a crucial first step to developing an effective community engagement strategy. A media content analysis of one local newspaper was completed in relation to a major federal nuclear facility. The content analysis is compared to the results of a telephone survey in the region served by the paper and the results suggest that there is a relationship between how the facility is portrayed in local media and public concern. This study has important implications for other nuclear facilities because of the role of local citizens in decision-making. - Highlights: ► Decisions about federal nuclear facilities include local citizen participation. ► Local media can play an important role in public perception of environmental risk. ► Local print media rely on a limited number in of sources for their stories. ► Effective risk communication should begin by understanding local public concerns.

  11. The development and localization of nuclear fuel technology for KMRR

    International Nuclear Information System (INIS)

    Kim, Seong Yun; Lee, Ji Bok; Suk, Ho Chun; Kuk, Il Hyun; Hwang, Woan; Kim, Bong Goo; Park, Joo Hwan; Kim, Young Jin; Kang, Thae Khapp; Lee, Jae Choon

    1988-05-01

    This project was implemented aiming at localizing the fabrication of the KMRR fuel by october 1993. The contents of this project were divided into three parts: fuel design, fuel fabrication and process criticality analysis. In the fuel design, the radial power distribution in the fuel core was modeled and formulated taking account of the neutron flux depression in the radial direction. It was also performed to model and formulate the thermal characteristics such as the thermal conductivity and specific heat of the fuel core, U3Si-Al, the swelling and the film coefficient of heat transfer between the aluminum clad and light water coolant. The two dimensional heat transfer in the finned fuel element was equated based on the general equation governing the heat transfer in materials in order to develope a computer code, TEMP2D. TEMP2D solves finite differenced equations to calculate a two dimensional fuel temperature distribution under the steady and transient states. In the fuel fabrication, the technologies of fabricating uranium silicide fuel meat were tried by using depleted uranium as a raw material. These were extended to find the problems in technologies and to establish the ways of approach. The end product, so called fuel meat, was a metallic powder compound, U3Six(1≤x≤2), dispersed in Al matrix. The fuel meat was fabricated by the horizontal extrusion technique, and powder extrusion technique. Fabrication technologies comprise five different continuous processes: melting and casting of metallic uranium with silicon and aluminum, heat treatment, chipping and crushing, pulverizing, and extrusion. In the process criticality analysis, AMPX-KENO benchmark calculation was performed and calculational error of AMPX-KENO system was established. (Author)

  12. Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery

    International Nuclear Information System (INIS)

    Li, Yong-Yong; Li, Lan; Dong, Hai-Qing; Cai, Xiao-Jun; Ren, Tian-Bin

    2013-01-01

    PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ∼ 100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery. - Highlights: ► A new nuclear targeted drug delivery system based on micelles is developed. ► This micellar system features a core-shell structure with the size peaked at 100 nm. ► PV7, a short peptide sequence, is adopted as a nuclear targeting ligand. ► PV7 functionalized drug loaded micelles are more potent in killing tumor cells

  13. Living with nuclear power: A Q-method study of local community perceptions.

    Science.gov (United States)

    Venables, Dan; Pidgeon, Nick; Simmons, Peter; Henwood, Karen; Parkhill, Karen

    2009-08-01

    The issue of new nuclear power is once again high up on the public policy agenda in many countries, and candidate sites for new civilian stations are likely to include those that have existing nuclear facilities. A common assumption is that existing nuclear communities will be more accepting of new build because of the direct economic and other benefits nuclear power already makes to a local area. Surprisingly, there is a dearth of contemporary data on perceptions of the risks, benefits, and values associated with nuclear power within such communities. This study uses Q-methodology to investigate the perspectives on living with nuclear risk among people (n = 84) drawn from communities near to two nuclear power stations in the United Kingdom. Both stations, at Bradwell-on-Sea and Oldbury-on-Severn, had been in operation for over 40 years. The Q-analysis identified four main perspectives, or points of view, accounting for 53% of total variance. These were interpreted as: Beneficial and Safe; Threat and Distrust; Reluctant Acceptance; and There's No Point Worrying. We conclude that the "landscape of beliefs" about nuclear power in such communities is both subtle and complex, avoiding simplistic bipolar dichotomies such as "for" or "against," and that there is a need for extensive and meaningful dialogue with such communities over any new build plans. The usefulness of Q-methodology for investigating the ways in which people live with risk is highlighted, as are the implications of the results for theories of risk and trust.

  14. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

    Directory of Open Access Journals (Sweden)

    MacMillan Christina

    2010-06-01

    Full Text Available Abstract Background Proteolytic cleavage of the extracellular domain (EpEx of Epithelial cell adhesion molecule (EpCAM and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. Methods EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. Results The anaplastic (ATC and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p Conclusion We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC.

  15. Nuclear Localization of PTEN by a Ran-dependent Mechanism Enhances Apoptosis: Involvement of an N-Terminal Nuclear Localization Domain and Multiple Nuclear Exclusion Motifs

    OpenAIRE

    Gil, Anabel; Andrés-Pons, Amparo; Fernández, Elena; Valiente, Miguel; Torres, Josema; Cervera, Javier; Pulido, Rafael

    2006-01-01

    The targeting of the tumor suppressor PTEN protein to distinct subcellular compartments is a major regulatory mechanism of PTEN function, by controlling its access to substrates and effector proteins. Here, we investigated the molecular basis and functional consequences of PTEN nuclear/cytoplasmic distribution. PTEN accumulated in the nucleus of cells treated with apoptotic stimuli. Nuclear accumulation of PTEN was enhanced by mutations targeting motifs in distinct PTEN domains, and it was de...

  16. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    Science.gov (United States)

    Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

    2015-01-01

    The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

  17. Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

    Directory of Open Access Journals (Sweden)

    Itzell Euridice Hernández-Sánchez

    2015-09-01

    Full Text Available The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

  18. Identification of a functional nuclear localization signal within the human USP22 protein

    International Nuclear Information System (INIS)

    Xiong, Jianjun; Wang, Yaqin; Gong, Zhen; Liu, Jianyun; Li, Weidong

    2014-01-01

    Highlights: • USP22 was accumulated in nucleus. • We identified of a functional USP22 NLS. • The KRRK amino acid residues are indispensable in NLS. • The KRRK motif is conserved in USP22 homologues. - Abstract: Ubiquitin-specific processing enzyme 22 (USP22), a member of the deubiquitinase family, is over-expressed in most human cancers and has been implicated in tumorigenesis. Because it is an enzymatic subunit of the human SAGA transcriptional cofactor, USP22 deubiquitylates histone H2A and H2B in the nucleus, thus participating in gene regulation and cell-cycle progression. However, the mechanisms regulating its nuclear translocation have not yet been elucidated. It was here demonstrated that USP22 is imported into the nucleus through a mechanism mediated by nuclear localization signal (NLS). The bipartite NLS sequence KRELELLKHNPKRRKIT (aa152–168), was identified as the functional NLS for its nuclear localization. Furthermore, a short cluster of basic amino acid residues KRRK within this bipartite NLS plays the primary role in nuclear localization and is evolutionarily conserved in USP22 homologues. In the present study, a functional NLS and the minimal sequences required for the active targeting of USP22 to the nucleus were identified. These findings may provide a molecular basis for the mechanism underlying USP22 nuclear trafficking and function

  19. Identification of a functional nuclear localization signal within the human USP22 protein

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Jianjun [Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang, Jiangxi Province 332000 (China); College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000 (China); Wang, Yaqin [Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060 (China); Gong, Zhen [Key Laboratory of Jiangxi Province for the Systems Bio-Medicine, Jiujiang, Jiangxi Province 332000 (China); Liu, Jianyun [College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000 (China); Li, Weidong, E-mail: lwd626518@163.com [College of Basic Medical Science, Jiujiang University, Jiujiang, Jiangxi Province 332000 (China)

    2014-06-20

    Highlights: • USP22 was accumulated in nucleus. • We identified of a functional USP22 NLS. • The KRRK amino acid residues are indispensable in NLS. • The KRRK motif is conserved in USP22 homologues. - Abstract: Ubiquitin-specific processing enzyme 22 (USP22), a member of the deubiquitinase family, is over-expressed in most human cancers and has been implicated in tumorigenesis. Because it is an enzymatic subunit of the human SAGA transcriptional cofactor, USP22 deubiquitylates histone H2A and H2B in the nucleus, thus participating in gene regulation and cell-cycle progression. However, the mechanisms regulating its nuclear translocation have not yet been elucidated. It was here demonstrated that USP22 is imported into the nucleus through a mechanism mediated by nuclear localization signal (NLS). The bipartite NLS sequence KRELELLKHNPKRRKIT (aa152–168), was identified as the functional NLS for its nuclear localization. Furthermore, a short cluster of basic amino acid residues KRRK within this bipartite NLS plays the primary role in nuclear localization and is evolutionarily conserved in USP22 homologues. In the present study, a functional NLS and the minimal sequences required for the active targeting of USP22 to the nucleus were identified. These findings may provide a molecular basis for the mechanism underlying USP22 nuclear trafficking and function.

  20. Nuclear localization of human DNA mismatch repair protein exonuclease 1 (hEXO1)

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Nielsen, Finn Cilius; Vinther, Lena

    2007-01-01

    localization signals (NLSs) in hEXO1. Using fluorescent fusion proteins, we show that the sequence 418KRPR421, which exhibit strong homology to other monopartite NLS sequences, is responsible for correct nuclear localization of hEXO1. This NLS sequence is located in a region that is also required for hEXO1......Human exonuclease 1 (hEXO1) is implicated in DNA mismatch repair (MMR) and mutations in hEXO1 may be associated with hereditary nonpolyposis colorectal cancer (HNPCC). Since the subcellular localization of MMR proteins is essential for proper MMR function, we characterized possible nuclear...... interaction with hMLH1 and we show that defective nuclear localization of hEXO1 mutant proteins could be rescued by hMLH1 or hMSH2. Both hEXO1 and hMLH1 form complexes with the nuclear import factors importin beta/alpha1,3,7 whereas hMSH2 specifically recognizes importin beta/alpha3. Taken together, we infer...

  1. Development of passive condensers for accident localization systems at nuclear power plants in the former USSR

    International Nuclear Information System (INIS)

    Kuznecov, M.V.

    1992-01-01

    The development is summarized of passive condensers for accident localization systems at nuclear power plants (with RBMK and WWER reactors) in the former USSR. Basic properties and criteria defining their availability are described, as are experimental tests and technical solution optimization results. (author) 2 fig

  2. Characterization, subcellular localization and nuclear targeting of casein kinase 2 from Zea mays

    DEFF Research Database (Denmark)

    Peracchia, G; Jensen, A B; Culiáñez-Macià, F A

    1999-01-01

    by using in-frame fusions of the maize CK2alpha subunit to the reporter gene encoding beta-glucuronidase (GUS) which were assayed in transiently transformed onion epidermal cells. Analysis of chimeric constructs identified one region containing a nuclear localization signal (NLS) that is highly conserved...

  3. Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

    International Nuclear Information System (INIS)

    Takahashi, Tadanobu; Moriyama, Yusuke; Ikari, Akira; Sugatani, Junko; Suzuki, Takashi; Miwa, Masao

    2008-01-01

    Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism

  4. 1. European conference on local democracies and nuclear power plants. Conference proceedings

    International Nuclear Information System (INIS)

    2000-01-01

    The Group of European Municipalities with Nuclear Facilities (GMF) was constituted in 1999. Its basic objectives are to keep and strengthen the relations between municipalities with the aim of consolidating a European network of municipalities with common problems; and to participate in European forums on the future of nuclear energy, contributing and helping in decision making processes. The GMF wants to become a support element to the local authorities of nuclear areas in order to foster their participation in the decision making processes, working continuously in collaboration with other agents of the nuclear sector, especially with the authorities of the European Commission, assuming that its major contribution is the knowledge of the everyday territorial reality, as a fundamental element that should be born in mind in all defined policies, whether on european or national level. It is stated that the debate on the future of nuclear energy represents a new era for the municipalities with nuclear facilities across Europe and that international cooperation will open the way for a better use of nuclear energy in Europe

  5. Characterization of Nuclear Localization Signals (NLSs) and Function of NLSs and Phosphorylation of Serine Residues in Subcellular and Subnuclear Localization of Transformer-2β (Tra2β)*

    Science.gov (United States)

    Li, Shu-Jing; Qi, Yao; Zhao, Jing-Jing; Li, Ya; Liu, Xiao-Yan; Chen, Xian-Hua; Xu, Ping

    2013-01-01

    The serine/arginine-rich (SR) proteins are one type of major actors in regulation of pre-mRNA splicing. Their functions are closely related to the intracellular spatial organization. The RS domain and phosphorylation status of SR proteins are two critical factors in determining the subcellular distribution. Mammalian Transformer-2β (Tra2β) protein, a member of SR proteins, is known to play multiple important roles in development and diseases. In the present study, we characterized the subcellular and subnuclear localization of Tra2β protein and its related mechanisms. The results demonstrated that in the brain the nuclear and cytoplasmic localization of Tra2β were correlated with its phosphorylation status. Using deletional mutation analysis, we showed that the nuclear localization of Tra2β was determined by multiple nuclear localization signals (NLSs) in the RS domains. The point-mutation analysis disclosed that phosphorylation of serine residues in the NLSs inhibited the function of NLS in directing Tra2β to the nucleus. In addition, we identified at least two nuclear speckle localization signals within the RS1 domain, but not in the RS2 domain. The nuclear speckle localization signals determined the localization of RS1 domain-contained proteins to the nuclear speckle. The function of the signals did not depend on the presence of serine residues. The results provide new insight into the mechanisms by which the subcellular and subnuclear localization of Tra2β proteins are regulated. PMID:23396973

  6. A novel bipartite nuclear localization signal with an atypically long linker in DOF transcription factors.

    Science.gov (United States)

    Krebs, Jonas; Mueller-Roeber, Bernd; Ruzicic, Slobodan

    2010-05-01

    Large molecules require a nuclear localization signal (NLS) for translocation into the nucleus. Classical NLSs are rich in basic amino acids and they represent three groups, based on their structural features: SV40 T-antigen-type, yeast mating factor Matalpha-2-type, and bipartite NLSs. DNA-binding-with-one-finger (DOF) transcription factors play important roles in plants, and although their nuclear localization has been demonstrated in several cases, public protein localization prediction tools fail to detect NLS motifs in these proteins. Here, we demonstrate that an atypical bipartite NLS with a 17 amino acid long linker between its flanking basic regions directs Arabidopsis thaliana DOF proteins to the cell nucleus. The novel bipartite NLS is highly conserved in plant DOF transcription factors, including the single DOF protein in the green alga Chlamydomonas reinhardtii. Copyright 2010 Elsevier GmbH. All rights reserved.

  7. EpCAM nuclear localization identifies aggressive Thyroid Cancer and is a marker for poor prognosis

    International Nuclear Information System (INIS)

    Ralhan, Ranju; Cao, Jun; Lim, Terence; MacMillan, Christina; Freeman, Jeremy L; Walfish, Paul G

    2010-01-01

    Proteolytic cleavage of the extracellular domain (EpEx) of Epithelial cell adhesion molecule (EpCAM) and nuclear signaling by its intracellular oncogenic domain Ep-ICD has recently been implicated in increased proliferation of cancer cells. The clinical significance of Ep-ICD in human tumors remains an enigma. EpEx, Ep-ICD and β-catenin immunohistochemistry using specific antibodies was conducted on 58 archived thyroid cancer (TC) tissue blocks from 34 patients and correlated with survival analysis of these patients for up to 17 years. The anaplastic (ATC) and aggressive thyroid cancers showed loss of EpEx and increased nuclear and cytoplasmic accumulation of Ep-ICD. In contrast, the low grade papillary thyroid cancers (PTC) showed membranous EpEx and no detectable nuclear Ep-ICD. The ATC also showed concomitant nuclear expression of Ep-ICD and β-catenin. Kaplan-Meier Survival analysis revealed reduced overall survival (OS) for TC patients showing nuclear Ep-ICD expression or loss of membranous EpEx (p < 0.0004), median OS = 5 months as compared to 198 months for patients who did not show nuclear Ep-ICD or demonstrated only membranous EpE. We report reciprocal loss of membrane EpEx but increased nuclear and cytoplasmic accumulation of Ep-ICD in aggressive TC; nuclear Ep-ICD correlated with poor OS of TC patients. Thus nuclear Ep-ICD localization may serve as a useful biomarker for aggressive TC and may represent a novel diagnostic, prognostic and therapeutic target for aggressive TC

  8. Troponin T nuclear localization and its role in aging skeletal muscle.

    Science.gov (United States)

    Zhang, Tan; Birbrair, Alexander; Wang, Zhong-Min; Taylor, Jackson; Messi, María Laura; Delbono, Osvaldo

    2013-04-01

    Troponin T (TnT) is known to mediate the interaction between Tn complex and tropomyosin (Tm), which is essential for calcium-activated striated muscle contraction. This regulatory function takes place in the myoplasm, where TnT binds Tm. However, recent findings of troponin I and Tm nuclear translocation in Drosophila and mammalian cells imply other roles for the Tn-Tm complex. We hypothesized that TnT plays a nonclassical role through nuclear translocation. Immunoblotting with different antibodies targeting the NH2- or COOH-terminal region uncovered a pool of fast skeletal muscle TnT3 localized in the nuclear fraction of mouse skeletal muscle as either an intact or fragmented protein. Construction of TnT3-DsRed fusion proteins led to the further observation that TnT3 fragments are closely related to nucleolus and RNA polymerase activity, suggesting a role for TnT3 in regulating transcription. Functionally, overexpression of TnT3 fragments produced significant defects in nuclear shape and caused high levels of apoptosis. Interestingly, nuclear TnT3 and its fragments were highly regulated by aging, thus creating a possible link between the deleterious effects of TnT3 and sarcopenia. We propose that changes in nuclear TnT3 and its fragments cause the number of myonuclei to decrease with age, contributing to muscle damage and wasting.

  9. 'Nuclear emergency preparedness' for local residents. Support of on-site training of many kinds of places and people

    International Nuclear Information System (INIS)

    Kameda, Kazuhisa

    2005-01-01

    In order to support and ensure the nuclear emergency preparedness system and safety of residents in cities, towns and villages, NPO Nuclear Emergency Preparedness Support Center was established in May, 2003. 130 on-site training and education classes were held and above 2,000 participants attended to them for two years. Objects of the countermeasure of nuclear emergency preparedness in local area and residents, what is nuclear emergency for inhabitants, what is use of Table of International Nuclear Event Scale (INES)?, a use of INES, relation between INES level and the nuclear emergency preparedness system are discussed. (S.Y.)

  10. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  11. Characterization of the nuclear localization signal of the hepatitis delta virus antigen

    International Nuclear Information System (INIS)

    Alves, Carolina; Freitas, Natalia; Cunha, Celso

    2008-01-01

    The delta antigen (HDAg) is the only protein encoded by the hepatitis delta virus (HDV) RNA genome. The HDAg contains an RNA binding domain, a dimerization domain, and a nuclear localization signal (NLS). The nuclear import of HDV RNPs is thought to be one of the first tasks of the HDAg during the HDV replication cycle. Using c-myc-PK fusions with several regions of the HDAg in transfection assays in Huh7 cells, we found that the HDAg NLS consists of a single stretch of 10 amino acids, EGAPPAKRAR, located in positions 66-75. Deletion and mutation analysis of this region showed that both the acidic glutamic acid residue at position 66 and the basic arginine residue at position 75 are essential for promoting nuclear import

  12. Public attitudes to nuclear power: the role of local authority radiation monitoring

    International Nuclear Information System (INIS)

    Cassidy, W.

    1989-01-01

    We are all conscious of the importance of energy to our modern society. Unfortunately, every energy source available brings with its benefits some attendant hazards to the environment and health. These risks and benefits must be evaluated and weighed against one another. Somerset, in the west of England, has two nuclear reactors at Hinkley Point, a Magnox and an AGR. With a public inquiry to start in October 1988 into the building of a PWR at Hinkley Point, nuclear issues are very much in mind. This paper discusses local attitudes in Somerset to nuclear power and mentions some of the reasons for them. It identifies a need for more and better public information, focusing on information about radiation in the environment. It describes the actions Somerset has taken to meet this need, and considers the role of this action in the broader regional and national context. (author)

  13. Assessment of national systems for obtaining local acceptance of nuclear waste management siting activities

    International Nuclear Information System (INIS)

    Paige, H.W.; Owens, J.E.

    1984-01-01

    On behalf of the United States Department of Energy (DOE), International Energy Associates Limited (IEAL) of Washington, D.C. has conducted surveys and analyses of fourteen countries' plans and approaches for dealing with the problems of obtaining local siting acceptance for nuclear waste management facilities. It was determined that the following elements of the formal systems generally facilitate and/or expedite waste management siting decisions: (1) a clear-cut pro-nuclear power position on the part of the government; (2) a willingness on the part of the central government to exert (with prudence and restraint) its pre-emptive rights in nuclear matters; (3) political structures in which the heads of regional or provincial governments are appointed by the central government; (4) national laws that link reactor licensing with a detailed plan for waste management; (5) an established and stable policy with regard to reprocessing. In contrast, it was determined that the following elements of the formal system generally hinder waste management siting activities: (1) historically strong local land used veto laws; (2) the use of national referenda for making nuclear decisions; (3) requirements for public hearings. The informal approaches fall into the following five categories: (1) political: e.g. assertion of will by political leaders, activities to enlist support of local politicians, activities to broaden involvement in decision-making; (2) economic: e.g. emphasis on normal benefits, provision for additional economic benefits; (3) siting: e.g. at or near existing nuclear facilities, on government or utility property, at multiple locations to spread the political burden; (4) timing: e.g. decoupling drilling activities from ultimate repository site decision, deliberate deferral to (long-range) future; (5) education: e.g. creation of special government programmes, enlisting of media support

  14. Nuclear localization and secretion competence are conserved among henipavirus matrix proteins.

    Science.gov (United States)

    McLinton, Elisabeth C; Wagstaff, Kylie M; Lee, Alexander; Moseley, Gregory W; Marsh, Glenn A; Wang, Lin-Fa; Jans, David A; Lieu, Kim G; Netter, Hans J

    2017-04-01

    Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in Southeast Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus are highly virulent pathogens transmitted from bats to animals and humans, while the henipavirus Cedar virus seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell's cytoplasm, where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release. Comparative studies were performed to assess whether M protein nuclear localization is a common feature of the henipaviruses, including the recently sequenced (although not yet isolated) Ghanaian bat henipavirus (Kumasi virus, GH-M74a virus) and Mojiang virus. Live-cell confocal microscopy revealed that nuclear translocation of GFP-fused M protein is conserved between henipaviruses in both human- and bat-derived cell lines. However, the efficiency of M protein nuclear localization and virus-like particle budding competency varied. Additionally, Cedar virus-, Kumasi virus- and Mojiang virus-M proteins were mutated in a bipartite nuclear localization signal, indicating that a key lysine residue is essential for nuclear import, export and induction of budding events, as previously reported for NiV-M. The results of this study suggest that the M proteins of henipaviruses may utilize a similar nucleocytoplasmic trafficking pathway as an essential step during viral replication in both humans and bats.

  15. Analysis of nuclear localization of interleukin-1 family cytokines by flow cytometry.

    Science.gov (United States)

    Ross, Ralf; Grimmel, Jan; Goedicke, Sybelle; Möbus, Anna M; Bulau, Ana-Maria; Bufler, Philip; Ali, Shafaqat; Martin, Michael U

    2013-01-31

    The dual function cytokines IL-1α, IL-33 and IL-37 are members of the IL-1 cytokine family. Besides of being able to bind to their cognate receptors on target cells, they can act intracellularly in the producing cell. All three are able to translocate to the nucleus and have been discussed to affect gene expression. In order to compare and quantitate nuclear translocation of these IL-1 family members we established a robust technique which enables to measure nuclear localization on a single cell level by flow cytometry. Vectors encoding fusion proteins of different IL-1 family members with enhanced green fluorescent protein were cloned and cell lines transiently transfected with these. Fluorescent fusion proteins in intact cells or in isolated nuclei were detected subsequently by fluorescence microscopy and flow cytometry, respectively. Depending on the cellular system, cells and nuclei were distinguishable by flow cytometry in forward scatter/sideward scatter. Fluorescent fusion proteins were detectable in isolated nuclei up to three days following preparation. Signal intensity of fusion proteins of IL-33 and IL-37 in isolated nuclei but not of IL-1α, was markedly increased by fixation with paraformaldehyde, directly following cell lysis, indicating that IL-1α binds stronger to nuclear structures than IL-33 and IL-37. Nuclear translocation of fluorescent IL-37 fusion proteins in a stably transfected RAW264.7 mouse macrophage cell line required stimulation with lipopolysaccharide. Applying this method we demonstrated that a prolonged lag phase of more than 15h before LPS-stimulated nuclear translocation was detected. In summary, we present a robust method to analyze and quantitate nuclear localization of IL-1 cytokine family members. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. State and local planning procedures dealing with social and economic impacts from nuclear power plants

    International Nuclear Information System (INIS)

    Curry, M.; Goodrieght, J.; Green, M.; Merwin, D.; Smith, R.

    1977-01-01

    The roles of state and local agencies in planning for and managing social and economic impacts of nuclear power plants are studied. In order to be effective in these roles state and local agencies must work with each other as well as the NRC. A comparative case study approach is used which analyzes six sites in three West Coast states. The case studies included plants in operation, plants under construction, and plants still in the planning stages. In contrast to some states, all three of these states have moderately centralized procedures for siting power plants, and all have strong environmental laws

  17. Description of the local dose rate measuring system for the Angra 2 nuclear power plant

    International Nuclear Information System (INIS)

    Costa, Lilian Rose Sobral da; Souza Mendes, Jorge Eduardo de

    1995-01-01

    The equipment used and the measured value processing involved in the Local Dose Rate Measuring System is described including the installation points for the measuring equipment in the reactor building, the auxiliary building and at the main gate of Angra 2 Nuclear Power Plant. Under normal operating conditions protecting of the personnel is ensured by measuring the local dose rate at those points which are generally accessible. In some cases , fixed sensors are not suitable so that mobile equipment is used. (author). 2 refs., 1 fig

  18. Local negotiation on compensation siting of the spent nuclear fuel repository in Finland

    International Nuclear Information System (INIS)

    Kojo, Matti

    2007-01-01

    The aim of the paper is to analyse the local negotiation process between the Municipality of Eurajoki and the nuclear power company Teollisuuden Voima (TVO) and the nuclear waste management company Posiva Oy. The aim of the negotiations was to find an acceptable form of compensation for siting a spent nuclear fuel repository in Olkiluoto, Finland. The paper includes background information on the siting process in Finland, the local political setting in the Municipality of Eurajoki and a description of the negotiation process. The analysis of the negotiations on compensation is important for better understanding the progress of the Finnish siting process. The paper describes the picture of the contest to host the spent nuclear fuel repository. It also provides more information on the relationship between the Municipality of Eurajoki and the power company TVO. The negotiations on compensation and the roles of various players in the negotiations have not been studied in detail because the minutes of the Vuojoki liaison group were not available before the decision of the Supreme Administrative Court in May 2006. (author)

  19. Simulating the dynamics of the neutron flux in a nuclear reactor by locally recurrent neural networks

    International Nuclear Information System (INIS)

    Cadini, F.; Zio, E.; Pedroni, N.

    2007-01-01

    In this paper, a locally recurrent neural network (LRNN) is employed for approximating the temporal evolution of a nonlinear dynamic system model of a simplified nuclear reactor. To this aim, an infinite impulse response multi-layer perceptron (IIR-MLP) is trained according to a recursive back-propagation (RBP) algorithm. The network nodes contain internal feedback paths and their connections are realized by means of IIR synaptic filters, which provide the LRNN with the necessary system state memory

  20. A set of enhanced green fluorescent protein concatemers for quantitative determination of nuclear localization signal strength.

    Science.gov (United States)

    Böhm, Jennifer; Thavaraja, Ramya; Giehler, Susanne; Nalaskowski, Marcus M

    2017-09-15

    Regulated transport of proteins between nucleus and cytoplasm is an important process in the eukaryotic cell. In most cases, active nucleo-cytoplasmic protein transport is mediated by nuclear localization signal (NLS) and/or nuclear export signal (NES) motifs. In this study, we developed a set of vectors expressing enhanced GFP (EGFP) concatemers ranging from 2 to 12 subunits (2xEGFP to 12xEGFP) for analysis of NLS strength. As shown by in gel GFP fluorescence analysis and αGFP Western blotting, EGFP concatemers are expressed as fluorescent full-length proteins in eukaryotic cells. As expected, nuclear localization of concatemeric EGFPs decreases with increasing molecular weight. By oligonucleotide ligation this set of EGFP concatemers can be easily fused to NLS motifs. After determination of intracellular localization of EGFP concatemers alone and fused to different NLS motifs we calculated the size of a hypothetic EGFP concatemer showing a defined distribution of EGFP fluorescence between nucleus and cytoplasm (n/c ratio = 2). Clear differences of the size of the hypothetic EGFP concatemer depending on the fused NLS motif were observed. Therefore, we propose to use the size of this hypothetic concatemer as quantitative indicator for comparing strength of different NLS motifs. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Growth hormone-specific induction of the nuclear localization of porcine growth hormone receptor in porcine hepatocytes.

    Science.gov (United States)

    Lan, H N; Hong, P; Li, R N; Shan, A S; Zheng, X

    2017-10-01

    The phenomenon of nuclear translocation of growth hormone receptor (GHR) in human, rat, and fish has been reported. To date, this phenomenon has not been described in a domestic animal (such as pig). In addition, the molecular mechanisms of GHR nuclear translocation have not been thoroughly elucidated. To this end, porcine hepatocytes were isolated and used as a cell model. We observed that porcine growth hormone (pGH) can induce porcine GHR's nuclear localization in porcine hepatocytes. Subsequently, the dynamics of pGH-induced pGHR's nuclear localization were analyzed and demonstrated that pGHR's nuclear localization occurs in a time-dependent manner. Next, we explored the mechanism of pGHR nuclear localization using different pGHR ligands, and we demonstrated that pGHR's nuclear translocation is GH(s)-dependent. We also observed that pGHR translocates into cell nuclei in a pGH dimerization-dependent fashion, whereas further experiments indicated that IMPα/β is involved in the nuclear translocation of the pGH-pGHR dimer. The pGH-pGHR dimer may form a pGH-GHR-JAK2 multiple complex in cell nuclei, which would suggest that similar to its function in the cell membrane, the nuclear-localized pGH-pGHR dimer might still have the ability to signal. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Alimentary tract absorption (f1 values) for radionuclides in local and regional fallout from nuclear tests.

    Science.gov (United States)

    Ibrahim, Shawki A; Simon, Steven L; Bouville, André; Melo, Dunstana; Beck, Harold L

    2010-08-01

    This paper presents gastrointestinal absorption fractions (f1 values) for estimating internal doses from local and regional fallout radionuclides due to nuclear tests. The choice of f1 values are based on specific circumstances of weapons test conditions and a review of reported f1 values for elements in different physical and chemical states. Special attention is given to fallout from nuclear tests conducted at the Marshall Islands. We make a distinction between the f1 values for intakes of radioactive materials immediately after deposition (acute intakes) and intakes that occur in the course of months and years after deposition, following incorporation into terrestrial and aquatic foodstuffs (chronic intakes). Multiple f1 values for different circumstances where persons are exposed to radioactive fallout (e.g., local vs. regional fallout and coral vs. continental tests) are presented when supportive information is available. In some cases, our selected f1 values are similar to those adopted by the International Commission on Radiological Protection (ICRP) (e.g., iodine and most actinides). However, f1 values for cesium and strontium derived from urine bioassay data of the Marshallese population are notably lower than the generic f1 values recommended by ICRP, particularly for acute intakes from local fallout (0.4 and 0.05 for Cs and Sr, respectively). The f1 values presented here form the first complete set of values relevant to realistic dose assessments for exposure to local or regional radioactive fallout.

  3. Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells.

    Science.gov (United States)

    Landerer, Eduardo; Villegas, Jaime; Burzio, Veronica A; Oliveira, Luciana; Villota, Claudio; Lopez, Constanza; Restovic, Franko; Martinez, Ronny; Castillo, Octavio; Burzio, Luis O

    2011-08-01

    We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and -2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria. FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse. In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associated to heterochromatin. In cancer cells, only the SncmtRNA was expressed and was found associated to heterochromatin and nucleoli. The ubiquitous localization of these mitochondrial transcripts in the nucleus suggests that they are new players in the mitochondrial-nuclear communication pathway or retrograde signaling. Down regulation of the ASncmtRNAs seems to be an important step on neoplastic transformation and cancer progression.

  4. Drosophila proteins involved in metabolism of uracil-DNA possess different types of nuclear localization signals.

    Science.gov (United States)

    Merényi, Gábor; Kónya, Emese; Vértessy, Beáta G

    2010-05-01

    Adequate transport of large proteins that function in the nucleus is indispensable for cognate molecular events within this organelle. Selective protein import into the nucleus requires nuclear localization signals (NLS) that are recognized by importin receptors in the cytoplasm. Here we investigated the sequence requirements for nuclear targeting of Drosophila proteins involved in the metabolism of uracil-substituted DNA: the recently identified uracil-DNA degrading factor, dUTPase, and the two uracil-DNA glycosylases present in Drosophila. For the uracil-DNA degrading factor, NLS prediction identified two putative NLS sequences [PEKRKQE(320-326) and PKRKKKR(347-353)]. Truncation and site-directed mutagenesis using YFP reporter constructs showed that only one of these basic stretches is critically required for efficient nuclear localization in insect cells. This segment corresponds to the well-known prototypic NLS of SV40 T-antigen. An almost identical NLS segment is also present in the Drosophila thymine-DNA glycosylase, but no NLS elements were predicted in the single-strand-specific monofunctional uracil-DNA glycosylase homolog protein. This latter protein has a molecular mass of 31 kDa, which may allow NLS-independent transport. For Drosophila dUTPase, two isoforms with distinct features regarding molecular mass and subcellular distribution were recently described. In this study, we characterized the basic PAAKKMKID(10-18) segment of dUTPase, which has been predicted to be a putative NLS by in silico analysis. Deletion studies, using YFP reporter constructs expressed in insect cells, revealed the importance of the PAA(10-12) tripeptide and the ID(17-18) dipeptide, as well as the role of the PAAK(10-13) segment in nuclear localization of dUTPase. We constructed a structural model that shows the molecular basis of such recognition in three dimensions.

  5. Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer.

    Science.gov (United States)

    Vlug, Eva J; van de Ven, Robert A H; Vermeulen, Jeroen F; Bult, Peter; van Diest, Paul J; Derksen, Patrick W B

    2013-10-01

    Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to E-cadherin-dependent regulation of contact inhibition in breast cancer cells. In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p cancers and conditional mouse models of human lobular breast cancer. Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

  6. A functional nuclear localization sequence in the C. elegans TRPV channel OCR-2.

    Directory of Open Access Journals (Sweden)

    Meredith J Ezak

    Full Text Available The ability to modulate gene expression in response to sensory experience is critical to the normal development and function of the nervous system. Calcium is a key activator of the signal transduction cascades that mediate the process of translating a cellular stimulus into transcriptional changes. With the recent discovery that the mammalian Ca(v1.2 calcium channel can be cleaved, enter the nucleus and act as a transcription factor to control neuronal gene expression, a more direct role for the calcium channels themselves in regulating transcription has begun to be appreciated. Here we report the identification of a nuclear localization sequence (NLS in the C. elegans transient receptor potential vanilloid (TRPV cation channel OCR-2. TRPV channels have previously been implicated in transcriptional regulation of neuronal genes in the nematode, although the precise mechanism remains unclear. We show that the NLS in OCR-2 is functional, being able to direct nuclear accumulation of a synthetic cargo protein as well as the carboxy-terminal cytosolic tail of OCR-2 where it is endogenously found. Furthermore, we discovered that a carboxy-terminal portion of the full-length channel can localize to the nucleus of neuronal cells. These results suggest that the OCR-2 TRPV cation channel may have a direct nuclear function in neuronal cells that was not previously appreciated.

  7. Nuclear Pores Regulate Muscle Development and Maintenance by Assembling a Localized Mef2C Complex.

    Science.gov (United States)

    Raices, Marcela; Bukata, Lucas; Sakuma, Stephen; Borlido, Joana; Hernandez, Leanora S; Hart, Daniel O; D'Angelo, Maximiliano A

    2017-06-05

    Nuclear pore complexes (NPCs) are multiprotein channels connecting the nucleus with the cytoplasm. NPCs have been shown to have tissue-specific composition, suggesting that their function can be specialized. However, the physiological roles of NPC composition changes and their impacts on cellular processes remain unclear. Here we show that the addition of the Nup210 nucleoporin to NPCs during myoblast differentiation results in assembly of an Mef2C transcriptional complex required for efficient expression of muscle structural genes and microRNAs. We show that this NPC-localized complex is essential for muscle growth, myofiber maturation, and muscle cell survival and that alterations in its activity result in muscle degeneration. Our findings suggest that NPCs regulate the activity of functional gene groups by acting as scaffolds that promote the local assembly of tissue-specific transcription complexes and show how nuclear pore composition changes can be exploited to regulate gene expression at the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Identification and characterization of multiple conserved nuclear localization signals within adenovirus E1A

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Kris S.; Cohen, Michael J.; Fonseca, Greg J.; Todorovic, Biljana; King, Cason R. [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Yousef, Ahmed F. [Department of Chemical and Environmental Engineering, Masdar Institute, Abu Dhabi (United Arab Emirates); Zhang, Zhiying [College of Animal Science and Technologies, Northwest A and F University, Yangling, Shaanxi 712100 (China); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada); Department of Oncology, Western University, London Regional Cancer Program, London, ON, Canada N6A 4L6 (Canada)

    2014-04-15

    The human adenovirus 5 (HAdV-5) E1A protein has a well defined canonical nuclear localization signal (NLS) located at its C-terminus. We used a genetic assay in the yeast Saccharomyces cerevisiae to demonstrate that the canonical NLS is present and functional in the E1A proteins of each of the six HAdV species. This assay also detects a previously described non-canonical NLS within conserved region 3 and a novel active NLS within the N-terminal/conserved region 1 portion of HAdV-5 E1A. These activities were also present in the E1A proteins of each of the other five HAdV species. These results demonstrate that, despite substantial differences in primary sequence, HAdV E1A proteins are remarkably consistent in that they contain one canonical and two non-canonical NLSs. By utilizing independent mechanisms, these multiple NLSs ensure nuclear localization of E1A in the infected cell. - Highlights: • HAdV E1A uses multiple mechanisms for nuclear import. • We identified an additional non-canonical NLS in the N-terminal/CR1 portion of E1A. • The new NLS does not contact importin-alpha directly. • All NLSs are functionally conserved in the E1A proteins of all 6 HAdV species.

  9. Identification of two functional nuclear localization signals in the capsid protein of duck circovirus

    International Nuclear Information System (INIS)

    Xiang, Qi-Wang; Zou, Jin-Feng; Wang, Xin; Sun, Ya-Ni; Gao, Ji-Ming; Xie, Zhi-Jing; Wang, Yu; Zhu, Yan-Li; Jiang, Shi-Jin

    2013-01-01

    The capsid protein (CP) of duck circovirus (DuCV) is the major immunogenic protein and has a high proportion of arginine residues concentrated at the N terminus of the protein, which inhibits efficient mRNA translation in prokaryotic expression systems. In this study, we investigated the subcellular distribution of DuCV CP expressed via recombinant baculoviruses in Sf9 cells and the DNA binding activities of the truncated recombinant DuCV CPs. The results showed that two independent bipartite nuclear localization signals (NLSs) situated at N-terminal 1–17 and 18–36 amino acid residue of the CP. Moreover, two expression level regulatory signals (ELRSs) and two DNA binding signals (DBSs) were also mapped to the N terminus of the protein and overlapped with the two NLSs. The ability of CP to bind DNA, coupled with the karyophilic nature of this protein, strongly suggests that it may be responsible for nuclear targeting of the viral genome.

  10. Intense deuterium nuclear fusion of pycnodeuterium-lumps coagulated locally within highly deuterated atom clusters

    CERN Document Server

    Yoshiaki, A; Zhang, Y C

    2002-01-01

    Embedded nano-Pd particles of 5 nm in size instantly abundant D-atoms more than 250% in the atomic ratio against Pd-atoms at room temperature when they are kept in D sub 2 gas pressurized to less than 10 atm. In such ultrahigh densities, 2-4 D-atoms can be coagulated inside each octahedral space of Pd lattice (pycnodeuterium-lump). When a stimulation energy such as latticequake causing by ultrasonic wave was supplied to those highly deuterated Pd particles, intense deuterium nuclear fusion (''solid fusion'') was generated there and both excess heat and sup 4 He gas were abundantly produced. Naturally, these facts can not be realized at all in bulk Pd. The results show that the nuclear fusion occurs without any hazardous rays in pycnodeuterium-lumps coagulated locally inside the each cell of the host metal lattice. These unit cells correspond to minimum unit of the solid fusion reactor as a ''Lattice Reactor''. (author)

  11. OCT despeckling via weighted nuclear norm constrained non-local low-rank representation

    Science.gov (United States)

    Tang, Chang; Zheng, Xiao; Cao, Lijuan

    2017-10-01

    As a non-invasive imaging modality, optical coherence tomography (OCT) plays an important role in medical sciences. However, OCT images are always corrupted by speckle noise, which can mask image features and pose significant challenges for medical analysis. In this work, we propose an OCT despeckling method by using non-local, low-rank representation with weighted nuclear norm constraint. Unlike previous non-local low-rank representation based OCT despeckling methods, we first generate a guidance image to improve the non-local group patches selection quality, then a low-rank optimization model with a weighted nuclear norm constraint is formulated to process the selected group patches. The corrupted probability of each pixel is also integrated into the model as a weight to regularize the representation error term. Note that each single patch might belong to several groups, hence different estimates of each patch are aggregated to obtain its final despeckled result. Both qualitative and quantitative experimental results on real OCT images show the superior performance of the proposed method compared with other state-of-the-art speckle removal techniques.

  12. Identification of a nuclear localization sequence in the polyomavirus capsid protein VP2

    Science.gov (United States)

    Chang, D.; Haynes, J. I. 2nd; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    A nuclear localization signal (NLS) has been identified in the C-terminal (Glu307-Glu-Asp-Gly-Pro-Gln-Lys-Lys-Lys-Arg-Arg-Leu318) amino acid sequence of the polyomavirus minor capsid protein VP2. The importance of this amino acid sequence for nuclear transport of newly synthesized VP2 was demonstrated by a genetic "subtractive" study using the constructs pSG5VP2 (expressing full-length VP2) and pSG5 delta 3VP2 (expressing truncated VP2, lacking amino acids Glu307-Leu318). These constructs were transfected into COS-7 cells, and the intracellular localization of the VP2 protein was determined by indirect immunofluorescence. These studies revealed that the full-length VP2 was localized in the nucleus, while the truncated VP2 protein was localized in the cytoplasm and not transported to the nucleus. A biochemical "additive" approach was also used to determine whether this sequence could target nonnuclear proteins to the nucleus. A synthetic peptide identical to VP2 amino acids Glu307-Leu318 was cross-linked to the nonnuclear proteins bovine serum albumin (BSA) or immunoglobulin G (IgG). The conjugates were then labeled with fluorescein isothiocyanate and microinjected into the cytoplasm of NIH 3T6 cells. Both conjugates localized in the nucleus of the microinjected cells, whereas unconjugated BSA and IgG remained in the cytoplasm. Taken together, these genetic subtractive and biochemical additive approaches have identified the C-terminal sequence of polyoma-virus VP2 (containing amino acids Glu307-Leu318) as the NLS of this protein.

  13. Novel signal-dependent filter bank method for identification of multiple basal ganglia nuclei in Parkinsonian patients

    Science.gov (United States)

    Pinzon-Morales, R. D.; Orozco-Gutierrez, A. A.; Castellanos-Dominguez, G.

    2011-06-01

    Microelectrode recordings are a valuable tool for assisting localization targets during deep brain stimulation procedures in Parkinson's disease neurosurgery. Attempts to automate and standardize this process have been limited by variability in patient neurophysiology and strong dynamics of microelectrode recordings. In this paper, a methodology for the identification of basal ganglia nuclei is presented that is based on a signal-dependent filter bank method using microelectrode recordings. The method is a customized realization of the discrete wavelet transform via the lifting scheme that is optimally tuned by genetic algorithms. Using this method, unique mother wavelet functions that exhibit an adaptable spectrum to the microelectrode recording dynamic are generated. Additionally, by extracting morphological features from the space-transformed microelectrode recording, it is possible to integrate them into three-dimensional (3D) feature spaces with maximum class separability. Finally, high discriminant feature spaces are fed into basic classifiers to recognize up to four basal nuclei. Comparison with several existing wavelets highlights the characteristics of new mother wavelets. Additionally, classification results show that identification of addressed nuclei in the basal ganglia can be performed with 95% confidence.

  14. Arginine Methylation Regulates MEIS2 Nuclear Localization to Promote Neuronal Differentiation of Adult SVZ Progenitors

    Directory of Open Access Journals (Sweden)

    Jasmine Kolb

    2018-04-01

    Full Text Available Summary: Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate. : A hallmark of adult neurogenesis is its strong dependence on physiological stimuli and environmental signals. Schulte and colleagues show that the nuclear localization and activity of a transcriptional regulator of adult neurogenesis is controlled by posttranslational modification. Their results link intrinsic control over neuron production to external signals and help to explain how adult neurogenesis can occur “on demand.” Keywords: subventricular zone, stem cell niche, posttranslational modification, controlled nuclear import, TALE-homdomain protein, MEIS2, PBX1, CRM1, neurogenesis, stem cell niche

  15. State and local fiscal impacts associated with nuclear energy centers: some initial considerations

    International Nuclear Information System (INIS)

    Bjornstad, D.J.

    1976-04-01

    The concept of the nuclear energy center is designed to consolidate a number of electrical power reactors and/or related fuel cycle activities on a single site. Such a siting strategy would concentrate a great deal of economic activity in one area and, as a consequence, generate significant impacts on state and local governments by increasing tax bases and public service demands and by altering intergovernmental fiscal relations. This study was designed to place rough empirical measures on relevant impact variables and to highlight areas for which a need for further research was indicated.

  16. Numerical forecast test on local wind fields at Qinshan Nuclear Power Plant

    International Nuclear Information System (INIS)

    Chen Xiaoqiu

    2005-01-01

    Non-hydrostatic, full compressible atmospheric dynamics model is applied to perform numerical forecast test on local wind fields at Qinshan nuclear power plant, and prognostic data are compared with observed data for wind fields. The results show that the prognostic of wind speeds is better than that of wind directions as compared with observed results. As the whole, the results of prognostic wind field are consistent with meteorological observation data, 54% of wind speeds are within a factor of 1.5, about 61% of the deviation of wind direction within the 1.5 azimuth (≤33.75 degrees) in the first six hours. (authors)

  17. The nuclear localization of low risk HPV11 E7 protein mediated by its zinc binding domain is independent of nuclear import receptors

    International Nuclear Information System (INIS)

    Piccioli, Zachary; McKee, Courtney H.; Leszczynski, Anna; Onder, Zeynep; Hannah, Erin C.; Mamoor, Shahan; Crosby, Lauren; Moroianu, Junona

    2010-01-01

    We investigated the nuclear import of low risk HPV11 E7 protein using 1) transfection assays in HeLa cells with EGFP fusion plasmids containing 11E7 and its domains and 2) nuclear import assays in digitonin-permeabilized HeLa cells with GST fusion proteins containing 11E7 and its domains. The EGFP-11E7 and EGFP-11cE7 39-98 localized mostly to the nucleus. The GST-11E7 and GST-11cE7 39-98 were imported into the nuclei in the presence of either Ran-GDP or RanG19V-GTP mutant and in the absence of nuclear import receptors. This suggests that 11E7 enters the nucleus via a Ran-dependent pathway, independent of nuclear import receptors, mediated by a nuclear localization signal located in its C-terminal domain (cNLS). This cNLS contains the zinc binding domain consisting of two copies of Cys-X-X-Cys motif. Mutagenesis of Cys residues in these motifs changed the localization of the EGFP-11cE7/-11E7 mutants to cytoplasmic, suggesting that the zinc binding domain is essential for nuclear localization of 11E7.

  18. Application of the counterfactual method to assess of the local economic impact of a nuclear power station

    International Nuclear Information System (INIS)

    Gallo-Rivera, María Teresa; Mancha-Navarro, Tomás; Garrido-Yserte, Rubén

    2013-01-01

    Several studies have examined the local economic effects of nuclear power stations. However, their heterogeneity within countries and between countries indicate that one must be very cautious in drawing general conclusions about the positive and negative local economic effects of nuclear power stations over time. Using information about a specific nuclear facility in Spain and its zone of influence, we investigate the local economic impact of a nuclear facility by applying an infrequently used methodology called the “counterfactual” method. The purpose of this application of the counterfactual method is to establish what would have happened if the nuclear power plant had not been built where it was. This method permits observation of the impact of the nuclear power plant on the evolution of a set of variables whose influence is extremely important for the local area, such as the population, unemployment level, per capita income, and municipal governments’ revenues. Generalization of this method could offer the possibility of providing comparative results. However, the method must be complemented with other short-term approaches to provide a more specific analysis of the economic effects on the local actors involved and to offer incentives to policymakers to design and develop policies aimed at boosting economic activity in the area. - Highlights: • The Trillo Nuclear Power Plant plays a key role in stimulating its local environment. • The counterfactual method is estimated based on the performance of control group. • At least at the beginning of its operation the population dynamism was clear. • There is not strong evidence about the rise of employment and local public revenues. • The expenditure flow assesses the local turnover, jobs and municipal revenues

  19. Nuclear Localization of Diacylglycerol Kinase Alpha in K562 Cells Is Involved in Cell Cycle Progression.

    Science.gov (United States)

    Poli, Alessandro; Fiume, Roberta; Baldanzi, Gianluca; Capello, Daniela; Ratti, Stefano; Gesi, Marco; Manzoli, Lucia; Graziani, Andrea; Suh, Pann-Ghill; Cocco, Lucio; Follo, Matilde Y

    2017-09-01

    Phosphatidylinositol (PI) signaling is an essential regulator of cell motility and proliferation. A portion of PI metabolism and signaling takes place in the nuclear compartment of eukaryotic cells, where an array of kinases and phosphatases localize and modulate PI. Among these, Diacylglycerol Kinases (DGKs) are a class of phosphotransferases that phosphorylate diacylglycerol and induce the synthesis of phosphatidic acid. Nuclear DGKalpha modulates cell cycle progression, and its activity or expression can lead to changes in the phosphorylated status of the Retinoblastoma protein, thus, impairing G1/S transition and, subsequently, inducing cell cycle arrest, which is often uncoupled with apoptosis or autophagy induction. Here we report for the first time not only that the DGKalpha isoform is highly expressed in the nuclei of human erythroleukemia cell line K562, but also that its nuclear activity drives K562 cells through the G1/S transition during cell cycle progression. J. Cell. Physiol. 232: 2550-2557, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  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. Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ping [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Wang, Ningling [Department of Assisted Reproduction, Shanghai Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Lin, Xianhua; Jin, Li [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Xu, Hong, E-mail: xuhong1168@126.com [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Li, Rong [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Huang, Hefeng, E-mail: huanghefg@hotmail.com [The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China)

    2016-02-26

    Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. - Highlights: • HnRNP K localizes in the nucleus of GV-stage oocyte in a punctate distribution. • HnRNP K strongly accumulates in zygotic pronuclei as condensed spots. • The localization of hnRNP K during oogenesis and embryogenesis is characteristic. • HnRNP K might have an important role in oogenesis and embryonic development.

  2. Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos

    International Nuclear Information System (INIS)

    Zhang, Ping; Wang, Ningling; Lin, Xianhua; Jin, Li; Xu, Hong; Li, Rong; Huang, Hefeng

    2016-01-01

    Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. - Highlights: • HnRNP K localizes in the nucleus of GV-stage oocyte in a punctate distribution. • HnRNP K strongly accumulates in zygotic pronuclei as condensed spots. • The localization of hnRNP K during oogenesis and embryogenesis is characteristic. • HnRNP K might have an important role in oogenesis and embryonic development.

  3. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rahayu, Retno; Ohsaki, Eriko [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Omori, Hiroko [Central Instrumentation Laboratory Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871 (Japan); Ueda, Keiji, E-mail: kueda@virus.med.osaka-u.ac.jp [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

  4. A study on the feasibility and a possible form of local residents participation in nuclear safety regulation

    International Nuclear Information System (INIS)

    Lee, Sang Hoon; Son, Moon Kyu; Kim, Seong Sook

    2003-02-01

    It is expected that the results of this study will help policy makers in the government and nuclear industry enhance the confidence of local residents and citizens in the safety of nuclear energy. It is also believed that the citizen confidence on the nuclear energy will help them implement nuclear policies more efficiently and more safely. Considering that the newly sworn-in government is to involve citizens in wide variety of policy areas, this study fits with the policy directions of the new government. Most importantly, desirable citizen participation in public decision-making is to contribute to the enhancement of the working democracy

  5. A study on the feasibility and a possible form of local residents participation in nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Son, Moon Kyu [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kim, Seong Sook [Shila Univ., Busan (Korea, Republic of)

    2003-02-15

    It is expected that the results of this study will help policy makers in the government and nuclear industry enhance the confidence of local residents and citizens in the safety of nuclear energy. It is also believed that the citizen confidence on the nuclear energy will help them implement nuclear policies more efficiently and more safely. Considering that the newly sworn-in government is to involve citizens in wide variety of policy areas, this study fits with the policy directions of the new government. Most importantly, desirable citizen participation in public decision-making is to contribute to the enhancement of the working democracy.

  6. Protein Sub-Nuclear Localization Based on Effective Fusion Representations and Dimension Reduction Algorithm LDA

    Directory of Open Access Journals (Sweden)

    Shunfang Wang

    2015-12-01

    Full Text Available An effective representation of a protein sequence plays a crucial role in protein sub-nuclear localization. The existing representations, such as dipeptide composition (DipC, pseudo-amino acid composition (PseAAC and position specific scoring matrix (PSSM, are insufficient to represent protein sequence due to their single perspectives. Thus, this paper proposes two fusion feature representations of DipPSSM and PseAAPSSM to integrate PSSM with DipC and PseAAC, respectively. When constructing each fusion representation, we introduce the balance factors to value the importance of its components. The optimal values of the balance factors are sought by genetic algorithm. Due to the high dimensionality of the proposed representations, linear discriminant analysis (LDA is used to find its important low dimensional structure, which is essential for classification and location prediction. The numerical experiments on two public datasets with KNN classifier and cross-validation tests showed that in terms of the common indexes of sensitivity, specificity, accuracy and MCC, the proposed fusing representations outperform the traditional representations in protein sub-nuclear localization, and the representation treated by LDA outperforms the untreated one.

  7. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins

    International Nuclear Information System (INIS)

    Okada, Masashi; Hozumi, Yasukazu; Ichimura, Tohru; Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya; Iseki, Ken; Yagisawa, Hitoshi; Shinkawa, Takashi; Isobe, Toshiaki; Goto, Kaoru

    2011-01-01

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGKζ, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGKζ. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGKζ binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGKζ and NAP1Ls prohibits nuclear import of DGKζ because binding of NAP1Ls to DGKζ blocks import carrier proteins, Qip1 and NPI1, to interact with DGKζ, leading to cytoplasmic tethering of DGKζ. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGKζ and provide a clue to examine functional significance of its translocation under pathological conditions.

  8. Nuclear Localization of Mitochondrial TCA Cycle Enzymes as a Critical Step in Mammalian Zygotic Genome Activation.

    Science.gov (United States)

    Nagaraj, Raghavendra; Sharpley, Mark S; Chi, Fangtao; Braas, Daniel; Zhou, Yonggang; Kim, Rachel; Clark, Amander T; Banerjee, Utpal

    2017-01-12

    Transcriptional control requires epigenetic changes directed by mitochondrial tricarboxylic acid (TCA) cycle metabolites. In the mouse embryo, global epigenetic changes occur during zygotic genome activation (ZGA) at the 2-cell stage. Pyruvate is essential for development beyond this stage, which is at odds with the low activity of mitochondria in this period. We now show that a number of enzymatically active mitochondrial enzymes associated with the TCA cycle are essential for epigenetic remodeling and are transiently and partially localized to the nucleus. Pyruvate is essential for this nuclear localization, and a failure of TCA cycle enzymes to enter the nucleus correlates with loss of specific histone modifications and a block in ZGA. At later stages, however, these enzymes are exclusively mitochondrial. In humans, the enzyme pyruvate dehydrogenase is transiently nuclear at the 4/8-cell stage coincident with timing of human embryonic genome activation, suggesting a conserved metabolic control mechanism underlying early pre-implantation development. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Protein Sub-Nuclear Localization Based on Effective Fusion Representations and Dimension Reduction Algorithm LDA.

    Science.gov (United States)

    Wang, Shunfang; Liu, Shuhui

    2015-12-19

    An effective representation of a protein sequence plays a crucial role in protein sub-nuclear localization. The existing representations, such as dipeptide composition (DipC), pseudo-amino acid composition (PseAAC) and position specific scoring matrix (PSSM), are insufficient to represent protein sequence due to their single perspectives. Thus, this paper proposes two fusion feature representations of DipPSSM and PseAAPSSM to integrate PSSM with DipC and PseAAC, respectively. When constructing each fusion representation, we introduce the balance factors to value the importance of its components. The optimal values of the balance factors are sought by genetic algorithm. Due to the high dimensionality of the proposed representations, linear discriminant analysis (LDA) is used to find its important low dimensional structure, which is essential for classification and location prediction. The numerical experiments on two public datasets with KNN classifier and cross-validation tests showed that in terms of the common indexes of sensitivity, specificity, accuracy and MCC, the proposed fusing representations outperform the traditional representations in protein sub-nuclear localization, and the representation treated by LDA outperforms the untreated one.

  10. Expression, localization and polymorphisms of the nuclear receptor PXR in Barrett's esophagus and esophageal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Kusters Johannes G

    2011-10-01

    Full Text Available Abstract Background The continuous exposure of esophageal epithelium to refluxate may induce ectopic expression of bile-responsive genes and contribute to the development of Barrett's esophagus (BE and esophageal adenocarcinoma. In normal physiology of the gut and liver, the nuclear receptor Pregnane × Receptor (PXR is an important factor in the detoxification of xenobiotics and bile acid homeostasis. This study aimed to investigate the expression and genetic variation of PXR in reflux esophagitis (RE, Barrett's esophagus (BE and esophageal adenocarcinoma. Methods PXR mRNA levels and protein expression were determined in biopsies from patients with adenocarcinoma, BE, or RE, and healthy controls. Esophageal cell lines were stimulated with lithocholic acid and rifampicin. PXR polymorphisms 25385C/T, 7635A/G, and 8055C/T were genotyped in 249 BE patients, 233 RE patients, and 201 controls matched for age and gender. Results PXR mRNA levels were significantly higher in adenocarcinoma tissue and columnar Barrett's epithelium, compared to squamous epithelium of these BE patients (P P = 0.003. Immunohistochemical staining of PXR showed predominantly cytoplasmic expression in BE tissue, whereas nuclear expression was found in adenocarcinoma tissue. In cell lines, stimulation with lithocholic acid did not increase PXR mRNA levels, but did induce nuclear translocation of PXR protein. Genotyping of the PXR 7635A/G polymorphism revealed that the G allele was significantly more prevalent in BE than in RE or controls (P = 0.037. Conclusions PXR expresses in BE and adenocarcinoma tissue, and showed nuclear localization in adenocarcinoma tissue. Upon stimulation with lithocholic acid, PXR translocates to the nuclei of OE19 adenocarcinoma cells. Together with the observed association of a PXR polymorphism and BE, this data implies that PXR may have a function in prediction and treatment of esophageal disease.

  11. Evaluation of the basic concepts of approaches for the coexistence of nuclear energy and people/local community

    International Nuclear Information System (INIS)

    Kondo, Shunsuke; Kuroki, Shinichi; Nakagiri, Yuko

    2007-01-01

    In November 2007, the Policy Evaluation Committee compiled the report, which evaluated the basic concepts of approaches to the coexistence of nuclear energy and people/local community, specified in the Framework for Nuclear Energy Policy. The report states that the 'concerned administrative bodies are carrying out measures related to the coexistence of nuclear energy and people/local communities in line with these basic concept' and summarizes fifteen proposals conductive to the betterment and improvement of these measures, which were classified as 1) secure transparency and promotion of mutual understanding with the public, 2) development and enrichment of learning opportunities and public participation, 3) relationship between the government and local governments and 4) coexistence with local residents. The Japan Atomic Energy Commission (JAEC) considers this report to be reasonable. This article presented an overview of this activity. (T. Tanaka)

  12. Intraoperative localization of recurrent medullary carcinoma of the thyroid using indium-111 pentetreotide and a nuclear surgical probe

    Energy Technology Data Exchange (ETDEWEB)

    Waddington, W.A. (Inst. of Nuclear Medicine, Univ. Coll., London Medical School (United Kingdom)); Kettle, A.G. (Dept. of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom)); Heddle, R.M. (Dept. of Surgery, Kent and Canterbury Hospital, Canterbury (United Kingdom)); Coakley, A.J. (Dept. of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom))

    1994-04-01

    A patient with recurrent medullary thyroid cancer in the neck in whom previous surgery for recurrence had been undertaken with only partial success had the diseased tissue localized preoperatively by indium-111 pentetreotide. Scanning with technetium-99m V dimercaptosuccinic acid and iodine-123 metaiodobenzylguanidine failed to localize the tumor. Utilization of a nuclear surgical probe after preoperative [sup 111]In pentetreotide allowed accurate surgical localization of the tumour tissue. (orig.)

  13. Analysis of a predicted nuclear localization signal: implications for the intracellular localization and function of the Saccharomyces cerevisiae RNA-binding protein Scp160.

    Science.gov (United States)

    Brykailo, Melissa A; McLane, Laura M; Fridovich-Keil, Judith; Corbett, Anita H

    2007-01-01

    Gene expression is controlled by RNA-binding proteins that modulate the synthesis, processing, transport and stability of various classes of RNA. Some RNA-binding proteins shuttle between the nucleus and cytoplasm and are thought to bind to RNA transcripts in the nucleus and remain bound during translocation to the cytoplasm. One RNA-binding protein that has been hypothesized to function in this manner is the Saccharomyces cerevisiae Scp160 protein. Although the steady-state localization of Scp160 is cytoplasmic, previous studies have identified putative nuclear localization (NLS) and nuclear export (NES) signals. The goal of this study was to test the hypothesis that Scp160 is a nucleocytoplasmic shuttling protein. We exploited a variety of yeast export mutants to capture any potential nuclear accumulation of Scp160 and found no evidence that Scp160 enters the nucleus. These localization studies were complemented by a mutational analysis of the predicted NLS. Results indicate that key basic residues within the predicted NLS of Scp160 can be altered without severely affecting Scp160 function. This finding has important implications for understanding the function of Scp160, which is likely limited to the cytoplasm. Additionally, our results provide strong evidence that the presence of a predicted nuclear localization signal within the sequence of a protein should not lead to the assumption that the protein enters the nucleus in the absence of additional experimental evidence.

  14. Neural Network with Local Memory for Nuclear Reactor Power Level Control

    International Nuclear Information System (INIS)

    Uluyol, Oender; Ragheb, Magdi; Tsoukalas, Lefteri

    2001-01-01

    A methodology is introduced for a neural network with local memory called a multilayered local output gamma feedback (LOGF) neural network within the paradigm of locally-recurrent globally-feedforward neural networks. It appears to be well-suited for the identification, prediction, and control tasks in highly dynamic systems; it allows for the presentation of different timescales through incorporation of a gamma memory. A learning algorithm based on the backpropagation-through-time approach is derived. The spatial and temporal weights of the network are iteratively optimized for a given problem using the derived learning algorithm. As a demonstration of the methodology, it is applied to the task of power level control of a nuclear reactor at different fuel cycle conditions. The results demonstrate that the LOGF neural network controller outperforms the classical as well as the state feedback-assisted classical controllers for reactor power level control by showing a better tracking of the demand power, improving the fuel and exit temperature responses, and by performing robustly in different fuel cycle and power level conditions

  15. Colloquium / Preparation for nuclear post-accident. Citizens and local authorities involvement in major risks governance - proceedings

    International Nuclear Information System (INIS)

    Pascal, Michel; Villers, Anita; Sene, Monique; Godin, Francois; Quilichini, Jean-Michel; Rollinger, Francois; Delalonde, Jean-Claude; Mehl-Auget, Isabelle; Autret, Jean-Claude; Heriard Dubreuil, Gilles; Petitfrere, Michael; Lochard, Jacques; Demet, Michel; Boucherie, Jean-Claude; Calafat, Alexis; Sommade, Christian; Villain, Alain; Ragazzo, Romeo; Rengot, Marielle; Sename, Jean; Thellier, Yvette; Tremelet, David; Olszewski, Richard; Fournier, Nicolas

    2009-12-01

    During 40 years, France has chosen nuclear energy as main energy source for power generation. Today, nuclear energy covers 80% of the French electricity needs. For this reason, in France, each inhabitant lives at less than 200 km of a nuclear power plant. The September 11, 2001 terror attack has led to reconsider the nuclear risk in terms of security. In 2005, the French nuclear safety authority (ASN) has been entrusted with the preparation of a nuclear post-accident management study. This study has been mainly based on the experience feedback of the Chernobyl accident and on the dialogue with different actors of the French territory: the local authorities, the habitants, the associations and the health, environment and education actors. This colloquium represents the opening act of the joint elaboration of the management of a potential nuclear accident at the region scale. The colloquium was organized around 5 round tables: 1 - Did the nuclear safety transparency law change the situation?; 2 - Examples of pluralistic dialogues: the long-term management of a nuclear accident; 3 - How to encourage the necessary skills development of citizens? 4 - Regional development strategies in terms of nuclear risks management (incidents, effluents, wastes, transports..); 5 - New territory liabilities and citizens' legitimate aspiration in terms of health/environment: building something together. This document is the proceedings of this colloquium. It reports the exchanges between the participants

  16. Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

    Directory of Open Access Journals (Sweden)

    Zhao J

    2012-09-01

    Full Text Available Jingmou Yu,1 Xin Xie,1 Meirong Zheng,1 Ling Yu,2 Lei Zhang,1 Jianguo Zhao,1 Dengzhao Jiang,1 Xiangxin Che11Key Laboratory of Systems Biology Medicine of Jiangxi Province, College of Basic Medical Science, Jiujiang University, Jiujiang, 2Division of Nursing, 2nd Affiliated Hospital, Yichun University, Yichun, People's Republic of ChinaBackground: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS-modified polymeric micelles were studied with the aim of improving nuclear drug delivery.Methods: In this research, cholesterol-modified glycol chitosan (CHGC was synthesized. NLS-conjugated CHGC (NCHGC was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX, an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay in HeLa and HepG2 cells.Results: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater

  17. Monodisperse magnetite nanoparticles coupled with nuclear localization signal peptide for cell-nucleus targeting.

    Science.gov (United States)

    Xu, Chenjie; Xie, Jin; Kohler, Nathan; Walsh, Edward G; Chin, Y Eugene; Sun, Shouheng

    2008-03-07

    Functionalization of monodisperse superparamagnetic magnetite (Fe(3)O(4)) nanoparticles for cell specific targeting is crucial for cancer diagnostics and therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), to improve the efficiency in anticancer drug delivery, and to eliminate tumor cells by magnetic fluid hyperthermia. Herein we report the nucleus-targeting Fe(3)O(4) nanoparticles functionalized with protein and nuclear localization signal (NLS) peptide. These NLS-coated nanoparticles were introduced into the HeLa cell cytoplasm and nucleus, where the particles were monodispersed and non-aggregated. The success of labeling was examined and identified by fluorescence microscopy and MRI. The work demonstrates that monodisperse magnetic nanoparticles can be readily functionalized and stabilized for potential diagnostic and therapeutic applications.

  18. Evolutionary gradient of predicted nuclear localization signals (NLS)-bearing proteins in genomes of family Planctomycetaceae.

    Science.gov (United States)

    Guo, Min; Yang, Ruifu; Huang, Chen; Liao, Qiwen; Fan, Guangyi; Sun, Chenghang; Lee, Simon Ming-Yuen

    2017-04-04

    The nuclear envelope is considered a key classification marker that distinguishes prokaryotes from eukaryotes. However, this marker does not apply to the family Planctomycetaceae, which has intracellular spaces divided by lipidic intracytoplasmic membranes (ICMs). Nuclear localization signal (NLS), a short stretch of amino acid sequence, destines to transport proteins from cytoplasm into nucleus, and is also associated with the development of nuclear envelope. We attempted to investigate the NLS motifs in Planctomycetaceae genomes to demonstrate the potential molecular transition in the development of intracellular membrane system. In this study, we identified NLS-like motifs that have the same amino acid compositions as experimentally identified NLSs in genomes of 11 representative species of family Planctomycetaceae. A total of 15 NLS types and 170 NLS-bearing proteins were detected in the 11 strains. To determine the molecular transformation, we compared NLS-bearing protein abundances in the 11 representative Planctomycetaceae genomes with them in genomes of 16 taxonomically varied microorganisms: nine bacteria, two archaea and five fungi. In the 27 strains, 29 NLS types and 1101 NLS-bearing proteins were identified, principal component analysis showed a significant transitional gradient from bacteria to Planctomycetaceae to fungi on their NLS-bearing protein abundance profiles. Then, we clustered the 993 non-redundant NLS-bearing proteins into 181 families and annotated their involved metabolic pathways. Afterwards, we aligned the ten types of NLS motifs from the 13 families containing NLS-bearing proteins among bacteria, Planctomycetaceae or fungi, considering their diversity, length and origin. A transition towards increased complexity from non-planctomycete bacteria to Planctomycetaceae to archaea and fungi was detected based on the complexity of the 10 types of NLS-like motifs in the 13 NLS-bearing proteins families. The results of this study reveal that

  19. Successful reprogramming of epiblast stem cells by blocking nuclear localization of β-catenin.

    Science.gov (United States)

    Murayama, Hideyuki; Masaki, Hideki; Sato, Hideyuki; Hayama, Tomonari; Yamaguchi, Tomoyuki; Nakauchi, Hiromitsu

    2015-01-13

    Epiblast stem cells (EpiSCs) in mice and rats are primed pluripotent stem cells (PSCs). They barely contribute to chimeric embryos when injected into blastocysts. Reprogramming of EpiSCs to embryonic stem cell (ESC)-like cells (rESCs) may occur in response to LIF-STAT3 signaling; however, low reprogramming efficiency hampers potential use of rESCs in generating chimeras. Here, we describe dramatic improvement of conversion efficiency from primed to naive-like PSCs through upregulation of E-cadherin in the presence of the cytokine LIF. Analysis revealed that blocking nuclear localization of β-CATENIN with small-molecule inhibitors significantly enhances reprogramming efficiency of mouse EpiSCs. Although activation of Wnt/β-catenin signals has been thought desirable for maintenance of naive PSCs, this study provides the evidence that inhibition of nuclear translocation of β-CATENIN enhances conversion of mouse EpiSCs to naive-like PSCs (rESCs). This affords better understanding of gene regulatory circuits underlying pluripotency and reprogramming of PSCs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. The identification of FANCD2 DNA binding domains reveals nuclear localization sequences.

    Science.gov (United States)

    Niraj, Joshi; Caron, Marie-Christine; Drapeau, Karine; Bérubé, Stéphanie; Guitton-Sert, Laure; Coulombe, Yan; Couturier, Anthony M; Masson, Jean-Yves

    2017-08-21

    Fanconi anemia (FA) is a recessive genetic disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. The FA pathway consists of at least 21 FANC genes (FANCA-FANCV), and the encoded protein products interact in a common cellular pathway to gain resistance against DNA interstrand crosslinks. After DNA damage, FANCD2 is monoubiquitinated and accumulates on chromatin. FANCD2 plays a central role in the FA pathway, using yet unidentified DNA binding regions. By using synthetic peptide mapping and DNA binding screen by electromobility shift assays, we found that FANCD2 bears two major DNA binding domains predominantly consisting of evolutionary conserved lysine residues. Furthermore, one domain at the N-terminus of FANCD2 bears also nuclear localization sequences for the protein. Mutations in the bifunctional DNA binding/NLS domain lead to a reduction in FANCD2 monoubiquitination and increase in mitomycin C sensitivity. Such phenotypes are not fully rescued by fusion with an heterologous NLS, which enable separation of DNA binding and nuclear import functions within this domain that are necessary for FANCD2 functions. Collectively, our results enlighten the importance of DNA binding and NLS residues in FANCD2 to activate an efficient FA pathway. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Frequent Nuclear/Cytoplasmic Localization of β-Catenin without Exon 3 Mutations in Malignant Melanoma

    Science.gov (United States)

    Rimm, David L.; Caca, Karel; Hu, Gang; Harrison, Frank B.; Fearon, Eric R.

    1999-01-01

    β-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3β phosphorylation sites near the β-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render β-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3β, adenomatous polyposis coli, and axin proteins. As a result, β-catenin accumulates in the cytosol and nucleus and activates T-cell factor/lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have β-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790–1792). To assess the role of β-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of β-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in β-catenin was found in only one case (codon 45 Ser→Pro). Our findings demonstrate that β-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of β-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor. PMID:10027390

  2. Gene delivery: A single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus

    OpenAIRE

    Zanta, Maria Antonietta; Belguise-Valladier, Pascale; Behr, Jean-Paul

    1999-01-01

    Translocation of exogenous DNA through the nuclear membrane is a major concern of gene delivery technologies. To take advantage of the cellular import machinery, we have synthesized a capped 3.3-kbp CMVLuciferase-NLS gene containing a single nuclear localization signal peptide (PKKKRKVEDPYC). Transfection of cells with the tagged gene remained effective down to nanogram amounts of DNA. Transfection enhancement (10- to 1,000-fold) as a result of the signal peptide was observed irrespective of ...

  3. Phosphatidic acid interacts with a MYB transcription factor and regulates its nuclear localization and function in Arabidopsis.

    Science.gov (United States)

    Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

    2013-12-01

    Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with werewolf (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER's nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization.

  4. Phosphatidic Acid Interacts with a MYB Transcription Factor and Regulates Its Nuclear Localization and Function in Arabidopsis[C][W

    Science.gov (United States)

    Yao, Hongyan; Wang, Geliang; Guo, Liang; Wang, Xuemin

    2013-01-01

    Phosphatidic acid (PA) has emerged as a class of cellular mediators involved in various cellular and physiological processes, but little is known about its mechanism of action. Here we show that PA interacts with WEREWOLF (WER), a R2R3 MYB transcription factor involved in root hair formation. The PA-interacting region is confined to the end of the R2 subdomain. The ablation of the PA binding motif has no effect on WER binding to DNA, but abolishes its nuclear localization and its function in regulating epidermal cell fate. Inhibition of PA production by phospholipase Dζ also suppresses WER’s nuclear localization, root hair formation, and elongation. These results suggest a role for PA in promoting protein nuclear localization. PMID:24368785

  5. Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer.

    LENUS (Irish Health Repository)

    Sullivan, Shane

    2012-02-01

    Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro- and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro-Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.

  6. Nuclear localization of the transcriptional regulator MIER1α requires interaction with HDAC1/2 in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Shengnan Li

    Full Text Available MIER1α is a transcriptional regulator that functions in gene repression through its ability to interact with various chromatin modifiers and transcription factors. We have also shown that MIER1α interacts with ERα and inhibits estrogen-stimulated growth. While MIER1α is localized in the nucleus of MCF7 cells, previous studies have shown that it does not contain a nuclear localization signal. In this report, we investigate the mechanism involved in transporting MIER1α into the nucleus. We explored the possibility that MIER1α is transported into the nucleus through a 'piggyback' mechanism. One obvious choice is via interaction with ERα, however we demonstrate that nuclear targeting of MIER1α does not require ERα. Knockdown of ERα reduced protein expression to 22% of control, but did not alter the percentage of cells with nuclear MIER1α (98% nuclear with scrambled shRNA vs. 95% with ERα shRNA. Further evidence was obtained using two stable transfectants derived from the ER-negative MDA231 cell line: MC2 (ERα+ and VC5 (ERα-. Confocal analysis showed no difference in MIER1α localization (86% nuclear in MC2 vs. 89% in VC5. These data demonstrate that ERα is not involved in nuclear localization of MIER1α. To identify the critical MIER1α sequence, we performed a deletion analysis and determined that the ELM2 domain was necessary and sufficient for nuclear localization. This domain binds HDAC1 & 2, therefore we investigated their role. Confocal analysis of an MIER1α containing an ELM2 point mutation previously shown to abolish HDAC binding revealed that this mutation results in almost complete loss of nuclear targeting: 10% nuclear vs. 97% with WT-MIER1α. Moreover, double knockdown of HDAC1 and 2 caused a reduction in percent nuclear from 86% to 44%. The results of this study demonstrate that nuclear targeting of MIER1α requires an intact ELM2 domain and is dependent on interaction with HDAC1/2.

  7. Localization of 4q35.2 to the nuclear periphery: is FSHD a nuclear envelope disease?

    NARCIS (Netherlands)

    Masny, P.S.; Bengtsson, U.; Chung, S.A.; Martin, J.H.; Engelen, B.G.M. van; Maarel, S.M. van der; Winokur, S.T.

    2004-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) may be a new member of the class of neuromuscular diseases (NMD) due to defects in the nuclear envelope. Unlike other NMDs with primary defects in nuclear envelope proteins, however, FSHD may result from inappropriate chromatin interactions at the

  8. Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules.

    Science.gov (United States)

    Masoodi, Khalid Z; Xu, Yadong; Dar, Javid A; Eisermann, Kurtis; Pascal, Laura E; Parrinello, Erica; Ai, Junkui; Johnston, Paul A; Nelson, Joel B; Wipf, Peter; Wang, Zhou

    2017-10-01

    The androgen receptor (AR) is a ligand-dependent transcription factor that controls the expression of androgen-responsive genes. A key step in androgen action, which is amplified in castration-resistant prostate cancer (CRPC), is AR nuclear translocation. Small molecules capable of inhibiting AR nuclear localization could be developed as novel therapeutics for CRPC. We developed a high-throughput screen and identified two structurally-related pyrroloimidazoles that could block AR nuclear localization in CRPC cells. We show that these two small molecules, 3-(4-ethoxyphenyl)-6,7-dihydro-5 H -pyrrolo[1,2- a ]imidazole (EPPI) and 3-(4-chlorophenyl)-6,7-dihydro-5 H -pyrrolo[1,2- a ]imidazole (CPPI) can inhibit the nuclear localization and transcriptional activity of AR and reduce the proliferation of AR-positive but not AR-negative prostate cancer cell lines. EPPI and CPPI did not inhibit nuclear localization of the glucocorticoid receptor or the estrogen receptor, suggesting they selectively target AR. In LNCaP tumor xenografts, CPPI inhibited the proliferation of relapsed LNCaP tumors. These findings suggest that EPPI and CPPI could serve as lead structures for the development of therapeutic agents for CRPC. Mol Cancer Ther; 16(10); 2120-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  10. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Edward I. [Charles Sturt University, School of Animal and Veterinary Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Dombrovski, Andrew K. [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Swarbrick, Crystall M.D. [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Raidal, Shane R. [Charles Sturt University, School of Animal and Veterinary Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); Forwood, Jade K., E-mail: jforwood@csu.edu.au [Charles Sturt University, School of Biomedical Sciences, Boorooma St., Wagga Wagga, New South Wales 2678 (Australia); EH Graham Centre for Agricultural Innovation (NSW Department of Primary Industries and Charles Sturt University), Boorooma St., Wagga Wagga, New South Wales 2678 (Australia)

    2013-09-06

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.

  11. Consumption of locally grown foods by the populations residing near nuclear power stations

    International Nuclear Information System (INIS)

    Mathieu, P.Y.

    1980-01-01

    The studies carried out by the Geographical Institute of Aix-en-Provence and the B.E.G.E.A. are in three forms: the first studies the local rural production (farming, animal rearing and fishing); the second is concerned with the food intake of the population within a radius of 5 to 10 km around the site; the third consists in working out a soil utilization map covering an area of about 2500 hectares around the site in order to determine the agricultural and urban areas as well as the open spaces, and the exact sort of cultivation carried out, plot by plot. The map also represents all the phenomena concerning hydrography, irrigation, watering and the supply of potable water. All these studies concern only a few parishes and enable an accurate knowledge of the environment to be acquired. The food studies seek an order of magnitude of the amount of local produce consumed by the populations of the nuclear power station sites with a view to determining radioactive contamination levels. The results show the specific food consumption features of a population bearing the deep stamp of its environment and its rural origin [fr

  12. Dynamic localization of tripartite motif-containing 22 in nuclear and nucleolar bodies

    Energy Technology Data Exchange (ETDEWEB)

    Sivaramakrishnan, Gayathri; Sun, Yang; Tan, Si Kee [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Lin, Valerie C.L., E-mail: cllin@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

    2009-05-01

    Tripartite motif-containing 22 (TRIM22) exhibits antiviral and growth inhibitory properties, but there has been no study on the localization and dynamics of the endogenous TRIM22 protein. We report here that TRIM22 is dramatically induced by progesterone in MDA-MB-231-derived ABC28 cells and T47D cells. This induction was associated with an increase in TRIM22 nuclear bodies (NB), and an even more prominent increase in nucleolar TRIM22 bodies. Distinct endogenous TRIM22 NB were also demonstrated in several other cell lines including MCF7 and HeLa cells. These TRIM22 NB resemble Cajal bodies, co-localized with these structures and co-immunoprecipitated with p80-coilin. However, IFN{gamma}-induced TRIM22 in HeLa and MCF7 cells did not form NB, implying the forms and distribution of TRIM22 are regulated by specific cellular signals. This notion is also supported by the observation that TRIM22 NB undergoes dynamic cell-cycle dependent changes in distribution such that TRIM22 NB started to form in early G0/G1 but became dispersed in the S-phase. In light of its potential antiviral and antitumor properties, the findings here provide an interesting gateway to study the relationship between the different forms and functions of TRIM22.

  13. Development of the local stress analysis methodology for nuclear class 1 piping welded to the seal plate

    International Nuclear Information System (INIS)

    Lee, Dae Hee; Kim, Jong Min

    1996-04-01

    Lugs, brackets, stiffners and other attachments may be welded, bolted and studded to the outside or inside of piping and the local stress arise because of the radial thermal expansion of the piping, the dilatation of the piping due to its internal pressure, the circumferential contraction of the pipe as a results of an axial tensile force (Poisson's effect), etc., being constrained by those. So the evaluation of the local stress for the piping constrained by those. So the evaluation of the local stress for the piping constrained by the attachments in accordance with the ASME Section III NB-3651.3 is required for the nuclear class 1 piping. In this report the local stress analysis procedure for the nuclear class 1 piping welded to the seal plate was established. SInce the stress analysis for the nuclear class 1 piping require the fatigue analysis procedure was established using the commercial code ANSYS 5.1 for the structure analysis in this report. The procedure which was developed in this report can be used very effectively for the design for the seal plate and the local stress analysis of the nuclear class 1 piping welded to the seal plate. 14 figs., 5 refs. (Author) .new

  14. Functional analysis of the C-terminal region of human adenovirus E1A reveals a misidentified nuclear localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Michael J.; King, Cason R.; Dikeakos, Jimmy D. [Department of Microbiology and Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada (Canada); Mymryk, Joe S., E-mail: jmymryk@uwo.ca [Department of Microbiology and Immunology, The University of Western Ontario, A4-833 London Regional Cancer Centre, 800 Commissioners Road E., London, Ontario, N6A 4L6 Canada (Canada); Department of Oncology, The University of Western Ontario, London Regional Cancer Centre, Ontario (Canada)

    2014-11-15

    The immortalizing function of the human adenovirus 5 E1A oncoprotein requires efficient localization to the nucleus. In 1987, a consensus monopartite nuclear localization sequence (NLS) was identified at the C-terminus of E1A. Since that time, various experiments have suggested that other regions of E1A influence nuclear import. In addition, a novel bipartite NLS was recently predicted at the C-terminal region of E1A in silico. In this study, we used immunofluorescence microscopy and co-immunoprecipitation analysis with importin-α to verify that full nuclear localization of E1A requires the well characterized NLS spanning residues 285–289, as well as a second basic patch situated between residues 258 and 263 ({sup 258}RVGGRRQAVECIEDLLNEPGQPLDLSCKRPRP{sup 289}). Thus, the originally described NLS located at the C-terminus of E1A is actually a bipartite signal, which had been misidentified in the existing literature as a monopartite signal, altering our understanding of one of the oldest documented NLSs. - Highlights: • Human adenovirus E1A is localized to the nucleus. • The C-terminus of E1A contains a bipartite nuclear localization signal (NLS). • This signal was previously misidentified to be a monopartite NLS. • Key basic amino acid residues within this sequence are highly conserved.

  15. Effect on localized waste-container failure on radionuclide transport from an underground nuclear waste vault

    International Nuclear Information System (INIS)

    Cheung, S.C.H.; Chan, T.

    1983-07-01

    In the geological disposal of nuclear fuel waste, one option is to emplace the waste container in a borehole drilled into the floor of the underground vault. In the borehole, the waste container is surrounded by a compacted soil material known as the buffer. A finite-element simulation has been performed to study the effect of localized partial failure of the waste container on the steady-state radionuclide transport by diffusion from the container through the buffer to the surrounding rock and/or backfill. In this study, the radionuclide concentration at the buffer-backfill interface is assumed to be zero. Two cases are considered at the interface between the buffer and the rock. In case 1, a no-flux boundary condition is used to simulate intact rock. In case 2, a constant radionuclide concentration condition is used to simulate fractured rock with groundwater flow. The results show that the effect of localized partial failure of the waste container on the total flux is dependent on the boundary condition at the buffer-rock interface. For the intact rock condition, the total flux is mainly dependent on the location of the failure. The total flux increases as the location changes from the bottom to the top of the emplaced waste container. For a given localized failure of the waste container, the total flux remains unaffected by the area of failed surface below the top of the failure. For fractured rock, the total flux is directly proportional to the failed surface area of the waste container regardless of the failure location

  16. Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

    Directory of Open Access Journals (Sweden)

    Allen C T Teng

    Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

  17. Nuclear, but not cytoplasmic, localization of survivin as a negative prognostic factor for survival in upper urinary tract urothelial carcinoma.

    Science.gov (United States)

    Kitamura, Hiroshi; Torigoe, Toshihiko; Hirohashi, Yoshihiko; Asanuma, Hiroko; Inoue, Ryuta; Nishida, Sachiyo; Tanaka, Toshiaki; Masumori, Naoya; Sato, Noriyuki; Tsukamoto, Taiji

    2013-01-01

    Survivin, a member of the inhibitor of apoptosis protein gene family, inhibits apoptosis and promotes mitosis. We determined whether nuclear or cytoplasmic localization of survivin could predict survival of patients with upper urinary tract urothelial carcinoma (UUTUC). Immunohistochemical staining for survivin was carried out on archival specimens from 125 consecutive patients with UUTUC who underwent radical nephroureterectomy. Nuclear and cytoplasmic staining of survivin was scored and compared with clinicopathologic features and cancer-specific survival (CSS). Nuclear expression of survivin was significantly correlated with tumor grade (p nuclear expression of survivin vs. 73 % for those without nuclear expression of survivin (hazard ratio = 2.19; 95 % confidence interval = 1.02-4.70; p = 0.043). The 5-year cancer-specific survival rates of patients with cytoplasmic survivin-negative and -positive tumors were 66 and 67 %, respectively. There was no difference in survival between patients with cytoplasmic survivin-negative tumors and those with cytoplasmic survivin-positive tumors. Using univariate analysis, nuclear survivin expression, tumor grade, pathological T stage, pathological N stage, and lymphovascular invasion were the predictive variables for CSS. In contrast, cytoplasmic survivin expression had no prognostic relevance. These data suggest that nuclear accumulation of survivin represents biologic aggressiveness and that nuclear survivin is a negative prognostic marker in patients with resected UUTUC.

  18. Attention-dependent modulation of cortical taste circuits revealed by Granger causality with signal-dependent noise.

    Directory of Open Access Journals (Sweden)

    Qiang Luo

    2013-10-01

    Full Text Available We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention.

  19. A Study of Community Leaders in a Nuclear Host Community: Local Issues, Expectations and Support and Opposition.

    Science.gov (United States)

    Bronfman, B. H.

    As part of a continuing effort to assess the social impacts on communities of energy facility planning, construction, operation, and decommissioning, a May 1977 survey of 37 community leaders in Hartsville, Tennessee (site of a nuclear power plant) establishes major local issues (past, present, and future) which leaders feel are important to…

  20. Local variance of atmospheric 14C concentrations around Fukushima Dai-ichi Nuclear Power Plant from 2010 to 2012

    DEFF Research Database (Denmark)

    Chen, Biying; Xu, Sheng; Cook, Gordon T.

    2017-01-01

    Radiocarbon (14C) has been measured in single tree ring samples collected from the southwest of the Fukushima Dai-ichi Nuclear Power Plant. Our data indicate south-westwards dispersion of radiocarbon and the highest 14C activity observed so far in the local environment during the 2011 accident...

  1. Local synthesis of nuclear-encoded mitochondrial proteins in the presynaptic nerve terminal.

    Science.gov (United States)

    Gioio, A E; Eyman, M; Zhang, H; Lavina, Z S; Giuditta, A; Kaplan, B B

    2001-06-01

    One of the central tenets in neuroscience has been that the protein constituents of distal compartments of the neuron (e.g., the axon and nerve terminal) are synthesized in the nerve cell body and are subsequently transported to their ultimate sites of function. In contrast to this postulate, we have established previously that a heterogeneous population of mRNAs and biologically active polyribosomes exist in the giant axon and presynaptic nerve terminals of the photoreceptor neurons in squid. We report that these mRNA populations contain mRNAs for nuclear-encoded mitochondrial proteins to include: cytochrome oxidase subunit 17, propionyl-CoA carboxylase (EC 6.4.1.3), dihydrolipoamide dehydrogenase (EC 1.8.1.4), and coenzyme Q subunit 7. The mRNA for heat shock protein 70, a chaperone protein known to be involved in the import of proteins into mitochondria, has also been identified. Electrophoretic gel analysis of newly synthesized proteins in the synaptosomal fraction isolated from the squid optic lobe revealed that the large presynaptic terminals of the photoreceptor neuron contain a cytoplasmic protein synthetic system. Importantly, a significant amount of the cycloheximide resistant proteins locally synthesized in the terminal becomes associated with mitochondria. PCR analysis of RNA from synaptosomal polysomes establishes that COX17 and CoQ7 mRNAs are being actively translated. Taken together, these findings indicate that proteins required for the maintenance of mitochondrial function are synthesized locally in the presynaptic nerve terminal, and call attention to the intimacy of the relationship between the terminal and its energy generating system. J. Neurosci. Res. 64:447-453, 2001. Published 2001 Wiley-Liss, Inc.

  2. Analytic approach to constructing effective local potentials in nuclear reaction theory

    International Nuclear Information System (INIS)

    Blokhintsev, L.D.; Safronov, A.N.; Safronov, A.A.

    2004-01-01

    Full text: Recently a method of constructing effective local potentials between strongly interacting composite particles was suggested [1]. The approach is based on the requirement of the proper structure of the nearest to the physical region singularities of scattering amplitudes as well as on the methods of the inverse scattering problem. In the given work the method is generalized to the case of the presence of the long-range Coulomb interaction which drastically changes the analytic structure of the S matrix. The effective potential is defined as the local operator which, being inserted into the Lippmann-Schwinger equation, generates required discontinuities of partial-wave scattering amplitudes. Its strong part is written in the form V(r)=∫ μ 0 C(α)e -ar dα, where μ is determined by the position of the nearest to the physical region dynamical singularity. For all the processes considered, these singularities correspond to pole Feynman diagrams describing the elastic transfer mechanism. The C(α) function is found as a solution of the inverse scattering problem equations, the kernels of which are determined by the discontinuities at the nearest dynamical cuts. The Coulomb interaction is treated by introducing reduced Coulomb-nuclear scattering amplitudes and, in addition, by taking into account Coulomb corrections in the three-particle intermediate states and in the vertex functions of the pole diagrams. The processes of nd, pd, p 3 He, nα, pα and 3 Heα scattering were considered. To calculate the required discontinuities, the information on the corresponding vertex constants and binding energies was used. Effective potentials, scattering lengths and low-energy phase shifts for the processes under consideration were obtained. The work was supported by the Russian Foundation for Basic Research (grant No.04-02-16602) and by the 'Russian Universities' program (grant No. 02.02.027)

  3. New nuclear data service at CNEA: retrieval of the update libraries from a local Web-Server

    International Nuclear Information System (INIS)

    Suarez, Patricia M.; Pepe, Maria E.; Sbaffoni, Maria M.

    2000-01-01

    A new On-line Nuclear Data Service was implemented at National Atomic Energy Commission (CNEA) Web-Site. The information usually issued by the Nuclear Data Section of IAEA (NDS-IAEA) on CD-ROM, as well as complementary libraries periodically downloaded from the a mirror server of NDS-IAEA Service located at IPEN, Brazil are available on the new CNEA Web page. In the site, users can find numerical data on neutron, charged-particle, and photonuclear reactions, nuclear structure, and decay data, with related bibliographic information. This data server is permanently maintained and updated by CNEA staff members. This crew also offers assistance on the use and retrieval of nuclear data to local users. (author)

  4. Allocation of responsibilities between central and local authorities concerning nuclear power plant licensing

    International Nuclear Information System (INIS)

    Peltzer, P.

    1983-01-01

    This paper examines Belgian regulations on licences to construct and operate nuclear power plants in the context of implementation of the 1980 Act concerning regionalisation. It also reviews the relevant nuclear legislation in certain other countries. (NEA) [fr

  5. Autographa californica multiple nucleopolyhedrovirus DNA polymerase C terminus is required for nuclear localization and viral DNA replication.

    Science.gov (United States)

    Feng, Guozhong; Krell, Peter J

    2014-09-01

    The DNA polymerase (DNApol) of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is essential for viral DNA replication. The DNApol exonuclease and polymerase domains are highly conserved and are considered functional in DNA replication. However, the role of the DNApol C terminus has not yet been characterized. To identify whether only the exonuclease and polymerase domains are sufficient for viral DNA replication, several DNApol C-terminal truncations were cloned into a dnapol-null AcMNPV bacmid with a green fluorescent protein (GFP) reporter. Surprisingly, most of the truncation constructs, despite containing both exonuclease and polymerase domains, could not rescue viral DNA replication and viral production in bacmid-transfected Sf21 cells. Moreover, GFP fusions of these same truncations failed to localize to the nucleus. Truncation of the C-terminal amino acids 950 to 984 showed nuclear localization but allowed for only limited and delayed viral spread. The C terminus contains a typical bipartite nuclear localization signal (NLS) motif at residues 804 to 827 and a monopartite NLS motif at residues 939 to 948. Each NLS, as a GFP fusion peptide, localized to the nucleus, but both NLSs were required for nuclear localization of DNApol. Alanine substitutions in a highly conserved baculovirus DNApol sequence at AcMNPV DNApol amino acids 972 to 981 demonstrated its importance for virus production and DNA replication. Collectively, the data indicated that the C terminus of AcMNPV DNApol contains two NLSs and a conserved motif, all of which are required for nuclear localization of DNApol, viral DNA synthesis, and virus production. The baculovirus DNA polymerase (DNApol) is a highly specific polymerase that allows viral DNA synthesis and hence virus replication in infected insect cells. We demonstrated that the exonuclease and polymerase domains of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) alone are insufficient for viral

  6. Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-12-01

    Full Text Available The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Acr3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence (NLS, a short cationic peptide. To further improve the antimicrobial activity of our agent, dimeric (Acr3-NLS2 was simultaneously synthesized by joining two monomeric Acr3-NLS together via a disulfide linker. Our results show that Acr3-NLS and especially (Acr3-NLS2 display significant antimicrobial activity against gram-negative and gram-positive bacteria compared to that of the NLS. Subsequently, the results derived from the study on the mechanism of action demonstrate that Acr3-NLS and (Acr3-NLS2 can kill bacteria by membrane disruption and DNA binding. The double targets–cell membrane and intracellular DNA–will reduce the risk of bacteria developing resistance to Acr3-NLS and (Acr3-NLS2. Overall, this study provides a novel strategy to design highly effective antimicrobial agents with a dual mode of action for infection treatment.

  7. Improved radiological/nuclear source localization in variable NORM background: An MLEM approach with segmentation data

    Science.gov (United States)

    Penny, Robert D.; Crowley, Tanya M.; Gardner, Barbara M.; Mandell, Myron J.; Guo, Yanlin; Haas, Eric B.; Knize, Duane J.; Kuharski, Robert A.; Ranta, Dale; Shyffer, Ryan; Labov, Simon; Nelson, Karl; Seilhan, Brandon; Valentine, John D.

    2015-06-01

    A novel approach and algorithm have been developed to rapidly detect and localize both moving and static radiological/nuclear (R/N) sources from an airborne platform. Current aerial systems with radiological sensors are limited in their ability to compensate for variable naturally occurring radioactive material (NORM) background. The proposed approach suppresses the effects of NORM background by incorporating additional information to segment the survey area into regions over which the background is likely to be uniform. The method produces pixelated Source Activity Maps (SAMs) of both target and background radionuclide activity over the survey area. The task of producing the SAMs requires (1) the development of a forward model which describes the transformation of radionuclide activity to detector measurements and (2) the solution of the associated inverse problem. The inverse problem is ill-posed as there are typically fewer measurements than unknowns. In addition the measurements are subject to Poisson statistical noise. The Maximum-Likelihood Expectation-Maximization (MLEM) algorithm is used to solve the inverse problem as it is well suited for under-determined problems corrupted by Poisson noise. A priori terrain information is incorporated to segment the reconstruction space into regions within which we constrain NORM background activity to be uniform. Descriptions of the algorithm and examples of performance with and without segmentation on simulated data are presented.

  8. An analysis of inhabitants opinion on energy issues. Comparison between localities of nuclear installation sites and of urban communities

    International Nuclear Information System (INIS)

    Takahashi, Reiko; Nakagome, Yoshihiro

    2004-01-01

    For the purpose of comparing the mental attitudes toward nuclear power generation held by the public between localities containing nuclear installation sites and those of urban communities, a survey has been conducted by mail and by direct interviews. The survey conversed Fukushima, Niigata and Fukui Prefectures, representing the former group of localities, whereas Tokyo and Osaka, representing the latter. The mail survey revealed differences between the two groups of localities in their image of power and in their perception of its present status, as well as in their sense of values in daily life. The interview survey indicated that the factors behind the differences included regional characteristics such as temperaments of resident population, and effects on the private life style brought by nuclear installation. Narrowing down this gap of mental attitude between the two groups of localities should call indispensably for better mutual understanding. In bringing this about, consideration should be given to particular local characteristics, including popular mentality and personal view of life, as well as image and knowledge of energy sources held by the individuals. (author)

  9. 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.

  10. Local seismic network for monitoring of a potential nuclear power plant area.

    Science.gov (United States)

    Tiira, Timo; Uski, Marja; Kortström, Jari; Kaisko, Outi; Korja, Annakaisa

    2016-01-01

    This study presents a plan for seismic monitoring of a region around a potential nuclear power plant. Seismic monitoring is needed to evaluate seismic risk. The International Atomic Energy Agency has set guidelines on seismic hazard evaluation and monitoring of such areas. According to these guidelines, we have made a plan for a local network of seismic stations to collect data for seismic source characterization and seismotectonic interpretations, as well as to monitor seismic activity and natural hazards. The detection and location capability of the network were simulated using different station configurations by computing spatial azimuthal coverages and detection threshold magnitudes. Background noise conditions around Pyhäjoki were analyzed by comparing data from different stations. The annual number of microearthquakes that should be detected with a dense local network centered around Pyhäjoki was estimated. The network should be dense enough to fulfill the requirements of azimuthal coverage better than 180° and automatic event location capability down to ML ∼ 0 within a distance of 25 km from the site. A network of 10 stations should be enough to reach these goals. With this setup, the detection threshold magnitudes are estimated to be ML = -0.1 and ML = 0.1 within a radius of 25 and 50 km from Pyhäjoki, respectively. The annual number of earthquakes detected by the network is estimated to be 2 (ML ≥ ∼ -0.1) within 25 km radius and 5 (ML ≥ ∼-0.1 to ∼0.1) within 50 km radius. The location accuracy within 25 km radius is estimated to be 1-2 and 4 km for horizontal coordinates and depth, respectively. Thus, the network is dense enough to map out capable faults with horizontal accuracy of 1-2 km within 25 km radius of the site. The estimation is based on the location accuracies of five existing networks in northern Europe. Local factors, such as seismic noise sources, geology and infrastructure might limit the station

  11. Interleaved localized 1H/31P nuclear magnetic resonance spectroscopy of skeletal muscle

    International Nuclear Information System (INIS)

    Meyerspeer, M.

    2005-09-01

    Nuclear magnetic resonance (NMR) has been used as a spectroscopic method in physics and chemistry before it was developed to become a diagnostic imaging tool in medicine. When NMR spectroscopy is applied to human tissue, metabolism can be studied in normal physiological and pathological states in vivo. Metabolite concentrations and rates can be monitored dynamically and with localization of a defined region of interest. The 'window' which is opened for observation, i.e. which quantities are measured, depends on the nucleus used for RF excitation. Mechanisms of adenosine tri-phosphate (ATP) resynthesis, as a direct source of energy for muscle contraction, are phosphocreatine (PCr) splitting, glycolysis, beta-oxidation and, finally, oxidative phosphorylation. Whilst the dependency of these processes' fractional contribution to muscular energy supply on exercise type and duration is well known, quantitative models of the regulating mechanisms involved are still subject of current research. A large fraction of the established knowledge about metabolism is based on biochemical analysis of tissue acquired invasively (e.g. microdialysis and open-flow microperfusion) or representing averaged metabolic concentrations for the whole body (via serum metabolites or gas exchange analysis). Localized NMR spectroscopy, however, is capable of non-invasively acquiring time-resolved data from a defined volume of interest, in vivo. In contrast to the vast majority of MRS studies investigating metabolism, where spectra of a single nucleus (commonly 1 H, 31 P or 13 C) were acquired or several MR spectra with different nuclei were measured in separate experiments, this work opens an additional 'window' on muscle metabolism by interleaved localized acquisition of 1 H and 31 P NMR spectra from human calf muscle in vivo, during rest, exercise and recovery, in a single experiment. Using this technique, the time courses of the concentrations of phosphocreatine, inorganic phosphate (Pi), ATP

  12. Role of a nuclear localization signal on the minor capsid Proteins VP2 and VP3 in BKPyV nuclear entry

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Shauna M. [Cellular and Molecular Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States); Zhao, Linbo [Doctoral Program in Cancer Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States); Bosard, Catherine [Department of Microbiology and Immunology University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States); Imperiale, Michael J., E-mail: imperial@umich.edu [Cellular and Molecular Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States); Doctoral Program in Cancer Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States); Department of Microbiology and Immunology University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109 (United States)

    2015-01-01

    BK Polyomavirus (BKPyV) is a ubiquitous nonenveloped human virus that can cause severe disease in immunocompromised populations. After internalization into renal proximal tubule epithelial cells, BKPyV traffics through the ER and enters the cytosol. However, it is unclear how the virus enters the nucleus. In this study, we elucidate a role for the nuclear localization signal located on the minor capsid proteins VP2 and VP3 during infection. Site-directed mutagenesis of a single lysine in the basic region of the C-terminus of the minor capsid proteins abrogated their nuclear localization, and the analogous genomic mutation reduced infectivity. Additionally, through use of the inhibitor ivermectin and knockdown of importin β1, we found that the importin α/β pathway is involved during infection. Overall these data are the first to show the significance of the NLS of the BKPyV minor capsid proteins during infection in a natural host cell. - Highlights: • Polyomaviruses must deliver their genome to the nucleus to replicate. • The minor capsid proteins have a well-conserved nuclear localization signal. • Mutation of this NLS diminishes, but does not completely inhibit, infection.

  13. Threats and benefits updated information on local opinions regarding the spent nuclear fuel repository in Finland - 16128

    International Nuclear Information System (INIS)

    Kojo, Matti; Kari, Mika; Litmanen, Tapio

    2009-01-01

    The aim of the paper is to provide updated information on local opinion regarding the siting of a spent nuclear fuel repository in Finland. The main question is how the residents of the municipality perceive the threats and benefits of the repository. In accordance with the Decision in Principle by the Council of State passed in 2000, the Olkiluoto area in Municipality of Eurajoki was chosen as the location for the repository to accommodate spent nuclear fuel produced in Finland. Updated information on local opinions is needed as the siting process is approaching the next phase, the application for a construction license by 2012. The nuclear waste management company Posiva, owned by the utilities Teollisuuden Voima and Fortum Power and Heat, has also applied for a new Decision in Principle (DiP) for expansion of the repository. The data provided in this paper is based on a survey carried out in June 2008. The respondents were selected from the residents of the municipality of Eurajoki and the neighbouring municipalities using stratified random sampling (N=3000). The response rate of the survey was 20% (N=606). The paper is part of a joint research project between the University of Jyvaeskylae and the University of Tampere. The research project 'Follow-up research regarding socio-economic effects and communication of final disposal facility of spent nuclear fuel in Eurajoki and its neighbouring municipalities' is funded by the Finnish Research Programme on Nuclear Waste Management (KYT2010). (authors)

  14. A combined nuclear and nucleolar localization motif in activation-induced cytidine deaminase (AID) controls immunoglobulin class switching.

    Science.gov (United States)

    Hu, Yi; Ericsson, Ida; Torseth, Kathrin; Methot, Stephen P; Sundheim, Ottar; Liabakk, Nina B; Slupphaug, Geir; Di Noia, Javier M; Krokan, Hans E; Kavli, Bodil

    2013-01-23

    Activation-induced cytidine deaminase (AID) is a DNA mutator enzyme essential for adaptive immunity. AID initiates somatic hypermutation and class switch recombination (CSR) by deaminating cytosine to uracil in specific immunoglobulin (Ig) gene regions. However, other loci, including cancer-related genes, are also targeted. Thus, tight regulation of AID is crucial to balance immunity versus disease such as cancer. AID is regulated by several mechanisms including nucleocytoplasmic shuttling. Here we have studied nuclear import kinetics and subnuclear trafficking of AID in live cells and characterized in detail its nuclear localization signal. Importantly, we find that the nuclear localization signal motif also directs AID to nucleoli where it colocalizes with its interaction partner, catenin-β-like 1 (CTNNBL1), and physically associates with nucleolin and nucleophosmin. Moreover, we demonstrate that release of AID from nucleoli is dependent on its C-terminal motif. Finally, we find that CSR efficiency correlates strongly with the arithmetic product of AID nuclear import rate and DNA deamination activity. Our findings suggest that directional nucleolar transit is important for the physiological function of AID and demonstrate that nuclear/nucleolar import and DNA cytosine deamination together define the biological activity of AID. This is the first study on subnuclear trafficking of AID and demonstrates a new level in its complex regulation. In addition, our results resolve the problem related to dissociation of deamination activity and CSR activity of AID mutants. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Potential human factors deficiencies in the design of local control stations and operator interfaces in nuclear power plants

    International Nuclear Information System (INIS)

    Hartley, C.S.; Levy, I.S.; Fecht, B.A.

    1984-04-01

    The Pacific Northwest Laboratory has completed a project to identify human factors deficiencies in safety-significant control stations outside the control room of a nuclear power plant and to determine whether NUREG-0700, Guidelines for Control Room Design Reviews, would be sufficient for reviewing those local control stations (LCSs). The project accomplished this task by first, reviewing existing data pertaining to human factors deficiencies in LCSs involved in significant safety actions; second, surveying LCSs environments and design features at several operating nuclear power plants; and third, assessing the results of that survey relative to the contents of NUREG-0700

  16. Early localization of NPA58, a rat nuclear pore-associated protein, to ...

    Indian Academy of Sciences (India)

    Unknown

    and assembled using Adobe Photoshop 5⋅0. 3. Results. 3.1 Association of NPA58 with the nuclear pore complex. The vertebrate nucleoporins that have been identified so far exhibit characteristic punctate staining of the peri- phery of the nucleus due to the perforation of the nuclear membranes at intervals by the NPCs.

  17. Knockdown of aberrantly expressed nuclear localized decorin attenuates tumour angiogenesis related mediators in oral cancer progression model in vitro.

    Science.gov (United States)

    Dil, Nyla; Banerjee, Abhijit G

    2012-06-08

    Oral cancer accounts for roughly 3% of cancer cases in the world with about 350,000 newly reported cases annually and a 5-year survival rate of only 50%. Majority of oral cancers are squamous cell carcinomas that originate in the oral mucosal epithelial linings. We have previously shown that in human malignant squamous cells carcinoma (SCC-25) as well as in dysplastic oral keratinocytes (DOK), a small leucine-rich multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus where it interacts with nuclear epidermal growth factor receptor (EGFR). Post-transcriptional silencing of nuclear decorin significantly reduced IL-8 and IL8-dependent migration and invasion in these dysplastic and malignant oral epithelia. The objective of this study was to further examine the effects of nuclear decorin silencing on angiogenesis and angiogenesis related mediators in this oral cancer progression cell line model. We have used multiplex PCR, western blotting, and in vitro endothelial tube formation assay to study angiogenesis and related pathways in nuclear decorin silenced (stable knockdown) DOK and SCC-25 cells. Nuclear decorin knockdown resulted in significant down regulation of IL-8 expression, however IL-10, and TGF-β expression was not affected in either DOK or SCC25 cells as measured by multiplex RT PCR. IL-8 receptor CXCR 1 and 2 expression was slightly lower in nuclear decorin silenced cells indicating a contributing mechanism in previously shown reduced IL-8 mediated migration and invasion phenotype in these cells. IL-8 is known to induce Matrix metalloproteinase 9 (MMP9) which not only plays a role in tumour migration and invasion but also induces angiogenic switch. We found MMP9 to be significantly reduced in nuclear decorin silenced dysplastic and malignant oral epithelia. Other potent angiogenic mediators, VEGF189 and ANG-1 were either significantly reduced or completely abrogated in these cells. Angiogenesis as measured by endothelial

  18. Distinct functional domains of PNMA5 mediate protein-protein interaction, nuclear localization, and apoptosis signaling in human cancer cells.

    Science.gov (United States)

    Lee, Yong Hoi; Pang, Siew Wai; Poh, Chit Laa; Tan, Kuan Onn

    2016-09-01

    Members of paraneoplastic Ma (PNMA) family have been identified as onconeuronal antigens, which aberrant expressions in cancer cells of patients with paraneoplastic disorder (PND) are closely linked to manifestation of auto-immunity, neuro-degeneration, and cancer. The purpose of present study was to determine the role of PNMA5 and its functional relationship to MOAP-1 (PNMA4) in human cancer cells. PNMA5 mutants were generated through deletion or site-directed mutagenesis and transiently expressed in human cancer cell lines to investigate their role in apoptosis, subcellular localization, and potential interaction with MOAP-1 through apoptosis assays, fluorescence microscopy, and co-immunoprecipitation studies, respectively. Over-expressed human PNMA5 exhibited nuclear localization pattern in both MCF-7 and HeLa cells. Deletion mapping and mutagenesis studies showed that C-terminus of PNMA5 is responsible for nuclear localization, while the amino acid residues (391KRRR) within the C-terminus of PNMA5 are required for nuclear targeting. Deletion mapping and co-immunoprecipitation studies showed that PNMA5 interacts with MOAP-1 and N-terminal domain of PNMA5 is required for interaction with MOAP-1. Furthermore, co-expression of PNMA5 and MOAP-1 in MCF-7 cells significantly enhanced chemo-sensitivity of MCF-7 to Etoposide treatment, indicating that PNMA5 and MOAP-1 interact synergistically to promote apoptotic signaling in MCF-7 cells. Our results show that PNMA5 promotes apoptosis signaling in HeLa and MCF-7 cells and interacts synergistically with MOAP-1 through its N-terminal domain to promote apoptosis and chemo-sensitivity in human cancer cells. The C-terminal domain of PNMA5 is required for nuclear localization; however, both N-and C-terminal domains of PNMA5 appear to be required for pro-apoptotic function.

  19. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans

    OpenAIRE

    Mukhopadhyay, Saikat; Lu, Yun; Shaham, Shai; Sengupta, Piali

    2008-01-01

    Non-motile primary cilia are sensory organelles comprised of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis and signaling protein targeting and localization via as yet poorly understood mechanisms. Here we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory s...

  20. A role for aberrantly expressed nuclear localized decorin in migration and invasion of dysplastic and malignant oral epithelial cells.

    Science.gov (United States)

    Dil, Nyla; Banerjee, Abhijit G

    2011-09-29

    Oral cancer is the sixth most common malignancy worldwide with a mortality rate that is higher than many other cancers. Death usually occurs as a result of local invasion and regional lymph node metastases. Decorin is a multifunctional proteoglycan of the extracellular matrix that affects the biology of various types of cancer. Previously; we have shown that decorin is aberrantly expressed in the nucleus in human dysplastic oral keratinocytes (DOK) and malignant squamous cells carcinoma (SCC-25) and human biopsy tissues. In this study, we examined the role of nuclear decorin in oral cancer progression. We have used a post-transcriptional gene silencing (RNA interference) approach to stably knockdown nuclear decorin gene expression in DOK and SCC-25 cells using a specific shRNA plasmid and a combination of immunological and molecular techniques to study nuclear decorin function in these oral epithelial cell lines. More than 80% decorin silencing/knockdown was achieved as confirmed by real time PCR and western blot analysis in both DOK and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin expression resulted in significantly reduced invasion and migration in these cell lines as measured by Matrigel™ coated and uncoated Trans well chamber assays respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with recombinant human IL-8 or IL-8 containing conditioned medium from respective un-transfected cells for 24 h prior to migration and invasion experiments, resulted in the salvation of reduced migration and invasion phenotype. Furthermore, we found that nuclear localized decorin interacts with EGFR in the nuclear fractions of both DOK and SCC-25 cells. Interestingly, EGFR (trans) activation has previously been shown to be involved in IL-8 production in various epithelia. Taken together, our results indicate that nuclear localized decorin plays an

  1. Visualization of nuclear localization of transcription factors with cyan and green fluorescent proteins in the red alga Porphyra yezoensis.

    Science.gov (United States)

    Uji, Toshiki; Takahashi, Megumu; Saga, Naotsune; Mikami, Koji

    2010-04-01

    Transcription factors play a central role in expression of genomic information in all organisms. The objective of our study is to analyze the function of transcription factors in red algae. One way to analyze transcription factors in eukaryotic cells is to study their nuclear localization, as reported for land plants and green algae using fluorescent proteins. There is, however, no report documenting subcellular localization of transcription factors from red algae. In the present study, using the marine red alga Porphyra yezoensis, we confirmed for the first time successful expression of humanized fluorescent proteins (ZsGFP and ZsYFP) from a reef coral Zoanthus sp. and land plant-adapted sGFP(S65T) in gametophytic cells comparable to expression of AmCFP. Following molecular cloning and characterization of transcription factors DP-E2F-like 1 (PyDEL1), transcription elongation factor 1 (PyElf1) and multiprotein bridging factor 1 (PyMBF1), we then demonstrated that ZsGFP and AmCFP can be used to visualize nuclear localization of PyElf1 and PyMBF1. This is the first report to perform visualization of subcellular localization of transcription factors as genome-encoded proteins in red algae.

  2. Adaptor-mediated recruitment of RNA polymerase II to a signal-dependent activator.

    Science.gov (United States)

    Kee, B L; Arias, J; Montminy, M R

    1996-02-02

    The second messenger cAMP stimulates the expression of a number of target genes via the protein kinase A-mediated phosphorylation of CREB at Ser-133 (Gonzalez, G. A., and Montminy, M. R. (1989) Cell 59, 675-680). Ser-133 phosphorylation enhances CREB activity by promoting interaction with a 265-kDa CREB binding protein referred to as CBP (Arias, J., Alberts, A., Brindle, P., Claret, F., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-228; Chrivia, J. C., Kwok, R. P., Lamb, N., Hagiwara, M., Montminy, M. R., and Goodman, R. H. (1993) Nature 365, 855-859). The mechanism by which CBP in turn mediates induction of cAMP-responsive genes is unknown but is thought to involve recruitment of basal transcription factors to the promoter. Here we demonstrate that CBP associates specifically with RNA polymerase II in HeLa nuclear extracts. This association in turn permits RNA polymerase II to be recruited to CREB in a phospho-(Ser-133)-dependent manner. As anti-CBP antiserum, which inhibits recruitment of CBP and RNA polymerase II to phospho-(Ser-133) CREB, attenuates transcriptional induction by protein kinase A in vitro, our results demonstrate that the CBP-RNA polymerase II complex is critical for expression of cAMP-responsive genes.

  3. Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans.

    Science.gov (United States)

    Mukhopadhyay, Saikat; Lu, Yun; Shaham, Shai; Sengupta, Piali

    2008-05-01

    Nonmotile primary cilia are sensory organelles composed of a microtubular axoneme and a surrounding membrane sheath that houses signaling molecules. Optimal cellular function requires the precise regulation of axoneme assembly, membrane biogenesis, and signaling protein targeting and localization via as yet poorly understood mechanisms. Here, we show that sensory signaling is required to maintain the architecture of the specialized AWB olfactory neuron cilia in C. elegans. Decreased sensory signaling results in alteration of axoneme length and expansion of a membraneous structure, thereby altering the topological distribution of a subset of ciliary transmembrane signaling molecules. Signaling-regulated alteration of ciliary structures can be bypassed by modulation of intracellular cGMP or calcium levels and requires kinesin-II-driven intraflagellar transport (IFT), as well as BBS- and RAB8-related proteins. Our results suggest that compensatory mechanisms in response to altered levels of sensory activity modulate AWB cilia architecture, revealing remarkable plasticity in the regulation of cilia structure.

  4. A nuclear localization of the infectious haematopoietic necrosis virus NV protein is necessary for optimal viral growth.

    Directory of Open Access Journals (Sweden)

    Myeong Kyu Choi

    Full Text Available The nonvirion (NV protein of infectious hematopoietic necrosis virus (IHNV has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection in RTG-2 cells of NV fused to green fluorescent protein (GFP, a nuclear localization of NV was demonstrated. Deletion analyses showed that the (32EGDL(35 residues were essential for nuclear localization of NV protein, and fusion of these 4 amino acids to GFP directed its transport to the nucleus. We generated a recombinant IHNV, rIHNV-NV-ΔEGDL in which the (32EGDL(35 was deleted from the NV. rIHNVs with wild-type NV (rIHNV-NV or with the NV gene replaced with GFP (rIHNV-ΔNV-GFP were used as controls. RTG-2 cells infected with rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL yielded 12- and 5-fold less infectious virion, respectively, than wild type rIHNV-infected cells at 48 h post-infection (p.i.. While treatment with poly I∶C at 24 h p.i. did not inhibit replication of wild-type rIHNVs, replication rates of rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL were inhibited by poly I∶C. In addition, both rIHNV-ΔNV and rIHNV-NV-ΔEGDL induced higher levels of expressions of both IFN1 and Mx1 than wild-type rIHNV. These data suggest that the IHNV NV may support the growth of IHNV through inhibition of the INF system and the amino acid residues of (32EGDL(35 responsible for nuclear localization are important for the inhibitory activity of NV.

  5. A nuclear localization of the infectious haematopoietic necrosis virus NV protein is necessary for optimal viral growth

    Science.gov (United States)

    Choi, M.K.; Moon, C.H.; Ko, M.S.; Lee, U.-H.; Cho, W.; Cha, S.J.; Do, J.W.; Heo, G.J.; Jeong, S.G.; Hahm, Y.S.; Harmache, A.; Bremont, M.; Kurath, G.; Park, J.-W.

    2011-01-01

    The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection in RTG-2 cells of NV fused to green fluorescent protein (GFP), a nuclear localization of NV was demonstrated. Deletion analyses showed that the 32EGDL35 residues were essential for nuclear localization of NV protein, and fusion of these 4 amino acids to GFP directed its transport to the nucleus. We generated a recombinant IHNV, rIHNV-NV-ΔEGDL in which the 32EGDL35 was deleted from the NV. rIHNVs with wild-type NV (rIHNV-NV) or with the NV gene replaced with GFP (rIHNV-ΔNV-GFP) were used as controls. RTG-2 cells infected with rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL yielded 12- and 5-fold less infectious virion, respectively, than wild type rIHNV-infected cells at 48 h post-infection (p.i.). While treatment with poly I:C at 24 h p.i. did not inhibit replication of wild-type rIHNVs, replication rates of rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL were inhibited by poly I:C. In addition, both rIHNV-ΔNV and rIHNV-NV-ΔEGDL induced higher levels of expressions of both IFN1 and Mx1 than wild-type rIHNV. These data suggest that the IHNV NV may support the growth of IHNV through inhibition of the INF system and the amino acid residues of 32EGDL35 responsible for nuclear localization are important for the inhibitory activity of NV.

  6. Nuclear localization domains of GATA activator Gln3 are required for transcription of target genes through dephosphorylation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Numamoto, Minori; Tagami, Shota; Ueda, Yusuke; Imabeppu, Yusuke; Sasano, Yu; Sugiyama, Minetaka; Maekawa, Hiromi; Harashima, Satoshi

    2015-08-01

    The GATA transcription activator Gln3 in the budding yeast (Saccharomyces cerevisiae) activates transcription of nitrogen catabolite repression (NCR)-sensitive genes. In cells grown in the presence of preferred nitrogen sources, Gln3 is phosphorylated in a TOR-dependent manner and localizes in the cytoplasm. In cells grown in non-preferred nitrogen medium or treated with rapamycin, Gln3 is dephosphorylated and is transported from the cytoplasm to the nucleus, thereby activating the transcription of NCR-sensitive genes. Caffeine treatment also induces dephosphorylation of Gln3 and its translocation to the nucleus and transcription of NCR-sensitive genes. However, the details of the mechanism by which phosphorylation controls Gln3 localization and transcriptional activity are unknown. Here, we focused on two regions of Gln3 with nuclear localization signal properties (NLS-K, and NLS-C) and one with nuclear export signal (NES). We constructed various mutants for our analyses: gln3 containing point mutations in all potential phosphoacceptor sites (Thr-339, Ser-344, Ser-347, Ser-355, Ser-391) in the NLS and NES regions to produce non-phosphorylatable (alanine) or mimic-phosphorylatable (aspartic acid) residues; and deletion mutants. We found that phosphorylation of Gln3 was impaired in all of these mutations and that the aspartic acid substitution mutants showed drastic reduction of Gln3-mediated transcriptional activity despite the fact that the mutations had no effect on nuclear localization of Gln3. Our observations suggest that these regions are required for transcription of target genes presumably through dephosphorylation. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. When it is unfamiliar to me: Local acceptance of planned nuclear power plants in China in the post-fukushima era

    International Nuclear Information System (INIS)

    Guo, Yue; Ren, Tao

    2017-01-01

    Many contributions have been made in the studies of the factors that influence public acceptance of nuclear power. However, previous studies seldom focused on nuclear power plants in the planning stage. Actually public perception is usually more sensitive at the preliminary planning stage of a nuclear power station. Mainly utilizing questionnaire survey and focus group methods, we have identified the factors that are correlated with local acceptance of planned nuclear power plants in China. We conducted our survey in two cities, Huludao, Liaoning province in northern China, and Shanwei, Guangdong province in southern China, where the local government was planning to build its first nuclear power plant. We find that people who live closer to the plant sites are less willing to accept nuclear power than those who live farther away. As for “surface psychology” factors, perceived benefits and risks significantly influence local acceptance. As for “deep psychology” factors, emotional identification and social trust can significantly influence local acceptance, while perceived knowledge cannot. When citizens are unfamiliar with nuclear power plants, they are more inclined to evaluate the benefits and risks through emotional identification and social trust, rather than through pure rational deduction based on concrete facts. - Highlights: • We focus on the local acceptance of nuclear power in the planning stages. • People who live closer to plant sites are less willing to accept nuclear power. • Perceived benefits and risks significantly influence local acceptance. • Emotional identification and trust can significantly influence local acceptance. • While perceived knowledge cannot significantly influence local acceptance.

  8. Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent.

    Science.gov (United States)

    Davis, F M; Azimi, I; Faville, R A; Peters, A A; Jalink, K; Putney, J W; Goodhill, G J; Thompson, E W; Roberts-Thomson, S J; Monteith, G R

    2014-05-01

    Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of

  9. A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

    Science.gov (United States)

    Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

    2012-01-01

    Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

  10. [Effect of Nm23-H1 Nuclear Localization on Proliferation of 
Human Lung Adenocarcinoma Cell Line A549].

    Science.gov (United States)

    Sheng, Ya; Xiong, Yanli; Xu, Mingfang; Kuang, Xunjie; Wang, Dong; Yang, Xueqin

    2017-04-20

    Recent studies have indicated that Nm23-H1 is found in the nucleus, but previous studies have been based on the overexpression or suppression of Nm23-H1 in the cytoplasm. Due to the lacking nuclear localization signal of Nm23-H1, these results cannot reflect or repeat cells in which Nm23-H1 mainly positioned in nuclei and whether they cause clinical biological effects. Therefore, to explore the effects of transposing Nm23-H1 from the cytoplasm to the nucleus during lung cancer cell proliferation, a vector with a nuclear localization signal of Nm23-H1 was constructed and A549 cells were transfected. Gene recombination technology was used to construct pLentis-CMV-NME1-IRES2-PURO lentiviral vectors using a nuclear localization signal sequence, and the recombinant plasmid was verified using restriction enzyme analysis and sequencing. Nm23-H1 positioning and expression were performed after the stably transfected A549 cells were assessed by Western blot and confocal laser scanning microscope. The A549 cell proliferation was assessed using a cell counting kit-8. Flow cytometry was performed to assess the cell cycle distribution of A549 cells. The directional Nm23-H1 lentiviral vector was successfully constructed within the nucleus. Compared with that of the empty vector group, the proliferation rates of the transfection groups at 72 h, 96 h, and 120 h were remarkably increased (PA549 cells in the G0/G1 phase proportion was 35.69%, which was higher than the 28.28% of the transfection group (t=1.461, P=0.217); furthermore, the transfection group of A549 cells in the G2/M phase proportion was 58.7% and that of the empty vector group was 31.30% (t=4.560, P=0.010). Human lung adenocarcinoma cell line A549 cells of Nm23-H1 nuclear localized mainly in the G2/M phase and the nuclear Nm23-H1 promoted A549 cell proliferation in vitro.

  11. Cysteine (C)-X-C Receptor 4 Undergoes Transportin 1-Dependent Nuclear Localization and Remains Functional at the Nucleus of Metastatic Prostate Cancer Cells

    Science.gov (United States)

    Don-Salu-Hewage, Ayesha S.; Chan, Siu Yuen; McAndrews, Kathleen M.; Chetram, Mahandranauth A.; Dawson, Michelle R.; Bethea, Danaya A.; Hinton, Cimona V.

    2013-01-01

    The G-protein coupled receptor (GPCR), Cysteine (C)-X-C Receptor 4 (CXCR4), plays an important role in prostate cancer metastasis. CXCR4 is generally regarded as a plasma membrane receptor where it transmits signals that support transformation, progression and eventual metastasis. Due to the central role of CXCR4 in tumorigenesis, therapeutics approaches such as antagonist and monoclonal antibodies have focused on receptors that exist on the plasma membrane. An emerging concept for G-protein coupled receptors is that they may localize to and associate with the nucleus where they retain function and mediate nuclear signaling. Herein, we demonstrate that CXCR4 associated with the nucleus of malignant prostate cancer tissues. Likewise, expression of CXCR4 was detected in nuclear fractions among several prostate cancer cell lines, compared to normal prostate epithelial cells. Our studies identified a nuclear pool of CXCR4 and we defined a nuclear transport pathway for CXCR4. We reveal a putative nuclear localization sequence (NLS), ‘RPRK’, within CXCR4 that contributed to nuclear localization. Additionally, nuclear CXCR4 interacted with Transportinβ1 and Transportinβ1-binding to CXCR4 promoted its nuclear translocation. Importantly, Gαi immunoprecipitation and calcium mobilization studies indicated that nuclear CXCR4 was functional and participated in G-protein signaling, revealing that the nuclear pool of CXCR4 retained function. Given the suggestion that functional, nuclear CXCR4 may be a mechanism underlying prostate cancer recurrence, increased metastatic ability and poorer prognosis after tumors have been treated with therapy that targets plasma membrane CXCR4, these studies addresses a novel mechanism of nuclear signaling for CXCR4, a novel mechanism of clinical targeting, and demonstrate an active nuclear pool that provides important new information to illuminate what has been primarily clinical reports of nuclear CXCR4. PMID:23468933

  12. On-site storage of high level nuclear waste: attitudes and perceptions of local residents.

    Science.gov (United States)

    Bassett, G W; Jenkins-Smith, H C; Silva, C

    1996-06-01

    No public policy issue has been as difficult as high-level nuclear waste. Debates continue regarding Yucca Mountain as a disposal site, and-more generally-the appropriateness of geologic disposal and the need to act quickly. Previous research has focused on possible social, political, and economic consequences of a facility in Nevada. Impacts have been predicted to be potentially large and to emanate mainly from stigmatization of the region due to increased perceptions of risk. Analogous impacts from leaving waste at power plants have been either ignored or assumed to be negligible. This paper presents survey results on attitudes of residents in three counties where nuclear waste is currently stored. Topics include perceived risk, knowledge of nuclear waste and radiation, and impacts on jobs, tourism, and housing values from leaving waste on site. Results are similar to what has been reported for Nevada; the public is concerned about possible adverse effects from on-site storage of waste.

  13. Growing from a local into an international nuclear services provider - challenges and opportunities

    International Nuclear Information System (INIS)

    Androjna, A.; Storrick, D.; Lesnjak, A.

    2014-01-01

    Apart from nuclear power plants' (NPPs) internally staffed expert resources, the support of qualified external nuclear maintenance and modification services providers (NSPs) is extremely important. The postponement of the nuclear power renaissance along with an aging workforce is pushing the industry to search for different approaches to maintain and improve the required level of expertise and quality. Operating in a domestic market with only one NPP unit, the leading Slovenian NSP has been partnering with complimentary companies to jointly satisfy the needs of the domestic, US and EU customers. By remaining competitive in quality and price and sharing resources, global experience and good practices, results in added value to all of the interested parties is achieved. In addition to supporting peak outage season shortages of qualified resources, the concept also aids in load-levelling the resource needs throughout the year. The challenges and the opportunities related to the concept are discussed in the paper. (authors)

  14. Assessment of national systems for obtaining local siting acceptance of nuclear-waste-management facilities (1981). Final report

    International Nuclear Information System (INIS)

    1981-01-01

    There is a rich mixture of formal and informal approaches being used in our sister nuclear democracies in their attempts to deal with the difficulties in obtaining local siting acceptance of national waste management facilities. Some of these are meeting with a degree of success not yet achieved in the US. Although this survey documents and assesses many of these approaches, the scope of the study did not include an assessment of their relevance to common problems in the US. It would appear that in addition to a periodic updating of the approaches and progress of other countries in dealing with the siting of nuclear waste facilities, an assessment of the applicability of the more successful of these approaches to the US political system could make good use of the information developed in the preparation of this report

  15. Multi-region fuzzy logic controller with local PID controllers for U-tube steam generator in nuclear power plant

    Directory of Open Access Journals (Sweden)

    Puchalski Bartosz

    2015-12-01

    Full Text Available In the paper, analysis of multi-region fuzzy logic controller with local PID controllers for steam generator of pressurized water reactor (PWR working in wide range of thermal power changes is presented. The U-tube steam generator has a nonlinear dynamics depending on thermal power transferred from coolant of the primary loop of the PWR plant. Control of water level in the steam generator conducted by a traditional PID controller which is designed for nominal power level of the nuclear reactor operates insufficiently well in wide range of operational conditions, especially at the low thermal power level. Thus the steam generator is often controlled manually by operators. Incorrect water level in the steam generator may lead to accidental shutdown of the nuclear reactor and consequently financial losses. In the paper a comparison of proposed multi region fuzzy logic controller and traditional PID controllers designed only for nominal condition is presented. The gains of the local PID controllers have been derived by solving appropriate optimization tasks with the cost function in a form of integrated squared error (ISE criterion. In both cases, a model of steam generator which is readily available in literature was used for control algorithms synthesis purposes. The proposed multi-region fuzzy logic controller and traditional PID controller were subjected to broad-based simulation tests in rapid prototyping software - Matlab/Simulink. These tests proved the advantage of multi-region fuzzy logic controller with local PID controllers over its traditional counterpart.

  16. Local panels and maintainability human factors assessment for AP1000 nuclear power plant

    International Nuclear Information System (INIS)

    Li, Zhonghai; Reed, Julie I.

    2011-01-01

    A document entitled 'AP1000 Local Panels and Maintainability Human Factors Design Guidelines' was produced to aid the designers to specifically include human factors (HF) considerations in the design, operation, and maintenance of local control stations and plant equipment. To ensure that the applicable HF design guidelines are appropriately applied to the design of local panels and maintenance activities, and identify any HF improvement opportunities that can readily be implemented at the design stage, a HF assessment of maintenance activities and local plant operations is underway. This assessment gives priority to local control stations and equipment which have been identified as having a potential impact on safety. This includes risk-significant systems, structures and components (SSCs) identified through the probabilistic risk assessment (PRA), and local operator actions as required by the Emergency Operating Procedures (EOPs). Local actions, maintenance activities and associated operator interfaces are reviewed against the relevant HF guidelines. The results of the assessment include a description of the component, associated local actions and/or required maintenance activities, good design features and/or potential issues, and recommendations for change or improvement. These results are communicated to responsible design engineers who evaluate the impact to plant design and implement design changes, if deemed necessary. (author)

  17. Localization of nuclear retained mRNAs in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Thomsen, Rune; Libri, Domenico; Boulay, Jocelyne

    2003-01-01

    In the yeast Saccharomyces cerevisiae, a common conditional phenotype associated with deletion or mutation of genes encoding mRNA export factors is the rapid accumulation of mRNAs in intranuclear foci, suggested to be near transcription sites. The nuclear RNA exosome has been implicated in retain...

  18. Nuclear localization of Src-family tyrosine kinases is required for growth factor-induced euchromatinization

    International Nuclear Information System (INIS)

    Takahashi, Akinori; Obata, Yuuki; Fukumoto, Yasunori; Nakayama, Yuji; Kasahara, Kousuke; Kuga, Takahisa; Higashiyama, Yukihiro; Saito, Takashi; Yokoyama, Kazunari K.; Yamaguchi, Naoto

    2009-01-01

    Src-family kinases (SFKs), which participate in various signaling events, are found at not only the plasma membrane but also several subcellular compartments, including the nucleus. Nuclear structural changes are frequently observed during transcription, cell differentiation, senescence, tumorigenesis, and cell cycle. However, little is known about signal transduction in the alteration of chromatin texture. Here, we develop a pixel imaging method for quantitatively evaluating chromatin structural changes. Growth factor stimulation increases euchromatic hypocondensation and concomitant heterochromatic hypercondensation in G 1 phase, and the levels reach a plateau by 30 min, sustain for at least 5 h and return to the basal levels after 24 h. Serum-activated SFKs in the nucleus were more frequently detected in the euchromatin areas than the heterochromatin areas. Nuclear expression of kinase-active SFKs, but not unrelated Syk kinase, drastically increases both euchromatinization and heterochromatinization in a manner dependent on the levels of nuclear tyrosine phosphorylation. However, growth factor stimulation does not induce chromatin structural changes in SYF cells lacking SFKs, and reintroduction of one SFK member into SYF cells can, albeit insufficiently, induce chromatin structural changes. These results suggest that nuclear tyrosine phosphorylation by SFKs plays an important role in chromatin structural changes upon growth factor stimulation.

  19. Participation of local citizens groups in the Swedish nuclear waste process

    International Nuclear Information System (INIS)

    Holmstrand, O.

    1999-01-01

    The Waste Network's conclusions and views on the nuclear waste issue are summarised in the following points: The management of the nuclear waste is not solved. In order to minimise the amount of waste, the further operating of nuclear reactors should be questioned. The choice of method should be made before the siting. The deadlock to the KBS method must come to an end. The choice of method must be based on clearly expressed functional conditions formulated in advance. The siting must be based on considerations to environment and security, not political acceptance. The pilot studies in municipalities must cease and should be replaced by a clear and understandable sieving process at a national scale. An independent authority must control and supervise the EIA process instead of the nuclear industry. A well performed EIA process is the necessary condition to give the choice of method and site enough legitimacy and acceptance. Environmental organisations being the representatives of the public must be given reasonable conditions and resources to take part in the EIA process to handle the question

  20. Early localization of NPA58, a rat nuclear pore-associated protein, to ...

    Indian Academy of Sciences (India)

    Unknown

    to the reforming nuclear envelope during mitosis. RADHIKA GANESHAN, NANDINI RANGARAJ and VEENA K PARNAIK*. Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. *Corresponding author (Fax, + 91-40-7171195; Email, veenap@ccmb.ap.nic.in). We have studied the mitotic ...

  1. Nuclear localization of beta-catenin involved in precancerous change in oral leukoplakia

    Science.gov (United States)

    Ishida, Kosei; Ito, Satoshi; Wada, Naoyuki; Deguchi, Hiroyo; Hata, Tsuyoshi; Hosoda, Masaru; Nohno, Tsutomu

    2007-01-01

    Background Oral leukoplakia is a precancerous change developed in the oral mucosa, and the mechanism that oral leukoplakia becomes malignant through atypical epithelium is not known. Here we compared the β-catenin expression detected by immunohistochemical staining in the normal oral epithelium and in the oral leukoplakia with or without dysplasia. Results The normal oral epithelium showed β-catenin expression only in the cell membrane, but not in the nuclei. In the oral leukoplakia without dysplasia, 7 out of 17 samples (41%) showed β-catenin expression in the cell membrane, and 5 samples (29%) showed expression in the nuclei. In the oral leukoplakia with dysplasia, nuclear expression of β-catenin was shown in 11 out of 12 samples (92%). Incidence of nuclear β-catenin expression was significantly different between dysplasia and normal oral epithelium (P oral leukoplakia with dysplasia and those without dysplasia (P oral leukoplakia where nuclear expression of β-catenin was evident, but not in epithelial cells without nuclear expression of β-catenin. Conclusion The components of canonical Wnt pathway, such as Wnt3, β-catenin, and cyclin D1, were detected, implying that this pathway is potentially involved in the progression of dysplasia in oral leukoplakia. PMID:17922924

  2. Participation of local citizens groups in the Swedish nuclear waste process

    Energy Technology Data Exchange (ETDEWEB)

    Holmstrand, O. [The Waste Network, Lerum (Sweden)

    1999-12-01

    The Waste Network's conclusions and views on the nuclear waste issue are summarised in the following points: The management of the nuclear waste is not solved. In order to minimise the amount of waste, the further operating of nuclear reactors should be questioned. The choice of method should be made before the siting. The deadlock to the KBS method must come to an end. The choice of method must be based on clearly expressed functional conditions formulated in advance. The siting must be based on considerations to environment and security, not political acceptance. The pilot studies in municipalities must cease and should be replaced by a clear and understandable sieving process at a national scale. An independent authority must control and supervise the EIA process instead of the nuclear industry. A well performed EIA process is the necessary condition to give the choice of method and site enough legitimacy and acceptance. Environmental organisations being the representatives of the public must be given reasonable conditions and resources to take part in the EIA process to handle the question.

  3. Approach for evaluating the general and localized corrosion of carbon-steel containers for nuclear waste disposal

    International Nuclear Information System (INIS)

    Marsh, G.P.; Taylor, K.J.; Sharland, S.M.; Tasker, P.W.

    1987-01-01

    The paper considers the long term corrosion of carbon-steel containers for heat generating nuclear waste in a granitic repository. Under such conditions carbon steel may exhibit general, localized or passive corrosion behavior depending on the exact composition and redox potential of the groundwater contacting the containers; localized corrosion being of most concern because it has the fastest propagation rate. It is well established, however, that such localized corrosion is only possible when the environment is sufficiently oxidizing to maintain a positive potential gradient between the cathodic surface and the corrosion sites, which requires that species with oxidizing potentials greater than water need to be present. This fact provides a basis for estimating the periods during which containers may be subject to localized and subsequently to general corrosion, and hence for making an overall assessment of the metal allowance required for a specified container life. A model for the diffusion transport of oxygen has been developed, and a sensitivity analysis has shown that the period of possible localized attack is strongly dependent on the passive film leakage current, the radiation dose rate and the oxygen diffusion coefficient. 20 references, 5 figures

  4. Characterization of amino acid residues within the N-terminal region of Ubc9 that play a role in Ubc9 nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Sekhri, Palak [Department of Biological Sciences, Wayne State University, 5947 Gullen Mall, Detroit, MI 48202 (United States); Tao, Tao [School of Life Sciences, Xiamen University, Xiamen (China); Kaplan, Feige [Department of Human Genetics, McGill University, Montreal (Canada); Zhang, Xiang-Dong, E-mail: xzhang@wayne.edu [Department of Biological Sciences, Wayne State University, 5947 Gullen Mall, Detroit, MI 48202 (United States)

    2015-02-27

    As the sole E2 enzyme for SUMOylation, Ubc9 is predominantly nuclear. However, the underlying mechanisms of Ubc9 nuclear localization are still not well understood. Here we show that RNAi-depletion of Imp13, an importin known to mediate Ubc9 nuclear import, reduces both Ubc9 nuclear accumulation and global SUMOylation. Furthermore, Ubc9-R13A or Ubc9-H20D mutation previously shown to interrupt the interaction of Ubc9 with nucleus-enriched SUMOs reduces the nuclear enrichment of Ubc9, suggesting that the interaction of Ubc9 with the nuclear SUMOs may enhance Ubc9 nuclear retention. Moreover, Ubc9-R17E mutation, which is known to disrupt the interaction of Ubc9 with both SUMOs and Imp13, causes a greater decrease in Ubc9 nuclear accumulation than Ubc9-R13A or Ubc9-H20D mutation. Lastly, Ubc9-K74A/S89D mutations that perturb the interaction of Ubc9 with nucleus-enriched SUMOylation-consensus motifs has no effect on Ubc9 nuclear localization. Altogether, our results have elucidated that the amino acid residues within the N-terminal region of Ubc9 play a pivotal role in regulation of Ubc9 nuclear localization. - Highlights: • Imp13-mediated nuclear import of Ubc9 is critical for global SUMOylation. • Ubc9 mutations disrupting Ubc9-SUMO interaction decrease Ubc9 nuclear accumulation. • N-terminal amino acid residues of Ubc9 are critical for Ubc9 nuclear enrichment.

  5. Aberrant nuclear localization of β-catenin without genetic alterations in β-catenin or Axin genes in esophageal cancer

    Directory of Open Access Journals (Sweden)

    Shinoda Noriyuki

    2007-02-01

    Full Text Available Abstract Background β-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. β-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of β-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the β-catenin gene and Axin gene in esophageal squamous cell carcinoma. Materials and methods Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for β-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the β-catenin gene and Axin gene were performed on tumors with nuclear β-catenin expression. Results Four (8% esophageal cancer tissues showed high nuclear β-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54% patients. All four cases that showed nuclear β-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of β-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in β-catenin exon 3 in the four cases with nuclear β-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302–2409 which was present in the paired normal mucosa. Conclusion A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of β-catenin accompanied with increased cyclin D1 expression. Mutations in β-catenin or axin genes are not responsible for this abnormal localization of β-catenin.

  6. Review study 1995. Localization of the repository for spent nuclear fuel; Oeversiktsstudie 95. Lokalisering av djupfoervar foer anvaent kaernbraensle

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-10-01

    This report gives an overview of the studies performed by SKB pertinent to selection of a site for the Swedish repository for spent nuclear fuels, and is written for both experts in the various fields involved, decision-makers and the interested general public. The review can not comprise all detailed factors necessary for deciding the localization, but deals mainly with conditions on the land surface and can point out areas which are not well suited or less interesting as a site. It also treats several scientific, technical and social bases in different parts of the country. 120 refs, 53 figs.

  7. The social and economic impact created by construction of a nuclear power station: the part played by local companies

    International Nuclear Information System (INIS)

    Rongere, H.

    1983-01-01

    The president of the Sedan Chamber of Commerce and Industry and managing director of a public works company indicates how local and regional firms involved in the construction of the Chooz B power plant in the Ardennes organized themselves to cater for the requirements of the EDF. The measures taken by these firms to adapt themselves to the demanding and complex nuclear power market are indicated and further the repercussions of the on site work on employment levels and business activity are indicated [fr

  8. The Hsp90 Inhibitor, 17-AAG, Prevents the Ligand-Independent Nuclear Localization of Androgen Receptor in Refractory Prostate Cancer Cells

    Science.gov (United States)

    Saporita, Anthony J.; Ai, Junkui; Wang, Zhou

    2010-01-01

    BACKGROUND Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgen-refractory prostate cancer cells. METHODS AND RESULTS We demonstrate increased nuclear localization of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells compared to parental androgen-sensitive human prostate cancer LNCaP cells. Analysis of AR mutants impaired in ligand-binding indicates that the nuclear localization of AR in C4-2 cells is truly androgen-independent. The hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA expression and disrupts the ligand-independent nuclear localization of AR at doses much lower than required to inhibit androgen-induced nuclear import. CONCLUSIONS Hsp90 is a key regulator of ligand-independent nuclear localization and activation of AR in androgen-refractory prostate cancer cells. PMID:17221841

  9. Distinct Structural Features of G Protein-Coupled Receptor Kinase 5 (GRK5) Regulate Its Nuclear Localization and DNA-Binding Ability

    Science.gov (United States)

    Johnson, Laura R.; Robinson, James D.; Lester, Katrina N.; Pitcher, Julie A.

    2013-01-01

    G protein-coupled receptor kinases (GRKs) act to desensitize G protein-coupled receptors (GPCRs). In addition to this role at the plasma membrane, a nuclear function for GRK5, a member of the GRK4 subfamily of GRKs, has been reported. GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5. Here we demonstrate that the possession of a nuclear localization sequence (NLS) is a common feature of GRK4 subfamily members (GRKs 4, 5 and 6). However, the location of the NLS and the ability of these GRKs to bind DNA in vitro are different. The NLSs of GRK5 and 6 bind DNA in vitro, whilst the NLS of GRK4 does not. Using mutants of GRK5 we identify the regions of GRK5 required for DNA-binding in vitro and nuclear localization in cells. The DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site. A functional nuclear export sequence (NES), required for CaM-dependent nuclear export of the kinase, is also identified. Based on our observations we propose a model to explain how nuclear localization of GRK5 may be regulated. Notably, the nuclear localization of GRK5 and 6 is differentially regulated. These results suggest subfamily specific nuclear functions for the GRK4 subfamily members. Identification of GRK specific small molecule inhibitors of nuclear localization and/or function for the GRK4 subfamily may thus be an achievable goal. PMID:23658733

  10. Local control of nuclear calcium signaling in cardiac myocytes by perinuclear microdomains of sarcolemmal insulin-like growth factor 1 receptors.

    Science.gov (United States)

    Ibarra, Cristian; Vicencio, Jose M; Estrada, Manuel; Lin, Yingbo; Rocco, Paola; Rebellato, Paola; Munoz, Juan P; Garcia-Prieto, Jaime; Quest, Andrew F G; Chiong, Mario; Davidson, Sean M; Bulatovic, Ivana; Grinnemo, Karl-Henrik; Larsson, Olle; Szabadkai, Gyorgy; Uhlén, Per; Jaimovich, Enrique; Lavandero, Sergio

    2013-01-18

    The ability of a cell to independently regulate nuclear and cytosolic Ca(2+) signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca(2+) signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca(2+) signals locally has not been explored. To study the role of perinuclear sarcolemma in selective nuclear Ca(2+) signaling. We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca(2+) signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca(2+) signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca(2+) release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca(2+) buffers--parvalbumin--with cytosolic or nuclear localization demonstrated that the nuclear Ca(2+) handling system is physically and functionally segregated from the cytosolic Ca(2+) signaling machinery. These data reveal the existence of an inositol 1,4,5-trisphosphate-dependent nuclear Ca(2+) toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca(2+) signaling in response to an extracellular ligand.

  11. Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization.

    Science.gov (United States)

    Yang, Jr-M; Schiapparelli, P; Nguyen, H-N; Igarashi, A; Zhang, Q; Abbadi, S; Amzel, L M; Sesaki, H; Quiñones-Hinojosa, A; Iijima, M

    2017-06-29

    PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

  12. Does nuclear power-related facility siting always lower the local property Values? Comparative analysis among the sites in Japan

    International Nuclear Information System (INIS)

    Yamane, Fumihiro; Ohgaki, Hideaki; Asano, Kota

    2011-01-01

    Yamane et al. (2011) carried out hedonic house rent analyses for several nuclear power plant sites in Japan, compared the result for each plant, and obtained some empirical results indicating that the local residents' marginal willingness-to-pay (MWTP) for living near the plant was not necessarily positive and that the MWTP was correlated with operation years of the plants and some of the host communities' attributes (i.e., population density, financial condition and public service improvement). However, these results may suffer from biases and inefficiency in estimating hedonic functions, caused by spatial dependency: spatial autoregression and spatial autocorrelation. In this paper, we introduce spatial econometric techniques to settle this problem. As a revised result, it is indicated that the local residents' MWTP is correlated with past accidents in the plants, education service improvement in the host communities and so on. (author)

  13. Control room, emergency control system and local control panels in nuclear power plants

    International Nuclear Information System (INIS)

    1988-01-01

    The requirements on planning and construction of control boards including ergonomic-technical designing are specified in this rule. The specifications put the requirements on the design of place, process and environment of work, which are mentioned in the sections 90 and 91 of the labor-management relations act, into more concrete terms for the safety-relevant control panels as work places in a nuclear power station. The work places at control panels are not considered as video workstations in the sense of the 'Safety Rules for Video Workstations in the Office Sector' published by the General Association of the Industrial Trade Associations. The requirements are based on the operation and information technology realized at present in control panels of stationary nuclear power plants. (orig./HP) [de

  14. Monodisperse Magnetite Nanoparticles Coupled with Nuclear Localization Signal Peptide for Cell-Nucleus Targeting

    OpenAIRE

    Xu, Chenjie; Xie, Jin; Kohler, Nathan; Walsh, Edward G.; Chin, Y. Eugene; Sun, Shouheng

    2008-01-01

    Functionalization of monodisperse superparamagnetic magnetite (Fe3O4) nanoparticles for cell specific targeting is crucial for cancer diagnostics and therapeutics. Targeted magnetic nanoparticles can be used to enhance the tissue contrast in magnetic resonance imaging (MRI), to improve the efficiency in anticancer drug delivery, and to eliminate tumor cells by magnetic fluid hyperthermia. Herein we report the nucleus-targeting Fe3O4 nanoparticles functionalized with protein and nuclear locali...

  15. On-site storage of high level nuclear waste: Attitudes and perceptions of local residents

    International Nuclear Information System (INIS)

    Bassett, G.W. Jr.; Jenkins-Smith, H.C.; Silva, C.

    1996-01-01

    No public policy issue has been as difficult as high-level nuclear waste. Debates continue regarding Yucca Mountain as a disposal site, and - more generally - the appropriateness of geologic disposal and the need to act quickly. Previous research has focused on possible social, political, and economic consequences of a facility in Nevada. Impacts have been predicted to be potentially large and to emanate mainly from stigmatization of the region due to increased perceptions of risk. Analogous impacts from leaving waste at power plants have been either ignored or assumed to be negligible. This paper presents survey results on attitudes of residents in three countries where nuclear waste is currently stored. Topics include perceived risk, knowledge of nuclear waste and radiation, and impacts on jobs, tourism, and housing values from leaving waste on site. Results are similar to what has been reported for Nevada; the public is concerned about possible adverse effects from on-site storage of waste. 24 refs., 7 figs., 5 tabs

  16. Local stakeholder involvement in the perspective of nuclear waste management: lessons form the Cowam network

    International Nuclear Information System (INIS)

    Heriard Dubreuil, G.; Gadbois, S.

    2004-01-01

    The management of high level radioactive waste is nowadays recognised as a complex decision-making process entailing technical, environmental, ethical, social, political and economic dimensions where no solution can be reached solely on the basis of technical considerations. While this issue is acknowledged as a problem for the community as a whole, waste management remains a global problem looking for a local solution. Starting from this view, COWAM network (Community Waste Management), developed under the Fifth Framework Programme of the European Commission, addressed the following objectives: 1) To empower local actors through a networking process; 2) To gather and discuss the available experiences of decision-making processes at the local level within their national context in Europe; 3) To set up an arena for balanced exchanges between local actors, NGOs, regulators and implementers; 4) To promote new approaches to decision-making in national contexts in Europe. COWAM network comprises 230 delegates from 10 European countries, involving in priority local communities and NGOs. The emphasis put on the local participation enabled members of COWAM network to overcome distrust and to build common lessons and views beyond usual stakeholder positions. Through the analysis of case studies different issues were identified, among them two relate more specifically to: 1) Expertise what is the purpose of expertise on environmental impact in the decision-making process? How is this expertise linked with other scientific and non scientific issues? What is the role of stakeholders in expertise? 2) Environmental quality in the long term and sustainable development how is the impact of radioactive waste management facilities on the environment in the long term taken into account? how is this associated with the sustainable development of the hosting community? How are local stakeholders involved in these issues and what is the expected benefit from their participation? (author)

  17. hnRNP M interacts with PSF and p54{sup nrb} and co-localizes within defined nuclear structures

    Energy Technology Data Exchange (ETDEWEB)

    Marko, Marija; Leichter, Michael; Patrinou-Georgoula, Meropi [RNA Processing Laboratory, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, 11635 Athens (Greece); Guialis, Apostolia, E-mail: aguial@eie.gr [RNA Processing Laboratory, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, 11635 Athens (Greece)

    2010-02-01

    The abundant heterogeneous nuclear ribonucleoprotein M (hnRNP M) is able to associate with early spliceosomes and to influence splicing patterns of specific pre-mRNAs. Here, by a combination of immunoprecipitation and pull-down assays, we have identified PSF (polypyrimidine tract-binding protein-associated splicing factor) and p54{sup nrb}, two highly related proteins involved in transcription and RNA processing, as new binding partners of hnRNP M. HnRNP M was found to co-localize with PSF within a subset of nuclear paraspeckles and to largely co-fractionate with PSF and p54{sup nrb} in biochemical nuclear matrix preparations. In cells transfected with an alternatively spliced preprotachykinin (PPT) minigene expression of hnRNP M promoted exon skipping while expression of PSF favours exon inclusion. The latter effect was reverted specifically by co-expressing the full length hnRNP M or a deletion mutant capable of interaction with PSF and p54{sup nrb}. Together our data provide new insights and some functional implications on the hnRNP M network of interactions.

  18. 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

  19. Nuclear localization and cytosolic overexpression of LASP-1 correlates with tumor size and nodal-positivity of human breast carcinoma

    International Nuclear Information System (INIS)

    Grunewald, Thomas GP; Kammerer, Ulrike; Kapp, Michaela; Eck, Matthias; Dietl, Johannes; Butt, Elke; Honig, Arnd

    2007-01-01

    LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration, which was reported to be overexpressed in 8–12 % of human breast cancers and thought to be exclusively located in cytoplasm. In the present work we analyzed the cellular and histological expression pattern of LASP-1 and its involvement in biological behavior of human breast cancer through correlation with standard clinicopathological parameters and expression of c-erbB2 (HER-2/neu), estrogen- (ER) and progesterone-receptors (PR). For this purpose immunohistochemical staining intensity and percentage of stained cells were semi-quantitatively rated to define a LASP-1 immunoreactive score (LASP-1-IRS). LASP-1-IRS was determined in 83 cases of invasive ductal breast carcinomas, 25 ductal carcinomas in situ (DCIS) and 18 fibroadenomas. Cellular LASP-1 distribution and expression pattern was visualized by immunofluorescence and confocal microscopy and assessed through separate Western blots of nuclear and cytosol preparations of BT-20, MCF-7, MDA-MB231, and ZR-75/1 breast cancer cells. Statistical analysis revealed that the resulting LASP-1-IRS was significantly higher in invasive carcinomas compared to fibroadenomas (p = 0.0176). Strong cytoplasmatic expression of LASP-1 was detected in 55.4 % of the invasive carcinomas, which correlated significantly with nuclear LASP-1-positivity (p = 0.0014), increased tumor size (p = 0.0159) and rate of nodal-positivity (p = 0.0066). However, levels of LASP-1 expression did not correlate with average age at time point of diagnosis, histological tumor grading, c-erbB2-, ER- or PR-expression. Increased nuclear localization and cytosolic expression of LASP-1 was found in breast cancer with higher tumor stage as well as in rapidly proliferating epidermal basal cells. Confocal microscopy and separate Western blots of cytosolic and nuclear preparations confirmed nuclear

  20. Evaluation of the uncertainty in the azimuth calculation for the detection and localization of atmospheric nuclear explosions

    International Nuclear Information System (INIS)

    Schuff, J.A.

    2006-01-01

    Low-frequency acoustic signal below about 1 Hz can travel for hundreds or thousands of kilometers through in the Earth atmosphere. If a source produces infrasonic energy, it can be detected by a remote sensor. Atmospheric strong explosions as the nuclear detonation contains low-frequency components that can travel long distances with measurable signal levels. This fact can be useful for detection and localization of clandestine events. The international regime on the non-proliferation of nuclear requires the ability to detect, localize, and discriminate nuclear events on a global scale. Monitoring systems such as the Inter national Monitoring System (I.M.S.) rely on several sensor technologies to perform these functions. The current I.M.S. infra sound system design includes a network of low-frequency atmospheric acoustic sensor arrays, which contribute primarily to the detection and localization of atmospheric nuclear events. There have been observed differences between the azimuth measurements and the true directions of the sources of infra sound waves in artificial and natural events such as explosive eruptions of strong volcanoes. The infra sound waves are reflected in stratospheric and thermospheric layers near 50 km and 120 km in height respectively. The azimuth deviation is affected by meteorological disturbances in the troposphere and stratosphere. This paper describe new elements to obtain the uncertainty in the azimuth calculation of arrival wave plane passing across of a not plane array of infra sound sensors. It also presents a 3D computation of infra sound propagation and estimation of the azimuth deviation using the zonal horizontal wind model and M.S.I.S.E.-90 model of the upper atmosphere to obtain temperature, density and concentration of the principal components of the air for altitudes of up to 120 km. Deviations of up to 12 degrees in the azimuth were obtained, depending on the location of the source of infra sound, the point of measurement and

  1. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGK{zeta} by attenuating its association with importins

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masashi; Hozumi, Yasukazu [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Ichimura, Tohru [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Iseki, Ken [Department of Emergency and Critical Care Medicine, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Yagisawa, Hitoshi [Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Hyogo 678-1297 (Japan); Shinkawa, Takashi; Isobe, Toshiaki [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Goto, Kaoru, E-mail: kgoto@med.id.yamagata-u.ac.jp [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan)

    2011-12-10

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGK{zeta}, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGK{zeta}. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGK{zeta} binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGK{zeta} and NAP1Ls prohibits nuclear import of DGK{zeta} because binding of NAP1Ls to DGK{zeta} blocks import carrier proteins, Qip1 and NPI1, to interact with DGK{zeta}, leading to cytoplasmic tethering of DGK{zeta}. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGK{zeta} and provide a clue to examine functional significance of its translocation under pathological conditions.

  2. Hypercholesterolemia Increases the Production of Leukotriene B4 in Neutrophils by Enhancing the Nuclear Localization of 5-Lipoxygenase

    Directory of Open Access Journals (Sweden)

    Xiao-Feng Lai

    2014-11-01

    Full Text Available Aims: Neutrophils can synthesize leukotriene B4 (LTB4 by activating the 5-lipoxygenase (5-LOsignaling pathway. LTB4 is a pro-inflammatory mediator associated with the etiology and progression of atherosclerosis. It can increase function and number of neutrophils in an autocrine manner. Since hypercholesterolemia is associated with an increase in the number and function of neutrophils, we hypothesized that this effect could be mediated through increased production of LTB4 in neutrophils. Methods/Results: Hypercholesterolemia was modeled in Wistar rats by feeding them with a high cholesterol diet. The induction of hypercholesterolemia caused an increase in the plasma levels of LTB4, following lipopolysaccharide stimulation. This effect was recapitulated in vitro, both in the presence and absence of stimulation with the activator of 5-LO, A23187. Neutrophils in hypercholesterolemia rats expressed similar total levels of 5-LO as control rats, but displayed increased nuclear localization of 5-LO, as well as elevated levels of phosphorylated 5-LO and ERK1/2. In vitro, MβCD/cholesterol complexes enriched cholesterol in neutrophils, resulted in similar changes in 5-LO/LTB4. In addition, these alterations could be inhibited with the ERK inhibitor PD98059. Conclusion: Hypercholesterolemia increases LTB4 production in neutrophils by increasing the nuclear localization of 5-LO, which is the result of its phosphorylation by activated ERK1/2.

  3. Inactivation of the FLCN tumor suppressor gene induces TFE3 transcriptional activity by increasing its nuclear localization.

    Directory of Open Access Journals (Sweden)

    Seung-Beom Hong

    2010-12-01

    Full Text Available Germline mutations in a tumor suppressor gene FLCN lead to development of fibrofolliculomas, lung cysts and renal cell carcinoma (RCC in Birt-Hogg-Dubé syndrome. TFE3 is a member of the MiTF/TFE transcription factor family and Xp11.2 translocations found in sporadic RCC involving TFE3 result in gene fusions and overexpression of chimeric fusion proteins that retain the C-terminal DNA binding domain of TFE3. We found that GPNMB expression, which is regulated by MiTF, was greatly elevated in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Since TFE3 is implicated in RCC, we hypothesized that elevated GPNMB expression was due to increased TFE3 activity resulting from the inactivation of FLCN.TFE3 knockdown reduced GPNMB expression in renal cancer cells harboring either TFE3 translocations or FLCN inactivation. Moreover, FLCN knockdown induced GPNMB expression in FLCN-restored renal cancer cells. Conversely, wildtype FLCN suppressed GPNMB expression in FLCN-null cells. FLCN inactivation was correlated with increased TFE3 transcriptional activity accompanied by its nuclear localization as revealed by elevated GPNMB mRNA and protein expression, and predominantly nuclear immunostaining of TFE3 in renal cancer cells, mouse embryo fibroblast cells, mouse kidneys and mouse and human renal tumors. Nuclear localization of TFE3 was associated with TFE3 post-translational modifications including decreased phosphorylation.Increased TFE3 activity is a downstream event induced by FLCN inactivation and is likely to be important for renal tumor development. This study provides an important novel mechanism for induction of TFE3 activity in addition to TFE3 overexpression resulting from Xp11.2 translocations, suggesting that TFE3 may be more broadly involved in tumorigenesis.

  4. Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

    Science.gov (United States)

    Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

    2017-01-01

    Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Extra nuclear localization of steroid receptors and non genomic activation mechanisms

    OpenAIRE

    Bottino, Maria Cecilia; Lanari, Claudia Lee Malvina

    2017-01-01

    Los receptores de hormonas esteroides han sido considerados históricamente como factores de transcripción nucleares. Sin embargo, en los últimos años surgieron evidencias que indican que su activación desencadena eventos rápidos, independientes de la transcripción y que involucran a diferentes segundos mensajeros; muchos de estos receptores han sido localizados en la membrana celular. Por otra parte, se han caracterizado varios receptores de hormonas esteroides noveles, de estructura molecula...

  6. Sizewell nuclear power station: investigation of radiation exposure pathways from liquid effluents. Local habits survey 1981

    International Nuclear Information System (INIS)

    Leonard, D.R.P.; Smith, B.D.

    1982-01-01

    A habits and consumption survey to review radiation exposure pathways due to liquid effluents released from the CEGB Sizewell site is described. It is relevant to both the Sizewell A and proposed Sizewell B nuclear power stations. The main objectives are to provide input data to a radiological assessment by means of identifying critical groups and to provide data for guidance in a review of environmental monitoring programmes. The way in which data for the different pathways should be combined in order to aid the subsequent radiological assessment is discussed. Recommendations are made for adjustments to the present monitoring programmes. (U.K.)

  7. Nuclear localization of phosphorylated c-Myc protein in human tumor cells.

    Directory of Open Access Journals (Sweden)

    C. Soldani

    2010-05-01

    Full Text Available Using immunocytochemical techniques at light and electron microscopy, we analysed the distribution of phosphorylated c-Myc in actively proliferating human HeLa cells. The distribution pattern of c-Myc was also compared with those of other ribonucleoprotein (RNP-containing components (PANA, hnRNP-core proteins, fibrillarin or RNP-associated nuclear proteins (SC-35 splicing factor. Our results provide the first evidence that phosphorylated c-Myc accumulates in the nucleus of tumor cells, where it colocalizes with fibrillarin, both in the nucleolus and in extranucleolar structures.

  8. Functional characterization of nuclear localization and export signals in hepatitis C virus proteins and their role in the membranous web.

    Directory of Open Access Journals (Sweden)

    Aviad Levin

    Full Text Available The hepatitis C virus (HCV is a positive strand RNA virus of the Flavivirus family that replicates in the cytoplasm of infected hepatocytes. Previously, several nuclear localization signals (NLS and nuclear export signals (NES have been identified in HCV proteins, however, there is little evidence that these proteins travel into the nucleus during infection. We have recently shown that nuclear pore complex (NPC proteins (termed nucleoporins or Nups are present in the membranous web and are required during HCV infection. In this study, we identify a total of 11 NLS and NES sequences in various HCV proteins. We show direct interactions between HCV proteins and importin α5 (IPOA5/kapα1, importin β3 (IPO5/kap β3, and exportin 1 (XPO1/CRM1 both in-vitro and in cell culture. These interactions can be disrupted using peptides containing the specific NLS or NES sequences of HCV proteins. Moreover, using a synchronized infection system, we show that these peptides inhibit HCV infection during distinct phases of the HCV life cycle. The inhibitory effects of these peptides place them in two groups. The first group binds IPOA5 and inhibits infection during the replication stage of HCV life cycle. The second group binds IPO5 and is active during both early replication and early assembly. This work delineates the entire life cycle of HCV and the active involvement of NLS sequences during HCV replication and assembly. Given the abundance of NLS sequences within HCV proteins, our previous finding that Nups play a role in HCV infection, and the relocation of the NLS double-GFP reporter in HCV infected cells, this work supports our previous hypothesis that NPC-like structures and nuclear transport factors function in the membranous web to create an environment conducive to viral replication.

  9. Understanding of the characteristics of the local newspapers providing media coverage on the matters of nuclear energy in the regions where nuclear facilities are located. Based on analysis of the media reports and interviews with journalists

    International Nuclear Information System (INIS)

    Tsuchida, Tatsuro; Kimura, Hiroshi

    2011-01-01

    Taking into consideration the influence of the media coverage, this research aims to analyze the characteristics of the local newspapers that cover diverse events relevant to nuclear energy in regional areas where nuclear facilities are located (hereinafter called the 'region'). According to the previous surveys, local residents in the region are more interested in the nuclear energy matters than those who live in urban areas. Plus, the local newspapers turn out to report more events of nuclear energy from a variety of angles. Through interviews with executives and journalists of the local newspaper companies in the regions, it is revealed that the local newspapers tend not to report news sensationally, but they would rather take a supportive stance toward the development in their regions. The interviewees hope that various activities of the nuclear industry will promote education, employment and cooperation among government, industry and academia. They also desire that the industry's activities will help to increase benefits in their regions. It appears that the interviewees' awareness reflects articles of the local newspapers. As a result of the surveys conducted for this research, it is considered that the journalists expect that their region will make particularly qualitative progress in the future. (author)

  10. Nuclear accident at Three Mile Island: its effect on a local community

    International Nuclear Information System (INIS)

    Behler, G.T. Jr.

    1987-01-01

    This dissertation consists of a longitudinal case study of the extent to which the structure of community power in Riverside, (a pseudonym) Pennsylvania (the largest community located within five miles of the Three Mile Island nuclear facility) changed as a result of the March, 1979 accident. The investigation centers around testing a basic working hypothesis. Simply stated, this working hypothesis argues that Riverside's power structure has become more pluralistic in response to the Three Mile Island nuclear accident. An additional corollary to this working hypothesis is also tested. This corollary asserts that many of Riverside's community power actors have become much more cosmopolitan in their political-action tactics and problem-solving orientations as a results of the TMI crisis. The aforementioned working hypothesis and associated corollary are tested via the combined utilization of three different techniques for measuring the distribution of social power. The findings of the study clearly demonstrate the existence of increased pluralism, politicization, and cosmopolitanism within Riverside since March of 1979. Furthermore, these research results, and the entire dissertation itself, contribute to a number of subfields within the discipline of sociology. In particular,contributions are noted for the subfields of community power, social movements, and disaster research

  11. Nuclear accident at Three Mile Island: its effect on a local community

    Energy Technology Data Exchange (ETDEWEB)

    Behler, G.T. Jr.

    1987-01-01

    This dissertation consists of a longitudinal case study of the extent to which the structure of community power in Riverside, (a pseudonym) Pennsylvania (the largest community located within five miles of the Three Mile Island nuclear facility) changed as a result of the March, 1979 accident. The investigation centers around testing a basic working hypothesis. Simply stated, this working hypothesis argues that Riverside's power structure has become more pluralistic in response to the Three Mile Island nuclear accident. An additional corollary to this working hypothesis is also tested. This corollary asserts that many of Riverside's community power actors have become much more cosmopolitan in their political-action tactics and problem-solving orientations as a results of the TMI crisis. The aforementioned working hypothesis and associated corollary are tested via the combined utilization of three different techniques for measuring the distribution of social power. The findings of the study clearly demonstrate the existence of increased pluralism, politicization, and cosmopolitanism within Riverside since March of 1979. Furthermore, these research results, and the entire dissertation itself, contribute to a number of subfields within the discipline of sociology. In particular,contributions are noted for the subfields of community power, social movements, and disaster research.

  12. A localized navigation algorithm for radiation evasion for nuclear facilities: Optimizing the “Radiation Evasion” criterion: Part I

    Energy Technology Data Exchange (ETDEWEB)

    Khasawneh, Mohammed A., E-mail: mkha@ieee.org [Department of Electrical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan); Al-Shboul, Zeina Aman M., E-mail: xeinaaman@gmail.com [Department of Electrical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan); Jaradat, Mohammad A., E-mail: majaradat@just.edu.jo [Department of Mechanical Engineering, Jordan University of Science and Technology, Irbid 221 10 (Jordan)

    2013-06-15

    Highlights: ► A new navigation algorithm for radiation evasion around nuclear facilities. ► An optimization criteria minimized under algorithm operation. ► A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. ► Benefits of using localized navigation as opposed to global navigation schemas. ► A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. -- Abstract: In this paper, we introduce a navigation algorithm having general utility for occupational workers at nuclear facilities and places where radiation poses serious health hazards. This novel algorithm leverages the use of localized information for its operation. Therefore, the need for central processing and decision resources is avoided, since information processing and the ensuing decision-making are done aboard a man-borne device. To acquire the information needed for path planning in radiation avoidance, a well-designed and distributed wireless sensory infrastructure is needed. This will automatically benefit from the most recent trends in technology developments in both sensor networks and wireless communication. When used to navigate based on local radiation information, the algorithm will behave more reliably when accidents happen, since no long-haul communication links are required for information exchange. In essence, the proposed algorithm is designed to leverage nearest neighbor information coming in through the sensory network overhead, to compute successful navigational paths from one point to another. The proposed algorithm is tested under the “Radiation Evasion” criterion. It is also tested for the case when more information, beyond nearest neighbors, is made available; here, we test its operation for different numbers of step look-ahead. We verify algorithm performance by means of simulations, whereby navigational paths are calculated for different radiation fields.

  13. A localized navigation algorithm for radiation evasion for nuclear facilities: Optimizing the “Radiation Evasion” criterion: Part I

    International Nuclear Information System (INIS)

    Khasawneh, Mohammed A.; Al-Shboul, Zeina Aman M.; Jaradat, Mohammad A.

    2013-01-01

    Highlights: ► A new navigation algorithm for radiation evasion around nuclear facilities. ► An optimization criteria minimized under algorithm operation. ► A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. ► Benefits of using localized navigation as opposed to global navigation schemas. ► A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. -- Abstract: In this paper, we introduce a navigation algorithm having general utility for occupational workers at nuclear facilities and places where radiation poses serious health hazards. This novel algorithm leverages the use of localized information for its operation. Therefore, the need for central processing and decision resources is avoided, since information processing and the ensuing decision-making are done aboard a man-borne device. To acquire the information needed for path planning in radiation avoidance, a well-designed and distributed wireless sensory infrastructure is needed. This will automatically benefit from the most recent trends in technology developments in both sensor networks and wireless communication. When used to navigate based on local radiation information, the algorithm will behave more reliably when accidents happen, since no long-haul communication links are required for information exchange. In essence, the proposed algorithm is designed to leverage nearest neighbor information coming in through the sensory network overhead, to compute successful navigational paths from one point to another. The proposed algorithm is tested under the “Radiation Evasion” criterion. It is also tested for the case when more information, beyond nearest neighbors, is made available; here, we test its operation for different numbers of step look-ahead. We verify algorithm performance by means of simulations, whereby navigational paths are calculated for different radiation fields

  14. Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear localization of XRCC4 and DNA ligase IV

    Energy Technology Data Exchange (ETDEWEB)

    Fukuchi, Mikoto; Wanotayan, Rujira; Liu, Sicheng; Imamichi, Shoji; Sharma, Mukesh Kumar; Matsumoto, Yoshihisa, E-mail: yoshim@nr.titech.ac.jp

    2015-06-12

    XRCC4 and DNA Ligase IV (LIG4) cooperate to join two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). However, it is not fully understood how these proteins are localized to the nucleus. Here we created XRCC4{sup K271R} mutant, as Lys271 lies within the putative nuclear localization signal (NLS), and XRCC4{sup K210R} mutant, as Lys210 was reported to undergo SUMOylation, implicated in the nuclear localization of XRCC4. Wild-type and mutated XRCC4 with EGFP tag were introduced into HeLa cell, in which endogenous XRCC4 had been knocked down using siRNA directed to 3′-untranslated region, and tested for the nuclear localization function by fluorescence microscopy. XRCC4{sup K271R} was defective in the nuclear localization of itself and LIG4, whereas XRCC4{sup K210R} was competent for the nuclear localization with LIG4. To examine DSB repair function, wild-type and mutated XRCC4 were introduced into XRCC4-deficient M10. M10-XRCC4{sup K271R}, but not M10-XRCC4{sup K210R}, showed significantly reduced surviving fraction after 2 Gy γ-ray irradiation as compared to M10-XRCC4{sup WT}. The number of γ-H2AX foci remaining 2 h after 2 Gy γ-ray irradiation was significantly greater in M10-XRCC4{sup K271R} than in M10-XRCC4{sup WT}, whereas it was only marginally increased in M10-XRCC4{sup K210R} as compared to M10-XRCC4{sup WT}. The present results collectively indicated that Lys271, but not Lys210, of XRCC4 is required for the nuclear localization of XRCC4 and LIG4 and that the nuclear localizing ability is essential for DSB repair function of XRCC4. - Highlights: • XRCC4{sup K271R} is defective in the nuclear localization of itself and LIG4. • XRCC4{sup K210R} is competent for the nuclear localization of itself and LIG4. • XRCC4{sup K271R} is deficient in DSB repair function. • XRCC4{sup K210R} is mostly normal in DSB repair function.

  15. Support of disaster prevention of earthquake for nuclear installation and local area

    International Nuclear Information System (INIS)

    Kamae, Katsuhiro; Kawabe, Hidenori

    2005-01-01

    There have been many strong earthquakes in Japan since 10 years ago, especially in Tokai, Higashitokai and Nankai area. The characteristics of earthquake in the Osaka plains, the differences of ground motions between it and the local earthquake and the support plans of disaster prevention in the local area using the real time earthquake information and the prediction results of ground motion of earthquake are described. Strong ground acceleration of earthquake is predicted by using the empirical green's function. The earthquake source model is illustrated. The ground motion (0.1-10Hz) and simulated speed response spectrum at KURRI (Kyoto University Research Reactor Institute) in Kumatori are shown. The observation results of the ground motion of earthquake in the coast of south east of the Kii peninsula in 2004 are explained. (S.Y.)

  16. Nuclear Enhanced X-ray Maximum Entropy Method Used to Analyze Local Distortions in Simple Structures

    DEFF Research Database (Denmark)

    Christensen, Sebastian; Bindzus, Niels; Christensen, Mogens

    was conceived to analyse local distortions in the thermoelectric lead chalcogenides, PbX (X = S, Se, Te). Their extraordinary thermoelectric performance has caused huge research activity, but the mechanisms governing their unexpected low thermal conductivity still remain a controversial topic. It has been...... present in PbX. In the future it may be used for widespread characterization of subtle atomic features in crystals with unusual properties....

  17. Local multigrid mesh refinement in view of nuclear fuel 3D modelling in pressurised water reactors

    International Nuclear Information System (INIS)

    Barbie, L.

    2013-01-01

    The aim of this study is to improve the performances, in terms of memory space and computational time, of the current modelling of the Pellet-Cladding mechanical Interaction (PCI), complex phenomenon which may occurs during high power rises in pressurised water reactors. Among the mesh refinement methods - methods dedicated to efficiently treat local singularities - a local multi-grid approach was selected because it enables the use of a black-box solver while dealing few degrees of freedom at each level. The Local Defect Correction (LDC) method, well suited to a finite element discretization, was first analysed and checked in linear elasticity, on configurations resulting from the PCI, since its use in solid mechanics is little widespread. Various strategies concerning the implementation of the multilevel algorithm were also compared. Coupling the LDC method with the Zienkiewicz-Zhu a posteriori error estimator in order to automatically detect the zones to be refined, was then tested. Performances obtained on two-dimensional and three-dimensional cases are very satisfactory, since the algorithm proposed is more efficient than h-adaptive refinement methods. Lastly, the LDC algorithm was extended to nonlinear mechanics. Space/time refinement as well as transmission of the initial conditions during the re-meshing step were looked at. The first results obtained are encouraging and show the interest of using the LDC method for PCI modelling. (author) [fr

  18. Localization and spectral isolation of special nuclear material using stochastic image reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Hamel, M.C., E-mail: mchamel@umich.edu; Polack, J.K., E-mail: kpolack@umich.edu; Poitrasson-Rivière, A., E-mail: alexispr@umich.edu; Clarke, S.D., E-mail: clarkesd@umich.edu; Pozzi, S.A., E-mail: pozzisa@umich.edu

    2017-01-01

    In this work we present a technique for isolating the gamma-ray and neutron energy spectra from multiple radioactive sources localized in an image. Image reconstruction algorithms for radiation scatter cameras typically focus on improving image quality. However, with scatter cameras being developed for non-proliferation applications, there is a need for not only source localization but also source identification. This work outlines a modified stochastic origin ensembles algorithm that provides localized spectra for all pixels in the image. We demonstrated the technique by performing three experiments with a dual-particle imager that measured various gamma-ray and neutron sources simultaneously. We showed that we could isolate the peaks from {sup 22}Na and {sup 137}Cs and that the energy resolution is maintained in the isolated spectra. To evaluate the spectral isolation of neutrons, a {sup 252}Cf source and a PuBe source were measured simultaneously and the reconstruction showed that the isolated PuBe spectrum had a higher average energy and a greater fraction of neutrons at higher energies than the {sup 252}Cf. Finally, spectrum isolation was used for an experiment with weapons grade plutonium, {sup 252}Cf, and AmBe. The resulting neutron and gamma-ray spectra showed the expected characteristics that could then be used to identify the sources.

  19. Study of community leaders in a nuclear host community: local issues, expectations and support and opposition

    Energy Technology Data Exchange (ETDEWEB)

    Bronfman, B. H.

    1977-08-01

    A study of community leaders was undertaken in Hartsville, Tennessee, site of the TVA Hartsville Nuclear Power Plant currently under construction. Leaders were found to be extremely supportive of the plant and of TVA's efforts to mitigate impacts expected to result from construction. Like their citizen counterparts, leaders expect economic benefits and some growth-related disruption to occur as a result of the plant, while environmental impacts are seen as extremely unlikely to occur. Plant-related issues, such as housing availability and traffic congestion, dominate leaders' thinking about current issues. These issues are expected to continue to be important in the future, and new issues dealing with growth and planning, employment and taxation are expected to arise.

  20. Compatibility of localized wave packets and unrestricted single particle dynamics for cluster formation in nuclear collisions

    International Nuclear Information System (INIS)

    Ono, A.

    2002-03-01

    Anti-symmetrized molecular dynamics with quantum branching is generalized so as to allow finite time duration of the unrestricted coherent mean field propagation which is followed by the decoherence into wave packets. In this new model, the wave packet shrinking by the mean field propagation is respected as well as the diffusion, so that it predicts a one-body dynamics similar to that in mean field models. The shrinking effect is expected to change the diffusion property of nucleons in nuclear matter and the global one-body dynamics. The central 129 Xe + Sn collisions at 50 MeV/nucleon are calculated by the models with and without shrinking, and it is shown that the inclusion of the wave packet shrinking has a large effect on the multifragmentation in a big expanding system with a moderate expansion velocity. (author)

  1. Study of community leaders in a nuclear host community: local issues, expectations and support and opposition

    International Nuclear Information System (INIS)

    Bronfman, B.H.

    1977-08-01

    A study of community leaders was undertaken in Hartsville, Tennessee, site of the TVA Hartsville Nuclear Power Plant currently under construction. Leaders were found to be extremely supportive of the plant and of TVA's efforts to mitigate impacts expected to result from construction. Like their citizen counterparts, leaders expect economic benefits and some growth-related disruption to occur as a result of the plant, while environmental impacts are seen as extremely unlikely to occur. Plant-related issues, such as housing availability and traffic congestion, dominate leaders' thinking about current issues. These issues are expected to continue to be important in the future, and new issues dealing with growth and planning, employment and taxation are expected to arise

  2. The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

    Energy Technology Data Exchange (ETDEWEB)

    Manzo-Merino, Joaquin [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Massimi, Paola [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy); Lizano, Marcela, E-mail: lizanosoberon@gmail.com [Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, México/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México. Av. San Fernando No. 22, Col. Sección XVI, Tlalpan 14080 (Mexico); Banks, Lawrence, E-mail: banks@icgeb.org [International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste (Italy)

    2014-02-15

    The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins to recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.

  3. The nuclear mitotic apparatus (NuMA) protein: localization and dynamics in human oocytes, fertilization and early embryos.

    Science.gov (United States)

    Alvarez Sedó, Cristian; Schatten, Heide; Combelles, Catherine M; Rawe, Vanesa Y

    2011-06-01

    The oocyte's meiotic spindle is a dynamic structure that relies on microtubule organization and regulation by centrosomes. Disorganization of centrosomal proteins, including the nuclear mitotic apparatus (NuMA) protein and the molecular motor complex dynein/dynactin, can lead to chromosomal instability and developmental abnormalities. The present study reports the distribution and function of these proteins in human oocytes, zygotes and early embryos. A total of 239 oocytes, 90 zygotes and discarded embryos were fixed and analyzed with confocal microscopy for NuMA and dynactin distribution together with microtubules and chromatin. Microtubule-associated dynein-dependent transport functions were explored by inhibiting phosphatase and ATPase activity with sodium-orthovanadate (SOV). At germinal vesicle (GV) stages, NuMA was dispersed across the nucleoplasm. After GV breaks down, NuMA became cytoplasmic before localizing at the spindle poles in metaphase I and II oocytes. Aberrant NuMA localization patterns were found during oocyte in vitro maturation. After fertilization, normal and abnormal pronuclear stage zygotes and embryos displayed translocation of NuMA to interphase nuclei. SOV treatment for up to 2 h induced lower maturation rates with chromosomal scattering and ectopic localization of NuMA. Accurate distribution of NuMA is important for oocyte maturation, zygote and embryo development in humans. Proper assembly of NuMA is likely necessary for bipolar spindle organization and human oocyte developmental competence.

  4. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Ichida, Yu, E-mail: ichida-y@ncchd.go.jp; Utsunomiya, Yuko; Onodera, Masafumi

    2016-03-18

    Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are required for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.

  5. Behaviour of model particles of local precipitations of surface nuclear explosion in food chain and digestive tract of farm animals

    International Nuclear Information System (INIS)

    Koz'min, G.V.; Epimakhov, V.G.; Sanzharova, N.I.

    2016-01-01

    The behaviour regularities of radioactive particles - simulators of nuclear surface explosion local fall outs in food chain and gastrointestinal tract (GIT) of farm animals are analyzed. The results show that there is a large difference in transport regularities of radioactive silicate particles and radioactive solutions in GIT. At intake of young fission products high concentrations of radionuclides in GIT content deal with sorption and concentrating of radionuclides on food particles and observe in third stomach, blind gut, terminals of middle and bung guts. Transport regularities of fused radioactive particles depend on digestive apparatus mobility, content consistency and morphological peculiarities of mucosa, which work towards transport slowing and storage of such particles in the part of sheep GIT with minimal dry substance content - abomasum [ru

  6. Hydrogeological modelling of the eastern region of Areco river locally detailed on Atucha I and II nuclear power plants area

    International Nuclear Information System (INIS)

    Grattone, Natalia I.; Fuentes, Nestor O.

    2009-01-01

    Water flow behaviour of Pampeano aquifer was modeled using Visual Mod-flow software Package 2.8.1 with the assumption of a free aquifer, within the region of the Areco river and extending to the rivers of 'Canada Honda' and 'de la Cruz'. Steady state regime was simulated and grid refinement allows obtaining locally detailed calculation in the area of Atucha I and II Nuclear power plants, in order to compute unsteady situations as the consequence of water flow variations from and to the aquifer, enabling the model to study the movement of possible contaminant particles in the hydrogeologic system. In this work the effects of rivers action, the recharge conditions and the flow lines are analyzed, taking always into account the range of reliability of obtained results, considering the incidence of uncertainties introduced by data input system, the estimates and interpolation of parameters used. (author)

  7. Measurement of local dose rates in controlled areas of nuclear power plants. Version 6/85

    International Nuclear Information System (INIS)

    1985-01-01

    Local dose rate measurements according to this regulation, serve the following purposes: Development of preventive measures for radiation protection with respect to maintenance and modifications in controlled areas, e.g. determination of individual measures for personnel protection, development of flow charts and dose rate estimates; monitoring of the personnel's location of activity within the controlled area, including determination of time-dependence of local dose rates and determination of immediate radiation protection measures required; limitation and identification of controlled areas. Such measurements are performed to ensure that the principles of radiation protection as stated in Art. 28 (1) of the Radiation Protection Ordinance with respect to external radiation exposure of the personnel, and the requirements of Art. 61 (1) of the Radiation Protection Ordinance relating to controlled areas are met and the limitation and identification of controlled areas as prescribed in Art 57 (1) of the Radiation Protection Ordinance can be performed. They are not used to determine body doses as per Art. 63 of the Radiation Protection Ordinance. (orig./HP) [de

  8. Improvement of traditional local rice varieties through induced mutations using nuclear techniques

    International Nuclear Information System (INIS)

    Pham Van Ro; Do Huu At

    2001-01-01

    'Improvement of local rice varieties for high yield, resistance to disease and insect pests (brown plant hopper and rice blast) and export quality through induced mutations for the Mekong Delta' started in 1993. After six years, it showed effecting on the field in the MD as well as at the south of Vietnam. TNDB-100 manifest very wide adaptation and yield stable variety. THDB is suitable for deepwater rice region, coastal area, where rice cultivation effected by acid sulphate and salinity conditions. Both varieties are good example for the method. Thank to good Co-operation from extension center from provinces, hundred classes of extension were organized to recommend to the farmers. And thank to the strongly supporting from IAEA so that nearly 400,000 ha of TNDB-100 occupied at the south of Vietnam as well as nearly 15,000 ha of THDB grown in the coastal as well as rainfed lowland rice areas at the South of Vietnam. To continue the rice improvement by this technique, seeds of six traditional local varieties were exposed under different dose of gamma rays to create new mutants. At present day hundred improved breeding lines were selected, a dozen of uniform lines were isolated and entranced the yield trail as well as regional testing program. From these improved varieties would be selected to contribute to the rice cultivation at the south of Vietnam in the next years. (author)

  9. Improvement of traditional local rice varieties through induced mutations using nuclear techniques

    Energy Technology Data Exchange (ETDEWEB)

    Pham Van Ro; Do Huu At [Cuu Long Delta Rice Research Institute (Viet Nam)

    2001-03-01

    'Improvement of local rice varieties for high yield, resistance to disease and insect pests (brown plant hopper and rice blast) and export quality through induced mutations for the Mekong Delta' started in 1993. After six years, it showed effecting on the field in the MD as well as at the south of Vietnam. TNDB-100 manifest very wide adaptation and yield stable variety. THDB is suitable for deepwater rice region, coastal area, where rice cultivation effected by acid sulphate and salinity conditions. Both varieties are good example for the method. Thank to good Co-operation from extension center from provinces, hundred classes of extension were organized to recommend to the farmers. And thank to the strongly supporting from IAEA so that nearly 400,000 ha of TNDB-100 occupied at the south of Vietnam as well as nearly 15,000 ha of THDB grown in the coastal as well as rainfed lowland rice areas at the South of Vietnam. To continue the rice improvement by this technique, seeds of six traditional local varieties were exposed under different dose of gamma rays to create new mutants. At present day hundred improved breeding lines were selected, a dozen of uniform lines were isolated and entranced the yield trail as well as regional testing program. From these improved varieties would be selected to contribute to the rice cultivation at the south of Vietnam in the next years. (author)

  10. Genomic origin and nuclear localization of TERRA telomeric repeat-containing RNA: from Darkness to Dawn.

    Science.gov (United States)

    Diman, Aurélie; Decottignies, Anabelle

    2017-12-14

    Long noncoding RNAs, produced from distinct regions of the chromosomes, are emerging as new key players in several important biological processes. The long noncoding RNAs add a new layer of complexity to cellular regulatory pathways, from transcription to cellular trafficking or chromatin remodeling. More than 25 years ago, the discovery of a transcriptional activity at telomeres of protozoa ended the long-lasting belief that telomeres were transcriptionally silent. Since then, progressively accumulating evidences established that production of TElomeric Repeat-containing RNA (TERRA) was a general feature of eukaryotic cells. Whether TERRA molecules always originate from the telomeres or whether they can be transcribed from internal telomeric repeats as well is however still a matter of debate. Whether TERRA transcripts always localize to telomeres and play similar roles in all eukaryotic cells is also unclear. We review the studies on TERRA localization in the cell, its composition and some aspects of its transcriptional regulation to summarize the current knowledge and controversies about the genomic origin of TERRA, with a focus on human and mouse TERRA. © 2017 Federation of European Biochemical Societies.

  11. Structure of Importin-α from a Filamentous Fungus in Complex with a Classical Nuclear Localization Signal.

    Directory of Open Access Journals (Sweden)

    Natalia E Bernardes

    Full Text Available Neurospora crassa is a filamentous fungus that has been extensively studied as a model organism for eukaryotic biology, providing fundamental insights into cellular processes such as cell signaling, growth and differentiation. To advance in the study of this multicellular organism, an understanding of the specific mechanisms for protein transport into the cell nucleus is essential. Importin-α (Imp-α is the receptor for cargo proteins that contain specific nuclear localization signals (NLSs that play a key role in the classical nuclear import pathway. Structures of Imp-α from different organisms (yeast, rice, mouse, and human have been determined, revealing that this receptor possesses a conserved structural scaffold. However, recent studies have demonstrated that the Impα mechanism of action may vary significantly for different organisms or for different isoforms from the same organism. Therefore, structural, functional, and biophysical characterization of different Impα proteins is necessary to understand the selectivity of nuclear transport. Here, we determined the first crystal structure of an Impα from a filamentous fungus which is also the highest resolution Impα structure already solved to date (1.75 Å. In addition, we performed calorimetric analysis to determine the affinity and thermodynamic parameters of the interaction between Imp-α and the classical SV40 NLS peptide. The comparison of these data with previous studies on Impα proteins led us to demonstrate that N. crassa Imp-α possess specific features that are distinct from mammalian Imp-α but exhibit important similarities to rice Imp-α, particularly at the minor NLS binding site.

  12. Reconstruction of local fallout composition and gamma-ray exposure in a village contaminated by the first USSR nuclear test in the Semipalatinsk nuclear test site in Kazakhstan.

    Science.gov (United States)

    Imanaka, Tetsuji; Yamamoto, Masayoshi; Kawai, Kenta; Sakaguchi, Aya; Hoshi, Masaharu; Chaizhunusova, Nailya; Apsalikov, Kazbek

    2010-11-01

    After the disintegration of the USSR in end of 1991, it became possible for foreign scientists to visit Kazakhstan, in order to investigate the radiological consequences of nuclear explosions that had been conducted at the Semipalatinsk nuclear test site (SNTS). Since the first visit in 1994, our group has been continuing expeditions for soil sampling at various areas around SNTS. The current level of local fallout at SNTS was studied through γ-spectrometry for (137)Cs as well as α-spectrometry for (239,240)Pu. Average values of soil inventory from wide areas around SNTS were 3,500 and 3,700 Bq m(-2) for (137)Cs and (239,240)Pu, respectively, as of January 1, 2000. The average level of (137)Cs is comparable to that in Japan due to global fallout, while the level of (239,240)Pu is several tens of times larger than that in Japan. Areas of strong contamination were found along the trajectories of radioactive fallout, information on which was declassified after the collapse of the USSR. Our recent efforts of soil sampling were concentrated on the area around the Dolon village heavily affected by the radioactive plume from the first USSR atomic bomb test in 1949 and located 110 km east from ground zero of the explosion. Using soil inventory data, retrospective dosimetry was attempted by reconstructing γ-ray exposure from fission product nuclides deposited on the ground. Adopting representative parameters for the initial (137)Cs deposition (13 kBq m(-2)), the refractory/volatile deposition ratio (3.8) and the plume arrival time after explosion (2.5 h), an absorbed dose in air of 600 mGy was obtained for the 1-year cumulative dose in Dolon village, due to the first bomb test in 1949. Considering possible ranges of the parameters, 350 and 910 mGy were estimated for high and low cases of γ-ray dose in air, respectively. It was encouraging that the deduced value was consistent with other estimations using thermal luminescence and archived monitoring data. The present

  13. Characterization, subcellular localization and nuclear targeting of casein kinase 2 from Zea mays

    DEFF Research Database (Denmark)

    Peracchia, G; Jensen, A B; Culiáñez-Macià, F A

    1999-01-01

    for an alphaCK2-2 subunit. We studied the regulation of the enzyme in embryos at the mRNA level, at the protein level and by activity testing. By using immunocytochemistry the CK2 protein was localized in several types of cells of mature embryos. Particularly strong signals were visible in the cytoplasm...... around 100-150 bp. The sequence of the exons is 100% homologous to the sequence of the alphaCK2-1 cDNA. Southern hybridization of total genomic DNA from maize embryos with aCK2 cDNA indicated that the alphaCK2-1 gene is part of a multigenic family. We also isolated a new embryo cDNA clone coding...

  14. Impact of the Fukushima Daiichi nuclear power plant accident on local community and healthcare services

    International Nuclear Information System (INIS)

    Oikawa, Tomoyoshi

    2013-01-01

    The Soso region of Japan, located in the northern part of the Pacific side of Fukushima Prefecture, has suffered tremendously from widespread damage caused by the earthquake, tsunami and the Fukushima Dai-ichi nuclear power plant accident. Immediately after the disaster it even seemed that the restoration of this region itself would not be possible. However after six months, the Indoor Restriction Order and evacuation orders within a 20 to 30 km zone from the plant, such as the Evacuation-Prepared Area in Case of Emergency, were lifted and all of those restrictions for the planned evaluation zone has been eased in line with the actual conditions of each region. A year and a month after the earthquake, the Caution Zone, which was declared to prohibit the entry to the zone within the 20 km radius from the plant, was lifted. Thus people can now enter as close as 10 km from the plant. Minami-Soma city is an administrative district which had the largest population (approximately 71,500 residents) within the 20 to 30 km zone prior to the earthquake. It was, also, the only district where the evacuation was not conducted by the municipality. The city is now called the Genpatsu frontline district as it is the closest city to the plant where people have continued to live. Due to the damage caused by the earthquake and Tsunami, the city has suffered both from destruction by the tsunami and radiation, and people are still facing numerous problems despite the fact that the city appears to have been restored on its surface. It is very unfortunate that much of the medical data from the region was lost in the confusion after the Great East Japan Earthquake. In this paper various facts after the disaster based on the data left in the So-so region, Minamisoma city, and Minamisoma municipal general hospital are reported. (author)

  15. Molecular cloning, expression analysis and transcript localization of testicular orphan nuclear receptor 2 in the male catfish, Clarias batrachus.

    Science.gov (United States)

    Murugananthkumar, R; Akhila, M V; Rajakumar, A; Mamta, S K; Sudhakumari, C C; Senthilkumaran, B

    2016-12-01

    Testicular receptor 2 (TR2; also known as Nr2c1) is one of the first orphan nuclear receptors identified and known to regulate various physiological process with or without any ligand. In this study, we report the cloning of full length nr2c1 and its expression analysis during gonadal development, seasonal testicular cycle and after human chorionic gonadotropin (hCG) induction. In addition, in situ hybridization (ISH) was performed to localize nr2c1 transcripts in adult testis and whole catfish (1day post hatch). Tissue distribution and gonadal ontogeny studies revealed high expression of nr2c1 in developing and adult testis. Early embryonic stage-wise expression of nr2c1 seems to emphasize its importance in cellular differentiation and development. Substantial expression of nr2c1 during pre-spawning phase and localization of nr2c1 transcripts in sperm/spermatids were observed. Significant upregulation after hCG induction indicate that nr2c1 is under the regulation of gonadotropins. Whole mount ISH analysis displayed nr2c1 expression in notochord indicating its role in normal vertebrate development. Taken together, our findings suggest that nr2c1 may have a plausible role in the testicular and embryonic development of catfish. Copyright © 2015. Published by Elsevier Inc.

  16. Systematic determination of replication activity type highlights interconnections between replication, chromatin structure and nuclear localization.

    Science.gov (United States)

    Farkash-Amar, Shlomit; David, Yaara; Polten, Andreas; Hezroni, Hadas; Eldar, Yonina C; Meshorer, Eran; Yakhini, Zohar; Simon, Itamar

    2012-01-01

    compact chromatin and are located significantly closer to the nuclear envelope. Supplementary material is available. Raw and processed data were deposited in Geo (GSE17236).

  17. Systematic determination of replication activity type highlights interconnections between replication, chromatin structure and nuclear localization.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    associated with compact chromatin and are located significantly closer to the nuclear envelope. Supplementary material is available. Raw and processed data were deposited in Geo (GSE17236.

  18. Standard deviation of local tallies in global Monte Carlo calculation of nuclear reactor core

    International Nuclear Information System (INIS)

    Ueki, Taro

    2010-01-01

    Time series methodology has been studied to assess the feasibility of statistical error estimation in the continuous space and energy Monte Carlo calculation of the three-dimensional whole reactor core. The noise propagation was examined and the fluctuation of track length tallies for local fission rate and power has been formally shown to be represented by the autoregressive moving average process of orders p and p-1 [ARMA(p,p-1)], where p is an integer larger than or equal to two. Therefore, ARMA(p,p-1) fitting was applied to the real standard deviation estimation of the power of fuel assemblies at particular heights. Numerical results indicate that straightforward ARMA(3,2) fitting is promising, but a stability issue must be resolved toward the incorporation in the distributed version of production Monte Carlo codes. The same numerical results reveal that the average performance of ARMA(3,2) fitting is equivalent to that of the batch method with a batch size larger than 100 and smaller than 200 cycles for a 1,100 MWe pressurized water reactor. (author)

  19. A quantal transport theory for nuclear collective motion: the merits of a locally harmonic approximation

    International Nuclear Information System (INIS)

    Hofmann, H.

    1997-01-01

    A transport theory is developed for collective motion of systems such as an atomic nucleus, which may be considered as a typical representative of a self-bound micro-system. Albeit for pragmatic reasons, collective variables are introduced as shape parameters, self-consistency with respect to the nucleonic degrees of freedom has been implemented at various important stages. This feature leads to subsidiary conditions which are obeyed locally for both the average motion as well as for the quantized Hamiltonian constructed through a Bohm-Pines procedure. Furthermore, self-consistency governs the definition of the transport coefficients appearing in the equations for collective motion. The latter is associated to the time evolution of the density in collective phase space, for which the concept of the Wigner function is employed. Global motion is described by propagating the system in successive time laps which are macroscopically small, but microscopically large. This enables one to exploit linearization procedures and to take advantage of the benefits of linear response theory. A microscopic damping mechanism is introduced by dressing the energies of the independent particle model by complex self-energies, the parameters of which are determined from optical model considerations. Numerical evaluations of transport coefficients are described and tested for the case of fission in the light of recent experimental findings. The theory allows one to extend both Kramers' picture of this process as well as his equation for the density distribution into the quantum regime. (orig.)

  20. Post-translational modification directs nuclear and hyphal tip localization of Candida albicans mRNA-binding protein Slr1.

    Science.gov (United States)

    Ariyachet, Chaiyaboot; Beißel, Christian; Li, Xiang; Lorrey, Selena; Mackenzie, Olivia; Martin, Patrick M; O'Brien, Katharine; Pholcharee, Tossapol; Sim, Sue; Krebber, Heike; McBride, Anne E

    2017-05-01

    The morphological transition of the opportunistic fungal pathogen Candida albicans from budding to hyphal growth has been implicated in its ability to cause disease in animal models. Absence of SR-like RNA-binding protein Slr1 slows hyphal formation and decreases virulence in a systemic candidiasis model, suggesting a role for post-transcriptional regulation in these processes. SR (serine-arginine)-rich proteins influence multiple steps in mRNA metabolism and their localization and function are frequently controlled by modification. We now demonstrate that Slr1 binds to polyadenylated RNA and that its intracellular localization is modulated by phosphorylation and methylation. Wildtype Slr1-GFP is predominantly nuclear, but also co-fractionates with translating ribosomes. The non-phosphorylatable slr1-6SA-GFP protein, in which six serines in SR/RS clusters are substituted with alanines, primarily localizes to the cytoplasm in budding cells. Intriguingly, hyphal cells display a slr1-6SA-GFP focus at the tip near the Spitzenkörper, a vesicular structure involved in molecular trafficking to the tip. The presence of slr1-6SA-GFP hyphal tip foci is reduced in the absence of the mRNA-transport protein She3, suggesting that unphosphorylated Slr1 associates with mRNA-protein complexes transported to the tip. The impact of SLR1 deletion on hyphal formation and function thus may be partially due to a role in hyphal mRNA transport. © 2017 John Wiley & Sons Ltd.

  1. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle

    International Nuclear Information System (INIS)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S.; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-01-01

    The voltage-gated calcium channel (Ca v ) β 1a subunit (Ca v β 1a ) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca v β 1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca v β 1a NH 2 -terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca v β 1a /YFP shows that TnT3 facilitates Ca v β 1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca v β 1a is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca v β 1a . • We mapped TnT3 and Ca v β 1a interaction domain. • TnT3 facilitates Ca v β 1a nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation

  2. Directly converted patient-specific induced neurons mirror the neuropathology of FUS with disrupted nuclear localization in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Lim, Su Min; Choi, Won Jun; Oh, Ki-Wook; Xue, Yuanchao; Choi, Ji Young; Kim, Sung Hoon; Nahm, Minyeop; Kim, Young-Eun; Lee, Jinhyuk; Noh, Min-Young; Lee, Seungbok; Hwang, Sejin; Ki, Chang-Seok; Fu, Xiang-Dong; Kim, Seung Hyun

    2016-01-22

    Mutations in the fused in sarcoma (FUS) gene have been linked to amyotrophic lateral sclerosis (ALS). ALS patients with FUS mutations exhibit neuronal cytoplasmic mislocalization of the mutant FUS protein. ALS patients' fibroblasts or induced pluripotent stem cell (iPSC)-derived neurons have been developed as models for understanding ALS-associated FUS (ALS-FUS) pathology; however, pathological neuronal signatures are not sufficiently present in the fibroblasts of patients, whereas the generation of iPSC-derived neurons from ALS patients requires relatively intricate procedures. Here, we report the generation of disease-specific induced neurons (iNeurons) from the fibroblasts of patients who carry three different FUS mutations that were recently identified by direct sequencing and multi-gene panel analysis. The mutations are located at the C-terminal nuclear localization signal (NLS) region of the protein (p.G504Wfs*12, p.R495*, p.Q519E): two de novo mutations in sporadic ALS and one in familial ALS case. Aberrant cytoplasmic mislocalization with nuclear clearance was detected in all patient-derived iNeurons, and oxidative stress further induced the accumulation of cytoplasmic FUS in cytoplasmic granules, thereby recapitulating neuronal pathological features identified in mutant FUS (p.G504Wfs*12)-autopsied ALS patient. Importantly, such FUS pathological hallmarks of the patient with the p.Q519E mutation were only detected in patient-derived iNeurons, which contrasts to predominant FUS (p.Q519E) in the nucleus of both the transfected cells and patient-derived fibroblasts. Thus, iNeurons may provide a more reliable model for investigating FUS mutations with disrupted NLS for understanding FUS-associated proteinopathies in ALS.

  3. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Science.gov (United States)

    Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen

    2017-01-01

    The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution. PMID:28991190

  4. Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

    Directory of Open Access Journals (Sweden)

    Wentao Wu

    2017-10-01

    Full Text Available The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens to 63 (Glycine max. The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

  5. The Way of Representation of Ideology in Local and International Newspapers about Iran’s Nuclear Program

    Directory of Open Access Journals (Sweden)

    Gity Taki

    2015-06-01

    Full Text Available Ideology is a meaningful structure that involves in production, reproduction and changing unequal power relations. By means of meaning, ideology connects to discourse and language which is the device of meaning production. Ideologies are generated and transformed in actual discursive events. Press headlines are also discursive events. Based on critical discourse analysis and by using Van Leeuwen's theoretical framework (1996 and socio-semantic features of the framework like exclusion, inclusion, appraisement, association and differentiation, this study will try to analyze the way of representation of ideologies about Iran's nuclear program in a selection of national and international newspapers’ headlines during 2011-2012. By determining and comparing the frequency of the socio-semantic features during 2011- 2012, this question will be answered that how ideology is represented in national and international newspapers about Iran's nuclear program by using socio-semantic features during 2011- 2012, and whether the way of representation and the amount of these features are the same in both groups? To do this 242 headlines of two national newspapers, Keyhan and Iran, and two foreign newspapers, The Washington post and The Guardian were selected. Then the headlines were analyzed by using an analytical–descriptive method. The findings showed that both local and international newspapers use the same kind of features to reflect the news, but the amount of the features, especially in using of exclusion, and the way they are used, is different according to the newspaper's policy. In fact by utilizing specific features, the newspapers actually show the ideology they advocate. Actually having different ideologies have led to use the features in different ways.

  6. Importin alpha binding and nuclear localization of PARP-2 is dependent on lysine 36, which is located within a predicted classical NLS

    Directory of Open Access Journals (Sweden)

    Valovka Taras

    2008-07-01

    Full Text Available Abstract Background The enzymes responsible for the synthesis of poly-ADP-ribose are named poly-ADP-ribose polymerases (PARP. PARP-2 is a nuclear protein, which regulates a variety of cellular functions that are mainly controlled by protein-protein interactions. A previously described non-conventional bipartite nuclear localization sequence (NLS lies in the amino-terminal DNA binding domain of PARP-2 between amino acids 1–69; however, this targeting sequence has not been experimentally examined or validated. Results Using a site-directed mutagenesis approach, we found that lysines 19 and 20, located within a previously described bipartite NLS, are not required for nuclear localization of PARP-2. In contrast, lysine 36, which is located within a predicted classical monopartite NLS, was required for PARP-2 nuclear localization. While wild type PARP-2 interacted with importin α3 and to a very weak extent with importin α1 and importin α5, the mutant PARP-2 (K36R did not interact with importin α3, providing a molecular explanation why PARP-2 (K36R is not targeted to the nucleus. Conclusion Our results provide strong evidence that lysine 36 of PARP-2 is a critical residue for proper nuclear targeting of PARP-2 and consequently for the execution of its biological functions.

  7. Results of calculations of external gamma radiation exposure rates from local fallout and the related radionuclide compositions of two hypothetical 1-MT nuclear bursts. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, H.

    1984-12-01

    This report presents data on calculated gamma radiation exposure rates and local surface deposition of related radionuclides resulting from two hypothetical 1-Mt nuclear bursts. Calculations are made of the debris from two types of bombs: one containing /sup 235/U as a fissionable material (designated oralloy), the other containing /sup 238/U (designated tuballoy). 4 references.

  8. A localized navigation algorithm for Radiation Evasion for nuclear facilities. Part II: Optimizing the “Nearest Exit” Criterion

    International Nuclear Information System (INIS)

    Khasawneh, Mohammed A.; Al-Shboul, Zeina Aman M.; Jaradat, Mohammad A.; Malkawi, Mohammad I.

    2013-01-01

    Highlights: ► A new navigation algorithm for Radiation Evasion around nuclear facilities. ► An optimization criteria minimized under algorithm operation. ► A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. ► Benefits of using localized navigation as opposed to global navigation schemas. ► A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. -- Abstract: In this extension from part I (Khasawneh et al., in press), we modify the navigation algorithm which was presented with the objective of optimizing the “Radiation Evasion” Criterion so that navigation would optimize the criterion of “Nearest Exit”. Under this modification, algorithm would yield navigation paths that would guide occupational workers towards Nearest Exit points. Again, under this optimization criterion, algorithm leverages the use of localized information acquired through a well designed and distributed wireless sensor network, as it averts the need for any long-haul communication links or centralized decision and monitoring facility thereby achieving a more reliable performance under dynamic environments. As was done in part I, the proposed algorithm under the “Nearest Exit” Criterion is designed to leverage nearest neighbor information coming in through the sensory network overhead, in computing successful navigational paths from one point to another. For comparison purposes, the proposed algorithm is tested under the two optimization criteria: “Radiation Evasion” and “Nearest Exit”, for different numbers of step look-ahead. We verify the performance of the algorithm by means of simulations, whereby navigational paths are calculated for different radiation fields. We, via simulations, also, verify the performance of the algorithm in comparison with a well-known global navigation algorithm upon which we draw our conclusions

  9. A localized navigation algorithm for Radiation Evasion for nuclear facilities. Part II: Optimizing the “Nearest Exit” Criterion

    Energy Technology Data Exchange (ETDEWEB)

    Khasawneh, Mohammed A., E-mail: mkha@ieee.org [Department of Electrical Engineering, Jordan University of Science and Technology (Jordan); Al-Shboul, Zeina Aman M., E-mail: xeinaaman@gmail.com [Department of Electrical Engineering, Jordan University of Science and Technology (Jordan); Jaradat, Mohammad A., E-mail: majaradat@just.edu.jo [Department of Mechanical Engineering, Jordan University of Science and Technology (Jordan); Malkawi, Mohammad I., E-mail: mmalkawi@aimws.com [College of Engineering, Jadara University, Irbid 221 10 (Jordan)

    2013-06-15

    Highlights: ► A new navigation algorithm for Radiation Evasion around nuclear facilities. ► An optimization criteria minimized under algorithm operation. ► A man-borne device guiding the occupational worker towards paths that warrant least radiation × time products. ► Benefits of using localized navigation as opposed to global navigation schemas. ► A path discrimination function for finding the navigational paths exhibiting the least amounts of radiation. -- Abstract: In this extension from part I (Khasawneh et al., in press), we modify the navigation algorithm which was presented with the objective of optimizing the “Radiation Evasion” Criterion so that navigation would optimize the criterion of “Nearest Exit”. Under this modification, algorithm would yield navigation paths that would guide occupational workers towards Nearest Exit points. Again, under this optimization criterion, algorithm leverages the use of localized information acquired through a well designed and distributed wireless sensor network, as it averts the need for any long-haul communication links or centralized decision and monitoring facility thereby achieving a more reliable performance under dynamic environments. As was done in part I, the proposed algorithm under the “Nearest Exit” Criterion is designed to leverage nearest neighbor information coming in through the sensory network overhead, in computing successful navigational paths from one point to another. For comparison purposes, the proposed algorithm is tested under the two optimization criteria: “Radiation Evasion” and “Nearest Exit”, for different numbers of step look-ahead. We verify the performance of the algorithm by means of simulations, whereby navigational paths are calculated for different radiation fields. We, via simulations, also, verify the performance of the algorithm in comparison with a well-known global navigation algorithm upon which we draw our conclusions.

  10. Troponin T3 regulates nuclear localization of the calcium channel Cavβ1a subunit in skeletal muscle.

    Science.gov (United States)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang; Pereyra, Andrea S; Messi, Maria Laura; Wang, Zhong-Min; Hereñú, Claudia; Delbono, Osvaldo

    2015-08-15

    The voltage-gated calcium channel (Cav) β1a subunit (Cavβ1a) plays an important role in excitation-contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Cavβ1a subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160-244 aa) and Cavβ1a NH2-terminus (1-99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Cavβ1a/YFP shows that TnT3 facilitates Cavβ1a nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Obesity-Linked Phosphorylation of SIRT1 by Casein Kinase 2 Inhibits Its Nuclear Localization and Promotes Fatty Liver.

    Science.gov (United States)

    Choi, Sung E; Kwon, Sanghoon; Seok, Sunmi; Xiao, Zhen; Lee, Kwan-Woo; Kang, Yup; Li, Xiaoling; Shinoda, Kosaku; Kajimura, Shingo; Kemper, Byron; Kemper, Jongsook Kim

    2017-08-01

    Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity. Mechanistically, phosphorylation of SIRT1 at Ser-164 substantially inhibited its nuclear localization and modestly affected its deacetylase activity. Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant. Remarkably, phosphorylated S164-SIRT1 and CK2 levels were also highly elevated in liver samples of NAFLD patients and correlated with disease severity. Thus, inhibition of phosphorylation of SIRT1 by CK2 may serve as a new therapeutic approach for treatment of NAFLD and other obesity-related diseases. Copyright © 2017 American Society for Microbiology.

  12. Local structures of mesoporous bioactive glasses and their surface alterations in vitro: inferences from solid-state nuclear magnetic resonance

    Science.gov (United States)

    Gunawidjaja, Philips N.; Mathew, Renny; Lo, Andy Y. H.; Izquierdo-Barba, Isabel; García, Ana; Arcos, Daniel; Mattias Edén, María Vallet-Regí

    2012-01-01

    We review the benefits of using 29Si and 1H magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy for probing the local structures of both bulk and surface portions of mesoporous bioactive glasses (MBGs) of the CaO–SiO2−(P2O5) system. These mesoporous materials exhibit an ordered pore arrangement, and are promising candidates for improved bone and tooth implants. We discuss experimental MAS NMR results from three MBGs displaying different Ca, Si and P contents: the 29Si NMR spectra were recorded either directly by employing radio-frequency pulses to 29Si, or by magnetization transfers from neighbouring protons using cross polarization, thereby providing quantitative information about the silicate speciation present in the pore wall and at the MBG surface, respectively. The surface modifications were monitored for the three MBGs during their immersion in a simulated body fluid (SBF) for intervals between 30 min and one week. The results were formulated as a reaction sequence describing the interconversions between the distinct silicate species. We generally observed a depletion of Ca2+ ions at the MBG surface, and a minor condensation of the silicate-surface network over one week of SBF soaking. PMID:22349247

  13. Absence of PTHrP nuclear localization and carboxyl terminus sequences leads to abnormal brain development and function.

    Directory of Open Access Journals (Sweden)

    Zhen Gu

    Full Text Available We assessed whether the nuclear localization sequences (NLS and C terminus of parathyroid hormone-related protein (PTHrP play critical roles in brain development and function. We used histology, immunohistochemistry, histomorphometry, Western blots and electrophysiological recordings to compare the proliferation and differentiation of neural stem cells, neuronal hippocampal synaptic transmission, and brain phenotypes including shape and structures, in Pthrp knock-in mice, which express PTHrP (1-84, a truncated form of the protein that is missing the NLS and the C-terminal region of the protein, and their wild-type littermates. Results showed that Pthrp knock-in mice display abnormal brain shape and structures; decreased neural cell proliferative capacity and increased apoptosis associated with up-regulation of cyclin dependent kinase inhibitors p16, p21, p27 and p53 and down-regulation of the Bmi-1 oncogene; delayed neural cell differentiation; and impaired hippocampal synaptic transmission and plasticity. These findings provide in vivo experimental evidence that the NLS and C-terminus of PTHrP are essential not only for the regulation of neural cell proliferation and differentiation, but also for the maintenance of normal neuronal synaptic transmission and plasticity.

  14. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity

    Science.gov (United States)

    Görner, Wolfram; Durchschlag, Erich; Martinez-Pastor, Maria Teresa; Estruch, Francisco; Ammerer, Gustav; Hamilton, Barbara; Ruis, Helmut; Schüller, Christoph

    1998-01-01

    Msn2p and the partially redundant factor Msn4p are key regulators of stress-responsive gene expression in Saccharomyces cerevisiae. They are required for the transcription of a number of genes coding for proteins with stress-protective functions. Both Msn2p and Msn4p are Cys2His2 zinc finger proteins and bind to the stress response element (STRE). In vivo footprinting studies show that the occupation of STREs is enhanced in stressed cells and dependent on the presence of Msn2p and Msn4p. Both factors accumulate in the nucleus under stress conditions, such as heat shock, osmotic stress, carbon-source starvation, and in the presence of ethanol or sorbate. Stress-induced nuclear localization was found to be rapid, reversible, and independent of protein synthesis. Nuclear localization of Msn2p and Msn4p was shown to be correlated inversely to cAMP levels and protein kinase A (PKA) activity. A region with significant homologies shared between Msn2p and Msn4p is sufficient to confer stress-regulated localization to a SV40–NLS–GFP fusion protein. Serine to alanine or aspartate substitutions in a conserved PKA consensus site abolished cAMP-driven nuclear export and cytoplasmic localization in unstressed cells. We propose stress and cAMP-regulated intracellular localization of Msn2p to be a key step in STRE-dependent transcription and in the general stress response. PMID:9472026

  15. Enhanced effect of nuclear localization signal peptide during ultrasound‑targeted microbubble destruction‑mediated gene transfection.

    Science.gov (United States)

    Cao, Sheng; Zhou, Qing; Chen, Jin-Ling; Jiang, Nan; Wang, Yi-Jia; Deng, Qing; Hu, Bo; Guo, Rui-Qiang

    2017-07-01

    Ultrasound‑targeted microbubble destruction (UTMD) can promote the entry of plasmid DNA (pDNA) into the cell cytoplasm, by increasing the permeability of the cell membrane. But the transfection efficiency remains low due to inability of the pDNA to enter the nucleus. Various methods have been explored to improve the UTMD transfection efficiency, but with little success. In cells, the classic nuclear localization signal (cNLS) peptide is an amino acid sequence that signals proteins that are due for nuclear transport. The present study aimed to investigate whether binding of a cNLS peptide to the pDNA may improve the transfection efficiency of UTMD. Four experimental groups were analyzed: Control group (UTMD + pDNA), group with cNLS (UTMD + pDNA + cNLS), group with mutated NLS (mNLS; UTMD + pDNA + mNLS), and group with cNLS and the nuclear import blocker, wheat germ agglutinin (WGA; UTMD + pDNA + cNLS + WGA). The NLS was labeled by fluorescein isothiocyanate, whereas pDNA was labeled with Cy3. Different molar ratios were tested for the NLS and pDNA combination in order to achieve optimal binding of the two molecules. Human umbilical vein endothelial cells were then transfected using the optimum ultrasonic irradiation parameters and NLS/pDNA molar ratio. At 6 h post‑transfection, the rates of Cy3‑labeled pDNA inside the cells and their nuclei were detected by flow cytometry and laser confocal microscopy, and the cellular vs. nuclear uptake of pDNA was calculated. In order to further evaluate the effect of NLS on UTMD‑mediated gene transfection, the transfection efficiency and relative expression levels of mRNA and protein were detected at 48 h post‑transfection. The results demonstrated that the optimal molar ratio of NLS with pDNA was 104:1. The rates of pDNA successful entry into the cell and nucleus were significantly higher in the cNLS group compared with the control group. The transfection efficiency, and relative expression levels of mRNA and protein

  16. The use of additive and subtractive approaches to examine the nuclear localization sequence of the polyomavirus major capsid protein VP1

    Science.gov (United States)

    Chang, D.; Haynes, J. I. 2nd; Brady, J. N.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    A nuclear localization signal (NLS) has been identified in the N-terminal (Ala1-Pro-Lys-Arg-Lys-Ser-Gly-Val-Ser-Lys-Cys11) amino acid sequence of the polyomavirus major capsid protein VP1. The importance of this amino acid sequence for nuclear transport of VP1 protein was demonstrated by a genetic "subtractive" study using the constructs pSG5VP1 (full-length VP1) and pSG5 delta 5'VP1 (truncated VP1, lacking amino acids Ala1-Cys11). These constructs were used to transfect COS-7 cells, and expression and intracellular localization of the VP1 protein was visualized by indirect immunofluorescence. These studies revealed that the full-length VP1 was expressed and localized in the nucleus, while the truncated VP1 protein was localized in the cytoplasm and not transported to the nucleus. These findings were substantiated by an "additive" approach using FITC-labeled conjugates of synthetic peptides homologous to the NLS of VP1 cross-linked to bovine serum albumin or immunoglobulin G. Both conjugates localized in the nucleus after microinjection into the cytoplasm of 3T6 cells. The importance of individual amino acids found in the basic sequence (Lys3-Arg-Lys5) of the NLS was also investigated. This was accomplished by synthesizing three additional peptides in which lysine-3 was substituted with threonine, arginine-4 was substituted with threonine, or lysine-5 was substituted with threonine. It was found that lysine-3 was crucial for nuclear transport, since substitution of this amino acid with threonine prevented nuclear localization of the microinjected, FITC-labeled conjugate.

  17. Beyond defense-in-depth: cost and funding of state and local government radiological emergency response plans and preparedness in support of commercial nuclear power stations

    International Nuclear Information System (INIS)

    Salomon, S.N.

    1979-10-01

    Inadequate, sporadic, uncertain and frustrating are words local, state and Federal officials use to describe the current hodgepodge funding approach to State and local government radiological emergency response plans and preparedeness in support of commercial nuclear power stations. The creation of a Radiological Emergency Response Plans and Preparedness Fund for State and Local Government is offered as a preferred solution. Monies for the Fund could be derived from a one time Fee of $1 million levied on the operator of each nuclear power station. Every five years, adjustments could be made in the Fee to assure full recovery of costs because of inflation, revised criteria and other cost related factors. Any surplus would be refunded to the utilities. Any state that has obtained NRC concurrence or is in the process could be reimbursed for previous expenditures up to two years prior to NRC concurrence. Concurrence in all state and local government plans is the objective of the funding program. The Fund should be administered by the Nuclear Regulatory Commission. The report also discusses actions by Federal and state agencies and points to long range considerations, such as a training institute, including transportation and non-commercial and other fixed nuclear facilities, where preparedness could be enhanced by a coherent funding mechanism. All recommendations are based on an inquiry by the Office of state Programs, NRC, into the historical and future costs and funding of radiological emergency response plans and preparedness at the state and local government levels and are derived from discussions with many local, State and Federal officials

  18. 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

  19. ORF73 LANA homologs of RRV and MneRV2 contain an extended RGG/RG-rich nuclear and nucleolar localization signal that interacts directly with importin β1 for non-classical nuclear import.

    Science.gov (United States)

    Howard, Kellie; Cherezova, Lidia; DeMaster, Laura K; Rose, Timothy M

    2017-11-01

    The latency-associated nuclear antigens (LANA) of KSHV and macaque RFHVMn, members of the RV1 rhadinovirus lineage, are closely related with conservation of complex nuclear localization signals (NLS) containing bipartite KR-rich motifs and RG-rich domains, which interact distinctly with importins α and ß1 for nuclear import via classical and non-classical pathways, respectively. RV1 LANAs are expressed in the nucleus of latently-infected cells where they inhibit replication and establish a dominant RV1 latency. Here we show that LANA homologs of macaque RRV and MneRV2 from the more distantly-related RV2 lineage, lack the KR-rich NLS, and instead have a large RG-rich NLS with multiple RG dipeptides and a conserved RGG motif. The RG-NLS interacts uniquely with importin β1, which mediates nuclear import and accumulation of RV2 LANA in the nucleolus. The alternative nuclear import and localization of RV2 LANA homologs may contribute to the dominant RV2 lytic replication phenotype. Copyright © 2017. Published by Elsevier Inc.

  20. [Report from Minamisoma City: diversity and complexity of psychological distress in local residents after a nuclear power plant accident].

    Science.gov (United States)

    Hori, Arinobu; Tsumuraya, Kunihiro; Kanamori, Ryo; Maeda, Masaharu; Yabe, Hirooki; Niwa, Shinichi

    2014-01-01

    Natural disasters can severely impact local communities. When a disaster is limited in type or scope, the loss and distress felt by individual residents can be sympathetically visualized and shared, and this can help bring the community together. In 2011, however, Japan experienced the Great East Japan Earthquake and accompanying tsunami, and the scale of this disaster was compounded by the Fukushima nuclear power plant accident. As a result of this complex disaster, residents experienced very different problems, particularly in Fukushima Prefecture. In this paper, we describe the situation in Minamisoma City, which is located to the north of the Fukushima Daiichi nuclear power plant. After the accident, the city was divided into three zones. The southern part of the city, which is within 20 km of the plant, was designated as a restricted area; the middle section, located between 20 and 30 km of the plant, was initially designated as an evacuation readiness area; and the northern part of the city received no evacuation-related designation. In April 2012, ordinary residents were finally allowed to visit the restricted area, but utilities and municipal services in the area had not yet been restored, and residents were still prohibited from staying overnight even in August 2013. The overall situation was further complicated by the existence of conflicting opinions regarding exposure to low dose ionizing radiation and compensation for subsequent distress. Things became so complex that residents of the same city sometimes struggled to imagine their neighbors' feelings and state of mind. After the disaster, aging of the city accelerated dramatically. The proportion of elders (those aged 65 or older) in the population stood at 25.9% in March 2011, but this had increased to 32.9% by March 2013. Elders tend to have strong emotional ties to their hometowns, while younger generations are more likely to move away and start over. As some young people have left the area or

  1. AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lorenzato, Annalisa; Biolatti, Marta [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Delogu, Giuseppe [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Capobianco, Giampiero [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Farace, Cristiano [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); Dessole, Salvatore; Cossu, Antonio; Tanda, Francesco [Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari (Italy); Madeddu, Roberto [Department of Biomedical Sciences-Histology, University of Sassari, Sassari (Italy); National Institute of Biostructures and Biosystems, Rome (Italy); Olivero, Martina [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy); Di Renzo, Maria Flavia, E-mail: mariaflavia.direnzo@unito.it [Department of Oncology, University of Torino School of Medicine, Torino (Italy); Institute for Cancer Research at Candiolo, Candiolo, Torino (Italy)

    2013-10-15

    The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. - highlights: • CSE1L is a key player in nucleocytoplasmic traffic by forming complex with Ran. • AKT phosphorylates RanBP3 that regulates the nucleocytoplasmic gradient of Ran. • The activated oncogenic AKT drives the nuclear accumulation of CSE1L. • CSE1L in the nucleus up-regulates genes conveying pro-oncogenic signals. • CSE1L might contribute to tumor progression driven by the activated oncogenic AKT.

  2. Effects of local-scale decontamination in a secondary forest contaminated after the Fukushima nuclear power plant accident.

    Science.gov (United States)

    Ayabe, Yoshiko; Hijii, Naoki; Takenaka, Chisato

    2017-09-01

    We investigated whether local-scale decontamination (removal of the litter layer, superficial soil layer, and understory) in a secondary forest contaminated by the Fukushima nuclear power plant accident reduced 137 Cs contamination of the soil and litter. We also measured 137 Cs concentrations in plants and in the web-building spider Nephila clavata (Nephilidae: Arachnida), as an indicator species, to examine 137 Cs contamination in arthropods. One month after decontamination, the total 137 Cs contamination (soil + litter) was reduced by 20% (100 kBq·m -2 ) relative to that in an adjacent untreated (i.e., contaminated) area, which was however not statistically significant. Four months after decontamination, 137 Cs in the decontaminated area had increased to a level similar to those in the untreated area, and the air radiation dose in the decontaminated area was about 2.1 μSv·h -1 , significantly higher than that in the untreated area (1.9 μSv·h -1 ). This may have been attributed to a torrential rain event. Although no statistically significant reduction was observed, most spiders had a lower 137 Cs contamination than that before the decontamination. This implied that the decontamination may have reduced 137 Cs transfer from soil via litter to N. clavata through the detrital food chains, but may not have reduced the amount of 137 Cs transfer through grazing food chains because the concentration of 137 Cs in living tree leaves was not reduced by the decontamination. In autumn, about 2 kBq·m -2 of 137 Cs was supplied from foliage to the ground by litterfall. The results suggested that removal of the litter and superficial soil layers in a contaminated forest may be ineffective. The present study suggests that the local-scale decontamination in a secondary forest had no effect on the reduction of 137 Cs contamination in the treated area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Information of French people about nuclear. Detailed results. Ifop for the National Association of local information committees and commissions (ANCCLI)

    International Nuclear Information System (INIS)

    2014-05-01

    After a brief presentation of the survey method (sample, survey mode, dates, error margins and confidence interval), this report presents and briefly comments the main results of a survey on perception French people have on nuclear industry and activities. More precisely, questions asked to the people addressed the following issues: the perception of nuclear as a taboo issue, words associated with nuclear, and the perception of the safety distance to be observed in case of a nuclear accident. For these three questions, tables of data are given which contain answers and social and demographic characteristics

  4. Novel nuclear localization and potential function of insulin-like growth factor-1 receptor/insulin receptor hybrid in corneal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yu-Chieh Wu

    Full Text Available BACKGROUND: Type I insulin-like growth factor receptor (IGF-1R and insulin receptor (INSR are highly homologous molecules, which can heterodimerize to form an IGF-1R/INSR hybrid (Hybrid-R. The presence and biological significance of the Hybrid-R in human corneal epithelium has not yet been established. In addition, while nuclear localization of IGF-1R was recently reported in cancer cells and human corneal epithelial cells, the function and profile of nuclear IGF-1R is unknown. In this study, we characterized the nuclear localization and function of the Hybrid-R and the role of IGF-1/IGF-1R and Hybrid-R signaling in the human corneal epithelium. METHODOLOGY/PRINCIPLE FINDINGS: IGF-1-mediated signaling and cell growth were examined in a human telomerized corneal epithelial (hTCEpi cell line using co-immunoprecipitation, immunoblotting and cell proliferation assays. The presence of Hybrid-R in hTCEpi and primary cultured human corneal epithelial cells was confirmed by immunofluorescence and reciprocal immunoprecipitation of whole cell lysates. We found that IGF-1 stimulated Akt and promoted cell growth through IGF-1R activation, which was independent of the Hybrid-R. The presence of Hybrid-R, but not IGF-1R/IGF-1R, was detected in nuclear extracts. Knockdown of INSR by small interfering RNA resulted in depletion of the INSR/INSR and preferential formation of Hybrid-R. Chromatin-immunoprecipitation sequencing assay with anti-IGF-1R or anti-INSR was subsequently performed to identify potential genomic targets responsible for critical homeostatic regulatory pathways. CONCLUSION/SIGNIFICANCE: In contrast to previous reports on nuclear localized IGF-1R, this is the first report identifying the nuclear localization of Hybrid-R in an epithelial cell line. The identification of a nuclear Hybrid-R and novel genomic targets suggests that IGF-1R traffics to the nucleus as an IGF-1R/INSR heterotetrameric complex to regulate corneal epithelial homeostatic

  5. Coordinate regulation/localization of the carbohydrate responsive binding protein (ChREBP) by two nuclear export signal sites: Discovery of a new leucine-rich nuclear export signal site

    International Nuclear Information System (INIS)

    Fukasawa, Masashi; Ge, Qing; Wynn, R. Max; Ishii, Seiji; Uyeda, Kosaku

    2010-01-01

    Carbohydrate response element binding protein (ChREBP) is responsible for conversion of dietary carbohydrate to storage fat in liver by coordinating expression of the enzymes that channel glycolytic pyruvate into lipogenesis. The activation of ChREBP in response to high glucose is nuclear localization and transcription, and the inactivation of ChREBP under low glucose involves export from the nucleus to the cytosol. Here we report a new nuclear export signal site ('NES1') of ChREBP. Together these signals provide ChREBP with two NES sequences, both the previously reported NES2 and now the new NES1 coordinate to interact together with CRM1 (exportin) for nuclear export of the carbohydrate response element binding protein.

  6. Survey the of building and dietary structure of local residents around Yangjiang and Hongyanhe nuclear power plants

    International Nuclear Information System (INIS)

    Qian Yekan; Lei Cuiping; Sun Quanfu; Fan Yaohua; Huang Zhibiao; Cui Yong

    2011-01-01

    Objective: To provide a guide in the course of the daily operation and accident emergency response. Methods: The survey was conducted with questionnaires among heads of households collected by stratified radom sampling. The head of a household was asked about residential type and structure, the sources of drinking water, milk, type and frequency of main vegetables. Results: Two-storied and more than two-storied houses were dominant around Yangjiang nuclear power plant, single-storey houses and tile-roofed houses were dominant around Hongyanhe nuclear power plant. The top three of wall construction materials around the two nuclear power plants were orderly brick, stone and beton. Glass window shelters were in the majority. Drinking water of residents was mainly from wells and waterworks. Milk comes from nonlocal packaged products. The top five high frequency vegetables the residents around Yangjiang nuclear power plants eat were orderly cabbage, zucchini, string beans, tong dish, cucumber, and those around Yangjiang nuclear power plant were orderly chinese cabbage, leek, celery, cabbage, spinach. Conclusion: Building and dietary structure around Yangjiang and Hongyanhe nuclear power plants are incongruence. Government can make decisions to collect foods for nuclides monitoring according to building and dietary structure baseline data, and take emergency measures to direct nuclear safety radiation protection for residents when nuclear accident takes place. (authors)

  7. A case study of economic incentives and local citizens' attitudes toward hosting a nuclear power plant in Japan: Impacts of the Fukushima accident

    International Nuclear Information System (INIS)

    Kato, Takaaki; Takahara, Shogo; Nishikawa, Masashi; Homma, Toshimitsu

    2013-01-01

    The attitude of local communities near a nuclear power plant (NPP) is a key factor in nuclear policy decision making in Japan. This case study compared local citizens' attitudes in 2010 and 2011 toward the benefits and drawbacks of hosting Kashiwazaki–Kariwa NPP. The Fukushima accident occurred in this period. After the accident, benefit recognition of utility bill refunds clearly declined, while that of public facilities did not, suggesting the influence of a bribery effect. The negative shift of attitudes about hosting the NPP after the accident was more modest in Kariwa Village, which saw a large expansion of social welfare programs, than in the other two areas, which lacked such a budget expansion. Policy implications of these results regarding the provision of economic incentives in NPP host areas after the Fukushima accident were discussed. - Highlights: • The Fukushima accident shocked Japan's nuclear policy. • Citizens' attitudes toward incentives of hosting a nuclear power plant surveyed. • More citizens thought negatively about incentives after the Fukushima accident. • The bribery effect, mode and amount of incentives affected citizens' attitudes

  8. Prostate-derived sterile 20-like kinase 1-alpha induces apoptosis. JNK- and caspase-dependent nuclear localization is a requirement for membrane blebbing.

    Science.gov (United States)

    Zihni, Ceniz; Mitsopoulos, Costas; Tavares, Ignatius A; Baum, Buzz; Ridley, Anne J; Morris, Jonathan D H

    2007-03-02

    We have demonstrated previously that full-length prostate-derived sterile 20-like kinase 1-alpha (PSK1-alpha) binds to microtubules via its C terminus and regulates their organization and stability independently of its catalytic activity. Here we have shown that apoptotic and microtubule-disrupting agents promote catalytic activation, C-terminal cleavage, and nuclear translocation of endogenous phosphoserine 181 PSK1-alpha and activated N-terminal PSK1-alpha-induced apoptosis. PSK1-alpha, unlike its novel isoform PSK1-beta, stimulated the c-Jun N-terminal kinase (JNK) pathway, and the nuclear localization of PSK1-alpha and its induction of cell contraction, membrane blebbing, and apoptotic body formation were dependent on JNK activity. PSK1-alpha was also a caspase substrate, and the broad spectrum caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone or mutation of a putative caspase recognition motif ((916)DPGD(919)) blocked nuclear localization of PSK1-alpha and its induction of membrane blebs. Additional inhibition of caspase 9 was needed to prevent cell contraction. PSK1-alpha is therefore a bifunctional kinase that associates with microtubules, and JNK- and caspase-mediated removal of its C-terminal microtubule-binding domain permits nuclear translocation of the N-terminal region of PSK1-alpha and its induction of apoptosis.

  9. Influence of agrochemical characteristics of 85Sr and 137Cs in soil samples from the localities around nuclear power plants in Slovak Republic

    International Nuclear Information System (INIS)

    Cipakova, A.; Mitro, A.

    1997-01-01

    Sorption of radiostrontium and radiocesium, two biologically available radionuclides in soils was studied. Experiments were carried out on the soil samples from the localities around nuclear power plants. Adsorption processes are the function of many factors. Multi-para-metrical regression analysis was used for studying of the influence of agrochemical characteristics on sorption of 85 Sr and 137 Cs in observed soil types. (authors)

  10. Endogenous RGS14 is a cytoplasmic-nuclear shuttling protein that localizes to juxtanuclear membranes and chromatin-rich regions of the nucleus

    Science.gov (United States)

    Hepler, John R.

    2017-01-01

    Regulator of G protein signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates G protein and H-Ras/MAPkinase signaling pathways to regulate synaptic plasticity important for hippocampal learning and memory. However, to date, little is known about the subcellular distribution and roles of endogenous RGS14 in a neuronal cell line. Most of what is known about RGS14 cellular behavior is based on studies of tagged, recombinant RGS14 ectopically overexpressed in unnatural host cells. Here, we report for the first time a comprehensive assessment of the subcellular distribution and dynamic localization of endogenous RGS14 in rat B35 neuroblastoma cells. Using confocal imaging and 3D-structured illumination microscopy, we find that endogenous RGS14 localizes to subcellular compartments not previously recognized in studies of recombinant RGS14. RGS14 localization was observed most notably at juxtanuclear membranes encircling the nucleus, at nuclear pore complexes (NPC) on both sides of the nuclear envelope and within intranuclear membrane channels, and within both chromatin-poor and chromatin-rich regions of the nucleus in a cell cycle-dependent manner. In addition, a subset of nuclear RGS14 localized adjacent to active RNA polymerase II. Endogenous RGS14 was absent from the plasma membrane in resting cells; however, the protein could be trafficked to the plasma membrane from juxtanuclear membranes in endosomes derived from ER/Golgi, following constitutive activation of endogenous RGS14 G protein binding partners using AlF4¯. Finally, our findings show that endogenous RGS14 behaves as a cytoplasmic-nuclear shuttling protein confirming what has been shown previously for recombinant RGS14. Taken together, the findings highlight possible cellular roles for RGS14 not previously recognized that are distinct from the regulation of conventional GPCR-G protein signaling, in particular undefined roles for RGS14 in the nucleus. PMID:28934222

  11. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    Energy Technology Data Exchange (ETDEWEB)

    Bejerman, Nicolás, E-mail: n.bejerman@uq.edu.au [Instituto de Patología Vegetal (IPAVE), Centro de Investigaciones Agropecuarias (CIAP), Instituto Nacional de Tecnología Agropecuaria INTA, Camino a 60 Cuadras k 5,5, Córdoba X5020ICA (Argentina); Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072 (Australia); Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio [Instituto de Patología Vegetal (IPAVE), Centro de Investigaciones Agropecuarias (CIAP), Instituto Nacional de Tecnología Agropecuaria INTA, Camino a 60 Cuadras k 5,5, Córdoba X5020ICA (Argentina); Dietzgen, Ralf G. [Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072 (Australia)

    2015-09-15

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

  12. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    International Nuclear Information System (INIS)

    Bejerman, Nicolás; Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio; Dietzgen, Ralf G.

    2015-01-01

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses

  13. The N terminus of the influenza B virus nucleoprotein is essential for virus viability, nuclear localization, and optimal transcription and replication of the viral genome.

    Science.gov (United States)

    Sherry, Lee; Smith, Matt; Davidson, Sophie; Jackson, David

    2014-11-01

    The nucleoprotein (NP) of influenza viruses is a multifunctional protein with essential roles throughout viral replication. Despite influenza A and B viruses belonging to separate genera of the Orthomyxoviridae family, their NP proteins share a relatively high level of sequence conservation. However, NP of influenza B viruses (BNP) contains an evolutionarily conserved N-terminal 50-amino-acid extension that is absent from NP of influenza A viruses. There is conflicting evidence as to the functions of the BNP N-terminal extension; however, this has never been assessed in the context of viral infection. We have used reverse genetics to assess the significance of this region on the functions of BNP and virus viability. The truncation of more than three amino acids prevented virus recovery, suggesting that the N-terminal extension is essential for virus viability. Mutational analysis indicated that multiple regions of the protein are involved in the nuclear localization of BNP, with the entire N-terminal extension required for this to function efficiently. Viruses containing mutations in the first 10 residues of BNP demonstrated few differences in nuclear localization; however, the viruses exhibited significant reductions in viral mRNA transcription and genome replication, resulting in significantly attenuated phenotypes. Mutations introduced to ablate a previously reported nuclear localization signal also resulted in a significant decrease in mRNA production during early stages of viral replication. Overall, our results demonstrate that the N-terminal extension of BNP is essential to virus viability not only for directing nuclear localization of BNP but also for regulating viral mRNA transcription and genome replication. The multifunctional NP of influenza viruses has roles throughout the viral replication cycle; therefore, it is essential for virus viability. Despite high levels of homology between the NP of influenza A and B viruses, the NP of influenza B virus

  14. Overexpression of a soybean nuclear localized type-III DnaJ domain-containing HSP40 reveals its roles in cell death and disease resistance.

    Science.gov (United States)

    Liu, Jian-Zhong; Whitham, Steven A

    2013-04-01

    Heat-shock proteins such as HSP70 and HSP90 are important molecular chaperones that play critical roles in biotic and abiotic stress responses; however, the involvement of their co-chaperones in stress biology remains largely uninvestigated. In a screen for candidate genes stimulating cell death in Glycine max (soybean), we transiently overexpressed full-length cDNAs of soybean genes that are highly induced during soybean rust infection in Nicotiana benthamiana leaves. Overexpression of a type-III DnaJ domain-containing HSP40 (GmHSP40.1), a co-chaperone of HSP70, caused hypersensitive response (HR)-like cell death. The HR-like cell death was dependent on MAPKKKα and WIPK, because silencing each of these genes suppressed the HR. Consistent with the presence of a nuclear localization signal (NLS) motif within the GmHSP40.1 coding sequence, GFP-GmHSP40.1 was exclusively present in nuclear bodies or speckles. Nuclear localization of GmHSP40.1 was necessary for its function, because deletion of the NLS or addition of a nuclear export signal abolished its HR-inducing ability. GmHSP40.1 co-localized with HcRed-SE, a protein involved in pri-miRNA processing, which has been shown to be co-localized with SR33-YFP, a protein involved in pre-mRNA splicing, suggesting a possible role for GmHSP40.1 in mRNA splicing or miRNA processing, and a link between these processes and cell death. Silencing GmHSP40.1 enhanced the susceptibility of soybean plants to Soybean mosaic virus, confirming its positive role in pathogen defense. Together, the results demonstrate a critical role of a nuclear-localized DnaJ domain-containing GmHSP40.1 in cell death and disease resistance in soybean. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

  15. Localization of Daucus carota NMCP1 to the nuclear periphery: the role of the N-terminal region and an NLS-linked sequence motif, RYNLRR, in the tail domain

    Science.gov (United States)

    Kimura, Yuta; Fujino, Kaien; Ogawa, Kana; Masuda, Kiyoshi

    2014-01-01

    Recent ultrastructural studies revealed that a structure similar to the vertebrate nuclear lamina exists in the nuclei of higher plants. However, plant genomes lack genes for lamins and intermediate-type filament proteins, and this suggests that plant-specific nuclear coiled-coil proteins make up the lamina-like structure in plants. NMCP1 is a protein, first identified in Daucus carota cells, that localizes exclusively to the nuclear periphery in interphase cells. It has a tripartite structure comprised of head, rod, and tail domains, and includes putative nuclear localization signal (NLS) motifs. We identified the functional NLS of DcNMCP1 (carrot NMCP1) and determined the protein regions required for localizing to the nuclear periphery using EGFP-fused constructs transiently expressed in Apium graveolens epidermal cells. Transcription was driven under a CaMV35S promoter, and the genes were introduced into the epidermal cells by a DNA-coated microprojectile delivery system. Of the NLS motifs, KRRRK and RRHK in the tail domain were highly functional for nuclear localization. Addition of the N-terminal 141 amino acids from DcNMCP1 shifted the localization of a region including these NLSs from the entire nucleus to the nuclear periphery. Using this same construct, the replacement of amino acids in RRHK or its preceding sequence, YNL, with alanine residues abolished localization to the nuclear periphery, while replacement of KRRRK did not affect localization. The sequence R/Q/HYNLRR/H, including YNL and the first part of the sequence of RRHK, is evolutionarily conserved in a subclass of NMCP1 sequences from many plant species. These results show that NMCP1 localizes to the nuclear periphery by a combined action of a sequence composed of R/Q/HYNLRR/H, NLS, and the N-terminal region including the head and a portion of the rod domain, suggesting that more than one binding site is implicated in localization of NMCP1. PMID:24616728

  16. Localization of Daucus carota NMCP1 to the nuclear periphery: the role of the N-terminal region and an NLS-linked sequence motif, RYNLRR, in the tail domain

    Directory of Open Access Journals (Sweden)

    Yuta eKimura

    2014-02-01

    Full Text Available Recent ultrastructural studies revealed that a structure similar to the vertebrate nuclear lamina exists in the nuclei of higher plants. However, plant genomes lack genes for lamins and intermediate-type filament proteins, and this suggests that plant-specific nuclear coiled-coil proteins make up the lamina-like structure in plants. NMCP1 is a protein, first identified in Daucus carota cells, that localizes exclusively to the nuclear periphery in interphase cells. It has a tripartite structure comprised of head, rod, and tail domains, and includes putative nuclear localization signal (NLS motifs. We identified the functional NLS of DcNMCP1 (carrot NMCP1 and determined the protein regions required for localizing to the nuclear periphery using EGFP-fused constructs transiently expressed in Apium graveolens epidermal cells. Transcription was driven under a CaMV35S promoter, and the genes were introduced into the epidermal cells by a DNA-coated microprojectile delivery system. Of the NLS motifs, KRRRK and RRHK in the tail domain were highly functional for nuclear localization. Addition of the N-terminal 141 amino acids from DcNMCP1 shifted the localization of a region including these NLSs from the entire nucleus to the nuclear periphery. Using this same construct, the replacement of amino acids in RRHK or its preceding sequence, YNL, with alanine residues abolished localization to the nuclear periphery, while replacement of KRRRK did not affect localization. The sequence R/Q/HYNLRR/H, including YNL and the first part of the sequence of RRHK, is evolutionarily conserved in a subclass of NMCP1 sequences from many plant species. These results show that NMCP1 localizes to the nuclear periphery by a combined action of a sequence composed of R/Q/HYNLRR/H, NLS, and the N-terminal region including the head and a portion of the rod domain, suggesting that more than one binding site is implicated in localization of NMCP1.

  17. The Arginine/Lysine-Rich Element within the DNA-Binding Domain Is Essential for Nuclear Localization and Function of the Intracellular Pathogen Resistance 1.

    Science.gov (United States)

    Yao, Kezhen; Wu, Yongyan; Chen, Qi; Zhang, Zihan; Chen, Xin; Zhang, Yong

    2016-01-01

    The mouse intracellular pathogen resistance 1 (Ipr1) gene plays important roles in mediating host immunity and previous work showed that it enhances macrophage apoptosis upon mycobacterium infection. However, to date, little is known about the regulation pattern of Ipr1 action. Recent studies have investigated the protein-coding genes and microRNAs regulated by Ipr1 in mouse macrophages, but the structure and the functional motif of the Ipr1 protein have yet to be explored. In this study, we analyzed the domains and functional motif of the Ipr1 protein. The resulting data reveal that Ipr1 protein forms a homodimer and that the Sp100-like domain mediates the targeting of Ipr1 protein to nuclear dots (NDs). Moreover, we found that an Ipr1 mutant lacking the classic nuclear localization signal (cNLS) also translocated into the nuclei, suggesting that the cNLS is not the only factor that directs Ipr1 nuclear localization. Additionally, mechanistic studies revealed that an arginine/lysine-rich element within the DNA-binding domain (SAND domain) is critical for Ipr1 binding to the importin protein receptor NPI-1, demonstrating that this element plays an essential role in mediating the nuclear localization of Ipr1 protein. Furthermore, our results show that this arginine/lysine-rich element contributes to the transcriptional regulation and apoptotic activity of Ipr1. These findings highlight the structural foundations of Ipr1 action and provide new insights into the mechanism of Ipr1-mediated resistance to mycobacterium.

  18. Collaboration of local government and experts responding to increase in environmental radiation level due to the nuclear disaster: focusing on their activities and latest radiological discussion

    International Nuclear Information System (INIS)

    Iimoto, T.; Nunokawa, J.; Fujii, H.; Takashima, R.; Hashimoto, M.; Fukuhara, T.; Yajima, T.; Matsuzawa, H.; Kurosawa, K.; Yanagawa, Y.; Someya, S.

    2015-01-01

    Activities were introduced in Kashiwa city in the Tokyo metropolitan area to correspond to the elevated environmental radiation level after the disaster of the Fukushima Daiichi nuclear power plant. These were based on a strong cooperation between local governments and experts. Ambient dose rate and radioactivity of foodstuff produced inside of the city have been monitored. Representative ambient dose rates around living environments have almost already become their original levels of the pre-accident because of the decontamination activity, natural washout and effective half-lives of radioactivity. The internal annual dose due to radioactive cesium under the policy of 'Local Production for Local Consumption' is estimated as extremely low comparing the variation range due to natural radioactivity. Systematic survey around a retention basin has been started. All of these latest monitoring data would be one of the core information for the policy making as well as a cost-benefit discussion and risk communication. (authors)

  19. Development and implementation of monitoring for the reactor core of unit No. 5 of the Novovoronezh nuclear plant by local parameters

    Science.gov (United States)

    Prytkov, A. N.; Tereshchenko, A. B.; Kravchenko, Yu. N.; Boldyrev, N. V.; Pozychaniuk, I. V.; Lisitsyn, D. I.; Golubev, E. I.

    2014-04-01

    In the course of upgrading the unit no. 5 reactor core of the Novovoronezh nuclear power plant, operational limits by local parameters, which limit the admissible linear power density and the relative power of fuel elements, were established. Due to applying modern computer technologies in systems of the in-core monitoring, the calculation of power density for all fuel elements in the real-time mode is implemented. To monitor the power density of fuel elements, the algorithm for determining the limiting linear power density is developed depending on the reactor core height and on the average nuclear fuel burnup. The admissible relative power of fuel elements is determined. In the course of the performed work, the excessive conservative limitations on nonuniformity of the reactor power density are excluded. The monitoring of power density by local parameters instead of indirect K q (fuel-assembly relative power) and K v (relative power of the fuel assembly section) made it possible to increase the fuel efficiency and to improve the economic parameters of fuel cycles of the unit no. 5 reactor core of the Novovoronezh nuclear power plant.

  20. Assessment of extreme hydrological conditions in the Bothnian Bay, Baltic Sea, and the impact of the nuclear power plant "Hanhikivi-1" on the local thermal regime

    Science.gov (United States)

    Dvornikov, Anton Y.; Martyanov, Stanislav D.; Ryabchenko, Vladimir A.; Eremina, Tatjana R.; Isaev, Alexey V.; Sein, Dmitry V.

    2017-04-01

    The results of the study aimed to assess the influence of future nuclear power plant Hanhikivi-1 upon the local thermal conditions in the Bothnian Bay in the Baltic Sea are presented. A number of experiments with different numerical models were also carried out in order to estimate the extreme hydro-meteorological conditions in the area of the construction. The numerical experiments were fulfilled both with analytically specified external forcing and with real external forcing for 2 years: a cold year (2010) and a warm year (2014). The study has shown that the extreme values of sea level and water temperature and the characteristics of wind waves and sea ice in the vicinity of the future nuclear power plant can be significant and sometimes catastrophic. Permanent release of heat into the marine environment from an operating nuclear power plant will lead to a strong increase in temperature and the disappearance of ice cover within a 2 km vicinity of the station. These effects should be taken into account when assessing local climate changes in the future.

  1. AHM1, a Novel Type of Nuclear Matrix–Localized, MAR Binding Protein with a Single AT Hook and a J Domain–Homologous Region

    Science.gov (United States)

    Morisawa, Gaku; Han-yama, Atsushi; Moda, Ichiro; Tamai, Atsushi; Iwabuchi, Masaki; Meshi, Tetsuo

    2000-01-01

    Interactions between the nuclear matrix and special regions of chromosomal DNA called matrix attachment regions (MARs) have been implicated in various nuclear functions. We have identified a novel protein from wheat, AT hook–containing MAR binding protein1 (AHM1), that binds preferentially to MARs. A multidomain protein, AHM1 has the special combination of a J domain–homologous region and a Zn finger–like motif (a J-Z array) and an AT hook. For MAR binding, the AT hook at the C terminus was essential, and an internal portion containing the Zn finger–like motif was additionally required in vivo. AHM1 was found in the nuclear matrix fraction and was localized in the nucleoplasm. AHM1 fused to green fluorescent protein had a speckled distribution pattern inside the nucleus. AHM1 is most likely a nuclear matrix component that functions between intranuclear framework and MARs. J-Z arrays can be found in a group of (hypothetical) proteins in plants, which may share some functions, presumably to recruit specific Hsp70 partners as co-chaperones. PMID:11041885

  2. A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity.

    Science.gov (United States)

    Lim, Bobae; Kim, Ah-young; Jun, Hee Jung; Kim, Jungho

    2013-12-15

    Human EMCs (extraskeletal myxoid chondrosarcomas) are soft tissue tumours characterized by specific chromosomal abnormalities. Recently, a proportion of EMCs were found to harbour a characteristic translocation, t(3;9)(q11-12;q22), involving the TFG (TRK-fused gene) at 3q11-12 and the TEC (translocated in extraskeletal chondrosarcoma) gene at 9q22. The present study used both in vitro and in vivo systems to show that the TFG-TEC protein self-associates, and that this is dependent upon the CC (coiled-coil) domain (amino acids 97-124), the AF1 (activation function 1) domain (amino acids 275-562) and the DBD (DNA-binding domain) (amino acids 563-655). The TFG-TEC protein also associated with a mutant NLS-TFG-TEC (AAAA) protein, which harbours mutations in the NLS (nuclear localization signal). Subcellular localization assays showed that the NLS mutant TFG-TEC (AAAA) protein interfered with the nuclear localization of wild-type TFG-TEC. Most importantly, the mutant protein inhibited TFG-TEC-mediated transcriptional activation in vivo. Thus mutations in the TFG-TEC NLS yield a dominant-negative protein. These results show that the biological functions of the TFG-TEC oncogene can be modulated by a dominant-negative mutant.

  3. Case-study session 2: Nuclear facilities and local information. The way we work with public relations at the Oskarshamn nuclear power plant

    International Nuclear Information System (INIS)

    Wahlberg, Lars-Goeran

    1989-01-01

    The Oskarshamn NPP is owned by OKG Aktiebolag, the only private company in Sweden operating NPPs. The site is situated 350 kilometres south of Stockholm, in the community of Oskarshamn with 30 000 inhabitants and in the county of Kalmar with about 250 000 inhabitants. OKG now owns and operates three BWRs of ABB Atom design, with a total net production of 15 TWh/year, i.e. 1 - 12% of the total electricity generation in Sweden. OKG also operates CLAB that is owned by SKB. On the site, SKB has now decided to build a hard-rock laboratory 500 metres down in the bedrock. OKG is the nuclear pioneer of Sweden, the first reactor has been in operation since 1972. Company policy has always been maximum open communication and encouraging the employees to engage themselves into debates about energy and nuclear and into social life as a whole. OKG also sponsors several cultural and sport events in Oskarshamn. The goal is to create confidence between society and the plant. Two different areas of influence are defined: organization of the information department taking care of both external and internal information which is considered an essential part of the work

  4. Local consequences and reactions to the closing down of nuclear reactors in Sweden, a KSO report, 1999

    International Nuclear Information System (INIS)

    Carlsson, T.

    2000-01-01

    The Swedish Government decision to close down the Barsebaeck-1 NPP resulted in a studi funded by the Organisation of Municipalities with Nuclear Operation (KSO). It was meant to evaluate the scenario if all nuclear reactors in Sweden were closed down by year 2005 or if the phase out took place in an orderly manner after 40 years i.e. between 2012 and 2025. Most important consequence would be the loss of approximately 8000 jobs mostly in five municipalities concerned. This should also be regarded from a qualitative viewpoint, namely as a significant loss of labour opportunities for highly educated personnel. The estimates show in addition, a dramatic increase in migration from nuclear power plant municipalities of particularly younger population. In conclusion it is mentioned that Sweden still has 11 nuclear reactors in operation supplying 50% of the electricity used in the country. If the government would demand immediate closure of all reactors, Sweden would be a dark and cold country at least during the six months of winter

  5. Close or renew? Factors affecting local community support for rebuilding nuclear power plants in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil; Malý, Jiří

    2017-01-01

    Roč. 140, č. 140 (2017), s. 134-143 ISSN 0301-4215 R&D Projects: GA ČR GA16-04483S Institutional support: RVO:68145535 Keywords : nuclear power plants * rebuilding * community acceptance Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 4.140, year: 2016 http://www.sciencedirect.com/science/article/pii/S0301421517300599

  6. SU-E-J-61: Electrodynamics and Nano-Scale Fluid Dynamics in Protein Localization of Nuclear Pore Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, J; Gatenby, R [Moffitt Cancer Research Institute, Tampa, FL (United States)

    2014-06-01

    Purpose: To develop a simulation to catalyze a reevaluation of common assumptions about 3 dimensional diffusive processes and help cell biologists gain a more nuanced, intuitive understanding of the true physical hurdles of protein signaling cascades. Furthermore, to discuss the possibility of intracellular electrodynamics as a critical, unrecognized component of cellular biology and protein dynamics that is necessary for optimal information flow from the cell membrane to the nucleus. Methods: The Unity 3D gaming physics engine was used to build an accurate virtual scale model of the cytoplasm within a few hundred nanometers of the nuclear membrane. A cloud of simulated pERK proteins is controlled by the physics simulation, where diffusion is based on experimentally measured values and the electrodynamics are based on theoretical nano-fluid dynamics. The trajectories of pERK within the cytoplasm and through the 1250 nuclear pores on the nuclear surface is recorded and analyzed. Results: The simulation quickly demonstrates that pERKs moving solely by diffusion will rarely locate and come within capture distance of a nuclear pore. The addition of intracellular electrodynamics between charges on the nuclear pore complexes and on pERKs increases the number of successful translocations by allowing the electro-physical attractive effects to draw in pERKs from the cytoplasm. The effects of changes in intracellular shielding ion concentrations allowed for estimation of the “capture radius” under varying conditions. Conclusion: The simulation allows a shift in perspective that is paramount in attempting to communicate the scale and dynamics of intracellular protein cascade mechanics. This work has allowed researchers to more fully understand the parameters involved in intracellular electrodynamics, such as shielding anion concentration and protein charge. As these effects are still far below the spatial resolution of currently available measurement technology this

  7. Low probability of intercept-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems

    Science.gov (United States)

    Shi, Chenguang; Salous, Sana; Wang, Fei; Zhou, Jianjiang

    2016-12-01

    In this paper, we investigate the problem of low probability of intercept (LPI)-based adaptive radar waveform optimization in signal-dependent clutter for joint radar and cellular communication systems, where the radar system optimizes the transmitted waveform such that the interference caused to the cellular communication systems is strictly controlled. Assuming that the precise knowledge of the target spectra, the power spectral densities (PSDs) of signal-dependent clutters, the propagation losses of corresponding channels and the communication signals is known by the radar, three different LPI based criteria for radar waveform optimization are proposed to minimize the total transmitted power of the radar system by optimizing the multicarrier radar waveform with a predefined signal-to-interference-plus-noise ratio (SINR) constraint and a minimum required capacity for the cellular communication systems. These criteria differ in the way the communication signals scattered off the target are considered in the radar waveform design: (1) as useful energy, (2) as interference or (3) ignored altogether. The resulting problems are solved analytically and their solutions represent the optimum power allocation for each subcarrier in the multicarrier radar waveform. We show with numerical results that the LPI performance of the radar system can be significantly improved by exploiting the scattered echoes off the target due to cellular communication signals received at the radar receiver.

  8. Nuclear Localization of the Autism Candidate Gene Neurobeachin and Functional Interaction with the NOTCH1 Intracellular Domain Indicate a Role in Regulating Transcription.

    Science.gov (United States)

    Tuand, Krizia; Stijnen, Pieter; Volders, Karolien; Declercq, Jeroen; Nuytens, Kim; Meulemans, Sandra; Creemers, John

    2016-01-01

    Neurobeachin (NBEA) is an autism spectrum disorders (ASD) candidate gene. NBEA deficiency affects regulated secretion, receptor trafficking, synaptic architecture and protein kinase A (PKA)-mediated phosphorylation. NBEA is a large multidomain scaffolding protein. From N- to C-terminus, NBEA has a concanavalin A-like lectin domain flanked by armadillo repeats (ACA), an A-kinase anchoring protein domain that can bind to PKA, a domain of unknown function (DUF1088) and a BEACH domain, preceded by a pleckstrin homology-like domain and followed by WD40 repeats (PBW). Although most of these domains mediate protein-protein interactions, no interaction screen has yet been performed. Yeast two-hybrid screens with the ACA and PBW domain modules of NBEA gave a list of interaction partners, which were analyzed for Gene Ontology (GO) enrichment. Neuro-2a cells were used for confocal microscopy and nuclear extraction analysis. NOTCH-mediated transcription was studied with luciferase reporter assays and qRT-PCR, combined with NBEA knockdown or overexpression. Both domain modules showed a GO enrichment for the nucleus. PBW almost exclusively interacted with transcription regulators, while ACA interacted with a number of PKA substrates. NBEA was partially localized in the nucleus of Neuro-2a cells, albeit much less than in the cytoplasm. A nuclear localization signal was found in the DUF1088 domain, which was shown to contribute to the nuclear localization of an EGFP-DPBW fusion protein. Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated. Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for neural development.

  9. Nuclear localization of CD26 induced by a humanized monoclonal antibody inhibits tumor cell growth by modulating of POLR2A transcription.

    Directory of Open Access Journals (Sweden)

    Kohji Yamada

    Full Text Available CD26 is a type II glycoprotein known as dipeptidyl peptidase IV and has been identified as one of the cell surface markers associated with various types of cancers and a subset of cancer stem cells. Recent studies have suggested that CD26 expression is involved in tumor growth, tumor invasion, and metastasis. The CD26 is shown in an extensive intracellular distribution, ranging from the cell surface to the nucleus. We have previously showed that the humanized anti-CD26 monoclonal antibody (mAb, YS110, exhibits inhibitory effects on various cancers. However, functions of CD26 on cancer cells and molecular mechanisms of impaired tumor growth by YS110 treatment are not well understood. In this study, we demonstrated that the treatment with YS110 induced nuclear translocation of both cell-surface CD26 and YS110 in cancer cells and xenografted tumor. It was shown that the CD26 and YS110 were co-localized in nucleus by immunoelectron microscopic analysis. In response to YS110 treatment, CD26 was translocated into the nucleus via caveolin-dependent endocytosis. It was revealed that the nuclear CD26 interacted with a genomic flanking region of the gene for POLR2A, a subunit of RNA polymerase II, using a chromatin immunoprecipitation assay. This interaction with nuclear CD26 and POLR2A gene consequently led to transcriptional repression of the POLR2A gene, resulting in retarded cell proliferation of cancer cells. Furthermore, the impaired nuclear transport of CD26 by treatment with an endocytosis inhibitor or expressions of deletion mutants of CD26 reversed the POLR2A repression induced by YS110 treatment. These findings reveal that the nuclear CD26 functions in the regulation of gene expression and tumor growth, and provide a novel mechanism of mAb-therapy related to inducible translocation of cell-surface target molecule into the nucleus.

  10. Depth determination and source characteristics of the North Korean Nuclear Tests (2006, 2009, 2013 and 2016) using local and teleseismic arrays

    Science.gov (United States)

    Kim, S. G.

    2016-12-01

    Depth determination and source characteristics of the North Korea Nuclear tests (2006, 2009, 2013 and 2016) using seismic arrays with azimuthal optium coverage So Gu Kim1,*, Yefim Gitterman2, Václav Vavryčuk3 and Seoung-kyu Lee1 1Korea Seismological Institute, Goyang 10332, Republic of Korea 2Seismology Division, Geophysical Institute of Israel, P.O.B. 182, Lod 71100, Israel 3Institute of Geophysics, Academy of Sciences, Prague 14100, Czech Republic Abstract The source depths for the North Korean nuclear tests (2006, 2009, 2013 and 2016) were determined using depth phases (pP, sP, pPn and sPn) and Rayleigh wave spectra from local and global arrays. The emplacement depths were estimated at 2.21, 2.10, 2.10 and 2.08 km for the 2006, 2009. 2013 and 2016 nuclear tests respectively. It was also found that the mechanism of the 2006 test generated roughly a reverse faulting accompanying mostly Rayleigh waves, whereas the 2009 and 2013 tests were an oblique-reverse faulting generating SH and Love waves as well as Rayleigh waves. The generation of SH and Love waves for the 2009 and 2013 nuclear tests was attributed to not only release of tectonic stress but also other factors such as relaxation of cavity fractures, source configuration and source mechanism. We infer that the 2009, 2013 and 2016 tests must have well contained nuclear debris through long winding horizontal drifts in the light of the absence of radioisotopes to the atmosphere compared with 2006 test which may have been conducted in the vertical shift as a vertically distributed source. ______________________________________________ *Corresponding author: So Gu Kim (sogukim@hanmail.net)

  11. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation.

    Directory of Open Access Journals (Sweden)

    Walter Rossmanith

    Full Text Available RNase Z is an endonuclease responsible for the removal of 3' extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase Z(L encoded by ELAC2, and a short form (RNase Z(S; ELAC1. We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase Z(S was found in the cytosol, whereas RNase Z(L localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase Z(L. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase Z(L is the enzyme involved in both, nuclear and mitochondrial tRNA 3' end maturation.

  12. Nuclear Localization of the C1 Factor (Host Cell Factor) in Sensory Neurons Correlates with Reactivation of Herpes Simplex Virus from Latency

    Science.gov (United States)

    Kristie, Thomas M.; Vogel, Jodi L.; Sears, Amy E.

    1999-02-01

    After a primary infection, herpes simplex virus is maintained in a latent state in neurons of sensory ganglia until complex stimuli reactivate viral lytic replication. Although the mechanisms governing reactivation from the latent state remain unknown, the regulated expression of the viral immediate early genes represents a critical point in this process. These genes are controlled by transcription enhancer complexes whose assembly requires and is coordinated by the cellular C1 factor (host cell factor). In contrast to other tissues, the C1 factor is not detected in the nuclei of sensory neurons. Experimental conditions that induce the reactivation of herpes simplex virus in mouse model systems result in rapid nuclear localization of the protein, indicating that the C1 factor is sequestered in these cells until reactivation signals induce a redistribution of the protein. The regulated localization suggests that C1 is a critical switch determinant of the viral lytic-latent cycle.

  13. Characterization and intracellular localization of the Epstein-Barr virus protein BFLF2: interactions with BFRF1 and with the nuclear lamina.

    Science.gov (United States)

    Gonnella, Roberta; Farina, Antonella; Santarelli, Roberta; Raffa, Salvatore; Feederle, Regina; Bei, Roberto; Granato, Marisa; Modesti, Andrea; Frati, Luigi; Delecluse, Henri-Jacques; Torrisi, Maria Rosaria; Angeloni, Antonio; Faggioni, Alberto

    2005-03-01

    We have reported in the accompanying paper that the BFRF1 protein of Epstein-Barr virus (EBV) is important for efficient primary viral envelopment and egress (A. Farina, R. Feederle, S. Raffa, R. Gonnella, R. Santarelli, L. Frati, A. Angeloni, M. R. Torrisi, A. Faggioni, and H.-J. Delecluse, J. Virol. 79:3703-3712). Here we describe the characterization of the product of the EBV BFLF2 gene, which belongs to a family of conserved herpesviral genes which include the UL31 genes of herpes simplex virus and of pseudorabies virus and whose products are known to interact with UL34, the positional homolog of BFRF1. BFLF2 is an early transcript and is expressed in a variety of cell lines upon EBV lytic cycle activation. Western blotting of purified virion preparations showed that BFLF2 is a component of intracellular virions but is absent from mature extracellular virions. Coimmunoprecipitation experiments indicated that BFLF2 interacts with BFRF1, which was confirmed by immunofluorescence confocal microscopy showing that the two proteins colocalize on the nuclear membrane not only upon cotransfection in epithelial cells but also during viral replication. In cells carrying an EBV mutant with the BFRF1 gene deleted (293-BFRF1-KO cells) BFLF2 expression was low, and it was restored to wild-type levels upon treatment of the cells with the proteasome inhibitor MG132. Furthermore, recomplementing the 293-BFRF1-KO cells by BFRF1 transfection restored BFLF2 expression to the wild-type level. In addition, when expressed alone BFLF2 was localized diffusely inside the nucleus, whereas in the presence of BFRF1 the two proteins colocalized at the nuclear rim. Finally, 293 epithelial cells transfected with either protein or cotransfected were analyzed by electron microscopy to investigate potential alterations in the morphology of the nuclear membrane. The ultrastructural analysis revealed that (i) BFRF1 caused duplications of the nuclear membrane, similar to those reported to occur

  14. Dynamic Changes in the Protein Localization in the Nuclear Environment in Pancreatic β-Cell after Brief Glucose Stimulation

    DEFF Research Database (Denmark)

    Kang, Taewook; Jensen, Pia; Solovyeva, Vita

    2018-01-01

    Characterization of molecular mechanisms underlying pancreatic β-cell function in relation to glucose-stimulated insulin secretion is incomplete, especially with respect to global response in the nuclear environment. We focus on the characterization of proteins in the nuclear environment of β...... or export to/from the nucleus to the cytoplasm. Putative insulin mRNA transcription-associated factors were identified among the regulated proteins, and they were cross-validated by Western blotting and confocal immunofluorescence imaging. Collectively, our data suggest that protein translocation between...... the nucleus and the cytoplasm is an important process, highly involved in the initial molecular mechanism underlying glucose-stimulated insulin secretion in pancreatic β-cells....

  15. Close or renew? Factors affecting local community support for rebuilding nuclear power plants in the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil; Malý, Jiří

    2017-01-01

    Roč. 140, č. 140 (2017), s. 134-143 ISSN 0301-4215 R&D Projects: GA ČR GA16-04483S Institutional support: RVO:68145535 Keywords : nuclear power plants * rebuilding * community acceptance Subject RIV: DE - Earth Magnetism, Geodesy, Geography OBOR OECD: Cultural and economic geography Impact factor: 4.140, year: 2016 http://www.sciencedirect.com/science/article/pii/S0301421517300599

  16. Distance matters. Assessing socioeconomic impacts of the Dukovany nuclear power plant in the Czech Republic: Local perceptions and statistical evidence

    Czech Academy of Sciences Publication Activity Database

    Frantál, Bohumil; Malý, Jiří; Ouředníček, M.; Nemeškal, J.

    2016-01-01

    Roč. 24, č. 1 (2016), s. 2-13 ISSN 1210-8812 R&D Projects: GA MŠk(CZ) EE2.3.20.0025 Institutional support: RVO:68145535 Keywords : nuclear power plant impacts * spatial analysis * risk perceptions Subject RIV: DE - Earth Magnetism, Geodesy, Geography Impact factor: 2.149, year: 2016 http://www.degruyter.com/view/j/mgr.2016.24.issue-1/mgr-2016-0001/mgr-2016-0001.xml?format=INT

  17. One pot synthesis of highly luminescent polyethylene glycol anchored carbon dots functionalized with a nuclear localization signal peptide for cell nucleus imaging

    Science.gov (United States)

    Yang, Lei; Jiang, Weihua; Qiu, Lipeng; Jiang, Xuewei; Zuo, Daiying; Wang, Dongkai; Yang, Li

    2015-03-01

    Strong blue fluorescent polyethylene glycol (PEG) anchored carbon nitride dots (CDs@PEG) with a high quantum yield (QY) of 75.8% have been synthesized by a one step hydrothermal treatment. CDs with a diameter of ca. 6 nm are well dispersed in water and present a graphite-like structure. Photoluminescence (PL) studies reveal that CDs display excitation-dependent behavior and are stable under various test conditions. Based on the as-prepared CDs, we designed novel cell nucleus targeting imaging carbon dots functionalized with a nuclear localization signal (NLS) peptide. The favourable biocompatibilities of CDs and NLS modified CDs (NLS-CDs) are confirmed by in vitro cytotoxicity assays. Importantly, intracellular localization experiments in MCF7 and A549 cells demonstrate that NLS-CDs could be internalized in the nucleus and show blue light, which indicates that CDs may serve as cell nucleus imaging probes.Strong blue fluorescent polyethylene glycol (PEG) anchored carbon nitride dots (CDs@PEG) with a high quantum yield (QY) of 75.8% have been synthesized by a one step hydrothermal treatment. CDs with a diameter of ca. 6 nm are well dispersed in water and present a graphite-like structure. Photoluminescence (PL) studies reveal that CDs display excitation-dependent behavior and are stable under various test conditions. Based on the as-prepared CDs, we designed novel cell nucleus targeting imaging carbon dots functionalized with a nuclear localization signal (NLS) peptide. The favourable biocompatibilities of CDs and NLS modified CDs (NLS-CDs) are confirmed by in vitro cytotoxicity assays. Importantly, intracellular localization experiments in MCF7 and A549 cells demonstrate that NLS-CDs could be internalized in the nucleus and show blue light, which indicates that CDs may serve as cell nucleus imaging probes. Electronic supplementary information (ESI) available: The formulation of PEGylation CD optimization procedure, Table S1 and Fig. S1-S7. See DOI: 10.1039/c5nr01080

  18. Corrosion of zirconium alloys in nuclear reactors: A model for irradiation induced enhancement by local radiolysis in the porous oxide

    International Nuclear Information System (INIS)

    Lemaignan, C.; Salot, R.

    1997-01-01

    An analysis has been undertaken of the various cases of local enhancement of corrosion rate of zirconium alloys under irradiation. It is observed that in most cases a strong emission of energetic β - is present leading to a local energy deposition rate higher than the core average. This suggests that the local transient radiolytic oxidizing species produced in the coolant by the β - particles could contribute to corrosion enhancement, by increasing the local corrosion potential. This process is applicable to the local enhanced corrosion found in front of stainless steels structural parts, due to the contribution of Mn, and in front of Pt inserts or Cu-rich cruds. It explains also the irradiation corrosion enhancement of Cu-Zr alloys. Enhanced corrosion around neutron absorbing material is explained similarly by pair production from conversion of high energy capture photons in the cladding, leading to energetic electrons. The same process was found to be active with other highly ionizing species like α from Ni-rich alloys and fission products in homogeneous reactors. Due to the changes induced by the irradiation intensity on the concentration of the radiolytic species, the coolant chemistry, that controls the boundary conditions for oxide growth, has to be analyzed with respect to the local value of the energy deposition rate. An analysis has been undertaken which shows that, in a porous media, the water is exposed to a higher intensity than bulk water. This leads to a higher concentration of oxidizing radiolytic species at the root of the cracks of the porous oxide, and increases the corrosion rate under irradiation. This mechanism, deduced from the explanation proposed for localized irradiation enhanced corrosion, can be extended to the whole reactor core, where the general enhancement of Zr alloys corrosion under irradiation could be attributed to the general radiolysis in the porous zirconia. (author). 18 refs, 3 figs, 3 tabs

  19. The Site Selected. The Local Decision-Making Regarding the Siting of the Spent Nuclear Fuel Repository in Olkiluoto

    International Nuclear Information System (INIS)

    Kojo, Matti

    2006-01-01

    In May 1999 Posiva, the company responsible for the final disposal of spent nuclear fuel in Finland, suggested that the Finnish Government considers only Olkiluoto in Eurajoki in its application of a decision in principle to be a final disposal site. In January 2000 the municipal council of Eurajoki made a positive statement on the decision in principle. The Government made the decision in principle in Dec 2000, and the Parliament ratified the decision in May 2001. The paper is focused on the decision making of Eurajoki municipality regarding the siting of the spent nuclear fuel repository. The paper shows how the interaction between the representatives of the candidate municipality and the nuclear energy industry was the crucial factor in the decision-making. Eurajoki serves as an example, in where the parties reached an agreement of the compensations for the final disposal repository. The negotiations between the Eurajoki municipality and the nuclear energy industry in reaching a positive decision are analysed from the beginning of the 1980s. The main emphasis is however on the years 1996-99, when the nuclear energy industry negotiated with the municipality on the compensation for the final disposal repository. The loss of income was an important reason why some of the councillors of Eurajoki were interested in having the final disposal repository in Olkiluoto. The industry's problem on the other hand was to safeguard the final disposal site. From the TVO's angle Olkiluoto was a potential final disposal site for example for its limited need for transport and for the existing infrastructure. The company used the financial benefits of the project as its trump card. The attitude of Eurajoki municipality to the final disposal of spent nuclear fuel turned positive with the Olkiluoto vision in December 1998, when still five years earlier the municipal council was prepared to act and prevent the final disposal. The future image presented by the municipality now matched

  20. Arginine-rich cross-linking peptides with different SV40 nuclear localization signal content as vectors for intranuclear DNA delivery.

    Science.gov (United States)

    Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton

    2017-11-01

    The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP4 and ICP0

    International Nuclear Information System (INIS)

    Lengyel, Joy; Strain, Anna K.; Perkins, Keith D.; Rice, Stephen A.

    2006-01-01

    It was previously shown that herpes simplex virus type 1 (HSV-1) is sensitive to leptomycin B (LMB), an inhibitor of nuclear export factor CRM1, and that a single methionine to threonine change at residue 50 (M50T) of viral immediate-early (IE) protein ICP27 can confer LMB resistance. In this work, we show that deletion of residues 21-63 from ICP27 can also confer LMB resistance. We further show that neither the M50T mutation nor the presence of LMB affects the nuclear shuttling activity of ICP27, suggesting that another function of ICP27 determines LMB resistance. A possible clue to this function emerged when it was discovered that LMB treatment of HSV-1-infected cells dramatically enhances the cytoplasmic accumulation of two other IE proteins, ICP0 and ICP4. This effect is completely dependent on ICP27 and is reversed in cells infected with LMB-resistant mutants. Moreover, LMB-resistant mutations in ICP27 enhance the nuclear localization of ICP0 and ICP4 even in the absence of LMB, and this effect can be discerned in transfected cells. Thus, the same amino (N)-terminal region of ICP27 that determines sensitivity to LMB also enhances ICP27's previously documented ability to promote the cytoplasmic accumulation of ICP4 and ICP0. We speculate that ICP27's effects on ICP4 and ICP0 may contribute to HSV-1 LMB sensitivity

  2. Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect

    Directory of Open Access Journals (Sweden)

    Sakamoto Michiie

    2009-06-01

    Full Text Available Abstract Background CD26 is a type II, cell surface glycoprotein known as dipeptidyl peptidase (DPP IV. Previous studies have revealed CD26 expression in T cell leukemia/lymphoma and malignant mesothelioma, and an inhibitory effect of anti-CD26 monoclonal antibody (mAb against the growth of CD26+ cancer cells in vitro and in vivo. The function of CD26 in tumor development is unknown and the machinery with which the CD26 mAb induces its anti-tumor effect remains uncharacterized. Results The localization of CD26 in the nucleus of T cell leukemia/lymphoma cells and mesothelioma cells was shown by biochemical and immuno-electron microscopic analysis. The DPPIV enzyme activity was revealed in the nuclear fraction of T cell leukemia/lymphoma cells. These expressions of intra-nuclear CD26 were augmented by treatment with the CD26 mAb, 1F7, with anti-tumor effect against the CD26+ T cell leukemia/lymphoma cells. In contrast, the CD26 mAb, 5F8, without anti-tumor effect, did not augment CD26 expressions in the nucleus. Biotin-labeled, cell surface CD26 translocated into the nucleus constantly, and this translocation was enhanced with 1F7 treatment but not with 5F8. Conclusion These results indicate that the intra-nuclear CD26 which moves from plasma membrane may play certain roles in cell growth of human cancer cells.

  3. A proposal on restart rule of nuclear power plants with piping having local wall thinning subjected to an earthquake. Former part. Aiming at further application

    International Nuclear Information System (INIS)

    Urabe, Yoshio

    2011-01-01

    Restart rule of nuclear power plants (NPPs) with piping having local wall thinning subjected to an earthquake was proposed taking account of local wall thinning, seismic effects and restart of NPPs with applicability of 'Guidelines for NPP Response to an Earthquake (EPRI NP-6695)' in Japan. Japan Earthquake Damage Intensity Scale (JEDIS) and Earthquake Ground Motion Level (EGML) were introduced. JEDIS was classified into four scales obtained from damage level of components and structures of NPPs subjected to an earthquake, while EGML was divided into four levels by safe shutdown earthquake ground motion (So), elastic design earthquake ground motion (Sd) and design earthquake ground motion (Ss). Combination of JEDIS and EGML formulated 4 x 4 matrix and determined detailed conditions of restart of NPPs. As a response to an earthquake, operator walk inspections and evaluation of earthquake ground motion were conducted to know the level of JEDIS. JEDIS level requested respective allowable conditions of restart of NPP, which were scale level dependent and consisted of weighted combination of damage inspection (operator walk inspections, focused inspections/tests and expanded inspections), integrity evaluation and repair/replacement. If JEDIS were assigned greater than 3 with expanded inspections, inspection of piping with local wall thinning, its integrity evaluation and repair/replacement if necessary were requested. Inspection and evaluation of piping with local wall thinning was performed based on JSME or ASME codes. Detailed work flow charts were presented. Carbon steel piping and elbow was chosen for evaluation. (T. Tanaka)

  4. The Cell Death Triggered by the Nuclear Localized RxLR Effector PITG_22798 from Phytophthora infestans Is Suppressed by the Effector AVR3b.

    Science.gov (United States)

    Wang, Hongyang; Ren, Yajuan; Zhou, Jing; Du, Juan; Hou, Juan; Jiang, Rui; Wang, Haixia; Tian, Zhendong; Xie, Conghua

    2017-02-14

    Phytopathogenic oomycetes, such as Phytophthora infestans , potentially secrete many RxLR effector proteins into plant cells to modulate plant immune responses and promote colonization. However, the molecular mechanisms by which these RxLR effectors suppress plant immune responses are largely unknown. Here we describe an RxLR effector PITG_22798 (Gene accession: XM_002998349) that was upregulated during early infection of potato by P. infestans . By employment of agroinfiltration, we observed that PITG_22798 triggers cell death in Nicotiana benthamiana . Confocal microscopic examination showed that PITG_22798-GFP (Green Fluorescent Protein) located in the host nucleus when expressed transiently in N. benthamiana leaves. A nuclear localization signal (NLS) domain of PITG_22798 is important for nuclear localization and cell death-inducing activity. Sequence alignment and transient expression showed that PITG_22798 from diverse P. infestans isolates are conserved, and transient expression of PITG_22798 enhances P. infestans colonization of N. benthamiana leaves, which suggests that PITG_22798 contributes to P. infestans infection. PITG_22798 -triggered cell death is dependent on SGT1-mediated signaling and is suppressed by the P. infestans avirulence effector 3b (AVR3b). The present research provides a clue for further investigation of how P. infestans effector PITG_22798 associates with and modulates host immunity.

  5. Nuclear localization of lymphocyte-specific protein tyrosine kinase (Lck) and its role in regulating LIM domain only 2 (Lmo2) gene

    Energy Technology Data Exchange (ETDEWEB)

    Venkitachalam, Srividya; Chueh, Fu-Yu [Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064 (United States); Yu, Chao-Lan, E-mail: chaolan.yu@rosalindfranklin.edu [Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064 (United States)

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer Lmo2 expression is elevated in Lck-transformed cells. Black-Right-Pointing-Pointer Both endogenous and exogenous Lck localize in the nucleus. Black-Right-Pointing-Pointer Nuclear Lck is active in Lck-transformed cells. Black-Right-Pointing-Pointer Lck binds to the promoter region of Lmo2 gene in vivo. Black-Right-Pointing-Pointer In contrast to JAK2, Lck does not increase histone H3 phosphorylation on Tyr 41. -- Abstract: LIM domain only protein 2 (Lmo2) is a transcription factor that plays a critical role in the development of T-acute lymphoblastic leukemia (T-ALL). A previous report established a link between Lmo2 expression and the nuclear presence of oncogenic Janus kinase 2 (JAK2), a non-receptor protein tyrosine kinase. The oncogenic JAK2 kinase phosphorylates histone H3 on Tyr 41 that leads to the relief of Lmo2 promoter repression and subsequent gene expression. Similar to JAK2, constitutive activation of lymphocyte-specific protein tyrosine kinase (Lck) has been implicated in lymphoid malignancies. However, it is not known whether oncogenic Lck regulates Lmo2 expression through a similar mechanism. We show here that Lmo2 expression is significantly elevated in T cell leukemia LSTRA overexpressing active Lck kinase and in HEK 293 cells expressing oncogenic Y505FLck kinase. Nuclear localization of active Lck kinase was confirmed in both Lck-transformed cells by subcellular fractionation and immunofluorescence microscopy. More importantly, in contrast to oncogenic JAK2, oncogenic Lck kinase does not result in significant increase in histone H3 phosphorylation on Tyr 41. Instead, chromatin immunoprecipitation experiment shows that oncogenic Y505FLck kinase binds to the Lmo2 promoter in vivo. This result raises the possibility that oncogenic Lck may activate Lmo2 promoter through direct interaction.

  6. Quantitative and subcellular localization analysis of the nuclear isoform dUTP pyrophosphatase in alkylating agent-induced cell responses

    International Nuclear Information System (INIS)

    Hu, Xiaolan; Yu, Yingnian; Li, Qian; Wu, Danxiao; Tan, Zhengning; Wang, Cheng; Wang, Jvping; Wu, Meiping

    2011-01-01

    Highlights: → MNNG-induced appearance of DUT-N in the extracellular fluid has cellular specificity. → MNNG alters the subcellular distribution of DUT-N in human cells in different ways. → DUT-N may be a potential biomarker to assess the risk of alkylating agents exposure. -- Abstract: Our previous proteome analysis showed that the nuclear isoform of dUTP pyrophosphatase (DUT-N) was identified in the culture medium of human amnion FL cells after exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These results suggest that DUT-N may be a potential early biomarker to assess the risk of alkylating agents exposure. DUT-N is one of the two isoforms of deoxyuridine triphosphate nucleotidohydrolase (dUTPase). Our current knowledge of DUT-N expression in human cells is very limited. In the current study, we first investigated the appearance of DUT-N in the culture medium of different human cell lines in response to a low concentration of MNNG exposure. We verified that the MNNG-induced appearance of DUT-N in the extracellular environment is cell-specific. Western blot analysis confirmed that the intracellular DUT-N changes responded to MNNG in a concentration-dependent and cell-specific manner. Furthermore, subcellular fraction experiments showed that 0.25 μM MNNG treatment dramatically increased the DUT-N expression levels in the cytoplasmic extracts prepared from both FL and HepG2 cells, increased DUT-N levels in nuclear extracts prepared from HepG2 cells, and decreased DUT-N levels in nuclear extracts from FL cells. Morphological studies using immunofluorescence showed that a low concentration of MNNG could alter the distribution of DUT-N in FL and HepG2 cells in different ways. Taken together, these studies indicate a role of DUT-N in alkylating agent-induced cell responses.

  7. Specific nuclear localizing sequence directs two myosin isoforms to the cell nucleus in calmodulin-sensitive manner

    Czech Academy of Sciences Publication Activity Database

    Dzijak, Rastislav; Yildirim, Sukriye; Kahle, Michal; Novák, Petr; Hnilicová, Jarmila; Venit, Tomáš; Hozák, Pavel

    2012-01-01

    Roč. 7, č. 1 (2012), e30529 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GA204/07/1592; GA ČR(CZ) GD204/09/H084; GA ČR GAP305/11/2232; GA MŠk LC545; GA MŠk(CZ) LC06063 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : NM1 * nuclear import * NLS * calmodulin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  8. Deletion of the nuclear localization sequences and C-terminus of PTHrP impairs embryonic mammary development but also inhibits PTHrP production.

    Directory of Open Access Journals (Sweden)

    Kata Boras-Granic

    Full Text Available Parathyroid hormone-related protein (PTHrP can be secreted from cells and interact with its receptor, the Type 1 PTH/PTHrP Receptor (PTHR1 in an autocrine, paracrine or endocrine fashion. PTHrP can also remain inside cells and be transported into the nucleus, where its functions are unclear, although recent experiments suggest that it may broadly regulate cell survival and senescence. Disruption of either the PTHrP or PTHR1 gene results in many abnormalities including a failure of embryonic mammary gland development in mice and in humans. In order to examine the potential functions of nuclear PTHrP in the breast, we examined mammary gland development in PTHrP (1-84 knock-in mice, which express a mutant form of PTHrP that lacks the C-terminus and nuclear localization signals and which can be secreted but cannot enter the nucleus. Interestingly, we found that PTHrP (1-84 knock-in mice had defects in mammary mesenchyme differentiation and mammary duct outgrowth that were nearly identical to those previously described in PTHrP-/- and PTHR1-/- mice. However, the mammary buds in PTHrP (1-84 knock-in mice had severe reductions in mutant PTHrP mRNA levels, suggesting that the developmental defects were due to insufficient production of PTHrP by mammary epithelial cells and not loss of PTHrP nuclear function. Examination of the effects of nuclear PTHrP in the mammary gland in vivo will require the development of alternative animal models.

  9. Study of the influence of central nuclear power plants at Valdaliga (Civitavecchia) on the chemical composition of local rain

    International Nuclear Information System (INIS)

    Bargagli, A.; Morabito, R.; Basili, N.; Tidei, F.

    1989-05-01

    Data from a wet deposition sampling over the area collocated nearby Civitavecchia power plants are here presented and discussed. In order to establish the possible influence of the power plants emission on the chemical composition of the rain collected, the experimental data have been correlated with synoptic and local meteorological conditions. (author)

  10. Modelling the local atomic structure of molybdenum in nuclear waste glasses with ab initio molecular dynamics simulations.

    Science.gov (United States)

    Konstantinou, Konstantinos; Sushko, Peter V; Duffy, Dorothy M

    2016-09-21

    The nature of chemical bonding of molybdenum in high level nuclear waste glasses has been elucidated by ab initio molecular dynamics simulations. Two compositions, (SiO 2 ) 57.5 -(B 2 O 3 ) 10 -(Na 2 O) 15 -(CaO) 15 -(MoO 3 ) 2.5 and (SiO 2 ) 57.3 -(B 2 O 3 ) 20 -(Na 2 O) 6.8 -(Li 2 O) 13.4 -(MoO 3 ) 2.5 , were considered in order to investigate the effect of ionic and covalent components on the glass structure and the formation of the crystallisation precursors (Na 2 MoO 4 and CaMoO 4 ). The coordination environments of Mo cations and the corresponding bond lengths calculated from our model are in excellent agreement with experimental observations. The analysis of the first coordination shell reveals two different types of molybdenum host matrix bonds in the lithium sodium borosilicate glass. Based on the structural data and the bond valence model, we demonstrate that the Mo cation can be found in a redox state and the molybdate tetrahedron can be connected with the borosilicate network in a way that inhibits the formation of crystalline molybdates. These results significantly extend our understanding of bonding in Mo-containing nuclear waste glasses and demonstrate that tailoring the glass composition to specific heavy metal constituents can facilitate incorporation of heavy metals at high concentrations.

  11. Influence of local UV-micro-irradiation on nuclear apparatus and cytoplasm of a ciliate Paramecium caudatum

    International Nuclear Information System (INIS)

    Fokin, S.I.; Osipov, D.V.

    1975-01-01

    The paper describes the first attempt to use ultra-violet microirradiation (u.v. injection) in the study of nuclear dualism of infusoria. The u.v. injection affords a means of selectively inactivating individual components of the nuclear apparatus of living infusoria and observing the consequences of an operation in the remote progeny of an irradiated cell. The procedures for applying the u.v. injection have been developed for the infusoria Paramecium caudatum. A rotating compressor of novel design was used to immobilize the infusoria at the time of operation. The effective u.v. doses were chosen and comparative sensitivities of the cytoplasm, the macronucleus, the micronucleus and the symbiotic bacteria of the micronucleus - omega particles - were determined. Healthy infected cells were irradiated in different variants. Depending on dose, the u.v. injection can result in a reduction in the cloning efficiency, the loss of omega particles from the micronucleus and the appearance of cells with 2-3 micronuclei and, possibly, amicronuclear cells. Visible light repairs the damage caused by the u.v. injection. (photoreactivation). (author)

  12. Localization microscopy of DNA in situ using Vybrant{sup ®} DyeCycle™ Violet fluorescent probe: A new approach to study nuclear nanostructure at single molecule resolution

    Energy Technology Data Exchange (ETDEWEB)

    Żurek-Biesiada, Dominika [Laboratory of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków (Poland); Szczurek, Aleksander T. [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Prakash, Kirti [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Institute for Pharmacy and Molecular Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany); Mohana, Giriram K. [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Lee, Hyun-Keun [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Department of Physics, University of Mainz (JGU), Staudingerweg 7, 55128 Mainz (Germany); Roignant, Jean-Yves [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Birk, Udo J. [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Department of Physics, University of Mainz (JGU), Staudingerweg 7, 55128 Mainz (Germany); Dobrucki, Jurek W., E-mail: jerzy.dobrucki@uj.edu.pl [Laboratory of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków (Poland); Cremer, Christoph, E-mail: c.cremer@imb-mainz.de [Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz (Germany); Institute for Pharmacy and Molecular Biotechnology (IPMB), University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany); Department of Physics, University of Mainz (JGU), Staudingerweg 7, 55128 Mainz (Germany)

    2016-05-01

    Higher order chromatin structure is not only required to compact and spatially arrange long chromatids within a nucleus, but have also important functional roles, including control of gene expression and DNA processing. However, studies of chromatin nanostructures cannot be performed using conventional widefield and confocal microscopy because of the limited optical resolution. Various methods of superresolution microscopy have been described to overcome this difficulty, like structured illumination and single molecule localization microscopy. We report here that the standard DNA dye Vybrant{sup ®} DyeCycle™ Violet can be used to provide single molecule localization microscopy (SMLM) images of DNA in nuclei of fixed mammalian cells. This SMLM method enabled optical isolation and localization of large numbers of DNA-bound molecules, usually in excess of 10{sup 6} signals in one cell nucleus. The technique yielded high-quality images of nuclear DNA density, revealing subdiffraction chromatin structures of the size in the order of 100 nm; the interchromatin compartment was visualized at unprecedented optical resolution. The approach offers several advantages over previously described high resolution DNA imaging methods, including high specificity, an ability to record images using a single wavelength excitation, and a higher density of single molecule signals than reported in previous SMLM studies. The method is compatible with DNA/multicolor SMLM imaging which employs simple staining methods suited also for conventional optical microscopy. - Highlights: • Super-resolution imaging of nuclear DNA with Vybrant Violet and blue excitation. • 90nm resolution images of DNA structures in optically thick eukaryotic nuclei. • Enhanced resolution confirms the existence of DNA-free regions inside the nucleus. • Optimized imaging conditions enable multicolor super-resolution imaging.

  13. Nuclear Localization of DNAJB6 Is Associated With Survival of Patients With Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells.

    Science.gov (United States)

    Yu, Valen Zhuoyou; Wong, Victor Chun-Lam; Dai, Wei; Ko, Josephine Mun-Yee; Lam, Alfred King-Yin; Chan, Kwok Wah; Samant, Rajeev S; Lung, Hong Lok; Shuen, Wai Ho; Law, Simon; Chan, Yuen Piu; Lee, Nikki Pui-Yue; Tong, Daniel King Hung; Law, Tsz Ting; Lee, Victor Ho-Fun; Lung, Maria Li

    2015-12-01

    The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulates chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients who underwent esophagectomy with no preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1 ± 2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs, or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2 ± 1.8 months; 95% confidence interval [CI], 15.6-22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 ± 1.4 mo; 95% CI, 9.8-15.4 mo; P = .004, log-rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379-0.834; P = .004). Based on log-rank analysis and Cox regression analysis, the combination of the nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or

  14. Effects of surface chromium depletion on localized corrosion of alloy 825 as a high-level nuclear waste container material

    International Nuclear Information System (INIS)

    Dunn, D.S.; Sridhar, N.; Cragnolino, G.A.

    1995-01-01

    Effects of the chromium-depleted, mill-finished surface on the localized corrosion resistance of alloy 825 (UNS N08825) were investigated. Tests were conducted in solutions based on the ground water at Yucca mountain, Nevada, but with a higher concentration of chloride. Results indicated that breakdown (E p ) and repassivation (E rp ) potentials for mill-finished surfaces were more active than those for polished surfaces. Potentiodynamic polarization tests indicated pits could be initiated on the chromium-depleted surface at potentials of 220 mV SCE in a solution containing 1,000 ppm Cl - at 95 C. Potentiostatic tests identified a similar pit initiation potential for the mill-finished surface. However, under longterm potentiostatic tests, a higher potential of 300 mV SCE was needed to sustain stable pit growth beyond the chromium-depleted layer. An increase in surface roughness also was observed to decrease localized corrosion resistance of the material

  15. Initial Evaluation of the Heat-Affected Zone, Local Embrittlement Phenomenon as it Applies to Nuclear Reactor Vessels

    International Nuclear Information System (INIS)

    McCabe, D.E.

    1999-01-01

    The objective of this project was to determine if the local brittle zone (LBZ) problem, encountered in the testing of the heat-affected zone (HAZ) part of welds in offshore platform construction, can also be found in reactor pressure vessel (RPV) welds. Both structures have multipass welds and grain coarsening along the fusion line. Literature was obtained that described the metallurgical evidence and the type of research work performed on offshore structure welds

  16. Case-study, session 2. Nuclear facilities and local information. Speech by Lennart Franzon (together with L.G. Wahlberg, OKG)

    International Nuclear Information System (INIS)

    Franzon, Lennart; Wahlberg, L.G.

    1989-01-01

    Forsmark NPP is situated 100 miles north of Stockholm on the east coast. The plant has 3 units of about 1 000 MWe each. The annual net production is about 16% of the Swedish electric power consumption. Forsmark was the only Swedish nuclear power plant not yet operating at all at the time of te nuclear power referendum in 1980. The neighbourhood of Forsmark means a radius of about 50 miles from the station, which means about 100 000 inhabitants, including a lot of summer house owners. The first building in use in Forsmark 1973 - seven years before operation start - was a visitors center. Since then 400 000 people have visited Forsmark. The visitors programmes are the most important activities towards the Swedes. To let visitors into a reactor hall balcony, a few meters above the high level waste close to the reactor, is a good way to explain the nuclear power. Many visitors also feel privileged when they together with their friends are able to investigate the radiation protection monitors, where the Chernobyl disaster was detected for the first time outside the Soviet Union in April 1986. Since 1983 both positive and negative aspect of reactor operation are advertised. Data related to electricity supply availability, employment, radiation doses of the employees, radioactive release into air and sea, operational problems, events etc. are all published by the operator in the local newspapers quarterly. The experience is that negative publicity, based on authority reports has decreased. It was found that the most important for the owner/operator is to have the initiative all the time. Similar to Oskarshamn Power Group Forsmark edits a magazine - Forsmarks Tidning - twice a year since 1980, the year of operation start. The magazine is distributed to about 65.000 homes, to authorities, politicians, employees, private companies, etc. About 50% of the neighbours read the magazine. This is considered as success. Through the years of operation of Forsmark it was founds that

  17. Detection of localized and general corrosion of mild steel in simulated defense nuclear waste solutions using electrochemical noise analysis

    International Nuclear Information System (INIS)

    Edgemon, G.L.; Ohl, P.C.; Bell, G.E.C.; Wilson, D.F.

    1995-12-01

    Underground waste tanks fabricated from mild steel store more than 60 million gallons of radioactive waste from 50 years of weapons production. Leaks are suspected in a significant number of tanks. The probable modes of corrosion failures are reported to be localized corrosion (e.g. nitrate stress corrosion cracking and pitting). The use of electrochemical noise (EN) for the monitoring and detection of localized corrosion processes has received considerable attention and application over the last several years. Proof of principle laboratory tests were conducted to verify the capability of EN evaluation to detect localized corrosion and to compare the predictions of general corrosion obtained from EN with those derived from other sources. Simple, pre-fabricated flat and U-bend specimens of steel alloys A516-Grade 60 (UNS K02100) and A537-CL 1 (UNS K02400) were immersed in temperature controlled simulated waste solutions. The simulated waste solution was either 5M NaNO 3 with 0.3M NaOH at 90 C or 11M NaNO 3 with 0.15M NaOH at 95 C. The electrochemical noise activity from the specimens was monitored and recorded for periods ranging between 140 and 240 hours. At the end of each test period, the specimens were metallographically examined to correlated EN data with corrosion damage

  18. Present state and some problem of health services for residents of local government neighboring Fukushima Daiichi Nuclear Power Station

    International Nuclear Information System (INIS)

    Ohira, Yoko

    2012-01-01

    After nuclear disaster, residents of 8 towns and villages of Futaba county within Alert area moved to the west and further removed far. Public offices were also moved. On March 12 health services were started to accept refugee residents at the first refuge. From the end of March to the first part of April they moved to second refuge at specified hotel or inn prepared for a long-term refugee life and then they removed from second refuge to temporary dwelling or loan house. Some of them moved to temporary dwelling at Iwaki city and totaled to more than 20000. New organization of the Fukushima prefecture was established in Iwaki city to start health services for refugee including mental cares. (T. Tanaka)

  19. 16. national conference of the presidents of the local commissions of information (C.L.I.) around nuclear facilities

    International Nuclear Information System (INIS)

    2005-01-01

    This conference contained two plenary sessions. The first one concerned the epidemiology with the following subjects: the epidemiology, its contributions and its limits; the epidemiological surveillance of cancers in France: role of registers within the device; the aggregates of leukaemia near the nuclear installations; perception and management of the risk; the point of view of the scientific committee of the A.N.C.L.I.; Followed a work in a workshop on the subjects relative to the functioning of the C.L.I. (Organization, relations, information) then the second plenary session with as subjects: organization and functioning of C.L.I., relations and links with A.N.C.L.I., information received and diffused by the C.L.I. (N.C.)

  20. v-Src-induced nuclear localization of YAP is involved in multipolar spindle formation in tetraploid cells.

    Science.gov (United States)

    Kakae, Keiko; Ikeuchi, Masayoshi; Kuga, Takahisa; Saito, Youhei; Yamaguchi, Naoto; Nakayama, Yuji

    2017-01-01

    The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events, including cell division. We have reported that v-Src, which is a mutant variant of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase, resulting in a furrow regression in cytokinesis and the generation of multinucleated cells. However, the effect of v-Src on mitotic spindle formation is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo abnormal cell division, in which cells separate into more than two cells. Upon v-Src expression, the proportion of multinucleated cells is increased in a time-dependent manner. Flow cytometry analysis revealed that v-Src increases the number of cells having a ≥4N DNA content. Microscopic analysis showed that v-Src induces the formation of multipolar spindles with excess centrosomes. These results suggest that v-Src induces multipolar spindle formation by generating multinucleated cells. Tetraploidy activates the tetraploidy checkpoint, leading to a cell cycle arrest of tetraploid cells at the G1 phase, in which the nuclear exclusion of the transcription co-activator YAP plays a critical role. In multinucleated cells that are induced by cytochalasin B and the Plk1 inhibitor, YAP is excluded from the nucleus. However, v-Src prevents this nuclear exclusion of YAP through a decrease in the phosphorylation of YAP at Ser127 in multinucleated cells. Furthermore, v-Src decreases the expression level of p53, which also plays a critical role in the cell cycle arrest of tetraploid cells. These results suggest that v-Src promotes abnormal spindle formation in at least two ways: generation of multinucleated cells and a weakening of the tetraploidy checkpoint. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

    Science.gov (United States)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-12-02

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Concentrations of Radiocesium in Local Foods Collected in Kawauchi Village after the Accident at the Fukushima Dai-ichi Nuclear Power Station

    Science.gov (United States)

    Orita, Makiko; Nakashima, Kanami; Hayashida, Naomi; Endo, Yuuko; Yamashita, Shunichi; Takamura, Noboru

    2016-06-01

    We evaluated the current concentrations of radiocesium in local foods collected in Kawauchi Village, which is located less than 30 km from Fukushima Daiichi Nuclear Power Station, to minimize public anxiety regarding internal radiation exposure through the consumption of locally produced foods after the 2011 Fukushima accident. The number of samples exceeding the regulatory radiocesium limit (100 Bq/kg for general foods) was five out of 4,080 vegetables (0.1%), 652 of 1,986 (32.8%) among edible wild plants and fungi, and eight of 647 (1.2%) in fruits. Our study confirmed that the internal radiation doses of ingesting these foods are acceptably low compared to the public dose limit, ranging from 24.4 to 42.7 μSv for males and from 21.7 to 43.4 μSv for females, although the potential for radiation exposure still exists. Long-term comprehensive follow-up should take place to clarify trends in radiocesium concentrations in local foods and the committed effective doses found in Fukushima-area residents. By constructing a system that allows residents to access information on radiocesium concentration in foods, a risk communication model between specialists and residents could be developed in the recovery phase after the Fukushima accident.

  3. Nuclear membrane localization during pollen development and apex-focused polarity establishment of SYP124/125 during pollen germination in Arabidopsis thaliana.

    Science.gov (United States)

    Ichikawa, Mie; Iwano, Megumi; Sato, Masa H

    2015-12-01

    Establishment of apex-polarity. Elongation of the pollen tube is a highly coordinated process involving polarized secretion of cell wall and membrane materials to the apical region. We investigated changes in the localization of soluble NSF attachment proteins (SNAREs) in developing pollen grains and the pollen tube for transgenic Arabidopsis expressing pollen-specific plasma-membrane Qa-SNAREs (SYP124, 125 and 131) fused with the green fluorescent protein (GFP). The expression of SYP124 and SYP125 was firstly detected in the microspore nuclear membrane during pollen mitosis II. Although SYP124, 125 and 131 accumulated throughout the cytosol in the mature pollen grain, GFP-SYP124 and GFP-SYP125 were highly concentrated in the apical or subapical regions of the elongating pollen tube with slightly different localization patterns, whereas GFP-SYP131 was uniformly localized to the plasma membrane of the pollen tube. The apex-focused polarity of GFP-SYP125 was established coincident with formation of a Ca(2+) gradient before pollen germination. These results suggest that SNAREs function differentially in the same cells and that at least two distinct membrane transport pathways are involved in the pollen development and the pollen tube germination and elongation.

  4. The C-terminal region of Rad52 is essential for Rad52 nuclear and nucleolar localization, and accumulation at DNA damage sites immediately after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Res., National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2013-05-31

    Highlights: •Rad52 might play a key role in the repair of DSB immediately after irradiation. •EYFP-Rad52 accumulates rapidly at DSB sites and colocalizes with Ku80. •Accumulation of Rad52 at DSB sites is independent of the core NHEJ factors. •Localization and recruitment of Rad52 to DSB sites are dependent on the Rad52 CTR. •Basic amino acids in Rad52 CTR are highly conserved among vertebrate species. -- Abstract: Rad52 plays essential roles in homologous recombination (HR) and repair of DNA double-strand breaks (DSBs) in Saccharomyces cerevisiae. However, in vertebrates, knockouts of the Rad52 gene show no hypersensitivity to agents that induce DSBs. Rad52 localizes in the nucleus and forms foci at a late stage following irradiation. Ku70 and Ku80, which play an essential role in nonhomologous DNA-end-joining (NHEJ), are essential for the accumulation of other core NHEJ factors, e.g., XRCC4, and a HR-related factor, e.g., BRCA1. Here, we show that the subcellular localization of EYFP-Rad52(1–418) changes dynamically during the cell cycle. In addition, EYFP-Rad52(1–418) accumulates rapidly at microirradiated sites and colocalizes with the DSB sensor protein Ku80. Moreover, the accumulation of EYFP-Rad52(1–418) at DSB sites is independent of the core NHEJ factors, i.e., Ku80 and XRCC4. Furthermore, we observed that EYFP-Rad52(1–418) localizes in nucleoli in CHO-K1 cells and XRCC4-deficient cells, but not in Ku80-deficient cells. We also found that Rad52 nuclear localization, nucleolar localization, and accumulation at DSB sites are dependent on eight amino acids (411–418) at the end of the C-terminal region of Rad52 (Rad52 CTR). Furthermore, basic amino acids on Rad52 CTR are highly conserved among mammalian, avian, and fish homologues, suggesting that Rad52 CTR is important for the regulation and function of Rad52 in vertebrates. These findings also suggest that the mechanism underlying the regulation of subcellular localization of Rad52 is

  5. Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human β-globin locus

    Science.gov (United States)

    Schübeler, Dirk; Francastel, Claire; Cimbora, Daniel M.; Reik, Andreas; Martin, David I.K.; Groudine, Mark

    2000-01-01

    We have investigated the mechanism, structural correlates, and cis-acting elements involved in chromatin opening and gene activation, using the human β-globin locus as a model. Full transcriptional activity of the human β-globin locus requires the locus control region (LCR), composed of a series of nuclease hypersensitive sites located upstream of this globin gene cluster. Our previous analysis of naturally occurring and targeted LCR deletions revealed that chromatin opening and transcriptional activity in the endogenous β-globin locus are dissociable and dependent on distinct cis-acting elements. We now report that general histone H3/H4 acetylation and relocation of the locus away from centromeric heterochromatin in the interphase nucleus are correlated and do not require the LCR. In contrast, LCR-dependent promoter activation is associated with localized histone H3 hyperacetylation at the LCR and the transcribed β-globin-promoter and gene. On the basis of these results, we suggest a multistep model for gene activation; localization away from centromeric heterochromatin is required to achieve general hyperacetylation and an open chromatin structure of the locus, whereas a mechanism involving LCR/promoter histone H3 hyperacetylation is required for high-level transcription of the β-globin genes. PMID:10783166

  6. Resolvin D1 limits 5-lipoxygenase nuclear localization and leukotriene B4 synthesis by inhibiting a calcium-activated kinase pathway.

    Science.gov (United States)

    Fredman, Gabrielle; Ozcan, Lale; Spolitu, Stefano; Hellmann, Jason; Spite, Matthew; Backs, Johannes; Tabas, Ira

    2014-10-07

    Imbalances between proinflammatory and proresolving mediators can lead to chronic inflammatory diseases. The balance of arachidonic acid-derived mediators in leukocytes is thought to be achieved through intracellular localization of 5-lipoxygenase (5-LOX): nuclear 5-LOX favors the biosynthesis of proinflammatory leukotriene B4 (LTB4), whereas, in theory, cytoplasmic 5-LOX could favor the biosynthesis of proresolving lipoxin A4 (LXA4). This balance is shifted in favor of LXA4 by resolvin D1 (RvD1), a specialized proresolving mediator derived from docosahexaenoic acid, but the mechanism is not known. Here we report a new pathway through which RvD1 promotes nuclear exclusion of 5-LOX and thereby suppresses LTB4 and enhances LXA4 in macrophages. RvD1, by activating its receptor formyl peptide receptor2/lipoxin A4 receptor, suppresses cytosolic calcium and decreases activation of the calcium-sensitive kinase calcium-calmodulin-dependent protein kinase II (CaMKII). CaMKII inhibition suppresses activation P38 and mitogen-activated protein kinase-activated protein kinase 2 kinases, which reduces Ser271 phosphorylation of 5-LOX and shifts 5-LOX from the nucleus to the cytoplasm. As such, RvD1's ability to decrease nuclear 5-LOX and the LTB4:LXA4 ratio in vitro and in vivo was mimicked by macrophages lacking CaMKII or expressing S271A-5-LOX. These findings provide mechanistic insight into how a specialized proresolving mediator from the docosahexaenoic acid pathway shifts the balance toward resolution in the arachidonic acid pathway. Knowledge of this mechanism may provide new strategies for promoting inflammation resolution in chronic inflammatory diseases.

  7. Developmental and adult expression patterns of the G-protein-coupled receptor GPR88 in the rat: Establishment of a dual nuclear-cytoplasmic localization.

    Science.gov (United States)

    Massart, Renaud; Mignon, Virginie; Stanic, Jennifer; Munoz-Tello, Paola; Becker, Jerôme A J; Kieffer, Brigitte L; Darmon, Michèle; Sokoloff, Pierre; Diaz, Jorge

    2016-10-01

    GPR88 is a neuronal cerebral orphan G-protein-coupled receptor (GPCR) that has been linked to various psychiatric disorders. However, no extensive description of its localization has been provided so far. Here, we investigate the spatiotemporal expression of the GPR88 in prenatal and postnatal rat tissues by using in situ hybridization and immunohistochemistry. GPR88 protein was initially detected at embryonic day 16 (E16) in the striatal primordium. From E16-E20 to adulthood, the highest expression levels of both protein and mRNA were observed in striatum, olfactory tubercle, nucleus accumbens, amygdala, and neocortex, whereas in spinal cord, pons, and medulla GPR88 expression remains discrete. We observed an intracellular redistribution of GPR88 during cortical lamination. In the cortical plate of the developing cortex, GPR88 presents a classical GPCR plasma membrane/cytoplasmic localization that shifts, on the day of birth, to nuclei of neurons progressively settling in layers V to II. This intranuclear localization remains throughout adulthood and was also detected in monkey and human cortex as well as in the amygdala and hypothalamus of rats. Apart from the central nervous system, GPR88 was transiently expressed at high levels in peripheral tissues, including adrenal cortex (E16-E21) and cochlear ganglia (E19-P3), and also at moderate levels in retina (E18-E19) and spleen (E21-P7). The description of the GPR88 anatomical expression pattern may provide precious functional insights into this novel receptor. Furthermore, the GRP88 nuclear localization suggests nonclassical GPCR modes of action of the protein that could be relevant for cortical development and psychiatric disorders. J. Comp. Neurol. 524:2776-2802, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.

    Science.gov (United States)

    Cardoso, Maira Arruda; Fontenele, Marcio; Lim, Bomyi; Bisch, Paulo Mascarello; Shvartsman, Stanislav Y; Araujo, Helena Marcolla

    2017-08-15

    The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals. © 2017. Published by The Company of Biologists Ltd.

  9. Structural and energetic basis of ALS-causing mutations in the atypical proline-tyrosine nuclear localization signal of the Fused in Sarcoma protein (FUS)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zi Chao; Chook, Yuh Min [UTSMC

    2012-10-02

    Mutations in the proline/tyrosine–nuclear localization signal (PY-NLS) of the Fused in Sarcoma protein (FUS) cause amyotrophic lateral sclerosis (ALS). Here we report the crystal structure of the FUS PY-NLS bound to its nuclear import receptor Karyopherinβ2 (Kapβ2; also known as Transportin). The FUS PY-NLS occupies the structurally invariant C-terminal arch of Kapβ2, tracing a path similar to that of other characterized PY-NLSs. Unlike other PY-NLSs, which generally bind Kapβ2 in fully extended conformations, the FUS peptide is atypical as its central portion forms a 2.5-turn α-helix. The Kapβ2-binding epitopes of the FUS PY-NLS consist of an N-terminal PGKM hydrophobic motif, a central arginine-rich α-helix, and a C-terminal PY motif. ALS mutations are found almost exclusively within these epitopes. Each ALS mutation site makes multiple contacts with Kapβ2 and mutations of these residues decrease binding affinities for Kapβ2 (KD for wild-type FUS PY-NLS is 9.5 nM) up to ninefold. Thermodynamic analyses of ALS mutations in the FUS PY-NLS show that the weakening of FUS-Kapβ2 binding affinity, the degree of cytoplasmic mislocalization, and ALS disease severity are correlated.

  10. Distance matters. Assessing socioeconomic impacts of the Dukovany nuclear power plant in the Czech Republic: Local perceptions and statistical evidence

    Directory of Open Access Journals (Sweden)

    Frantál Bohumil

    2016-03-01

    Full Text Available The effect of geographical distance on the extent of socioeconomic impacts of the Dukovany nuclear power plant in the Czech Republic is assessed by combining two different research approaches. First, we survey how people living in municipalities in the vicinity of the power plant perceive impacts on their personal quality of life. Second, we explore the effects of the power plant on regional development by analysing long-term statistical data about the unemployment rate, the share of workers in the energy sector and overall job opportunities in the respective municipalities. The results indicate that the power plant has had significant positive impacts on surrounding communities both as perceived by residents and as evidenced by the statistical data. The level of impacts is, however, significantly influenced by the spatial and social distances of communities and individuals from the power plant. The perception of positive impacts correlates with geographical proximity to the power plant, while the hypothetical distance where positive effects on the quality of life are no longer perceived was estimated at about 15 km. Positive effects are also more likely to be reported by highly educated, young and middle-aged and economically active persons, whose work is connected to the power plant.

  11. The 21.5-kDa isoform of myelin basic protein has a non-traditional PY-nuclear-localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Graham S.T.; Seymour, Lauren V. [Molecular and Cellular Biology, University of Guelph, Guelph, Ontario (Canada); Boggs, Joan M. [Molecular Structure and Function, Research Institute, Hospital for Sick Children, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario (Canada); Harauz, George, E-mail: gharauz@uoguelph.ca [Molecular and Cellular Biology, University of Guelph, Guelph, Ontario (Canada)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Full-length 21.5-kDa MBP isoform is translocated to the nucleus. Black-Right-Pointing-Pointer We hypothesized that the exon-II-encoded sequence contained the NLS. Black-Right-Pointing-Pointer We mutated this sequence in RFP-tagged constructs and transfected N19-cells. Black-Right-Pointing-Pointer Abolition of two key positively-charged residues resulted in loss of nuclear-trafficking. Black-Right-Pointing-Pointer The 21.5-kDa isoform of classic MBP contains a non-traditional PY-NLS. -- Abstract: The predominant 18.5-kDa classic myelin basic protein (MBP) is mainly responsible for compaction of the myelin sheath in the central nervous system, but is multifunctional, having numerous interactions with Ca{sup 2+}-calmodulin, actin, tubulin, and SH3-domains, and can tether these proteins to a lipid membrane in vitro. The full-length 21.5-kDa MBP isoform has an additional 26 residues encoded by exon-II of the classic gene, which causes it to be trafficked to the nucleus of oligodendrocytes (OLGs). We have performed site-directed mutagenesis of selected residues within this segment in red fluorescent protein (RFP)-tagged constructs, which were then transfected into the immortalized N19-OLG cell line to view protein localization using epifluorescence microscopy. We found that 21.5-kDa MBP contains two non-traditional PY-nuclear-localization signals, and that arginine and lysine residues within these motifs were involved in subcellular trafficking of this protein to the nucleus, where it may have functional roles during myelinogenesis.

  12. Inhibition of protein 4.1 R and NuMA interaction by mutagenization of their binding-sites abrogates nuclear localization of 4.1 R.

    Science.gov (United States)

    Mattagajasingh, Subhendra N; Huang, Shu-Ching; Benz, Edward J

    2009-04-01

    Protein 4.1R(4.1R) is a multifunctional structural protein recently implicated in nuclear assembly and cell division. We earlier demonstrated that 4.1R forms a multiprotein complex with mitotic spindle and spindle pole organizing proteins, such as NuMA, dynein, and dynactin, by binding to residues 1788-1810 of NuMA through amino acids encoded by exons 20 and 21 in 24 kD domain. Employing random-and site-directed mutagenesis combined with glycine- and alanine-scanning, we have identified amino acids of 4.1 R and NuMA that sustain their interaction, and have analyzed the effect of mutating the binding sites on their intracellular colocalization. We found that V762, V765, and V767 of 4.1 R, and 11800, 11801,11803, Tl 804, and M1805 of NuMA are necessary for their interaction. GST-fusion peptides of the 4.1R24 kD domain bound to residues 1785-2115 of NuMA in in vitro binding assays, but the binding was inhibited by alanine substitutions of V762, V765, and V767 of 4.1 R, or residues 1800-1805 of NuMA. Additionally, expression of variants of 4.1 R or NuMA that inhibit their in vitro binding also abrogated nuclear localization of 4.1 Rand colocalization with NuMA. Our findings suggest a crucial role of 4.1 R/NuMA interaction in localization and function of 4.1 R in the nucleus.

  13. Local and integral ulrasonic gauges for two-phase flow instrumentation in nuclear reactor and safety technology. Final report

    International Nuclear Information System (INIS)

    Chochlov, V.N.; Duncev, A.V.; Ivanov, V.V.; Kontelev, V.V.; Melnikov, V.I.; Stoppel, L.K.; Prasser, H.M.; Zippe, W.; Zschau, J.; Zboray, R.

    2000-11-01

    The present project was executed in the frame of a co-operation agreement between FZR and the scientific group of Prof. Melnikov of the technical University of Nishny Novgorod (TUNN) in the Russian Federation. It is part of the Federal Government's programme for the provision of advice for Eastern Europe on the building up of democracy and social market economy (TRANSFORM Programme). New methods of two-phase flow instrumentation were developed: Intrusive wave-guide probes can be used for local void fraction measurements. The new ultrasonic mesh sensors allow a fast two-phase flow visualisation with about 250 frames per second. Experiments carried out at the test loop in Rossendorf, but also the tests at the DESIRE facility in Delft have shown that both local wave-guide probes and ultrasonic mesh sensors can be successfully applied under the conditions of high pressure and temperature steam-water mixture, as well as in organic liquids and refrigerants. Furthermore, non-intrusive wave-guide sensors as well as density sensors based on the measurement of the wave propagation velocity in wave-guides immersed into the measuring liquid were developed and tested. In the present stage of the development, the non-intrusive sensors can rather be used for a qualitative gas respectively level detection than for void fraction measurements. The wave-guide density sensor was successfully demonstrated that it is able to measure densities of single-phase liquids. It requires further development of the electronic circuitry. The main innovation was achieved by the development of the ultrasonic mesh sensor, the resoluting capability of which is comparable to methods like electrical wire-mesh sensors and ultra-fast X-ray tomography, while the device itself is robust and low expensive. (orig.) [de

  14. Macro-localization study of a commercial CAREM nuclear power plant in the province of Formosa : state of progress

    International Nuclear Information System (INIS)

    Torino Araoz, Ines

    2011-01-01

    The framework agreement signed between Formosa Province and the National Atomic Energy Commission (CNEA) in order to establish formal relations of cooperation with regard to projects of common interest, research and development, technology services, human resource training in the areas inherent to CNEA functions, resulted in a specific agreement in order to analyze the potential location of a CAREM commercial nuclear power plant in the Province. Thus, the site survey study which is under development aims at the determination of one or more sites, which meet the criteria set - security related and not related - and is/are eligible for the installation of the plant. The site selection methodology used to develop the study was based on documentation and bibliography of the International Atomic Energy Agency and CNEA. Taking into account these references, the study began divided into 3 levels; currently, Level I is approved and the analysis of Level II is completed. Each of these levels covers different aspects that must be evaluated during the selection process. That one is a complex analysis, which was carried out through the participation and joint efforts of a multidisciplinary team consisting of CNEA’s staff and the Province of Formosa, which in turn had the cooperation of various institutions. Partial results of the Level II document, determine the pre selection of three potential areas in the province. In turn, it is important to remember that the site survey (regional) study is the first stage in the selection process. Then, the site evaluation stage (micro siting study) and the preparation of the Preliminary Safety Report have to be implemented, in order to establish the definitive site for the plant installation. (author) [es

  15. Transcriptional activity and nuclear localization of Cabut, the Drosophila ortholog of vertebrate TGF-β-inducible early-response gene (TIEG proteins.

    Directory of Open Access Journals (Sweden)

    Yaiza Belacortu

    Full Text Available BACKGROUND: Cabut (Cbt is a C(2H(2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs, which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein. METHODOLOGY/PRINCIPAL FINDINGS: To determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2. CONCLUSIONS/SIGNIFICANCE: Our results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the

  16. Human herpesvirus 6B U19 protein is a PML-regulated transcriptional activator that localizes to nuclear foci in a PML-independent manner

    DEFF Research Database (Denmark)

    Kofod-Olsen, Emil; Ross-Hansen, Katrine; Mikkelsen, Jacob Giehm

    2008-01-01

    Human herpesvirus 6B (HHV-6B) contains an IE-B domain spanning open reading frames U16/17-U19, based on homology with human cytomegalovirus. Here, the protein product, U19, of the HHV-6B U19 gene is identified as a 47 kDa transcriptional activator. HHV-6B infection or overexpression of U19...... transactivated the RANTES promoter. Mutational analysis of the promoter indicated that transactivation was not critically dependent on the promoter sites CRE, NF-kappaB, ISRE or NF-IL6. ND10 are nuclear substructures that are involved in several cellular regulatory pathways, including those controlling gene...... structure, U19 also localized to the centre of ND10. Knockdown of PML by small interfering RNA did not prevent U19 localization to ND10-like foci, but instead led to a fourfold increase in U19-induced transcription from the RANTES promoter. Generation of four truncated U19 proteins indicated that the N...

  17. Light Water Reactor Sustainability Program: Evaluation of Localized Cable Test Methods for Nuclear Power Plant Cable Aging Management Programs

    Energy Technology Data Exchange (ETDEWEB)

    Glass, Samuel W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fifield, Leonard S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hartman, Trenton S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-05-30

    This Pacific Northwest National Laboratory (PNNL) milestone report describes progress to date on the investigation of nondestructive test (NDE) methods focusing particularly on local measurements that provide key indicators of cable aging and damage. The work includes a review of relevant literature as well as hands-on experimental verification of inspection capabilities. As NPPs consider applying for second, or subsequent, license renewal (SLR) to extend their operating period from 60 years to 80 years, it important to understand how the materials installed in plant systems and components will age during that time and develop aging management programs (AMPs) to assure continued safe operation under normal and design basis events (DBE). Normal component and system tests typically confirm the cables can perform their normal operational function. The focus of the cable test program is directed toward the more demanding challenge of assuring the cable function under accident or DBE. Most utilities already have a program associated with their first life extension from 40 to 60 years. Regrettably, there is neither a clear guideline nor a single NDE that can assure cable function and integrity for all cables. Thankfully, however, practical implementation of a broad range of tests allows utilities to develop a practical program that assures cable function to a high degree. The industry has adopted 50% elongation at break (EAB) relative to the un-aged cable condition as the acceptability standard. All tests are benchmarked against the cable EAB test. EAB is a destructive test so the test programs must apply an array of other NDE tests to assure or infer the overall set of cable’s system integrity. These cable NDE programs vary in rigor and methodology. As the industry gains experience with the efficacy of these programs, it is expected that implementation practice will converge to a more common approach. This report addresses the range of local NDE cable tests that are

  18. Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle

    International Nuclear Information System (INIS)

    Lee, Choongho; Wooldridge, Tonia R.; Laimins, Laimonis A.

    2007-01-01

    The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another α-helical domain protein, E6AP. When HPV 31 genomes containing mutations at amino acid 128 were transfected into human keratinocytes, the viral DNAs were not stably maintained as episomes indicating the importance of this residue for pathogenesis. Many E6 binding partners including E6TP1 are cytoplasmic proteins, but E6 has been also reported to be localized to the nucleus. We therefore investigated the importance of E6 localization to the nucleus in the viral life cycle. Using a fusion of E6 to Green Fluorescent Protein, we mapped one component of the nuclear localization sequences to residues 121 to 124 of HPV 31 E6. Mutation of these residues in the context of the HPV 31 genome abrogated the ability for episomes to be stably maintained and impaired the ability to extend the life span of cells. These studies identify two activities of HPV 31 E6 that are important for its function in the viral life cycle and for extension of cell life span

  19. Local and integral ulrasonic gauges for two-phase flow instrumentation in nuclear reactor and safety technology. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Chochlov, V.N.; Duncev, A.V.; Ivanov, V.V.; Kontelev, V.V.; Melnikov, V.I.; Stoppel, L.K. [Technical State Univ. of Nishny Novgorod (Russian Federation); Prasser, H.M.; Zippe, W.; Zschau, J. [Forschungszentrum Rossendorf e.V. (FZR) (Germany). Inst. fuer Sicherheitsforschung; Zboray, R. [Technische Univ. Delft (Netherlands). Interfacultair Reactor Inst.

    2000-11-01

    The present project was executed in the frame of a co-operation agreement between FZR and the scientific group of Prof. Melnikov of the technical University of Nishny Novgorod (TUNN) in the Russian Federation. It is part of the Federal Government's programme for the provision of advice for Eastern Europe on the building up of democracy and social market economy (TRANSFORM Programme). New methods of two-phase flow instrumentation were developed: Intrusive wave-guide probes can be used for local void fraction measurements. The new ultrasonic mesh sensors allow a fast two-phase flow visualisation with about 250 frames per second. Experiments carried out at the test loop in Rossendorf, but also the tests at the DESIRE facility in Delft have shown that both local wave-guide probes and ultrasonic mesh sensors can be successfully applied under the conditions of high pressure and temperature steam-water mixture, as well as in organic liquids and refrigerants. Furthermore, non-intrusive wave-guide sensors as well as density sensors based on the measurement of the wave propagation velocity in wave-guides immersed into the measuring liquid were developed and tested. In the present stage of the development, the non-intrusive sensors can rather be used for a qualitative gas respectively level detection than for void fraction measurements. The wave-guide density sensor was successfully demonstrated that it is able to measure densities of single-phase liquids. It requires further development of the electronic circuitry. The main innovation was achieved by the development of the ultrasonic mesh sensor, the resoluting capability of which is comparable to methods like electrical wire-mesh sensors and ultra-fast X-ray tomography, while the device itself is robust and low expensive. (orig.) [German] Das vorliegende Projekt wurde im Rahmen einer Kooperationsvereinbarung zwischen dem Forschungszentrum Rossendorf (FZR) und der wissenschaftlichen Gruppe von Prof. Melnikov von der

  20. Characterization of a GM7 glioblastoma cell line showing CD133 positivity and both cytoplasmic and nuclear localization of nestin.

    Science.gov (United States)

    Loja, Tomas; Chlapek, Petr; Kuglik, Petr; Pesakova, Martina; Oltova, Alexandra; Cejpek, Pavel; Veselska, Renata

    2009-01-01

    A newly established GM7 cell line was derived from the tumor tissue of a 65-year-old man surgically treated for a relapse of glioblastoma multiforme that occurred 10 months after first surgery following radiotherapy. GM7 cells exhibit spindle or glia-like morphology, and multinucleated giant cells are also present in the culture. The cells proliferate rapidly (PDT is about 18 h) and tend to grow in multilayer without contact inhibition. Using G-banding and SKY, the GM7 cell line was identified as near-triploid with a large number of structural and numerical abnormalities. Repeated karyotyping during long-term cultivation confirmed a chromosome number of 70+/-3 chromosomes per cell. Special attention was paid to the immunocytochemical analysis of protein markers in this cell line; GM7 cells showed strong positivity for CD133, vimentin, nestin, NF-160 and S-100 protein and weak positivity for GFAP and NSE, but were negative for synaptophysin. The most important features of the GM7 cell line are its stable phenotype CD133+/nestin+, which are accepted as stem cell markers in neural stem/progenitor cells, and especially unusual intracellular localization of the IF protein nestin, which was detected and repeatedly confirmed both in the cytoplasm and cell nucleus. For this reason, the new GM7 glioblastoma cell line represents an important model suitable not only for further studies on glioblastoma biology and cancer stem cells, but particularly for the detailed investigation of the role of nestin in transformed cells.

  1. The meganuclease I-SceI containing nuclear localization signal (NLS-I-SceI) efficiently mediated mammalian germline transgenesis via embryo cytoplasmic microinjection.

    Science.gov (United States)

    Wang, Yong; Zhou, Xiao-Yang; Xiang, Peng-Ying; Wang, Lu-Lu; Tang, Huan; Xie, Fei; Li, Liang; Wei, Hong

    2014-01-01

    The meganuclease I-SceI has been effectively used to facilitate transgenesis in fish eggs for nearly a decade. I-SceI-mediated transgenesis is simply via embryo cytoplasmic microinjection and only involves plasmid vectors containing I-SceI recognition sequences, therefore regarding the transgenesis process and application of resulted transgenic organisms, I-SceI-mediated transgenesis is of minimal bio-safety concerns. However, currently no transgenic mammals derived from I-SceI-mediated transgenesis have been reported. In this work, we found that the native I-SceI molecule was not capable of facilitating transgenesis in mammalian embryos via cytoplasmic microinjection as it did in fish eggs. In contrast, the I-SceI molecule containing mammalian nuclear localization signal (NLS-I-SceI) was shown to be capable of transferring DNA fragments from cytoplasm into nuclear in porcine embryos, and cytoplasmic microinjection with NLS-I-SceI mRNA and circular I-SceI recognition sequence-containing transgene plasmids resulted in transgene expression in both mouse and porcine embryos. Besides, transfer of the cytoplasmically microinjected mouse and porcine embryos into synchronized recipient females both efficiently resulted in transgenic founders with germline transmission competence. These results provided a novel method to facilitate mammalian transgenesis using I-SceI, and using the NLS-I-SceI molecule, a simple, efficient and species-neutral transgenesis technology based on embryo cytoplasmic microinjection with minimal bio-safety concerns can be established for mammalian species. As far as we know, this is the first report for transgenic mammals derived from I-SceI-mediated transgenesis via embryo cytoplasmic microinjection.

  2. Predictions of local, regional and global radiation doses from iodine-129 for four different disposal methods and an all-nuclear future

    International Nuclear Information System (INIS)

    Wuschke, D.M.; Barnard, J.W.; O'Connor, P.A.; Johnson, J.R.

    1985-01-01

    The radioactive isotope 129 I produced by nuclear fission becomes globally distributed if released to the environment. The consequences of several options for management of 129 I are discussed. Estimates are presented of radiation doses from the 129 I produced in generating 1000 GW(e).a of nuclear electricity, the total production expected in Canada up to about 2040. Individual thyroid dose rates from 129 I, and accumulated collective effective dose equivalents to three groups are compared for four 129 I management strategies. These groups are: local persons living in the immediate vicinity of a discharge zone from a fuel reprocessing facility or waste disposal vault in the Canadian Shield, regional persons living in the lower Great Lakes basin, and average global persons. The four management strategies studied were: atmospheric discharge from a reprocessing facility, ocean dumping, subseabed disposal, and isolation in a deep vault in plutonic rock in the Canadian Shield. Doses associated with each of these options are compared with each other and with proposed Canadian regulatory limits. Estimates are also presented of doses to the same groups from fission-product 129 I, if fission supplied all future world energy needs. The two management options considered were geological disposal in vaults that would each eventually discharge 129 I at the rate estimated for a disposal vault in the Canadian Shield, and ocean dumping. Again, doses arising from these options are compared with each other and with proposed regulatory limits. The second comparison allows estimates to be made of the time at which such intensive use of fission could produce unacceptable levels of 129 I in the environment

  3. Characterization of nuclear localization signals in the type III effectors HsvG and HsvB of the gall-forming bacterium Pantoea agglomerans.

    Science.gov (United States)

    Weinthal, Dan M; Barash, Isaac; Tzfira, Tzvi; Gaba, Victor; Teper, Doron; Sessa, Guido; Manulis-Sasson, Shulamit

    2011-05-01

    HsvG and HsvB, two paralogous type III effectors of the gall-forming bacteria Pantoea agglomerans pv. gypsophilae and P. agglomerans pv. betae, determine host specificity on gypsophila and beet, respectively. They were previously shown to be DNA-binding proteins imported into host and non-host nuclei and might act as transcriptional activators. Sequence analysis of these effectors did not detect canonical nuclear localization signals (NLSs), but two basic amino acid clusters designated putative NLS1 and NLS2 were detected in their N-terminal and C-terminal regions, respectively. pNIA assay for nuclear import in yeast and bombardment of melon leaves with each of the NLSs fused to a 2xYFP reporter indicated that putative NLS1 and NLS2 were functional in transport of HsvG into the nucleus. A yeast two-hybrid assay showed that HsvB, HsvG, putative NLS1, putative NLS2, HsvG converted into HsvB, or HsvB converted into HsvG by exchanging the repeat domain, all interacted with AtKAP-α and importin-α3 of Arabidopsis thaliana. Deletion analysis of the NLS domains in HsvG suggested that putative NLS1 or NLS2 were required for pathogenicity on gypsophila cuttings and presumably for import of HsvG into the nucleus. This study demonstrates the presence of two functional NLSs in the type III effectors HsvG and HsvB.

  4. Emission of 14C by the Almirante Alvaro Alberto Nuclear Power Plant 1 and 2 and their local effects on the environmental levels

    International Nuclear Information System (INIS)

    Dias, Cintia Melazo

    2006-01-01

    14 C is a is a long-lived beta-emitting nuclide (T 1/2 = 5730 years) produced naturally in the upper atmosphere as a result of reactions between neutrons and stable 14 N( 14 N(n,p) 14 C). Although in a lesser extent, nuclear power plants produce 14 C as well during their routine operation. Since it is converted in 14 CO 2 and mixed throughout the atmosphere, it is incorporated into plant tissues, via photosynthesis process, and hence in food chain. Because of the biological importance of 14 C and long half-life, it is of interest to quantify the amounts released by nuclear industry. The Brazilian nuclear central named Nuclear Central Admiral Alvaro Alberto (CNAAA) has two nuclear reactors of PWR type in operation, Angra I (657 MWe) and Angra II (1350 MWe), and one under construction, Angra III (1309 MWe PWR). The aim of this study was to determine the strength of the sources and the 14 C content in the environment through analyses of air, vegetation and soils taken within 5 km (the influenced area) of CNAAA. The thesis consists of an extensive review about the subject (part one) and of four papers (part two). The first paper is about the determination of 14 C concentrations released by reactors (source strength). For Angra I, a device was developed in order to sample the gaseous effluents and for Angra II, a commercial monitoring system had already been implemented since its initial operation (2001). The 14 C can be emitted as hydrocarbons, CO or CO 2 , depending on the type of reactor. For PWRs, the main chemical form released is hydrocarbons (80 %). The monitoring system of Angra I was planned to determine both CO 2 and hydrocarbon fractions but in Angra II, all hydrocarbons are converted to CO 2 by using a Pd/Al 2 O 3 catalyst at 450 deg C. The liquid scintillation was the method employed to measure the samples. The second one concerns the atmospheric dispersion of the released radiocarbon through measurements of air samples taken with 3 km from power plants, in

  5. Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Local Osteoporotic Canine Mandible Model for the Evaluation of Peri-Implant Bone Regeneration.

    Science.gov (United States)

    Chang, Ah Ryum; Cho, Tae Hyung; Hwang, Soon Jung

    2017-11-01

    The canine mandible is useful for studying bone regeneration after dental implant placement. However, it is limited in investigations of peri-implant osteogenesis under osteoporotic conditions due to the insignificant osteoporotic effect of ovariectomy. This study aimed at establishing a local osteoporotic model without ovariectomy by using receptor activator of nuclear factor kappa-B ligand (RANKL) in a canine mandible model. This new model was used to evaluate the effects of injectable β-tricalcium phosphate (TCP) microsphere bone grafts on peri-implant bone regeneration under osteoporotic conditions with combinations of recombinant human bone morphogenetic protein-2 (rhBMP-2). A local osteoporotic canine mandible model was designed by creating a hole in the mandibular alveolar bone, then implanting a collagen sponge soaked with 20, 40, or 60 μg RANKL into the hole, and leaving it for 2 weeks. After the establishment of the dose for maximum osteoporotic bone loss at 40 μg of RANKL, the main surgery was performed. RANKL-soaked collagen sponges were removed, and dental implants were placed with bone grafts in five groups: implant only, TCP, and TCP + rhBMP-2 at 5, 15, and 45 μg. Peri-implant bone generation was determined by radiologic and histologic evaluations at 6 weeks after dental implant placement. On performing micro-computed tomography analysis, the group with TCP + 5 μg rhBMP-2 showed the highest bone volume than the other groups and a 22% increase (p osteoporotic canine mandible model was useful for peri-implant bone regeneration under osteoporotic conditions such as those found in geriatric patients. The injectable β-TCP bone grafts used in this study were effective in peri-implant bone generation under osteoporotic conditions, and their efficiency was enhanced at 5 μg BMP-2 compared with higher concentrations of BMP-2.

  6. Calpastatin-mediated inhibition of calpains in the mouse brain prevents mutant ataxin 3 proteolysis, nuclear localization and aggregation, relieving Machado-Joseph disease.

    Science.gov (United States)

    Simões, Ana T; Gonçalves, Nélio; Koeppen, Arnulf; Déglon, Nicole; Kügler, Sebastian; Duarte, Carlos Bandeira; Pereira de Almeida, Luís

    2012-08-01

    Machado-Joseph disease is the most frequently found dominantly-inherited cerebellar ataxia. Over-repetition of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within the ataxin 3 protein, which upon proteolysis may trigger Machado-Joseph disease. We investigated the role of calpains in the generation of toxic ataxin 3 fragments and pathogenesis of Machado-Joseph disease. For this purpose, we inhibited calpain activity in mouse models of Machado-Joseph disease by overexpressing the endogenous calpain-inhibitor calpastatin. Calpain blockage reduced the size and number of mutant ataxin 3 inclusions, neuronal dysfunction and neurodegeneration. By reducing fragmentation of ataxin 3, calpastatin overexpression modified the subcellular localization of mutant ataxin 3 restraining the protein in the cytoplasm, reducing aggregation and nuclear toxicity and overcoming calpastatin depletion observed upon mutant ataxin 3 expression. Our findings are the first in vivo proof that mutant ataxin 3 proteolysis by calpains mediates its translocation to the nucleus, aggregation and toxicity and that inhibition of calpains may provide an effective therapy for Machado-Joseph disease.

  7. Geological disposal of radioactive waste: national commitment, local and regional involvement - A Collective Statement of the OECD Nuclear Energy Agency Radioactive Waste Management Committee Adopted March 2012

    International Nuclear Information System (INIS)

    2012-01-01

    Disposal in engineered facilities built in stable, deep geological formations is the reference solution for permanently isolating long-lived radioactive waste from the human biosphere. This management method is designed to be intrinsically safe and final, meaning that it is not dependent on human presence or intervention in order to fulfil its safety goal. Selecting the site of a waste repository brings up a range of issues involving scientific knowledge, technical capacity, ethical values, territorial planning, community well-being and more. Bringing to fruition the multi-decade task of siting and developing a repository demands a strong national commitment and significant regional and local involvement. This collective statement by the Radioactive Waste Management Committee of the OECD Nuclear Energy Agency recognises the advances made towards greater transparency and dialogue among the diverse stakeholders concerned and identifies the fundamental elements needed to support national commitment and to foster territorial involvement. It concludes that technical and societal partners can develop shared confidence in the safety of geological repositories and jointly carry these projects forward [fr

  8. Correction Technique for Raman Water Vapor Lidar Signal-Dependent Bias and Suitability for Water Wapor Trend Monitoring in the Upper Troposphere

    Science.gov (United States)

    Whiteman, D. N.; Cadirola, M.; Venable, D.; Calhoun, M.; Miloshevich, L; Vermeesch, K.; Twigg, L.; Dirisu, A.; Hurst, D.; Hall, E.; hide

    2012-01-01

    The MOHAVE-2009 campaign brought together diverse instrumentation for measuring atmospheric water vapor. We report on the participation of the ALVICE (Atmospheric Laboratory for Validation, Interagency Collaboration and Education) mobile laboratory in the MOHAVE-2009 campaign. In appendices we also report on the performance of the corrected Vaisala RS92 radiosonde measurements during the campaign, on a new radiosonde based calibration algorithm that reduces the influence of atmospheric variability on the derived calibration constant, and on other results of the ALVICE deployment. The MOHAVE-2009 campaign permitted the Raman lidar systems participating to discover and address measurement biases in the upper troposphere and lower stratosphere. The ALVICE lidar system was found to possess a wet bias which was attributed to fluorescence of insect material that was deposited on the telescope early in the mission. Other sources of wet biases are discussed and data from other Raman lidar systems are investigated, revealing that wet biases in upper tropospheric (UT) and lower stratospheric (LS) water vapor measurements appear to be quite common in Raman lidar systems. Lower stratospheric climatology of water vapor is investigated both as a means to check for the existence of these wet biases in Raman lidar data and as a source of correction for the bias. A correction technique is derived and applied to the ALVICE lidar water vapor profiles. Good agreement is found between corrected ALVICE lidar measurments and those of RS92, frost point hygrometer and total column water. The correction is offered as a general method to both quality control Raman water vapor lidar data and to correct those data that have signal-dependent bias. The influence of the correction is shown to be small at regions in the upper troposphere where recent work indicates detection of trends in atmospheric water vapor may be most robust. The correction shown here holds promise for permitting useful upper

  9. Correction technique for Raman water vapor lidar signal-dependent bias and suitability for water vapor trend monitoring in the upper troposphere

    Directory of Open Access Journals (Sweden)

    D. N. Whiteman

    2012-11-01

    Full Text Available The MOHAVE-2009 campaign brought together diverse instrumentation for measuring atmospheric water vapor. We report on the participation of the ALVICE (Atmospheric Laboratory for Validation, Interagency Collaboration and Education mobile laboratory in the MOHAVE-2009 campaign. In appendices we also report on the performance of the corrected Vaisala RS92 radiosonde measurements during the campaign, on a new radiosonde based calibration algorithm that reduces the influence of atmospheric variability on the derived calibration constant, and on other results of the ALVICE deployment. The MOHAVE-2009 campaign permitted the Raman lidar systems participating to discover and address measurement biases in the upper troposphere and lower stratosphere. The ALVICE lidar system was found to possess a wet bias which was attributed to fluorescence of insect material that was deposited on the telescope early in the mission. Other sources of wet biases are discussed and data from other Raman lidar systems are investigated, revealing that wet biases in upper tropospheric (UT and lower stratospheric (LS water vapor measurements appear to be quite common in Raman lidar systems. Lower stratospheric climatology of water vapor is investigated both as a means to check for the existence of these wet biases in Raman lidar data and as a source of correction for the bias. A correction technique is derived and applied to the ALVICE lidar water vapor profiles. Good agreement is found between corrected ALVICE lidar measurments and those of RS92, frost point hygrometer and total column water. The correction is offered as a general method to both quality control Raman water vapor lidar data and to correct those data that have signal-dependent bias. The influence of the correction is shown to be small at regions in the upper troposphere where recent work indicates detection of trends in atmospheric water vapor may be most robust. The correction shown here holds promise for

  10. Global and local cancer risks after the Fukushima Nuclear Power Plant accident as seen from Chernobyl: a modeling study for radiocaesium ((134)Cs &(137)Cs).

    Science.gov (United States)

    Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Møller, Anders Pape

    2014-03-01

    The accident at the Fukushima Daiichi Nuclear Power Plant (NPP) in Japan resulted in the release of a large number of fission products that were transported worldwide. We study the effects of two of the most dangerous radionuclides emitted, (137)Cs (half-life: 30.2years) and (134)Cs (half-life: 2.06years), which were transported across the world constituting the global fallout (together with iodine isotopes and noble gasses) after nuclear releases. The main purpose is to provide preliminary cancer risk estimates after the Fukushima NPP accident, in terms of excess lifetime incident and death risks, prior to epidemiology, and compare them with those occurred after the Chernobyl accident. Moreover, cancer risks are presented for the local population in the form of high-resolution risk maps for 3 population classes and for both sexes. The atmospheric transport model LMDZORINCA was used to simulate the global dispersion of radiocaesium after the accident. Air and ground activity concentrations have been incorporated with monitoring data as input to the LNT-model (Linear Non-Threshold) frequently used in risk assessments of all solid cancers. Cancer risks were estimated to be small for the global population in regions outside Japan. Women are more sensitive to radiation than men, although the largest risks were recorded for infants; the risk is not depended on the sex at the age-at-exposure. Radiation risks from Fukushima were more enhanced near the plant, while the evacuation measures were crucial for its reduction. According to our estimations, 730-1700 excess cancer incidents are expected of which around 65% may be fatal, which are very close to what has been already published (see references therein). Finally, we applied the same calculations using the DDREF (Dose and Dose Rate Effectiveness Factor), which is recommended by the ICRP, UNSCEAR and EPA as an alternative reduction factor instead of using a threshold value (which is still unknown). Excess lifetime cancer

  11. Troponin T3 regulates nuclear localization of the calcium channel Ca{sub v}β{sub 1a} subunit in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Tan; Taylor, Jackson; Jiang, Yang [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Pereyra, Andrea S. [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Messi, Maria Laura; Wang, Zhong-Min [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Hereñú, Claudia [Department of Histology, National University of La Plata, 1900 La Plata (Argentina); Delbono, Osvaldo, E-mail: odelbono@wakehealth.edu [Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States); Neuroscience Program, Wake Forest School of Medicine, Winston-Salem, NC 27157 (United States)

    2015-08-15

    The voltage-gated calcium channel (Ca{sub v}) β{sub 1a} subunit (Ca{sub v}β{sub 1a}) plays an important role in excitation–contraction coupling (ECC), a process in the myoplasm that leads to muscle-force generation. Recently, we discovered that the Ca{sub v}β{sub 1a} subunit travels to the nucleus of skeletal muscle cells where it helps to regulate gene transcription. To determine how it travels to the nucleus, we performed a yeast two-hybrid screening of the mouse fast skeletal muscle cDNA library and identified an interaction with troponin T3 (TnT3), which we subsequently confirmed by co-immunoprecipitation and co-localization assays in mouse skeletal muscle in vivo and in cultured C2C12 muscle cells. Interacting domains were mapped to the leucine zipper domain in TnT3 COOH-terminus (160–244 aa) and Ca{sub v}β{sub 1a} NH{sub 2}-terminus (1–99 aa), respectively. The double fluorescence assay in C2C12 cells co-expressing TnT3/DsRed and Ca{sub v}β{sub 1a}/YFP shows that TnT3 facilitates Ca{sub v}β{sub 1a} nuclear recruitment, suggesting that the two proteins play a heretofore unknown role during early muscle differentiation in addition to their classical role in ECC regulation. - Highlights: • Previously, we demonstrated that Ca{sub v}β{sub 1a} is a gene transcription regulator. • Here, we show that TnT3 interacts with Ca{sub v}β{sub 1a}. • We mapped TnT3 and Ca{sub v}β{sub 1a} interaction domain. • TnT3 facilitates Ca{sub v}β{sub 1a} nuclear enrichment. • The two proteins play a heretofore unknown role during early muscle differentiation.

  12. Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins andCas9mRNA for Genome Editing in Zebrafish.

    Science.gov (United States)

    Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

    2018-01-02

    CRISPR/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N, C, or both N and C termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7E1 assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that high frequency of indels occurred in the target sites ( tyr1 >63%, tyr2 >74%, gol1 >50% and gol2 >35%), as well as various types ( > 6 ) of indel mutations observed in all four types of Cas9 injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNA have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on gRNAs and gene loci These findings may help to simplify selection of Cas9 for gene editing using the CRISPR/Cas9 system. Copyright © 2018, G3: Genes, Genomes, Genetics.

  13. Effective gene delivery into adipose-derived stem cells: transfection of cells in suspension with the use of a nuclear localization signal peptide-conjugated polyethylenimine.

    Science.gov (United States)

    Park, Eulsoon; Cho, Hong-Baek; Takimoto, Koichi

    2015-05-01

    Adipose-derived stem cells have the ability to turn into several clinically important cell types. However, it is difficult to transfect these cells with the use of conventional cationic lipid-based reagents. Polyethylenimine (PEI) is considered to be an inexpensive and effective tool for delivery of nucleic acids into mammalian cells. We used a linear PEI conjugated with the nuclear localization signal (NLS) peptide of Simian vacuolating virus 40 large T antigen (PEI-NLS) for transfection of plasmid DNA into adipose-derived cells. We also tested if transfection of cells in suspension might improve the degree and duration of exogenous gene expression. Transfection of cells in suspension with the use of a PEI conjugated with an NLS peptide resulted in high levels of reporter gene expression for an extended period of time in clonal 3T3-L1 preadipocytes and native human adipose-derived stem cells. The reporter gene expression increased for 3 days after the addition of the PEI-NLS peptide-DNA mixture in cell suspension and remained significant for at least 7 days. Cell density did not influence the level of reporter gene expression. Thus, the suspension method with the use of an NLS peptide-conjugated PEI leads to a robust and sustained expression of exogenous genes in adipose-derived cells. The devised transfection method may be useful for reprogramming of adipose-derived stem cells and cell-based therapy. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Taperin (c9orf75, a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1α docking protein

    Directory of Open Access Journals (Sweden)

    Tony Ferrar

    2012-02-01

    The promiscuous activity of protein phosphatase one (PP1 is controlled in the cell by associated proteins termed regulatory or targeting subunits. Using biochemical and proteomic approaches we demonstrate that the autosomal recessive nonsyndromic hearing loss gene, taperin (C9orf75, encodes a protein that preferentially docks the alpha isoform of PP1. Taperin associates with PP1 through a classic ‘RVxF’ motif and suppresses the general phosphatase activity of the enzyme. The steady-state localization of taperin is predominantly nuclear, however we demonstrate here that the protein can shuttle between the nucleus and cytoplasm and that it is found complexed to PP1 in both of these cellular compartments. Although originally identified as a hearing loss gene, Western blot analyses with taperin-specific antibodies revealed that the protein is widely expressed across mammalian tissues as multiple splice variants. Taperin is a recent proteome addition appearing during the vertebrate lineage with the PP1 binding site embedded within the most conserved region of the protein. Taperin also shares an ancestral relationship with the cytosolic actin binding protein phostensin, another PP1 interacting partner. Quantitative Stable Isotope Labeling by Amino acids in Culture (SILAC-based mass spectrometry was employed to uncover additional taperin binding partners, and revealed an interaction with the DNA damage response proteins Ku70, Ku80, PARP and topoisomerases I and IIα. Consistent with this, we demonstrate the active recruitment of taperin to sites of DNA damage. This makes taperin a new addition to the family of PP1 targeting subunits involved in the DNA damage repair pathway.

  15. Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish

    Science.gov (United States)

    Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

    2018-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites (tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. PMID:29295818

  16. Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish

    Directory of Open Access Journals (Sweden)

    Peinan Hu

    2018-03-01

    Full Text Available The clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1 assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites (tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%, as well as various types (more than six of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system.

  17. Transferred nuclear Overhauser enhancement experiments show that the monoclonal antibody strep 9 selects a local minimum conformation of a Streptococcus group A trisaccharide-hapten.

    Science.gov (United States)

    Weimar, T; Harris, S L; Pitner, J B; Bock, K; Pinto, B M

    1995-10-17

    Transferred nuclear Overhauser enhancement (TRNOE) experiments have been performed to investigate the bound conformation of the trisaccharide repeating unit of the Streptococcus Group A cell-wall polysaccharide. Thus, the conformations of propyl 3-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-O-(alpha-L-rhamnopyran osyl)- alpha-L-rhamnopyranoside [C(A')B] (1) as a free ligand and when complexed to the monoclonal antibody Strep 9 were examined. Improved insights about the conformational preferences of the glycosidic linkages of the trisaccharide ligand showed that the free ligand populates various conformations in aqueous solution, thus displaying relatively flexible behavior. The NOE HNAc-H2A', which was not detected in previous work, accounts for a conformation at the beta-(1-->3) linkage with a phi angle of approximately 180 degrees. Observed TRNOEs for the complex are weak, and their analysis was further complicated by spin diffusion. With the use of transferred rotating-frame Overhauser enhancement (TRROE) experiments, the amount of spin diffusion was assessed experimentally, proving that all of the observed long-range TRNOEs arose through spin diffusion. Four interglycosidic distances, derived from the remaining TRNOEs and TRROEs, together with repulsive constraints, derived from the absence of TRROE effects, were used as input parameters in simulated annealing and molecular mechanics calculations to determine the bound conformation of the trisaccharide. Complexation by the antibody results in the selection of one defined conformation of the carbohydrate hapten. This bound conformation, which is a local energy minimum on the energy maps calculated for the trisaccharide ligand, shows only a change from a +gauche to a -gauche orientation at the psi angle of the alpha-(1-->2) linkage when compared to the global minimum conformation. The results infer that the bound conformation of the Streptococcus Group A cell-wall polysaccharide is different from its

  18. Nuclear imaging

    International Nuclear Information System (INIS)

    Miller, J.H.; Reid, B.S.

    1985-01-01

    Nuclear imaging, utilizing relatively low photon energy emitting isotopes, allows an assessment of anatomic configuration and organ function. This method of imaging is predicted on the utilization of physiologically active radioisotope-labeled compounds or biologically active radioisotopes. Localization of such isotopes in normal or abnormal concentrations may be due to varying physiological or pathological mechanisms

  19. Collaboration of local governments and experts responding to the increase of the environmental radiation level secondary to the nuclear accident: a unique activity to relieve residents' anxiety

    International Nuclear Information System (INIS)

    Fujii, H.; Hamamichi, S.; Iimoto, T.; Tsuzuki, T.; Iiizumi, S.; Someya, S.; Kessler, M.M.

    2015-01-01

    After the Fukushima nuclear power plant accident, 'hot spots' were found in Tokatsu area in Chiba prefecture. Although ambient radiation dose in this area was too low to harm residents' health, local residents were particularly worried about possible adverse effects from exposure to radiation. To avoid unnecessary panic reactions in the public, local governments in Tokatsu area collaborated with radiation specialists and conducted activities to provide local residents with accurate information on health effects from radiation. In addition to these activities, the authors offered one-to-one consultations with a radiologist for parents of small children and expecting mothers. They herein report this unique attempt, focusing on parents' anxiety and the age of their children. Taken together, this unique collaborative activity between local government and experts would be one of the procedures to relieve residents' anxiety. (authors)

  20. Loss of Nuclear Localized and Tyrosine Phosphorylated Stat5 in Breast Cancer Predicts Poor Clinical Outcome and Increased Risk of Antiestrogen Therapy Failure

    Science.gov (United States)

    Peck, Amy R.; Witkiewicz, Agnieszka K.; Liu, Chengbao; Stringer, Ginger A.; Klimowicz, Alexander C.; Pequignot, Edward; Freydin, Boris; Tran, Thai H.; Yang, Ning; Rosenberg, Anne L.; Hooke, Jeffrey A.; Kovatich, Albert J.; Nevalainen, Marja T.; Shriver, Craig D.; Hyslop, Terry; Sauter, Guido; Rimm, David L.; Magliocco, Anthony M.; Rui, Hallgeir

    2011-01-01

    Purpose To investigate nuclear localized and tyrosine phosphorylated Stat5 (Nuc-pYStat5) as a marker of prognosis in node-negative breast cancer and as a predictor of response to antiestrogen therapy. Patients and Methods Levels of Nuc-pYStat5 were analyzed in five archival cohorts of breast cancer by traditional diaminobenzidine-chromogen immunostaining and pathologist scoring of whole tissue sections or by immunofluorescence and automated quantitative analysis (AQUA) of tissue microarrays. Results Nuc-pYStat5 was an independent prognostic marker as measured by cancer-specific survival (CSS) in patients with node-negative breast cancer who did not receive systemic adjuvant therapy, when adjusted for common pathology parameters in multivariate analyses both by standard chromogen detection with pathologist scoring of whole tissue sections (cohort I; n = 233) and quantitative immunofluorescence of a tissue microarray (cohort II; n = 291). Two distinct monoclonal antibodies gave concordant results. A progression array (cohort III; n = 180) revealed frequent loss of Nuc-pYStat5 in invasive carcinoma compared to normal breast epithelia or ductal carcinoma in situ, and general loss of Nuc-pYStat5 in lymph node metastases. In cohort IV (n = 221), loss of Nuc-pYStat5 was associated with increased risk of antiestrogen therapy failure as measured by univariate CSS and time to recurrence (TTR). More sensitive AQUA quantification of Nuc-pYStat5 in antiestrogen-treated patients (cohort V; n = 97) identified by multivariate analysis patients with low Nuc-pYStat5 at elevated risk for therapy failure (CSS hazard ratio [HR], 21.55; 95% CI, 5.61 to 82.77; P < .001; TTR HR, 7.30; 95% CI, 2.34 to 22.78; P = .001). Conclusion Nuc-pYStat5 is an independent prognostic marker in node-negative breast cancer. If confirmed in prospective studies, Nuc-pYStat5 may become a useful predictive marker of response to adjuvant hormone therapy. PMID:21576635

  1. Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer's disease brain.

    Science.gov (United States)

    Love, Julia E; Day, Ryan J; Gause, Justin W; Brown, Raquel J; Pu, Xinzhu; Theis, Dustin I; Caraway, Chad A; Poon, Wayne W; Rahman, Abir A; Morrison, Brad E; Rohn, Troy T

    2017-01-01

    Although harboring the apolipoprotein E4 ( APOE4 ) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment. In addition, this antibody also detected a ~17 kDa amino-terminal fragment of apoE4 following incubation with collagenase and matrix metalloproteinase-9 (MMP-9), but did not react with full-length apoE4. Application of this amino-terminal apoE cleavage-fragment (nApoECFp17) antibody, revealed nuclear labeling within glial cells and labeling of a subset of neurofibrillary tangles in the human AD brain. A quantitative analysis indicated that roughly 80% of labeled nuclei were microglia. To confirm these findings, cultured BV2 microglia cells were incubated with the amino-terminal fragment of apoE4 corresponding to the cleavage site at D151. The results indicated efficient uptake of this fragment and trafficking to the nucleus that also resulted in significant cell death. In contrast, a similarly designed apoE3 fragment showed no toxicity and primarily localized within the cytoplasm. These data suggest a novel cleavage event by which apoE4 is cleaved by the extracellular proteases, collagenase and MMP-9, generating an amino-terminal fragment that is then taken up by microglia, traffics to the nucleus and promotes cell death. Collectively, these findings provide important mechanistic insights into the mechanism by which harboring the APOE4 allele may elevate dementia risk observed in AD.

  2. Emission of {sup 14}C by the Almirante Alvaro Alberto Nuclear Power Plant 1 and 2 and their local effects on the environmental levels; Emissao de {sup 14}C pelas unidades 1 e 2 da Central Nuclear Almirante Alvaro Alberto (CNAAA) e seu efeito local nos niveis ambientais

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Cintia Melazo

    2006-07-01

    {sup 14}C is a is a long-lived beta-emitting nuclide (T{sub 1/2} = 5730 years) produced naturally in the upper atmosphere as a result of reactions between neutrons and stable {sup 14}N({sup 14}N(n,p){sup 14}C). Although in a lesser extent, nuclear power plants produce {sup 14}C as well during their routine operation. Since it is converted in {sup 14}CO{sub 2} and mixed throughout the atmosphere, it is incorporated into plant tissues, via photosynthesis process, and hence in food chain. Because of the biological importance of {sup 14}C and long half-life, it is of interest to quantify the amounts released by nuclear industry. The Brazilian nuclear central named Nuclear Central Admiral Alvaro Alberto (CNAAA) has two nuclear reactors of PWR type in operation, Angra I (657 MWe) and Angra II (1350 MWe), and one under construction, Angra III (1309 MWe PWR). The aim of this study was to determine the strength of the sources and the {sup 14}C content in the environment through analyses of air, vegetation and soils taken within 5 km (the influenced area) of CNAAA. The thesis consists of an extensive review about the subject (part one) and of four papers (part two). The first paper is about the determination of {sup 14}C concentrations released by reactors (source strength). For Angra I, a device was developed in order to sample the gaseous effluents and for Angra II, a commercial monitoring system had already been implemented since its initial operation (2001). The {sup 14}C can be emitted as hydrocarbons, CO or CO{sub 2}, depending on the type of reactor. For PWRs, the main chemical form released is hydrocarbons (80 %). The monitoring system of Angra I was planned to determine both CO{sub 2} and hydrocarbon fractions but in Angra II, all hydrocarbons are converted to CO{sub 2} by using a Pd/Al{sub 2}O{sub 3} catalyst at 450 deg C. The liquid scintillation was the method employed to measure the samples. The second one concerns the atmospheric dispersion of the released

  3. Argentine nuclear program

    International Nuclear Information System (INIS)

    Leibovich, H.; Takacs, E.A.

    1983-01-01

    The paper describes Argentina's nuclear program, detailing its objectives, the schedule of construction of nuclear plants and local production of required equipment. The technologies adopted so far, the local industrial and engineering participation, the preliminary study for the construction of the next power station and Argentina's nonproliferation nuclear policy are analyzed. Argentina's point of view on Canadian nonproliferation policy and CANDU reactor export is discussed

  4. Nuclear energy and nuclear technology in Switzerland

    International Nuclear Information System (INIS)

    Graf, P.

    1975-01-01

    The energy crisis, high fuel costs and slow progress in the development of alternative energy sources, e.g. solar energy have given further impetus to nuclear power generation. The Swiss nuclear energy programme is discussed and details are given of nuclear station in operation, under construction, in the project stage and of Swiss participation in foreign nuclear stations. Reference is made to the difficulties, delays and resulting cost increases caused by local and regional opposition to nuclear power stations. The significant contributions made by Swiss industry and Swiss consulting engineers are discussed. (P.G.R.)

  5. Nuclear microprobe

    International Nuclear Information System (INIS)

    Engelmann, C.

    1989-01-01

    The nuclear microprobe allows punctual analysis and localization of detected elements inside the volume swept by the particle beam. Particularly well adapted for light elements (and their isotopes) determination. They are detected by nuclear reaction and selectivity is obtained by choice of particles and their energy. Other elements are analyzed by X-ray spectra obtained with the primary ion beam. In some cases concentration profils are obtained in few micrometers and are non-destructive. Operation principle, equipment, performance and examples of applications are reviewed. 71 refs [fr

  6. Nuclear law - Nuclear safety

    International Nuclear Information System (INIS)

    Pontier, Jean-Marie; Roux, Emmanuel; Leger, Marc; Deguergue, Maryse; Vallar, Christian; Pissaloux, Jean-Luc; Bernie-Boissard, Catherine; Thireau, Veronique; Takahashi, Nobuyuki; Spencer, Mary; Zhang, Li; Park, Kyun Sung; Artus, J.C.

    2012-01-01

    This book contains the contributions presented during a one-day seminar. The authors propose a framework for a legal approach to nuclear safety, a discussion of the 2009/71/EURATOM directive which establishes a European framework for nuclear safety in nuclear installations, a comment on nuclear safety and environmental governance, a discussion of the relationship between citizenship and nuclear, some thoughts about the Nuclear Safety Authority, an overview of the situation regarding the safety in nuclear waste burying, a comment on the Nome law with respect to electricity price and nuclear safety, a comment on the legal consequences of the Fukushima accident on nuclear safety in the Japanese law, a presentation of the USA nuclear regulation, an overview of nuclear safety in China, and a discussion of nuclear safety in the medical sector

  7. Assessment of extreme hydrological conditions in the Bothnian Bay, Baltic Sea, and the impact of the nuclear power plant ''Hanhikivi-1'' on the local thermal regime

    Energy Technology Data Exchange (ETDEWEB)

    Dvornikov, Anton Y.; Martyanov, Stanislav D.; Ryabchenko, Vladimir A.; Isaev, Alexey V. [Russian Academy of Sciences, St. Petersburg (Russian Federation). P.P. Shirshov Inst. of Oceanology; Eremina, Tatjana R. [Russian State Hydrometeorological Univ., St. Petersburg (Russian Federation); Sein, Dmitry V. [Helmholtz Centre for Polar and Marine Research, Bremerhaven (Germany). Alfred Wegener Inst.

    2017-07-01

    The results of the study aimed to assess the influence of future nuclear power plant ''Hanhikivi-1'' upon the local thermal conditions in the Bothnian Bay in the Baltic Sea are presented. A number of experiments with different numerical models were also carried out in order to estimate the extreme hydro-meteorological conditions in the area of the construction. The numerical experiments were fulfilled both with analytically specified external forcing and with real external forcing for 2 years: a cold year (2010) and a warm year (2014). The study has shown that the extreme values of sea level and water temperature and the characteristics of wind waves and sea ice in the vicinity of the future nuclear power plant can be significant and sometimes catastrophic. Permanent release of heat into the marine environment from an operating nuclear power plant will lead to a strong increase in temperature and the disappearance of ice cover within a 2 km vicinity of the station. These effects should be taken into account when assessing local climate changes in the future.

  8. Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo

    International Nuclear Information System (INIS)

    Hoeflich, A.; Reisinger, R.; Schuett, B.S.; Elmlinger, M.W.; Russo, V.C.; Vargas, G.A.; Jehle, P.M.; Lahm, H.; Renner-Mueller, I.; Wolf, E.

    2004-01-01

    Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most important IGFBPs has never been assessed in the intracellular compartment in vivo. Since there is evidence for novel intracellular functions of distinct IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In peri/nuclear fractions of various tissues isolated from IGFBP-2 transgenic and non-transgenic mice we were able to show the presence of intact IGFBP-2. In addition, we demonstrate the presence of a highly conserved carboxyl-terminal IGFBP-2 fragment in the peri/nuclear fraction by using different peptide-induced antibodies. In pancreatic sections, confocal microscopy revealed the presence of IGFBP-2 on the nuclear surface but not within the nucleus. Our findings suggest novel functions of intact IGFBP-2 and IGFBP-2 fragments within the cell

  9. Chinese nuclear insurance and Chinese nuclear insurance pool

    International Nuclear Information System (INIS)

    Gong Zhiqi

    2000-01-01

    Chinese Nuclear Insurance Started with Daya Bay Nuclear Power Station, PICC issued the insurance policy. Nuclear insurance cooperation between Chinese and international pool's organizations was set up in 1989. In 1996, the Chinese Nuclear Insurance Pool was prepared. The Chinese Nuclear Insurance Pool was approved by The Chinese Insurance Regulatory Committee in May of 1999. The principal aim is to centralize maximum the insurance capacity for nuclear insurance from local individual insurers and to strengthen the reinsurance relations with international insurance pools so as to provide the high quality insurance service for Chinese nuclear industry. The Member Company of Chinese Nuclear Pool and its roles are introduced in this article

  10. LOCALIZATION OF TRANSCRIPTS OF THE RELATED NUCLEAR ORPHAN RECEPTORS COUP-TF-I AND ARP-1 IN THE ADULT-MOUSE BRAIN

    NARCIS (Netherlands)

    DASILVA, SL; COX, JJ; JONK, LJC; KRUIJER, W; BURBACH, JPH

    The chicken ovalbumin upstream promoter transcription factor, COUP-TF I, and the protein ARP-1 (COUP-TF II) are two highly homologous orphan receptors of the nuclear hormone receptor family. In this study we investigated their expression patterns in the adult nervous system of the mouse. In situ

  11. Impact of natural disaster combined with nuclear power plant accidents on local medical services: a case study of Minamisoma Municipal General Hospital after the Great East Japan Earthquake.

    Science.gov (United States)

    Kodama, Yuko; Oikawa, Tomoyoshi; Hayashi, Kaoru; Takano, Michiko; Nagano, Mayumi; Onoda, Katsuko; Yoshida, Toshiharu; Takada, Akemi; Hanai, Tatsuo; Shimada, Shunji; Shimada, Satoko; Nishiuchi, Yasuyuki; Onoda, Syuichi; Monma, Kazuo; Tsubokura, Masaharu; Matsumura, Tomoko; Kami, Masahiro; Kanazawa, Yukio

    2014-12-01

    To elucidate the impacts of nuclear plant accidents on neighboring medical centers, we investigated the operations of our hospital within the first 10 days of the Great East Japan Earthquake followed by the Fukushima Daiichi nuclear power plant accident. Data were extracted from medical records and hospital administrative records covering 11 to 20 March 2011. Factual information on the disaster was obtained from public access media. A total of 622 outpatients and 241 inpatients were treated. Outpatients included 43 injured, 6 with cardiopulmonary arrest, and 573 with chronic diseases. Among the 241 inpatients, 5 died, 137 were discharged, and the other 99 were transferred to other hospitals. No communication methods or medical or food supplies were available for 4 days after the earthquake. Hospital directors allowed employees to leave the hospital on day 4. All 39 temporary workers were evacuated immediately, and 71 of 239 full-time employees remained. These employees handled extra tasks besides patient care and patient transfer to other hospitals. Committed effective doses indicating the magnitude of health risks due to an intake of radioactive cesium into the human body were found to be minimal according to internal radiation exposure screening carried out from July to August 2011. After the disaster, hospitals located within the evacuation zone of a 30-km radius of the nuclear power plant were isolated. Maintenance of the health care system in such an event becomes difficult.

  12. Nuclear Medicine

    Science.gov (United States)

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  13. The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

    OpenAIRE

    He, Shanping; Huang, Kuowei; Zhang, Xu; Yu, Xiangchun; Huang, Ping; An, Chengcai

    2011-01-01

    BACKGROUND: Genetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein-protein interaction. METHODOLOGY/PRINCIPAL FINDINGS: To further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog ...

  14. 16. national conference of the presidents of the local commissions of information (C.L.I.) around nuclear facilities; 16. conference nationale des presidents de commissions locales d'information (CLI) autour des installations nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This conference contained two plenary sessions. The first one concerned the epidemiology with the following subjects: the epidemiology, its contributions and its limits; the epidemiological surveillance of cancers in France: role of registers within the device; the aggregates of leukaemia near the nuclear installations; perception and management of the risk; the point of view of the scientific committee of the A.N.C.L.I.; Followed a work in a workshop on the subjects relative to the functioning of the C.L.I. (Organization, relations, information) then the second plenary session with as subjects: organization and functioning of C.L.I., relations and links with A.N.C.L.I., information received and diffused by the C.L.I. (N.C.)

  15. Invisible nuclear; converting nuclear

    International Nuclear Information System (INIS)

    Park, Jongmoon

    1993-03-01

    This book consists of 14 chapters which are CNN era and big science, from East and West to North and South, illusory nuclear strategy, UN and nuclear arms reduction, management of armaments, advent of petroleum period, the track of nuclear power generation, view of energy, internationalization of environment, the war over water in the Middle East, influence of radiation and an isotope technology transfer and transfer armament into civilian industry, the end of nuclear period and the nuclear Nonproliferation, national scientific and technological power and political organ and executive organ.

  16. Anti-nuclear movements

    International Nuclear Information System (INIS)

    Ruedig, W.

    1990-01-01

    Nuclear power, heralded in the years after World War II as the answer to the world's energy needs, has in more recent times become the focus of intense ecological, political and economic debate. In this study, the current worldwide opposition to nuclear power is examined from its origins in expert dissent to the widespread development of grassroots activity. Chapter headings include: Social Movements: A Theoretical Framework; Creating the Preconditions for Public Protest; Local and Regional Opposition: Mobilizing the Grass Roots; Local Opposition and the Politicization of Nuclear Power; The Use of Local Opposition as a Political Resource; Local Opposition and Social Movement Analysis; The Removal of Political Stimuli: The Unpolitics of Nuclear Siting; Analyzing Host Community Attitudes: The Survey Evidence; Attitudes and Political Action of Nuclear Host Communities: Approaches and Explanations; Novel Siting Approaches and their Political Implications; Siting and Social Movement Analysis; Patterns and Outcomes of Nuclear Energy Conflicts; The Future of the Nuclear Energy Conflict. Throughout the text, analysis and theory are blended with detailed accounts of the growth and activities of individual anti-nuclear organizations in different countries. (author)

  17. Nuclear desalination

    International Nuclear Information System (INIS)

    Huyghe, J.

    1975-01-01

    The use of small or medium size nuclear reactors for the desalination of sea water has gained economic interest since the increase of oil prices. These reactors, with a wide range of power from 135 to 1,100Mwth, are parrticularly interesting because their production of fresh water or electricity is tailored to the present need. The replacement of conventional fuel boilers by nuclear reactor boilers does not change the traditional desalination technology and alters very little the coupling of the electricity and water producing parts of the plant. It is a reasonable assumption that the performance of desalination plants will increase with the optimization of the design technology of a mixed plant. The cost of the water produced in a mixed plant is mainly related to local conditions and to the method of splitting the cost between water and electricity. It is therefore impossible to give in this paper a cost for the fresh water production [fr

  18. Localización extra nuclear de receptores esteroides y activación de mecanismos no genómicos Extra nuclear localization of steroid receptors and non genomic activation mechanisms

    Directory of Open Access Journals (Sweden)

    María Cecilia Bottino

    2010-04-01

    Full Text Available Los receptores de hormonas esteroides han sido considerados históricamente como factores de transcripción nucleares. Sin embargo, en los últimos años surgieron evidencias que indican que su activación desencadena eventos rápidos, independientes de la transcripción y que involucran a diferentes segundos mensajeros; muchos de estos receptores han sido localizados en la membrana celular. Por otra parte, se han caracterizado varios receptores de hormonas esteroides noveles, de estructura molecular diferente al receptor clásico, localizados principalmente en la membrana celular. Esta revisión enfoca los diferentes efectos iniciados por los glucocorticoides, mineralocorticoides, andrógenos, estrógenos y progesterona, y los posibles receptores involucrados en los mismos.Steroid hormone receptors have been historically considered as nuclear transcription factors. Nevertheless, in the last years, many of them have been detected in the cellular membrane. It has been postulated that their activation can induce transcription independent rapid events involving different second messengers. In addition, several novel steroid hormone receptors, showing a different molecular structure than the classical ones, have also been characterized and most of them are also located in the plasmatic membrane. This review focuses on the variety of effects initiated by glucocorticoids, mineralocorticoids, androgens, estrogens and progesterone, and the possible receptors involved mediating these effects.

  19. A gene delivery system containing nuclear localization signal: Increased nucleus import and transfection efficiency with the assistance of RanGAP1.

    Science.gov (United States)

    Chen, Kang; Guo, Lingling; Zhang, Jiulong; Chen, Qing; Wang, Kuanglei; Li, Chenxi; Li, Weinan; Qiao, Mingxi; Zhao, Xiuli; Hu, Haiyang; Chen, Dawei

    2017-01-15

    In the present report, a degradable gene delivery system (PAMS/DNA/10NLS) containing nucleus location signal peptide (NLS) was prepared. The agarose gel electrophoresis, particle size and zeta potential of PAMS/DNA/10NLS were similar to those of PAMS/DNA, which proved that NLS did not affect the interaction between PAMS and DNA. PAMS/DNA/10NLS exhibited marked extracellular and intracellular degradation under acidic conditions. The degradation was believed to allow NLS to come into contact with importins easily, which was able to mediate the nucleus import. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection capability than PAMS/DNA. Moreover, the transfection of PAMS/DNA/10NLS was less dependent on the breakdown of the nucleus envelope than PAMS/DNA. Considering that GTPase-activating protein 1 (RanGAP1) was able to activate the endogenous GTPase, which was necessary for NLS-mediated nucleus import, RanGAP1 overexpressed cells (RanGAP1 cells) were produced. This result showed that RanGAP1 cells had higher GTPase activities than normal cells. Both the nucleus import and transfection efficiency of PAMS/DNA/10NLS were markedly higher in RanGAP1 cells than that in normal cells. The in vivo transfection results also showed that the transfection efficiency of PAMS/DNA/10NLS was higher in RanGAP1 pre-treated mice than that in normal mice. These findings showed that PAMS/DNA/10NLS is a promising gene delivery system with the assistance of RanGAP1. The present report describes the increased transfection efficiency of a degradable gene delivery system (PAMS/DNA/10NLS) containing nuclear location signal (NLS) with the assistance of GTPase-activating protein 1 (RanGAP1). The physicochemical properties of PAMS/DNA/10NLS were similar to those of PAMS/DNA. PAMS/DNA/10NLS exhibited great extracellular and intracellular degradations, which might allow NLS to contact with importins easily. With the help of NLS, PAMS/DNA/10NLS exhibited a higher transfection

  20. Assessment of Nutritional Status of Iodine Through Urinary Iodine Screening Among Local Children and Adolescents After the Fukushima Daiichi Nuclear Power Plant Accident.

    Science.gov (United States)

    Tsubokura, Masaharu; Nomura, Shuhei; Watanobe, Hajime; Nishikawa, Yoshitaka; Suzuki, Chiaki; Ochi, Sae; Leppold, Claire; Kinoshita, Hirokatsu; Kato, Shigeaki; Saito, Yasutoshi

    2016-12-01

    Iodine deficiency is an important modifier of the risk of thyroid cancer following irradiation. However, little information is available on the prevalence of iodine deficiency in Fukushima and its surroundings after the Fukushima Daiichi nuclear power plant accident that occurred in March 2011. In order to assess urinary iodine concentrations (UIC) and the prevalence of iodine deficiency and to elucidate any associations between demographic characteristics and UIC levels among children and adolescents aged ≤18 years at the time of the accident in Fukushima Prefecture and its surroundings, the data on voluntary UIC testing conducted by Hirata Central Hospital, Fukushima, were evaluated. A total of 4410 children and adolescents with a median age of 10 years at examination underwent UIC testing between October 2012 and October 2015. Calculated for all the participants, the median UIC level was 204 μg/L (range 25-21,100 μg/L). There were 133 (3.0%), 732 (16.6%), and 1472 (33.4%) participants with UIC levels of nutritional iodine status, no participants were severely iodine deficient (<20 μg/L), but 16.6% of the population were mildly (50-100 μg/L) or moderately (20-50 μg/L) iodine deficient. While no significant difference in UIC was noted between those who did and did not increase dietary iodine intake after the accident (p = 0.93), there were significant differences by year (p < 0.01), school level (p < 0.001), and residential area at the time of the accident (p < 0.001). This study demonstrates that the children and adolescents examined had a sufficient amount of iodine during the period 1.5-4.5 years after the nuclear accident. In addition to the differences in the scale and the countermeasures undertaken between the Fukushima and Chernobyl accidents, differences in dietary iodine intake might have played an additional role in resulting in the reportedly different radiation doses to the thyroid between the two nuclear accidents.

  1. Correlation among nuclear localization of NuMA-RARα, deregulation of gene expression and leukemic phenotype of hCG-NuMA-RARα transgenic mice.

    Science.gov (United States)

    Sukhai, Mahadeo A; Thomas, Mariam; Hamadanizadeh, Soheila A; Xuan, Yali; Wells, Richard A; Kamel-Reid, Suzanne

    2011-05-01

    Acute promyelocytic leukemia (APL) is a model system of aberrant transcription in cancer. We sought to elucidate the mechanism of action of the variant fusion NuMA-RARα in APL, using the hCG-NuMA-RARα transgenic model. We report that subcellular localization of NuMA-RARα in transgenic mice is dependent upon its protein expression and transgene dosage. Subcellular localization of the fusion is inversely correlated with extent of gene deregulation at the mRNA level for Cebpα, Cebpɛ and Pu.1. Finally, we report that phenotype onset is correlated with NuMA-RARα copy number; mice with higher copy number developing disease later than those with lower copy number. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Localization of a sound source in in a guided medium and reverberating field. Contribution to a study on leak localization in the internal wall of containment of a nuclear reactor in the case of a severe reactor accident

    International Nuclear Information System (INIS)

    Thomann, F.

    1996-01-01

    Basic data necessary for the localization of a leak in the internal wall of the containment are presented by studying the sound generated by gas jets coming out of (leaking fissures) as well as propagation in a guided medium. The results acquired have led us to choose the simple intercorrelation method and the matched filed processing method, both of which are likely to adequately handle our problems. Whereas the intercorrelation method appears to be limited in scope when dealing in the guided medium, the matched field processing is suited to leak localization over a surface of approximately 1000 m 2 (for a total surface of 10 000 m 2 ). Preliminary studies on the leak signal and on replicated signals have led us to limit the frequency band to 2600 - 3000 Hz. We have succeeded in locating a leak situated in an ordinary position with a minimum amount of replicated signals and basic data. We have improved on the estimation of Bartlett and MVDE (minimum variance distortion less filter) rendering them even more effective. Afterwards, we considered the severe accident situation and showed that the system can be installed in situ. (author)

  3. Nevada Nuclear Waste Storage Investigations: A review of requirements for biological information in federal, state, and local environmental laws and regulations

    International Nuclear Information System (INIS)

    Collins, E.; O'Farrell, T.P.

    1987-01-01

    Biological information concerning Yucca Mountain collected since 1980 is evaluated to determine if it is sufficient to satisfy the requirements of the various federal, state, and local laws and regulations that pertain to environmental protection or to development of waste repositories. The pertinent requirements of each law are summarized, missing information is identified, and recommendations are made for studies to fill these gaps. 11 refs., 2 figs., 1 tab

  4. Non local separable interactions in the description of some nuclear properties. Recoil and finite range effects in the CRC formalism for the study of heavy ion transfers

    International Nuclear Information System (INIS)

    Meyer, J.

    1976-01-01

    Some simplifications given by the nonlocal separable interactions (NLSI) allowed an exhaustive study of the three body problem to be performed. This work is intended to show that NLSI are also useful in studying the properties of nuclei. Some satisfactory results obtained in the infinite nuclear matter and also in the Hartree-Fock study of some 3s-1d nuclei are then given. A coupled reaction formalism has been developed for the analysis of heavy ion induced reactions. The recoil and finite range effects, which are necessary tools in heavy-ion induced reactions, have been introduced from the work of Coker et al. for the ( 3 He,t) reaction [fr

  5. Nuclear liability - nuclear insurance

    International Nuclear Information System (INIS)

    Roesch, H.

    1981-01-01

    In the fourth concluding article on this subject (following articles in VW 1981 pp. 483, 552 and 629), the author explains procedures, duties and obligations according to the Para. Para. 5, 6 and 7 of the AHBKA. These obligations are to be observed before or after the occurrence of damages. In addition, legal consequences following violations of duties - loss of right - joint, insurance, transfer ban, period for filing suit, duty to notify, 'The German Nuclear Reactor Insurance and Reinsurance Community', the insurance according to the 'General terms and conditions governing the liability insurance of licensed activities involving nuclear fuels and other radioactive substances outside nuclear installations (AHBStr.)', object, beginning and exclusion of coverage, 'Special conditions governing the transport of nuclear fuels according to Para. 25 (2) of the Atomic Energy Law' are attached to the General Terms and Conditions governing the liability insurance of licenced activities involving nuclear fuels and other radioactive substances outside nuclear installations. (HSCH) [de

  6. Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

    Science.gov (United States)

    Okubo, Shinya; Uto, Takuhiro; Goto, Aya; Tanaka, Hiroyuki; Nishioku, Tsuyoshi; Yamada, Katsushi; Shoyama, Yukihiro

    2017-01-01

    Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.

  7. [Nuclear theory

    International Nuclear Information System (INIS)

    Haxton, W.

    1990-01-01

    This report discusses research in nuclear physics. Topics covered in this paper are: symmetry principles; nuclear astrophysics; nuclear structure; quark-gluon plasma; quantum chromodynamics; symmetry breaking; nuclear deformation; and cold fusion

  8. Localized deformation as a key precursor to initiation of intergranular stress corrosion cracking of austenitic stainless steels employed in nuclear power plants

    Science.gov (United States)

    Karlsen, Wade; Diego, Gonzalo; Devrient, Bastian

    2010-11-01

    Cold-work has been associated with the occurrence of intergranular cracking of stainless steels employed in light water reactors. This study examined the deformation behavior of AISI 304, AISI 347 and a higher stacking fault energy model alloy subjected to bulk cold-work and (for 347) surface deformation. Deformation microstructures of the materials were examined and correlated with their particular mechanical response under different conditions of temperature, strain rate and degree of prior cold-work. Select slow-strain rate tensile tests in autoclaves enabled the role of local strain heterogeneity in crack initiation in pressurized water reactor environments to be considered. The high stacking fault energy material exhibited uniform strain hardening, even at sub-zero temperatures, while the commercial stainless steels showed significant heterogeneity in their strain response. Surface treatments introduced local cold-work, which had a clear effect on the surface roughness and hardness, and on near-surface residual stress profiles. Autoclave tests led to transgranular surface cracking for a circumferentially ground surface, and intergranular crack initiation for a polished surface.

  9. Phenotypic switching induced by damaged matrix is associated with DNA methyltransferase 3A (DNMT3A activity and nuclear localization in smooth muscle cells (SMC.

    Directory of Open Access Journals (Sweden)

    Jia-Xin Jiang

    Full Text Available Extracellular matrix changes are often crucial inciting events for fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are critical factors underlying differentiated phenotypes. We examined the dependency of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases. The cooperativity of matrix with growth factors, cell density and hypoxia was also examined. Primary rat visceral SMC of early passage (0-2 were plated on native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3% O2 (balanced 5% CO2 and 95% N2 over 48 hours. Inhibitors were applied 2-3 hours after cells were plated on matrix, or immediately before hypoxia. Cells were fixed and stained for DNMT3A and smooth muscle actin (SMA or smooth muscle myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite-converted DNA from smooth muscle cells on damaged matrix vs native collagen. Matrix exquisitely regulates DNMT3A localization and expression, and influences differentiation in SMCs exposed to denatured matrix +/- hypoxia. Analysis of DNA methylation signatures showed that Matrix caused significant DNA methylation alterations in a discrete number of CpG sites proximal to genes related to SMC differentiation. Matrix has a profound effect on the regulation of SMC phenotype, which is associated with altered expression, localization of DNMTs and discrete changes DNA methylation.

  10. ANCCLI Scientific Committee - Examination of the authorization request for the creation of the Flamanville 3 Power Production Nuclear Plant. Performed on the request of the ANCCLI (National Association of Local Information Commissions)

    International Nuclear Information System (INIS)

    2006-07-01

    After a synthetic and critical comment, this report proposes a critical analysis of the content of the different volumes of the authorization request made by EDF for the creation of the Flamanville 3 nuclear plant. The volume 1 gathers elements related to information from the public inquiry and for general public. It addresses various aspects which are herein commented: a presentation note, project presentation and location, installation operation principles, site environment, water takings, gaseous and liquid radioactive releases, chemical releases in the Channel, conventional and radioactive waste management, noise, landscape and local economy, management of risks related to the installation, consequences of potential accidents, measures planned at the end of exploitation for dismantling. The other documents of the first volume of the request file address hazards related to the creation of the electric power production unit, and an impact study related to this creation. The volume 2 addresses the identification of potential risks related to the installation, measures adopted to face risks and to limit the consequences of a possible accident during exploitation (safety objectives and principles, safety approach, design principles and evolution), the management of risks of nuclear origin (fuel criticality, loss of control of reactivity, loss of fuel cooling means, risk of dissemination), the management of internal risks of non-nuclear origin, and the management of external risks. The volume 3 addresses the presentation of the studied area and of the impact assessment, the impact on the environment and on health, the background of the choice of the EPR technology, measures to suppress, reduce and, if possible, compensate the consequences and impacts of the project on the environment and health, and the analysis of methods used to assess the project effects on the environment and health

  11. Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk nuclear test site. Part 2: International exposure to thyroid

    International Nuclear Information System (INIS)

    Gordeev, Konstantin; Shinkarev, Sergey; Ilyin, Leonid; Bouville, Andre; Luckyanov, Nickolas; Simon, Steven L.; Hoshi, Masaharu

    2006-01-01

    A methodology to assess internal exposure to thyroid from radioiodines for the residents living in settlements located in the vicinity of the Semipalatinsk Nuclear Test Site is described that is the result of many years of research, primarily at the Moscow Institute of Biophysics. This methodology introduces two important concepts. First, the biologically active fraction, is defined as the fraction of the total activity on fallout particles with diameter less than 50 microns. That fraction is retained by vegetation and will ultimately result in contamination of dairy products. Second, the relative distance is derived as a dimensionless quantity from information on test yield, maximum height of cloud, and average wind velocity and describes how the biologically active fraction is distributed with distance from the site of the explosion. The parameter is derived in such a way that at locations with equal values of relative distance, the biologically active fraction will be the same for any test. The estimates of internal exposure to thyroid for the residents of Dolon and Kanonerka villages, for which the external exposure were assessed and given in a companion paper (Gordeev et al. 2006) in this conference, are presented. The main sources of uncertainty in the estimates are identified. (author)

  12. Perturbation in the 240Pu/239Pu global fallout ratio in local sediment following the nuclear accidents at Thule (Greenland) and Palomares (Spain)

    International Nuclear Information System (INIS)

    Mitchell, P.I.; Vintro, L.L.; Gasco, C.; Sanchez-Cabeza, J.A.

    1995-01-01

    It is well established that the main source of the plutonium found in marine sediments throughout the Northern Hemisphere is global stratospheric fallout, characterized by a typical 240 Pu/ 239 Pu atom ratio of ∼0.18. Measurements of perturbations in this ratio at various sites which had been subjected to close-in fallout, mainly from surface-based testing, has confirmed the feasibility of using this ratio to distinguish plutonium from different fallout sources. In the present study, the 240 Pu/ 239 Pu ratio has been examined in samples of sediment collected at Thule (Greenland) and Palomares (Spain), where accidents involving the release and dispersion of plutonium from fractured nuclear weapons occurred in 1968 and 1966, respectively. The 240 Pu/ 239 Pu ratio was measured by high-resolution alpha spectrometry and spectral deconvolution. The analytical results showed that at Thule the mean 240 Pu/ 239 Pu atom ratio was 0.033±0.004, while at Palomares the equivalent ratio appeared to be significantly higher at 0.056±0.003. Both ratios are consistent with those reported for soils samples at the Nevada site and Nagasaki, and are clearly indicative of weapons-grade plutonium. 27 refs., 1 fig., 2 tabs

  13. History on foundation of Korea nuclear power

    International Nuclear Information System (INIS)

    Park, Ik Su

    1999-12-01

    This reports the history on foundation of Korea nuclear power from 1955 to 1980, which is divided ten chapters. The contents of this book are domestic and foreign affairs before foundation of nuclear power center, establishment of nuclear power and research center, early activity and internal conflict about nuclear power center, study for nuclear power business and commercialization of the studying ordeal over nuclear power administration and new phase, dispute for jurisdiction on nuclear power business and the process, permission for nuclear reactor, regulation and local administration, the process of deliberation and decision of reactor 3. 4 in Yonggwang, introduction of nuclear reprocessing facilities and activities for social organization.

  14. Nuclear cardiology

    International Nuclear Information System (INIS)

    Vos, P.H.

    1982-01-01

    This thesis deals with two topics in nuclear cardiology. In the first, left ventricular wall motion assessment using Fourier transform of local left ventricular time-activity curves in gated blood pool studies is evaluated. In the second, the interpretation of myocardial perfusion scintigrams is assessed which are obtained with thallium-201 or with another radiopharmaceutical with different physical, but identical biological properties. In all these investigations data acquisition and analysis by computer played an essential role. In chapter 1 the desirable properties of a nuclear medicine computer system are given and the computer system used for this work is described. Wall motion analysis of the left ventricle using Fourier transform of local time-activity curves in the left ventricular region in gated blood pool studies is described in chapter 2. In chapter 3 detection of non-perfused lesions in myocardial perfusion scintigraphy with thallium-201 is described. Detection of partly perfused lesions and the influence of scatter and photon energy on myocardial perfusion scintigraphy is described in chapter 4. (Auth.)

  15. Japanese local authorities are reluctant to the reviving of nuclear energy. In Fukushima, the endless decontamination. Despite the hostility of the Japanese opinion, the reviving seems to be established. Japan revives nuclear despite the hostility of its population. Fukushima: a first totally evacuated town is inhabitable again

    International Nuclear Information System (INIS)

    Mesmer, Philippe; Le Hir, Pierre

    2015-01-01

    This document gathers several articles published by Le Monde. The first one comments the opposition of local authorities to the project of restart of 48 Japanese nuclear reactors which have been stopped after the Fukushima accident. A second one discusses the comments made by the IAEA on the progress made by decontamination activities and on its diagnosis of a still very complex situation around Fukushima (the problem of contaminated waters and damaged vessels is notably outlined, as well as the problem of contamination of the Pacific Ocean and measures aimed at limiting this contamination); the issue of poisoned fish and the problem of extraction of contaminated fuel bars are also evoked. The third and fourth articles outline that, despite the opposition of the Japanese opinion and also some political and legal factors (withholding of information, issue of seismic risk), the restart of Japanese nuclear reactors seems to be established, and describe the situation and the commitment of the local population at the vicinity of the Sendai power station. The last article describes the case of the town of Nahara which had been totally evacuated after the Fukushima accident, and is now officially inhabitable again, even though fears are still present

  16. The MRS [Monitored Retrievable Storage] task force: Economic and non-economic incentives for local public acceptance of a proposed nuclear waste packaging and storage facility

    International Nuclear Information System (INIS)

    Peelle, E.

    1987-03-01

    A joint Oak Ridge - Roane County citizen task force (TF) evaluated the Department of Energy's (DOE) proposal to site a Monitored Retrievable Storage facility in Tennessee in terms of environmental, transportation, and socioeconomic impacts. The case study examines how the TF used mitigation, compensation and incentives (economic and non-economic) to address the problem of distrust of DOE and to change the net local impact balance from negative to positive. Intensive group interaction during their investigations and development of trust within the TF led to consensus decisions on safety and conditional acceptance. DOE accepted most of the TF conditions after informal negotiations. The siting process was stopped by extensive state-wide opposition resulting in legal challenge by the state and vetoes by the governor and state legislature

  17. An antifungal peptide from Coffea canephora seeds with sequence homology to glycine-rich proteins exerts membrane permeabilization and nuclear localization in fungi.

    Science.gov (United States)

    Zottich, Umberto; Da Cunha, Maura; Carvalho, André O; Dias, Germana B; Casarin, Nádia; Vasconcelos, Ilka M; Gomes, Valdirene M

    2013-06-01

    The superfamily of glycine-rich proteins (GRPs) corresponds to a large and complex group of plant proteins that may be involved in many developmental and physiological processes such as RNA biogenesis, stress tolerance, pollen hydration and plant-pathogen interactions, showing defensive activity against fungi, bacteria and viruses. In this study, the peptides from Coffea canephora seeds were extracted according to the methods of Egorov et al. (2005). The purified peptide was submitted for amino acid sequencing and antimicrobial activity measurement. The purified peptide with a molecular weight of 7kDa, named Cc-GRP, was observed to display homology to GRPs. The Cc-GRP-fungi interaction led to morphological changes and membrane permeability, including the formation of pseudohyphae, which were visualized with the aid of SYTOX green dye. Additionally, Cc-GRP also prevented colony formation by yeasts. Antifungal assays of Fusarium oxysporum and Colletotrichum lindemuthianum, observed by light microscopy, showed that the two molds exhibited morphological changes after the growth assay. Cc-GRP coupled to FITC and its subsequent treatment with DAPI revealed the presence of the peptide in the cell wall, cell surface and nucleus of F. oxysporum. In this work we purified, characterized and evaluated the in vitro effect on fungi of a new peptide from coffee, named Cc-GRP, which is involved in the plant defense system against pathogens by acting through a membrane permeabilization mechanism and localized in the nuclei of fungal cells. We also showed, for the first time, the intracellular localization of Cc-GRP during antimicrobial assay. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Nuclear power and nuclear weapons

    International Nuclear Information System (INIS)

    Vaughen, V.C.A.

    1983-01-01

    The proliferation of nuclear weapons and the expanded use of nuclear energy for the production of electricity and other peaceful uses are compared. The difference in technologies associated with nuclear weapons and nuclear power plants are described

  19. The testis-specific VAD1.3/AEP1 interacts with {beta}-actin and syntaxin 1 and directs peri-nuclear/Golgi expression with bipartite nucleus localization (BNL) sequence

    Energy Technology Data Exchange (ETDEWEB)

    Zuo, Yan; Gao, Jing [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam (Hong Kong); Yeung, William S.B. [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam (Hong Kong); Centre for Reproduction, Development and Growth, Hong Kong Jockey Club Clinical Research Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Lee, Kai-Fai, E-mail: ckflee@hkucc.hku.hk [Department of Obstetrics and Gynaecology, The University of Hong Kong, Pokfulam (Hong Kong); Centre for Reproduction, Development and Growth, Hong Kong Jockey Club Clinical Research Centre, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong)

    2010-10-15

    Research highlights: {yields} VAD1.3 interacts {beta}-actin and syntaxin 1. {yields} VAD1.3 colocalizes {beta}-actin in spermatids. {yields} The bipartite nucleus localization (BNL) signal is important for peri-nuclear/Golgi expression in transfected cells. {yields} The C-terminal region of VAD1.3 direct nuclei localization. -- Abstract: VAD1.3 (AEP1), a novel testis-specific gene, was first isolated from the testis of a retinol-treated vitamin-A-deficient (VAD) rat model. It is expressed at the acrosomal region of spermatids from postnatal day 25. VAD1.3 immunoreactivity is present in rat, human, monkey and porcine spermatids and spermatozoa, suggesting that VAD1.3 may play a role in acrosome formation. However, direct evidence on the detailed sub-cellular localization of the VAD1.3 protein in the acrosome and how VAD1.3 is involved in acrosome formation remains largely unknown. Here, we isolated and identified VAD1.3 interacting proteins by immunoprecipitation followed by mass spectrometry, and determined the functional motifs of VAD1.3 that were important for its specific sub-cellular location in vitro. We found that VAD1.3 bound to syntaxin 1 and {beta}-actin proteins in vitro. Immunogold electron microscopic study localized VAD1.3 immunoreactivity to the acrosome membranes and matrix, and colocalized it with the {beta}-actin protein. The full-length GFP-VAD (1-3601) and GFP-VAD (1-730) fusion proteins that contain the bipartite nucleus localization (BNL) signal were located in the peri-nucleus/Golgi of the transfected cells. In addition, the GFP signal colocalized with the endoplasmic reticulum marker and the syntaxin 1 protein in the transfected HeLa and GC-2spd cells. The C-terminal GFP-VAD (1770-3601) was expressed in the nucleus. Taken together, VAD1.3 interacts with {beta}-actin and syntaxin 1 in vitro. The BNL signal may mediate the peri-nuclei localization of the protein that may interact with syntaxin 1 and {beta}-actin for acrosome formation in

  20. MAPPING FLOW LOCALIZATION PROCESSES IN DEFORMATION OF IRRADIATED REACTOR STRUCTURAL ALLOYS - FINAL REPORT. Nuclear Energy Research Initiative Program No. MSF99-0072. Period: August 1999 through September 2002. (ORNL/TM-2003/63)

    Energy Technology Data Exchange (ETDEWEB)

    Farrell, K.

    2003-09-26

    Metals that can sustain plastic deformation homogeneously throughout their bulk tend to be tough and malleable. Often, however, if a metal has been hardened it will no longer deform uniformly. Instead, the deformation occurs in narrow bands on a microscopic scale wherein stresses and strains become concentrated in localized zones. This strain localization degrades the mechanical properties of the metal by causing premature plastic instability failure or by inducing the formation of cracks. Irradiation with neutrons hardens a metal and makes it more prone to deformation by strain localization. Although this has been known since the earliest days of radiation damage studies, a full measure of the connection between neutron irradiation hardening and strain localization is wanting, particularly in commercial alloys used in the construction of nuclear reactors. Therefore, the goal of this project is to systematically map the extent of involvement of strain localization processes in plastic deformation of three reactor alloys that have been neutron irradiated. The deformation processes are to be identified and related to changes in the tensile properties of the alloys as functions of neutron fluence (dose) and degree of plastic strain. The intent is to define the role of strain localization in radiation embrittlement phenomena. The three test materials are a tempered bainitic A533B steel, representing reactor pressure vessel steel, an annealed 316 stainless steel and annealed Zircaloy-4 representing reactor internal components. These three alloys cover the range of crystal structures usually encountered in structural alloys, i.e. body-centered cubic (bcc), face-centered cubic (fcc), and close-packed hexagonal (cph), respectively. The experiments were conducted in three Phases, corresponding to the three years duration of the project. Phases 1 and 2 addressed irradiations and tensile tests made at near-ambient temperatures, and covered a wide range of neutron fluences

  1. Extent of local participation

    International Nuclear Information System (INIS)

    Albisu, F.

    1977-01-01

    After a brief historical comment on national participation on past nuclear projects, a description is made of the desirable situation to be achieved as regards local content. The reasons, the procedures and the areas for that participation (i.e., the why, how and where) are suggested, as well as the means to promote it. (orig.) [de

  2. Quantitative evaluation of mental health status of local residents around radio-contaminated area after the Chernobyl nuclear power plant accident

    International Nuclear Information System (INIS)

    Masunaga, Tomoko; Takamura, Noboru; Yamashita, Shunichi; Kozlovsky, A.; Lyzikov, A.

    2012-01-01

    Mental health situation of residents who were born after the Accident around the Area in the title was evaluated by General Health Questionnaire (GHQ)-12 and Additional Questions (AQ) in Sep-Oct, 2010, for the possible reference of future mental deal of such people as had experienced nuclear accidents. The Area still had a region of prohibited entrance. The evaluation of GHQ-12/AQ replies from 697 university students (138 men, average age of 20.48 y and 559 women, 20.24 y), was performed in Gomel State Medical University, Gomel, The Republic of Belarus. AQ contained questions about demographic, social and mental items like birthplace, marriage, living/economical states, history of illness, parents' experience of the Accident, concern/knowledge of radiation, etc. GHQ-12 total score data were defined to be High (score 4 or more, bad mental health situation) and Low (score<4, good situation) based on reply score 1 (worse than usual) and 0 (as or better than usual), respectively. GHQ-12 score data of High/Low were related to AQ items and analyzed with Chi-square, where items of significance between scores were made predictor variables for binominal logistic regression analysis. The scores were significantly high in students replying items of economical state, history of circulatory diseases, and association of the exposure and health. Logistic analysis based on these, revealed that the respective odds ratios (0.31, 1.78) of the first and third items above were significant, suggesting the direct concern of the people about exposure and health. This investigation was conducted in the limited location and on the limited group of people without comparison with those in other areas, but resolving the mental health situation was thought to be an important task in future. (T.T.)

  3. The early UL31 gene of equine herpesvirus 1 encodes a single-stranded DNA-binding protein that has a nuclear localization signal sequence at the C-terminus

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seongman; Chul Ahn, Byung; O' Callaghan, Dennis J. [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932 (United States); Kim, Seong Kee, E-mail: skim1@lsuhsc.edu [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932 (United States)

    2012-10-25

    The amino acid sequence of the UL31 protein (UL31P) of equine herpesvirus 1 (EHV-1) has homology to that of the ICP8 of herpes simplex virus type 1 (HSV-1). Here we show that the UL31 gene is synergistically trans-activated by the IEP and the UL5P (EICP27). Detection of the UL31 RNA transcript and the UL31P in EHV-1-infected cells at 6 h post-infection (hpi) as well as metabolic inhibition assays indicated that UL31 is an early gene. The UL31P preferentially bound to single-stranded DNA over double-stranded DNA in gel shift assays. Subcellular localization of the green fluorescent protein (GFP)-UL31 fusion proteins revealed that the C-terminal 32 amino acid residues of the UL31P are responsible for the nuclear localization. These findings may contribute to defining the role of the UL31P single-stranded DNA-binding protein in EHV-1 DNA replication.

  4. The early UL31 gene of equine herpesvirus 1 encodes a single-stranded DNA-binding protein that has a nuclear localization signal sequence at the C-terminus

    International Nuclear Information System (INIS)

    Kim, Seongman; Chul Ahn, Byung; O’Callaghan, Dennis J.; Kim, Seong Kee

    2012-01-01

    The amino acid sequence of the UL31 protein (UL31P) of equine herpesvirus 1 (EHV-1) has homology to that of the ICP8 of herpes simplex virus type 1 (HSV-1). Here we show that the UL31 gene is synergistically trans-activated by the IEP and the UL5P (EICP27). Detection of the UL31 RNA transcript and the UL31P in EHV-1-infected cells at 6 h post-infection (hpi) as well as metabolic inhibition assays indicated that UL31 is an early gene. The UL31P preferentially bound to single-stranded DNA over double-stranded DNA in gel shift assays. Subcellular localization of the green fluorescent protein (GFP)–UL31 fusion proteins revealed that the C-terminal 32 amino acid residues of the UL31P are responsible for the nuclear localization. These findings may contribute to defining the role of the UL31P single-stranded DNA-binding protein in EHV-1 DNA replication.

  5. On the validation of an Eulerian model with the Fukushima Nuclear Power Plant (FNPP) accident. Global and local results for Europe and Japan

    Energy Technology Data Exchange (ETDEWEB)

    Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne [CEA-CNRS-UVSQ UMR 8212, IPSL/LSCE - Laboratoire des Sciences du Climat et de l' Environnement, L' Orme des Merisiers, 91191 Gif-sur-Yvette Cedex (France); Florou, Heleni; Eleftheriadis, Konstantinos; Kritidis, Panayotis [NCSR ' Demokritos' , Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), Environmental Radioactivity Laboratory, 15310 Athens (Greece)

    2014-07-01

    A large debate about the exact emissions after the Fukushima NPP accident is still ongoing more than 3 years after the original disaster. Terada et al. (2012) reported the total release of {sup 137}Cs to be 13 PBq (x10{sup 15} Bq), based on an inverse modelling using Japanese data only, whereas the IRSN reported releases of {sup 137}Cs to be 20.6 PBq (IRSN, 2011). In the present study, we used the emission inventories for {sup 137}Cs and {sup 133}Xe reported by Stohl et al. (2012) estimated by inverse modelling using the CTBTO (Comprehensive Nuclear Test Ban Treaty Organisation) and Japanese networks (36.7 PBq of {sup 137}Cs and 15.3 EBq of {sup 133}Xe). For the simulations of the accident, three different versions of the LMDZORINCA model were used; A regular one with a grid resolution of 2.50 deg. x 1.27 deg. for the global comparison with the CTBTO network (19 and 39 vertical layers), and a zoom version over Europe and Asia (0.45 deg. x 0.51 deg. for 19 levels) resulting after 'stretching' the grid using the same number of grid points to assess what happened in Greece, and Japan. Cesium isotopes were treated as sub-micronic aerosols, whereas {sup 133}Xe as a passive tracer within the model, whereas several other radionuclides were estimated from reported isotopic ratios. Our results for the global assessment fit well to the observations. They differ about 0.04% from the measurements for {sup 137}Cs, and around 40% for xenon. The most significant deviations were observed for the northernmost stations due to both scavenging processes and transport over the Arctic. Scattered measurements of several radionuclides from Japan were adopted from literature (Shininaga et al., 2014). The comparison showed a significant quality of our model, although some isotopes are miscalculated. This shows that the reported isotopic ratios might be biased somehow. Finally, in Greece, few measurements of {sup 131}I, {sup 134}Cs and {sup 137}Cs were adopted from Potiriadis et al

  6. Simulation of Local Seismic Ground Motions from the FLASK Underground Nuclear Explosion near the Source Physics Experiment Dry Alluvium Geology Site

    Science.gov (United States)

    Rodgers, A. J.; Pitarka, A.; Wagoner, J. L.; Helmberger, D. V.

    2017-12-01

    The FLASK underground nuclear explosion (UNE) was conducted in Area 2 of Yucca Flat at the Nevada Test Site on May 26, 1970. The yield was 105 kilotons (DOE/NV-209-Rev 16) and the working point was 529 m below the surface. This test was detonated in faulted Tertiary volcanic rocks of Yucca Flat. Coincidently, the FLASK UNE ground zero (GZ) is close (conducting Phase II of its chemical high explosives test series in the so-called Dry Alluvium Geology (DAG) site. Ground motions from FLASK were recorded by twelve (12) three-component seismic stations in the near-field at ranges 3-4 km. We digitized the paper records and used available metadata on peak particle velocity measurements made at the time to adjust the amplitudes. These waveforms show great variability in amplitudes and waveform complexity with azimuth from the shot, likely due to along propagation path structure such as the geometry of the hard-rock/alluvium contact above the working point. Peak particle velocities at stations in the deeper alluvium to the north, east and south of GZ have larger amplitudes than those to the west where the basement rock is much shallower. Interestingly, the transverse components show a similar trend with azimuth. In fact, the transverse component amplitudes are similar to the other components for many stations overlying deeper basement. In this study, we simulated the seismic response at the available near-field stations using the SW4 three-dimensional (3D) finite difference code. SW4 can simulate seismic wave propagation in 3D inelastic earth structure, including surface topography. SW4 includes vertical mesh refinement which greatly reduces the computational resources needed to run a specific problem. Simulations are performed on high-performance computers with grid spacing as small as 10 meters and resolution to 6 Hz. We are testing various subsurface models to identify the role of 3D structure on path propagation effects from the source. We are also testing 3D models to

  7. A novel alkaloid, evodiamine causes nuclear localization of cytochrome-c and induces apoptosis independent of p53 in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mohan, Vijay [School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat (India); Agarwal, Rajesh [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO (United States); Singh, Rana P., E-mail: ranaps@hotmail.com [School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat (India); Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi (India)

    2016-09-02

    Lung cancer is the most frequently diagnosed malignancy that contributes to high proportion of deaths globally among patients who die due to cancer. Chemotherapy remains the common mode of treatment for lung cancer patients though with limited success. We assessed the biological effects and associated molecular changes of evodiamine, a plant alkaloid, on human lung cancer A549 and H1299 cells along with other epithelial cancer and normal lung SAEC cells. Our data showed that 20–40 μM evodiamine treatment for 24–48 h strongly (up to 73%, P < 0.001) reduced the growth and survival of these cancer cells. However, it also moderately inhibited growth and survival of SAEC cells. A strong inhibition (P < 0.001) was observed on clonogenicity of A549 cells. Further, evodiamine increased (4-fold) mitochondrial membrane depolarization with 6-fold increase in apoptosis and a slight increase in Bax/Bcl-2 ratio. It increased the cytochrome-c release from mitochondria into the cytosol as well as nucleus. Cytosolic cytochrome-c activated cascade of caspase-9 and caspase-3 intrinsic pathway, however, DR5 and caspase-8 extrinsic pathway was also activated which could be due to nuclear cytochrome-c. Pan-caspase inhibitor (z-VAD.fmk) partially reversed evodiamine induced apoptosis. An increase in p53 as well as its serine 15 phosphorylation was also observed. Pifithrin-α, a p53 inhibitor, slightly inhibited growth of A549 cells and under p53 inhibitory condition evodiamine-induced apoptosis could not be reversed. Together these findings suggest that evodiamine is a strong inducer of apoptosis in lung epithelial cancer cells independent of their p53 status and that could involve both intrinsic as well as extrinsic pathway of apoptosis. Thus evodiamine could be a potential anticancer agent against lung cancer. - Highlights: • Evodiamine, a novel plant alkaloid, relatively selectively inhibited growth and survival of human lung cancer cells. • Increased cancer cell

  8. Identification of a PTEN mutation with reduced protein stability, phosphatase activity, and nuclear localization in Hong Kong patients with autistic features, neurodevelopmental delays, and macrocephaly.

    Science.gov (United States)

    Wong, Chi Wai; Or, Penelope Mei Yu; Wang, Yubing; Li, Lisha; Li, Jing; Yan, Mingfei; Cao, Ye; Luk, Ho Ming; Tong, Tony Ming For; Leslie, Nick R; Lo, Ivan Fai-Man; Choy, Kwong Wai; Chan, Andrew Man Lok

    2018-04-02

    PTEN is a tumor suppressor gene inactivated in over 30% of human cancers. It encodes a lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase signaling pathway. Germline mutation frequently occurs in this gene in patients diagnosed with PTEN Hamartoma Tumor Syndrome (PHTS). PHTS individuals are characterized by macrocephaly, benign growth of multiple tissues and increased tumor risk. In addition, autistic phenotypes are found in 10-20% of individuals carrying the germline PTEN mutation with macrocephaly. In this report, 13 suspected PHTS patients were screened for mutation in the PTEN gene. A missense variant (c. 302T > C) substituting the isoleucine at codon 101 to a threonine, a single nucleotide insertion (c. 327-328insC) causing a frame shift mutation and termination at codon 109, and a nonsense variant (c. 1003C > T) truncated the protein at codon 335 were identified. The I101T mutation significantly reduced PTEN protein expression levels by 2.5- to 4.0-fold. Mechanistically, I101T reduced the protein half-life of PTEN possibly due to enhanced polyubiquitination at Lysine 13. However, the I101T mutant retained almost 30% of the lipid phosphatase activity of the wild-type protein. Finally, the I101T mutant has reduced phosphorylation at a PTEN auto-dephosphorylation site at Threonine 366 and a lowered ratio of nuclear to cytosolic protein level. These partial losses of multiple PTEN biochemical functions may contribute to the tissue overgrowth and autistic features of this PHTS patient. Autism Res 2018. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. The genetics of autism spectrum disorders is highly complex with individual risk influenced by both genetic and environmental factors. Mutation in the human PTEN gene confers a high risk of developing autistic behavior. This report revealed that PTEN mutations occurred in 23% of a selected group of Hong Kong

  9. Nevada state and local government comments on the US Department of Energy's report to Congress pursuant to Section 175 of the Nuclear Waste Policy Act, as amended

    International Nuclear Information System (INIS)

    1989-03-01

    The State of Nevada and affected local governments and Indian Tribes recognize the difficulties Department of Energy (DOE) encountered in attempting to compile a meaningful report on possible repository-related impacts in the relatively short amount of time available for the task. Overall, the Section 175 Report represents a positive beginning in what must, necessarily, be a much more thorough and detailed impact assessment effort. Although the current Report Does not identify the full range of repository impacts, nor seek to quantify them, it is useful as a framework or scoping document which, when supplemented with information on the specifics of impacts and costs/strategies for mitigation, may be useful in understanding the effects a repository will have upon the State of Nevada and affected communities. Subsequent socioeconomic analyses should follow-up this positive beginning and specify in greater detail the areas where undefined impacts may occur. Such analyses should expand the geographic scope of the Report, address transportation impacts along potential high-level waste routes, complete the project description (i.e., uncertainties with regard to labor force, materials requirements, etc.) used in forecasting effects within various categories of impacts, refine the section on impact mitigation strategies, and give fuller treatment to tourism and economic development impacts

  10. Nuclear rights - nuclear wrongs

    Energy Technology Data Exchange (ETDEWEB)

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  11. Nuclear moments

    CERN Document Server

    Kopferman, H; Massey, H S W

    1958-01-01

    Nuclear Moments focuses on the processes, methodologies, reactions, and transformations of molecules and atoms, including magnetic resonance and nuclear moments. The book first offers information on nuclear moments in free atoms and molecules, including theoretical foundations of hyperfine structure, isotope shift, spectra of diatomic molecules, and vector model of molecules. The manuscript then takes a look at nuclear moments in liquids and crystals. Discussions focus on nuclear paramagnetic and magnetic resonance and nuclear quadrupole resonance. The text discusses nuclear moments and nucl

  12. Nuclear science education in Taiwan

    International Nuclear Information System (INIS)

    Chung, Chien

    1990-01-01

    The nuclear science education has been established in Taiwan at the National Tsing Hua University (NTHU) since 1956. Support from the well-developed local nuclear power industry and government agencies is converged with rapid growth rate toward the College of Nuclear Science at NTHU, the only one among 123 universities and colleges in Taiwan where nuclear-related education is offered. The College, with 53 faculty members, offers bachelor's degree in Nuclear Engineering and master's and doctorate degrees in Nuclear Science, Nuclear Engineering, and Radiation Biology. Lectures and lab classes of radiochemistry, health physics, nuclear instruments, reactor experiment, nuclear medicine, and environmental monitoring are given to the 240 undergraduate students and 200 postgraduate students. The 1988 annual budget and research contracts for the College amounted USD600,000 and USD2,220,000, respectively

  13. Nuclear war hazards

    International Nuclear Information System (INIS)

    Chazov, E.I.; Il'in, L.A.; Gus'kova, A.K.

    1982-01-01

    An attempt is made to forecast medical and bilogical and aftereffects of nuclear weapons application in a number of situations. In particular, the effects of a single high-yield air or surface nuclear explosion on a city with 1 mln population are considered as well as the aftereffects of the exposure of human beings to local radioactive fallouts outside the ground zero of a surface nuclear explosion. The aftereffects for the population of local and global radioactive fallouts caused by the realization of one of the adopted in the West variants of mass nuclear strives exchange between the hostile sides are estimated. Certain aspects of medical and biological aftereffects of neutron weapons application are discussed

  14. Nuclear power

    OpenAIRE

    2005-01-01

    David Waller and Alan McDonald ask whether a nuclear renaissance can be predicted; Judith M. Greenwald discusses keeping the nuclear power option open; Paul Mobbs considers the availability of uranium and the future of nuclear energy.

  15. Nuclear Medicine.

    Science.gov (United States)

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  16. Nuclear power in Korea

    International Nuclear Information System (INIS)

    Rim, C.S.

    1990-01-01

    Before addressing the issue of public and utility acceptance of nuclear power in Korea, let me briefly explain the Korean nuclear power program and development plan for a passively safe nuclear power plant in Korea. At present, there are eight PWRs and one CANDU in operation; two PWRs are under construction, and contract negotiations are underway for one more CANDU and two more PWRs, which are scheduled to be completed by 1997,1998 and 1999, respectively. According to a recent forecast for electricity demand in Korea, about fifty additional nuclear power plants with a generating capacity of 1000MWe are required by the year 2030. Until around 2006, Korean standardized nuclear power plants with evolutionary features such as those in the ALWR program are to be built, and a new type of nuclear power plant with passive safety features is expected to be constructed after 2006. The Korean government is making a serious effort to increase public understanding of the safety of nuclear power plants and radioactive waste storage and disposal. In addition, the Korean government has recently introduced a program of benefits for residents near nuclear power plants. By this program, common facilities such as community centers and new roads are constructed, and scholarships are given to the local students. Nuclear power is accepted positively by the utility and reasonably well by the public in Korea

  17. Nuclear power plant exports

    International Nuclear Information System (INIS)

    Degot, D.

    1987-01-01

    Framatome export expertise is discussed. Framatome can accept different types of contracts - for the supply of nuclear steam supply systems or for nuclear islands (both of which can be produced solely by Framatome) or for complete plants. Cooperation with the local industry is possible -this can involve technology transfer. Examples of exports in the following countries are given; Belgium (where there is close cooperation between Framatome and two major companies), South Africa (where Framatome has been involved in the building of a two-992 MWe unit at Koeberg), South Korea (where Framatome is building two-900 MWe nuclear islands in cooperation with Korean industry, Knu 9 and Knu 10) and China (where Framatome is to build two-1000 MWe class pressurized water reactors at Daya Bay). As well as supplying the French domestic nuclear market Framatome is a major force in the future of nuclear power in the world. (UK)

  18. Local Publications.

    Science.gov (United States)

    Wilson, Yvonne; And Others

    1991-01-01

    Includes annotations for 23 local government publications that reflect the main issues confronting local communities, including AIDS, children at risk, homelessness, human rights, and environmental decline. The shift of local problem solving from the federal and state government levels to the local level is briefly discussed. (LRW)

  19. Local formularies

    Science.gov (United States)

    Reynolds, D John M; Fajemisin, Olubunmi; Wilds, Sara

    2012-01-01

    The widespread availability of authoritative guidance on prescribing from a wide variety of international and national bodies calls into question the need for additional local formulary advice. This article describes contemporary local formulary management in the United Kingdom and discusses the areas where local decision making remains valuable. Local formularies can fulfil important roles which justify their continued existence, including ensuring local ownership and acceptance of advice, rapid dissemination of information, responsiveness to local circumstances and service design, sensitivity to local pricing arrangements and close professional links with commissioners, pharmacists and prescribers. PMID:22420709

  20. Local formularies

    OpenAIRE

    Reynolds, D John M; Fajemisin, Olubunmi; Wilds, Sara

    2012-01-01

    The widespread availability of authoritative guidance on prescribing from a wide variety of international and national bodies calls into question the need for additional local formulary advice. This article describes contemporary local formulary management in the United Kingdom and discusses the areas where local decision making remains valuable. Local formularies can fulfil important roles which justify their continued existence, including ensuring local ownership and acceptance of advice, r...

  1. Nuclear power in western society

    International Nuclear Information System (INIS)

    Franklin, N.L.

    1977-01-01

    The degree to which problems of public acceptance have contributed to the slowdown in progress of nuclear power in Western European countries and the USA is discussed. Some of the effects on the nuclear power industry, i.e. the electrical utilities, the power station suppliers, and the fuel cycle contractors are described. The problem of the lack of public acceptance is examined by consideration of four areas: the position of the employee working in nuclear installations, opposition from the local community, the question of terrorism and its impact on nuclear policy, and finally, what is felt to constitute the greatest anxiety concerning nuclear power, that of proliferation. (U.K.)

  2. Geological disposal of radioactive wastes: national commitment, local and regional involvement. A Collective Statement of the OECD Nuclear Energy Agency 'Radioactive Waste Management Committee', adopted March 2011

    International Nuclear Information System (INIS)

    2012-01-01

    Disposal in engineered facilities built in stable, deep geological formations is the reference solution for permanently isolating long-lived radioactive waste from the human biosphere. This management method is designed to be intrinsically safe and final, i.e. not dependent on human presence and intervention in order to fulfil its safety goal. Siting waste repositories brings up a range of issues that touch on scientific knowledge, technical capacity, ethical values, territorial planning, community well-being, and more. Bringing to fruition the multi-decades task of siting and developing a repository demands a strong national commitment and a significant regional and local involvement. This Collective Statement by the Radioactive Waste Management Committee of the OECD Nuclear Energy Agency recognizes the advances made toward greater transparency and dialogue among the diverse relevant stakeholders and identifies the fundamental ingredients needed to support national commitment and foster territorial involvement. It concludes that technical and societal partners can develop shared confidence in the safety of geological repositories and jointly carry these projects forward

  3. Comments on nuclear reactor safety in Ontario

    International Nuclear Information System (INIS)

    1987-08-01

    The Chalk River Technicians and Technologists Union representing 500 technical employees at the Chalk River Nuclear Laboratories of AECL submit comments on nuclear reactor safety to the Ontario Nuclear Safety Review. Issues identified by the Review Commissioner are addressed from the perspective of both a labour organization and experience in the nuclear R and D field. In general, Local 1568 believes Ontario's CANDU nuclear reactors are not only safe but also essential to the continued economic prosperity of the province

  4. BS degree in nuclear engineering or a nuclear option

    International Nuclear Information System (INIS)

    Williams on, T.G.

    1988-01-01

    Many nuclear engineering educators are concerned about the health of nuclear engineering academic departments. As part of a review of the BS nuclear engineering degree program at the University of Virginia, the authors surveyed several local utilities with operating nuclear plants about their needs for nuclear engineering graduates. The perception of many of the utility executives about a nuclear engineering degree and about a nuclear option in another engineering curriculum does not agree with the way the authors view these two degrees. The responses to two of the survey questions were of particular interest: (1) does your company have a preference between nuclear engineering graduates and graduates in other fields with a nuclear option? (2) what do you consider to be a minimum level of education in nuclear engineering for a nuclear option in mechanical engineering? All of the four utilities that were surveyed stated a preference for mechanical or electrical engineers with a nuclear option, although two indicated that there are certain jobs for which a nuclear engineering graduate is desired

  5. Local anesthetics: interaction with human erythrocyte membranes as studied by {sup 1}H and {sup 31}P nuclear magnetic resonance; Anestesicos locais: interacao com membranas de eritrocitos de sangue humano, estudada por ressonancia magnetica nuclear de {sup 1}H e {sup 31}P

    Energy Technology Data Exchange (ETDEWEB)

    Fraceto, Leonardo Fernandes; Paula, Eneida de [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia. Dept. de Bioquimica]. E-mail: depaula@unicamp.br

    2004-02-01

    The literature carries many theories about the mechanism of action of local anesthetics (LA). We can highlight those focusing the direct effect of LA on the sodium channel protein and the ones that consider the interaction of anesthetic molecules with the lipid membrane phase. The interaction between local anesthetics and human erythrocyte membranes has been studied by {sup 1}H and {sup 31}P nuclear magnetic resonance spectroscopy. It was found that lidocaine (LDC) and benzocaine (BZC) bind to the membranes, increase the mobility of the protons of the phospholipids acyl chains, and decrease the mobility and/or change the structure of the polar head groups. The results indicate that lidocaine molecules are inserted across the polar and liquid interface of the membrane, establishing both electrostatic (charged form) and hydrophobic (neutral form) interactions. Benzocaine locates itself a little deeper in the bilayer, between the interfacial glycerol region and the hydrophobic core. These changes in mobility or conformation of membrane lipids could affect the Na{sup +}-channel protein insertion in the bilayer, stabilizing it in the inactivated state, thus causing anesthesia. (author)

  6. Chemical analysis of carbon stars in the local group - l.  The small magnetic cloud and the Sagittarius Dwarf Spheroidal galaxy

    DEFF Research Database (Denmark)

    de Laverny...[], P.; Abia, C.; Dominguez, I

    2006-01-01

    Stars: abundances, stars: carbon, nuclear reactions, nucleosynthesis, abundances, galaxies: Local Group Udgivelsesdato: Feb.......Stars: abundances, stars: carbon, nuclear reactions, nucleosynthesis, abundances, galaxies: Local Group Udgivelsesdato: Feb....

  7. Nuclear medicine

    International Nuclear Information System (INIS)

    Lentle, B.C.

    1986-01-01

    Several growth areas for nuclear medicine were defined. Among them were: cardiac nuclear medicine, neuro-psychiatric nuclear medicine, and cancer diagnosis through direct tumor imaging. A powerful new tool, Positron Emission Tomography (PET) was lauded as the impetus for new developments in nuclear medicine. The political environment (funding, degree of autonomy) was discussed, as were the economic and scientific environments

  8. Nuclear links

    International Nuclear Information System (INIS)

    1981-01-01

    The subject is dealt with in sections: introduction; energy and the third world; world energy consumption 1978; oil -the energy dilemma; nuclear chains - introduction; uranium; Namibia; enrichment and reprocessing; countries with enrichment and reprocessing facilities; waste; conclusion; why take the nuclear option; third world countries with nuclear reactors; the arms connection; government spending and human resources 1977 (by countries); nuclear power - the final solution; the fascists; world bank; campaigns; community action in Plogoff; Australian labour movement; NUM against nuclear power; Scottish campaign; students against nuclear energy; anti-nuclear campaign; partizans; 3W1 disarmament and development; campaign ATOM; CANUC; 3W1; SANE. (U.K.)

  9. Act local, think global

    International Nuclear Information System (INIS)

    Lewis, Chris; McRoberts, Doug

    2002-01-01

    Tip O'Neill, one of the grand old men of modem US politics, once famously remarked that all politics is local. Like most politicians who succeed on the national stage - and not just in the US - it was a truth he never lost sight of. What is true for politicians is equally true in the communications business. We may increasingly live in a global village, but successful companies - even multi-nationals - forget the importance of local and regional public relations at their peril. Think of Douglas Ivester, the CEO of Coca-Cola at the time of the 1999 Belgian contamination scandal, who allegedly reacted to first reports of the crisis by asking: 'Where the hell is Belgium?' A more appropriate question today - several years after Coke's share price toppled and the CEO was unceremoniously sacked - might be: 'Who the hell is Douglas Nester?' But - to adapt another famous phrase - the fact that communications (and marketing) professionals still need to 'act local' as much as ever before should not blind us to the growing need to 'think global'. In the nuclear industry, as in the world economy generally, increasing global integration is a reality, as are the international nature of the news media and the increasingly global nature of the anti-nuclear pressure groups. Indeed, it was the growing need for a truly global information network to counter these trends, by increasing the overall speed and accuracy of the worldwide nuclear information flow, that led the nuclear community to establish NucNet in 1991. So where exactly is the line between local and regional nuclear communications on the one hand, and global communications on the other? Is there one spin for a regional audience, and another for a global audience? This presentation proposes some guiding principles, by examining the response of nuclear communicators world-wide to the new communications agenda imposed in the wake of the September 11th suicide attacks in the US. NucNet President Doug McRoberts and Executive

  10. Nuclear terrorism

    OpenAIRE

    RUTIC SRDJAN Z.

    2016-01-01

    The paper has analyzed different manifestations of terrorism with nuclear weapons and ionizing radiation as a special kind of terrorism. Possibilities that terrorist groups come into possession of nuclear weapons and apply them for terrorist purposes have been analysed. The forms and methods of terrorist activities with nuclear means have been given as well. It has been concluded that nuclear terrorism includes various forms of threats, including not only nuclear weapons but also the sources ...

  11. Nuclear safeguards and nuclear shutdowns

    International Nuclear Information System (INIS)

    Worthington, J.D.

    1976-01-01

    The issues involved in the California nuclear initiative (Proposition 15) are described. Some of the characteristics of the anti-nuclear lobby are outlined. Some do's and don'ts for the nuclear group are listed. The nuclear shutdown effort was concentrated on the safeguards and high-level waste disposal issues

  12. Optimal Local Dimming for LC Image Formation With Controllable Backlighting

    DEFF Research Database (Denmark)

    Shu, Xiao; Wu, Xiaolin; Forchhammer, Søren

    2013-01-01

    concern for visual quality. To fully realize the potential of LED-backlit LCDs and reduce the artifacts that often occur in current systems, we propose a novel local dimming technique that can achieve the theoretical highest fidelity of intensity reproduction in either $\\ell_{1}$ or $\\ell_{2}$ metrics....... Both the exact and fast approximate versions of the optimal local dimming algorithm are proposed. Simulation results demonstrate superior performances of the proposed algorithm in terms of visual quality and power consumption.......Light emitting diode (LED)-backlit liquid crystal displays (LCDs) hold the promise of improving image quality while reducing the energy consumption with signal-dependent local dimming. However, most existing local dimming algorithms are mostly motivated by simple implementation, and they often lack...

  13. Nuclear medicine in pediatrics

    International Nuclear Information System (INIS)

    Gumplova, H.

    1982-01-01

    The methods of nuclear medicine are outlined used for examining children. The problems are discussed of children's exposure in isotope methods, diagnostic localization methods, in central nervous system examinations, skeleton, hematopoietic organs, gastrointestinal tract, respiratory organs, blood circulation system, and thyroid examinations. (J.B.)

  14. Optimal local dimming for LED-backlit LCD displays via linear programming

    DEFF Research Database (Denmark)

    Shu, Xiao; Wu, Xiaolin; Forchhammer, Søren

    2012-01-01

    LED-backlit LCD displays hold the promise of improving the image quality while reducing the energy consumption with signal-dependent local dimming. To fully realize such potentials we propose a novel local dimming technique that jointly optimizes the intensities of LED backlights...... and the attenuations of LCD pixels. The objective is to minimize the distortion in luminance reproduction due to the leakage of LCD and the coarse granularity of the LED lights. The optimization problem is formulated as one of linear programming, and both exact and approximate algorithms are proposed. Simulation...... results demonstrate superior performances of the proposed algorithms over the existing local dimming algorithms....

  15. Alteration of 'R7T7' type nuclear glasses: statistical approach, experimental validation, local evolution model; Alteration des verres nucleaires de type 'R7T7': demarche statistique, validation experimentale, modele local d'evolution

    Energy Technology Data Exchange (ETDEWEB)

    Thierry, F

    2003-02-01

    The aim of this work is to propose an evolution of nuclear (R7T7-type) glass alteration modeling. The first part of this thesis is about development and validation of the 'r(t)' model. This model which predicts the decrease of alteration rates in confined conditions is based upon a coupling between a first-order dissolution law and a diffusion barrier effect of the alteration gel layer. The values and the uncertainties regarding the main adjustable parameters of the model ({alpha}, Dg and C*) have been determined from a systematic study of the available experimental data. A program called INVERSION has been written for this purpose. This work lead to characterize the validity domain of the 'r(t)' model and to parametrize it. Validation experiments have been undertaken, confirming the validity of the parametrization over 200 days. A new model is proposed in the second part of this thesis. It is based on an inhibition of glass dissolution reaction by silicon coupled with a local description of silicon retention in the alteration gel layer. This model predicts the evolutions of boron and silicon concentrations in solution as well as the concentrations and retention profiles in the gel layer. These predictions have been compared to measurements of retention profiles by the secondary ion mass spectrometry (SIMS) method. The model has been validated on fractions of gel layer which reactivity present low or moderate disparitie