WorldWideScience

Sample records for regulator scr domains

  1. Functional characterization of sucrose phosphorylase and scrR, a regulator of sucrose metabolism in Lactobacillus reuteri.

    Science.gov (United States)

    Teixeira, Januana S; Abdi, Reihaneh; Su, Marcia Shu-Wei; Schwab, Clarissa; Gänzle, Michael G

    2013-12-01

    Lactobacillus reuteri harbours alternative enzymes for sucrose metabolism, sucrose phosphorylase, fructansucrases, and glucansucrases. Sucrose phosphorylase and fructansucrases additionally contribute to raffinose metabolism. Glucansucrases and fructansucrases produce exopolysaccharides as alternative to sucrose hydrolysis. L. reuteri LTH5448 expresses a levansucrase (ftfA) and sucrose phosphorylase (scrP), both are inducible by sucrose. This study determined the contribution of scrP to sucrose and raffinose metabolism in L. reuteri LTH5448, and elucidated the role of scrR in regulation sucrose metabolism. Disruption of scrP and scrR was achieved by double crossover mutagenesis. L. reuteri LTH5448, LTH5448ΔscrP and LTH5448ΔscrR were characterized with respect to growth and metabolite formation with glucose, sucrose, or raffinose as sole carbon source. Inactivation of scrR led to constitutive transcription of scrP and ftfA, demonstrating that scrR is negative regulator. L. reuteri LTH5448 and the LTH5448ΔscrP or LTH5448ΔscrR mutant strains did not differ with respect to glucose, sucrose or raffinose utilization. However, L. reuteri LTH5448ΔscrP produced more levan, indicating that the lack of sucrose phosphorylase is compensated by an increased metabolic flux through levansucrase. In conclusion, the presence of alternate pathways for sucrose and raffinose metabolism and their regulation indicate that these substrates, which are abundant in plants, are preferred carbohydrate sources for L. reuteri. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Analysis of the offshore installations regulations 2005 (SCR05r12) within Brazilian reality; Analise da regulacao das instalacoes offshore 2005 (SCR05r12) dentro da realidade brasileira

    Energy Technology Data Exchange (ETDEWEB)

    Nalvarte, Gladys; Storch, Rafael; Araujo, Pedro; Oliveira, Luiz Fernando [Det Norske Veritas (Brazil)

    2008-07-01

    The main motivation for the present study is the modifications presented in the guidance Offshore Installations (Safety Case) Regulations 2005 (SCR05 r12), released by HSE, in relation to the Offshore Installation Regulation 1992, SCR92. A critical analysis of the new regulation issued by HSE is developed and conclusions are obtained. A cost-benefit approach applied to the Quantitative Risk Analysis (QRA), using computational fluid dynamics (CFD) techniques, is suggested. Thereby, a method to identify the mitigation measures that most reduces the risks with the minimum cost is obtained. On the other hand, this new QRA approach combined with a cost benefit analysis is intended to have a total cost diminished. In this case, the cost of the new QRA study is dependant on the number of reevaluations needed to determine the mitigation measures to be applied. (author)

  3. Cloning and Characterization of ThSHRs and ThSCR Transcription Factors in Taxodium Hybrid 'Zhongshanshan 406'.

    Science.gov (United States)

    Wang, Zhiquan; Yin, Yunlong; Hua, Jianfeng; Fan, Wencai; Yu, Chaoguang; Xuan, Lei; Yu, Fangyuan

    2017-07-20

    Among the GRAS family of transcription factors, SHORT ROOT (SHR) and SCARECROW (SCR) are key regulators of the formation of root tissues. In this study, we isolated and characterized two genes encoding SHR proteins and one gene encoding an SCR protein: ThSHR1 (Accession Number MF045148), ThSHR2 (Accession Number MF045149) and ThSCR (Accession Number MF045152) in the adventitious roots of Taxodium hybrid 'Zhongshanshan'. Gene structure analysis indicated that ThSHR1 , ThSHR2 and ThSCR are all intron free. Multiple protein sequence alignments showed that each of the corresponding proteins, ThSHR1, ThSHR2 and ThSCR, contained five well-conserved domains: leucine heptad repeat I (LHRI), the VHIID motif, leucine heptad repeat II (LHR II), the PFYRE motif, and the SAW motif. The phylogenetic analysis indicated that ThSCR was positioned in the SCR clade with the SCR proteins from eight other species, while ThSHR1 and ThSHR2 were positioned in the SHR clade with the SHR proteins from six other species. Temporal expression patterns of these genes were profiled during the process of adventitious root development on stem cuttings. Whereas expression of both ThSHR2 and ThSCR increased up to primary root formation before declining, that of ThSHR1 increased steadily throughout adventitious root formation. Subcellular localization studies in transgenic poplar protoplasts revealed that ThSHR1, ThSHR2 and ThSCR were localized in the nucleus. Collectively, these results suggest that the three genes encode Taxodium GRAS family transcription factors, and the findings contribute to improving our understanding of the expression and function of SHR and SCR during adventitious root production, which may then be manipulated to achieve high rates of asexual propagation of valuable tree species.

  4. Bph32, a novel gene encoding an unknown SCR domain-containing protein, confers resistance against the brown planthopper in rice

    Science.gov (United States)

    Ren, Juansheng; Gao, Fangyuan; Wu, Xianting; Lu, Xianjun; Zeng, Lihua; Lv, Jianqun; Su, Xiangwen; Luo, Hong; Ren, Guangjun

    2016-01-01

    An urgent need exists to identify more brown planthopper (Nilaparvata lugens Stål, BPH) resistance genes, which will allow the development of rice varieties with resistance to BPH to counteract the increased incidence of this pest species. Here, using bioinformatics and DNA sequencing approaches, we identified a novel BPH resistance gene, LOC_Os06g03240 (MSU LOCUS ID), from the rice variety Ptb33 in the interval between the markers RM19291 and RM8072 on the short arm of chromosome 6, where a gene for resistance to BPH was mapped by Jirapong Jairin et al. and renamed as “Bph32”. This gene encodes a unique short consensus repeat (SCR) domain protein. Sequence comparison revealed that the Bph32 gene shares 100% sequence identity with its allele in Oryza latifolia. The transgenic introgression of Bph32 into a susceptible rice variety significantly improved resistance to BPH. Expression analysis revealed that Bph32 was highly expressed in the leaf sheaths, where BPH primarily settles and feeds, at 2 and 24 h after BPH infestation, suggesting that Bph32 may inhibit feeding in BPH. Western blotting revealed the presence of Pph (Ptb33) and Tph (TN1) proteins using a Penta-His antibody, and both proteins were insoluble. This study provides information regarding a valuable gene for rice defence against insect pests. PMID:27876888

  5. Bph32, a novel gene encoding an unknown SCR domain-containing protein, confers resistance against the brown planthopper in rice.

    Science.gov (United States)

    Ren, Juansheng; Gao, Fangyuan; Wu, Xianting; Lu, Xianjun; Zeng, Lihua; Lv, Jianqun; Su, Xiangwen; Luo, Hong; Ren, Guangjun

    2016-11-23

    An urgent need exists to identify more brown planthopper (Nilaparvata lugens Stål, BPH) resistance genes, which will allow the development of rice varieties with resistance to BPH to counteract the increased incidence of this pest species. Here, using bioinformatics and DNA sequencing approaches, we identified a novel BPH resistance gene, LOC_Os06g03240 (MSU LOCUS ID), from the rice variety Ptb33 in the interval between the markers RM19291 and RM8072 on the short arm of chromosome 6, where a gene for resistance to BPH was mapped by Jirapong Jairin et al. and renamed as "Bph32". This gene encodes a unique short consensus repeat (SCR) domain protein. Sequence comparison revealed that the Bph32 gene shares 100% sequence identity with its allele in Oryza latifolia. The transgenic introgression of Bph32 into a susceptible rice variety significantly improved resistance to BPH. Expression analysis revealed that Bph32 was highly expressed in the leaf sheaths, where BPH primarily settles and feeds, at 2 and 24 h after BPH infestation, suggesting that Bph32 may inhibit feeding in BPH. Western blotting revealed the presence of Pph (Ptb33) and Tph (TN1) proteins using a Penta-His antibody, and both proteins were insoluble. This study provides information regarding a valuable gene for rice defence against insect pests.

  6. ANALYSIS OF SEQUENCE POLYMORPHISM OF SCR CLASS I AND II ALLELES AND STUDY REGULATION OF THEIR EXPRESSION

    Directory of Open Access Journals (Sweden)

    Jana ŽALUDOVÁ

    2012-06-01

    Full Text Available Self-incompatibility (AI is a widespread mechanism used by flowering plants to prevent inbreeding depression and helps create and maintain genetic diversity within a species. Oilseed rape (Brassica napus L. and especially its modern varieties are characterized by high level of self-fertility. In an effort to increase the production current breeding is focused on the production of inbred lines for making the F1 hybrids and the self-incompatibility can be an interesting tool for production self- sterile lines. In Brassica napus, we found two recessive alleles of a gene SCR II. Different expression of both alleles does not correspond to phenotypic manifestation of self-incompatibility and we can assume that it is prevailed by repressor gene that does not lie on the S-locus. This is also reason, why the SCR gene cannot serve as a molecular marker of self-incompatibility in Brassica napus, although many authors believe that this gene is essential in AI reaction. Brassica napus belong to plants with complex genetic constitution, is composed by two genomes, A and C, which give the possibility of different interactions and makes it difficult to study compared with diploid B. rapa and B. oleracea. In further study it is therefore important to focus on the interactions between genes SCR, SRK and SLG, and their influence on others, such as supressor gene systems.

  7. Technical presentation of SCR

    CERN Multimedia

    FI Department

    2008-01-01

    SCR Société des Composants Record, Montierchaume, France Monday 20 October 2008 from 9:45 to 12:00 – Room A Main Building (Bldg. 61/1-017) http://www.scr.fr SCR develops, manufactures and markets plastic dielectric capacitors (polypropylene, polyester, Teflon) for use in various applications: audio amplifiers, high-end loudspeakers, fans and extractors (multi-capacitance capacitors), pulsed lasers, flash lamps, defibrillators, beacons, power supplies, converters for rail traction drives, railway signalling devices, voltage dividers and multipliers, high voltage laboratories, etc. The company is renowned for its precision wire-wound resistors for use in power electronics and consumer electronics marketed under the SETA brand name. SCR is also experienced in the design and production of electronic circuits for various applications, such as speed variators for mono and three-phase motors, dimmers, passive filters for audio speakers, etc. Contact : M. Urs V. Rölli, e-mail: mailto:info@technictrade.ch.

  8. Ammonia sensor for closed-loop SCR control

    NARCIS (Netherlands)

    Wang, D.Y.; Yao, S.; Shost, M.; Yoo, J.H.; Cabush, D.; Racine, D.; Cloudt, R.P.M.; Willems, F.P.T.

    2009-01-01

    Selective Catalytic Reduction (SCR) is the dominant solution for meeting future NOx reduction regulations for heavy-duty diesel powertrains. SCR systems benefit from closed-loop control if an appropriate exhaust gas sensor were available. An ammonia sensor has recently been developed for use as a

  9. Ammonia sensor for closed-loop SCR control

    NARCIS (Netherlands)

    Wang, D.Y.; Yao, S.; Shost, M.; Yoo, J.H.; Cabush, D.; Racine, D.; Cloudt, R.P.M.; Willems, F.P.T.

    2008-01-01

    Selective Catalytic Reduction (SCR) is the dominant solution for meeting future NOx reduction regulations for heavy-duty diesel powertrains. SCR systems benefit from closed-loop control if an appropriate exhaust gas sensor were available. An ammonia sensor has recently been developed for use as a

  10. BAR domain proteins regulate Rho GTPase signaling.

    Science.gov (United States)

    Aspenström, Pontus

    2014-01-01

    BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

  11. Outstanding low temperature HC-SCR of NOx over platinum-group catalysts supported on mesoporous materials expecting diesel-auto emission regulation

    International Nuclear Information System (INIS)

    Komatsu, Tamikuni; Tomokuni, Keizou; Yamada, Issaku

    2006-01-01

    Outstanding low temperature HC-SCR of NOx over platinum-group catalysts supported on mesoporous materials, which does not rely on the conventional NOx-absorption-reduction-catalysts, is presented for the purpose of de-NOx of diesel-auto emissions. The established catalysts basically consist of mesoporous silica or metal-substituted mesoporous silicates for supports and platinum for active species, which is operated under lean- and rich-conditions. The new catalysts are very active at 150-200 o C and free from difficult problems of SOx-deactivation and hydrothermal ageing of the NOx-absorption-reduction catalyst. (author)

  12. A role for chromatin topology in imprinted domain regulation.

    Science.gov (United States)

    MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

    2016-02-01

    Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

  13. The protective effect of SCR(15-18) on cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Li, Shu; Xian, Jinhong; He, Li; Luo, Xue; Tan, Bing; Yang, Yongtao; Liu, Gaoke; Wang, Zhengqing

    2011-10-01

    Soluble complement receptor type 1 (sCR1), a potent inhibitor of complement activation, has been shown to protect brain cells against cerebral ischemic/reperfusion (CI/R) injury due to its decay-accelerating activity for C3/C5 convertase and co-factor activity for C3b/C4b degradation. However, the effect of short consensus repeats (SCRs) 15-18, one of active domains of sCR1 with high C3b/C4b degradability, has not been demonstrated. Here, we investigated the protective effect of recombinant SCR(15-18) protein in middle cerebral artery occlusion (MCAO)-induced focal CI/R injury. Recombinant SCR(15-18) protein was successfully expressed in Escherichia coli and refolded to its optimal bioactivity. Seventy-five Sprague-Dawley rats were randomly assigned into three groups: sham-operated group, CI/R group, and SCR(15-18)+CI/R group pretreated with 20 mg/kg SCR(15-18) protein. After 2 hours of MCAO and subsequent 24 hours of reperfusion, rats were evaluated for neurological deficits and cerebral infarction. Polymorphonuclear leukocyte accumulation, C3b deposition, and morphological changes in cerebral tissue were also estimated. SCR(15-18) pretreatment induced a 20% reduction of infarct size and an improvement of neurological function with 22·2% decrease of neurological deficit scores. Inhibition of cerebral neutrophils infiltration by SCR(15-18) was indicated from the reduction of myeloperoxidase activity in SCR(15-18)+CI/R rats. Decreased C3b deposition and improved morphological changes were also found in cerebral tissue of SCR(15-18)-treated rats. Our studies suggest a definitive moderately protective effect of SCR(15-18) against CI/R damage and provide preclinical experimental evidence supporting the possibility of using it as a small anti-complement therapeutic agent for CI/R injury therapy.

  14. State Estimation for the Automotive SCR Process

    DEFF Research Database (Denmark)

    Zhou, Guofeng; Huusom, Jakob Kjøbsted; Jørgensen, John Bagterp

    2012-01-01

    Selective catalytic reduction (SCR) of NOx is a widely applied diesel engine exhaust gas aftertreatment technology. For advanced SCR process control, like model predictive control, full state information of the process is required. The ammonia coverage ratio inside the catalyst is difficult to me...

  15. Hydrolysis of isocyanic acid on SCR catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Elsener, M; Kleemann, M; Koebel, M [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Standard SCR catalysts possess high activity for the hydrolysis of HNCO and thus explain the suitability of urea as a selective reducing agent for NO{sub x}. At high space velocities HNCO-slip can get perceptible over the entire temperature range. This can be attributed to the fact that the temperature dependence is strong for the SCR reaction, but weak for the hydrolysis reaction. (author) 3 figs., 5 refs.

  16. Prolyl hydroxylase domain enzymes: important regulators of cancer metabolism

    Directory of Open Access Journals (Sweden)

    Yang M

    2014-08-01

    Full Text Available Ming Yang,1 Huizhong Su,1 Tomoyoshi Soga,2 Kamil R Kranc,3 Patrick J Pollard1 1Cancer Biology and Metabolism Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK; 2Institute for Advanced Biosciences, Keio University, Mizukami, Tsuruoka, Yamagata, Japan; 3MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK Abstract: The hypoxia-inducible factor (HIF prolyl hydroxylase domain enzymes (PHDs regulate the stability of HIF protein by post-translational hydroxylation of two conserved prolyl residues in its α subunit in an oxygen-dependent manner. Trans-4-prolyl hydroxylation of HIFα under normal oxygen (O2 availability enables its association with the von Hippel-Lindau (VHL tumor suppressor pVHL E3 ligase complex, leading to the degradation of HIFα via the ubiquitin-proteasome pathway. Due to the obligatory requirement of molecular O2 as a co-substrate, the activity of PHDs is inhibited under hypoxic conditions, resulting in stabilized HIFα, which dimerizes with HIFβ and, together with transcriptional co-activators CBP/p300, activates the transcription of its target genes. As a key molecular regulator of adaptive response to hypoxia, HIF plays important roles in multiple cellular processes and its overexpression has been detected in various cancers. The HIF1α isoform in particular has a strong impact on cellular metabolism, most notably by promoting anaerobic, whilst inhibiting O2-dependent, metabolism of glucose. The PHD enzymes also seem to have HIF-independent functions and are subject to regulation by factors other than O2, such as by metabolic status, oxidative stress, and abnormal levels of endogenous metabolites (oncometabolites that have been observed in some types of cancers. In this review, we aim to summarize current understandings of the function and regulation of PHDs in cancer with an emphasis on their roles in metabolism. Keywords: prolyl hydroxylase domain (PHD

  17. SCR at bio fuel combustion

    International Nuclear Information System (INIS)

    Andersson, Christer; Odenbrand, I.; Andersson, L.H.

    1998-10-01

    by sulphatisation with sulphur dioxide. After a sulphatisation procedure with 500 ppm SO 2 (without washing) the activity was regained to at least 90 % even for heavily deactivated samples. The use of sulphatisation, periodic washing, lower flue gas temperature and use of an optimised catalyst are very promising measures to increase the catalyst lifetime and to reduce the operation costs for SCR in bio fuel fluidized bed based power plants. Therefore, a thorough investigation of these measures is warranted Figures and tables with text in English. 36 refs, 26 figs, 5 tabs

  18. Influence of hydrogen treatment on SCR catalysts

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes

    stream, i.e. by in situ treatment of the Pt-catalyst by reductive H2-gas. However, the introduction of H2 gas in the gas stream could also affect other units in the tail pipe gas cleaning system. Of special interest in this study is the effect of hydrogen gas on the performance of the selective catalytic...... reduction (SCR) process, i.e. the catalytic removal of NOx from the flue gas. A series of experiments was conducted to reveal the impact on the NO SCR activity of a industrial DeNOX catalyst (3%V2O5-7%WO3/TiO2) by treatment of H2. Standard conditions were treatment of the SCR catalyst for 60 min with three...... different concentrations of H2 (0-2%) in a 8% O2/N2 mixture, where the SCR activity was measured before and after the hydrogen treatment. The results show that the activity of the SCR catalyst is only negligible affected during exposure to the H2/O2 gas and in all cases it returned reversibly to the initial...

  19. HiSCR (Hidradenitis Suppurativa Clinical Response)

    DEFF Research Database (Denmark)

    Kimball, B. A.; Sobell, J. M.; Zouboulis, C C

    2016-01-01

    Background: Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective: Evaluate the novel, validated endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an out......Background: Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. Objective: Evaluate the novel, validated endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility...... as an outcome measure. Methods: Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count...... week, or placebo (1 : 1 : 1). Results: The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6...

  20. Regulation of Exocytotic Fusion Pores by SNARE Protein Transmembrane Domains

    Directory of Open Access Journals (Sweden)

    Zhenyong Wu

    2017-10-01

    Full Text Available Calcium-triggered exocytotic release of neurotransmitters and hormones from neurons and neuroendocrine cells underlies neuronal communication, motor activity and endocrine functions. The core of the neuronal exocytotic machinery is composed of soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs. Formation of complexes between vesicle-attached v- and plasma-membrane anchored t-SNAREs in a highly regulated fashion brings the membranes into close apposition. Small, soluble proteins called Complexins (Cpx and calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium concentrations, but trigger release upon calcium increase. A growing body of evidence suggests that the transmembrane domains (TMDs of SNARE proteins play important roles in regulating the processes of fusion and release, but the mechanisms involved are only starting to be uncovered. Here we review recent evidence that SNARE TMDs exert influence by regulating the dynamics of the fusion pore, the initial aqueous connection between the vesicular lumen and the extracellular space. Even after the fusion pore is established, hormone release by neuroendocrine cells is tightly controlled, and the same may be true of neurotransmitter release by neurons. The dynamics of the fusion pore can regulate the kinetics of cargo release and the net amount released, and can determine the mode of vesicle recycling. Manipulations of SNARE TMDs were found to affect fusion pore properties profoundly, both during exocytosis and in biochemical reconstitutions. To explain these effects, TMD flexibility, and interactions among TMDs or between TMDs and lipids have been invoked. Exocytosis has provided the best setting in which to unravel the underlying mechanisms, being unique among membrane fusion reactions in that single fusion pores can be probed using high-resolution methods. An important role will likely be played by methods that can probe single fusion pores

  1. Comparison of structure, function and regulation of plant cold shock domain proteins to bacterial and animal cold shock domain proteins.

    Science.gov (United States)

    Chaikam, Vijay; Karlson, Dale T

    2010-01-01

    The cold shock domain (CSD) is among the most ancient and well conserved nucleic acid binding domains from bacteria to higher animals and plants. The CSD facilitates binding to RNA, ssDNA and dsDNA and most functions attributed to cold shock domain proteins are mediated by this nucleic acid binding activity. In prokaryotes, cold shock domain proteins only contain a single CSD and are termed cold shock proteins (Csps). In animal model systems, various auxiliary domains are present in addition to the CSD and are commonly named Y-box proteins. Similar to animal CSPs, plant CSPs contain auxiliary C-terminal domains in addition to their N-terminal CSD. Cold shock domain proteins have been shown to play important roles in development and stress adaptation in wide variety of organisms. In this review, the structure, function and regulation of plant CSPs are compared and contrasted to the characteristics of bacterial and animal CSPs. [BMB reports 2010; 43(1): 1-8].

  2. The J3 SCR model applied to resonant converter simulation

    Science.gov (United States)

    Avant, R. L.; Lee, F. C. Y.

    1985-01-01

    The J3 SCR model is a continuous topology computer model for the SCR. Its circuit analog and parameter estimation procedure are uniformly applicable to popular computer-aided design and analysis programs such as SPICE2 and SCEPTRE. The circuit analog is based on the intrinsic three pn junction structure of the SCR. The parameter estimation procedure requires only manufacturer's specification sheet quantities as a data base.

  3. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2012-12-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system.Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies.Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field.Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis.Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models.Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes. The

  4. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2013-02-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system. Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies. Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field. Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis. Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models. Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes

  5. Deactivation of SCR Catalysts by Additives

    DEFF Research Database (Denmark)

    Castellino, Francesco

    2008-01-01

    forskellige opløsninger af K3PO4. Resultaterne viste, at hvis K bindes i K-P saltforbindelser ville dette ikke reducere hastigheden af katalysatorens deaktivering. Regenereringstest udført i laboratoriet på katalysatorplader viste, at regenerering af de eksponerede katalysatorer var muligt ved at vaske demmed...... 0.5Mvandig opløsning af H2SO4. Somdet sidste blev en kommerciel V2O5-WO3-TiO2 SCR monolit eksponer et i 1000 timer for røggas tilsat en vandig opløsning af KCl, Ca(OH)2, H3PO4 og H2SO4 i en pilotopstilling. Blandingens sammensætning blev justeret med henblik på at have et P/K og P/Ca forhold på...... for KCl eller K3PO4. Dette faktum indikerer at kemisk binding af K i P-K-Ca-forbindelser er en effektiv måde at reducere den negative indflydelse på levetiden af vanadium baserede SCR katalysatorer hidrørende fra alkalimetaller. På den anden side blev fosforafsætning og -belægningsdannelse favoriseret ved...

  6. Rejuvenation of the SCR catalyst at Mehrum

    Energy Technology Data Exchange (ETDEWEB)

    Nagai, Y.; Inatsume, Y.; Morita, I.; Kato, Y.; Yokoyama, K.; Ito, K. [Babcock Hitachi K.K., Kure-shi, Hiroshima-ken (Japan)

    2004-07-01

    Babcock Hitachi K.K. (BHK) received the contract of the rejuvenation of the SCR catalyst at the 750 MW coal-fired Mehrum Power Station (in Hohenhameln, Germany) in March 2003. The contractual coverage was 160 m{sup 3} of the entire catalyst layer. The catalyst, which had been in operation for 16 years since 1987, was originally supplied by BHK. The rejuvenation process developed for the Mehrum project consisted of two major steps: the first is to dust off the catalyst and remove the catalyst poison, and the second step is to add active material to enhance the catalyst activity. The catalyst must be dried after each washing. In order to minimize transportation cost and time, the rejuvenation work was done at the Mehrum station site. The scope of the rejuvenation work was shared between the owner and BHK. It took about one and a half months to complete the (total) on-site rejuvenation worked. The performance of the rejuvenated catalyst was superior to show the same level of activity as the unused catalyst and maintain the same SO{sub 2} conversion rate as the spent catalyst. This paper gives the details of the spent coal-fired SCR catalyst rejuvenation work. 13 figs., 1 tab.

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

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

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

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

    Science.gov (United States)

    Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

    2012-01-01

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

  9. BET domain co-regulators in obesity, inflammation and cancer.

    Science.gov (United States)

    Belkina, Anna C; Denis, Gerald V

    2012-06-22

    The bromodomain is a highly conserved motif of 110 amino acids that is bundled into four anti-parallel α-helices and found in proteins that interact with chromatin, such as transcription factors, histone acetylases and nucleosome remodelling complexes. Bromodomain proteins are chromatin 'readers'; they recruit chromatin-regulating enzymes, including 'writers' and 'erasers' of histone modification, to target promoters and to regulate gene expression. Conventional wisdom held that complexes involved in chromatin dynamics are not 'druggable' targets. However, small molecules that inhibit bromodomain and extraterminal (BET) proteins have been described. We examine these developments and discuss the implications for small molecule epigenetic targeting of chromatin networks in cancer.

  10. The SS-SCR Scheme for Dynamic Spectrum Access

    Directory of Open Access Journals (Sweden)

    Vinay Thumar

    2012-01-01

    Full Text Available We integrate the two models of Cognitive Radio (CR, namely, the conventional Sense-and-Scavenge (SS Model and Symbiotic Cooperative Relaying (SCR. The resultant scheme, called SS-SCR, improves the efficiency of spectrum usage and reliability of the transmission links. SS-SCR is enabled by a suitable cross-layer optimization problem in a multihop multichannel CR network. Its performance is compared for different PU activity patterns with those schemes which consider SS and SCR separately and perform disjoint resource allocation. Simulation results depict the effectiveness of the proposed SS-SCR scheme. We also indicate the usefulness of cloud computing for a practical deployment of the scheme.

  11. An SCR inverter for electric vehicles

    Science.gov (United States)

    Latos, T.; Bosack, D.; Ehrlich, R.; Jahns, T.; Mezera, J.; Thimmesch, D.

    1980-01-01

    An inverter for an electric vehicle propulsion application has been designed and constructed to excite a polyphase induction motor from a fixed propulsion battery source. The inverter, rated at 35kW peak power, is fully regenerative and permits vehicle operation in both the forward and reverse directions. Thyristors are employed as the power switching devices arranged in a dc bus commutated topology. This paper describes the major role the controller plays in generating the motor excitation voltage and frequency to deliver performance similar to dc systems. Motoring efficiency test data for the controller are presented. It is concluded that an SCR inverter in conjunction with an ac induction motor is a viable alternative to present dc vehicle propulsion systems on the basis of performance and size criteria.

  12. Understanding NOx SCR Mechanism and Activity on Cu/Chabazite Structures throughout the Catalyst Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Fabio; Delgass, Nick; Gounder, Rajmani; Schneider, William F.; Miller, Jeff; Yezerets, Aleksey; McEwen, Jean-Sabin; Peden, Charles HF; Howden, Ken

    2014-12-09

    Oxides of nitrogen (NOx) compounds contribute to acid rain and photochemical smog and have been linked to respiratory ailments. NOx emissions regulations continue to tighten, driving the need for high performance, robust control strategies. The goal of this project is to develop a deep, molecular level understanding of the function of Cu-SSZ-13 and Cu-SAPO-34 materials that catalyze the SCR of NOx with NH3.

  13. Impacts of acid gases on mercury oxidation across SCR catalyst

    International Nuclear Information System (INIS)

    Zhuang, Ye; Laumb, Jason; Liggett, Richard; Holmes, Mike; Pavlish, John

    2007-01-01

    A series of bench-scale experiments were completed to evaluate acid gases of HCl, SO 2 , and SO 3 on mercury oxidation across a commercial selective catalytic reduction (SCR) catalyst. The SCR catalyst was placed in a simulated flue gas stream containing O 2 , CO 2 , H 2 O, NO, NO 2 , and NH 3 , and N 2 . HCl, SO 2 , and SO 3 were added to the gas stream either separately or in combination to investigate their interactions with mercury over the SCR catalyst. The compositions of the simulated flue gas represent a medium-sulfur and low- to medium-chlorine coal that could represent either bituminous or subbituminous. The experimental data indicated that 5-50 ppm HCl in flue gas enhanced mercury oxidation within the SCR catalyst, possibly because of the reactive chlorine species formed through catalytic reactions. An addition of 5 ppm HCl in the simulated flue gas resulted in mercury oxidation of 45% across the SCR compared to only 4% mercury oxidation when 1 ppm HCl is in the flue gas. As HCl concentration increased to 50 ppm, 63% of Hg oxidation was reached. SO 2 and SO 3 showed a mitigating effect on mercury chlorination to some degree, depending on the concentrations of SO 2 and SO 3 , by competing against HCl for SCR adsorption sites. High levels of acid gases of HCl (50 ppm), SO 2 (2000 ppm), and SO 3 (50 ppm) in the flue gas deteriorate mercury adsorption on the SCR catalyst. (author)

  14. Proteins with GGDEF and EAL domains regulate Pseudomonas putida biofilm formation and dispersal

    DEFF Research Database (Denmark)

    Gjermansen, Morten; Ragas, Paula Cornelia; Tolker-Nielsen, Tim

    2006-01-01

    Microbial biofilm formation often causes problems in medical and industrial settings, and knowledge about the factors that are involved in biofilm development and dispersion is useful for creating strategies to control the processes. In this report, we present evidence that proteins with GGDEF...... and EAL domains are involved in the regulation of biofilm formation and biofilm dispersion in Pseudomonas putida. Overexpression in P. putida of the Escherichia coli YedQ protein, which contains a GGDEF domain, resulted in increased biofilm formation. Overexpression in P. putida of the E. coli Yhj......H protein, which contains an EAL domain, strongly inhibited biofilm formation. Induction of YhjH expression in P. putida cells situated in established biofilms led to rapid dispersion of the biofilms. These results support the emerging theme that GGDEF-domain and EAL-domain proteins are involved...

  15. A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.

    Directory of Open Access Journals (Sweden)

    Alexandr P Kornev

    2008-04-01

    Full Text Available Cyclic nucleotides (cAMP and cGMP regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1 the phosphate binding cassette (PBC, which binds the cAMP ribose-phosphate, 2 the "hinge," a flexible helix, which contacts the PBC, 3 the beta(2,3 loop, which provides precise positioning of an invariant arginine from the PBC, and 4 a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif. The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the beta(2,3 loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.

  16. Design of a periodically operated SCR reactor

    International Nuclear Information System (INIS)

    Kotter, M.; Lintz, H.G.; Turek, T.

    1993-01-01

    A new NO x abatement process uses the rotating Ljungstroem air heater of the power plant for the selective catalytic reduction (SCR) of nitrogen monoxide with ammonia. For this purpose the air heater elements are covered by a catalytically active layer. The transformation can be carried out by simple replacement of the original air heater elements. Thus nitrogen monoxide control is possible without requiring major modifications of existing power plant equipment. Two oxidic catalysts have been developed to be employed in the different temperature sections of the air heater. The activity of the catalysts has been quantified with the aid of laboratory scale experiments. The results can be described using a simple expression for the rate of the chemical reaction. NO conversion and NH 3 slip to be expected in a catalytically active Ljungstroem heat exchanger are calculated with a reactor model taking into account the gas phase mass transfer resistances. The calculations show that the proposed device can be used if the NO concentration in the flue gas does not exceed 300 ppm. Recently Kraftanlagen AG, Heidelberg, installed a catalyst air heater system at Mandalay Generating Station in Oxnard, California. The comparison of the predicted results with preliminary experimental data proves the validity of the chosen reactor model. Under the given conditions NO conversions of more than 60% can be achieved maintaining the NH 3 slip below the specified value of 10 ppm. (orig.). 19 figs., 35 refs [de

  17. SCR in biomass and waste fuelled plants. Benchmarking of Swedish and European plants; SCR i biobraensle- och avfallseldade anlaeggningar. Erfarenheter fraan svenska och europeiska anlaeggningar

    Energy Technology Data Exchange (ETDEWEB)

    Goldschmidt, Barbara; Olsson, Henrik; Lindstroem, Erica

    2010-11-15

    In this report the state-of-art of SCR technology in biomass and waste fired plants is investigated. The aim of the investigation is to answer the question why new Swedish biomass combustion and co-combustion plants often prefer SNCR technology, whilst European waste combustion plants often choose SCR technology. In the report positives and negatives of various types of SCR installations are discussed, high-dust versus tail-end, 'normal' SCR versus low-temperature SCR, etc. Experiences, e g catalyst lifetime, deactivation and maintenance requirement, are discussed. The investigation is based partly on literature, but mainly on interviews with plant owners and with suppliers of SCR installations. The interviewed suppliers are mentioned in the reference list and the interviewed plant owners are mentioned in appendix A and B. The experiences from the Swedish and European plants are quite similar. Tail-end SCR is often operated without serious problems in both biomass and waste fuelled plants. The catalyst lifetimes are as long or even longer than for coal fired plants with high-dust SCR. In waste incineration plants high-dust SCR causes big problems and these plants are almost always equipped with tail-end SCR. In co-combustion boilers, where coal and biomass is co-combusted, high-dust SCR is more common, especially if the boilers were originally coal fired. In plants with both SNCR and high-dust SCR, i.e. slip-SCR, the SCR installation is considered to be much less of a problem. Although the activity loss of the catalyst is as quick as in conventional high-dust SCR, the catalyst can be changed less often. This is due to the fact that installed slip-SCR catalysts often are as large as conventional SCR catalysts, although less NO{sub x} reduction is required after the initial SNCR step. Thus, the catalyst lifetime is prolonged.

  18. Mordenite - Type Zeolite SCR Catalysts with Iron or Copper

    DEFF Research Database (Denmark)

    2012-01-01

    Cu/mordenite catalysts were found to be highly active for the SCR of NO with NH3 and exhibited high resistance to alkali poisoning. Redox and acidic properties of Cu/mordenite were well preserved after poisoning with potassium unlike that of vanadium catalysts. Fe-mordenite catalysts also reveale...... to be essential requirements for the high alkali resistance. Mordenite-type zeolite based catalysts could therefore be attractive alternatives to conventional SCR catalysts for biomass fired power plant flue gas treatment....

  19. CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems

    Directory of Open Access Journals (Sweden)

    Kira eMakarova

    2014-04-01

    Full Text Available CRISPR-Cas adaptive immunity systems of bacteria and archaea insert fragments of virus or plasmid DNA as spacer sequences into CRISPR repeat loci. Processed transcripts encompassing these spacers guide the cleavage of the cognate foreign DNA or RNA. Most CRISPR-Cas loci, in addition to recognized cas genes, also include genes that are not directly implicated in spacer acquisition, CRISPR transcript processing or interference. Here we comprehensively analyze sequences, structures and genomic neighborhoods of one of the most widespread groups of such genes that encode proteins containing a predicted nucleotide-binding domain with a Rossmann-like fold, which we denote CARF (CRISPR-associated Rossmann fold. Several CARF protein structures have been determined but functional characterization of these proteins is lacking. The CARF domain is most frequently combined with a C-terminal winged helix-turn-helix DNA-binding domain and effector domains most of which are predicted to possess DNase or RNase activity. Divergent CARF domains are also found in RtcR proteins, sigma-54 dependent regulators of the rtc RNA repair operon. CARF genes frequently co-occur with those coding for proteins containing the WYL domain with the Sm-like SH3 β-barrel fold, which is also predicted to bind ligands. CRISPR-Cas and possibly other defense systems are predicted to be transcriptionally regulated by multiple ligand-binding proteins containing WYL and CARF domains which sense modified nucleotides and nucleotide derivatives generated during virus infection. We hypothesize that CARF domains also transmit the signal from the bound ligand to the fused effector domains which attack either alien or self nucleic acids, resulting, respectively, in immunity complementing the CRISPR-Cas action or in dormancy/programmed cell death.

  20. L-Cysteine inhibits root elongation through auxin/PLETHORA and SCR/SHR pathway in Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Zhen; Mao, Jie-Li; Zhao, Ying-Jun; Li, Chuan-You; Xiang, Cheng-Bin

    2015-02-01

    L-Cysteine plays a prominent role in sulfur metabolism of plants. However, its role in root development is largely unknown. Here, we report that L-cysteine reduces primary root growth in a dosage-dependent manner. Elevating cellular L-cysteine level by exposing Arabidopsis thaliana seedlings to high L-cysteine, buthionine sulphoximine, or O-acetylserine leads to altered auxin maximum in root tips, the expression of quiescent center cell marker as well as the decrease of the auxin carriers PIN1, PIN2, PIN3, and PIN7 of primary roots. We also show that high L-cysteine significantly reduces the protein level of two sets of stem cell specific transcription factors PLETHORA1/2 and SCR/SHR. However, L-cysteine does not downregulate the transcript level of PINs, PLTs, or SCR/SHR, suggesting that an uncharacterized post-transcriptional mechanism may regulate the accumulation of PIN, PLT, and SCR/SHR proteins and auxin transport in the root tips. These results suggest that endogenous L-cysteine level acts to maintain root stem cell niche by regulating basal- and auxin-induced expression of PLT1/2 and SCR/SHR. L-Cysteine may serve as a link between sulfate assimilation and auxin in regulating root growth. © 2014 Institute of Botany, Chinese Academy of Sciences.

  1. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4

    OpenAIRE

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-01-01

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which prov...

  2. Neurofilament subunit (NFL) head domain phosphorylation regulates axonal transport of neurofilaments.

    LENUS (Irish Health Repository)

    Yates, Darran M

    2009-04-01

    Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.

  3. Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner

    DEFF Research Database (Denmark)

    Kny, Melanie; Standera, Sybille; Hartmann-Petersen, Rasmus

    2011-01-01

    in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane. Here we present the first evidence that Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like (UBL) domain-dependent manner. We...

  4. Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

    Science.gov (United States)

    Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

    2003-08-15

    DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

  5. The JH2 domain and SH2-JH2 linker regulate JAK2 activity: A detailed kinetic analysis of wild type and V617F mutant kinase domains.

    Science.gov (United States)

    Sanz Sanz, Arturo; Niranjan, Yashavanthi; Hammarén, Henrik; Ungureanu, Daniela; Ruijtenbeek, Rob; Touw, Ivo P; Silvennoinen, Olli; Hilhorst, Riet

    2014-10-01

    JAK2 tyrosine kinase regulates many cellular functions. Its activity is controlled by the pseudokinase (JH2) domain by still poorly understood mechanisms. The V617F mutation in the pseudokinase domain activates JAK2 and causes myeloproliferative neoplasms. We conducted a detailed kinetic analysis of recombinant JAK2 tyrosine kinase domain (JH1) and wild-type and V617F tandem kinase (JH1JH2) domains using peptide microarrays to define the functions of the kinase domains. The results show that i) JAK2 follows a random Bi-Bi reaction mechanism ii) JH2 domain restrains the activity of the JH1 domain by reducing the affinity for ATP and ATP competitive inhibitors iii) V617F decreases affinity for ATP but increases catalytic activity compared to wild-type and iv) the SH2-JH2 linker region participates in controlling activity by reducing the affinity for ATP. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Regulation of plant plasma membrane H+- and Ca2+-ATPases by terminal domains

    DEFF Research Database (Denmark)

    Bækgaard, Lone; Fuglsang, Anja Thoe; Palmgren, Michael Gjedde

    2005-01-01

    In the last few years, major progress has been made to elucidate the structure, function, and regulation of P-type plasma membrane H(+)-and Ca(2+)-ATPases. Even though a number of regulatory proteins have been identified, many pieces are still lacking in order to understand the complete regulatory...... mechanisms of these pumps. In plant plasma membrane H(+)- and Ca(2+)-ATPases, autoinhibitory domains are situated in the C- and N-terminal domains, respectively. A model for a common mechanism of autoinhibition is discussed....

  7. Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

    Directory of Open Access Journals (Sweden)

    Adam Z. Blatt

    2017-11-01

    Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

  8. Regulation of the Hsp104 middle domain activity is critical for yeast prion propagation.

    Directory of Open Access Journals (Sweden)

    Jennifer E Dulle

    Full Text Available Molecular chaperones play a significant role in preventing protein misfolding and aggregation. Indeed, some protein conformational disorders have been linked to changes in the chaperone network. Curiously, in yeast, chaperones also play a role in promoting prion maintenance and propagation. While many amyloidogenic proteins are associated with disease in mammals, yeast prion proteins, and their ability to undergo conformational conversion into a prion state, are proposed to play a functional role in yeast biology. The chaperone Hsp104, a AAA+ ATPase, is essential for yeast prion propagation. Hsp104 fragments large prion aggregates to generate a population of smaller oligomers that can more readily convert soluble monomer and be transmitted to daughter cells. Here, we show that the middle (M domain of Hsp104, and its mobility, plays an integral part in prion propagation. We generated and characterized mutations in the M-domain of Hsp104 that are predicted to stabilize either a repressed or de-repressed conformation of the M-domain (by analogy to ClpB in bacteria. We show that the predicted stabilization of the repressed conformation inhibits general chaperone activity. Mutation to the de-repressed conformation, however, has differential effects on ATP hydrolysis and disaggregation, suggesting that the M-domain is involved in coupling these two activities. Interestingly, we show that changes in the M-domain differentially affect the propagation of different variants of the [PSI+] and [RNQ+] prions, which indicates that some prion variants are more sensitive to changes in the M-domain mobility than others. Thus, we provide evidence that regulation of the M-domain of Hsp104 is critical for efficient prion propagation. This shows the importance of elucidating the function of the M-domain in order to understand the role of Hsp104 in the propagation of different prions and prion variants.

  9. Evaluation of the first SCR-plants in Sweden; Utvaerdering av de foersta SCR-anlaeggningarna i Sverige

    Energy Technology Data Exchange (ETDEWEB)

    Hanell, B [Vattenfall AB, Stockholm (Sweden); and others

    1996-05-01

    This report presents operational experience of SCR systems at five power plants in Sweden; the diesel cogeneration plants in Linkoeping, Oskarshamn, Skultuna and Visby and the coal fired power plant in Vaesteraas. The experience represents the first years of operation of the SCR systems. The SCR-systems involved in this project achieve the following: * Uneven flue gas flow and concentration of ammonia and NO{sub x} through the SCR reactor results in lower efficiency. Hence it is important to achieve a thorough mixing of the ammonia in the flue gas in order to achieve high NO{sub x} reduction efficiencies, * Inferior control systems can cause unnecessary ammonia slip, * The diesel plants with an operating time of a couple of thousand hours have had major problems with deposits on the catalyst surface, * Guarantees regarding the lifetime of the catalyst are important. At commissioning the catalyst has to be over-dimensioned since the system has to reach the guaranteed emissions during the whole guarantee period, * There should be enough space in the reactor to install additional catalyst layers. This project verifies that additional layers need to be installed at later stages, * The mechanical construction of the SCR-reactor is important. The efficiency decreases when there is a leakage of flue gases past the reactor, * No considerable amounts of N{sub 2}O are generated by the catalyst. 21 refs, 27 figs, 47 tabs

  10. State Estimation in the Automotive SCR DeNOx Process

    DEFF Research Database (Denmark)

    Zhou, Guofeng; Jørgensen, John Bagterp; Duwig, Christophe

    2012-01-01

    on exhaust gas emissions. For advanced control, e.g. Model Predictive Control (MPC), of the SCR process, accurate state estimates are needed. We investigate the performance of the ordinary and the extended Kalman filters based on a simple first principle system model. The performance is tested through......Selective catalytic reduction (SCR) of nitrogen oxides (NOx) is a widely applied diesel engine exhaust gas after-treatment technology. For effective NOx removal in a transient operating automotive application, controlled dosing of urea can be used to meet the increasingly restrictive legislations...

  11. Alternative SILP-SCR Catalysts based on Guanidinium Chromates

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Riisager, Anders; Ståhl, Kenny

    There is an increasing global concern about human caused emissions of pollutants like sulfur and nitrogen oxides to the atmosphere leading to, e.g. smog and acid rain damaging to the human health and the environment. Selective catalytic reduction (SCR) of NOx with ammonia as reductant is the most...... duct. There is therefore a demand for alkali-resistant SCR catalysts more flexible regarding temperature of operation and position in the duct. Supported ionic liquid phase (SILP) catalysts with 1,1,3,3-Tetramethylguanidinium (TMGH+) and a chromium oxide anion supported on anatase have exhibited...

  12. High voltage series resonant inverter ion engine screen supply. [SCR series resonant inverter for space applications

    Science.gov (United States)

    Biess, J. J.; Inouye, L. Y.; Shank, J. H.

    1974-01-01

    A high-voltage, high-power LC series resonant inverter using SCRs has been developed for an Ion Engine Power Processor. The inverter operates within 200-400Vdc with a maximum output power of 2.5kW. The inverter control logic, the screen supply electrical and mechanical characteristics, the efficiency and losses in power components, regulation on the dual feedback principle, the SCR waveforms and the component weight are analyzed. Efficiency of 90.5% and weight density of 4.1kg/kW are obtained.

  13. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.

    Science.gov (United States)

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-07-30

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. The epigenetic regulator Smchd1 contains a functional GHKL-type ATPase domain.

    Science.gov (United States)

    Chen, Kelan; Dobson, Renwick C J; Lucet, Isabelle S; Young, Samuel N; Pearce, F Grant; Blewitt, Marnie E; Murphy, James M

    2016-06-15

    Structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is an epigenetic regulator that plays critical roles in gene regulation during development. Mutations in SMCHD1 were recently implicated in the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD), although the mechanistic basis remains of outstanding interest. We have previously shown that Smchd1 associates with chromatin via its homodimeric C-terminal hinge domain, yet little is known about the function of the putative GHKL (gyrase, Hsp90, histidine kinase, MutL)-type ATPase domain at its N-terminus. To formally assess the structure and function of Smchd1's ATPase domain, we have generated recombinant proteins encompassing the predicted ATPase domain and the adjacent region. Here, we show that the Smchd1 N-terminal region exists as a monomer and adopts a conformation resembling that of monomeric full-length heat shock protein 90 (Hsp90) protein in solution, even though the two proteins share only ∼8% overall sequence identity. Despite being monomeric, the N-terminal region of Smchd1 exhibits ATPase activity, which can be antagonized by the reaction product, ADP, or the Hsp90 inhibitor, radicicol, at a nanomolar concentration. Interestingly, introduction of an analogous mutation to that identified in SMCHD1 of an FSHD patient compromised protein stability, suggesting a possible molecular basis for loss of protein function and pathogenesis. Together, these results reveal important structure-function characteristics of Smchd1 that may underpin its mechanistic action at the chromatin level. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  15. The Eag domain regulates the voltage-dependent inactivation of rat Eag1 K+ channels.

    Directory of Open Access Journals (Sweden)

    Ting-Feng Lin

    Full Text Available Eag (Kv10 and Erg (Kv11 belong to two distinct subfamilies of the ether-à-go-go K+ channel family (KCNH. While Erg channels are characterized by an inward-rectifying current-voltage relationship that results from a C-type inactivation, mammalian Eag channels display little or no voltage-dependent inactivation. Although the amino (N-terminal region such as the eag domain is not required for the C-type inactivation of Erg channels, an N-terminal deletion in mouse Eag1 has been shown to produce a voltage-dependent inactivation. To further discern the role of the eag domain in the inactivation of Eag1 channels, we generated N-terminal chimeras between rat Eag (rEag1 and human Erg (hERG1 channels that involved swapping the eag domain alone or the complete cytoplasmic N-terminal region. Functional analyses indicated that introduction of the homologous hERG1 eag domain led to both a fast phase and a slow phase of channel inactivation in the rEag1 chimeras. By contrast, the inactivation features were retained in the reverse hERG1 chimeras. Furthermore, an eag domain-lacking rEag1 deletion mutant also showed the fast phase of inactivation that was notably attenuated upon co-expression with the rEag1 eag domain fragment, but not with the hERG1 eag domain fragment. Additionally, we have identified a point mutation in the S4-S5 linker region of rEag1 that resulted in a similar inactivation phenotype. Biophysical analyses of these mutant constructs suggested that the inactivation gating of rEag1 was distinctly different from that of hERG1. Overall, our findings are consistent with the notion that the eag domain plays a critical role in regulating the inactivation gating of rEag1. We propose that the eag domain may destabilize or mask an inherent voltage-dependent inactivation of rEag1 K+ channels.

  16. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    Science.gov (United States)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  17. COST OF SELECTIVE CATALYTIC REDUCTION (SCR) APPLICATION FOR NOX CONTROL ON COAL-FIRED BOILERS

    Science.gov (United States)

    The report provides a methodology for estimating budgetary costs associated with retrofit applications of selective catalytic reduction (SCR) technology on coal-fired boilers. SCR is a postcombustion nitrogen oxides (NOx) control technology capable of providing NOx reductions >90...

  18. Selective catalytic reduction (SCR) NOx control for small natural gas-fired prime movers

    International Nuclear Information System (INIS)

    Shareef, G.S.; Stone, D.K.; Ferry, K.R.; Johnson, K.L.; Locke, K.S.

    1992-01-01

    The application of selective catalytic reduction (SCR) to small natural gas-fired prime movers at cogeneration facilities and compressor stations could possibly increase due to regulatory forces to limit NO x from such sources. The natural gas industry is presently without a current database with which to evaluate the cost and operating characteristics of SCR under the conditions anticipated for small prime movers. This paper presents the results from a two-phase study undertaken to document SCR applications with emphasis on SCR system performance and costs. The database of small natural gas-fired prime mover SCR experience, focusing on prime mover characterization, SCR system performance, and SCR system costs will be described. Result from analysis of performance and cost data will be discussed, including analytical tools developed to project SCR system performance and costs

  19. Conformational switching in the coiled-coil domains of a proteasomal ATPase regulates substrate processing.

    Science.gov (United States)

    Snoberger, Aaron; Brettrager, Evan J; Smith, David M

    2018-06-18

    Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conformations: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN's symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases' coiled-coils. Furthermore, we find that one coiled-coil can be conformationally constrained even while unfolding substrates, and conformational changes in two of the coiled-coils regulate PAN switching between resting and active states. This switching functionally mimics similar states proposed for the 26S proteasome from cryo-EM. These findings thus build a mechanistic framework to understand regulation of proteasome activity.

  20. The PH Domain of PDK1 Exhibits a Novel, Phospho-Regulated Monomer-Dimer Equilibrium With Important Implications for Kinase Domain Activation: Single Molecule and Ensemble Studies†

    Science.gov (United States)

    Ziemba, Brian P.; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J.

    2013-01-01

    Phosphoinositide-Dependent Kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4-5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric state(s) of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. The present study investigates the binding of purified WT and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single molecule and ensemble measurements. Single molecule analysis of the brightness of fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric, while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single molecule analysis of 2-D diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little protein penetration into the bilayer as observed for other PH domains. The 2-D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that enables greater protein insertion into

  1. Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

    Directory of Open Access Journals (Sweden)

    Forest H. Andrews

    2016-09-01

    Full Text Available MORC3 is linked to inflammatory myopathies and cancer; however, the precise role of MORC3 in normal cell physiology and disease remains poorly understood. Here, we present detailed genetic, biochemical, and structural analyses of MORC3. We demonstrate that MORC3 is significantly upregulated in Down syndrome and that genetic abnormalities in MORC3 are associated with cancer. The CW domain of MORC3 binds to the methylated histone H3K4 tail, and this interaction is essential for recruitment of MORC3 to chromatin and accumulation in nuclear bodies. We show that MORC3 possesses intrinsic ATPase activity that requires DNA, but it is negatively regulated by the CW domain, which interacts with the ATPase domain. Natively linked CW impedes binding of the ATPase domain to DNA, resulting in a decrease in the DNA-stimulated enzymatic activity. Collectively, our studies provide a molecular framework detailing MORC3 functions and suggest that its modulation may contribute to human disease.

  2. Vanadia supported on zeolites for SCR of NO by ammonia

    DEFF Research Database (Denmark)

    Putluru, Siva Sankar Reddy; Riisager, Anders; Fehrmann, Rasmus

    2010-01-01

    , acidity and micropore structure of the support. Apparently the support hosted the potassium oxide on the acid sites, thereby protecting the active vanadium species from poisoning. Zeolite based catalysts might therefore prove useful for SCR of NO in alkali-containing flue gases from, e.g. biomass fired...

  3. Regenerative Snubber For GTO-Commutated SCR Inverter

    Science.gov (United States)

    Rippel, Wally E.; Edwards, Dean B.

    1992-01-01

    Proposed regenerative snubbing circuit substituted for dissipative snubbing circuit in inverter based on silicon controlled rectifiers (SCR's) commutated by gate-turn-off thyristor (GTO). Intended to reduce loss of power that occurs in dissipative snubber. Principal criteria in design: low cost, simplicity, and reliability.

  4. Cost and Fuel Efficient SCR-only Solution for post-2010 HD Emission Standards

    NARCIS (Netherlands)

    Cloudt, R.P.M.; Willems, F.P.T.; Heijden, van der P.

    2009-01-01

    A promising SCR-only solution is presented to meetpost-2010 NOx emission targets for heavy dutyapplications. The proposed concept is based on anengine from a EURO IV SCR application, which isconsidered optimal with respect to fuel economy andcosts. The addition of advanced SCR after

  5. Cost and fuel efficient SCR-only solution for post-2010 HD emission standards

    NARCIS (Netherlands)

    Cloudt, R.P.M.; Willems, F.P.T.; Heijden, P.V.A.M. van der

    2009-01-01

    A promising SCR-only solution is presented to meet post-2010 NOx emission targets for heavy duty applications. The proposed concept is based on an engine from a EURO IV SCR application, which is considered optimal with respect to fuel economy and costs. The addition of advanced SCR after treatment

  6. Structural transitions in conserved, ordered Beclin 1 domains essential to regulating autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Glover, Karen; Li, Yue; Mukhopadhyay, Shreya; Leuthner, Zoe; Chakravarthy, Srinivas; Colbert, Christopher L.; Sinha, Sangita C. (NDSU); (IIT)

    2017-08-10

    Beclin 1 (BECN1) is a key regulator of autophagy, a critical catabolic homeostasis pathway that involves sequestration of selected cytoplasmic components by multilayered vesicles called autophagosomes, followed by lysosomal fusion and degradation. BECN1 is a core component of class III phosphatidylinositol-3-kinase complexes responsible for autophagosome nucleation. Without heterologous binding partners, BECN1 forms an antiparallel homodimer via its coiled-coil domain (CCD). However, the last 16 CCD residues, composing an “overlap helix” (OH), have been crystallized in two mutually exclusive states: either as part of the CCD or packed against the C-terminal β-α repeated, autophagy-specific domain (BARAD). Here, using CD spectroscopy, isothermal titration calorimetry, and small-angle X-ray scattering, we show that in the homodimeric state, the OH transitions between these two different packing states, with the predominant state comprising the OH packed against the BARAD, contrary to expectations based on known BECN1 interactions with heterologous partners. We confirmed this observation by comparing the impact of mutating four residues that mediate packing of the OH against both the CCD and BARAD on structure and stability of the CCD, the OH+BARAD, and the two-domain CCD–BARAD. Last, we used cellular assays to demonstrate that mutation of these OH-interface residues abrogates starvation-induced up-regulation of autophagy but does not affect basal autophagy. In summary, we have identified a BECN1 helical region that transitions between packing as part of either one of two conserved domains (i.e. the CCD or the BARAD). Our findings have important implications for the relative stability of autophagy-inactive and autophagy-active BECN1 complexes.

  7. LPV gain-scheduled control of SCR aftertreatment systems

    Science.gov (United States)

    Meisami-Azad, Mona; Mohammadpour, Javad; Grigoriadis, Karolos M.; Harold, Michael P.; Franchek, Matthew A.

    2012-01-01

    Hydrocarbons, carbon monoxide and some of other polluting emissions produced by diesel engines are usually lower than those produced by gasoline engines. While great strides have been made in the exhaust aftertreatment of vehicular pollutants, the elimination of nitrogen oxide (NO x ) from diesel vehicles is still a challenge. The primary reason is that diesel combustion is a fuel-lean process, and hence there is significant unreacted oxygen in the exhaust. Selective catalytic reduction (SCR) is a well-developed technology for power plants and has been recently employed for reducing NO x emissions from automotive sources and in particular, heavy-duty diesel engines. In this article, we develop a linear parameter-varying (LPV) feedforward/feedback control design method for the SCR aftertreatment system to decrease NO x emissions while keeping ammonia slippage to a desired low level downstream the catalyst. The performance of the closed-loop system obtained from the interconnection of the SCR system and the output feedback LPV control strategy is then compared with other control design methods including sliding mode, and observer-based static state-feedback parameter-varying control. To reduce the computational complexity involved in the control design process, the number of LPV parameters in the developed quasi-LPV (qLPV) model is reduced by applying the principal component analysis technique. An LPV feedback/feedforward controller is then designed for the qLPV model with reduced number of scheduling parameters. The designed full-order controller is further simplified to a first-order transfer function with a parameter-varying gain and pole. Finally, simulation results using both a low-order model and a high-fidelity and high-order model of SCR reactions in GT-POWER interfaced with MATLAB/SIMULINK illustrate the high NO x conversion efficiency of the closed-loop SCR system using the proposed parameter-varying control law.

  8. Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

    Science.gov (United States)

    Caldo, Kristian Mark P; Acedo, Jeella Z; Panigrahi, Rashmi; Vederas, John C; Weselake, Randall J; Lemieux, M Joanne

    2017-10-01

    Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT1 1-113 ) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Transactivation domain of p53 regulates DNA repair and integrity in human iPS cells.

    Science.gov (United States)

    Kannappan, Ramaswamy; Mattapally, Saidulu; Wagle, Pooja A; Zhang, Jianyi

    2018-05-18

    The role of p53 transactivation domain (p53-TAD), a multifunctional and dynamic domain, on DNA repair and retaining DNA integrity in human iPS cells has never been studied. p53-TAD was knocked out in iPS cells using CRISPR/Cas9 and was confirmed by DNA sequencing. p53-TAD KO cells were characterized by: accelerated proliferation, decreased population doubling time, and unaltered Bcl2, BBC3, IGF1R, Bax and altered Mdm2, p21, and PIDD transcripts expression. In p53-TAD KO cells p53 regulated DNA repair proteins XPA, DNA polH and DDB2 expression were found to be reduced compared to p53-WT cells. Exposure to low dose of doxorubicin (Doxo) induced similar DNA damage and DNA damage response (DDR) measured by RAD50 and MRE11 expression, Checkpoint kinase 2 activation and γH2A.X recruitment at DNA strand breaks in both the cell groups indicating silencing p53-TAD do not affect DDR mechanism upstream of p53. Following removal of Doxo p53-WT hiPS cells underwent DNA repair, corrected their damaged DNA and restored DNA integrity. Conversely, p53-TAD KO hiPS cells did not undergo complete DNA repair and failed to restore DNA integrity. More importantly continuous culture of p53-TAD KO hiPS cells underwent G2/M cell cycle arrest and expressed cellular senescent marker p16 INK4a . Our data clearly shows that silencing transactivation domain of p53 did not affect DDR but affected the DNA repair process implying the crucial role of p53 transactivation domain in maintaining DNA integrity. Therefore, activating p53-TAD domain using small molecules may promote DNA repair and integrity of cells and prevent senescence.

  10. Protein domain analysis of genomic sequence data reveals regulation of LRR related domains in plant transpiration in Ficus.

    Science.gov (United States)

    Lang, Tiange; Yin, Kangquan; Liu, Jinyu; Cao, Kunfang; Cannon, Charles H; Du, Fang K

    2014-01-01

    Predicting protein domains is essential for understanding a protein's function at the molecular level. However, up till now, there has been no direct and straightforward method for predicting protein domains in species without a reference genome sequence. In this study, we developed a functionality with a set of programs that can predict protein domains directly from genomic sequence data without a reference genome. Using whole genome sequence data, the programming functionality mainly comprised DNA assembly in combination with next-generation sequencing (NGS) assembly methods and traditional methods, peptide prediction and protein domain prediction. The proposed new functionality avoids problems associated with de novo assembly due to micro reads and small single repeats. Furthermore, we applied our functionality for the prediction of leucine rich repeat (LRR) domains in four species of Ficus with no reference genome, based on NGS genomic data. We found that the LRRNT_2 and LRR_8 domains are related to plant transpiration efficiency, as indicated by the stomata index, in the four species of Ficus. The programming functionality established in this study provides new insights for protein domain prediction, which is particularly timely in the current age of NGS data expansion.

  11. Synthesis of FBD-based PLC design from NuSCR formal specification

    International Nuclear Information System (INIS)

    Yoo, Junbeom; Cha, Sungdeok; Kim, Chang Hwoi; Song, Duck Yong

    2005-01-01

    NuSCR is a formal specification language to document requirements for real-time embedded software with nuclear engineering applications in mind. Domain experts actively participated in selecting how to best represent various aspects. It uses tabular notations to specify required computations and automata to document state- or time-dependent behavior. As programmable logic controllers (PLCs) are widely used to implement real-time embedded software, synthesis of PLC code from a formal specification is desirable if transformation rules can be rigorously defined. In addition to improved productivity, results of safety analysis performed on requirements remain valid. In this paper, we demonstrate how NuSCR specification can be translated into semantically equivalent function block diagram (FBD) code. The process, except the initial phase where user provides information on missing or implicit details, is automated. Since executable code can be automatically generated using CASE tools from FBD, much of software development is automated. Proposed technique is currently being used in developing reactor protection system (RPS) for nuclear power plants in Korea, and experience to date has been positive. We demonstrate the proposed approach using the fixed set-point rising trip which is one of the most complex trip logics included in the RPS

  12. Selective Catalytic Reduction (SCR) for mobile application - heavy duty diesel; Selektive Katalytische Reduktion (SCR) fuer die mobile Anwendung - LKW

    Energy Technology Data Exchange (ETDEWEB)

    Huennekes, E.; Neubauer, T. [Engelhard Technologies GmbH, Hannover (Germany); Roth, S.A.; Patchett, J.A. [Engelhard Corp., R and D, Iselin, NJ (United States)

    2006-07-01

    Different system configurations of particulate and NOx control via selective catalytic reduction (SCR) were discussed. Advantages and disadvantages were described and the final choice of the optimum system will strongly depend on the application, the market (US, EU) and the system costs. Especially when considering low temperature NOx control, the optimum adjustment of the NO{sub 2}/NO{sub x} ratio in front of an SCR system plays an important role. When generating NO2 over an oxidation catalyst, the resulting NO{sub 2}/NO{sub x} ratio strongly depends on temperature and space velocity. Steady state data show an optimum NO{sub 2}/NO{sub x} ratio between 35 and 60% at temperatures about 240 C. Three DOC systems in front of an SCR system were investigated with the purpose to generate high, low and optimum NO{sub 2}/NO{sub x} ratios. The fast SCR reaction at 1:1 NO: NO2 with NH{sub 3} is the preferred reaction pathway until either NO or NO{sub 2} are consumed. The benefit of an optimum designed DOC system can be seen in the transient response after a sudden increase in urea dosing. The time for the optimum designed system to reach maximum NO{sub x} conversion is much shorter compared with systems having excess NO or NO{sub 2} Ammonia oxidation catalysts (AMOX) are effective means in controlling ammonia from SCR systems. To be effective, AMOX must have selectivity to nitrogen over N{sub 2}O and NO{sub x}. (orig.)

  13. Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.

    Science.gov (United States)

    Garcia-Olivares, Jennie; Alekov, Alexi; Boroumand, Mohammad Reza; Begemann, Birgit; Hidalgo, Patricia; Fahlke, Christoph

    2008-11-15

    Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.

  14. Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.

    Science.gov (United States)

    Danthi, Pranav; Coffey, Caroline M; Parker, John S L; Abel, Ty W; Dermody, Terence S

    2008-12-01

    Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. To evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infection, phi mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in phi diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in phi affect the apoptotic potential of reovirus, suggesting that phi initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective phi mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the phi domain of mu1 plays an important regulatory role in reovirus-induced apoptosis and disease.

  15. Independent regulation of reovirus membrane penetration and apoptosis by the mu1 phi domain.

    Directory of Open Access Journals (Sweden)

    Pranav Danthi

    2008-12-01

    Full Text Available Apoptosis plays an important role in the pathogenesis of reovirus encephalitis. Reovirus outer-capsid protein mu1, which functions to penetrate host cell membranes during viral entry, is the primary regulator of apoptosis following reovirus infection. Ectopic expression of full-length and truncated forms of mu1 indicates that the mu1 phi domain is sufficient to elicit a cell death response. To evaluate the contribution of the mu1 phi domain to the induction of apoptosis following reovirus infection, phi mutant viruses were generated by reverse genetics and analyzed for the capacity to penetrate cell membranes and elicit apoptosis. We found that mutations in phi diminish reovirus membrane penetration efficiency by preventing conformational changes that lead to generation of key reovirus entry intermediates. Independent of effects on membrane penetration, amino acid substitutions in phi affect the apoptotic potential of reovirus, suggesting that phi initiates apoptosis subsequent to cytosolic delivery. In comparison to wild-type virus, apoptosis-defective phi mutant viruses display diminished neurovirulence following intracranial inoculation of newborn mice. These results indicate that the phi domain of mu1 plays an important regulatory role in reovirus-induced apoptosis and disease.

  16. Regulation of Na+ channel inactivation by the DIII and DIV voltage-sensing domains.

    Science.gov (United States)

    Hsu, Eric J; Zhu, Wandi; Schubert, Angela R; Voelker, Taylor; Varga, Zoltan; Silva, Jonathan R

    2017-03-06

    Functional eukaryotic voltage-gated Na + (Na V ) channels comprise four domains (DI-DIV), each containing six membrane-spanning segments (S1-S6). Voltage sensing is accomplished by the first four membrane-spanning segments (S1-S4), which together form a voltage-sensing domain (VSD). A critical Na V channel gating process, inactivation, has previously been linked to activation of the VSDs in DIII and DIV. Here, we probe this interaction by using voltage-clamp fluorometry to observe VSD kinetics in the presence of mutations at locations that have been shown to impair Na V channel inactivation. These locations include the DIII-DIV linker, the DIII S4-S5 linker, and the DIV S4-S5 linker. Our results show that, within the 10-ms timeframe of fast inactivation, the DIV-VSD is the primary regulator of inactivation. However, after longer 100-ms pulses, the DIII-DIV linker slows DIII-VSD deactivation, and the rate of DIII deactivation correlates strongly with the rate of recovery from inactivation. Our results imply that, over the course of an action potential, DIV-VSDs regulate the onset of fast inactivation while DIII-VSDs determine its recovery. © 2017 Hsu et al.

  17. The SH2 domain of Abl kinases regulates kinase autophosphorylation by controlling activation loop accessibility

    Science.gov (United States)

    Lamontanara, Allan Joaquim; Georgeon, Sandrine; Tria, Giancarlo; Svergun, Dmitri I.; Hantschel, Oliver

    2014-11-01

    The activity of protein kinases is regulated by multiple molecular mechanisms, and their disruption is a common driver of oncogenesis. A central and almost universal control element of protein kinase activity is the activation loop that utilizes both conformation and phosphorylation status to determine substrate access. In this study, we use recombinant Abl tyrosine kinases and conformation-specific kinase inhibitors to quantitatively analyse structural changes that occur after Abl activation. Allosteric SH2-kinase domain interactions were previously shown to be essential for the leukemogenesis caused by the Bcr-Abl oncoprotein. We find that these allosteric interactions switch the Abl activation loop from a closed to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker. Disruption of the SH2-kinase interaction abolishes activation loop phosphorylation. Our analysis provides a molecular mechanism for the SH2 domain-dependent activation of Abl that may also regulate other tyrosine kinases.

  18. The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

    Science.gov (United States)

    Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

    2004-08-13

    WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

  19. Structural basis for different phosphoinositide specificities of the PX domains of sorting nexins regulating G-protein signaling.

    Science.gov (United States)

    Mas, Caroline; Norwood, Suzanne J; Bugarcic, Andrea; Kinna, Genevieve; Leneva, Natalya; Kovtun, Oleksiy; Ghai, Rajesh; Ona Yanez, Lorena E; Davis, Jasmine L; Teasdale, Rohan D; Collins, Brett M

    2014-10-10

    Sorting nexins (SNXs) or phox homology (PX) domain containing proteins are central regulators of cell trafficking and signaling. A subfamily of PX domain proteins possesses two unique PX-associated domains, as well as a regulator of G protein-coupled receptor signaling (RGS) domain that attenuates Gαs-coupled G protein-coupled receptor signaling. Here we delineate the structural organization of these RGS-PX proteins, revealing a protein family with a modular architecture that is conserved in all eukaryotes. The one exception to this is mammalian SNX19, which lacks the typical RGS structure but preserves all other domains. The PX domain is a sensor of membrane phosphoinositide lipids and we find that specific sequence alterations in the PX domains of the mammalian RGS-PX proteins, SNX13, SNX14, SNX19, and SNX25, confer differential phosphoinositide binding preferences. Although SNX13 and SNX19 PX domains bind the early endosomal lipid phosphatidylinositol 3-phosphate, SNX14 shows no membrane binding at all. Crystal structures of the SNX19 and SNX14 PX domains reveal key differences, with alterations in SNX14 leading to closure of the binding pocket to prevent phosphoinositide association. Our findings suggest a role for alternative membrane interactions in spatial control of RGS-PX proteins in cell signaling and trafficking. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Urea thermolysis and NOx reduction with and without SCR catalysts

    International Nuclear Information System (INIS)

    Fang, Howard L.; DaCosta, Herbert F.M.

    2003-01-01

    Urea-selective catalytic reduction (SCR) has been a leading contender for removal of nitrogen oxides (deNO x ) from diesel engine emissions. Despite its advantages, the SCR technology faces some critical detriments to its catalytic performance such as catalyst surface passivation (caused by deposit formation) and consequent stoichiometric imbalance of the urea consumption. Deposit formation deactivates catalytic performance by not only consuming part of the ammonia produced during urea decomposition but also degrading the structural and thermal properties of the catalyst surface. We have characterized the urea thermolysis with and without the urea-SCR catalyst using both spectroscopic (DRIFTS and Raman) and thermal techniques (thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC)) to identify the deposit components and their corresponding thermal properties. Urea thermolysis exhibits two decomposition stages, involving ammonia generation and consumption, respectively. The decomposition after the second stage leads to the product of melamine complexes, (HNC=NH) x (HNCO) y , that hinder catalytic performance. The presence of catalyst accompanied with a good spray of the urea solution helps to eliminate the second stage. In this work, kinetics of the direct reduction of NO x by urea is determined and the possibility of using additives to the urea solution in order to rejuvenate the catalyst surface and improve its performance will be discussed

  1. Alloy SCR-3 resistant to stress corrosion cracking

    International Nuclear Information System (INIS)

    Kowaka, Masamichi; Fujikawa, Hisao; Kobayashi, Taiki

    1977-01-01

    Austenitic stainless steel is used widely because the corrosion resistance, workability and weldability are excellent, but the main fault is the occurrence of stress corrosion cracking in the environment containing chlorides. Inconel 600, most resistant to stress corrosion cracking, is not necessarily safe under some severe condition. In the heat-affected zone of SUS 304 tubes for BWRs, the cases of stress corrosion cracking have occurred. The conventional testing method of stress corrosion cracking using boiling magnesium chloride solution has been problematical because it is widely different from actual environment. The effects of alloying elements on stress corrosion cracking are remarkably different according to the environment. These effects were investigated systematically in high temperature, high pressure water, and as the result, Alloy SCR-3 with excellent stress corrosion cracking resistance was found. The physical constants and the mechanical properties of the SCR-3 are shown. The states of stress corrosion cracking in high temperature, high pressure water containing chlorides and pure water, polythionic acid, sodium phosphate solution and caustic soda of the SCR-3, SUS 304, Inconel 600 and Incoloy 800 are compared and reported. (Kako, I.)

  2. Regulation of embryonic hematopoiesis by a cytokine-inducible SH2 domain homolog in zebrafish.

    Science.gov (United States)

    Lewis, Rowena S; Noor, Suzita M; Fraser, Fiona W; Sertori, Robert; Liongue, Clifford; Ward, Alister C

    2014-06-15

    Cytokine-inducible SH2 domain-containing protein (CISH), a member of the suppressor of cytokine signaling family of negative feedback regulators, is induced by cytokines that activate STAT5 and can inhibit STAT5 signaling in vitro. However, demonstration of a definitive in vivo role for CISH during development has remained elusive. This study employed expression analysis and morpholino-mediated knockdown in zebrafish in concert with bioinformatics and biochemical approaches to investigate CISH function. Two zebrafish CISH paralogs were identified, cish.a and cish.b, with high overall conservation (43-46% identity) with their mammalian counterparts. The cish.a gene was maternally derived, with transcripts present throughout embryogenesis, and increasing at 4-5 d after fertilization, whereas cish.b expression commenced at 8 h after fertilization. Expression of cish.a was regulated by the JAK2/STAT5 pathway via conserved tetrameric STAT5 binding sites (TTCN3GAA) in its promoter. Injection of morpholinos targeting cish.a, but not cish.b or control morpholinos, resulted in enhanced embryonic erythropoiesis, myelopoiesis, and lymphopoiesis, including a 2- 3-fold increase in erythrocytic markers. This occurred concomitantly with increased activation of STAT5. This study indicates that CISH functions as a conserved in vivo target and regulator of STAT5 in the control of embryonic hematopoiesis. Copyright © 2014 by The American Association of Immunologists, Inc.

  3. Phospho-Caveolin-1 Mediates Integrin-Regulated Membrane Domain Internalisation

    Science.gov (United States)

    del Pozo, Miguel A.; Alderson, Nazilla B.; Grande-García, Araceli; Balasubramanian, Nagaraj; Schwartz, Martin A.; Kiosses, William B.; Anderson, Richard G.W.

    2005-01-01

    Growth of normal cells is anchorage-dependent because signalling through multiple pathways including Erk, PI 3-kinase and Rac requires integrin-mediated cell adhesion 1. Components of these pathways localize to low density, cholesterol-rich domains in the plasma membrane named “lipid rafts” 2,3 or “cholesterol enriched membrane microdomains” (CEMM) 4. We previously reported that integrin-mediated adhesion regulates CEMM trafficking such that cell detachment from the extracellular matrix (ECM) triggers CEMM internalisation and clearance from the plasma membrane 5. We now report that this internalisation is mediated by dynamin-2 and caveolin-1. Internalisation requires phosphorylation of caveolin-1 on tyrosine 14. A shift in localisation of phospho-caveolin-1 from focal adhesions to caveolae induces CEMM internalisation upon cell detachment, which mediates inhibition of Erk, PI 3-kinase and Rac. These data define a novel molecular mechanism for growth and tumour suppression by caveolin-1. PMID:16113676

  4. Engineering FKBP-Based Destabilizing Domains to Build Sophisticated Protein Regulation Systems.

    Directory of Open Access Journals (Sweden)

    Wenlin An

    Full Text Available Targeting protein stability with small molecules has emerged as an effective tool to control protein abundance in a fast, scalable and reversible manner. The technique involves tagging a protein of interest (POI with a destabilizing domain (DD specifically controlled by a small molecule. The successful construction of such fusion proteins may, however, be limited by functional interference of the DD epitope with electrostatic interactions required for full biological function of proteins. Another drawback of this approach is the remaining endogenous protein. Here, we combined the Cre-LoxP system with an advanced DD and generated a protein regulation system in which the loss of an endogenous protein, in our case the tumor suppressor PTEN, can be coupled directly with a conditionally fine-tunable DD-PTEN. This new system will consolidate and extend the use of DD-technology to control protein function precisely in living cells and animal models.

  5. Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

    Science.gov (United States)

    Pripfl, Jürgen; Lamm, Claus

    2015-02-01

    Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  6. Allosteric Regulation in the Ligand Binding Domain of Retinoic Acid Receptorγ.

    Directory of Open Access Journals (Sweden)

    Yassmine Chebaro

    Full Text Available Retinoic acid (RA plays key roles in cell differentiation and growth arrest through nuclear retinoic acid receptors (RARs, which are ligand-dependent transcription factors. While the main trigger of RAR activation is the binding of RA, phosphorylation of the receptors has also emerged as an important regulatory signal. Phosphorylation of the RARγ N-terminal domain (NTD is known to play a functional role in neuronal differentiation. In this work, we investigated the phosphorylation of RARγ ligand binding domain (LBD, and present evidence that the phosphorylation status of the LBD affects the phosphorylation of the NTD region. We solved the X-ray structure of a phospho-mimetic mutant of the LBD (RARγ S371E, which we used in molecular dynamics simulations to characterize the consequences of the S371E mutation on the RARγ structural dynamics. Combined with simulations of the wild-type LBD, we show that the conformational equilibria of LBD salt bridges (notably R387-D340 are affected by the S371E mutation, which likely affects the recruitment of the kinase complex that phosphorylates the NTD. The molecular dynamics simulations also showed that a conservative mutation in this salt bridge (R387K affects the dynamics of the LBD without inducing large conformational changes. Finally, cellular assays showed that the phosphorylation of the NTD of RARγ is differentially regulated by retinoic acid in RARγWT and in the S371N, S371E and R387K mutants. This multidisciplinary work highlights an allosteric coupling between phosphorylations of the LBD and the NTD of RARγ and supports the importance of structural dynamics involving electrostatic interactions in the regulation of RARs activity.

  7. Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice

    International Nuclear Information System (INIS)

    Kawai, Ikuma; Hisaki, Tomoka; Sugiura, Koji; Naito, Kunihiko; Kano, Kiyoshi

    2012-01-01

    Highlights: ► Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase. ► DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. ► We produced in vitro and in vivo model to better understand the role of DDR2. ► DDR2 might play an inhibitory role in the proliferation of chondrocyte. -- Abstract: Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines. To investigate DDR2’s molecular role in endochondral cellular proliferation in vivo, we also produced transgenic mice in which the expression of truncated, kinase dead (KD) DDR2 protein is induced, and evaluated the DDR2 function in cellular proliferation in chondrocytes. Although the miDdr2-transfected ATDC5 cell lines retained normal differentiation ability, DDR2 reduction finally promoted cellular proliferation in proportion to the decreasing ratio of Ddr2 expression, and it also promoted earlier differentiation to cartilage cells by insulin induction. The layer of hypertrophic chondrocytes in KD Ddr2 transgenic mice was not significantly thicker than that of normal littermates, but the layer of proliferative chondrocytes in KD-Ddr2 transgenic mice was significantly thicker than that of normal littermates. Taken together, our data demonstrated that DDR2 might play a local and essential role in the

  8. Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Ikuma; Hisaki, Tomoka; Sugiura, Koji; Naito, Kunihiko [Laboratory of Applied Genetics, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo 113-8657 (Japan); Kano, Kiyoshi, E-mail: kanokiyo@yamaguchi-u.ac.jp [Laboratory of Developmental Biology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan. (Japan); Biomedical Science Center for Translational Research (BSCTR), The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi 753-8515 (Japan)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase. Black-Right-Pointing-Pointer DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. Black-Right-Pointing-Pointer We produced in vitro and in vivo model to better understand the role of DDR2. Black-Right-Pointing-Pointer DDR2 might play an inhibitory role in the proliferation of chondrocyte. -- Abstract: Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines. To investigate DDR2's molecular role in endochondral cellular proliferation in vivo, we also produced transgenic mice in which the expression of truncated, kinase dead (KD) DDR2 protein is induced, and evaluated the DDR2 function in cellular proliferation in chondrocytes. Although the miDdr2-transfected ATDC5 cell lines retained normal differentiation ability, DDR2 reduction finally promoted cellular proliferation in proportion to the decreasing ratio of Ddr2 expression, and it also promoted earlier differentiation to cartilage cells by insulin induction. The layer of hypertrophic chondrocytes in KD Ddr2 transgenic mice was not significantly thicker than that of normal littermates, but the layer of proliferative chondrocytes in KD-Ddr2 transgenic mice was significantly thicker than that of normal littermates

  9. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

    Science.gov (United States)

    Makino, Yuichi; Cao, Renhai; Svensson, Kristian; Bertilsson, Göran; Asman, Mikael; Tanaka, Hirotoshi; Cao, Yihai; Berkenstam, Anders; Poellinger, Lorenz

    2001-11-01

    Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

  10. The Human Escort Protein Hep Binds to the ATPase Domain of Mitochondrial Hsp70 and Regulates ATP Hydrolysis*

    Science.gov (United States)

    Zhai, Peng; Stanworth, Crystal; Liu, Shirley; Silberg, Jonathan J.

    2008-01-01

    Hsp70 escort proteins (Hep) have been implicated as essential for maintaining the function of yeast mitochondrial hsp70 molecular chaperones (mtHsp70), but the role that escort proteins play in regulating mammalian chaperone folding and function has not been established. We present evidence that human mtHsp70 exhibits limited solubility due to aggregation mediated by its ATPase domain and show that human Hep directly enhances chaperone solubility through interactions with this domain. In the absence of Hep, mtHsp70 was insoluble when expressed in Escherichia coli, as was its isolated ATPase domain and a chimera having this domain fused to the peptide-binding domain of HscA, a soluble monomeric chaperone. In contrast, these proteins all exhibited increased solubility when expressed in the presence of Hep. In vitro studies further revealed that purified Hep regulates the interaction of mtHsp70 with nucleotides. Full-length mtHsp70 exhibited slow intrinsic ATP hydrolysis activity (6.8 ± 0.2 × 10-4 s-1) at 25 °C, which was stimulated up to 49-fold by Hep. Hep also stimulated the activity of the isolated ATPase domain, albeit to a lower maximal extent (11.5-fold). In addition, gel-filtration studies showed that formation of chaperone-escort protein complexes inhibited mtHsp70 self-association, and they revealed that Hep binding to full-length mtHsp70 and its isolated ATPase domain is strongest in the absence of nucleotides. These findings provide evidence that metazoan escort proteins regulate the catalytic activity and solubility of their cognate chaperones, and they indicate that both forms of regulation arise from interactions with the mtHsp70 ATPase domain. PMID:18632665

  11. The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis.

    Science.gov (United States)

    Zhai, Peng; Stanworth, Crystal; Liu, Shirley; Silberg, Jonathan J

    2008-09-19

    Hsp70 escort proteins (Hep) have been implicated as essential for maintaining the function of yeast mitochondrial hsp70 molecular chaperones (mtHsp70), but the role that escort proteins play in regulating mammalian chaperone folding and function has not been established. We present evidence that human mtHsp70 exhibits limited solubility due to aggregation mediated by its ATPase domain and show that human Hep directly enhances chaperone solubility through interactions with this domain. In the absence of Hep, mtHsp70 was insoluble when expressed in Escherichia coli, as was its isolated ATPase domain and a chimera having this domain fused to the peptide-binding domain of HscA, a soluble monomeric chaperone. In contrast, these proteins all exhibited increased solubility when expressed in the presence of Hep. In vitro studies further revealed that purified Hep regulates the interaction of mtHsp70 with nucleotides. Full-length mtHsp70 exhibited slow intrinsic ATP hydrolysis activity (6.8+/-0.2 x 10(-4) s(-1)) at 25 degrees C, which was stimulated up to 49-fold by Hep. Hep also stimulated the activity of the isolated ATPase domain, albeit to a lower maximal extent (11.5-fold). In addition, gel-filtration studies showed that formation of chaperone-escort protein complexes inhibited mtHsp70 self-association, and they revealed that Hep binding to full-length mtHsp70 and its isolated ATPase domain is strongest in the absence of nucleotides. These findings provide evidence that metazoan escort proteins regulate the catalytic activity and solubility of their cognate chaperones, and they indicate that both forms of regulation arise from interactions with the mtHsp70 ATPase domain.

  12. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

    Science.gov (United States)

    Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

    2017-03-17

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

  13. The MARVEL domain protein Nce102 regulates actin organization and invasive growth of Candida albicans.

    Science.gov (United States)

    Douglas, Lois M; Wang, Hong X; Konopka, James B

    2013-11-26

    Invasive growth of the fungal pathogen Candida albicans into tissues promotes disseminated infections in humans. The plasma membrane is essential for pathogenesis because this important barrier mediates morphogenesis and invasive growth, as well as secretion of virulence factors, cell wall synthesis, nutrient import, and other processes. Previous studies showed that the Sur7 tetraspan protein that localizes to MCC (membrane compartment occupied by Can1)/eisosome subdomains of the plasma membrane regulates a broad range of key functions, including cell wall synthesis, morphogenesis, and resistance to copper. Therefore, a distinct tetraspan protein found in MCC/eisosomes, Nce102, was investigated. Nce102 belongs to the MARVEL domain protein family, which is implicated in regulating membrane structure and function. Deletion of NCE102 did not cause the broad defects seen in sur7Δ cells. Instead, the nce102Δ mutant displayed a unique phenotype in that it was defective in forming hyphae and invading low concentrations of agar but could invade well in higher agar concentrations. This phenotype was likely due to a defect in actin organization that was observed by phalloidin staining. In support of this, the invasive growth defect of a bni1Δ mutant that mislocalizes actin due to lack of the Bni1 formin was also reversed at high agar concentrations. This suggests that a denser matrix provides a signal that compensates for the actin defects. The nce102Δ mutant displayed decreased virulence and formed abnormal hyphae in mice. These studies identify novel ways that Nce102 and the physical environment surrounding C. albicans regulate morphogenesis and pathogenesis. The plasma membrane promotes virulence of the human fungal pathogen Candida albicans by acting as a protective barrier around the cell and mediating dynamic activities, such as morphogenesis, cell wall synthesis, secretion of virulence factors, and nutrient uptake. To better understand how the plasma membrane

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

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

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

  15. Heteropoly acid promoted catalyst for SCR of NOx with ammonia

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention concerns the selective removal of nitrogen oxides (NOx) from gases. In particular, the invention concerns a process, a highly alkali metal resistant heteropoly acid promoted catalyst and the use of said catalyst for removal of NOx from exhaust or flue gases, said gases...... comprising alkali or earth alkali metals. Such gases comprise for example flue gases arising from the burning of biomass, combined biomass and fossil fuel, and from waste incineration units. The process comprises the selective catalytic reduction (SCR) of NOx, such as nitrogen dioxide (NO2) and nitrogen...

  16. Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions.

    Science.gov (United States)

    Groveman, Bradley R; Xue, Sheng; Marin, Vedrana; Xu, Jindong; Ali, Mohammad K; Bienkiewicz, Ewa A; Yu, Xian-Min

    2011-02-01

    Previous studies demonstrated that intra-domain interactions between Src family kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2 domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the molecules in a closed conformation, disrupt the kinase active site, and inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate receptors (NMDARs) induced by expression of constitutively active neuronal Src (n-Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F), is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role than the SH3 domain. Our data also show that n-Src binds directly to the C-terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent, and dysfunctions of the SH2 and/or SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src, which is important in the regulation of NMDAR functions. © 2010 The Authors Journal compilation © 2010 FEBS.

  17. Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain.

    Directory of Open Access Journals (Sweden)

    Victoria Lewis

    Full Text Available There is increasing evidence of molecular and cellular links between Alzheimer's disease (AD and prion diseases. The cellular prion protein, PrP(C, modulates the post-translational processing of the AD amyloid precursor protein (APP, through its inhibition of the β-secretase BACE1, and oligomers of amyloid-β bind to PrP(C which may mediate amyloid-β neurotoxicity. In addition, the APP intracellular domain (AICD, which acts as a transcriptional regulator, has been reported to control the expression of PrP(C. Through the use of transgenic mice, cell culture models and manipulation of APP expression and processing, this study aimed to clarify the role of AICD in regulating PrP(C. Over-expression of the three major isoforms of human APP (APP(695, APP(751 and APP(770 in cultured neuronal and non-neuronal cells had no effect on the level of endogenous PrP(C. Furthermore, analysis of brain tissue from transgenic mice over-expressing either wild type or familial AD associated mutant human APP revealed unaltered PrP(C levels. Knockdown of endogenous APP expression in cells by siRNA or inhibition of γ-secretase activity also had no effect on PrP(C levels. Overall, we did not detect any significant difference in the expression of PrP(C in any of the cell or animal-based paradigms considered, indicating that the control of cellular PrP(C levels by AICD is not as straightforward as previously suggested.

  18. Impact of the [delta]F508 Mutation in First Nucleotide-binding Domain of Human Cystic Fibrosis Transmembrane Conductance Regulator on Domain Folding and Structure

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Hal A.; Zhao, Xun; Wang, Chi; Sauder, J. Michael; Rooney, Isabelle; Noland, Brian W.; Lorimer, Don; Kearins, Margaret C.; Conners, Kris; Condon, Brad; Maloney, Peter C.; Guggino, William B.; Hunt, John F.; Emtage, Spencer (SG); (Columbia); (JHU)

    2010-07-19

    Cystic fibrosis is caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR), commonly the deletion of residue Phe-508 (DeltaF508) in the first nucleotide-binding domain (NBD1), which results in a severe reduction in the population of functional channels at the epithelial cell surface. Previous studies employing incomplete NBD1 domains have attributed this to aberrant folding of DeltaF508 NBD1. We report structural and biophysical studies on complete human NBD1 domains, which fail to demonstrate significant changes of in vitro stability or folding kinetics in the presence or absence of the DeltaF508 mutation. Crystal structures show minimal changes in protein conformation but substantial changes in local surface topography at the site of the mutation, which is located in the region of NBD1 believed to interact with the first membrane spanning domain of CFTR. These results raise the possibility that the primary effect of DeltaF508 is a disruption of proper interdomain interactions at this site in CFTR rather than interference with the folding of NBD1. Interestingly, increases in the stability of NBD1 constructs are observed upon introduction of second-site mutations that suppress the trafficking defect caused by the DeltaF508 mutation, suggesting that these suppressors might function indirectly by improving the folding efficiency of NBD1 in the context of the full-length protein. The human NBD1 structures also solidify the understanding of CFTR regulation by showing that its two protein segments that can be phosphorylated both adopt multiple conformations that modulate access to the ATPase active site and functional interdomain interfaces.

  19. DMPD: Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available and nucleotide oligomerisation domain inthe regulation of health and disease. Pu...bmedID 17535871 Title Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health...17535871 Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of heal...th and disease. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N. J

  20. Regulation of EGF receptor signaling by the MARVEL domain-containing protein CKLFSF8.

    Science.gov (United States)

    Jin, Caining; Ding, Peiguo; Wang, Ying; Ma, Dalong

    2005-11-21

    It is known that chemokine-like factor superfamily 8 (CKLFSF8), a member of the CKLF superfamily, has four putative transmembrane regions and a MARVEL domain. Its structure is similar to TM4SF11 (plasmolipin) and widely distributed in normal tissue. However, its function is not yet known. We show here that CKLFSF8 is associated with the epidermal growth factor receptor (EGFR) and that ectopic expression of CKLFSF8 in several cell lines suppresses EGF-induced cell proliferation, whereas knockdown of CKLFSF8 by siRNA promotes cell proliferation. In cells overexpressing CKLFSF8, the initial activation of EGFR was not affected, but subsequent desensitization of EGF-induced signaling occurred rapidly. This attenuation was correlated with an increased rate of receptor endocytosis. In contrast, knockdown of CKLFSF8 by siCKLFSF8 delayed EGFR endocytosis. These results identify CKLFSF8 as a novel regulator of EGF-induced signaling and indicate that the association of EGFR with four transmembrane proteins is critical for EGFR desensitization.

  1. Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions

    DEFF Research Database (Denmark)

    Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E

    2017-01-01

    The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effec...

  2. Regulation of abiotic stress signalling by Arabidopsis C-terminal domain phosphatase-like 1 requires interaction with a k-homology domain-containing protein.

    Directory of Open Access Journals (Sweden)

    In Sil Jeong

    Full Text Available Arabidopsis thaliana CARBOXYL-TERMINAL DOMAIN (CTD PHOSPHATASE-LIKE 1 (CPL1 regulates plant transcriptional responses to diverse stress signals. Unlike typical CTD phosphatases, CPL1 contains two double-stranded (ds RNA binding motifs (dsRBMs at its C-terminus. Some dsRBMs can bind to dsRNA and/or other proteins, but the function of the CPL1 dsRBMs has remained obscure. Here, we report identification of REGULATOR OF CBF GENE EXPRESSION 3 (RCF3 as a CPL1-interacting protein. RCF3 co-purified with tandem-affinity-tagged CPL1 from cultured Arabidopsis cells and contains multiple K-homology (KH domains, which were predicted to be important for binding to single-stranded DNA/RNA. Yeast two-hybrid, luciferase complementation imaging, and bimolecular fluorescence complementation analyses established that CPL1 and RCF3 strongly associate in vivo, an interaction mediated by the dsRBM1 of CPL1 and the KH3/KH4 domains of RCF3. Mapping of functional regions of CPL1 indicated that CPL1 in vivo function requires the dsRBM1, catalytic activity, and nuclear targeting of CPL1. Gene expression profiles of rcf3 and cpl1 mutants were similar during iron deficiency, but were distinct during the cold response. These results suggest that tethering CPL1 to RCF3 via dsRBM1 is part of the mechanism that confers specificity to CPL1-mediated transcriptional regulation.

  3. Experimental study on the particulate matter and nitrogenous compounds from diesel engine retrofitted with DOC+CDPF+SCR

    Science.gov (United States)

    Zhang, Yunhua; Lou, Diming; Tan, Piqiang; Hu, Zhiyuan

    2018-03-01

    The increasingly stringent emission regulations will mandate the retrofit of after-treatment devices for in-use diesel vehicles, in order to reduce their substantial particulate matter and nitrogen oxides (NOX) emissions. In this paper, a combination of DOC (diesel oxidation catalyst), CDPF (catalytic diesel particulate filter) and SCR (selective catalytic reduction) retrofit for a heavy-duty diesel engine was employed to perform experiment on the engine test bench to evaluate the effects on the particulate matter emissions including particle number (PN), particle mass (PM), particle size distributions and nitrogenous compounds emissions including NOX, nitrogen dioxide (NO2)/NOX, nitrous oxide (N2O) and ammonia (NH3) slip. In addition, the urea injection was also of our concern. The results showed that the DOC+CDPF+SCR retrofit almost had no adverse effect on the engine power and fuel consumption. Under the test loads, the upstream DOC and CDPF reduced the PN and PM by an average of 91.6% and 90.9%, respectively. While the downstream SCR brought about an average decrease of 85% NOX. Both PM and NOX emission factors based on this retrofit were lower than China-Ⅳ limits (ESC), and even lower than China-Ⅴ limits (ESC) at medium and high loads. The DOC and CDPF changed the particle size distributions, leading to the increase in the proportion of accumulation mode particles and the decrease in the percentage of nuclear mode particles. This indicates that the effect of DOC and CDPF on nuclear mode particles was better than that of accumulation mode ones. The upstream DOC could increase the NO2/NOX ratio to 40%, higher NO2/NOX ratio improved the efficiency of CDPF and SCR. Besides, the N2O emission increased by an average of 2.58 times after the retrofit and NH3 slip occurred with the average of 26.7 ppm. The rate of urea injection was roughly equal to 8% of the fuel consumption rate. The DOC+CDPF+SCR retrofit was proved a feasible and effective measurement in terms

  4. The external PASTA domain of the essential serine/threonine protein kinase PknB regulates mycobacterial growth.

    Science.gov (United States)

    Turapov, Obolbek; Loraine, Jessica; Jenkins, Christopher H; Barthe, Philippe; McFeely, Daniel; Forti, Francesca; Ghisotti, Daniela; Hesek, Dusan; Lee, Mijoon; Bottrill, Andrew R; Vollmer, Waldemar; Mobashery, Shahriar; Cohen-Gonsaud, Martin; Mukamolova, Galina V

    2015-07-01

    PknB is an essential serine/threonine protein kinase required for mycobacterial cell division and cell-wall biosynthesis. Here we demonstrate that overexpression of the external PknB_PASTA domain in mycobacteria results in delayed regrowth, accumulation of elongated bacteria and increased sensitivity to β-lactam antibiotics. These changes are accompanied by altered production of certain enzymes involved in cell-wall biosynthesis as revealed by proteomics studies. The growth inhibition caused by overexpression of the PknB_PASTA domain is completely abolished by enhanced concentration of magnesium ions, but not muropeptides. Finally, we show that the addition of recombinant PASTA domain could prevent regrowth of Mycobacterium tuberculosis, and therefore offers an alternative opportunity to control replication of this pathogen. These results suggest that the PknB_PASTA domain is involved in regulation of peptidoglycan biosynthesis and maintenance of cell-wall architecture.

  5. PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Donghoon M Lee

    Full Text Available The recruitment of GDP/GTP exchange factors (GEFs to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP-bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos.

  6. The Unstructured Paramyxovirus Nucleocapsid Protein Tail Domain Modulates Viral Pathogenesis through Regulation of Transcriptase Activity.

    Science.gov (United States)

    Thakkar, Vidhi D; Cox, Robert M; Sawatsky, Bevan; da Fontoura Budaszewski, Renata; Sourimant, Julien; Wabbel, Katrin; Makhsous, Negar; Greninger, Alexander L; von Messling, Veronika; Plemper, Richard K

    2018-04-15

    pathogenesis. We show that internal deletions in this Ntail region of up to 55 amino acids in length are compatible with efficient replication of recombinant viruses in cell culture but result in gradual viral attenuation in a lethal canine distemper virus (CDV)/ferret model. Mechanistically, we demonstrate a role of the intact Ntail region in the regulation of viral transcriptase activity. Recombinant viruses with Ntail truncations induce protective immunity against lethal challenge of ferrets with pathogenic CDV. This identification of the unstructured central Ntail domain as a nonessential paramyxovirus pathogenesis factor establishes a foundation for harnessing Ntail truncations for vaccine engineering against emerging and reemerging members of the paramyxovirus family. Copyright © 2018 American Society for Microbiology.

  7. Mercury Oxidation over Selective Catalytic Reduction (SCR) Catalysts - Ph.d. thesis Karin Madsen

    DEFF Research Database (Denmark)

    Madsen, Karin

    The vanadium-based SCR catalyst used for NOx-control promotes the oxidation of elemental mercury Hg0 to Hg2+ in flue gases from coal-fired power plants. Hg2+ is water soluble and can effectively be captured in a wet scrubber. This means that the combination of an SCR with a wet FGD can offer an e...

  8. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

    Science.gov (United States)

    Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

    2005-08-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

  9. Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins - role of the SH3 domain.

    Science.gov (United States)

    Malki, Idir; Cantrelle, François-Xavier; Sottejeau, Yoann; Lippens, Guy; Lambert, Jean-Charles; Landrieu, Isabelle

    2017-10-01

    Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects AD risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy. 1 H, 15 N spectra showed that the C-terminal SH3 domain of BIN1 isoform 1 (BIN1Iso1) is not mobile in solution but locked with the core of the protein. In contrast, the SH3 domain of BIN1 isoform 9 (BIN1Iso9) behaves as an independent mobile domain. This reveals an equilibrium between close and open conformations for the SH3 domain. Interestingly, a 334-376 peptide from the clathrin and AP-2-binding domain (CLAP) domain of BIN1Iso1, which contains a SH3-binding site, is able to compete with BIN1-SH3 intramolecular interaction. For both BIN1 isoforms, the SH3 domain can interact with Tau(210-240) sequence. Tau(210-240) peptide can indeed displace the intramolecular interaction of the BIN1-SH3 of BIN1Iso1 and form a complex with the released domain. The measured K d were in agreement with a stronger affinity of Tau peptide. Both CLAP and Tau peptides occupied the same surface on the BIN1-SH3 domain, showing that their interaction is mutually exclusive. These results emphasize an additional level of complexity in the regulation of the interaction between BIN1 and Tau dependent of the BIN1 isoforms. © 2017 Federation of European Biochemical Societies.

  10. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

    OpenAIRE

    Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

    2005-01-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test ...

  11. The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

    International Nuclear Information System (INIS)

    Vu, Hoang Anh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2009-01-01

    We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.

  12. The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.

    Science.gov (United States)

    Yu, Corey H; Yang, Nan; Bothe, Jameson; Tonelli, Marco; Nokhrin, Sergiy; Dolgova, Natalia V; Braiterman, Lelita; Lutsenko, Svetlana; Dmitriev, Oleg Y

    2017-11-03

    The human transporter ATP7B delivers copper to the biosynthetic pathways and maintains copper homeostasis in the liver. Mutations in ATP7B cause the potentially fatal hepatoneurological disorder Wilson disease. The activity and intracellular localization of ATP7B are regulated by copper, but the molecular mechanism of this regulation is largely unknown. We show that the copper chaperone Atox1, which delivers copper to ATP7B, and the group of the first three metal-binding domains (MBD1-3) are central to the activity regulation of ATP7B. Atox1-Cu binding to ATP7B changes domain dynamics and interactions within the MBD1-3 group and activates ATP hydrolysis. To understand the mechanism linking Atox1-MBD interactions and enzyme activity, we have determined the MBD1-3 conformational space using small angle X-ray scattering and identified changes in MBD dynamics caused by apo -Atox1 and Atox1-Cu by solution NMR. The results show that copper transfer from Atox1 decreases domain interactions within the MBD1-3 group and increases the mobility of the individual domains. The N-terminal segment of MBD1-3 was found to interact with the nucleotide-binding domain of ATP7B, thus physically coupling the domains involved in copper binding and those involved in ATP hydrolysis. Taken together, the data suggest a regulatory mechanism in which Atox1-mediated copper transfer activates ATP7B by releasing inhibitory constraints through increased freedom of MBD1-3 motions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Retrofit SCR system for NOx control from heavy-duty mining equipment

    International Nuclear Information System (INIS)

    Mannan, M.A.

    2009-01-01

    Diesel engines are used extensively in the mining industry and offer many advantages. However, particulate matter (PM) emissions and nitrogen oxide emissions (NOx) are among its disadvantages. A significant concern related to PM and NOx in an underground mine involves the use of diesel exhaust after treatment systems such as diesel particulate filters and selective catalytic reduction (SCR). This presentation discussed NOx and PM control and provided a description of an SCR system and examples of SCR retrofits. Options for NOx control were discussed and a case study involving the installation of an SCR retrofit system in an underground mine operated by Sifto Salt was also presented. The purpose of the case study was to identify cost effective retrofit solutions to lower nitrogen dioxide emissions from heavy-duty trucks operating in underground mines. The case study illustrated and presented the candidate vehicle, baseline emissions, a BlueMax SCR retrofit solution, and BlueMax installation. 1 tab., 6 figs.

  14. Probing the Role of Loops & Domains in Regulating Coagulation Factor VIIa Allostery and Specificity

    DEFF Research Database (Denmark)

    Sørensen, Anders Bundgård

    2016-01-01

    The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo).......The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo)....

  15. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    International Nuclear Information System (INIS)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

    2014-01-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

  16. Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.

    Science.gov (United States)

    Huang, Chao; Zhang, Zhe; Chen, Lihan; Lee, Hank W; Ayrapetov, Marina K; Zhao, Ting C; Hao, Yimei; Gao, Jinsong; Yang, Chunzhang; Mehta, Gautam U; Zhuang, Zhengping; Zhang, Xiaoren; Hu, Guohong; Chin, Y Eugene

    2018-06-01

    Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G 2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation. Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR . ©2018 American Association for Cancer Research.

  17. Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation.

    Science.gov (United States)

    Shizu, Ryota; Min, Jungki; Sobhany, Mack; Pedersen, Lars C; Mutoh, Shingo; Negishi, Masahiko

    2018-01-05

    The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor α (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CAR's DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion. Phosphomimetic substitution of Thr-38 with Asp increased co-immunoprecipitation of the CAR DBD with CAR LBD in Huh-7 cells. Isothermal titration calorimetry assays also revealed that recombinant CAR DBD-T38D, but not nonphosphorylated CAR DBD, bound the CAR LBD peptide. This DBD-LBD interaction masked CAR's dimer interface, preventing CAR homodimer formation. Of note, EGF signaling weakened the interaction of CAR DBD T38D with CAR LBD, converting CAR to the homodimer form. The DBD-T38D-LBD interaction also prevented CAR from forming a heterodimer with RXRα. However, this interaction opened up a CAR surface, allowing interaction with protein phosphatase 2A. Thr-38 dephosphorylation then dissociated the DBD-LBD interaction, allowing CAR heterodimer formation with RXRα. We conclude that the intramolecular interaction of phosphorylated DBD with the LBD enables CAR to adapt a transient monomer configuration that can be converted to either the inactive homodimer or the active heterodimer.

  18. Regulation of adhesion behavior of murine macrophage using supported lipid membranes displaying tunable mannose domains

    International Nuclear Information System (INIS)

    Kaindl, T; Oelke, J; Kaufmann, S; Tanaka, M; Pasc, A; Konovalov, O V; Funari, S S; Engel, U; Wixforth, A

    2010-01-01

    Highly uniform, strongly correlated domains of synthetically designed lipids can be incorporated into supported lipid membranes. The systematic characterization of membranes displaying a variety of domains revealed that the equilibrium size of domains significantly depends on the length of fluorocarbon chains, which can be quantitatively interpreted within the framework of an equivalent dipole model. A mono-dispersive, narrow size distribution of the domains enables us to treat the inter-domain correlations as two-dimensional colloidal crystallization and calculate the potentials of mean force. The obtained results demonstrated that both size and inter-domain correlation can precisely be controlled by the molecular structures. By coupling α-D-mannose to lipid head groups, we studied the adhesion behavior of the murine macrophage (J774A.1) on supported membranes. Specific adhesion and spreading of macrophages showed a clear dependence on the density of functional lipids. The obtained results suggest that such synthetic lipid domains can be used as a defined platform to study how cells sense the size and distribution of functional molecules during adhesion and spreading.

  19. Novel autophosphorylation sites of Src family kinases regulate kinase activity and SH2 domain-binding capacity.

    Science.gov (United States)

    Weir, Marion E; Mann, Jacqueline E; Corwin, Thomas; Fulton, Zachary W; Hao, Jennifer M; Maniscalco, Jeanine F; Kenney, Marie C; Roman Roque, Kristal M; Chapdelaine, Elizabeth F; Stelzl, Ulrich; Deming, Paula B; Ballif, Bryan A; Hinkle, Karen L

    2016-04-01

    Src family tyrosine kinases (SFKs) are critical players in normal and aberrant biological processes. While phosphorylation importantly regulates SFKs at two known tyrosines, large-scale phosphoproteomics have revealed four additional tyrosines commonly phosphorylated in SFKs. We found these novel tyrosines to be autophosphorylation sites. Mimicking phosphorylation at the C-terminal site to the activation loop decreased Fyn activity. Phosphomimetics and direct phosphorylation at the three SH2 domain sites increased Fyn activity while reducing phosphotyrosine-dependent interactions. While 68% of human SH2 domains exhibit conservation of at least one of these tyrosines, few have been found phosphorylated except when found in cis to a kinase domain. © 2016 Federation of European Biochemical Societies.

  20. Differential Roles of the Glycogen-Binding Domains of β Subunits in Regulation of the Snf1 Kinase Complex▿

    Science.gov (United States)

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R.; Elbing, Karin; Schmidt, Martin C.

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic α subunit and regulatory β and γ subunits. In this study, the role of the β subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (α), Snf4 (γ), and one of three alternative β subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three β subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the β subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation. PMID:19897735

  1. Differential roles of the glycogen-binding domains of beta subunits in regulation of the Snf1 kinase complex.

    Science.gov (United States)

    Mangat, Simmanjeet; Chandrashekarappa, Dakshayini; McCartney, Rhonda R; Elbing, Karin; Schmidt, Martin C

    2010-01-01

    Members of the AMP-activated protein kinase family, including the Snf1 kinase of Saccharomyces cerevisiae, are activated under conditions of nutrient stress. AMP-activated protein kinases are heterotrimeric complexes composed of a catalytic alpha subunit and regulatory beta and gamma subunits. In this study, the role of the beta subunits in the regulation of Snf1 activity was examined. Yeasts express three isoforms of the AMP-activated protein kinase consisting of Snf1 (alpha), Snf4 (gamma), and one of three alternative beta subunits, either Sip1, Sip2, or Gal83. The Gal83 isoform of the Snf1 complex is the most abundant and was analyzed in the greatest detail. All three beta subunits contain a conserved domain referred to as the glycogen-binding domain. The deletion of this domain from Gal83 results in a deregulation of the Snf1 kinase, as judged by a constitutive activity independent of glucose availability. In contrast, the deletion of this homologous domain from the Sip1 and Sip2 subunits had little effect on Snf1 kinase regulation. Therefore, the different Snf1 kinase isoforms are regulated through distinct mechanisms, which may contribute to their specialized roles in different stress response pathways. In addition, the beta subunits are subjected to phosphorylation. The responsible kinases were identified as being Snf1 and casein kinase II. The significance of the phosphorylation is unclear since the deletion of the region containing the phosphorylation sites in Gal83 had little effect on the regulation of Snf1 in response to glucose limitation.

  2. Drosophila Pumilio protein contains multiple autonomous repression domains that regulate mRNAs independently of Nanos and brain tumor.

    Science.gov (United States)

    Weidmann, Chase A; Goldstrohm, Aaron C

    2012-01-01

    Drosophila melanogaster Pumilio is an RNA-binding protein that potently represses specific mRNAs. In developing embryos, Pumilio regulates a key morphogen, Hunchback, in collaboration with the cofactor Nanos. To investigate repression by Pumilio and Nanos, we created cell-based assays and found that Pumilio inhibits translation and enhances mRNA decay independent of Nanos. Nanos robustly stimulates repression through interactions with the Pumilio RNA-binding domain. We programmed Pumilio to recognize a new binding site, which garners repression of new target mRNAs. We show that cofactors Brain Tumor and eIF4E Homologous Protein are not obligatory for Pumilio and Nanos activity. The conserved RNA-binding domain of Pumilio was thought to be sufficient for its function. Instead, we demonstrate that three unique domains in the N terminus of Pumilio possess the major repressive activity and can function autonomously. The N termini of insect and vertebrate Pumilio and Fem-3 binding factors (PUFs) are related, and we show that corresponding regions of human PUM1 and PUM2 have repressive activity. Other PUF proteins lack these repression domains. Our findings suggest that PUF proteins have evolved new regulatory functions through protein sequences appended to their conserved PUF repeat RNA-binding domains.

  3. Affinity between TBC1D4 (AS160 phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry

    Directory of Open Access Journals (Sweden)

    SangYoun Park*, Keon Young Kim, Sunmin Kim & Young Seok Yu

    2012-06-01

    Full Text Available Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucosetransporter 4 (GLUT4 vesicles from the intracellular compartmentto the plasma membrane. RabㆍGTPases are involvedin this vesicle trafficking, where RabㆍGTPase-activatingproteins (RabGAP enhance the GTP to GDP hydrolysis.TBC1D4 (AS160 and TBC1D1 are functional RabGAPs in theadipocytes and the skeletonal myocytes, respectively. Theseproteins contain two phosphotyrosine-binding domains (PTBsat the amino-terminus of the catalytic RabGAP domain. Thesecond PTB has been shown to interact with the cytoplasmicregion of the insulin-regulated aminopeptidase (IRAP of theGLUT4 vesicle. In this study, we quantitatively measured the∼μM affinity (KD between TBC1D4 PTB and IRAP using isothermaltitration calorimetry, and further showed that IRAP residues1-49 are the major region mediating this interaction. Wealso demonstrated that the IRAP residues 1-15 are necessarybut not sufficient for the PTB interaction.

  4. Urea-SCR Temperature Investigation for NOx Control of Diesel Engine

    Directory of Open Access Journals (Sweden)

    Asif Muhammad

    2015-01-01

    Full Text Available SCR (selective catalytic reduction system is continuously being analyzed by many researchers worldwide on various concerns due to the stringent nitrogen oxides (NOx emissions legislation for heavy-duty diesel engines. Urea-SCR includes AdBlue as urea source, which subsequently decomposes to NH3 (ammonia being the reducing agent. Reaction temperature is a key factor for the performance of urea-SCR system, as urea decomposition rate is sensitive to a specific temperature range. This particular study was directed to investigate the temperature of the SCR system in diesel engine with the objective to confirm that whether the appropriate temperature is attained for occurrence of urea based catalytic reduction or otherwise and how the system performs on the prescribed temperature range. Diesel engine fitted with urea-SCR exhaust system has been operated on European standard cycle for emission testing to monitor the temperature and corresponding nitrogen oxides (NOx values on specified points. Moreover, mathematical expressions for approximation of reaction temperature are also proposed which are derived by applying energy conservation principal and gas laws. Results of the investigation have shown that during the whole testing cycle system temperature has remained in the range where urea-SCR can take place with best optimum rate and the system performance on account of NOx reduction was exemplary as excellent NOx conversion rate is achieved. It has also been confirmed that selective catalytic reduction (SCR is the best suitable technology for automotive engine-out NOx control.

  5. Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

    Science.gov (United States)

    Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

    1993-01-01

    SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

  6. Simulation and Optimization of SCR System for Direct-injection Diesel Engine

    Directory of Open Access Journals (Sweden)

    Guanqiang Ruan

    2014-11-01

    Full Text Available The turbo diesel SCR system has been researched and analyzed in this paper. By using software of CATIA, three-dimensional physical model of SCR system has been established, and with software of AVL-FIRE, the boundary conditions have been set, simulated and optimized. In the process of SCR system optimizing, it mainly optimized the pray angle. Compare the effects of processing NO to obtain batter optimization results. At last the optimization results are compared by bench test, and the experimental results are quite consistent with simulation.

  7. Membrane Restructuring by Phospholipase A2 Is Regulated by the Presence of Lipid Domains

    DEFF Research Database (Denmark)

    Leidy, Chad; Ocampo, Jackson; Duelund, Lars

    2011-01-01

    Secretory phospholipase A2 (sPLA2) catalyzes the hydrolysis of glycerophospholipids. This enzyme is sensitive to membrane structure, and its activity has been shown to increase in the presence of liquid-crystalline/gel (Lα/Lβ) lipid domains. In this work, we explore whether lipid domains can also...... without necessarily destroying the membrane. We confirm by high-performance liquid chromatography the preferential hydrolysis of DMPC within the phase coexistence region of the DMPC/DSPC phase diagram, showing that this preferential hydrolysis is accentuated close to the solidus phase boundary...

  8. The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8+ T cells.

    Science.gov (United States)

    Guittard, Geoffrey; Dios-Esponera, Ana; Palmer, Douglas C; Akpan, Itoro; Barr, Valarie A; Manna, Asit; Restifo, Nicholas P; Samelson, Lawrence E

    2018-03-28

    Cish, participates within a multi-molecular E3 ubiquitin ligase complex, which ubiquitinates target proteins. It has an inhibitory effect on T cell activation mediated by PLC-γ1 regulation, and it functions as a potent checkpoint in CD8 + T cell tumor immunotherapy. To study the structural and functional relationships between Cish and PLC-γ1 during CD8 + T cell activation, we tested mutants of the Cish-SH2 (R107K) and D/BC (L222Q, C226Q) domains. We confirmed that Cish-SH2-specific binding was essential for PLC-γ1 ubiquitination and degradation. This domain was essential for the Cish-mediated inhibition of Ca 2+ release upon TCR stimulation. No effect on inhibition of cytokine release was observed with SH2 or D/BC mutants, although the absence of Cish led to an increased release of IFN-γ and TNF-α. Using imaging we showed that Cish was expressed mostly in the cytoplasm and we did not see any Cish clustering at the plasma membrane upon stimulation. We conclude that the Cish-SH2 domain is essential for PLC-γ1 regulation in TCR-stimulated CD8 + T cells.

  9. Deactivation of SCR catalysts by potassium: A study of potential alkali barrier materials

    DEFF Research Database (Denmark)

    Olsen, Brian Kjærgaard; Kügler, Frauke; Castellino, Francesco

    2017-01-01

    The use of coatings in order to protect vanadia based SCR catalysts against potassium poisoning has been studied by lab- and pilot-scale experiments. Three-layer pellets, consisting of a layer ofa potential coating material situated between layers of fresh and potassium poisoned SCR catalyst, were...... the coating process. Potassium had to some extent penetrated the MgO coat, and SEM analysis revealed it to be rather thick and fragile. Despite these observations, the coating did protect the SCR catalyst against potassium poisoning to some degree, leaving promise of further optimization....... used to test the ability of the barrier layer to block the diffusion of potassium across the pellet. Of MgO, sepiolite and Hollandite manganese oxide, MgO was the most effective potassium barrier, and no potassium was detected in the MgO layer upon exposure to SCR conditions for 7 days. Two monoliths...

  10. Evaluation of Mercury Emissions from Coal-Fired Facilities with SCR and FGD Systems

    Energy Technology Data Exchange (ETDEWEB)

    J. A. Withum; S. C. Tseng; J. E. Locke

    2006-01-31

    CONSOL Energy Inc., Research & Development (CONSOL), with support from the U.S. Department of Energy, National Energy Technology Laboratory (DOE) and the Electric Power Research Institute (EPRI), is evaluating the effects of selective catalytic reduction (SCR) on mercury (Hg) capture in coal-fired plants equipped with an electrostatic precipitator (ESP)--wet flue gas desulfurization (FGD) combination or a spray dyer absorber--fabric filter (SDA-FF) combination. In this program CONSOL is determining mercury speciation and removal at 10 coal-fired facilities. The principal purpose of this work is to develop a better understanding of the potential mercury removal ''co-benefits'' achieved by NO{sub x}, and SO{sub 2} control technologies. It is expected that these data will provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on mercury speciation and the efficacy of different FGD technologies for mercury capture. Ultimately, this insight could help to design and operate SCR and FGD systems to maximize mercury removal. The objectives are (1) to evaluate the effect of SCR on mercury capture in the ESP-FGD and SDA-FF combinations at coal-fired power plants, (2) evaluate the effect of SCR catalyst degradation on mercury capture; (3) evaluate the effect of low load operation on mercury capture in an SCR-FGD system, and (4) collect data that could provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on mercury speciation and the efficacy of different FGD technologies for mercury capture. This document, the ninth in a series of topical reports, describes the results and analysis of mercury sampling performed on Unit 1 at Plant 7, a 566 MW unit burning a bituminous coal containing 3.6% sulfur. The unit is equipped with a SCR, ESP, and wet FGD to control NO{sub x}, particulate, and SO

  11. Deactivation of SCR catalysts in biomass fired power plants

    DEFF Research Database (Denmark)

    Olsen, Brian Kjærgaard

    composition and operating conditions, is not available. The main objective of the work presented in this thesis has been to conduct an in depth investigation of the deactivation mechanism of vanadia based SCR catalysts, when subjected to potassium rich aerosols. It has furthermore been a goal to suggest...... for up to 600 hours. The activity of fresh and exposed catalysts was measured in the temperature range 250-400 °C in a laboratory-scale reactor. All samples exposed for more than 240 hours proved to have deactivated significantly, however, catalysts exposed at 150 °C showed higher remaining activity......-scale setup at 350 °C for up to 1100 hours, and their activities were followed by in situ measurements. A 3%V2O5-7%WO3/TiO2 reference catalyst deactivated with a rate of 0.91 %/day during 960 hours of exposure, and a subsequent SEM-EDS analysis showed complete potassium penetration of the catalyst wall...

  12. Dynamic flow control strategies of vehicle SCR Urea Dosing System

    Science.gov (United States)

    Lin, Wei; Zhang, Youtong; Asif, Malik

    2015-03-01

    Selective Catalyst Reduction(SCR) Urea Dosing System(UDS) directly affects the system accuracy and the dynamic response performance of a vehicle. However, the UDS dynamic response is hard to keep up with the changes of the engine's operating conditions. That will lead to low NO X conversion efficiency or NH3 slip. In order to optimize the injection accuracy and the response speed of the UDS in dynamic conditions, an advanced control strategy based on an air-assisted volumetric UDS is presented. It covers the methods of flow compensation and switching working conditions. The strategy is authenticated on an UDS and tested in different dynamic conditions. The result shows that the control strategy discussed results in higher dynamic accuracy and faster dynamic response speed of UDS. The inject deviation range is improved from being between -8% and 10% to -4% and 2% and became more stable than before, and the dynamic response time was shortened from 200 ms to 150 ms. The ETC cycle result shows that after using the new strategy the NH3 emission is reduced by 60%, and the NO X emission remains almost unchanged. The trade-off between NO X conversion efficiency and NH3 slip is mitigated. The studied flow compensation and switching working conditions can improve the dynamic performance of the UDS significantly and make the UDS dynamic response keep up with the changes of the engine's operating conditions quickly.

  13. PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner

    Directory of Open Access Journals (Sweden)

    Jin Wenying

    2010-12-01

    Full Text Available Abstract Background Acid-sensing ion channel 1a (ASIC1a is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1, an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown. Results Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1. Conclusions Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.

  14. Structural insights into the regulation and the recognition of histone marks by the SET domain of NSD1

    International Nuclear Information System (INIS)

    Morishita, Masayo; Di Luccio, Eric

    2011-01-01

    Highlights: → NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 are histone methyltransferases linked to numerous cancers. → Little is known about the NSD pathways and HMTase inhibitors are sorely needed in the epigenetic therapy of cancers. → We investigate the regulation and the recognition of histone marks by the SET domain of NSD1. → A unique and key mechanism is driven by a loop at the interface of the SET and postSET region. → Implications for developing specific and selective HMTase inhibitors are presented. -- Abstract: The development of epigenetic therapies fuels cancer hope. DNA-methylation inhibitors, histone-deacetylase and histone-methyltransferase (HMTase) inhibitors are being developed as the utilization of epigenetic targets is emerging as an effective and valuable approach to chemotherapy as well as chemoprevention of cancer. The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. A growing number of studies have reported alterations or amplifications of NSD1, NSD2, or NSD3 in numerous carcinogenic events. Reducing NSDs activity through specific lysine-HMTase inhibitors appears promising to help suppressing cancer growth. However, little is known about the NSD pathways and our understanding of the histone lysine-HMTase mechanism is partial. To shed some light on both the recognition and the regulation of epigenetic marks by the SET domain of the NSD family, we investigate the structural mechanisms of the docking of the histone-H4 tail on the SET domain of NSD1. Our finding exposes a key regulatory and recognition mechanism driven by the flexibility of a loop at the interface of the SET and postSET region. Finally, we prospect the special value of this regulatory region for developing specific and selective NSD inhibitors for the epigenetic therapy of cancers.

  15. A novel calmodulin-regulated Ca2+-ATPase (ACA2) from Arabidopsis with an N-terminal autoinhibitory domain

    Science.gov (United States)

    Harper, J. F.; Hong, B.; Hwang, I.; Guo, H. Q.; Stoddard, R.; Huang, J. F.; Palmgren, M. G.; Sze, H.; Evans, M. L. (Principal Investigator)

    1998-01-01

    To study transporters involved in regulating intracellular Ca2+, we isolated a full-length cDNA encoding a Ca2+-ATPase from a model plant, Arabidopsis, and named it ACA2 (Arabidopsis Ca2+-ATPase, isoform 2). ACA2p is most similar to a "plasma membrane-type" Ca2+-ATPase, but is smaller (110 kDa), contains a unique N-terminal domain, and is missing a long C-terminal calmodulin-binding regulatory domain. In addition, ACA2p is localized to an endomembrane system and not the plasma membrane, as shown by aqueous-two phase fractionation of microsomal membranes. ACA2p was expressed in yeast as both a full-length protein (ACA2-1p) and an N-terminal truncation mutant (ACA2-2p; Delta residues 2-80). Only the truncation mutant restored the growth on Ca2+-depleted medium of a yeast mutant defective in both endogenous Ca2+ pumps, PMR1 and PMC1. Although basal Ca2+-ATPase activity of the full-length protein was low, it was stimulated 5-fold by calmodulin (50% activation around 30 nM). In contrast, the truncated pump was fully active and insensitive to calmodulin. A calmodulin-binding sequence was identified within the first 36 residues of the N-terminal domain, as shown by calmodulin gel overlays on fusion proteins. Thus, ACA2 encodes a novel calmodulin-regulated Ca2+-ATPase distinguished by a unique N-terminal regulatory domain and a non-plasma membrane localization.

  16. Structural properties of the linkers connecting the N- and C- terminal domains in the MocR bacterial transcriptional regulators

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-12-01

    Full Text Available Peptide inter-domain linkers are peptide segments covalently linking two adjacent domains within a protein. Linkers play a variety of structural and functional roles in naturally occurring proteins. In this work we analyze the sequence properties of the predicted linker regions of the bacterial transcriptional regulators belonging to the recently discovered MocR subfamily of the GntR regulators. Analyses were carried out on the MocR sequences taken from the phyla Actinobacteria, Firmicutes, Alpha-, Beta- and Gammaproteobacteria. The results suggest that MocR linkers display phylum-specific characteristics and unique features different from those already described for other classes of inter-domain linkers. They show an average length significantly higher: 31.8 ± 14.3 residues reaching a maximum of about 150 residues. Compositional propensities displayed general and phylum-specific trends. Pro is dominating in all linkers. Dyad propensity analysis indicate Pro–Pro as the most frequent amino acid pair in all linkers. Physicochemical properties of the linker regions were assessed using amino acid indices relative to different features: in general, MocR linkers are flexible, hydrophilic and display propensity for β-turn or coil conformations. Linker sequences are hypervariable: only similarities between MocR linkers from organisms related at the level of species or genus could be found with sequence searches. The results shed light on the properties of the linker regions of the new MocR subfamily of bacterial regulators and may provide knowledge-based rules for designing artificial linkers with desired properties.

  17. MicroRNA-128 targets myostatin at coding domain sequence to regulate myoblasts in skeletal muscle development.

    Science.gov (United States)

    Shi, Lei; Zhou, Bo; Li, Pinghua; Schinckel, Allan P; Liang, Tingting; Wang, Han; Li, Huizhi; Fu, Lingling; Chu, Qingpo; Huang, Ruihua

    2015-09-01

    MicroRNAs (miRNAs or miRs) play a critical role in skeletal muscle development. In a previous study we observed that miR-128 was highly expressed in skeletal muscle. However, its function in regulating skeletal muscle development is not clear. Our hypothesis was that miR-128 is involved in the regulation of the proliferation and differentiation of skeletal myoblasts. In this study, through bioinformatics analyses, we demonstrate that miR-128 specifically targeted mRNA of myostatin (MSTN), a critical inhibitor of skeletal myogenesis, at coding domain sequence (CDS) region, resulting in down-regulating of myostatin post-transcription. Overexpression of miR-128 inhibited proliferation of mouse C2C12 myoblast cells but promoted myotube formation; whereas knockdown of miR-128 had completely opposite effects. In addition, ectopic miR-128 regulated the expression of myogenic factor 5 (Myf5), myogenin (MyoG), paired box (Pax) 3 and 7. Furthermore, an inverse relationship was found between the expression of miR-128 and MSTN protein expression in vivo and in vitro. Taken together, these results reveal that there is a novel pathway in skeletal muscle development in which miR-128 regulates myostatin at CDS region to inhibit proliferation but promote differentiation of myoblast cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The black rock series supported SCR catalyst for NO x removal.

    Science.gov (United States)

    Xie, Bin; Luo, Hang; Tang, Qing; Du, Jun; Liu, Zuohua; Tao, Changyuan

    2017-09-01

    Black rock series (BRS) is of great potential for their plenty of valued oxides which include vanadium, iron, alumina and silica oxides, etc. BRS was used for directly preparing of selective catalytic reduction (SCR) catalyst by modifying its surface texture with SiO 2 -TiO 2 sols and regulating its catalytic active constituents with V 2 O 5 and MoO 3 . Consequently, 90% NO removal ratio was obtained within 300-400 °C over the BRS-based catalyst. The structure and properties of the BRS-based catalyst were characterized by the techniques of N 2 adsorption-desorption, X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), H 2 -temperature programmed reduction (H 2 -TPR), and NH 3 -temperature programmed desorption (NH 3 -TPD). The results revealed that the BRS-based catalyst possesses favorable properties for NO x removal, including highly dispersed active components, abundant surface-adsorbed oxygen O α , well redox property, and numerous Brønsted acid sites. Particularly, the BRS-based catalyst exhibited considerable anti-poisoning performance compared with commercial TiO 2 -based catalyst. The former catalyst shows a NO conversion surpassing 80% from 300 to 400 °C for potassium poisoning, and a durability of SO 2 and H 2 O exceeding 85% at temperatures from 300 to 450 °C.

  19. Interaction of GlnK with the GAF domain of Herbaspirillum seropedicae NifA mediates NH₄⁺-regulation.

    Science.gov (United States)

    Oliveira, Marco A S; Aquino, Bruno; Bonatto, Ana Claudia; Huergo, Luciano F; Chubatsu, Leda S; Pedrosa, Fábio O; Souza, Emanuel M; Dixon, Ray; Monteiro, Rose A

    2012-04-01

    Nitrogen fixation in Herbaspirillum seropedicae is transcriptionally regulated by NifA, a σ(54) transcriptional activator with three structural domains: an N-terminal GAF domain, a catalytic AAA+ domain and a C-terminal DNA-binding domain. NifA is only active in H. seropedicae when cultures are grown in the absence of fixed nitrogen and at low oxygen tensions. There is evidence that the inactivation of NifA in response to fixed nitrogen is mediated by the regulatory GAF domain. However, the mechanism of NifA repression by the GAF domain, as well as the transduction of nitrogen status to NifA, is not understood. In order to study the regulation of NifA activity by fixed nitrogen independently of oxygen regulation, we constructed a chimeric protein containing the GAF domain of H. seropedicae NifA fused to the AAA+ and C-terminal domains of Azotobacter vinelandii NifA. This chimeric protein (NifAQ1) lacks the cysteine motif found in oxygen sensitive NifA proteins and is not oxygen responsive in vivo. Our results demonstrate that NifAQ1 responds to fixed nitrogen and requires GlnK protein for activity, a behavior similar to H. seropedicae NifA. In addition, protein footprinting analysis indicates that this response probably involves a protein-protein contact between the GAF domain and the GlnK protein. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. Focal adhesion kinase-dependent focal adhesion recruitment of SH2 domains directs SRC into focal adhesions to regulate cell adhesion and migration.

    Science.gov (United States)

    Wu, Jui-Chung; Chen, Yu-Chen; Kuo, Chih-Ting; Wenshin Yu, Helen; Chen, Yin-Quan; Chiou, Arthur; Kuo, Jean-Cheng

    2015-12-18

    Directed cell migration requires dynamical control of the protein complex within focal adhesions (FAs) and this control is regulated by signaling events involving tyrosine phosphorylation. We screened the SH2 domains present in tyrosine-specific kinases and phosphatases found within FAs, including SRC, SHP1 and SHP2, and examined whether these enzymes transiently target FAs via their SH2 domains. We found that the SRC_SH2 domain and the SHP2_N-SH2 domain are associated with FAs, but only the SRC_SH2 domain is able to be regulated by focal adhesion kinase (FAK). The FAK-dependent association of the SRC_SH2 domain is necessary and sufficient for SRC FA targeting. When the targeting of SRC into FAs is inhibited, there is significant suppression of SRC-mediated phosphorylation of paxillin and FAK; this results in an inhibition of FA formation and maturation and a reduction in cell migration. This study reveals an association between FAs and the SRC_SH2 domain as well as between FAs and the SHP2_N-SH2 domains. This supports the hypothesis that the FAK-regulated SRC_SH2 domain plays an important role in directing SRC into FAs and that this SRC-mediated FA signaling drives cell migration.

  1. Amyloid cores in prion domains: Key regulators for prion conformational conversion.

    Science.gov (United States)

    Fernández, María Rosario; Batlle, Cristina; Gil-García, Marcos; Ventura, Salvador

    2017-01-02

    Despite the significant efforts devoted to decipher the particular protein features that encode for a prion or prion-like behavior, they are still poorly understood. The well-characterized yeast prions constitute an ideal model system to address this question, because, in these proteins, the prion activity can be univocally assigned to a specific region of their sequence, known as the prion forming domain (PFD). These PFDs are intrinsically disordered, relatively long and, in many cases, of low complexity, being enriched in glutamine/asparagine residues. Computational analyses have identified a significant number of proteins having similar domains in the human proteome. The compositional bias of these regions plays an important role in the transition of the prions to the amyloid state. However, it is difficult to explain how composition alone can account for the formation of specific contacts that position correctly PFDs and provide the enthalpic force to compensate for the large entropic cost of immobilizing these domains in the initial assemblies. We have hypothesized that short, sequence-specific, amyloid cores embedded in PFDs can perform these functions and, accordingly, act as preferential nucleation centers in both spontaneous and seeded aggregation. We have shown that the implementation of this concept in a prediction algorithm allows to score the prion propensities of putative PFDs with high accuracy. Recently, we have provided experimental evidence for the existence of such amyloid cores in the PFDs of Sup35, Ure2, Swi1, and Mot3 yeast prions. The fibrils formed by these short stretches may recognize and promote the aggregation of the complete proteins inside cells, being thus a promising tool for targeted protein inactivation.

  2. HD-GYP domain proteins regulate biofilm formation and virulence in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Ryan, Robert P.; Lucey, Jean; O'Donovan, Karen

    2009-01-01

    residues (YN-GYP). Here we have investigated the role of these proteins in biofilm formation, virulence factor synthesis and virulence of P. aeruginosa. Mutation of PA4108 and PA4781 led to an increase in the level of cyclic-di-GMP in P. aeruginosa, consistent with the predicted activity of the encoded......2572 had a negative influence on swarming that was cryptic and was revealed only after removal of an uncharacterized C-terminal domain. Mutation of PA4108, PA4781 and PA2572 had distinct effects on biofilm formation and architecture of P. aeruginosa. All three proteins contributed to virulence of P...

  3. Tracing the origin of S-Cr. novac 'money'

    Directory of Open Access Journals (Sweden)

    Vlajić-Popović Jasna

    2010-01-01

    Full Text Available The paper points at the imprecision of the hitherto prevailing etymology of S-Cr. novac ‘money’ as an univerbization departing from the adjective nov ‘new’, through an undated and undefined *novi penez /dinar. After a review of previous interpretations and the corpus of lexicographic attestations of the noun novac, the areal distribution of its earliest Croatian and Serbian attestations (from the 16th and 17th centuries respectively, as well as the 18th century Sln. novz ‘nummus ungaricus’ is taken as an indication of Hungarian source of influence. Hence the nomination impulse is found in Latin, the official language in medieval Hungary, where in some 15th century legal documents from the Zagreb court the syntagm novorum denariorum (Gen. pl. occurs simultaneously and synonymously with the nominalized adj. novos (Acc. pl.. The semantic borrowing into local Slavic novac /novec ‘new coin (initially 1/100 of a dukat’, evolves into ‘coin of small value’ and eventually, through a negative phrase nemati ni novca ‘to be broke’ (lit.: ‘to have not a single penny’ into ‘money (in general; wealth’. In both meanings it entered the vernaculars of the entire Štokavian territory (some time during the 18th century, which is reflected in folk poetry, paremiology, etc. The term novac has suppressed the previously widespread Slavic term penezi /pjenezi /pinezi and entered a co-existence with the Turcism para f. ‘coin’, pare pl. ‘money’ which lasts into this day. Since the nomination from the adj. nov is unique among standardly known terms for money (cf. Buck s.v., a precious onomasiological parallelism to this formation is discovered in Serb. dial. novica ‘a Turkish 20 gr coin’, ‘a fake coin’.

  4. Cation diffusion facilitators transport initiation and regulation is mediated by cation induced conformational changes of the cytoplasmic domain.

    Directory of Open Access Journals (Sweden)

    Natalie Zeytuni

    Full Text Available Cation diffusion facilitators (CDF are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all domains of life. CDF's were shown to be involved in several human diseases, such as Type-II diabetes and neurodegenerative diseases. In this work, we employed a multi-disciplinary approach to study the activation mechanism of the CDF protein family. For this we used MamM, one of the main ion transporters of magnetosomes--bacterial organelles that enable magnetotactic bacteria to orientate along geomagnetic fields. Our results reveal that the cytosolic domain of MamM forms a stable dimer that undergoes distinct conformational changes upon divalent cation binding. MamM conformational change is associated with three metal binding sites that were identified and characterized. Altogether, our results provide a novel auto-regulation mode of action model in which the cytosolic domain's conformational changes upon ligand binding allows the priming of the CDF into its transport mode.

  5. A fraction of Crm1 locates at centrosomes by its CRIME domain and regulates the centrosomal localization of pericentrin

    International Nuclear Information System (INIS)

    Liu, Qinying; Jiang, Qing; Zhang, Chuanmao

    2009-01-01

    Crm1 plays a role in exporting proteins containing nuclear export signals (NESs) from the nucleus to the cytoplasm. Some proteins that are capable of interacting with Ran/Crm1 were reported to be localized at centrosomes and to function as centrosome checkpoints. But it remains unclear how Crm1 locates at centrosomes. In this study, we found that a fraction of Crm1 is located at centrosomes through its N-terminal CRM1, importin β etc. (CRIME) domain, which is responsible for interacting with RanGTP, suggesting that Crm1 might target to centrosomes through binding centrosomal RanGTP. Moreover, overexpression of the CRIME domain, which is free of NES binding domain, resulted in the dissociation of pericentrin and γ-tubulin complex from centrosomes and the disruption of microtubule nucleation. Deficiency of Crm1 provoked by RNAi also decreased the spindle poles localization of pericentrin and γ-tubulin complex, coupled with mitotic defects. Since pericentrin was sensitive to Crm1 specific inhibitor leptomycin B, we propose that the centrosomal Crm1 might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes.

  6. Androgen receptor regulates nuclear trafficking and nuclear domain residency of corepressor HDAC7 in a ligand-dependent fashion

    International Nuclear Information System (INIS)

    Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J.

    2006-01-01

    In addition to chromosomal proteins, histone deacetylases (HDACs) target transcription factors in transcriptional repression. Here, we show that the class II HDAC family member HDAC7 is an efficient corepressor of the androgen receptor (AR). HDAC7 resided in the cytoplasm in the absence of AR or a cognate ligand, but hormone-occupancy of AR induced nuclear transfer of HDAC7. Nuclear colocalization pattern of AR and HDAC7 was dependent on the nature of the ligand. In the presence of testosterone, a portion of HDAC7 localized to pearl-like nuclear domains, whereas AR occupied with antagonistic ligands cyproterone acetate- or casodex (bicalutamide) recruited HDAC7 from these domains to colocalize with the receptor in speckles and nucleoplasm in a more complete fashion. Ectopic expression of PML-3 relieved the repressive effect of HDAC7 on AR function by sequestering HDAC7 to PML-3 domains. AR acetylation at Lys630/632/633 was not the target of HDAC7 repression, since repression of AR function was independent of these acetylation sites. Moreover, the deacetylase activity of HDAC7 was in part dispensable in the repression of AR function. In sum, our results identify HDAC7 as a novel AR corepressor whose subcellular and subnuclear compartmentalization can be regulated in an androgen-selective manner

  7. Evaluation of Mercury Emissions from Coal-Fired Facilities with SCR and FGD Systems

    Energy Technology Data Exchange (ETDEWEB)

    J. A. Withum; J. E. Locke

    2006-02-01

    CONSOL Energy Inc., Research & Development (CONSOL), with support from the U.S. Department of Energy, National Energy Technology Laboratory (DOE) and the Electric Power Research Institute (EPRI), is evaluating the effects of selective catalytic reduction (SCR) on mercury (Hg) capture in coal-fired plants equipped with an electrostatic precipitator (ESP)--wet flue gas desulfurization (FGD) combination or a spray dyer absorber--fabric filter (SDA-FF) combination. In this program CONSOL is determining mercury speciation and removal at 10 coal-fired facilities. The principal purpose of this work is to develop a better understanding of the potential mercury removal ''co-benefits'' achieved by NO{sub x}, and SO{sub 2} control technologies. It is expected that this data will provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on mercury speciation and the efficacy of different FGD technologies for mercury capture. Ultimately, this insight could help to design and operate SCR and FGD systems to maximize mercury removal. The objectives are (1) to evaluate the effect of SCR on mercury capture in the ESP-FGD and SDA-FF combinations at coal-fired power plants, (2) evaluate the effect of SCR catalyst degradation on mercury capture; (3) evaluate the effect of low load operation on mercury capture in an SCR-FGD system, and (4) collect data that could provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on mercury speciation and the efficacy of different FGD technologies for mercury capture. This document, the tenth in a series of topical reports, describes the results and analysis of mercury sampling performed on two 468 MW units burning bituminous coal containing 1.3-1.7% sulfur. Unit 2 is equipped with an SCR, ESP, and wet FGD to control NO{sub x}, particulate, and SO{sub 2} emissions

  8. Generic concept to program the time domain of self-assemblies with a self-regulation mechanism.

    Science.gov (United States)

    Heuser, Thomas; Steppert, Ann-Kathrin; Lopez, Catalina Molano; Zhu, Baolei; Walther, Andreas

    2015-04-08

    Nature regulates complex structures in space and time via feedback loops, kinetically controlled transformations, and under energy dissipation to allow non-equilibrium processes. Although man-made static self-assemblies realize excellent control over hierarchical structures via molecular programming, managing their temporal destiny by self-regulation is a largely unsolved challenge. Herein, we introduce a generic concept to control the time domain by programming the lifetimes of switchable self-assemblies in closed systems. We conceive dormant deactivators that, in combination with fast promoters, enable a unique kinetic balance to establish an autonomously self-regulating, transient pH-state, whose duration can be programmed over orders of magnitude-from minutes to days. Coupling this non-equilibrium state to pH-switchable self-assemblies allows predicting their assembly/disassembly fate in time, similar to a precise self-destruction mechanism. We demonstrate a platform approach by programming self-assembly lifetimes of block copolymers, nanoparticles, and peptides, enabling dynamic materials with a self-regulation functionality.

  9. Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

    2017-11-01

    The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The SH2 Domain Regulates c-Abl Kinase Activation by a Cyclin-Like Mechanism and Remodulation of the Hinge Motion

    OpenAIRE

    Dölker, N.; Górna, M. W.; Sutto, L.; Torralba, A. S.; Superti-Furga, G.; Gervasio, F. L.

    2014-01-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys...

  11. The energy consumption and environmental impacts of SCR technology in China

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Zengying; Ma, Xiaoqian; Lin, Hai; Tang, Yuting [School of Electric Power, Guangdong Key Laboratory of Clean Energy Technology, South China University of Technology, Guangzhou 510640 (China)

    2011-04-15

    Energy and environment are drawing greater attention today, particularly with the rapid development of the economy and increase consumption of energy in China. At present, coal-fired power plants are mainly responsible for atmospheric air pollution. The selective catalytic reduction (SCR) technology is a highly effective method for NO{sub X} control. The present study identified and quantified the energy consumption and the environmental impacts of SCR system throughout the whole life cycle, including production and transportation of manufacturing materials, installation and operation of SCR technology. The analysis was conducted with the utilization of life cycle assessment (LCA) methodology which provided a quantitative basis for assessing potential improvements in the environmental performance of the system. The functional unit of the study was 5454 t NO{sub X} emission from an existing Chinese pulverized coal power plant for 1 year. The current study compared life cycle emissions from two types of de-NO{sub X} technologies, namely the SCR technology and the selective non-catalytic reduction (SNCR) technology, and the case that NO{sub X} was emitted into atmosphere directly. The results showed that the environmental impact loading resulting from SCR technology (66810 PET{sub 2000}) was smaller than that of flue gas emitted into atmosphere directly (164121 PET{sub 2000}) and SNCR technology (105225 PET{sub 2000}). More importantly, the SCR technology is much more effective at the elimination of acidification and nutrient enrichment than SNCR technology and the case that NO{sub X} emitted into atmosphere directly. This SCR technology is more friendly to the environment, and can play an important role in NO{sub X} control for coal-fired power plants as well as industrial boilers. (author)

  12. Regulation of β2-adrenergic receptor function by conformationally selective single-domain intrabodies

    DEFF Research Database (Denmark)

    Staus, Dean P; Wingler, Laura M; Strachan, Ryan T

    2014-01-01

    . However, a monomeric single-domain antibody (nanobody) from the Camelid family was recently found to allosterically bind and stabilize an active conformation of the β2-adrenergic receptor (β2AR). Here, we set out to study the functional interaction of 18 related nanobodies with the β2AR to investigate...... their roles as novel tools for studying GPCR biology. Our studies revealed several sequence-related nanobody families with preferences for active (agonist-occupied) or inactive (antagonist-occupied) receptors. Flow cytometry analysis indicates that all nanobodies bind to epitopes displayed...... on the intracellular receptor surface; therefore, we transiently expressed them intracellularly as "intrabodies" to test their effects on β2AR-dependent signaling. Conformational specificity was preserved after intrabody conversion as demonstrated by the ability for the intracellularly expressed nanobodies...

  13. Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain.

    Science.gov (United States)

    Loh, T P; Sievert, L L; Scott, R W

    1988-11-01

    An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.

  14. Arabidopsis SHR and SCR transcription factors and AUX1 auxin influx carrier control the switch between adventitious rooting and xylogenesis in planta and in in vitro cultured thin cell layers.

    Science.gov (United States)

    Della Rovere, F; Fattorini, L; D'Angeli, S; Veloccia, A; Del Duca, S; Cai, G; Falasca, G; Altamura, M M

    2015-03-01

    Adventitious roots (ARs) are essential for vegetative propagation. The Arabidopsis thaliana transcription factors SHORT ROOT (SHR) and SCARECROW (SCR) affect primary/lateral root development, but their involvement in AR formation is uncertain. LAX3 and AUX1 auxin influx carriers contribute to primary/lateral root development. LAX3 expression is regulated by SHR, and LAX3 contributes to AR tip auxin maximum. In contrast, AUX1 involvement in AR development is unknown. Xylogenesis is induced by auxin plus cytokinin as is AR formation, but the genes involved are largely unknown. Stem thin cell layers (TCLs) form ARs and undergo xylogenesis under the same auxin plus cytokinin input. The aim of this research was to investigate SHR, SCR, AUX1 and LAX3 involvement in AR formation and xylogenesis in intact hypocotyls and stem TCLs in arabidopsis. Hypocotyls of scr-1, shr-1, lax3, aux1-21 and lax3/aux1-21 Arabidopsis thaliana null mutant seedlings grown with or without auxin plus cytokinin were examined histologically, as were stem TCLs cultured with auxin plus cytokinin. SCR and AUX1 expression was monitored using pSCR::GFP and AUX1::GUS lines, and LAX3 expression and auxin localization during xylogenesis were monitored by using LAX3::GUS and DR5::GUS lines. AR formation was inhibited in all mutants, except lax3. SCR was expressed in pericycle anticlinally derived AR-forming cells of intact hypocotyls, and in cell clumps forming AR meristemoids of TCLs. The apex was anomalous in shr and scr ARs. In all mutant hypocotyls, the pericycle divided periclinally to produce xylogenesis. Xylary element maturation was favoured by auxin plus cytokinin in shr and aux1-21. Xylogenesis was enhanced in TCLs, and in aux1-21 and shr in particular. AUX1 was expressed before LAX3, i.e. in the early derivatives leading to either ARs or xylogenesis. AR formation and xylogenesis are developmental programmes that are inversely related, but they involve fine-tuning by the same proteins, namely SHR

  15. A20 Functional Domains Regulate Subcellular Localization and NF-Kappa B Activation

    Science.gov (United States)

    2013-08-15

    endothelial cells or if the effects of A20 are limited strictly to the process of apoptosis. The Ferran group began by taking bovine aortic endothelial...protein (64, 67, 81, 118, 122). Interestingly, A20 is also involved in the regulation of intracellular parasite infection (109, 123). Given the...was supplemented with a combination of heat inactivated 10% fetal bovine serum and 1% penicillin G/streptomycin sulfate/gentamycin sulfate

  16. The PH domain of phosphoinositide-dependent kinase-1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: single-molecule and ensemble studies.

    Science.gov (United States)

    Ziemba, Brian P; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J

    2013-07-16

    Phosphoinositide-dependent kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology, this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric states of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. This study investigates the binding of purified wild-type (WT) and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single-molecule and ensemble measurements. Single-molecule analysis of the brightness of the fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single-molecule analysis of two-dimensional (2D) diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate as a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little penetration of the protein into the bilayer as observed for other PH domains. The 2D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that allows

  17. Reactivity of Surface Nitrates in H2-Assisted SCR of NOx Over Ag/Al2O3 Catalyst

    DEFF Research Database (Denmark)

    Sadokhina, N. A.; Doronkin, Dmitry E.; Baeva, G. N.

    2013-01-01

    The role of nitrate ad-species in H2-assisted SCR over Ag/Al2O3 was compared in NH3-SCR and n-C6H14-SCR processes. It was found that nitrates could be reduced by NH3 or n-C6H14 at similar rates with H2 co-feeding which indicates a common rate-limiting step. However, contributions of surface nitrate...... reduction to the overall NH3-SCR or n-C6H14-SCR are different as revealed by comparing the rates of nitrate reduction with the rates of steady-state processes. The rate of the steady-state n-C6H14-SCR is virtually identical to the rate of surface nitrate reduction suggesting a significant contribution...... of the surface nitrates reduction to the overall n-C6H14-SCR process. On the other hand, the steady-state rate of NH3-SCR is by ~15 times higher, which indicates that the reduction of surface nitrates plays a marginal role in the overall NH3-SCR....

  18. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation

    DEFF Research Database (Denmark)

    Kieffer-Kwon, Kyong-Rim; Tang, Zhonghui; Mathe, Ewy

    2013-01-01

    IA-PET technologies to map the promoter-enhancer interactomes of pluripotent ES cells and differentiated B lymphocytes. We confirm that enhancer usage varies widely across tissues. Unexpectedly, we find that this feature extends to broadly transcribed genes, including Myc and Pim1 cell-cycle regulators, which...... associate with an entirely different set of enhancers in ES and B cells. By means of high-resolution CpG methylomes, genome editing, and digital footprinting, we show that these enhancers recruit lineage-determining factors. Furthermore, we demonstrate that the turning on and off of enhancers during...

  19. Domain- and nucleotide-specific Rev response element regulation of feline immunodeficiency virus production

    Science.gov (United States)

    Na, Hong; Huisman, Willem; Ellestad, Kristofor K.; Phillips, Tom R.; Power, Christopher

    2010-01-01

    Computational analysis of feline immunodeficiency virus (FIV) RNA sequences indicated that common FIV strains contain a rev response element (RRE) defined by a long unbranched hairpin with 6 stem-loop sub-domains, termed stem-loop A (SLA). To examine the role of the RNA secondary structure of the RRE, mutational analyses were performed in both an infectious FIV molecular clone and a FIV CAT-RRE reporter system. These studies disclosed that the stems within SLA (SA1, 2, 3, 4, and 5) of the RRE were critical but SA6 was not essential for FIV replication and CAT expression. These studies also revealed that the secondary structure rather than an antisense protein (ASP) mediates virus expression and replication in vitro. In addition, a single synonymous mutation within the FIV-RRE, SA3/45, reduced viral reverse transcriptase activity and p24 expression after transfection but in addition also showed a marked reduction in viral expression and production following infection. PMID:20570310

  20. A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45.

    Science.gov (United States)

    Courtney, Adam H; Amacher, Jeanine F; Kadlecek, Theresa A; Mollenauer, Marianne N; Au-Yeung, Byron B; Kuriyan, John; Weiss, Arthur

    2017-08-03

    The Src Family kinase Lck sets a critical threshold for T cell activation because it phosphorylates the TCR complex and the Zap70 kinase. How a T cell controls the abundance of active Lck molecules remains poorly understood. We have identified an unappreciated role for a phosphosite, Y192, within the Lck SH2 domain that profoundly affects the amount of active Lck in cells. Notably, mutation of Y192 blocks critical TCR-proximal signaling events and impairs thymocyte development in retrogenic mice. We determined that these defects are caused by hyperphosphorylation of the inhibitory C-terminal tail of Lck. Our findings reveal that modification of Y192 inhibits the ability of CD45 to associate with Lck in cells and dephosphorylate the C-terminal tail of Lck, which prevents its adoption of an active open conformation. These results suggest a negative feedback loop that responds to signaling events that tune active Lck amounts and TCR sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Low NOx combustion and SCR flow field optimization in a low volatile coal fired boiler.

    Science.gov (United States)

    Liu, Xing; Tan, Houzhang; Wang, Yibin; Yang, Fuxin; Mikulčić, Hrvoje; Vujanović, Milan; Duić, Neven

    2018-08-15

    Low NO x burner redesign and deep air staging have been carried out to optimize the poor ignition and reduce the NO x emissions in a low volatile coal fired 330 MW e boiler. Residual swirling flow in the tangentially-fired furnace caused flue gas velocity deviations at furnace exit, leading to flow field unevenness in the SCR (selective catalytic reduction) system and poor denitrification efficiency. Numerical simulations on the velocity field in the SCR system were carried out to determine the optimal flow deflector arrangement to improve flow field uniformity of SCR system. Full-scale experiment was performed to investigate the effect of low NO x combustion and SCR flow field optimization. Compared with the results before the optimization, the NO x emissions at furnace exit decreased from 550 to 650 mg/Nm³ to 330-430 mg/Nm³. The sample standard deviation of the NO x emissions at the outlet section of SCR decreased from 34.8 mg/Nm³ to 7.8 mg/Nm³. The consumption of liquid ammonia reduced from 150 to 200 kg/h to 100-150 kg/h after optimization. Copyright © 2018. Published by Elsevier Ltd.

  2. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells

    Energy Technology Data Exchange (ETDEWEB)

    Noah, Taeko K.; Kazanjian, Avedis [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Whitsett, Jeffrey [Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Neonatology and Pulmonary Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Shroyer, Noah F., E-mail: noah.shroyer@cchmc.org [Gastroenterology, Hepatology and Nutrition, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States); Developmental Biology, Cincinnati Children' s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2010-02-01

    Background and Aims: SPDEF (also termed PDEF or PSE) is an ETS family transcription factor that regulates gene expression in the prostate and goblet cell hyperplasia in the lung. Spdef has been reported to be expressed in the intestine. In this paper, we identify an important role for Spdef in regulating intestinal epithelial cell homeostasis and differentiation. Methods: SPDEF expression was inhibited in colon cancer cells to determine its ability to control goblet cell gene activation. The effects of transgenic expression of Spdef on intestinal differentiation and homeostasis were determined. Results: In LS174T colon cancer cells treated with Notch/{gamma}-secretase inhibitor to activate goblet cell gene expression, shRNAs that inhibited SPDEF also repressed expression of goblet cell genes AGR2, MUC2, RETLNB, and SPINK4. Transgenic expression of Spdef caused the expansion of intestinal goblet cells and corresponding reduction in Paneth, enteroendocrine, and absorptive enterocytes. Spdef inhibited proliferation of intestinal crypt cells without induction of apoptosis. Prolonged expression of the Spdef transgene caused a progressive reduction in the number of crypts that expressed Spdef, consistent with its inhibitory effects on cell proliferation. Conclusions: Spdef was sufficient to inhibit proliferation of intestinal progenitors and induce differentiation into goblet cells; SPDEF was required for activation of goblet cell associated genes in vitro. These data support a model in which Spdef promotes terminal differentiation into goblet cells of a common goblet/Paneth progenitor.

  3. Predicting mercury retention in utility gas cleaning systems with SCR/ESP/FGD combinations or activated carbon injection

    Energy Technology Data Exchange (ETDEWEB)

    Krishnakumar, Balaji; Naik, Chitralkumar V.; Niksa, Stephen [Niksa Energy Associates LLC, Belmont, CA (United States); Fujiwara, Naoki [Idemitsu Kosan Co., Ltd, Chiba (Japan). Coal and Environment Research Lab.

    2013-07-01

    This paper presents validations of the Hg speciation predicted by NEA's MercuRator trademark package with an American field test database for 28 full-scale utility gas cleaning systems. It emphasizes SCR/ESP/FGD combinations and activated carbon injection because these two applications present the best long- term prospects for Hg control by coal-burning utilities. Validations of the extents of Hg{sup 0} oxidation across SCRs and of Hg retention in wet FGDs gave correlation coefficients greater than 0.9 for both units. A transport-based FGD analysis correctly assessed the potential for Hg{sup 0} re-emission in one limestone wet FGD. Among the ten stations in the SCR/ESP/FGD validations, the simulations correctly identified 3 of 4 of the relatively high Hg emissions rates; all four of the sites with moderate emissions rates; and both sites with the lowest emission rates. The validations for ACI applications demonstrated that Hg removals can be accurately estimated for the full domain of coal quality, LOI, and ACI rates for both untreated and brominated carbon sorbents. The predictions for ACI depict the test-to-test variations in most cases, and accurately describe the impact of ACI configuration and sorbent type. ACI into FFs is the most effective configuration, although ACI into ESPs often removes 90% or more Hg, provided that there is sufficient residence time and Cl in the flue gas. Brominated sorbents perform better than untreated carbons, unless SO{sub 3} condensation inhibits Hg adsorption.

  4. Different domains of P21Cip1/waf1 regulate DNA replication and DNA repair-associated processes after UV

    International Nuclear Information System (INIS)

    Soria, Gaston; Speroni, Juliana; Podhajcer, Osvaldo L.; Gottifredi, Vanesa; Prives, Carol

    2007-01-01

    Full text: Many genotoxic insults result in p21 up-regulation and p21-dependent cell cycle arrest but UV irradiation triggers p21 proteolysis. The significance of the increased p21 turnover is unclear and might be associated to DNA repair. While the role of p21 in Nucleotide Excision Repair (NER) remains controversial, two recent reports explore its effect on Translesion DNA Synthesis (TLS), a process that avoids replication blockage during S phase. The first report shows that p21 degradation is required for efficient PCNA ubiquitination, a post transcriptional modification that is relevant for TLS. The second report demonstrates that p21 (-/-) cells have increased TLS-associated mutagenic rates. Herein we analyze the effect of p21 on different PCNA-driven processes including DNA replication, NER and TLS. Whereas only the CDK binding domain of p21 is required for cell cycle arrest in unstressed cells; neither the CDK- nor the PCNA-binding domains of p21 are able to block early and late steps of NER. Intriguingly, through its PCNA binding domain, p21 inhibited recruitment of the TLS-polymerase, polη to PCNA foci after UV. Moreover, this obstruction correlates with accumulation of γH2AX and increased apoptosis. Taking together, our data emphasizes the link between p21 turnover and efficient TLS. This might also suggest a potential effect of p21 on other activities of polζ, a DNA polymerase with central roles in other biological scenarios such as genetic conversion, homologous recombination and modulation of the cellular response to genotoxic agents [es

  5. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling

    DEFF Research Database (Denmark)

    Ungureanu, Daniela; Wu, Jinhua; Pekkala, Tuija

    2011-01-01

    Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of JAK2 remains unknown. Mutations in JH2 lead to increased...... JAK2 activity, contributing to myeloproliferative neoplasms (MPNs). Here we show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2: Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling....... Notably, different MPN mutations abrogated JH2 activity in cells, and in MPN (V617F) patient cells phosphorylation of Tyr570 was reduced, suggesting that loss of JH2 activity contributes to the pathogenesis of MPNs. These results identify the catalytic activity of JH2 as a previously unrecognized...

  6. FlnA binding to PACSIN2 F-BAR domain regulates membrane tubulation in megakaryocytes and platelets.

    Science.gov (United States)

    Begonja, Antonija Jurak; Pluthero, Fred G; Suphamungmee, Worawit; Giannini, Silvia; Christensen, Hilary; Leung, Richard; Lo, Richard W; Nakamura, Fumihiko; Lehman, William; Plomann, Markus; Hoffmeister, Karin M; Kahr, Walter H A; Hartwig, John H; Falet, Hervé

    2015-07-02

    Bin-Amphiphysin-Rvs (BAR) and Fes-CIP4 homology BAR (F-BAR) proteins generate tubular membrane invaginations reminiscent of the megakaryocyte (MK) demarcation membrane system (DMS), which provides membranes necessary for future platelets. The F-BAR protein PACSIN2 is one of the most abundant BAR/F-BAR proteins in platelets and the only one reported to interact with the cytoskeletal and scaffold protein filamin A (FlnA), an essential regulator of platelet formation and function. The FlnA-PACSIN2 interaction was therefore investigated in MKs and platelets. PACSIN2 associated with FlnA in human platelets. The interaction required FlnA immunoglobulin-like repeat 20 and the tip of PACSIN2 F-BAR domain and enhanced PACSIN2 F-BAR domain membrane tubulation in vitro. Most human and wild-type mouse platelets had 1 to 2 distinct PACSIN2 foci associated with cell membrane GPIbα, whereas Flna-null platelets had 0 to 4 or more foci. Endogenous PACSIN2 and transfected enhanced green fluorescent protein-PACSIN2 were concentrated in midstage wild-type mouse MKs in a well-defined invagination of the plasma membrane reminiscent of the initiating DMS and dispersed in the absence of FlnA binding. The DMS appeared less well defined, and platelet territories were not readily visualized in Flna-null MKs. We conclude that the FlnA-PACSIN2 interaction regulates membrane tubulation in MKs and platelets and likely contributes to DMS formation. © 2015 by The American Society of Hematology.

  7. Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ*

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J.; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W.; Horne, William T.; Lewis, Stephanie N.; Bevan, David R.; Hontecillas, Raquel

    2011-01-01

    Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E2 and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation. PMID:21088297

  8. Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J; Lu, Pinyi; Climent, Montse; Carbo, Adria; Sobral, Bruno W; Horne, William T; Lewis, Stephanie N; Bevan, David R; Hontecillas, Raquel

    2011-01-28

    Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation.

  9. The F-Actin Binding Protein Cortactin Regulates the Dynamics of the Exocytotic Fusion Pore through its SH3 Domain

    Science.gov (United States)

    González-Jamett, Arlek M.; Guerra, María J.; Olivares, María J.; Haro-Acuña, Valentina; Baéz-Matus, Ximena; Vásquez-Navarrete, Jacqueline; Momboisse, Fanny; Martinez-Quiles, Narcisa; Cárdenas, Ana M.

    2017-01-01

    Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca2+ signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism. We addressed this hypothesis by analyzing de novo actin polymerization and exocytosis in bovine adrenal chromaffin cells expressing different cortactin or N-WASP domains, or cortactin mutants that fail to interact with proline-rich domain (PRD)-containing proteins, including N-WASP, or to be phosphorylated by Ca2+-dependent kinases, such as ERK1/2 and Src. Our results show that the activation of nicotinic receptors in chromaffin cells promotes cortactin translocation to the cell cortex, where it colocalizes with actin filaments. We further found that, in association with PRD-containing proteins, cortactin contributes to the Ca2+-dependent formation of F-actin, and regulates fusion pore dynamics and the number of exocytotic events induced by activation of nicotinic receptors. However, whereas the actions of cortactin on the fusion pore dynamics seems to depend on the availability of monomeric actin and its phosphorylation by ERK1/2 and Src kinases, cortactin regulates the extent of exocytosis by a mechanism independent of actin polymerization. Together our findings point out a role for cortactin as a critical modulator of actin filament formation and exocytosis in neuroendocrine cells. PMID:28522963

  10. Signaling domain of Sonic Hedgehog as cannibalistic calcium-regulated zinc-peptidase.

    Directory of Open Access Journals (Sweden)

    Rocio Rebollido-Rios

    2014-07-01

    Full Text Available Sonic Hedgehog (Shh is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog, of which all members harbor a structurally well-defined Zn2+ center; however, it is remarkable that ShhN so far is the only LAS member without proven peptidase activity. Another unique feature of ShhN in the LAS group is a double-Ca2+ center close to the zinc. We have studied the effect of these calcium ions on ShhN structure, dynamics, and interactions. We find that the presence of calcium has a marked impact on ShhN properties, with the two calcium ions having different effects. The more strongly bound calcium ion significantly stabilizes the overall structure. Surprisingly, the binding of the second calcium ion switches the putative catalytic center from a state similar to LAS enzymes to a state that probably is catalytically inactive. We describe in detail the mechanics of the switch, including the effect on substrate co-ordinating residues and on the putative catalytic water molecule. The properties of the putative substrate binding site suggest that ShhN could degrade other ShhN molecules, e.g. by cleavage at highly conserved glycines in ShhN. To test experimentally the stability of ShhN against autodegradation, we compare two ShhN mutants in vitro: (1 a ShhN mutant unable to bind calcium but with putative catalytic center intact, and thus, according to our hypothesis, a constitutively active peptidase, and (2 a mutant carrying additionally mutation E177A, i.e., with the putative catalytically active residue knocked out. The in vitro results are consistent with ShhN being a cannibalistic zinc-peptidase. These experiments also reveal that the peptidase activity depends on pH.

  11. Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

    Science.gov (United States)

    Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

    1999-04-02

    Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the same domains when part of a larger SH(3+2) construct. Increased deuterium incorporation was observed for the SH3 domain in the joint construct, particularly near the SH2 interface and the short sequence that connects SH3 to SH2, implying greater flexibility of SH3 when it is part of SH(3+2). Slow cooperative unfolding of the SH3 domain occurred at the same rate in isolated SH3 as in the SH(3+2) construct, suggesting a functional significance for this unfolding. The SH2 domain displayed relatively smaller changes in flexibility when part of the SH(3+2) construct. These results suggest that the domains influence each other. Further, our results imply a link between functional regulation and structural dynamics of SH3 and SH2 domains. Copyright 1999 Academic Press.

  12. A comparative study on methods of improving SCR for ship detection in SAR image

    Science.gov (United States)

    Lang, Haitao; Shi, Hongji; Tao, Yunhong; Ma, Li

    2017-10-01

    Knowledge about ship positions plays a critical role in a wide range of maritime applications. To improve the performance of ship detector in SAR image, an effective strategy is improving the signal-to-clutter ratio (SCR) before conducting detection. In this paper, we present a comparative study on methods of improving SCR, including power-law scaling (PLS), max-mean and max-median filter (MMF1 and MMF2), method of wavelet transform (TWT), traditional SPAN detector, reflection symmetric metric (RSM), scattering mechanism metric (SMM). The ability of SCR improvement to SAR image and ship detection performance associated with cell- averaging CFAR (CA-CFAR) of different methods are evaluated on two real SAR data.

  13. The development and application of SCR denitrification technology in power plant

    Science.gov (United States)

    Wu, Junnan

    2017-12-01

    In recent decades, the emission of the nitrogen oxides (NOX) has been increasing with the years of the thermal power plant. The environment pollution caused by the emission of quantities of nitrogen oxides became more and more serious, so people now put more emphasis on the control of the emission of the nitrogen oxides. Especially, our country and the society are paying much more attention to the environment protection and the environment problems cannot be neglected. In this paper, we introduced the related research background of the technology of SCR denitrification which was as the symbol of the technology of the catalytic denitrification and discussed the reaction principles of the SCR denitrification and frequently used catalysts, the process of the technology, and the configuration. In the end, we pointed the way of the future research of the technology of the SCR denitrification.

  14. Operational Choices for Risk Aggregation in Insurance: PSDization and SCR Sensitivity

    Directory of Open Access Journals (Sweden)

    Xavier Milhaud

    2018-04-01

    Full Text Available This work addresses crucial questions about the robustness of the PSDization process for applications in insurance. PSDization refers to the process that forces a matrix to become positive semidefinite. For companies using copulas to aggregate risks in their internal model, PSDization occurs when working with correlation matrices to compute the Solvency Capital Requirement (SCR. We examine how classical operational choices concerning the modelling of risk dependence impacts the SCR during PSDization. These operations refer to the permutations of risks (or business lines in the correlation matrix, the addition of a new risk, and the introduction of confidence weights given to the correlation coefficients. The use of genetic algorithms shows that theoretically neutral transformations of the correlation matrix can surprisingly lead to significant sensitivities of the SCR (up to 6%. This highlights the need for a very strong internal control around the PSDization step.

  15. SCR-1: Design and construction of a small modular stellarator for magnetic confinement of plasma

    International Nuclear Information System (INIS)

    Barillas, L; Vargas, V I; Alpizar, A; Asenjo, J; Carranza, J M; Cerdas, F; Gutiérrez, R; Monge, J I; Mora, J; Morera, J; Peraza, H; Rojas, C; Rozen, D; Saenz, F; Sánchez, G; Sandoval, M; Trimiño, H; Umaña, J; Villegas, L F; Queral, V

    2014-01-01

    This paper describes briefly the design and construction of a small modular stellarator for magnetic confinement of plasma, called Stellarator of Costa Rica 1, or SCR-1; developed by the Plasma Physics Group of the Instituto Tecnológico de Costa Rica, PlasmaTEC. The SCR-1 is based on the small Spanish stellarator UST 1 , created by the engineer Vicente Queral. The SCR-1 will employ stainless steel torus-shaped vacuum vessel with a major radius of 460.33 mm and a cross section radius of 110.25 mm. A typical SCR-1 plasma will have an average radius 42.2 mm and a volume of 8 liters (0.01 m 3 ), and an aspect ratio of 5.7. The magnetic resonant field will be 0.0878 T, and a period of 2 (m=2) with a rotational transform of 0.3. The magnetic field will be provided by 12 modular coils, with 8 turns each, with an electrical current of 8704 A per coil (1088 A per turn of each coil). This current will be fed by a bank of cell batteries. The plasma will be heated by ECRH with magnetrons of a total power of 5 kW, in the first harmonic at 2.45 GHz. The expected electron temperature and density are 15 eV and 10 17 m −3 respectively with an estimated confinement time of 7.30 x 10 −4 ms. The initial diagnostics on the SCR-1 will consist of a Langmuir probe, a heterodyne microwave interferometer, and a field mapping system. The first plasma of the SCR-1 is expected at the end of 2011.

  16. System analysis regarding NO{sub x} reduction with combined SNCR/SCR; Systemstudie avseende kombinerad NO{sub x}-reducering med SNCR/SCR

    Energy Technology Data Exchange (ETDEWEB)

    Niemann, Therese; Henningsson, Claes [S.E.P. Scandinavian Energy Project AB, Stockholm (Sweden); Andersson, Christer [Vattenfall Utveckling AB, Stockholm (Sweden)

    2000-06-01

    Systems with combined SNCR/SCR on biomass fired CFB:s have been focused on lately since they are regarded as very load flexible. Furthermore, synergy effects between the two parts are supposed to result in better performance for the combined system than for the two systems separately. The aim of this study is to investigate whether the combined SNCR/SCR matches the outlined expectations above. The plant chosen for the measurements was Brista Kraft AB. This particular plant is equipped with a CFB boiler of 122 MW{sub th}, which in turn is equipped with the deNO{sub x} system mentioned above. The measurements are made by a 'concentration gradient measurement system', developed by Vattenfall. Consequently, the study indicates that it is very useful to add a catalyst to the SNCR system, both from an environmental- and an economical point of view. However, since the full scale data for the SCR alone is missing, the results for SCR compared with combined SNCR/SCR is harder to decide. Simulations indicate that both systems produces the same emission levels, although, the SCR system may be a bit more cost effective in the long run. The synergy effect between the systems in combination is obvious. Predominantly because the NO{sub x} reduction efficiency in the SNCR zone can be increased (in this case about 10-12%) since a higher amount of ammonia can be accepted downstream of the SNCR zone. Combined systems will achieve a comparable good load independence. The reduction in the SNCR will decrease at lower loads, simultaneously as the reduction in the SCR increases. Thus, the total reduction efficiency will almost be independent of the load. In the project investigations have been made to figure out if two points injection in SNCR give more or less mol distribution of NH{sub 3}/NO quota over the catalyst crosses sectional area. The measurements indicates that two point injection may cause a more uneven distribution of stoichiometries. However, the results seems to

  17. Fe-BEA Zeolite Catalysts for NH3-SCR of NOx

    DEFF Research Database (Denmark)

    Frey, Anne Mette; Mert, Selcuk; Due-Hansen, Johannes

    2009-01-01

    Iron-containing zeolites are known to be promising catalysts for the NH3-SCR reaction. Here, we will investigate the catalytic activity of iron-based BEA catalysts, which was found to exhibit improved activities compared to previously described iron-containing zeolite catalysts, such as ZSM-5...... and ZSM-12. Series of Fe-BEA zeolite catalysts were prepared using a range of different preparation methods. Furthermore, we found that an iron concentration around 3 wt% on BEA showed a small optimum in SCR activity compared to the other iron loadings studied....

  18. Experimental demonstration of a new model-based SCR control strategy for cleaner heavy-duty diesel engines

    NARCIS (Netherlands)

    Willems, F.P.T.; Cloudt, R.P.M.

    2011-01-01

    Selective catalytic reduction (SCR) is a promising diesel aftertreatment technology that enables low nitrogen oxides (NOx) tailpipe emissions with relatively low fuel consumption. Future emission legislation is pushing the boundaries for SCR control systems to achieve high NOx conversion within a

  19. Exhaust particle and NOx emission performance of an SCR heavy duty truck operating in real-world conditions

    Science.gov (United States)

    Saari, Sampo; Karjalainen, Panu; Ntziachristos, Leonidas; Pirjola, Liisa; Matilainen, Pekka; Keskinen, Jorma; Rönkkö, Topi

    2016-02-01

    Particle and NOx emissions of an SCR equipped HDD truck were studied in real-world driving conditions using the "Sniffer" mobile laboratory. Real-time CO2 measurement enables emission factor calculation for NOx and particles. In this study, we compared three different emission factor calculation methods and characterised their suitability for real-world chasing experiments. The particle number emission was bimodal and dominated by the nucleation mode particles (diameter below 23 nm) having emission factor up to 1 × 1015 #/kgfuel whereas emission factor for soot (diameter above 23 nm that is consistent with the PMP standard) was typically 1 × 1014 #/kgfuel. The effect of thermodenuder on the exhaust particles indicated that the nucleation particles consisted mainly of volatile compounds, but sometimes there also existed a non-volatile core. The nucleation mode particles are not controlled by current regulations in Europe. However, these particles consistently form under atmospheric dilution in the plume of the truck and constitute a health risk for the human population that is exposed to those. Average NOx emission was 3.55 g/kWh during the test, whereas the Euro IV emission limit over transient testing is 3.5 g NOx/kWh. The on-road emission performance of the vehicle was very close to the expected levels, confirming the successful operation of the SCR system of the tested vehicle. Heavy driving conditions such as uphill driving increased both the NOx and particle number emission factors whereas the emission factor for soot particle number remains rather constant.

  20. The SH2 Domain Regulates c-Abl Kinase Activation by a Cyclin-Like Mechanism and Remodulation of the Hinge Motion

    Science.gov (United States)

    Dölker, Nicole; Górna, Maria W.; Sutto, Ludovico; Torralba, Antonio S.; Superti-Furga, Giulio; Gervasio, Francesco L.

    2014-01-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors. PMID:25299346

  1. The SH2 domain regulates c-Abl kinase activation by a cyclin-like mechanism and remodulation of the hinge motion.

    Science.gov (United States)

    Dölker, Nicole; Górna, Maria W; Sutto, Ludovico; Torralba, Antonio S; Superti-Furga, Giulio; Gervasio, Francesco L

    2014-10-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors.

  2. The SH2 domain regulates c-Abl kinase activation by a cyclin-like mechanism and remodulation of the hinge motion.

    Directory of Open Access Journals (Sweden)

    Nicole Dölker

    2014-10-01

    Full Text Available Regulation of the c-Abl (ABL1 tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL. Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2 domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors.

  3. EVALUATION OF MERCURY EMISSIONS FROM COAL-FIRED FACILITIES WITH SCR AND FGD SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    J. A. Withum; S.C. Tseng; J. E. Locke

    2004-10-31

    CONSOL Energy Inc., Research & Development (CONSOL), with support from the U.S. Department of Energy, National Energy Technology Laboratory (DOE) is evaluating the effects of selective catalytic reduction (SCR) on mercury (Hg) capture in coal-fired plants equipped with an electrostatic precipitator (ESP) - wet flue gas desulfurization (FGD) combination or a spray dyer absorber--fabric filter (SDA-FF) combination. In this program CONSOL is determining mercury speciation and removal at 10 coal-fired facilities. The objectives are (1) to evaluate the effect of SCR on mercury capture in the ESP-FGD and SDA-FF combinations at coal-fired power plants, (2) evaluate the effect of catalyst degradation on mercury capture; (3) evaluate the effect of low load operation on mercury capture in an SCR-FGD system, and (4) collect data that could provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on Hg speciation and the efficacy of different FGD technologies for Hg capture. This document, the second in a series of topical reports, describes the results and analysis of mercury sampling performed on a 330 MW unit burning a bituminous coal containing 1.0% sulfur. The unit is equipped with a SCR system for NOx control and a spray dryer absorber for SO{sub 2} control followed by a baghouse unit for particulate emissions control. Four sampling tests were performed in March 2003. Flue gas mercury speciation and concentrations were determined at the SCR inlet, air heater outlet (ESP inlet), and at the stack (FGD outlet) using the Ontario Hydro method. Process stream samples for a mercury balance were collected to coincide with the flue gas measurements. Due to mechanical problems with the boiler feed water pumps, the actual gross output was between 195 and 221 MW during the tests. The results showed that the SCR/air heater combination oxidized nearly 95% of the elemental mercury. Mercury removal, on a

  4. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    OpenAIRE

    Wang Zheng; Ruiqi Cai; Laura Hofmann; Vasyl Nesin; Qiaolin Hu; Wentong Long; Mohammad Fatehi; Xiong Liu; Shaimaa Hussein; Tim Kong; Jingru Li; Peter E. Light; Jingfeng Tang; Veit Flockerzi; Leonidas Tsiokas

    2018-01-01

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function ...

  5. Structure of the second RRM domain of Nrd1, a fission yeast MAPK target RNA binding protein, and implication for its RNA recognition and regulation

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Ayaho; Kanaba, Teppei [Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji 192-0397 (Japan); Satoh, Ryosuke [Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku 141-0021, Tokyo (Japan); Fujiwara, Toshinobu [Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku 141-0021, Tokyo (Japan); Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku,Nagoya 467-8603 (Japan); Ito, Yutaka [Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji 192-0397 (Japan); Sugiura, Reiko [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502 (Japan); Mishima, Masaki, E-mail: mishima-masaki@tmu.ac.jp [Graduate School of Science and Engineering, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji 192-0397 (Japan)

    2013-07-19

    Highlights: •Solution structure of the second RRM of Nrd1 was determined. •RNA binding site of the second RRM was estimated. •Regulatory mechanism of RNA binding by phosphorylation is discussed. -- Abstract: Negative regulator of differentiation 1 (Nrd1) is known as a negative regulator of sexual differentiation in fission yeast. Recently, it has been revealed that Nrd1 also regulates cytokinesis, in which physical separation of the cell is achieved by a contractile ring comprising many proteins including actin and myosin. Cdc4, a myosin II light chain, is known to be required for cytokinesis. Nrd1 binds and stabilizes Cdc4 mRNA, and thereby suppressing the cytokinesis defects of the cdc4 mutants. Interestingly, Pmk1 MAPK phosphorylates Nrd1, resulting in markedly reduced RNA binding activity. Furthermore, Nrd1 localizes to stress granules in response to various stresses, and Pmk1 phosphorylation enhances the localization. Nrd1 consists of four RRM domains, although the mechanism by which Pmk1 regulates the RNA binding activity of Nrd1 is unknown. In an effort to delineate the relationship between Nrd1 structure and function, we prepared each RNA binding domain of Nrd1 and examined RNA binding to chemically synthesized oligo RNA using NMR. The structure of the second RRM domain of Nrd1 was determined and the RNA binding site on the second RRM domain was mapped by NMR. A plausible mechanism pertaining to the regulation of RNA binding activity by phosphorylation is also discussed.

  6. Structure of the second RRM domain of Nrd1, a fission yeast MAPK target RNA binding protein, and implication for its RNA recognition and regulation

    International Nuclear Information System (INIS)

    Kobayashi, Ayaho; Kanaba, Teppei; Satoh, Ryosuke; Fujiwara, Toshinobu; Ito, Yutaka; Sugiura, Reiko; Mishima, Masaki

    2013-01-01

    Highlights: •Solution structure of the second RRM of Nrd1 was determined. •RNA binding site of the second RRM was estimated. •Regulatory mechanism of RNA binding by phosphorylation is discussed. -- Abstract: Negative regulator of differentiation 1 (Nrd1) is known as a negative regulator of sexual differentiation in fission yeast. Recently, it has been revealed that Nrd1 also regulates cytokinesis, in which physical separation of the cell is achieved by a contractile ring comprising many proteins including actin and myosin. Cdc4, a myosin II light chain, is known to be required for cytokinesis. Nrd1 binds and stabilizes Cdc4 mRNA, and thereby suppressing the cytokinesis defects of the cdc4 mutants. Interestingly, Pmk1 MAPK phosphorylates Nrd1, resulting in markedly reduced RNA binding activity. Furthermore, Nrd1 localizes to stress granules in response to various stresses, and Pmk1 phosphorylation enhances the localization. Nrd1 consists of four RRM domains, although the mechanism by which Pmk1 regulates the RNA binding activity of Nrd1 is unknown. In an effort to delineate the relationship between Nrd1 structure and function, we prepared each RNA binding domain of Nrd1 and examined RNA binding to chemically synthesized oligo RNA using NMR. The structure of the second RRM domain of Nrd1 was determined and the RNA binding site on the second RRM domain was mapped by NMR. A plausible mechanism pertaining to the regulation of RNA binding activity by phosphorylation is also discussed

  7. Parameter estimation and analysis of an automotive heavy-duty SCR catalyst model

    DEFF Research Database (Denmark)

    Åberg, Andreas; Widd, Anders; Abildskov, Jens

    2017-01-01

    A single channel model for a heavy-duty SCR catalyst was derived based on first principles. The model considered heat and mass transfer between the channel gas phase and the wash coat phase. The parameters of the kinetic model were estimated using bench-scale monolith isothermal data. Validation ...

  8. Adaptive Model Predictive Control of Diesel Engine Selective Catalytic Reduction (SCR) Systems

    Science.gov (United States)

    McKinley, Thomas L.

    2009-01-01

    Selective catalytic reduction or SCR is coming into worldwide use for diesel engine emissions reduction for on- and off-highway vehicles. These applications are characterized by broad operating range as well as rapid and unpredictable changes in operating conditions. Significant nonlinearity, input and output constraints, and stringent performance…

  9. SCR activity of conformed CuOx/ZrO2-SO4 catalysts

    DEFF Research Database (Denmark)

    Rasmussen, Søren Birk; Yates, Malcolm; Due-Hansen, Johannes

    2010-01-01

    CuOX/ZrO2-SO4 catalysts have been synthesised as conformed materials with the use of sepiolite as agglomerant and the performance in the NH3-SCR reaction with relation to biomass fired boiler units have been studied. The optimal Cu-loading of the catalysts is 3 wt.% CuO, both in terms of activity...

  10. Deactivation of vanadia-based commercial SCR catalysts by polyphosphoric acids

    DEFF Research Database (Denmark)

    Castellino, Francesco; Rasmussen, Søren Birk; Jensen, Anker Degn

    2008-01-01

    Commercial vanadia-based SCR monoliths have been exposed to flue gases in a pilot-scale Setup into which phosphoric acid has been added and the deactivation has been followed during the exposure time. Separate measurements by SMPS showed that the phosphoric acid formed polyphosphoric acid aerosols...

  11. Low cost SCR lamp driver indicates contents of digital computer registers

    Science.gov (United States)

    Cliff, R. A.

    1967-01-01

    Silicon Controlled Rectifier /SCR/ lamp driver is adapted for use in integrated circuit digital computers where it indicates the contents of the various registers. The threshold voltage at which visual indication begins is very sharply defined and can be adjusted to suit particular system requirements.

  12. Training self-assessment and task-selection skills to foster self-regulated learning: Do trained skills transfer across domains?

    Science.gov (United States)

    Raaijmakers, Steven F; Baars, Martine; Paas, Fred; van Merriënboer, Jeroen J G; van Gog, Tamara

    2018-01-01

    Students' ability to accurately self-assess their performance and select a suitable subsequent learning task in response is imperative for effective self-regulated learning. Video modeling examples have proven effective for training self-assessment and task-selection skills, and-importantly-such training fostered self-regulated learning outcomes. It is unclear, however, whether trained skills would transfer across domains. We investigated whether skills acquired from training with either a specific, algorithmic task-selection rule or a more general heuristic task-selection rule in biology would transfer to self-regulated learning in math. A manipulation check performed after the training confirmed that both algorithmic and heuristic training improved task-selection skills on the biology problems compared with the control condition. However, we found no evidence that students subsequently applied the acquired skills during self-regulated learning in math. Future research should investigate how to support transfer of task-selection skills across domains.

  13. TaUBA, a UBA domain-containing protein in wheat (Triticum aestivum L.), is a negative regulator of salt and drought stress response in transgenic Arabidopsis.

    Science.gov (United States)

    Li, Xiao; Zhang, Shuang-shuang; Ma, Jun-xia; Guo, Guang-yan; Zhang, Xue-yong; Liu, Xu; Bi, Cai-li

    2015-05-01

    TaUBA functions as a negative regulator of salt and drought stress response in transgenic Arabidopsis, either the UBA domain or the zinc finger domain is crucial for TaUBA's function. TaUBA (DQ211935), which is a UBA domain-containing protein in wheat, was cloned and functionally characterized. Southern blot suggested that TaUBA is a low copy gene in common wheat. qRT-PCR assay showed that the expression of TaUBA was strongly induced by salt and drought stress. When suffering from drought and salt stresses, lower proline content and much higher MDA content in the TaUBA overexpressors were observed than those of the wild-type control, suggesting TaUBA may function as a negative regulator of salt and drought stress response in plants. To study whether the UBA domain or the zinc finger domain affects the function of TaUBA, TaUBAΔUBA (deletion of UBA domain) and TaUBA-M (Cys464Gly and Cys467Gly) overexpression vectors were constructed and transformed into Arabidopsis. Upon drought and salt stresses, the TaUBAΔUBA-and TaUBA-M-overexpressed plants accumulated much more proline and lower MDA than the wild-type control, the TaUBA-overexpressors lost water more quickly than TaUBAΔUBA-and TaUBA-M-overexpressed plants as well as the wild-type control, suggesting that overexpression of TaUBAΔUBA or TaUBA-M improved the drought and salt tolerance of transgenic Arabidopsis plants and the possibility of ubiquitination role in the regulation of osmolyte synthesis and oxidative stress responses in mediating stress tolerance. qRT-PCR assay of stress-related genes in transgenic plants upon drought and salt stresses suggested that TaUBA may function through down-regulating some stress related-transcription factors and by regulating P5CSs to cope with osmotic stress.

  14. Jasmonate ZIM-domain (JAZ protein regulates host and nonhost pathogen-induced cell death in tomato and Nicotiana benthamiana.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ishiga

    Full Text Available The nonhost-specific phytotoxin coronatine (COR produced by several pathovars of Pseudomonas syringae functions as a jasmonic acid-isoleucine (JA-Ile mimic and contributes to disease development by suppressing plant defense responses and inducing reactive oxygen species in chloroplast. It has been shown that the F-box protein CORONATINE INSENSITIVE 1 (COI1 is the receptor for COR and JA-Ile. JASMONATE ZIM DOMAIN (JAZ proteins act as negative regulators for JA signaling in Arabidopsis. However, the physiological significance of JAZ proteins in P. syringae disease development and nonhost pathogen-induced hypersensitive response (HR cell death is not completely understood. In this study, we identified JAZ genes from tomato, a host plant for P. syringae pv. tomato DC3000 (Pst DC3000, and examined their expression profiles in response to COR and pathogens. Most JAZ genes were induced by COR treatment or inoculation with COR-producing Pst DC3000, but not by the COR-defective mutant DB29. Tomato SlJAZ2, SlJAZ6 and SlJAZ7 interacted with SlCOI1 in a COR-dependent manner. Using virus-induced gene silencing (VIGS, we demonstrated that SlJAZ2, SlJAZ6 and SlJAZ7 have no effect on COR-induced chlorosis in tomato and Nicotiana benthamiana. However, SlJAZ2-, SlJAZ6- and SlJAZ7-silenced tomato plants showed enhanced disease-associated cell death to Pst DC3000. Furthermore, we found delayed HR cell death in response to the nonhost pathogen Pst T1 or a pathogen-associated molecular pattern (PAMP, INF1, in SlJAZ2- and SlJAZ6-silenced N. benthamiana. These results suggest that tomato JAZ proteins regulate the progression of cell death during host and nonhost interactions.

  15. Regulation of the Incorporation of Tissue Factor into Microparticles by Serine Phosphorylation of the Cytoplasmic Domain of Tissue Factor*

    Science.gov (United States)

    Collier, Mary E. W.; Ettelaie, Camille

    2011-01-01

    The mechanisms that regulate the incorporation and release of tissue factors (TFs) into cell-derived microparticles are as yet unidentified. In this study, we have explored the regulation of TF release into microparticles by the phosphorylation of serine residues within the cytoplasmic domain of TF. Wild-type and mutant forms of TF, containing alanine and aspartate substitutions at Ser253 and Ser258, were overexpressed in coronary artery and dermal microvascular endothelial cells and microparticle release stimulated with PAR2 agonist peptide (PAR2-AP). The release of TF antigen and activity was then monitored. In addition, the phosphorylation state of the two serine residues within the released microparticles and the cells was monitored for 150 min. The release of wild-type TF as procoagulant microparticles peaked at 90 min and declined thereafter in both cell types. The TF within these microparticles was phosphorylated at Ser253 but not at Ser258. Aspartate substitution of Ser253 resulted in rapid release of TF antigen but not activity, whereas TF release was reduced and delayed by alanine substitution of Ser253 or aspartate substitution of Ser258. Alanine substitution of Ser258 prolonged the release of TF following PAR2-AP activation. The release of TF was concurrent with phosphorylation of Ser253 and was followed by dephosphorylation at 120 min and phosphorylation of Ser258. We propose a sequential mechanism in which the phosphorylation of Ser253 through PAR2 activation results in the incorporation of TF into microparticles, simultaneously inducing Ser258 phosphorylation. Phosphorylation of Ser258 in turn promotes the dephosphorylation of Ser253 and suppresses the release of TF. PMID:21310953

  16. Special requirements for the fluid mechanical design of hard coal-fired SCR retrofit units

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    The system design of high-dust SCR units for retrofits is a challenge that is to be mastered in order to meet the fluid mechanical requirements. Retrofitting power plants with NOx control technologies is a cost-intensive adventure that many utilities are undertaking. Except for a few recent new boiler installations, SCR installations must be considered as retrofit projects. In most cases the limitation of space on site entails unfavorable conditions that do not allow appropriate upstream conditions for SCR catalysts. To comply with the requirements of high performance DeNOx systems and to lower the investment costs for retrofit units, several technical solutions and concepts for the reactor layout, for NOx and dust distribution, for flow stabilization in diffusers, and advanced ammonia injection systems are explained in this paper. Balcke-Duerr offers customer-tailored solutions for flow optimization, which are evaluated by model studies. Physical flow and dust model tests in an appropriate scale provide flexibility to test various engineering concepts. The experience of Balcke-Duerr is based on continuous research and development activities over the last 25 years and more than 350 executed projects for gas flow optimization applications. The success of these installations is a direct result of the key decisions based on the improved fluid mechanical design and proper system integration. This paper also identifies the sensible design particularities and solutions that have two be considered in the fluid mechanical design of high-dust SCR retrofit units. This article demonstrates that the layout of SCR units must be carefully reviewed in order to meet the performance requirements and to avoid problems, i.e. wear, catalyst plugging and ammonia slip. 9 refs., 18 figs.

  17. Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells

    International Nuclear Information System (INIS)

    Sun, Shaowei; Wen, Juan; Qiu, Fei; Yin, Yufang; Xu, Guina; Li, Tianping; Nie, Juan; Xiong, Guozuo; Zhang, Caiping; Liao, Duangfang; Chen, Jianxiong; Tuo, Qinhui

    2016-01-01

    Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626–740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626–740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells. - Highlights: • Daxx C-terminal domain reduces cholesterol levels. • Daxx C-terminal domain binds directly to AR. • The interaction of Daxx C-terminal domain and AR suppresses cholesterol synthesis.

  18. The structure of the first representative of Pfam family PF09836 reveals a two-domain organization and suggests involvement in transcriptional regulation

    International Nuclear Information System (INIS)

    Das, Debanu; Grishin, Nick V.; Kumar, Abhinav; Carlton, Dennis; Bakolitsa, Constantina; Miller, Mitchell D.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grzechnik, Anna; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2009-01-01

    The crystal structure of the NGO1945 gene product from N. gonorrhoeae (UniProt Q5F5IO) reveals that the N-terminal domain assigned as a domain of unknown function (DUF2063) is likely to bind DNA and that the protein may be involved in transcriptional regulation. Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (∼40–99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention

  19. Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

    International Nuclear Information System (INIS)

    Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun

    2016-01-01

    The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

  20. Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun, E-mail: tztong@bjmu.edu.cn

    2016-01-15

    The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

  1. EVALUATION OF MERCURY EMISSIONS FROM COAL-FIRED FACILITIES WITH SCR AND FGD SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Withum; S.C. Tseng; J.E. Locke

    2005-11-01

    CONSOL Energy Inc., Research & Development (CONSOL), with support from the U.S. Department of Energy, National Energy Technology Laboratory (DOE) and the Electric Power Research Institute (EPRI), is evaluating the effects of selective catalytic reduction (SCR) on mercury (Hg) capture in coal-fired plants equipped with an electrostatic precipitator (ESP)--wet flue gas desulfurization (FGD) combination or a spray dryer absorber--fabric filter (SDA-FF) combination. In this program CONSOL is determining mercury speciation and removal at 10 coal-fired facilities. The objectives are (1) to evaluate the effect of SCR on mercury capture in the ESP-FGD and SDA-FF combinations at coal-fired power plants, (2) evaluate the effect of catalyst degradation on mercury capture; (3) evaluate the effect of low load operation on mercury capture in an SCR-FGD system, and (4) collect data that could provide the basis for fundamental scientific insights into the nature of mercury chemistry in flue gas, the catalytic effect of SCR systems on mercury speciation and the efficacy of different FGD technologies for mercury capture. This document, the seventh in a series of topical reports, describes the results and analysis of mercury sampling performed on a 1,300 MW unit burning a bituminous coal containing three percent sulfur. The unit was equipped with an ESP and a limestone-based wet FGD to control particulate and SO2 emissions, respectively. At the time of sampling an SCR was not installed on this unit. Four sampling tests were performed in September 2003. Flue gas mercury speciation and concentrations were determined at the ESP outlet (FGD inlet), and at the stack (FGD outlet) using the Ontario Hydro method. Process stream samples for a mercury balance were collected to coincide with the flue gas measurements. The results show that the FGD inlet flue gas oxidized:elemental mercury ratio was roughly 2:1, with 66% oxidized mercury and 34% elemental mercury. Mercury removal, on a coal

  2. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC regulates inflammasomes

    Directory of Open Access Journals (Sweden)

    Rojanasakul Yon

    2010-05-01

    Full Text Available Abstract Background The apoptotic speck-like protein containing a caspase recruitment domain (ASC is the essential adaptor protein for caspase 1 mediated interleukin (IL-1β and IL-18 processing in inflammasomes. It bridges activated Nod like receptors (NLRs, which are a family of cytosolic pattern recognition receptors of the innate immune system, with caspase 1, resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence, macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1β. Furthermore, we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response, which triggers IL-1β processing and secretion. However, the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor. Methods To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors, IL-1β processing and secretion was investigated by ELISA in inflammasome reconstitution assays, stable expression in THP-1 and J774A1 cells, and by restoring the lack of endogenous ASC in mouse RAW264.7 macrophages. In addition, the localization of ASC and ASC isoforms was determined by immunofluorescence staining. Results The three novel ASC isoforms, ASC-b, ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor, with one of the isoforms even showing an inhibitory effect. Consistently, only the activating isoforms of ASC, ASC and ASC-b, co-localized with NLRP3 and caspase 1, while the inhibitory isoform ASC-c, co-localized only with caspase 1, but not with NLRP3. ASC-d did not co-localize with NLRP3 or with caspase 1 and consistently lacked the ability to function as an

  3. 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.

  4. Poly(ADP-ribosyl)ation of Methyl CpG Binding Domain Protein 2 Regulates Chromatin Structure*

    Science.gov (United States)

    Becker, Annette; Zhang, Peng; Allmann, Lena; Meilinger, Daniela; Bertulat, Bianca; Eck, Daniel; Hofstaetter, Maria; Bartolomei, Giody; Hottiger, Michael O.; Schreiber, Valérie; Leonhardt, Heinrich; Cardoso, M. Cristina

    2016-01-01

    The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphorylation and other posttranslational modifications of MeCP2 have been described recently to modulate its function. Here we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue. Consequently, we found that MeCP2 induced aggregation of pericentric heterochromatin and that its chromatin accumulation was enhanced in poly(ADP-ribose) polymerase (PARP) 1−/− compared with wild-type cells. We mapped the poly(ADP-ribosyl)ation domains and engineered MeCP2 mutation constructs to further analyze potential effects on DNA binding affinity and large-scale chromatin remodeling. Single or double deletion of the poly(ADP-ribosyl)ated regions and PARP inhibition increased the heterochromatin clustering ability of MeCP2. Increased chromatin clustering may reflect increased binding affinity. In agreement with this hypothesis, we found that PARP-1 deficiency significantly increased the chromatin binding affinity of MeCP2 in vivo. These data provide novel mechanistic insights into the regulation of MeCP2-mediated, higher-order chromatin architecture and suggest therapeutic opportunities to manipulate MeCP2 function. PMID:26772194

  5. RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis

    Directory of Open Access Journals (Sweden)

    Zhenzong Fa

    2017-09-01

    Full Text Available Fas-associated death domain (FADD and receptor interacting protein kinase 3 (RIPK3 are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C. neoformans expansion and rapid clinical deterioration in Ripk3−/− and Ripk3−/−Fadd−/− mice. The increased mortality of Ripk3−/− and even more accelerated mortality in Ripk3−/−Fadd−/− mice was attributed to profound pulmonary damage due to neutrophil-dominant infiltration with prominent upregulation of pro-inflammatory cytokines. This phenomenon was partially associated with selective alterations in the apoptotic frequency of some leukocyte subsets, such as eosinophils and neutrophils, in infected Ripk3−/−Fadd−/− mice. In conclusion, our study shows that RIPK3 in concert with FADD serve as physiological “brakes,” preventing the development of excessive inflammation and Th1 bias, which in turn contributes to pulmonary damage and defective fungal clearance. This novel link between the protective effect of FADD and RIPK3 in antifungal defense and sustenance of immune homeostasis may be important for the development of novel immunomodulatory therapies against invasive fungal infections.

  6. SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

    Science.gov (United States)

    Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

    2015-06-01

    Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients

  7. Structure of Thermotoga maritima TM0439: implications for the mechanism of bacterial GntR transcription regulators with Zn2+-binding FCD domains

    International Nuclear Information System (INIS)

    Zheng, Meiying; Cooper, David R.; Grossoehme, Nickolas E.; Yu, Minmin; Hung, Li-Wei; Cieslik, Marcin; Derewenda, Urszula; Lesley, Scott A.; Wilson, Ian A.; Giedroc, David P.; Derewenda, Zygmunt S.

    2009-01-01

    Here, the crystal structure of TM0439, a GntR regulator with an FCD domain found in the Thermotoga maritima genome, is described. The GntR superfamily of dimeric transcription factors, with more than 6200 members encoded in bacterial genomes, are characterized by N-terminal winged-helix DNA-binding domains and diverse C-terminal regulatory domains which provide a basis for the classification of the constituent families. The largest of these families, FadR, contains nearly 3000 proteins with all-α-helical regulatory domains classified into two related Pfam families: FadR-C and FCD. Only two crystal structures of FadR-family members, those of Escherichia coli FadR protein and LldR from Corynebacterium glutamicum, have been described to date in the literature. Here, the crystal structure of TM0439, a GntR regulator with an FCD domain found in the Thermotoga maritima genome, is described. The FCD domain is similar to that of the LldR regulator and contains a buried metal-binding site. Using atomic absorption spectroscopy and Trp fluorescence, it is shown that the recombinant protein contains bound Ni 2+ ions but that it is able to bind Zn 2+ with K d < 70 nM. It is concluded that Zn 2+ is the likely physiological metal and that it may perform either structural or regulatory roles or both. Finally, the TM0439 structure is compared with two other FadR-family structures recently deposited by structural genomics consortia. The results call for a revision in the classification of the FadR family of transcription factors

  8. A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

    Science.gov (United States)

    Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

    2017-08-21

    Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Forkhead-associated (FHA) Domain Containing ABC Transporter Rv1747 Is Positively Regulated by Ser/Thr Phosphorylation in Mycobacterium tuberculosis*

    Science.gov (United States)

    Spivey, Vicky L.; Molle, Virginie; Whalan, Rachael H.; Rodgers, Angela; Leiba, Jade; Stach, Lasse; Walker, K. Barry; Smerdon, Stephen J.; Buxton, Roger S.

    2011-01-01

    One major signaling method employed by Mycobacterium tuberculosis, the causative agent of tuberculosis, is through reversible phosphorylation of proteins mediated by protein kinases and phosphatases. This study concerns one of these enzymes, the serine/threonine protein kinase PknF, that is encoded in an operon with Rv1747, an ABC transporter that is necessary for growth of M. tuberculosis in vivo and contains two forkhead-associated (FHA) domains. FHA domains are phosphopeptide recognition motifs that specifically recognize phosphothreonine-containing epitopes. Experiments to determine how PknF regulates the function of Rv1747 demonstrated that phosphorylation occurs on two specific threonine residues, Thr-150 and Thr-208. To determine the in vivo consequences of phosphorylation, infection experiments were performed in bone marrow-derived macrophages and in mice using threonine-to-alanine mutants of Rv1747 that prevent specific phosphorylation and revealed that phosphorylation positively modulates Rv1747 function in vivo. The role of the FHA domains in this regulation was further demonstrated by isothermal titration calorimetry, using peptides containing both phosphothreonine residues. FHA-1 domain mutation resulted in attenuation in macrophages highlighting the critical role of this domain in Rv1747 function. A mutant deleted for pknF did not, however, have a growth phenotype in an infection, suggesting that other kinases can fulfill its role when it is absent. This study provides the first information on the molecular mechanism(s) regulating Rv1747 through PknF-dependent phosphorylation but also indicates that phosphorylation activates Rv1747, which may have important consequences in regulating growth of M. tuberculosis. PMID:21622570

  10. Critical Role of the Src Homology 2 (SH2) Domain of Neuronal SH2B1 in the Regulation of Body Weight and Glucose Homeostasis in Mice

    OpenAIRE

    Morris, David L.; Cho, Kae Won; Rui, Liangyou

    2010-01-01

    SH2B1 is an SH2 domain-containing adaptor protein that plays a key role in the regulation of energy and glucose metabolism in both rodents and humans. Genetic deletion of SH2B1 in mice results in obesity and type 2 diabetes. Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans. In cultured cells, SH2B1 promotes leptin and insulin signaling by binding via its SH2 domain to phosphorylated tyrosines ...

  11. SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

    Science.gov (United States)

    McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

    1992-01-01

    The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

  12. Major issues in the design and construction of the stellarator of Costa Rica: SCR-1

    International Nuclear Information System (INIS)

    Mora, J; Vargas, V I; Villegas, L F; Barillas, L; Monge, J I; Rivas, L

    2012-01-01

    This paper aims at briefly describing the design and construction issues of the stellarator of Costa Rica 1 (SCR-1). The SCR-1 is a small modular Stellarator for magnetic confinement of plasma developed by the Plasma Physics Group of the Instituto Tecnologico de Costa Rica (ITCR). The SCR-1 is based on the small Spanish Stellarator UST 1 (Ultra Small Torus 1), created by Eng. Vicente Queral. These mains issues consist of the size of the Stellarator, closeness between coils, coupling of ECH to the vacuum chamber and the device for support. The size has become a problem because the vacuum chamber does not allow a lot of space to attach diagnosis devices, the heating system, the vacuum system and the very same support of the chamber. As a result of this lack of space, the Stellarator's coils are placed very close to each other; this means that two of the coils around of the vacuum chamber clash and cannot be placed as designed. The issue regarding the coupling of the ECH (electron cyclotron radio-frequency) to the vacuum chamber comprises the fact that the wave guide with rectangular shape does not match the CF port with circular shape on the vacuum chamber. In addition, the device for supporting the Stellarator has presented a challenge because of its size and the placement of the coils; in other words, there is not enough space between the ports and coils in the Stellarator to place appropriately the device for support.

  13. The effect of the gas composition on hydrogen-assisted NH3-SCR over Ag/Al2O3

    DEFF Research Database (Denmark)

    Tamm, Stefanie; Fogel, Sebastian; Gabrielsson, Pär

    2013-01-01

    In addition to high activity in hydrocarbon-SCR, Ag/Al2O3 catalysts show excellent activity for NOx reduction for H2-assisted NH3-SCR already at 200°C. Here, we study the influence of different gas compositions on the activity of a pre-sulfated 6wt% Ag/Al2O3 catalyst for NOx reduction, and oxidat...

  14. Effects of NOX Storage Component on Ammonia Formation in TWC for Passive SCR NOX Control in Lean Gasoline Engines

    Energy Technology Data Exchange (ETDEWEB)

    Prikhodko, Vitaly Y. [ORNL; Pihl, Josh A. [ORNL; Toops, Todd J. [ORNL; Parks, II, James E. [ORNL

    2018-04-01

    A prototype three-way catalyst (TWC) with NOX storage component was evaluated for ammonia (NH3) generation on a 2.0-liter BMW lean burn gasoline direct injection engine as a component in a passive ammonia selective catalytic reduction (SCR) system. The passive NH3 SCR system is a potential approach for controlling nitrogen oxides (NOX) emissions from lean burn gasoline engines. In this system, NH3 is generated over a close-coupled TWC during periodic slightly-rich engine operation and subsequently stored on an underfloor SCR catalyst. Upon switching to lean, NOX passes through the TWC and is reduced by the stored NH3 on the SCR catalyst. Adding a NOX storage component to a TWC provides two benefits in the context of a passive SCR system: (1) enabling longer lean operation by storing NOX upstream and preserving NH3 inventory on the downstream SCR catalyst; and (2) increasing the quantity and rate of NH3 production during rich operation. Since the fuel penalty associated with passive SCR NOX control depends on the fraction of time that the engine is running rich rather than lean, both benefits (longer lean times and shorter rich times achieved via improved NH3 production) will decrease the passive SCR fuel penalty. However, these benefits are primarily realized at low to moderate temperatures (300-500 °C), where the NOX storage component is able to store NOX, with little to no benefit at higher temperatures (>500 °C), where NOX storage is no longer effective. This study discusses engine parameters and control strategies affecting the NH3 generation over a TWC with NOX storage component.

  15. Hybrid selective noncatalytic reduction (SNCR)/selective catalytic reduction (SCR) for NOx removal using low-temperature SCR with Mn-V2O5/TiO2 catalyst.

    Science.gov (United States)

    Choi, Sung-Woo; Choi, Sang-Ki; Bae, Hun-Kyun

    2015-04-01

    A hybrid selective noncatalytic reduction/selective catalytic reduction (SNCR/SCR) system that uses two types of technology, low-temperature SCR process and SNCR process, was designed to develop nitrogen oxide (NOx) reduction technology. SCR was conducted with space velocity (SV)=2400 hr(-1) and hybrid SNCR/SCR with SV=6000 hr(-1), since the study focused on reducing the amount of catalyst and both achieved 98% NOx reduction efficiency. Characteristics of NOx reduction by NH3 were studied for low-temperature SCR system at 150 °C using Mn-V2O5/TiO2 catalyst. Mn-added V2O5/TiO2 catalyst was produced, and selective catalyst reduction of NOx by NH3 was experimented. NOx reduction rate according to added Mn content in Mn-V2O5/TiO2 catalyst was studied with varying conditions of reaction temperature, normalized stoichiometric ratio (NSR), SV, and O2 concentration. In the catalyst experiment according to V2O5 concentration, 1 wt.% V2O5 catalyst showed the highest NOx reduction rate: 98% reduction at temperature window of 200~250 °C. As a promoter of the V2O5 catalyst, 5 wt.% Mn was added, and the catalyst showed 47~90% higher efficiency even with low temperatures, 100~200 °C. Mn-V2O5/TiO2 catalyst, prepared by adding 5 wt.% Mn in V2O5/TiO2 catalyst, showed increments of catalyst activation at 150 °C as well as NOx reduction. Mn-V2O5/TiO2 catalyst showed 8% higher rate for NOx reduction compared with V2O5/TiO2 catalyst in 150 °C SCR. Thus, (5 wt.%)Mn-(1 wt.%)V2O5/TiO2 catalyst was applied in SCR of hybrid SNCR/SCR system of low temperature at 150 °C. Low-temperature SCR hybrid SNCR/SCR (150 °C) system and hybrid SNCR/SCR (350 °C) showed 91~95% total reduction rate with conditions of SV=2400~6000 hr(-1) SCR and 850~1050 °C SNCR, NSR=1.5~2.0, and 5% O2. Hybrid SNCR/SCR (150 °C) system proved to be more effective than the hybrid SNCR/SCR (350 °C) system at low temperature. NOx control is very important, since they are the part of greenhouse gases as well as the

  16. Characteristics of Sucrose Transport through the Sucrose-Specific Porin ScrY Studied by Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Liping eSun

    2016-02-01

    Full Text Available Sucrose-specific porin (ScrY is a transmembrane protein that allows for the uptake of sucrose under growth-limiting conditions. The crystal structure of ScrY was resolved before by X-ray crystallography, both in its uncomplexed form and with bound sucrose. However, little is known about the molecular characteristics of the transport mechanism of ScrY. To date, there has not yet been any clear demonstration for sucrose transport through the ScrY.Here, the dynamics of the ScrY trimer embedded in a phospholipid bilayer as well as the characteristics of sucrose translocation were investigated by means of atomistic molecular dynamics (MD simulations. The potential of mean force (PMF for sucrose translocation through the pore showed two main energy barriers within the constriction region of ScrY. Energy decomposition allowed to pinpoint three aspartic acids as key residues opposing the passage of sucrose, all located within the L3 loop. Mutation of two aspartic acids to uncharged residues resulted in an accordingly modified electrostatics and decreased PMF barrier. The chosen methodology and results will aid in the design of porins with modified transport specificities.

  17. Crystallization and preliminary X-ray analysis of the receiver domain of a putative response regulator, BPSL0128, from Burkholderia pseudomallei

    International Nuclear Information System (INIS)

    Abd Aziz, Abd Ghani; Sedelnikova, Svetlana E.; Ruzheinikov, Sergey N.; Thorpe, Simon; Mohamed, Rahmah; Nathan, Sheila; Rafferty, John B.; Baker, Patrick J.; Rice, David W.

    2012-01-01

    The receiver domain of a putative response regulator from B. pseudomallei, BPSL0128, has been crystallized in a form suitable for X-ray analysis. bpsl0128, a gene encoding a putative response regulator from Burkholderia pseudomallei strain D286, has been cloned into a pETBLUE-1 vector system, overexpressed in Escherichia coli and purified. The full-length protein is degraded during purification to leave a fragment corresponding to the putative receiver domain, and crystals of this protein that diffracted to beyond 1.75 Å resolution have been grown by the hanging-drop vapour-diffusion technique using PEG 6000 as the precipitant. The crystals belonged to one of the enantiomorphic pair of space groups P3 1 21 and P3 2 21, with unit-cell parameters a = b = 65.69, c = 105.01 Å and either one or two molecules in the asymmetric unit

  18. Design and testing of an independently controlled urea SCR retrofit system for the reduction of NOx emissions from marine diesels.

    Science.gov (United States)

    Johnson, Derek R; Bedick, Clinton R; Clark, Nigel N; McKain, David L

    2009-05-15

    Diesel engine emissions for on-road, stationary and marine applications are regulated in the United States via standards set by the Environmental Protection Agency (EPA). A major component of diesel exhaust that is difficult to reduce is nitrogen oxides (NOx). Selective catalytic reduction (SCR) has been in use for many years for stationary applications, including external combustion boilers, and is promising for NOx abatement as a retrofit for mobile applications where diesel compression ignition engines are used. The research presented in this paper is the first phase of a program focused on the reduction of NOx by use of a stand-alone urea injection system, applicable to marine diesel engines typical of work boats (e.g., tugs). Most current urea SCR systems communicate with engine controls to predict NOx emissions based on signals such as torque and engine speed, however many marine engines in use still employ mechanical injection technology and lack electronic communication abilities. The system developed and discussed in this paper controls NOx emissions independentof engine operating parameters and measures NOx and exhaust flow using the following exhaust sensor inputs: absolute pressure, differential pressure, temperature, and NOx concentration. These sensor inputs were integrated into an independent controller and open loop architecture to estimate the necessary amount of urea needed, and the controller uses pulse width modulation (PWM) to power an automotive fuel injector for airless urea delivery. The system was tested in a transient test cell on a 350 hp engine certified at 4 g/bhp-hr of NOx, with a goal of reducing the engine out NOx levels by 50%. NOx reduction capabilities of 41-67% were shown on the non road transient cycle (NRTC) and ICOMIA E5 steady state cycles with system optimization during testing to minimize the dilute ammonia slip to cycle averages of 5-7 ppm. The goal of 50% reduction of NOx can be achieved dependent upon cycle. Further

  19. The Caenorhabditis elegans iodotyrosine deiodinase ortholog SUP-18 functions through a conserved channel SC-box to regulate the muscle two-pore domain potassium channel SUP-9.

    Directory of Open Access Journals (Sweden)

    Ignacio Perez de la Cruz

    2014-02-01

    Full Text Available Loss-of-function mutations in the Caenorhabditis elegans gene sup-18 suppress the defects in muscle contraction conferred by a gain-of-function mutation in SUP-10, a presumptive regulatory subunit of the SUP-9 two-pore domain K(+ channel associated with muscle membranes. We cloned sup-18 and found that it encodes the C. elegans ortholog of mammalian iodotyrosine deiodinase (IYD, an NADH oxidase/flavin reductase that functions in iodine recycling and is important for the biosynthesis of thyroid hormones that regulate metabolism. The FMN-binding site of mammalian IYD is conserved in SUP-18, which appears to require catalytic activity to function. Genetic analyses suggest that SUP-10 can function with SUP-18 to activate SUP-9 through a pathway that is independent of the presumptive SUP-9 regulatory subunit UNC-93. We identified a novel evolutionarily conserved serine-cysteine-rich region in the C-terminal cytoplasmic domain of SUP-9 required for its specific activation by SUP-10 and SUP-18 but not by UNC-93. Since two-pore domain K(+ channels regulate the resting membrane potentials of numerous cell types, we suggest that the SUP-18 IYD regulates the activity of the SUP-9 channel using NADH as a coenzyme and thus couples the metabolic state of muscle cells to muscle membrane excitability.

  20. The SRC homology 2 domain of Rin1 mediates its binding to the epidermal growth factor receptor and regulates receptor endocytosis.

    Science.gov (United States)

    Barbieri, M Alejandro; Kong, Chen; Chen, Pin-I; Horazdovsky, Bruce F; Stahl, Philip D

    2003-08-22

    Activated epidermal growth factor receptors (EGFRs) recruit intracellular proteins that mediate receptor signaling and endocytic trafficking. Rin1, a multifunctional protein, has been shown to regulate EGFR internalization (1). Here we show that EGF stimulation induces a specific, rapid, and transient membrane recruitment of Rin1 and that recruitment is dependent on the Src homology 2 (SH2) domain of Rin1. Immunoprecipitation of EGFR is accompanied by co-immunoprecipitation of Rin1 in a time- and ligand-dependent manner. Association of Rin1 and specifically the SH2 domain of Rin1 with the EGFR was dependent on tyrosine phosphorylation of the intracellular domain of the EGFR. The recruitment of Rin1, observed by light microscopy, indicated that although initially cytosolic, Rin1 was recruited to both plasma membrane and endosomes following EGF addition. Moreover, the expression of the SH2 domain of Rin1 substantially impaired the internalization of EGF without affecting internalization of transferrin. Finally, we found that Rin1 co-immunoprecipitated with a number of tyrosine kinase receptors but not with cargo endocytic receptors. These results indicate that Rin1 provides a link via its SH2 domain between activated tyrosine kinase receptors and the endocytic pathway through the recruitment and activation of Rab5a.

  1. Self-perceived successful weight regulators are less affected by self-regulatory depletion in the domain of eating behavior.

    Science.gov (United States)

    Friese, Malte; Engeler, Michèle; Florack, Arnd

    2015-01-01

    Weight loss and maintenance goals are highly prevalent in many affluent societies, but many weight regulators are not successful in the long term. Research started to reveal psychological mechanisms that help successful weight regulators in being successful. In the present study, we tested the assumption that these mechanisms facilitate successful self-regulation particularly under conditions of self-regulatory depletion. Participants exerted or did not exert self-control in a first task before engaging in a taste test of a tempting but unhealthy food. Participants who had initially exerted self-control ate more than participants in the control condition. This effect was reduced in self-perceived successful weight regulators as compared to perceived unsuccessful self-regulators. A reduced susceptibility to self-regulatory depletion may be an important contributor to long-term weight regulation success in successful weight regulators. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Crystal structure of Thermotoga maritima TM0439: implications for the mechanism of bacterial GntR transcription regulators with Zn2+-binding FCD domains

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Meiying; Cooper, David; Grossoehmerb, Nickolas; Yu, Minmin; Hung, Li-Wei; Cieslik, Murcin; Derewendaro, Urszula; Lesley, Scott; Wilson, Ian; Giedrocb, David; Derewenda, Zygmunt

    2009-06-06

    The GntR superfamily of dimeric transcription factors, with more than 6200 members encoded in bacterial genomes, are characterized by N-terminal winged helix (WH) DNA-binding domains and diverse C-terminal, regulatory domains, which provide a basis for the classification of the constituent families. The largest of these families, FadR, contains nearly 3000 proteins with all a-helical regulatory domains classified into two related Pfam families: FadR{_}C and FCD. Only two crystal structures of the FadR family members, i.e. the E. coli FadR protein and the LldR from C. glutamicum, have been described to date in literature. Here we describe the crystal structure of TM0439, a GntR regulator with an FCD domain, found in the Thermotoga maritima genome. The FCD domain is similar to that of the LldR regulator, and contains a buried metal binding site. Using atomic absorption spectroscopy and Trp fluorescence, we show that the recombinant protein contains bound Ni{sup 2+} ions, but it is able to bind Zn{sup 2+} with K{sub D} < 70 nM . We conclude that Zn{sup 2+} is the likely physiological metal, where it may perform either or both structural and regulatory roles. Finally, we compare the TM0439 structure to two other FadR family structures recently deposited by Structural Genomics consortia. The results call for a revision in the classification of the FadR family of transcription factors.

  3. The BEACH Domain Protein SPIRRIG Is Essential for Arabidopsis Salt Stress Tolerance and Functions as a Regulator of Transcript Stabilization and Localization.

    Directory of Open Access Journals (Sweden)

    Alexandra Steffens

    2015-07-01

    Full Text Available Members of the highly conserved class of BEACH domain containing proteins (BDCPs have been established as broad facilitators of protein-protein interactions and membrane dynamics in the context of human diseases like albinism, bleeding diathesis, impaired cellular immunity, cancer predisposition, and neurological dysfunctions. Also, the Arabidopsis thaliana BDCP SPIRRIG (SPI is important for membrane integrity, as spi mutants exhibit split vacuoles. In this work, we report a novel molecular function of the BDCP SPI in ribonucleoprotein particle formation. We show that SPI interacts with the P-body core component DECAPPING PROTEIN 1 (DCP1, associates to mRNA processing bodies (P-bodies, and regulates their assembly upon salt stress. The finding that spi mutants exhibit salt hypersensitivity suggests that the local function of SPI at P-bodies is of biological relevance. Transcriptome-wide analysis revealed qualitative differences in the salt stress-regulated transcriptional response of Col-0 and spi. We show that SPI regulates the salt stress-dependent post-transcriptional stabilization, cytoplasmic agglomeration, and localization to P-bodies of a subset of salt stress-regulated mRNAs. Finally, we show that the PH-BEACH domains of SPI and its human homolog FAN (Factor Associated with Neutral sphingomyelinase activation interact with DCP1 isoforms from plants, mammals, and yeast, suggesting the evolutionary conservation of an association of BDCPs and P-bodies.

  4. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2.

    Science.gov (United States)

    Zheng, Wang; Cai, Ruiqi; Hofmann, Laura; Nesin, Vasyl; Hu, Qiaolin; Long, Wentong; Fatehi, Mohammad; Liu, Xiong; Hussein, Shaimaa; Kong, Tim; Li, Jingru; Light, Peter E; Tang, Jingfeng; Flockerzi, Veit; Tsiokas, Leonidas; Chen, Xing-Zhen

    2018-02-06

    Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C) that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2

    Directory of Open Access Journals (Sweden)

    Wang Zheng

    2018-02-01

    Full Text Available Transient receptor potential (TRP channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2, with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3 N and C termini (N-C that is functionally essential. The interaction was mediated by aromatic Trp81 in pre-S1 domain and cationic Lys568 in TRP-like domain. Structure-function analyses revealed similar N-C interaction in TRPP2 as well as TRPM8/-V1/-C4 via highly conserved tryptophan and lysine/arginine residues. PIP2 bound to cationic residues in TRPP3, including K568, thereby disrupting the N-C interaction and negatively regulating TRPP3. PIP2 had similar negative effects on TRPP2. Interestingly, we found that PIP2 facilitates the N-C interaction in TRPM8/-V1, resulting in channel potentiation. The intramolecular N-C interaction might represent a shared mechanism underlying the gating and PIP2 regulation of TRP channels.

  6. Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice.

    Science.gov (United States)

    Morris, David L; Cho, Kae Won; Rui, Liangyou

    2010-08-01

    SH2B1 is an SH2 domain-containing adaptor protein that plays a key role in the regulation of energy and glucose metabolism in both rodents and humans. Genetic deletion of SH2B1 in mice results in obesity and type 2 diabetes. Single-nucleotide polymorphisms in the SH2B1 loci and chromosomal deletions of the SH2B1 loci associate with obesity and insulin resistance in humans. In cultured cells, SH2B1 promotes leptin and insulin signaling by binding via its SH2 domain to phosphorylated tyrosines in Janus kinase 2 and the insulin receptor, respectively. Here we generated three lines of mice to analyze the role of the SH2 domain of SH2B1 in the central nervous system. Transgenic mice expressing wild-type, SH2 domain-defective (R555E), or SH2 domain-alone (DeltaN503) forms of SH2B1 specifically in neurons were crossed with SH2B1 knockout mice to generate KO/SH2B1, KO/R555E, or KO/DeltaN503 compound mutant mice. R555E had a replacement of Arg(555) with Glu within the SH2 domain. DeltaN503 contained an intact SH2 domain but lacked amino acids 1-503. Neuron-specific expression of recombinant SH2B1, but not R555E or DeltaN503, corrected hyperphagia, obesity, glucose intolerance, and insulin resistance in SH2B1 null mice. Neuron-specific expression of R555E in wild-type mice promoted obesity and insulin resistance. These results indicate that in addition to the SH2 domain, N-terminal regions of neuronal SH2B1 are also required for the maintenance of normal body weight and glucose metabolism. Additionally, mutations in the SH2 domain of SH2B1 may increase the susceptibility to obesity and type 2 diabetes in a dominant-negative manner.

  7. The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N′ and Regulates Light-Dependent Cell Death1[OPEN

    Science.gov (United States)

    Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei

    2016-01-01

    One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N′, which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N′ results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N′ is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. PMID:26951433

  8. The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N' and Regulates Light-Dependent Cell Death.

    Science.gov (United States)

    Hamel, Louis-Philippe; Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei; Moffett, Peter

    2016-05-01

    One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N', which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N' results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N' is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. © 2016 American Society of Plant Biologists. All Rights Reserved.

  9. Extracellular Signal-Regulated Kinase 2 (ERK2) Phosphorylation Sites and Docking Domain on the Nuclear Pore Complex Protein Tpr Cooperatively Regulate ERK2-Tpr Interaction

    Czech Academy of Sciences Publication Activity Database

    Vomastek, Tomáš; Iwanicky, M. P.; Burack, W. R.; Tiwari, D.; Kumar, D.; Parsons, J. T.; Weber, M. J.; Nandicoori, V. K.

    2008-01-01

    Roč. 28, č. 22 (2008), s. 6954-6966 ISSN 0270-7306 R&D Projects: GA AV ČR IAA500200716 Institutional research plan: CEZ:AV0Z50200510 Keywords : erk * docking domain * cell growth Subject RIV: EE - Microbiology, Virology Impact factor: 5.942, year: 2008

  10. Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis.

    Directory of Open Access Journals (Sweden)

    Ping Li

    2017-06-01

    Full Text Available Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery.

  11. Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis

    Science.gov (United States)

    Koch, Bailey A.; Han, Xuemei

    2017-01-01

    Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery. PMID:28609436

  12. The PR/SET Domain Zinc Finger Protein Prdm4 Regulates Gene Expression in Embryonic Stem Cells but Plays a Nonessential Role in the Developing Mouse Embryo

    Science.gov (United States)

    Bogani, Debora; Morgan, Marc A. J.; Nelson, Andrew C.; Costello, Ita; McGouran, Joanna F.; Kessler, Benedikt M.

    2013-01-01

    Prdm4 is a highly conserved member of the Prdm family of PR/SET domain zinc finger proteins. Many well-studied Prdm family members play critical roles in development and display striking loss-of-function phenotypes. Prdm4 functional contributions have yet to be characterized. Here, we describe its widespread expression in the early embryo and adult tissues. We demonstrate that DNA binding is exclusively mediated by the Prdm4 zinc finger domain, and we characterize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential enrichment) and ChIP-seq (chromatin immunoprecipitation-sequencing) experiments. In embryonic stem cells (ESCs), Prdm4 regulates key pluripotency and differentiation pathways. Two independent strategies, namely, targeted deletion of the zinc finger domain and generation of a EUCOMM LacZ reporter allele, resulted in functional null alleles. However, homozygous mutant embryos develop normally and adults are healthy and fertile. Collectively, these results strongly suggest that Prdm4 functions redundantly with other transcriptional partners to cooperatively regulate gene expression in the embryo and adult animal. PMID:23918801

  13. NO_x reduction and N_2O emissions in a diesel engine exhaust using Fe-zeolite and vanadium based SCR catalysts

    International Nuclear Information System (INIS)

    Cho, Chong Pyo; Pyo, Young Dug; Jang, Jin Young; Kim, Gang Chul; Shin, Young Jin

    2017-01-01

    Highlights: • NO_x reduction and N_2O emission of urea-SCR catalysts with the oxidation precatalysts were investigated. • Fe-zeolite and V-based catalysts were noticeably affected by the NO_2/NOx ratio. • Remarkable N_2O formation was observed only for the Fe-zeolite catalyst. - Abstract: Among various approaches used to comply with strict diesel engine exhaust regulations, there is increasing interest in urea based selective catalytic reduction (SCR) as a NO_x reduction technology, due to its high reduction and excellent fuel efficiencies. NO_x reduction by SCR catalysts is affected by variations in the NO_2/NO_x ratio, caused by oxidation catalysts such as the diesel oxidation catalyst (DOC) and diesel particulate filter (DPF) installed in diesel engines. Recently, it has been reported that the greenhouse gas (GHG) variant N_2O, which is a by-product of the NO_x conversion process in the after-treatment system, will be subject to regulation. Using a real diesel engine installed with DOC and DPF, the NO_x reduction and N_2O emission performances of commonly used Fe-zeolite and V_2O_5-WO_3/TiO_2 catalysts were investigated under various operating conditions. The exhaust of the diesel engine used in this study had a NO_2/NO_x ratio of over 50% for temperatures below 400 °C due to the oxidation catalysts, while the NO_2/NO_x ratio was significantly lower for temperatures above 400 °C. Under such conditions, it was found that the Fe-zeolite and V_2O_5-WO_3/TiO_2 catalysts were noticeably affected by the NO_2/NOx ratio and exhaust temperature. Although both catalysts showed satisfactory NO conversions, the V_2O_5-WO_3/TiO_2 catalyst showed decreasing NO_2 conversion rates between 250 °C and 320 °C. The V_2O_5-WO_3/TiO_2 catalyst exhibited NH_3 slip relatively frequently because of its low NH_3 storage capacity. For the Fe-zeolite catalyst, a significant increase in the amount of generated N_2O was observed for high NO_x conversion conditions due to side

  14. Stabilization of a nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator yields insight into disease-causing mutations.

    Science.gov (United States)

    Vernon, Robert M; Chong, P Andrew; Lin, Hong; Yang, Zhengrong; Zhou, Qingxian; Aleksandrov, Andrei A; Dawson, Jennifer E; Riordan, John R; Brouillette, Christie G; Thibodeau, Patrick H; Forman-Kay, Julie D

    2017-08-25

    Characterization of the second nucleotide-binding domain (NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR) has lagged behind research into the NBD1 domain, in part because NBD1 contains the F508del mutation, which is the dominant cause of cystic fibrosis. Research on NBD2 has also been hampered by the overall instability of the domain and the difficulty of producing reagents. Nonetheless, multiple disease-causing mutations reside in NBD2, and the domain is critical for CFTR function, because channel gating involves NBD1/NBD2 dimerization, and NBD2 contains the catalytically active ATPase site in CFTR. Recognizing the paucity of structural and biophysical data on NBD2, here we have defined a bioinformatics-based method for manually identifying stabilizing substitutions in NBD2, and we used an iterative process of screening single substitutions against thermal melting points to both produce minimally mutated stable constructs and individually characterize mutations. We present a range of stable constructs with minimal mutations to help inform further research on NBD2. We have used this stabilized background to study the effects of NBD2 mutations identified in cystic fibrosis (CF) patients, demonstrating that mutants such as N1303K and G1349D are characterized by lower stability, as shown previously for some NBD1 mutations, suggesting a potential role for NBD2 instability in the pathology of CF. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Two memory associated genes regulated by amyloid precursor protein intracellular domain ovel insights into the pathogenesis of learning and memory impairment in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Chuandong Zheng; Xi Gu; Zhimei Zhong; Rui Zhu; Tianming Gao; Fang Wang

    2012-01-01

    In this study, we employed chromatin immunoprecipitation, a useful method for studying the locations of transcription factors bound to specific DNA regions in specific cells, to investigate amyloid precursor protein intracellular domain binding sites in chromatin DNA from hippocampal neurons of rats, and to screen out five putative genes associated with the learning and memory functions. The promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and glutamate receptor-2 genes were amplified by PCR from DNA products immunoprecipitated by amyloid precursor protein intracellular domain. An electrophoretic mobility shift assay and western blot analysis suggested that the promoter regions of these two genes associated with learning and memory were bound by amyloid precursor protein intracellular domain (in complex form). Our experimental findings indicate that the amyloid precursor protein intracellular domain is involved in the transcriptional regulation of learning- and memory-associated genes in hippocampal neurons. These data may provide new insights into the molecular mechanism underlying the symptoms of progressive memory loss in Alzheimer's disease.

  16. Experimental research of technology activating catalysts for SCR DeNOx in boiler

    Science.gov (United States)

    Zeng, Xi; Yang, Zhengde; Li, Yan; Chen, Donglin

    2018-01-01

    In order to improve activity of the catalysts used in SCR DeNOx system of flue gas, a series of catalysts activated by different activating liquids under varied conditions in boiler directly were conducted. Then these catalysts were characterized by SEM, FT-IR and BET technology. And NO conversions of the activated catalysts were studied and compared with that of inactivated catalyst. The above experiment shows that NO conversion of the activated catalyst can be up to 99%, which 30% higher than that of inactivated catalyst, so activity of catalysts were improved greatly. Furthermore, optimal activating liquid labeled L2 and effective technology parameters were gained in the experiment.

  17. Strategies of Coping with Deactivation of NH3-SCR Catalysts Due to Biomass Firing

    DEFF Research Database (Denmark)

    Schill, Leonhard; Fehrmann, Rasmus

    2018-01-01

    silicates, often in the form of coal fly ash, is an industrially proven method of removing K aerosols from flue gases. Tail-end placement of the SCR unit was also reported to result in acceptable catalyst stability; however, flue-gas reheating after the flue gas desulfurization is, at present, unavoidable...... number of acid sites. This can be achieved by, e.g., using zeolites as support, replacing WO3 with heteropoly acids, and by preparing highly loaded, high surface area, very active V2O5/TiO2 catalyst using a special sol-gel method....

  18. Alkali resistant Fe-zeolite catalysts for SCR of NO with NH3 in flue gases

    DEFF Research Database (Denmark)

    Putluru, Siva Sankar Reddy; Jensen, Anker Degn; Riisager, Anders

    2011-01-01

    . The effect of potassium doping on the acidic and redox properties of the Fe-zeolite catalysts were studied. The prepared catalysts showed high surface area and surface acidity. This is essential for increased alkali resistivity in comparison with conventional metal oxide supports like, e.g. TiO2 and ZrO2......, towards e.g. potassium salts in flue gases from biomass fired power plants. These properties allowed both undoped and potassium doped Fe-zeolite catalysts to posses high activity during the selective catalytic reduction (SCR) of NO with NH3. The extent of deactivation of the Fe-zeolite catalysts...

  19. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

  20. Radio-Frequency-Controlled Urea Dosing for NH₃-SCR Catalysts: NH₃ Storage Influence to Catalyst Performance under Transient Conditions.

    Science.gov (United States)

    Dietrich, Markus; Hagen, Gunter; Reitmeier, Willibald; Burger, Katharina; Hien, Markus; Grass, Philippe; Kubinski, David; Visser, Jaco; Moos, Ralf

    2017-11-28

    Current developments in exhaust gas aftertreatment led to a huge mistrust in diesel driven passenger cars due to their NO x emissions being too high. The selective catalytic reduction (SCR) with ammonia (NH₃) as reducing agent is the only approach today with the capability to meet upcoming emission limits. Therefore, the radio-frequency-based (RF) catalyst state determination to monitor the NH₃ loading on SCR catalysts has a huge potential in emission reduction. Recent work on this topic proved the basic capability of this technique under realistic conditions on an engine test bench. In these studies, an RF system calibration for the serial type SCR catalyst Cu-SSZ-13 was developed and different approaches for a temperature dependent NH₃ storage were determined. This paper continues this work and uses a fully calibrated RF-SCR system under transient conditions to compare different directly measured and controlled NH₃ storage levels, and NH₃ target curves. It could be clearly demonstrated that the right NH₃ target curve, together with a direct control on the desired level by the RF system, is able to operate the SCR system with the maximum possible NO x conversion efficiency and without NH₃ slip.

  1. SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65

    Directory of Open Access Journals (Sweden)

    Pengcheng Li

    2018-04-01

    Full Text Available Dengue virus (DENV is a mosquito-borne single-stranded RNA virus causing human disease with variable severity. The production of massive inflammatory cytokines in dengue patients has been associated with dengue disease severity. However, the regulation of these inflammatory responses remains unclear. In this study, we report that SIRT6 is a negative regulator of innate immune responses during DENV infection. Silencing of Sirt6 enhances DENV-induced proinflammatory cytokine and chemokine production. Overexpression of SIRT6 inhibits RIG-I-like receptor (RLR and Toll-like receptor 3 (TLR3 mediated NF-κB activation. The sirtuin core domain of SIRT6 is required for the inhibition of NF-κB p65 function. SIRT6 interacts with the DNA binding domain of p65 and competes with p65 to occupy the Il6 promoter during DENV infection. Collectively, our study demonstrates that SIRT6 negatively regulates DENV-induced inflammatory response via RLR and TLR3 signaling pathways.

  2. Suppressor of Cytokine Signaling (SOCS 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1.

    Directory of Open Access Journals (Sweden)

    Edmond M Linossi

    Full Text Available Suppressor of Cytokine Signaling (SOCS5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR. Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2 autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling.

  3. The F-BAR domains from srGAP1, srGAP2 and srGAP3 regulate membrane deformation differently

    Science.gov (United States)

    Coutinho-Budd, Jaeda; Ghukasyan, Vladimir; Zylka, Mark J.; Polleux, Franck

    2012-01-01

    Summary Coordination of membrane deformation and cytoskeletal dynamics lies at the heart of many biological processes critical for cell polarity, motility and morphogenesis. We have recently shown that Slit-Robo GTPase-activating protein 2 (srGAP2) regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation. Here, we demonstrate that the F-BAR domains of two closely related family members, srGAP1 and srGAP3 [designated F-BAR(1) and F-BAR(3), respectively] display significantly different membrane deformation properties in non-neuronal COS7 cells and in cortical neurons. F-BAR(3) induces filopodia in both cell types, though less potently than F-BAR(2), whereas F-BAR(1) prevents filopodia formation in cortical neurons and reduces plasma membrane dynamics. These three F-BAR domains can heterodimerize, and they act synergistically towards filopodia induction in COS7 cells. As measured by fluorescence recovery after photobleaching, F-BAR(2) displays faster molecular dynamics than F-BAR(3) and F-BAR(1) at the plasma membrane, which correlates well with its increased potency to induce filopodia. We also show that the molecular dynamic properties of F-BAR(2) at the membrane are partially dependent on F-Actin. Interestingly, acute phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] depletion in cells does not interfere with plasma membrane localization of F-BAR(2), which is compatible with our result showing that F-BAR(2) binds to a broad range of negatively-charged phospholipids present at the plasma membrane, including phosphatidylserine (PtdSer). Overall, our results provide novel insights into the functional diversity of the membrane deformation properties of this subclass of F-BAR-domains required for cell morphogenesis. PMID:22467852

  4. Differential Regulation of Disheveled in a Novel Vegetal Cortical Domain in Sea Urchin Eggs and Embryos: Implications for the Localized Activation of Canonical Wnt Signaling

    Science.gov (United States)

    Peng, ChiehFu Jeff; Wikramanayake, Athula H.

    2013-01-01

    Pattern formation along the animal-vegetal (AV) axis in sea urchin embryos is initiated when canonical Wnt (cWnt) signaling is activated in vegetal blastomeres. The mechanisms that restrict cWnt signaling to vegetal blastomeres are not well understood, but there is increasing evidence that the egg’s vegetal cortex plays a critical role in this process by mediating localized “activation” of Disheveled (Dsh). To investigate how Dsh activity is regulated along the AV axis, sea urchin-specific Dsh antibodies were used to examine expression, subcellular localization, and post-translational modification of Dsh during development. Dsh is broadly expressed during early sea urchin development, but immunolocalization studies revealed that this protein is enriched in a punctate pattern in a novel vegetal cortical domain (VCD) in the egg. Vegetal blastomeres inherit this VCD during embryogenesis, and at the 60-cell stage Dsh puncta are seen in all cells that display nuclear β-catenin. Analysis of Dsh post-translational modification using two-dimensional Western blot analysis revealed that compared to Dsh pools in the bulk cytoplasm, this protein is differentially modified in the VCD and in the 16-cell stage micromeres that partially inherit this domain. Dsh localization to the VCD is not directly affected by disruption of microfilaments and microtubules, but unexpectedly, microfilament disruption led to degradation of all the Dsh pools in unfertilized eggs over a period of incubation suggesting that microfilament integrity is required for maintaining Dsh stability. These results demonstrate that a pool of differentially modified Dsh in the VCD is selectively inherited by the vegetal blastomeres that activate cWnt signaling in early embryos, and suggests that this domain functions as a scaffold for localized Dsh activation. Localized cWnt activation regulates AV axis patterning in many metazoan embryos. Hence, it is possible that the VCD is an evolutionarily conserved

  5. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

    Science.gov (United States)

    Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

  6. Regulation of the heavy metal pump AtHMA4 by a metal-binding autoinhibitory domain

    DEFF Research Database (Denmark)

    Bækgaard, Lone; Roed, Maria Dalgaard; Zhang, Yang

    Heavy metal pumps, or P1B ATPases, are important for heavy metal homeostasis in most cells. In general, these pumps contain extended N- and/or C-termini with one or more metal-binding domains (MBDs), but the role of the extended termini is still not clear. The Arabidopsis thaliana Zn2+-ATPase At......HMA4 contains a very long C-terminus with 13 cysteine pairs and an 11 amino acid residue long histidine stretch at the end. To ascertain the role of the potentially metal-binding domains in the C-terminus of AtHMA4, the C-terminal region alone was expressed in yeast. This resulted in increased Zn...

  7. Modulation of brassinosteroid-regulated gene expression by jumonji domain-containing proteins ELF6 and REF6 in Arabidopsis

    OpenAIRE

    Yu, Xiaofei; Li, Li; Li, Lei; Guo, Michelle; Chory, Joanne; Yin, Yanhai

    2008-01-01

    Plant steroid hormones, brassinosteroids (BRs), are of great importance for plant growth and development. BRs signal through a cell surface receptor kinase, BRI1, and a GSK3-like kinase, BIN2, to regulate the BES1/BZR1 family of transcription factors, which directly bind to target gene promoters to activate or repress gene expression and mediate BR responses. To understand how BES1 regulates target gene expression, we identified two BES1-interacting proteins, ELF6 (early flowering 6) and its ...

  8. Oxidative Unfolding of the Rubredoxin Domain and the Natively Disordered N-terminal Region Regulate the Catalytic Activity of Mycobacterium tuberculosis Protein Kinase G.

    Science.gov (United States)

    Wittwer, Matthias; Luo, Qi; Kaila, Ville R I; Dames, Sonja A

    2016-12-30

    Mycobacterium tuberculosis escapes killing in human macrophages by secreting protein kinase G (PknG). PknG intercepts host signaling to prevent fusion of the phagosome engulfing the mycobacteria with the lysosome and, thus, their degradation. The N-terminal NORS (no regulatory secondary structure) region of PknG (approximately residues 1-75) has been shown to play a role in PknG regulation by (auto)phosphorylation, whereas the following rubredoxin-like metal-binding motif (RD, residues ∼74-147) has been shown to interact tightly with the subsequent catalytic domain (approximately residues 148-420) to mediate its redox regulation. Deletions or mutations in NORS or the redox-sensitive RD significantly decrease PknG survival function. Based on combined NMR spectroscopy, in vitro kinase assay, and molecular dynamics simulation data, we provide novel insights into the regulatory roles of the N-terminal regions. The NORS region is indeed natively disordered and rather dynamic. Consistent with most earlier data, autophosphorylation occurs in our assays only when the NORS region is present and, thus, in the NORS region. Phosphorylation of it results only in local conformational changes and does not induce interactions with the subsequent RD. Although the reduced, metal-bound RD makes tight interactions with the following catalytic domain in the published crystal structures, it can also fold in its absence. Our data further suggest that oxidation-induced unfolding of the RD regulates substrate access to the catalytic domain and, thereby, PknG function under different redox conditions, e.g. when exposed to increased levels of reactive oxidative species in host macrophages. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription

    OpenAIRE

    Hua, G; He, C; Lv, X; Fan, L; Wang, C; Remmenga, S W; Rodabaugh, K J; Yang, L; Lele, S M; Yang, P; Karpf, A R; Davis, J S; Wang, C

    2016-01-01

    The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexp...

  10. Light-induced conformational changes of LOV1 (light oxygen voltage-sensing domain 1) and LOV2 relative to the kinase domain and regulation of kinase activity in Chlamydomonas phototropin.

    Science.gov (United States)

    Okajima, Koji; Aihara, Yusuke; Takayama, Yuki; Nakajima, Mihoko; Kashojiya, Sachiko; Hikima, Takaaki; Oroguchi, Tomotaka; Kobayashi, Amane; Sekiguchi, Yuki; Yamamoto, Masaki; Suzuki, Tomomi; Nagatani, Akira; Nakasako, Masayoshi; Tokutomi, Satoru

    2014-01-03

    Phototropin (phot), a blue light (BL) receptor in plants, has two photoreceptive domains named LOV1 and LOV2 as well as a Ser/Thr kinase domain (KD) and acts as a BL-regulated protein kinase. A LOV domain harbors a flavin mononucleotide that undergoes a cyclic photoreaction upon BL excitation via a signaling state in which the inhibition of the kinase activity by LOV2 is negated. To understand the molecular mechanism underlying the BL-dependent activation of the kinase, the photochemistry, kinase activity, and molecular structure were studied with the phot of Chlamydomonas reinhardtii. Full-length and LOV2-KD samples of C. reinhardtii phot showed cyclic photoreaction characteristics with the activation of LOV- and BL-dependent kinase. Truncation of LOV1 decreased the photosensitivity of the kinase activation, which was well explained by the fact that the signaling state lasted for a shorter period of time compared with that of the phot. Small angle x-ray scattering revealed monomeric forms of the proteins in solution and detected BL-dependent conformational changes, suggesting an extension of the global molecular shapes of both samples. Constructed molecular model of full-length phot based on the small angle x-ray scattering data proved the arrangement of LOV1, LOV2, and KD for the first time that showed a tandem arrangement both in the dark and under BL irradiation. The models suggest that LOV1 alters its position relative to LOV2-KD under BL irradiation. This finding demonstrates that LOV1 may interact with LOV2 and modify the photosensitivity of the kinase activation through alteration of the duration of the signaling state in LOV2.

  11. Analysis and study on the performance variation of SCR DeNOx catalyst of Coal-Fired Boilers

    International Nuclear Information System (INIS)

    Jianxing, Ren; Fangqin, Li; Jiang, Wu; Qingrong, Liu; Yongwen, Yang; Zhongzhu, Qiu

    2010-01-01

    Nitrogen oxides (NO x ) are one kind of harmful substances from the burning process of fossil fuel and air at high temperature. NO x emissions cause serious pollution on atmospheric environment. In this paper, coal-fired utility boilers were chosen as the object, NO x formation mechanism and control were studied, and SCR deNO x technology was used to control NO x emissions from coal-fired boilers. Analyzed the relationship between deNO x efficiency and characteristics of SCR DeNO x catalyst. Through analysis, affecting SCR DeNO x catalyst failure factors, change law of catalytic properties and technical measures to extend the service life of the catalyst were gotten. (author)

  12. In situ DRIFTS investigation of NH3-SCR reaction over CeO2/zirconium phosphate catalyst

    Science.gov (United States)

    Zhang, Qiulin; Fan, Jie; Ning, Ping; Song, Zhongxian; Liu, Xin; Wang, Lanying; Wang, Jing; Wang, Huimin; Long, Kaixian

    2018-03-01

    A series of ceria modified zirconium phosphate catalysts were synthesized for selective catalytic reduction of NO with ammonia (NH3-SCR). Over 98% NOx conversion and 98% N2 selectivity were obtained by the CeO2/ZrP catalyst with 20 wt.% CeO2 loading at 250-425 °C. The interaction between CeO2 and zirconium phosphate enhanced the redox abilities and surface acidities of the catalysts, resulting in the improvement of NH3-SCR activity. The in situ DRIFTS results indicated that the NH3-SCR reaction over the catalysts followed both Eley-Rideal and Langmuir-Hinshelwood mechanisms. The amide (sbnd NH2) groups and the NH4+ bonded to Brønsted acid sites were the important intermediates of Eley-Rideal mechanism.

  13. A proposal to pulse the Bevatron/Bevalac main guide field magnet with SCR power supplies

    International Nuclear Information System (INIS)

    Frias, B.; Alonso, J.; Dwinell, R.; Lothrop, F.

    1989-01-01

    The Bevatron/Bevalac Main Guide Field Power Supply was originally designed to provide a 15,250 Volt DC. at sign 8400 Ampere peak magnet pulse. Protons were accelerated to 6.2 Gev. The 128 Megawatt (MW) pulse required two large motor-generator (MG) sets with 67 ton flywheels to store 680 Megajoules of energy. Ignitron rectifiers are used to rectify the generator outputs. Acceleration of heavy ions results in an operating schedule with a broad range of peak fields. The maximum field of 12.5 kilogauss requires a peak pulse of 80 MW. Acceleration of ions to 1.0 kilogauss requires an 8 MW peak pulse. One MG set can provide pulses below 45 MW. Peak pulses of less than 15 MW are now a large block of the operating schedule. A proposal has been made to replace the existing MG system with eight SCR power supplies for low field operation. The SCR supplies will be powered directly from the Lawrence Berkeley Laboratory's 12.3 KV. power distribution system. This paper describes the many advantages of the plan. 4 refs., 3 figs., 3 tabs

  14. Speciation analysis and leaching behaviors of selected trace elements in spent SCR catalyst.

    Science.gov (United States)

    Dai, Zejun; Wang, Lele; Tang, Hao; Sun, Zhijun; Liu, Wei; Sun, Yi; Su, Sheng; Hu, Song; Wang, Yi; Xu, Kai; Liu, Liang; Ling, Peng; Xiang, Jun

    2018-09-01

    This study investigated heavy metal chemical speciation and leaching behavior from a board-type spent selective catalytic reduction (SCR) catalyst containing high concentrations of vanadium, chromium, nickel, copper, zinc, and lead. A three-step sequential extraction method, standard toxicity characteristic leaching procedure (TCLP), and leaching characteristic tests have been performed. It was found that the mobility of six heavy metals in the spent SCR catalyst was significantly different. The mobility of the six heavy metals exhibited the following order: Ni > Zn > V > Cr > As > Cu. Meanwhile, TCLP test results revealed relatively high Zn and Cr leaching rate of 83.20% and 10.35%, respectively. It was found that leaching rate was positively correlated with available contents (sum of acid soluble, reducible and oxidizable fractions). Leaching characteristics tests indicated that pH substantially affected the leaching of these heavy metals. In particular, the leaching of Cr, Ni, Cu, and Zn was positively influenced by strong acid, while V and As were easily released in the presence of strong acid and strong alkali (pH 11). In terms of kinetics, the leaching of Cr, Ni, Cu, Zn, and As within the spent catalyst was dominated by erosion and dissolution processes, which were rapid reaction processes. V was released in large amounts within 1 h, but its leaching amount sharply decreased with time due to readsorption. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Study on Optimization Experiment of SCR Denitrification Technologies in a Coal-fired Power Plant

    Science.gov (United States)

    Zhang, Limeng; Dong, Xinguang; Hou, Fanjun; Liu, Ke; Che, Gang

    2018-01-01

    Optimization experiment of SCR denitrification technologies on a 300MW unit was conducted. Adjustment of ammonia injection quantity of corresponding AIG was conducted after measuring the SCR export NOx concentration field in 250MW load, the distribution uniformity of NOx volume fraction at the outlet of both reactor A and B was improved significantly, where the relative standard deviation of NOx reduced respectively from 29.83% to 13.01% and 24.54% to 9.26%, simultaneously, the amount of ammonia escape of A, B reactor decrease respectively by 24.76%, 19.45%. The results of optimization experiment show that, optimal adjustment can improve the NOx concentration distribution, reduce the amount of ammonia escape in a certain extent, and judge whether the catalytic activity of the regional catalyzer is in good condition. As to the area where catalyst is ineffective, the effect of optimization experiment is limited, the catalyzer should be the timely replacement, so as to better protect downstream equipment.

  16. Monitoring the ammonia loading of zeolite-based ammonia SCR catalysts by a microwave method

    Energy Technology Data Exchange (ETDEWEB)

    Reiss, S.; Schoenauer, D.; Hagen, G.; Moos, R. [University of Bayreuth, Department of Functional Materials, Bayreuth (Germany); Fischerauer, G. [University of Bayreuth, Department of Metrology and Control, Bayreuth (Germany)

    2011-05-15

    Exhaust gas aftertreatment systems, which reduce nitrogen oxide emissions of heavy-duty diesel engines, commonly use a selective catalytic reduction (SCR) catalyst. Currently, emissions are controlled by evaluating NO{sub x} or NH{sub 3} in the gas phase downstream the catalyst and calculating the NH{sub 3} loading via a chemical storage model. Here, a microwave-cavity perturbation method is proposed in which electromagnetic waves are excited by probe feeds and the reflected signals are measured. At distinct resonance frequencies, the reflection coefficient shows a pronounced minimum. These resonance frequencies depend almost linearly on the NH{sub 3} loading of a zeolite-based SCR catalyst. Since the NH{sub 3} loading-dependent electrical properties of the catalyst material itself are measured, the amount of stored ammonia can be determined directly and in situ. The cross-sensitivity towards water can be reduced almost completely by selecting an appropriate frequency range. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. Emission reduction from a diesel engine fueled by pine oil biofuel using SCR and catalytic converter

    Science.gov (United States)

    Vallinayagam, R.; Vedharaj, S.; Yang, W. M.; Saravanan, C. G.; Lee, P. S.; Chua, K. J. E.; Chou, S. K.

    2013-12-01

    In this work, we propose pine oil biofuel, a renewable fuel obtained from the resins of pine tree, as a potential substitute fuel for a diesel engine. Pine oil is endowed with enhanced physical and thermal properties such as lower viscosity and boiling point, which enhances the atomization and fuel/air mixing process. However, the lower cetane number of the pine oil hinders its direct use in diesel engine and hence, it is blended in suitable proportions with diesel so that the ignition assistance could be provided by higher cetane diesel. Since lower cetane fuels are prone to more NOX formation, SCR (selective catalyst reduction), using urea as reducing agent, along with a CC (catalytic converter) has been implemented in the exhaust pipe. From the experimental study, the BTE (brake thermal efficiency) was observed to be increased as the composition of pine oil increases in the blend, with B50 (50% pine oil and 50% diesel) showing 7.5% increase over diesel at full load condition. The major emissions such as smoke, CO, HC and NOX were reduced by 70.1%, 67.5%, 58.6% and 15.2%, respectively, than diesel. Further, the average emissions of B50 with SCR and CC assembly were observed to be reduced, signifying the positive impact of pine oil biofuel on atmospheric environment. In the combustion characteristics front, peak heat release rate and maximum in-cylinder pressure were observed to be higher with longer ignition delay.

  18. Long term deactivation test of high dust SCR catalysts by straw co-firing

    Energy Technology Data Exchange (ETDEWEB)

    Weigang Lin; Degn Jensen, A.; Bjerkvig, J.

    2009-12-15

    The consequences of carbon dioxide induced global warming cause major concern worldwide. The consumption of energy produced with fossil fuels is the major factor that contributes to the global warming. Biomass is a renewable energy resource and has a nature of CO{sub 2} neutrality. Co-combustion of biomass in existing coal fired power plants can maintain high efficiency and reduce the emission of CO{sub 2} at same time. However, one of the problems faced by co-firing is deactivation of the SCR catalysts. Understanding of the mechanisms of deactivation of the catalyst elements at co-firing conditions is crucial for long term runs of the power plants. Twenty six SCR catalyst elements were exposed at two units (SSV3 and SSV4) in the Studstrup Power Plant for a long period. Both units co-fire coal and straw with a typical fraction of 8-10% straw on an energy basis during co-firing. SSV4 unit operated in co-firing mode most of the time; SSV3 unit co-fired straw half of the operating time. The main objective of this PSO-project is to gain knowledge of a long term influence on catalyst activity when co-firing straw in coal-fired power plants, thus, to improve the basis for operating the SCR-plants for NO{sub x}-reduction. The exposure time of the applied catalyst elements (HTAS and BASF) varied from approximately 5000 to 19000 hours in the power plant by exchanging the element two times. The activity of all elements was measured before and after exposure in a bench scale test rig at the Department of Chemical and Biochemical Engineering, Technical University of Denmark. The results show that the activity, estimated by exclusion of channel clogging of the elements, decreases gradually with the total exposure time. It appears that the exposure time under co-firing condition has little effect on the deactivation of the catalyst elements and no sharp decrease of the activity was observed. The average deactivation rate of the catalyst elements is 1.6 %/1000 hours. SEM

  19. Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9

    International Nuclear Information System (INIS)

    Zhang, Ruoxi; Fang, Liurong; Wang, Dang; Cai, Kaimei; Zhang, Huan; Xie, Lilan; Li, Yi; Chen, Huanchun; Xiao, Shaobo

    2015-01-01

    To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses. - Highlights: • Porcine bocavirus (PBoV) NP1 interferes with the IFN α/β signaling pathway. • PBoV NP1 does not prevent STAT1/STAT2 phosphorylation and nuclear translocation. • PBoV NP1 inhibits the DNA-binding activity of ISGF3. • PBoV NP1 interacts with the DNA-binding domain of IRF9.

  20. Porcine bocavirus NP1 negatively regulates interferon signaling pathway by targeting the DNA-binding domain of IRF9

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ruoxi [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Fang, Liurong, E-mail: fanglr@mail.hzau.edu.cn [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Wang, Dang; Cai, Kaimei; Zhang, Huan [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China); Xie, Lilan; Li, Yi [College of Life Science and Technology, Wuhan Institute of Bioengineering, Wuhan 430415 (China); Chen, Huanchun; Xiao, Shaobo [State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070 (China)

    2015-11-15

    To subvert host antiviral immune responses, many viruses have evolved countermeasures to inhibit IFN signaling pathway. Porcine bocavirus (PBoV), a newly identified porcine parvovirus, has received attention because it shows clinically high co-infection prevalence with other pathogens in post-weaning multisystemic wasting syndrome (PWMS) and diarrheic piglets. In this study, we screened the structural and non-structural proteins encoded by PBoV and found that the non-structural protein NP1 significantly suppressed IFN-stimulated response element (ISRE) activity and subsequent IFN-stimulated gene (ISG) expression. However, NP1 affected neither the activation and translocation of STAT1/STAT2, nor the formation of the heterotrimeric transcription factor complex ISGF3 (STAT1/STAT2/IRF9). Detailed analysis demonstrated that PBoV NP1 blocked the ISGF3 DNA-binding activity by combining with the DNA-binding domain (DBD) of IRF9. In summary, these results indicate that PBoV NP1 interferes with type I IFN signaling pathway by blocking DNA binding of ISGF3 to attenuate innate immune responses. - Highlights: • Porcine bocavirus (PBoV) NP1 interferes with the IFN α/β signaling pathway. • PBoV NP1 does not prevent STAT1/STAT2 phosphorylation and nuclear translocation. • PBoV NP1 inhibits the DNA-binding activity of ISGF3. • PBoV NP1 interacts with the DNA-binding domain of IRF9.

  1. Arabidopsis COLD SHOCK DOMAIN PROTEIN2 is a RNA chaperone that is regulated by cold and developmental signals

    International Nuclear Information System (INIS)

    Sasaki, Kentaro; Kim, Myung-Hee; Imai, Ryozo

    2007-01-01

    Bacterial cold shock proteins (CSPs) are RNA chaperones that unwind RNA secondary structures. Arabidopsis COLD SHOCK DOMAIN PROTEIN2 (AtCSP2) contains a domain that is shared with bacterial CSPs. Here we showed that AtCSP2 binds to RNA and unwinds nucleic acid duplex. Heterologous expression of AtCSP2 complemented cold sensitivity of an Escherichia coli csp quadruple mutant, indicating that AtCSP2 function as a RNA chaperone in E. coli. AtCSP2 mRNA and protein levels increased during cold acclimation, but the protein accumulation was most prominent after 10 days of cold treatment. AtCSP2 promoter::GUS transgenic plants revealed that AtCSP2 is expressed only in root and shoot apical regions during vegetative growth but is expressed in reproductive organs such as pollens, ovules and embryos. These data indicated that AtCSP2 is involved in developmental processes as well as cold adaptation. Localization of AtCSP2::GFP in nucleolus and cytoplasm suggested different nuclear and cytosolic RNA targets

  2. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1

    NARCIS (Netherlands)

    Prattes, M.; Loibl, M.; Zisser, G.; Luschnig, D.; Kappel, L.; Rossler, I.; Grassegger, M.; Hromic, A.; Krieger, E.; Gruber, K.; Pertschy, B.; Bergler, H.

    2017-01-01

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP

  3. Effect of the amino acid substitution in the DNA-binding domain of the Fur regulator on production of pyoverdine

    Czech Academy of Sciences Publication Activity Database

    Valešová, Renata; Palyzová, Andrea; Marešová, Helena; Štěpánek, Václav; Babiak, Petr; Kyslík, Pavel

    2013-01-01

    Roč. 58, č. 4 (2013), s. 311-317 ISSN 0015-5632 R&D Projects: GA AV ČR KJB500200703 Institutional support: RVO:61388971 Keywords : FERRIC UPTAKE REGULATOR * STARVATION SIGMA-FACTOR * MEDIATED IRON TRANSPORT Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.145, year: 2013

  4. Regulation of DU145 prostate cancer cell growth by Scm-like with four mbt domains 2.

    Science.gov (United States)

    Lee, Kwanghyun; Na, Wonho; Maeng, Je-Heon; Wu, Hongjin; Ju, Bong-Gun

    2013-03-01

    Mammalian SFMBTs have been considered to be polycomb group repressors. However, molecular mechanisms underlying mammalian SFMBTs-mediated gene regulation and their biological function have not been characterized. In the present study, we identified YY1 and methylated histones as interacting proteins of human SFMBT2. We also found that human SFMBT2 binds preferentially to methylated histone H3 and H4 that are associated with transcriptional repression. Using DU145 prostate cancer cells as a model, we showed that SFMBT2 has a transcriptional repression activity on HOXB13 gene expression. In addition, occupancy of SFMBT2 coincided with enrichment of diand tri-methylated H3K9 and H4K20 as well as tri-methylated H3K27 at the HOXB13 gene promoter. When SFMBT2 was depleted by siRNA in DU145 prostate cancer cells, significant up-regulation of HOXB13 gene expression and decreased cell growth were observed. Collectively, our findings indicate that human SFMBT2 may regulate cell growth via epigenetic regulation of HOXB13 gene expression in DU145 prostate cancer cells.

  5. The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

    NARCIS (Netherlands)

    de Kreuk, Bart-Jan; Nethe, Micha; Fernandez-Borja, Mar; Anthony, Eloise C.; Hensbergen, Paul J.; Deelder, Andre M.; Plomann, Markus; Hordijk, Peter L.

    2011-01-01

    The Rac1 GTPase controls cytoskeletal dynamics and is a key regulator of cell spreading and migration mediated by signaling through effector proteins, such as the PAK kinases and the Scar and WAVE proteins. We previously identified a series of regulatory proteins that associate with Rac1 through its

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-19

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

  7. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions.

    Science.gov (United States)

    Pettit, S C; Moody, M D; Wehbie, R S; Kaplan, A H; Nantermet, P V; Klein, C A; Swanstrom, R

    1994-12-01

    The proteolytic processing sites of the human immunodeficiency virus type 1 (HIV-1) Gag precursor are cleaved in a sequential manner by the viral protease. We investigated the factors that regulate sequential processing. When full-length Gag protein was digested with recombinant HIV-1 protease in vitro, four of the five major processing sites in Gag were cleaved at rates that differ by as much as 400-fold. Three of these four processing sites were cleaved independently of the others. The CA/p2 site, however, was cleaved approximately 20-fold faster when the adjacent downstream p2/NC site was blocked from cleavage or when the p2 domain of Gag was deleted. These results suggest that the presence of a C-terminal p2 tail on processing intermediates slows cleavage at the upstream CA/p2 site. We also found that lower pH selectively accelerated cleavage of the CA/p2 processing site in the full-length precursor and as a peptide primarily by a sequence-based mechanism rather than by a change in protein conformation. Deletion of the p2 domain of Gag results in released virions that are less infectious despite the presence of the processed final products of Gag. These findings suggest that the p2 domain of HIV-1 Gag regulates the rate of cleavage at the CA/p2 processing site during sequential processing in vitro and in infected cells and that p2 may function in the proper assembly of virions.

  8. A phospho-sugar binding domain homologous to NagB enzymes regulates the activity of the central glycolytic genes repressor.

    Science.gov (United States)

    Doan, Thierry; Martin, Laetitia; Zorrilla, Silvia; Chaix, Denis; Aymerich, Stéphane; Labesse, Gilles; Declerck, Nathalie

    2008-06-01

    CggR belongs to the SorC family of bacterial transcriptional regulators which control the expression of genes and operons involved in carbohydrate catabolism. CggR was first identified in Bacillus subtilis where it represses the gapA operon encoding the five enzymes that catalyze the central part of glycolysis. Here we present a structure/function study demonstrating that the C-terminal region of CggR regulates the DNA binding activity of this repressor in response to binding of a phosphorylated sugar. Molecular modeling of CggR revealed a winged-helix DNA-binding motif followed by a C-terminal domain presenting weak but significant homology with glucosamine-6-phosphate deaminases from the NagB family. In silico ligand screening suggested that the CggR C-terminal domain would bind preferentially bi-phosphorylated compounds, in agreement with previous studies that proposed fructuose-1,6-biphosphate (FBP) as the inducer metabolite. In vitro, FBP was the only sugar compound capable of interfering with CggR cooperative binding to DNA. FBP was also found to protect CggR against trypsin degradation at two arginine residues predicted to reside in a mobile loop forming the active site lid of the NagB enzymes. Replacement of residues predicted to interact with FBP led to mutant CggR with altered repressor activity in vivo but retaining their structural integrity and DNA binding activity in vitro. Interestingly, some of the mutant repressors responded with different specificity towards mono- and di-phospho-fructosides. Based on these results, we propose that the activity of the CggR-like repressors is controlled by a phospho-sugar binding (PSB) domain presenting structural and functional homology with NagB enzymes. (c) 2008 Wiley-Liss, Inc.

  9. 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

  10. Associations among workplace environment, self-regulation, and domain-specific physical activities among white-collar workers: a multilevel longitudinal study.

    Science.gov (United States)

    Watanabe, Kazuhiro; Kawakami, Norito; Otsuka, Yasumasa; Inoue, Shigeru

    2018-05-31

    Psychological and environmental determinants have been discussed for promoting physical activity among workers. However, few studies have investigated effects of both workplace environment and psychological determinants on physical activity. It is also unknown which domains of physical activities are promoted by these determinants. This study aimed to investigate main and interaction effects of workplace environment and individual self-regulation for physical activity on domain-specific physical activities among white-collar workers. A multi-site longitudinal study was conducted at baseline and about 5-month follow-up. A total of 49 worksites and employees within the worksites were recruited. Inclusion criteria for the worksites (a) were located in the Kanto area, Japan and (b) employed two or more employees. Employee inclusion criteria were (a) employed by the worksites, (b) aged 18 years or older, and (c) white-collar workers. For outcomes, three domain-specific physical activities (occupational, transport-related, and leisure-time) at baseline and follow-up were measured. For independent variables, self-regulation for physical activity, workplace environments (parking/bike, signs/bulletin boards/advertisements, stairs/elevators, physical activity/fitness facilities, work rules, written policies, and health promotion programs), and covariates at baseline were measured. Hierarchical Linear Modeling was conducted to investigate multilevel associations. Of the recruited worksites, 23 worksites and 562 employees, and 22 worksites and 459 employees completed the baseline and the follow-up surveys. As results of Hierarchical Linear Modeling, stairs/elevator (γ=3.80 [SE=1.80], ppsychological approaches to increase effect sizes to promote overall physical activity.

  11. Blue light-excited LOV1 and LOV2 domains cooperatively regulate the kinase activity of full-length phototropin2 from Arabidopsis.

    Science.gov (United States)

    Oide, Mao; Okajima, Koji; Nakagami, Hirofumi; Kato, Takayuki; Sekiguchi, Yuki; Oroguchi, Tomotaka; Hikima, Takaaki; Yamamoto, Masaki; Nakasako, Masayoshi

    2018-01-19

    Phototropin2 (phot2) is a blue-light (BL) receptor that regulates BL-dependent activities for efficient photosynthesis in plants. phot2 comprises two BL-receiving light-oxygen-voltage-sensing domains (LOV1 and LOV2) and a kinase domain. BL-excited LOV2 is thought to be primarily responsible for the BL-dependent activation of the kinase. However, the molecular mechanisms by which small BL-induced conformational changes in the LOV2 domain are transmitted to the kinase remain unclear. Here, we used full-length wild-type and mutant phot2 proteins from Arabidopsis to study their molecular properties in the dark and under BL irradiation. Phosphorylation assays and absorption measurements indicated that the LOV1 domain assists the thermal relaxation of BL-excited LOV2 and vice versa. Using small-angle X-ray scattering and electron microscopy, we observed that phot2 forms a dimer and has a rod shape with a maximum length of 188 Å and a radius of gyration of 44 Å. Under BL, phot2 displayed large conformational changes that bent the rod shape. By superimposing the crystal structures of the LOV1 dimer, LOV2, and a homology model of the kinase to the observed changes, we inferred that the BL-dependent change consisted of positional shifts of both LOV2 and the kinase relative to LOV1. Furthermore, phot2 mutants lacking the photocycle in LOV1 or LOV2 still exhibited conformational changes under BL, suggesting that LOV1 and LOV2 cooperatively contribute to the conformational changes that activate the kinase. These results suggest that BL-activated LOV1 contributes to the kinase activity of phot2. We discuss the possible intramolecular interactions and signaling mechanisms in phot2. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Study for a stress joint at the top of a SCR (Steel Catenary Risers); Estudo de 'stress joints' para o topo de um SCR (Steel Catenary Risers)

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Elizabeth Frauches Netto; Andrade, Edmundo Queiroz de [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Steel Catenary Risers, SCRs, need a top connection that bears the force transmitted to the platform. Essentially, two types of connections exist on the market: flex joint and stress joint (SJ). PETROBRAS has a SCR with top connection of flex joint type installed on one of its platforms; however, the company has been studying SJ as an option out of SCR top connection. A stress joint is a monolithic structure and can be inspected during manufacture and service, without so many difficult. They are metal structures composed of a uniform bore inserted in a tapered wall that increases gradually to support the force coming from the riser. The objective of this paper is to present a SJ sensitivity study for a production SCR supposedly hardwired to a unit of production of the semi-submersible type. The data used is based on real SCR data. For this study, global and local analyses were conducted for some models of stress joints, varying some parameters such as material and dimensions, allowing for the verification of some of the critical points of this type of connection. The results obtained will be shown in graphs and tensions maps to illustrate comparatively the critical points of the models analyzed. (author)

  13. SCR96, a small cysteine-rich secretory protein of Phytophthora cactorum, can trigger cell death in the Solanaceae and is important for pathogenicity and oxidative stress tolerance.

    Science.gov (United States)

    Chen, Xiao-Ren; Li, Yan-Peng; Li, Qi-Yuan; Xing, Yu-Ping; Liu, Bei-Bei; Tong, Yun-Hui; Xu, Jing-You

    2016-05-01

    Peptides and small molecules produced by both the plant pathogen Phytophthora and host plants in the apoplastic space mediate the relationship between the interplaying organisms. Various Phytophthora apoplastic effectors, including small cysteine-rich (SCR) secretory proteins, have been identified, but their roles during interaction remain to be determined. Here, we identified an SCR effector encoded by scr96, one of three novel genes encoding SCR proteins in P. cactorum with similarity to the P. cactorum phytotoxic protein PcF. Together with the other two genes, scr96 was transcriptionally induced throughout the developmental and infection stages of the pathogen. These genes triggered plant cell death (PCD) in the Solanaceae, including Nicotiana benthamiana and tomato. The scr96 gene did not show single nucleotide polymorphisms in a collection of P. cactorum isolates from different countries and host plants, suggesting that its role is essential and non-redundant during infection. Homologues of SCR96 were identified only in oomycetes, but not in fungi and other organisms. A stable protoplast transformation protocol was adapted for P. cactorum using green fluorescent protein as a marker. The silencing of scr96 in P. cactorum caused gene-silenced transformants to lose their pathogenicity on host plants and these transformants were significantly more sensitive to oxidative stress. Transient expression of scr96 partially recovered the virulence of gene-silenced transformants on plants. Overall, our results indicate that the P. cactorum scr96 gene encodes an important virulence factor that not only causes PCD in host plants, but is also important for pathogenicity and oxidative stress tolerance. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  14. F42. CHONDROTIN-6 SULFATE CLUSTERS: ASSOCIATION OF SYNAPTIC DOMAINS AND REGULATION OF SYNAPTIC PLASTICITY DURING FEAR LEARNING

    Science.gov (United States)

    Chelini, Gabriele; Berciu, Cristina; Pilobello, Kanoelani; Peter, Durning; Rachel, Jenkins; Kahn, Moazzzam; Ramikie, Teniel; Subramanian, Siva; Ressler, Kerry; Pantazopoulos, Charalampos; Berretta, Sabina

    2018-01-01

    Abstract Background Emerging evidence from our group and others has brought the brain extracellular matrix (ECM) to the forefront of investigations on brain disorders. Our group has shown that organized perisynaptic ECM aggregates, i.e. perineuronal nets (PNNs) are decreased in several brain regions in people with schizophrenia (SZ) and bipolar disorder (BD). PNNs were detected by their expression of specific chondroitin sulfate proteoglycans (CSPGs), main components of the ECM, thought to play a key role in synaptic regulation during development and adulthood. Our studies have also shown that glial cells expressing CSPGs are altered in these disorders, suggesting a link between glial cell and PNN abnormalities. Finally, we have recently shown that novel CSPG structures, bearing a distinct CS-6 sulfation pattern and named CS-6 glial clusters, are decreased in the amygdala of people with SZ and BD. The morphology and function of CS-6 glial clusters is not currently known, but evidence from rodents and on the role of CSPGs in regulating synaptic functions strongly suggest that they may affect synaptic plasticity. We tested this hypothesis using a combination of human postmortem and rodent brain studies. Methods High Resolution electron microscopy was used to investigate the ultrastructural organization of CS-6 glia clusters. A transgenic mouse model expressing green fluorescent protein in a subset of excitatory pyramidal neurons was used to investigate dendritic spines association with CS-6 glia clusters. Mice were exposed to a single session of auditory fear conditioning for a total of 15 minutes. Animals were euthanized 4 hours after behavioral test. Multiplex immunocytochemistry was used to visualize CS-6 clusters. Results In human tissue, we show that CS-6 glia clusters are widespread in several brain regions, including the amygdala, entorhinal cortex, thalamus and hippocampus. Ultrastructural results show that CS-6 glia clusters are formed by CS-6 accumulations

  15. Bacillus subtilis Two-Component System Sensory Kinase DegS Is Regulated by Serine Phosphorylation in Its Input Domain

    DEFF Research Database (Denmark)

    Jers, Carsten; Kobir, Ahasanul; Søndergaard, Elsebeth Oline

    2011-01-01

    Bacillus subtilis two-component system DegS/U is well known for the complexity of its regulation. The cytosolic sensory kinase DegS does not receive a single predominant input signal like most two-component kinases, instead it integrates a wide array of metabolic inputs that modulate its activity......S phosphorylation can be carried out by at least two B. subtilis Hanks-type kinases in vitro, and this stimulates the phosphate transfer towards DegU. The consequences of this process were studied in vivo, using phosphomimetic (Ser76Asp) and non-phosphorylatable (Ser76Ala) mutants of DegS. In a number...

  16. The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

    Science.gov (United States)

    Dingemans, Jozef; Poudyal, Bandita

    2018-01-01

    ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two

  17. Human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activity is regulated by and potentially targetable through Bruton tyrosine kinase.

    Science.gov (United States)

    Liu, Xiao; Pichulik, Tica; Wolz, Olaf-Oliver; Dang, Truong-Minh; Stutz, Andrea; Dillen, Carly; Delmiro Garcia, Magno; Kraus, Helene; Dickhöfer, Sabine; Daiber, Ellen; Münzenmayer, Lisa; Wahl, Silke; Rieber, Nikolaus; Kümmerle-Deschner, Jasmin; Yazdi, Amir; Franz-Wachtel, Mirita; Macek, Boris; Radsak, Markus; Vogel, Sebastian; Schulte, Berit; Walz, Juliane Sarah; Hartl, Dominik; Latz, Eicke; Stilgenbauer, Stephan; Grimbacher, Bodo; Miller, Lloyd; Brunner, Cornelia; Wolz, Christiane; Weber, Alexander N R

    2017-10-01

    The Nod-like receptor NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive. We sought to identify novel regulators of the NLRP3 inflammasome in human cells with a view to exploring interference with inflammasome activity at the level of such regulators. After proteome-wide phosphoproteomics, the identified novel regulator BTK was studied in human and murine cells by using pharmacologic and genetic BTK ablation. Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration-approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1β processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB). BTK affected apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and caspase-1 cleavage and interacted with NLRP3 and ASC. S aureus infection control in vivo and IL-1β release from cells of patients with Muckle-Wells syndrome were impaired by ibrutinib. Notably, IL-1β processing and release from immune cells isolated from patients with cancer receiving ibrutinib therapy were reduced. Our data suggest that XLA might result in part from genetic inflammasome deficiency and that NLRP3 inflammasome-linked inflammation could potentially be targeted pharmacologically through BTK. Copyright © 2017 American Academy of Allergy

  18. Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective tissues of developing digits and regulates fibrogenic differentiation of limb mesodermal progenitors.

    Science.gov (United States)

    Lorda-Diez, C I; Montero, J A; Sanchez-Fernandez, C; Garcia-Porrero, J A; Chimal-Monroy, J; Hurle, J M

    2018-04-01

    Four and a half LIM domain 2 (FHL2) is a multifunctional scaffolding protein of well-known function regulating cell signalling cascades and gene transcription in cancer tissues. However, its function in embryonic systems is poorly characterized. Here, we show that Fhl2 is involved in the differentiation of connective tissues of developing limb autopod. We show that Fhl2 exhibits spatially restricted and temporally dynamic expression around the tendons of developing digits, interphalangeal joint capsules, and fibrous peridigital tissue. Immunolabelling analysis of the skeletal progenitors identified a predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated with focal adhesions and actin cytoskeleton. In the course of chondrogenic differentiation of cultures of limb skeletal progenitors, the expression of Fhl2 is down-regulated. Furthermore, cultures of skeletal progenitors overexpressing Fhl2 take on a predominant fibrogenic appearance. Both gain-of-function and loss-of-function experiments in the micromass culture assays revealed a positive transcriptional influence of Fhl2 in the expression of fibrogenic markers including Scleraxis, Tenomodulin, Tenascin C, βig-h3, and Tgif1. We further show that the expression of Fhl2 is positively regulated by profibrogenic signals including Tgfβ2, all-trans-retinoic acid, and canonical Wnt signalling molecules and negatively regulated by prochondrogenic factors of the bone morphogenetic protein family. Expression of Fhl2 is also regulated negatively in immobilized limbs, but this influence appears to be mediated by other connective tissue markers, such as Tgfβs and Scleraxis. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Methodology for Analysing the NOx-NH3 Trade-off for the Heavy-duty Automotive SCR Catalyst

    DEFF Research Database (Denmark)

    Åberg, Andreas; Widd, Anders; Abildskov, Jens

    2017-01-01

    This paper presents a methodology where pareto fronts were used to analyse how changes in the control structure for the urea dosing to the automotive SCR catalyst can improve the trade-o_ between NOx slip and NH3 slip. A previously developed simulation model was used to simulate the European...

  20. NOx Selective Catalytic Reduction (SCR) on Self-Supported V-W-doped TiO2 Nanofibers

    DEFF Research Database (Denmark)

    Marani, Debora; Silva, Rafael Hubert; Dankeaw, Apiwat

    2017-01-01

    Electrospun V–W–TiO2 catalysts, resulting in a solid solution of V and W in the anatase phase, are prepared as nonwoven nanofibers for NOx selective catalytic reduction (SCR). Preliminary catalytic characterization indicates their superior NOx conversion efficiency to the-state-of-the-art materia...

  1. STUDY OF THE EFFECT OF CHLORINE ADDITION ON MERCURY OXIDATION BY SCR CATALYST UNDER SIMULATED SUBBITUMINOUS COAL FLUE GAS

    Science.gov (United States)

    An entrained flow reactor is used to study the effect of addition of chlorine-containing species on the oxidation of elemental mercury (Hgo)by a selective catalytic reduction (SCR) catalyst in simulated subbituminous coal combustion flue gas. The combustion flue gas was doped wit...

  2. STUDY OF MERCURY OXIDATION BY SCR CATALYST IN AN ENTRAINED-FLOW REACTOR UNDER SIMULATED PRB CONDITIONS

    Science.gov (United States)

    A bench-scale entrained-flow reactor system was constructed for studying elemental mercury oxidation under selective catalytic reduction (SCR) reaction conditions. Simulated flue gas was doped with fly ash collected from a subbituminous Powder River Basin (PRB) coal-fired boiler ...

  3. A particle filter for ammonia coverage ratio and input simultaneous estimations in Diesel-engine SCR system.

    Science.gov (United States)

    Sun, Kangfeng; Ji, Fenzhu; Yan, Xiaoyu; Jiang, Kai; Yang, Shichun

    2018-01-01

    As NOx emissions legislation for Diesel-engines is becoming more stringent than ever before, an aftertreatment system has been widely used in many countries. Specifically, to reduce the NOx emissions, a selective catalytic reduction(SCR) system has become one of the most promising techniques for Diesel-engine vehicle applications. In the SCR system, input ammonia concentration and ammonia coverage ratio are regarded as essential states in the control-oriental model. Currently, an ammonia sensor placed before the SCR Can is a good strategy for the input ammonia concentration value. However, physical sensor would increase the SCR system cost and the ammonia coverage ratio information cannot be directly measured by physical sensor. Aiming to tackle this problem, an observer based on particle filter(PF) is investigated to estimate the input ammonia concentration and ammonia coverage ratio. Simulation results through the experimentally-validated full vehicle simulator cX-Emission show that the performance of observer based on PF is outstanding, and the estimation error is very small.

  4. Effect of selective catalytic reduction (SCR) on fine particle emission from two coal-fired power plants in China

    Science.gov (United States)

    Li, Zhen; Jiang, Jingkun; Ma, Zizhen; Wang, Shuxiao; Duan, Lei

    2015-11-01

    Nitrogen oxides (NOx) emission abatement of coal-fired power plants (CFPPs) requires large-scaled installation of selective catalytic reduction (SCR), which would reduce secondary fine particulate matter (PM2.5) (by reducing nitrate aerosol) in the atmosphere. However, our field measurement of two CFPPs equipped with SCR indicates a significant increase of SO42- and NH4+ emission in primary PM2.5, due to catalytic enhancement of SO2 oxidation to SO3 and introducing of NH3 as reducing agent. The subsequent formation of (NH4)2SO4 or NH4HSO4 aerosol is commonly concentrated in sub-micrometer particulate matter (PM1) with a bimodal pattern. The measurement at the inlet of stack also showed doubled primary PM2.5 emission by SCR operation. This effect should therefore be considered when updating emission inventory of CFPPs. By rough estimation, the enhanced primary PM2.5 emission from CFPPs by SCR operation would offset 12% of the ambient PM2.5 concentration reduction in cities as the benefit of national NOx emission abatement, which should draw attention of policy-makers for air pollution control.

  5. SCR series switch and impulse crowbar at the Lawrence Berkeley Laboratory for CTR neutral beam source development

    International Nuclear Information System (INIS)

    Franck, J.V.; Arthur, A.A.; Brusse, L.A.; Low, W.

    1977-10-01

    The series switch is designed to operate at 120kV and pass 65A for 0.5 sec every 30 sec on the Lawrence Berkeley Laboratory CTR Neutral Beam Source Test Stand IIIB. The series switch consists of 400 individual SCR circuits connected in series and is turned on by a simple system of cascaded pulse transformers with multiple single turn secondaries each driving the individual SCR gates. It is turned off by an SCR impulse crowbar that momentarily shorts the power supply allowing the series switch to recover. The SCR switch has been tested in the impulse crowbar configuration and will reliably commutate up to 90A at 120kV. The series switch and impulse crowbar are now in service in Test Stand IIIB. A series switch and impulse crowbar similar in concept is routinely powering a 10 x 10 cm source at 150kV, 20A, 0.5 sec with a 1% duty cycle on the Lawrence Berkeley Laboratory CTR NSB Test Stand IIIA

  6. Demonstration of SCR technology for the control of NOx emissions from high-sulfur coal-fired utility boilers

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, W.S. [W.S. Hinton and Associates, Cantonment, FL (United States); Maxwell, J.D.; Healy, E.C.; Hardman, R.R. [Southern Company Services, Inc., Birmingham, AL (United States); Baldwin, A.L. [Dept. of Energy, Pittsburgh, PA (United States)

    1997-12-31

    This paper describes the completed Innovative Clean Coal Technology project which demonstrated SCR technology for reduction of flue gas NO{sub x} emissions from a utility boiler burning US high-sulfur coal. The project was sponsored by the US Department of Energy, managed and co-funded by Southern Company Services, Inc. on behalf of the Southern Company, and also co-funded by the Electric Power Research Institute and Ontario Hydro. The project was located at Gulf Power Company`s Plant Crist Unit 5 (a 75 MW tangentially-fired boiler burning US coals that had a sulfur content ranging from 2.5--2.9%), near Pensacola, Florida. The test program was conducted for approximately two years to evaluate catalyst deactivation and other SCR operational effects. The SCR test facility had nine reactors: three 2.5 MW (5,000 scfm), and operated on low-dust flue gas. The reactors operated in parallel with commercially available SCR catalysts obtained from suppliers throughout the world. Long-term performance testing began in July 1993 and was completed in July 1995. A brief test facility description and the results of the project are presented in this paper.

  7. Tumor-extrinsic discoidin domain receptor 1 promotes mammary tumor growth by regulating adipose stromal interleukin 6 production in mice.

    Science.gov (United States)

    Sun, Xiujie; Gupta, Kshama; Wu, Bogang; Zhang, Deyi; Yuan, Bin; Zhang, Xiaowen; Chiang, Huai-Chin; Zhang, Chi; Curiel, Tyler J; Bendeck, Michelle P; Hursting, Stephen; Hu, Yanfen; Li, Rong

    2018-02-23

    Discoidin domain receptor 1 (DDR1) is a collagen receptor that mediates cell communication with the extracellular matrix (ECM). Aberrant expression and activity of DDR1 in tumor cells are known to promote tumor growth. Although elevated DDR1 levels in the stroma of breast tumors are associated with poor patient outcome, a causal role for tumor-extrinsic DDR1 in cancer promotion remains unclear. Here we report that murine mammary tumor cells transplanted to syngeneic recipient mice in which Ddr1 has been knocked out (KO) grow less robustly than in WT mice. We also found that the tumor-associated stroma in Ddr1- KO mice exhibits reduced collagen deposition compared with the WT controls, supporting a role for stromal DDR1 in ECM remodeling of the tumor microenvironment. Furthermore, the stromal-vascular fraction (SVF) of Ddr1 knockout adipose tissue, which contains committed adipose stem/progenitor cells and preadipocytes, was impaired in its ability to stimulate tumor cell migration and invasion. Cytokine array-based screening identified interleukin 6 (IL-6) as a cytokine secreted by the SVF in a DDR1-dependent manner. SVF-produced IL-6 is important for SVF-stimulated tumor cell invasion in vitro , and, using antibody-based neutralization, we show that tumor promotion by IL-6 in vivo requires DDR1. In conclusion, our work demonstrates a previously unrecognized function of DDR1 in promoting tumor growth. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine [beta]-synthase

    Energy Technology Data Exchange (ETDEWEB)

    Koutmos, Markos; Kabil, Omer; Smith, Janet L.; Banerjee, Ruma (Michigan-Med)

    2011-08-17

    The catalytic potential for H{sub 2}S biogenesis and homocysteine clearance converge at the active site of cystathionine {beta}-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes {beta}-replacement reactions of either serine or cysteine by homocysteine to give cystathionine and water or H{sub 2}S, respectively. In this study, high-resolution structures of the full-length enzyme from Drosophila in which a carbanion (1.70 {angstrom}) and an aminoacrylate intermediate (1.55 {angstrom}) have been captured are reported. Electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base. Additional stabilizing interactions between active site residues and the catalytic intermediates are observed. Furthermore, the structure of the regulatory 'energy-sensing' CBS domains, named after this protein, suggests a mechanism for allosteric activation by S-adenosylmethionine.

  9. Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B12 Enzyme IcmF.

    Science.gov (United States)

    Li, Zhu; Kitanishi, Kenichi; Twahir, Umar T; Cracan, Valentin; Chapman, Derrell; Warncke, Kurt; Banerjee, Ruma

    2017-03-10

    IcmF is a 5'-deoxyadenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the carbon skeleton rearrangement of isobutyryl-CoA to butyryl-CoA. It is a bifunctional protein resulting from the fusion of a G-protein chaperone with GTPase activity and the cofactor- and substrate-binding mutase domains with isomerase activity. IcmF is prone to inactivation during catalytic turnover, thus setting up its dependence on a cofactor repair system. Herein, we demonstrate that the GTPase activity of IcmF powers the ejection of the inactive cob(II)alamin cofactor and requires the presence of an acceptor protein, adenosyltransferase, for receiving it. Adenosyltransferase in turn converts cob(II)alamin to AdoCbl in the presence of ATP and a reductant. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Vanadia-based SCR Catalysts Supported on Tungstated and Sulfated Zirconia: Influence of Doping with Potassium

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Boghosian, Soghomon; Kustov, Arkadii

    2007-01-01

    A series of vanadium-based SCR catalysts supported on sulfated or tungstated ZrO2 were synthesized and characterized by means of N2-BET, XRD, NH3-TPD and in situ Raman spectroscopy. The effect of potassium doping on the properties of vanadia species is studied in detail. A number of catalyst...... and morphology, the surface composition and the molecular configuration of the dispersed vanadates. It was observed that poisoning with potassium had a negligible effect on the surface vanadate species (especially the V=O stretching frequency observed by in situ Raman spectroscopy) if supported on the sulfated...... the observed decrease in V=O stretching frequency and the higher proportion of dimers and higher polymers through coordination between K+ and two neighbouring V=O. The results suggest an increased resistance towards potassium doping for the vanadia-based catalysts supported on sulfated zirconia....

  11. SFMBT2 (Scm-like with four mbt domains 2) negatively regulates cell migration and invasion in prostate cancer cells.

    Science.gov (United States)

    Gwak, Jungsug; Shin, Jee Yoon; Lee, Kwanghyun; Hong, Soon Ki; Oh, Sangtaek; Goh, Sung-Ho; Kim, Won Sun; Ju, Bong Gun

    2016-07-26

    Metastatic prostate cancer is the leading cause of morbidity and mortality in men. In this study, we found that expression level of SFMBT2 is altered during prostate cancer progression and has been associated with the migration and invasion of prostate cancer cells. The expression level of SFMBT2 is high in poorly metastatic prostate cancer cells compared to highly metastatic prostate cancer cells. We also found that SFMBT2 knockdown elevates MMP-2, MMP-3, MMP-9, and MMP-26 expression, leading to increased cell migration and invasion in LNCaP and VCaP cells. SFMBT2 interacts with YY1, RNF2, N-CoR and HDAC1/3, as well as repressive histone marks such as H3K9me2, H4K20me2, and H2AK119Ub which are associated with transcriptional repression. In addition, SFMBT2 knockdown decreased KAI1 gene expression through up-regulation of N-CoR gene expression. Expression of SFMBT2 in prostate cancer was strongly associated with clinicopathological features. Patients having higher Gleason score (≥ 8) had substantially lower SFMBT2 expression than patients with lower Gleason score. Moreover, tail vein or intraprostatic injection of SFMBT2 knockdown LNCaP cells induced metastasis. Taken together, our findings suggest that regulation of SFMBT2 may provide a new therapeutic strategy to control prostate cancer metastasis as well as being a potential biomarker of metastatic prostate cancer.

  12. V-set and Ig domain-containing 4 (VSIG4)-expressing hepatic F4/80+ cells regulate oral antigen-specific responses in mouse.

    Science.gov (United States)

    Shin, Wonhwa; Jeon, Youkyoung; Choi, Inhak; Kim, Yeon-Jeong

    2018-04-01

    Oral tolerance can prevent unnecessary immune responses against dietary antigens. Members of the B7 protein family play critical roles in the positive and/or negative regulation of T cell responses to interactions between APCs and T cells. V-set and Ig domain-containing 4 (VSIG4), a B7-related co-signaling molecule, has been known to act as a co-inhibitory ligand and may be critical in establishing immune tolerance. Therefore, we investigated the regulation of VSIG4 signaling in a food allergy and experimental oral tolerance murine models. We analyzed the contributions of the two main sites involved in oral tolerance, the mesenteric lymph node (MLN) and the liver, in VSIG4-mediated oral tolerance induction. Through the comparative analysis of major APCs, dendritic cells (DCs) and macrophages, we found that Kupffer cells play a critical role in inducing regulatory T cells (Tregs) and establishing immune tolerance against oral antigens via VSIG4 signaling. Taken together, these results suggest the possibility of VSIG4 signaling-based regulation of orally administered antigens. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Tungsten Recovery from Spent SCR Catalyst Using Alkaline Leaching and Ion Exchange

    Directory of Open Access Journals (Sweden)

    Wen-Cheng Wu

    2016-10-01

    Full Text Available The recovery of tungsten (W from a honeycomb-type spent selective catalytic reduction (SCR catalyst using an alkaline leaching–ion exchange method was investigated. Spent SCR catalyst mainly consists of TiO2 and other oxides (6.37% W, 1.57% vanadium (V, and 2.81% silicon (Si, etc.. The ground catalyst was leached at the optimal conditions, as follows: NaOH concentration of 0.3 kg/kg of catalyst, pulp density of 3%, leaching temperature of 70 °C, particle size of −74 μm, and leaching time of 30 min. In this study, the leaching rate values of V and W under the above conditions were 87 wt %, and 91 wt %, respectively. The pregnant solution was then passed through a strong base anion exchange resin (Amberlite IRA900. At high pH conditions, the use of strong base anion exchange resin led to selective loading of divalent WO42− from the solution, because the fraction of two adjacent positively-charged sites on the IRA900 resin was higher and separate from the coexisting VO43−. The adsorbed W could then be eluted with 1 M NaCl + 0.5 M NaOH. The final concentrated W solution had 8.4 g/L of W with 98% purity. The application of this process in industry is expected to have an important impact on the recovery of W from secondary sources of these metals.

  14. Dominant gain-of-function mutations in transmembrane domain III of ERS1 and ETR1 suggest a novel role for this domain in regulating the magnitude of ethylene response in Arabidopsis.

    Science.gov (United States)

    Deslauriers, Stephen D; Alvarez, Ashley A; Lacey, Randy F; Binder, Brad M; Larsen, Paul B

    2015-10-01

    Prior work resulted in identification of an Arabidopsis mutant, eer5-1, with extreme ethylene response in conjunction with failure to induce a subset of ethylene-responsive genes, including AtEBP. EER5, which is a TREX-2 homolog that is part of a nucleoporin complex, functions as part of a cryptic aspect of the ethylene signaling pathway that is required for regulating the magnitude of ethylene response. A suppressor mutagenesis screen was carried out to identify second site mutations that could restore the growth of ethylene-treated eer5-1 to wild-type levels. A dominant gain-of-function mutation in the ethylene receptor ETHYLENE RESPONSE SENSOR 1 (ERS1) was identified, with the ers1-4 mutation being located in transmembrane domain III at a point nearly equivalent to the previously described etr1-2 mutation in the other Arabidopsis subfamily I ethylene receptor, ETHYLENE RESPONSE 1 (ETR1). Although both ers1-4 and etr1-2 partially suppress the ethylene hypersensitivity of eer5-1 and are at least in part REVERSION TO ETHYLENE SENSITIVITY 1 (RTE1)-dependent, ers1-4 was additionally found to restore the expression of AtEBP in ers1-4;eer5-1 etiolated seedlings after ethylene treatment in an EIN3-dependent manner. Our work indicates that ERS1-regulated expression of a subset of ethylene-responsive genes is related to controlling the magnitude of ethylene response, with hyperinduction of these genes correlated with reduced ethylene-dependent growth inhibition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  15. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Chapuis, Sophie [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France); Revers, Frédéric [INRA, Université de Bordeaux, UMR 1332 de Biologie du Fruit et Pathologie, 33882 Villenave d’Ornon (France); Ziegler-Graff, Véronique [Institut de Biologie Moléculaire des Plantes, Laboratoire propre du CNRS conventionné avec l’Université de Strasbourg, 12 rue du Général Zimmer, 67084 Strasbourg (France); Brault, Véronique, E-mail: veronique.brault@colmar.inra.fr [UMR 1131 SVQV INRA-UDS, 28 rue de Herrlisheim, 68021 Colmar (France)

    2015-12-15

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT{sub Cter}) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT{sub Cter}. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT{sub Cter} in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  16. Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Yuzhou Wu

    2018-03-01

    Full Text Available Transfer cells (TCs play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP cells of Arabidopsis leaf veins trans-differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018, as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in

  17. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation

    International Nuclear Information System (INIS)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-01-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74 kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RT_C_t_e_r) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RT_C_t_e_r. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. - Highlights: • The C-terminal domain of TuYV-RT is required for long-distance movement. • CIPK7 from Arabidopsis interacts with RT_C_t_e_r in yeast and in plants. • CIPK7 overexpression increases virus titer locally but not virus systemic movement. • CIPK7 localizes to plasmodesmata. • CIPK7 could be a defense protein regulating virus export.

  18. A jasmonate ZIM-domain protein NaJAZd regulates floral jasmonic acid levels and counteracts flower abscission in Nicotiana attenuata plants.

    Directory of Open Access Journals (Sweden)

    Youngjoo Oh

    Full Text Available Jasmonic acid is an important regulator of plant growth, development and defense. The jasmonate-ZIM domain (JAZ proteins are key regulators in jasmonate signaling ubiquitously present in flowering plants but their functional annotation remains largely incomplete. Recently, we identified 12 putative JAZ proteins in native tobacco, Nicotiana attenuata, and initiated systematic functional characterization of these proteins by reverse genetic approaches. In this report, Nicotiana attenuata plants silenced in the expression of NaJAZd (irJAZd by RNA interference were used to characterize NaJAZd function. Although NaJAZd transcripts were strongly and transiently up-regulated in the rosette leaves by simulated herbivory treatment, we did not observe strong defense-related phenotypes, such as altered herbivore performance or the constitutive accumulation of defense-related secondary metabolites in irJAZd plants compared to wild type plants, both in the glasshouse and the native habitat of Nicotiana attenuata in the Great Basin Desert, Utah, USA. Interestingly, irJAZd plants produced fewer seed capsules than did wild type plants as a result of increased flower abscission in later stages of flower development. The early- and mid-developmental stages of irJAZd flowers had reduced levels of jasmonic acid and jasmonoyl-L-isoleucine, while fully open flowers had normal levels, but these were impaired in NaMYB305 transcript accumulations. Previously, NaMYB305-silenced plants were shown to have strong flower abscission phenotypes and contained lower NECTARIN 1 transcript levels, phenotypes which are copied in irJAZd plants. We propose that the NaJAZd protein is required to counteract flower abscission, possibly by regulating jasmonic acid and jasmonoyl-L-isoleucine levels and/or expression of NaMYB305 gene in Nicotiana attenuata flowers. This novel insight into the function of JAZ proteins in flower and seed development highlights the diversity of functions

  19. Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

    Science.gov (United States)

    Cai, Wang-Yu; Lin, Ling-Yun; Hao, Han; Zhang, Sai-Man; Ma, Fei; Hong, Xin-Xin; Zhang, Hui; Liu, Qing-Feng; Ye, Guo-Dong; Sun, Guang-Bin; Liu, Yun-Jia; Li, Sheng-Nan; Xie, Yuan-Yuan; Cai, Jian-Chun; Li, Bo-An

    2017-04-01

    Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221). © 2016 by the American Association for the Study of Liver Diseases.

  20. KCNK10, a Tandem Pore Domain Potassium Channel, Is a Regulator of Mitotic Clonal Expansion during the Early Stage of Adipocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Makoto Nishizuka

    2014-12-01

    Full Text Available KCNK10, a member of tandem pore domain potassium channel family, gives rise to leak K+ currents. It plays important roles in stabilizing the negative resting membrane potential and in counterbalancing depolarization. We previously demonstrated that kcnk10 expression is quickly elevated during the early stage of adipogenesis of 3T3-L1 cells and that reduction of kcnk10 expression inhibits adipocyte differentiation. However, the molecular mechanism of KCNK10 in adipocyte differentiation remains unclear. Here we revealed that kcnk10 is induced by 3-isobutyl-1-methylxanthine, a cyclic nucleotide phosphodiesterase inhibitor and a potent inducer of adipogenesis, during the early stage of adipocyte differentiation. We also demonstrated that KCNK10 functions as a positive regulator of mitotic clonal expansion (MCE, a necessary process for terminal differentiation. The reduction of kcnk10 expression repressed the expression levels of CCAAT/enhancer-binding protein β (C/EBPβ and C/EBPδ as well as the phosphorylation level of Akt during the early phase of adipogenesis. In addition, knockdown of kcnk10 expression suppressed insulin-induced Akt phosphorylation. These results indicate that KCNK10 contributes to the regulation of MCE through the control of C/EBPβ and C/EBPδ expression and insulin signaling.

  1. Regeneration of Pt-catalysts deactivated in municipal waste flue gas with H2/N2 and the effect of regeneration step on the SCR catalyst

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Rasmussen, Søren Brik; Kustov, Arkady

    The deactivation performance of Pt-catalysts for CO oxidation has been studied in relation to use in sewage sludge municipal waste burners, where HMDS was found to poison the industrial catalyst in a similar way to the model Pt/TiO2 catalyst. A promising regeneration procedure was developed based...... on reduction with hydrogen. This procedure had negligible effect on the performance of the SCR catalyst. After treatment with 2% H2, 8% O2 in N2 for one hour, a slight better NO SCR activity was observed due to increase in the concentration V4+ sites. However, after exposure in normal NO SCR gases the activity...

  2. An engineering approach to the design and construction of a small modular stellarator for magnetic confinement of plasma. SCR-1

    International Nuclear Information System (INIS)

    Barillas, Laura; Vargas, V. Iván; Alpízar, Asdrúval

    2011-01-01

    This paper briefly describes the design and construction of Stellarator of Costa Rica 1 (SCR-1) from an engineering perspective. SCR-1 is a small modular Stellarator for magnetic confinement of plasma developed by the Plasma Physics Group of the Instituto Tecnológico de Costa Rica (ITCR). The SCR-1 is based on the small Spanish Stellarator UST 1 (Ultra Small Torus 1), created by engineer Vicente Queral. Some of the characteristics of the SCR-1 are the following: it will be a 2-field period modular stellarator with an aspect ratio ≈ 6; low shear configuration with core and edge rotational transform equal to 0.32 and 0.28; it will employ stainless steel torus-shaped vacuum vessel which will hold a plasma with an average radius a ≈ 42.2 mm, a volume of 8 liters (0.008 m 3 ), and major radius R = 238 mm. This plasma will be confined by a magnetic field (B ≈ 90 mT) given by 12 modular coils with 12 turns each, carrying a current of 725 A per turn providing a total toroidal field (TF) current of 8.7 kA-turn per coil. The coils will be supplied by a bank of cell batteries of 120 V. Typical length of the plasma pulse will be between 4 s to 10 s. The plasma heating will be achieved by electron cyclotron radio-frequency (ECH) from two magnetrons providing a total power of 5 kW, at a frequency of 2.45 GHz corresponding to the first harmonic (B 0 = 87.8 mT). The expected electron temperature and density are 15 eV and 7x10 16 m -3 respectively. The initial diagnostics on the SCR-1 will consist of a Langmuir probe with a displacement system, a heterodyne microwave interferometer (frequency of 28 GHz, corresponding to a wavelength of λ = 10.71 mm). The first plasma of the SCR-1 is expected at the beginning of 2012. (author)

  3. Fermilab main accelerator quadrupole transistorized regulators for improved tune stability

    International Nuclear Information System (INIS)

    Yarema, R.J.; Pfeffer, H.

    1977-01-01

    During early operation of the Fermilab Main Accelerator, tune fluctuations, caused by the SCR-controlled power supplies in the quad bus, limited the beam aperature at low energies. To correct this problem, two transistorized power supplies were built in 1975 to regulate and filter the main ring quad magnet current during injection and beam acceleration through the rf transistion region. There is one power supply in series with each quad bus. Each supply uses 320 parallel power transistors and is rated at 300A, 120V. Since the voltage and current capabilities of the transistorized supplies are limited, the supplies are turned-off at about 25GeV. A real-time computer system initiates turn-on of the SCR-controlled power supplies and regulation takeover by the SCR-controlled supplies, at the appropriate times

  4. Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds: Inhibition of response regulator QseB by antibiofilm compounds

    Energy Technology Data Exchange (ETDEWEB)

    Milton, Morgan E.; Allen, C. Leigh; Feldmann, Erik A.; Bobay, Benjamin G.; Jung, David K.; Stephens, Matthew D.; Melander, Roberta J.; Theisen, Kelly E.; Zeng, Daina; Thompson, Richele J.; Melander, Christian; Cavanagh, John (NCSU)

    2017-08-16

    With antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two-component system. Two-component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics and also to trigger production of virulence factors. Drugs that target the response regulator portion of two-component systems represent a potent new approach so far unexploited. Here, we focus efforts on the highly virulent bacterium Francisella tularensis tularensis. Francisella contains only three response regulators, making it an ideal system to study. In this study, we initially present the structure of the N-terminal domain of QseB, the response regulator responsible for biofilm formation. Subsequently, using binding assays, computational docking and cellular studies, we show that QseB interacts with2-aminoimidazole based compounds that impede its function. This information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics.

  5. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studies....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

  6. Innovative clean coal technology (ICCT): demonstration of selective catalytic reduction (SCR) technology for the control of nitrogen oxide (NOx) emission from high-sulfur, coal-fired boilers - economic evaluation of commercial-scale SCR applications for utility boilers

    International Nuclear Information System (INIS)

    Healy, E.C.; Maxwell, J.D.; Hinton, W.S.

    1996-09-01

    This report presents the results of an economic evaluation produced as part of the Innovative Clean Coal Technology project, which demonstrated selective catalytic reduction (SCR) technology for reduction of NO x emissions from utility boilers burning U.S. high-sulfur coal. The document includes a commercial-scale capital and O ampersand M cost evaluation of SCR technology applied to a new facility, coal-fired boiler utilizing high-sulfur U.S. coal. The base case presented herein determines the total capital requirement, fixed and variable operating costs, and levelized costs for a new 250-MW pulverized coal utility boiler operating with a 60-percent NO x removal. Sensitivity evaluations are included to demonstrate the variation in cost due to changes in process variables and assumptions. This report also presents the results of a study completed by SCS to determine the cost and technical feasibility of retrofitting SCR technology to selected coal-fired generating units within the Southern electric system

  7. The Nonreceptor Protein Tyrosine Phosphatase PTP1B Binds to the Cytoplasmic Domain of N-Cadherin and Regulates the Cadherin–Actin Linkage

    Science.gov (United States)

    Balsamo, Janne; Arregui, Carlos; Leung, TinChung; Lilien, Jack

    1998-01-01

    Cadherin-mediated adhesion depends on the association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated by a group of cytoplasmic proteins: α-and β- or γ- catenin. Phosphorylation of β-catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine phosphatase, bound to the cytoplasmic domain of N-cadherin, is responsible for removing tyrosine-bound phosphate residues from β-catenin, thus maintaining the cadherin–actin connection (Balsamo et al., 1996). Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship between the function of cadherin-bound PTP1B and cadherin-mediated adhesion, we tested the effect of expressing a catalytically inactive form of PTP1B in L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with actin, and β-catenin shows increased phosphorylation on tyrosine residues when compared with parental cells or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found associated with N-cadherin, and recombinant mutant PTP1B binds to N-cadherin in vitro, indicating that the catalytically inactive form acts as a dominant negative, displacing endogenous PTP1B, and rendering cadherin nonfunctional. Our results demonstrate a role for PTP1B in regulating cadherin-mediated cell adhesion. PMID:9786960

  8. Development of Optimal Catalyst Designs and Operating Strategies for Lean NOx Reduction in Coupled LNT-SCR Systems

    Energy Technology Data Exchange (ETDEWEB)

    Harold, Michael [Univ. of Houston, TX (United States); Crocker, Mark [Univ. of Kentucky, Lexington, KY (United States); Balakotaiah, Vemuri [Univ. of Houston, TX (United States); Luss, Dan [Univ. of Houston, TX (United States); Choi, Jae-Soon [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dearth, Mark [Ford Motor Company, Dearborn, MI (United States); McCabe, Bob [Ford Motor Company, Dearborn, MI (United States); Theis, Joe [Ford Motor Company, Dearborn, MI (United States)

    2013-09-30

    Oxides of nitrogen in the form of nitric oxide (NO) and nitrogen dioxide (NO2) commonly referred to as NOx, is one of the two chemical precursors that lead to ground-level ozone, a ubiquitous air pollutant in urban areas. A major source of NOx} is generated by equipment and vehicles powered by diesel engines, which have a combustion exhaust that contains NOx in the presence of excess O2. Catalytic abatement measures that are effective for gasoline-fueled engines such as the precious metal containing three-way catalytic converter (TWC) cannot be used to treat O2-laden exhaust containing NOx. Two catalytic technologies that have emerged as effective for NOx abatement are NOx storage and reduction (NSR) and selective catalytic reduction (SCR). NSR is similar to TWC but requires much larger quantities of expensive precious metals and sophisticated periodic switching operation, while SCR requires an on-board source of ammonia which serves as the chemical reductant of the NOx. The fact that NSR produces ammonia as a byproduct while SCR requires ammonia to work has led to interest in combining the two together to avoid the need for the cumbersome ammonia generation system. In this project a comprehensive study was carried out of the fundamental aspects and application feasibility of combined NSR/SCR. The project team, which included university, industry, and national lab researchers, investigated the kinetics and mechanistic features of the underlying chemistry in the lean NOx trap (LNT) wherein NSR was carried out, with particular focus on identifying the operating conditions such as temperature and catalytic properties which lead to the production of ammonia in the LNT. The performance features of SCR on both model and commercial catalysts focused on the synergy between the LNT and SCR converters in terms of utilizing the upstream-generated ammonia and

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

    Directory of Open Access Journals (Sweden)

    Caitlin L Rowe

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

  10. Redox behaviour of vanadium during hydrogen-oxygen exposure of the V2O5-WO3/TiO2 SCR catalyst at 250 degrees C

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Rasmussen, Søren B.; Mikolajska, Ewelina

    2011-01-01

    of H-2 (0-2%) in an 8% O-2/N-2 mixture, where the SCR activity was measured before and after the hydrogen treatment. The results show that the activity of the SCR catalyst is only negligibly affected during exposure to the H-2/O-2 gas and in all cases it returned reversibly to the initial NOx...... conversion rate after reexposure to the standard NH3-SCR gas. In situ electron paramagnetic resonance (EPR) and UV-vis spectroscopy at 250 degrees C suggest that a significant part of V4+ present during SCR conditions was oxidized to V5+ during exposure to 2% H-2 + 8% O-2. However, the distribution...

  11. p53 down-regulates SARS coronavirus replication and is targeted by the SARS-unique domain and PLpro via E3 ubiquitin ligase RCHY1

    Science.gov (United States)

    Ma-Lauer, Yue; Carbajo-Lozoya, Javier; Müller, Marcel A.; Deng, Wen; Lei, Jian; Meyer, Benjamin; Kusov, Yuri; von Brunn, Brigitte; Bairad, Dev Raj; Hünten, Sabine; Drosten, Christian; Hermeking, Heiko; Leonhardt, Heinrich; Mann, Matthias; Hilgenfeld, Rolf; von Brunn, Albrecht

    2016-01-01

    Highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) has developed strategies to inhibit host immune recognition. We identify cellular E3 ubiquitin ligase ring-finger and CHY zinc-finger domain-containing 1 (RCHY1) as an interacting partner of the viral SARS-unique domain (SUD) and papain-like protease (PLpro), and, as a consequence, the involvement of cellular p53 as antagonist of coronaviral replication. Residues 95–144 of RCHY1 and 389–652 of SUD (SUD-NM) subdomains are crucial for interaction. Association with SUD increases the stability of RCHY1 and augments RCHY1-mediated ubiquitination as well as degradation of p53. The calcium/calmodulin-dependent protein kinase II delta (CAMK2D), which normally influences RCHY1 stability by phosphorylation, also binds to SUD. In vivo phosphorylation shows that SUD does not regulate phosphorylation of RCHY1 via CAMK2D. Similarly to SUD, the PLpros from SARS-CoV, MERS-CoV, and HCoV-NL63 physically interact with and stabilize RCHY1, and thus trigger degradation of endogenous p53. The SARS-CoV papain-like protease is encoded next to SUD within nonstructural protein 3. A SUD–PLpro fusion interacts with RCHY1 more intensively and causes stronger p53 degradation than SARS-CoV PLpro alone. We show that p53 inhibits replication of infectious SARS-CoV as well as of replicons and human coronavirus NL63. Hence, human coronaviruses antagonize the viral inhibitor p53 via stabilizing RCHY1 and promoting RCHY1-mediated p53 degradation. SUD functions as an enhancer to strengthen interaction between RCHY1 and nonstructural protein 3, leading to a further increase in in p53 degradation. The significance of these findings is that down-regulation of p53 as a major player in antiviral innate immunity provides a long-sought explanation for delayed activities of respective genes. PMID:27519799

  12. Spectroscopic Insights into Copper-Based Microporous Zeolites for NH3-SCR of NOx and Methane-to-Methanol Activation

    OpenAIRE

    Oord, R.

    2017-01-01

    Smog has received a lot of attention and is still a major problem in big cities all over the world. A major contribution to smog are nitrogen oxides (NOx), which are mainly produced by road transport, industrial processes and power plants. A lot of research has been put into the reduction of these pollutants, and heterogeneous catalysts have made a major contribution to this field. Selective catalytic reduction (SCR) is an efficient technology to reduce these NOx, and is already used in diese...

  13. Developing the multiple stress-strain creep recovery (MS-SCR) test

    Science.gov (United States)

    Elnasri, Mahmoud; Airey, Gordon; Thom, Nick

    2018-04-01

    While most published work from Europe has been concerned with evaluating binders' resistance to rutting based on their stiffness (deformation resistance), work originating in the US has mainly been concerned with ranking binders based on their recoverability in a multiple stress form. This paper details the design of a new modified multiple stress-strain creep recovery (MS-SCR) test. The test is designed to evaluate binders' rutting resistance based on two rutting resistance mechanisms: stiffness and recoverability. A preliminary investigation is presented in this paper followed by details of the design of the new modified test. A 40/60 penetration grade bitumen and bitumen-filler mastics prepared with three filler concentrations (35%, 50%, and 65% filler content by mass of mastic) were tested. In addition, two polymer modified bitumens (PMBs) using the same base bitumen type were examined for validation. Two parameters are introduced to characterise the short and long recovery in the new test. In terms of stiffness, the test allows the behaviour of binders at different stress levels and loading cycles to be studied and produces a new parameter that can quantify the degree of modification. Finally, a relationship between nonlinearity and normal force in the test was investigated.

  14. Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

    Science.gov (United States)

    Parikh, Amay; Rizzo, John A; Canetta, Pietro; Forster, Catherine; Sise, Meghan; Maarouf, Omar; Singer, Eugenia; Elger, Antje; Elitok, Saban; Schmidt-Ott, Kai; Barasch, Jonathon; Nickolas, Thomas L

    2017-01-01

    Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

  15. Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL & serum creatinine (sCr for acute kidney injury (AKI diagnosis.

    Directory of Open Access Journals (Sweden)

    Amay Parikh

    Full Text Available Urine neutrophil gelatinase-associated lipocalin (uNGAL is a sensitive and specific diagnostic test for acute kidney injury (AKI in the Emergency Department (ED, but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone.A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr. A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated.For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients. Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs.Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

  16. SCR at bio fuels combustion - phase 2. Measures to extend catalyst life time; SCR vid biobraensleeldning - etapp 2. Aatgaerder foer att foerlaenga katalysatorns livslaengd

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Christer; Bodin, Henrik; Sahlqvist, Aasa [Vattenfall Utveckling AB, Aelvkarleby (Sweden); Khodayari, Raziyeh; Odenbrand, Ingemar [Lund Univ. (Sweden). Dept. of Chemical Engineering II

    2000-07-01

    In this project phase, the deactivation of catalysts during combustion of bio fuels, and different methods of regeneration have been investigated. The overall purpose is to improve the economic and technical possibilities to use SCR at bio fuels combustion. The two different methods for regeneration are washing with water and so called sulphation (treatment with sulphur dioxide). The results from wood fired FB-boilers show that the catalyst lose 25% (average) of the relative activity during a normal heat production season. The tendency is that a boiler with short residence time between final combustion and catalyst and/or high flame temperatures gives a faster deactivation. Such unfavourable conditions arise in FB-boilers with a large part of the combustion in freeboard/cyclone. The alkali content of the fuel (wood fuel) is of minor importance for the deactivation rate compared with the combustion conditions. The flue gas temperature within the interval 250 - 375 deg C is not an important parameter for the deactivation in the time interval 3 000 - 6 000 h. The 'new' honeycomb catalysts that were tested during phase two, BiotypA-C, evidently show different deactivation trends. The highly active BiotypC e.g. increases its activity during the first thousand hours. Calculations indicate that BiotypC at 315 deg C requires the smallest volume of catalyst over ten years of operation in order to maintain given performance. Practical consequences for downstream equipment also need to be carefully checked. Sulphation with SO{sub 2} works in the laboratory as a regeneration method for all of the tested samples. The sulphatised samples deactivation are almost comparable to a fresh sample when exposed to flue gas. About 80 % of the lost activity can be regained only by using sulphation. Plate-type catalysts gets a somewhat lower increase in activity compared to honeycomb-types, probably related to chemical rather than geometric design. High SO{sub 2}-concentration

  17. FTIR in situ mechanistic study of the NH3-NO/NO2 "Fast SCR" reaction over a commercial Fe-ZSM-5 catalyst

    Czech Academy of Sciences Publication Activity Database

    Ruggeri, M. P.; Grossale, A.; Nova, I.; Tronconi, E.; Jirglová, Hana; Sobalík, Zdeněk

    2012-01-01

    Roč. 184, č. 1 (2012), s. 107-114 ISSN 0920-5861 R&D Projects: GA AV ČR KAN100400702; GA ČR GA203/09/1627 Institutional research plan: CEZ:AV0Z40400503 Keywords : urea /NH3 SCR * fast SCR * NO2 adsorption Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.980, year: 2012

  18. Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

    Science.gov (United States)

    Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

    2016-09-01

    In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. CMTM3 (CKLF-Like Marvel Transmembrane Domain 3) Mediates Angiogenesis by Regulating Cell Surface Availability of VE-Cadherin in Endothelial Adherens Junctions.

    Science.gov (United States)

    Chrifi, Ihsan; Louzao-Martinez, Laura; Brandt, Maarten; van Dijk, Christian G M; Burgisser, Petra; Zhu, Changbin; Kros, Johan M; Duncker, Dirk J; Cheng, Caroline

    2017-06-01

    Decrease in VE-cadherin adherens junctions reduces vascular stability, whereas disruption of adherens junctions is a requirement for neovessel sprouting during angiogenesis. Endocytosis plays a key role in regulating junctional strength by altering bioavailability of cell surface proteins, including VE-cadherin. Identification of new mediators of endothelial endocytosis could enhance our understanding of angiogenesis. Here, we assessed the function of CMTM3 (CKLF-like MARVEL transmembrane domain 3), which we have previously identified as highly expressed in Flk1 + endothelial progenitor cells during embryonic development. Using a 3-dimensional coculture of human umbilical vein endothelial cells-GFP (green fluorescent protein) and pericytes-RFP (red fluorescent protein), we demonstrated that siRNA-mediated CMTM3 silencing in human umbilical vein endothelial cells impairs angiogenesis. In vivo CMTM3 inhibition by morpholino injection in developing zebrafish larvae confirmed that CMTM3 expression is required for vascular sprouting. CMTM3 knockdown in human umbilical vein endothelial cells does not affect proliferation or migration. Intracellular staining demonstrated that CMTM3 colocalizes with early endosome markers EEA1 (early endosome marker 1) and Clathrin + vesicles and with cytosolic VE-cadherin in human umbilical vein endothelial cells. Adenovirus-mediated CMTM3 overexpression enhances endothelial endocytosis, shown by an increase in Clathrin + , EEA1 + , Rab11 + , Rab5 + , and Rab7 + vesicles. CMTM3 overexpression enhances, whereas CMTM3 knockdown decreases internalization of cell surface VE-cadherin in vitro. CMTM3 promotes loss of endothelial barrier function in thrombin-induced responses, shown by transendothelial electric resistance measurements in vitro. In this study, we have identified a new regulatory function for CMTM3 in angiogenesis. CMTM3 is involved in VE-cadherin turnover and is a regulator of the cell surface pool of VE-cadherin. Therefore, CMTM

  20. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    International Nuclear Information System (INIS)

    Tsukamoto, Yuta; Kagiwada, Satoshi; Shimazu, Sayuri; Takegawa, Kaoru; Noguchi, Tetsuko; Miyamoto, Masaaki

    2015-01-01

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed

  1. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Yuta [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Kagiwada, Satoshi [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Shimazu, Sayuri [Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Takegawa, Kaoru [Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Noguchi, Tetsuko [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan)

    2015-03-20

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

  2. Process identification of the SCR system of coal-fired power plant for de-NOx based on historical operation data.

    Science.gov (United States)

    Li, Jian; Shi, Raoqiao; Xu, Chuanlong; Wang, Shimin

    2018-05-08

    The selective catalytic reduction (SCR) system, as one principal flue gas treatment method employed for the NO x emission control of the coal-fired power plant, is nonlinear and time-varying with great inertia and large time delay. It is difficult for the present SCR control system to achieve satisfactory performance with the traditional feedback and feedforward control strategies. Although some improved control strategies, such as the Smith predictor control and the model predictive control, have been proposed for this issue, a well-matched identification model is essentially required to realize a superior control of the SCR system. Industrial field experiment is an alternative way to identify the SCR system model in the coal-fired power plant. But it undesirably disturbs the operation system and is costly in time and manpower. In this paper, a process identification model of the SCR system is proposed and developed by applying the asymptotic method to the sufficiently excited data, selected from the original historical operation database of a 350 MW coal-fired power plant according to the condition number of the Fisher information matrix. Numerical simulations are carried out based on the practical historical operation data to evaluate the performance of the proposed model. Results show that the proposed model can efficiently achieve the process identification of the SCR system.

  3. The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.

    Science.gov (United States)

    Quilty, Douglas; Chan, Calvin J; Yurkiw, Katherine; Bain, Alexandra; Babolmorad, Ghazal; Melançon, Paul

    2018-04-19

    We previously proposed a novel mechanism by which the enzyme Golgi-specific Brefeldin A resistance factor 1 (GBF1) is recruited to the membranes of the cis -Golgi, based on in vivo experiments. Here, we extended our in vivo analysis on the production of regulatory Arf-GDP and observed that ArfGAP2 and ArfGAP3 do not play a role in GBF1 recruitment. We confirm that Arf-GDP localization is critical, as a TGN-localized Arf-GDP mutant protein fails to promote GBF1 recruitment. We also reported the establishment of an in vitro GBF1 recruitment assay that supports the regulation of GBF1 recruitment by Arf-GDP. This in vitro assay yielded further evidence for the requirement of a Golgi-localized protein because heat denaturation or protease treatment of Golgi membranes abrogated GBF1 recruitment. Finally, combined in vivo and in vitro measurements indicated that the recruitment to Golgi membranes via a putative receptor requires only the HDS1 and HDS2 domains in the C-terminal half of GBF1. © 2018. Published by The Company of Biologists Ltd.

  4. The cytoplasmic domain close to the transmembrane region of the glucagon-like peptide-1 receptor contains sequence elements that regulate agonist-dependent internalisation.

    Science.gov (United States)

    Vázquez, Patricia; Roncero, Isabel; Blázquez, Enrique; Alvarez, Elvira

    2005-07-01

    In order to gain better insight into the molecular events involved in the signal transduction generated through glucagon-like peptide-1 (GLP-1) receptors, we tested the effect of deletions and point mutations within the cytoplasmic tail of this receptor with a view to establishing relationships between signal transduction desensitisation and receptor internalisation. Wild-type and truncated (deletion of the last 27 amino acids (GLPR 435R) and deletion of 44 amino acids (GLPR 418R)) GLP-1 receptors bound the agonist with similar affinity. Deletion of the last 27 amino acids decreased the internalisation rate by 78%, while deletion of 44 amino acids containing all the phosphorylation sites hitherto described in this receptor decreased the internalisation rate by only 47%. Binding of the ligand to both receptors stimulated adenylyl cyclase. In contrast, deletion of the region containing amino acids 419 to 435 (GLPR 419delta435) increased the internalisation rate by 268%, and the replacement of EVQ(408-410) by alanine (GLPR A(408-410)) increased this process to 296%. In both receptors, the efficacy in stimulating adenylate cyclase was decreased. All the receptors studied were internalised by coated pits, except for the receptor with a deletion of the last 44 amino acids, which also had a faster resensitisation rate. Our findings indicate that the neighbouring trans-membrane domain of the carboxyl-terminal tail of the GLP-1 receptor contains sequence elements that regulate agonist-dependent internalisation and transmembrane signalling.

  5. A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population.

    Science.gov (United States)

    Ito, Yoshihito; Nakamura, Yukako; Takahashi, Nagahide; Saito, Shinichi; Aleksic, Branko; Iwata, Nakao; Inada, Toshiya; Ozaki, Norio

    2008-06-13

    The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primarily expressed in the brain. Phosphohippolin modulates the kinetic activity of Na,K-ATPase and has long-term physiological importance in maintaining cation homeostasis. A recent study reported that FXYD6 was associated with schizophrenia in the United Kingdom samples. Applying the gene-based association concept, we carried out an association study regarding FXYD6 and schizophrenia in a Japanese population, with a sample consisting of 2026 subjects (906 schizophrenics and 1120 controls). After linkage disequilibrium analysis, 23 single nucleotide polymorphisms (SNPs) were genotyped using 5'-exonuclease allelic discrimination assay. We found a significant association of two SNPs (rs11216573; genotypic P value: 0.022 and rs555577; genotypic P value: 0.026, allelic P value: 0.011, uncorrected). Nominal P values did not survive correction for multiple testing (rs11216573; genotypic P value: 0.47 and rs555577; genotypic P value: 0.55, allelic P value: 0.24, after SNPSpD correction). No association was observed between schizophrenia patients and controls in allelic, genotypic and haplotypic analyses. Our findings suggest that FXYD6 is unlikely to be related to the development of schizophrenia in a Japanese population.

  6. A protein kinase binds the C-terminal domain of the readthrough protein of Turnip yellows virus and regulates virus accumulation.

    Science.gov (United States)

    Rodriguez-Medina, Caren; Boissinot, Sylvaine; Chapuis, Sophie; Gereige, Dalya; Rastegar, Maryam; Erdinger, Monique; Revers, Frédéric; Ziegler-Graff, Véronique; Brault, Véronique

    2015-12-01

    Turnip yellows virus (TuYV), a phloem-limited virus, encodes a 74kDa protein known as the readthrough protein (RT) involved in virus movement. We show here that a TuYV mutant deleted of the C-terminal part of the RT protein (TuYV-∆RTCter) was affected in long-distance trafficking in a host-specific manner. By using the C-terminal domain of the RT protein as a bait in a yeast two-hybrid screen of a phloem cDNA library from Arabidopsis thaliana we identified the calcineurin B-like protein-interacting protein kinase-7 (AtCIPK7). Transient expression of a GFP:CIPK7 fusion protein in virus-inoculated Nicotiana benthamiana leaves led to local increase of wild-type TuYV accumulation, but not that of TuYV-∆RTCter. Surprisingly, elevated virus titer in inoculated leaves did not result in higher TuYV accumulation in systemic leaves, which indicates that virus long-distance movement was not affected. Since GFP:CIPK7 was localized in or near plasmodesmata, CIPK7 could negatively regulate TuYV export from infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

    Science.gov (United States)

    Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

    2015-11-01

    Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

  8. Numerical Investigation of AdBlue Droplet Evaporation and Thermal Decomposition in the Context of NOx-SCR Using a Multi-Component Evaporation Model

    Directory of Open Access Journals (Sweden)

    Kaushal Nishad

    2018-01-01

    Full Text Available To cope with the progressive tightening of the emission regulations, gasoline and diesel engines will continuously require highly improved exhaust after-treatment systems. In the case of diesel engines, the selective catalytic reduction (SCR appears as one of the widely adopted technologies to reduce NOx (nitrogen oxides emissions. Thereby, with the help of available heat from exhaust gas, the injected urea–water solution (UWS turns inside the exhaust port immediately into gaseous ammonia (NH3 by evaporation of mixture and thermal decomposition of urea. The reaction and conversion efficiency mostly depend upon the evaporation and subsequent mixing of the NH3 into the exhaust gas, which in turn depends upon the engine loading conditions. Up to now, the aggregation of urea after evaporation of water and during the thermal decomposition of urea is not clearly understood. Hence, various scenarios for the urea depletion in the gaseous phase that can be envisaged have to be appraised under SCR operating conditions relying on an appropriate evaporation description. The objective of the present paper is therefore fourfold. First, a reliable multi-component evaporation model that includes a proper binary diffusion coefficient is developed for the first time in the Euler–Lagrangian CFD (computational fluid dynamics framework to account properly for the distinct evaporation regimes of adBlue droplets under various operating conditions. Second, this model is extended for thermal decomposition of urea in the gaseous phase, where, depending on how the heat of thermal decomposition of urea is provided, different scenarios are considered. Third, since the evaporation model at and around the droplet surface is based on a gas film approach, how the material properties are evaluated in the film influences the process results is reported, also for the first time. Finally, the impact of various ambient temperatures on the adBlue droplet depletion characteristics

  9. Concrete domains

    OpenAIRE

    Kahn, G.; Plotkin, G.D.

    1993-01-01

    This paper introduces the theory of a particular kind of computation domains called concrete domains. The purpose of this theory is to find a satisfactory framework for the notions of coroutine computation and sequentiality of evaluation.

  10. Domain Engineering

    Science.gov (United States)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  11. Subtype-selective regulation of IP(3) receptors by thimerosal via cysteine residues within the IP(3)-binding core and suppressor domain.

    Science.gov (United States)

    Khan, Samir A; Rossi, Ana M; Riley, Andrew M; Potter, Barry V L; Taylor, Colin W

    2013-04-15

    IP(3)R (IP(3) [inositol 1,4,5-trisphosphate] receptors) and ryanodine receptors are the most widely expressed intracellular Ca(2+) channels and both are regulated by thiol reagents. In DT40 cells stably expressing single subtypes of mammalian IP(3)R, low concentrations of thimerosal (also known as thiomersal), which oxidizes thiols to form a thiomercurylethyl complex, increased the sensitivity of IP(3)-evoked Ca(2+) release via IP(3)R1 and IP(3)R2, but inhibited IP(3)R3. Activation of IP(3)R is initiated by IP(3) binding to the IBC (IP(3)-binding core; residues 224-604) and proceeds via re-arrangement of an interface between the IBC and SD (suppressor domain; residues 1-223). Thimerosal (100 μM) stimulated IP(3) binding to the isolated NT (N-terminal; residues 1-604) of IP(3)R1 and IP(3)R2, but not to that of IP(3)R3. Binding of a competitive antagonist (heparin) or partial agonist (dimeric-IP(3)) to NT1 was unaffected by thiomersal, suggesting that the effect of thimerosal is specifically related to IP(3)R activation. IP(3) binding to NT1 in which all cysteine residues were replaced by alanine was insensitive to thimerosal, so too were NT1 in which cysteine residues were replaced in either the SD or IBC. This demonstrates that thimerosal interacts directly with cysteine in both the SD and IBC. Chimaeric proteins in which the SD of the IP(3)R was replaced by the structurally related A domain of a ryanodine receptor were functional, but thimerosal inhibited both IP(3) binding to the chimaeric NT and IP(3)-evoked Ca(2+) release from the chimaeric IP(3)R. This is the first systematic analysis of the effects of a thiol reagent on each IP(3)R subtype. We conclude that thimerosal selectively sensitizes IP(3)R1 and IP(3)R2 to IP(3) by modifying cysteine residues within both the SD and IBC and thereby stabilizing an active conformation of the receptor.

  12. Subtype-selective regulation of IP3 receptors by thimerosal via cysteine residues within the IP3-binding core and suppressor domain

    Science.gov (United States)

    Khan, Samir A.; Rossi, Ana M.; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.

    2013-01-01

    IP3R (IP3 [inositol 1,4,5-trisphosphate] receptors) and ryanodine receptors are the most widely expressed intracellular Ca2+ channels and both are regulated by thiol reagents. In DT40 cells stably expressing single subtypes of mammalian IP3R, low concentrations of thimerosal (also known as thiomersal), which oxidizes thiols to form a thiomercurylethyl complex, increased the sensitivity of IP3-evoked Ca2+ release via IP3R1 and IP3R2, but inhibited IP3R3. Activation of IP3R is initiated by IP3 binding to the IBC (IP3-binding core; residues 224–604) and proceeds via re-arrangement of an interface between the IBC and SD (suppressor domain; residues 1–223). Thimerosal (100 μM) stimulated IP3 binding to the isolated NT (N-terminal; residues 1–604) of IP3R1 and IP3R2, but not to that of IP3R3. Binding of a competitive antagonist (heparin) or partial agonist (dimeric-IP3) to NT1 was unaffected by thiomersal, suggesting that the effect of thimerosal is specifically related to IP3R activation. IP3 binding to NT1 in which all cysteine residues were replaced by alanine was insensitive to thimerosal, so too were NT1 in which cysteine residues were replaced in either the SD or IBC. This demonstrates that thimerosal interacts directly with cysteine in both the SD and IBC. Chimaeric proteins in which the SD of the IP3R was replaced by the structurally related A domain of a ryanodine receptor were functional, but thimerosal inhibited both IP3 binding to the chimaeric NT and IP3-evoked Ca2+ release from the chimaeric IP3R. This is the first systematic analysis of the effects of a thiol reagent on each IP3R subtype. We conclude that thimerosal selectively sensitizes IP3R1 and IP3R2 to IP3 by modifying cysteine residues within both the SD and IBC and thereby stabilizing an active conformation of the receptor. PMID:23282150

  13. OXIDATION OF MERCURY ACROSS SCR CATALYSTS IN COAL-FIRED POWER PLANTS BURNING LOW RANK FUELS

    Energy Technology Data Exchange (ETDEWEB)

    Constance Senior; Temi Linjewile

    2003-07-25

    This is the first Quarterly Technical Report for DOE Cooperative Agreement No: DE-FC26-03NT41728. The objective of this program is to measure the oxidation of mercury in flue gas across SCR catalyst in a coal-fired power plant burning low rank fuels using a slipstream reactor containing multiple commercial catalysts in parallel. The Electric Power Research Institute (EPRI) and Ceramics GmbH are providing co-funding for this program. This program contains multiple tasks and good progress is being made on all fronts. During this quarter, analysis of the coal, ash and mercury speciation data from the first test series was completed. Good agreement was shown between different methods of measuring mercury in the flue gas: Ontario Hydro, semi-continuous emission monitor (SCEM) and coal composition. There was a loss of total mercury across the commercial catalysts, but not across the blank monolith. The blank monolith showed no oxidation. The data from the first test series show the same trend in mercury oxidation as a function of space velocity that has been seen elsewhere. At space velocities in the range of 6,000-7,000 hr{sup -1} the blank monolith did not show any mercury oxidation, with or without ammonia present. Two of the commercial catalysts clearly showed an effect of ammonia. Two other commercial catalysts showed an effect of ammonia, although the error bars for the no-ammonia case are large. A test plan was written for the second test series and is being reviewed.

  14. WW domains of the yes-kinase-associated-protein (YAP transcriptional regulator behave as independent units with different binding preferences for PPxY motif-containing ligands.

    Directory of Open Access Journals (Sweden)

    Manuel Iglesias-Bexiga

    Full Text Available YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.

  15. Changes in pH and NADPH regulate the DNA binding activity of neuronal PAS domain protein 2, a mammalian circadian transcription factor.

    Science.gov (United States)

    Yoshii, Katsuhiro; Tajima, Fumihisa; Ishijima, Sumio; Sagami, Ikuko

    2015-01-20

    Neuronal PAS domain protein 2 (NPAS2) is a core clock transcription factor that forms a heterodimer with BMAL1 to bind the E-box in the promoter of clock genes and is regulated by various environmental stimuli such as heme, carbon monoxide, and NAD(P)H. In this study, we investigated the effects of pH and NADPH on the DNA binding activity of NPAS2. In an electrophoretic mobility shift (EMS) assay, the pH of the reaction mixture affected the DNA binding activity of the NPAS2/BMAL1 heterodimer but not that of the BMAL1/BMAL1 homodimer. A change in pH from 7.0 to 7.5 resulted in a 1.7-fold increase in activity in the absence of NADPH, and NADPH additively enhanced the activity up to 2.7-fold at pH 7.5. The experiments using truncated mutants revealed that N-terminal amino acids 1-61 of NPAS2 were sufficient to sense the change in both pH and NADPH. We further analyzed the kinetics of formation and DNA binding of the NPAS2/BMAL1 heterodimer at various pH values. In the absence of NADPH, a change in pH from 6.5 to 8.0 decreased the KD(app) value of the E-box from 125 to 22 nM, with an 8-fold increase in the maximal level of DNA binding for the NPAS2/BMAL1 heterodimer. The addition of NADPH resulted in a further decrease in KD(app) to 9 nM at pH 8.0. Furthermore, NPAS2-dependent transcriptional activity in a luciferase assay using NIH3T3 cells also increased with the pH of the culture medium. These results suggest that NPAS2 has a role as a pH and metabolite sensor in regulating circadian rhythms.

  16. Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

    Science.gov (United States)

    Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

    2014-07-18

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. A mutation within the SH2 domain of slp-76 regulates the tissue distribution and cytokine production of iNKT cells in mice.

    Science.gov (United States)

    Danzer, Claudia; Koller, Anna; Baier, Julia; Arnold, Harald; Giessler, Claudia; Opoka, Robert; Schmidt, Stephanie; Willers, Maike; Mihai, Sidonia; Parsch, Hans; Wirtz, Stefan; Daniel, Christoph; Reinhold, Annegret; Engelmann, Swen; Kliche, Stefanie; Bogdan, Christian; Hoebe, Kasper; Mattner, Jochen

    2016-09-01

    TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76(ace/ace) mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP-deficient mice. Like ADAP(-/-) iNKT cells, slp-76(ace/ace) iNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate-early gene Nur77 and a decreased adhesion to ICAM-1. Furthermore, CD11b-intrinsic effects inhibited cytokine release, concanavalin A-mediated inflammation, and iNKT-cell accumulation in the liver. Unlike B6 and ADAP(-/-) mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP-1-expression was enhanced in slp-76(ace/ace) mice. Blockade of NP-1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP-1 as an iNKT-cell-specific adhesion factor. Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. A cupin domain-containing protein with a quercetinase activity (VdQase regulates Verticillium dahliae’s pathogenicity and contributes to counteracting host defenses

    Directory of Open Access Journals (Sweden)

    Abdel eElHadrami

    2015-06-01

    Full Text Available We previously identified rutin as part of potato root responses to its pathogen Verticillium dahliae. Rutin was directly toxic to the pathogen at doses greater than 160 μM, a threshold below which many V. dahliae pathogenicity-related genes were up-regulated. We identified and characterized a cupin domain-containing protein (VdQase with a dioxygenase activity and a potential role in V. dahliae-potato interactions. The pathogenicity of VdQase knock-out mutants generated through Agrobacterium tumefasciens-mediated transformation was significantly reduced on susceptible potato cultivar Kennebec compared to wild type isolates. Fluorescence microscopy revealed a higher accumulation of flavonols in the stems of infected potatoes and a higher concentration of rutin in the leaves in response to the VdQase mutants as compared to wild type isolates. This, along with the HPLC characterization of high residual and non-utilized quercetin in presence of the knockout mutants, indicates the involvement of VdQase in the catabolism of quercetin and possibly other flavonols in planta. Quantification of Salicylic and Jasmonic Acids (SA, JA in response to the mutants versus wild type isolates revealed involvement of VdQase in the interference with signaling, suggesting a role in pathogenicity. It is hypothesized that the by-product of dioxygenation 2-protocatechuoylphloroglucinolcarboxylic acid, after dissociating into phloroglucinol and protocatechuoyl moieties, becomes a starting point for benzoic acid and SA, thereby interfering with the JA pathway and affecting the interaction outcome. These events may be key factors for V. dahliae in countering potato defenses and becoming notorious in the rhizosphere.

  19. The -271 G>A polymorphism of kinase insert domain-containing receptor gene regulates its transcription level in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    An, She-Juan; Chen, Zhi-Hong; Lin, Qiu-Xiong; Su, Jian; Chen, Hua-Jun; Lin, Jia-Ying; Wu, Yi-Long

    2009-01-01

    Kinase insert domain-containing receptor (KDR) plays a critical role in the metastasis of cancer and is used as a molecular target in cancer therapy. We investigated the characteristics of the -271 G>A polymorphism of the KDR gene to gain information that may benefit the development of individualized therapies for patients with non-small cell lung cancer (NSCLC). The -271 G>A polymorphism of the KDR gene in 106 lung cancer patients and 203 healthy control individuals was analyzed by polymerase chain reaction (PCR) and DNA sequencing methods. Real-time quantitative PCR and immunohistochemical methods were used to evaluate KDR mRNA and protein expression levels, respectively, in frozen tumor specimens. The -271 G>A polymorphism was associated with the mRNA expression level of the KDR gene in tumor tissues (t = 2.178, P = 0.032, independent samples t-test). Compared with the AG/GG genotype, the AA genotype was associated with higher KDR mRNA expression in tumor tissues. We found no relationship between the genotype and the KDR protein expression level and no significant difference in the distribution of the KDR gene polymorphism genotypes between lung cancer patients and the control group (χ 2 = 1.269, P = 0.264, Fisher's exact test). This study is the first to show that the -271 G>A polymorphism of the KDR gene may be a functional polymorphism related to the regulation of gene transcription. These findings may have important implications for therapies targeting KDR in patients with NSCLC

  20. 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.

  1. Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression.

    Science.gov (United States)

    Dejima, Takashi; Imada, Kenjiro; Takeuchi, Ario; Shiota, Masaki; Leong, Jeffrey; Tombe, Tabitha; Tam, Kevin; Fazli, Ladan; Naito, Seiji; Gleave, Martin E; Ong, Christopher J

    2017-02-01

    LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy. Flow cytometry was used to analyze cell cycle. We designed LASP1 ASO for knockdown of LASP1 in vivo studies. The expression of LASP1 in TMA was increased after androgen ablation and persisted in castration resistant prostate cancer (CRPC). Also in TMA, compared with LNCaP cell, LASP1 expression is elevated in CRPC cell lines (C4-2 and VehA cells). Interestingly, suppression of AR elevated LASP1 expression conversely, AR activation decreased LASP1 expression. Silencing of LASP1 reduced cell growth through G1 arrest which was accompanied by a decrease of cyclin D1. Forced overexpression of LASP1 promoted cell cycle and induced cell growth which was accompanied by an increase of cyclin D1. Systemic administration of LASP1 ASO with athymic mice significantly inhibited tumor growth in CRPC xenografts. These results indicate that LASP1 is negatively regulated by AR at the transcriptional level and promotes tumor growth through induction of cell cycle, ultimately suggesting that LASP1 may be a potential target in prostate cancer treatment. Prostate 77:309-320, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Impacts of halogen additions on mercury oxidation, in a slipstream selective catalyst reduction (SCR), reactor when burning sub-bituminous coal.

    Science.gov (United States)

    Cao, Yan; Gao, Zhengyang; Zhu, Jiashun; Wang, Quanhai; Huang, Yaji; Chiu, Chengchung; Parker, Bruce; Chu, Paul; Pant, Wei-Ping

    2008-01-01

    This paper presents a comparison of impacts of halogen species on the elemental mercury (Hg(0)) oxidation in a real coal-derived flue gas atmosphere. It is reported there is a higher percentage of Hg(0) in the flue gas when burning sub-bituminous coal (herein Powder River Basin (PRB) coal) and lignite, even with the use of selective catalytic reduction (SCR). The higher Hg(0)concentration in the flue gas makes it difficult to use the wet-FGD process for the mercury emission control in coal-fired utility boilers. Investigation of enhanced Hg(0) oxidation by addition of hydrogen halogens (HF, HCl, HBr, and HI) was conducted in a slipstream reactor with and without SCR catalysts when burning PRB coal. Two commercial SCR catalysts were evaluated. SCR catalyst no. 1 showed higher efficiencies of both NO reduction and Hg(0) oxidation than those of SCR catalyst no. 2. NH3 addition seemed to inhibit the Hg(0) oxidation, which indicated competitive processes between NH3 reduction and Hg(0) oxidation on the surface of SCR catalysts. The hydrogen halogens, in the order of impact on Hg(0) oxidation, were HBr, HI, and HCl or HF. Addition of HBr at approximately 3 ppm could achieve 80% Hg(0) oxidation. Addition of HI at approximately 5 ppm could achieve 40% Hg(0) oxidation. In comparison to the empty reactor, 40% Hg(0) oxidation could be achieved when HCl addition was up to 300 ppm. The enhanced Hg(0) oxidation by addition of HBr and HI seemed not to be correlated to the catalytic effects by both evaluated SCR catalysts. The effectiveness of conversion of hydrogen halogens to halogen molecules or interhalogens seemed to be attributed to their impacts on Hg(0) oxidation.

  3. The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL.

    Science.gov (United States)

    Miles, Jennifer A; Frost, Mark G; Carroll, Eilis; Rowe, Michelle L; Howard, Mark J; Sidhu, Ateesh; Chaugule, Viduth K; Alpi, Arno F; Walden, Helen

    2015-08-21

    The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. A procedure to identify and to assess risk parameters in a SCR (Steel Catenary Riser) due to the fatigue failure

    Energy Technology Data Exchange (ETDEWEB)

    Stefane, Wania [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Faculdade de Engenharia Mecanica; Morooka, Celso K. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Dept. de Engenharia de Petroleo. Centro de Estudos de Petroleo; Pezzi Filho, Mario [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). E and P. ENGP/IPMI/ES; Matt, Cyntia G.C.; Franciss, Ricardo [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES)

    2009-12-19

    The discovery of offshore fields in ultra deep water and the presence of reservoirs located in great depths below the seabed requires innovative solutions for offshore oil production systems. Many riser configurations have emerged as economically viable technological solutions for these scenarios. Therefore the study and the development of methodologies applied to riser design and procedures to calculate and to dimension production risers, taken into account the effects of mete ocean conditions, such as waves, current and platform motion in the fatigue failure is fundamental. The random nature of these conditions as well as the mechanical characteristics of the riser components are critical to a probabilistic treatment to ensure the greatest reliability for risers and minimum risks associated to different aspects of the operation like the safety of the installation, economical concerns and the environment. The current work presents a procedure of the identification and the assessment of main parameters of risk when considering fatigue failure. Static and dynamic behavior of Steel Catenary Riser (SCR) under the effects of mete ocean conditions and uncertainties related to total cumulative damage (Miner-Palmgren's rule) are taken into account. The methodology adopted is probabilistic and the approach is analytical. The procedure is based on the First Order Reliability Method (FORM) which usually presents low computational effort and acceptable accuracy. The procedure suggested is applied for two practical cases, one using data available from the literature and the second with data collected from an actual Brazilian offshore field operation. For both cases, results of the probability of failure due to fatigue were obtained for different locations along the SCR length connected to a semi-submersible platform. From these results, the sensitivity of the probability of failure due to fatigue for a SCR could be verified, and the most effective parameter could also be

  5. Gaseous emissions from a heavy-duty engine equipped with SCR aftertreatment system and fuelled with diesel and biodiesel: Assessment of pollutant dispersion and health risk

    Energy Technology Data Exchange (ETDEWEB)

    Tadano, Yara S.; Borillo, Guilherme C.; Godoi, Ana Flávia L.; Cichon, Amanda; Silva, Thiago O.B.; Valebona, Fábio B.; Errera, Marcelo R. [Environmental Engineering Department, Federal University of Parana, 210 Francisco H. dos Santos St., Curitiba, PR, 81531-980 Brazil (Brazil); Penteado Neto, Renato A.; Rempel, Dennis; Martin, Lucas [Institute of Technology for Development, Lactec–Leme Division, 01 LothárioMeissner Ave., Curitiba, PR, 80210-170 (Brazil); Yamamoto, Carlos I. [Chemical Engineering Department, Federal University of Parana, 210 Francisco H. dos Santos St., Curitiba, PR, 81531-980 Brazil (Brazil); Godoi, Ricardo H.M., E-mail: rhmgodoi@ufpr.br [Environmental Engineering Department, Federal University of Parana, 210 Francisco H. dos Santos St., Curitiba, PR, 81531-980 Brazil (Brazil)

    2014-12-01

    The changes in the composition of fuels in combination with selective catalytic reduction (SCR) emission control systems bring new insights into the emission of gaseous and particulate pollutants. The major goal of our study was to quantify NO{sub x}, NO, NO{sub 2}, NH{sub 3} and N{sub 2}O emissions from a four-cylinder diesel engine operated with diesel and a blend of 20% soybean biodiesel. Exhaust fume samples were collected from bench dynamometer tests using a heavy-duty diesel engine equipped with SCR. The target gases were quantified by means of Fourier transform infrared spectrometry (FTIR). The use of biodiesel blend presented lower concentrations in the exhaust fumes than using ultra-low sulfur diesel. NO{sub x} and NO concentrations were 68% to 93% lower in all experiments using SCR, when compared to no exhaust aftertreatment. All fuels increased NH{sub 3} and N{sub 2}O emission due to SCR, a precursor secondary aerosol, and major greenhouse gas, respectively. An AERMOD dispersion model analysis was performed on each compound results for the City of Curitiba, assumed to have a bus fleet equipped with diesel engines and SCR system, in winter and summer seasons. The health risks of the target gases were assessed using the Risk Assessment Information System For 1-h exposure of NH{sub 3}, considering the use of low sulfur diesel in buses equipped with SCR, the results indicated low risk to develop a chronic non-cancer disease. The NO{sub x} and NO emissions were the lowest when SCR was used; however, it yielded the highest NH{sub 3} concentration. The current results have paramount importance, mainly for countries that have not yet adopted the Euro V emission standards like China, India, Australia, or Russia, as well as those already adopting it. These findings are equally important for government agencies to alert the need of improvements in aftertreatment technologies to reduce pollutants emissions. - Highlights: • Emission, dispersion and risk assessment

  6. Investigation of PCDD/F emissions from mobile source diesel engines: impact of copper zeolite SCR catalysts and exhaust aftertreatment configurations.

    Science.gov (United States)

    Liu, Z Gerald; Wall, John C; Barge, Patrick; Dettmann, Melissa E; Ottinger, Nathan A

    2011-04-01

    This study investigated the impact of copper zeolite selective catalytic reduction (SCR) catalysts and exhaust aftertreatment configurations on the emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) from mobile source diesel engines. Emissions of PCDD/Fs, reported as the weighted sum of 17 congeners called the toxic equivalency quotient (TEQ), were measured using a modified EPA Method 0023A in the absence and presence of exhaust aftertreatment. Engine-out emissions were measured as a reference, while aftertreatment configurations included various combinations of diesel oxidation catalyst (DOC), diesel particulate filter (DPF), Cu-zeolite SCR, Fe-zeolite SCR, ammonia oxidation catalyst (AMOX), and aqueous urea dosing. In addition, different chlorine concentrations were evaluated. Results showed that all aftertreatment configurations reduced PCDD/F emissions in comparison to the engine-out reference, consistent with reduction mechanisms such as thermal decomposition or combined trapping and hydrogenolysis reported in the literature. Similarly low PCDD/F emissions from the DOC-DPF and the DOC-DPF-SCR configurations indicated that PCDD/F reduction primarily occurred in the DOC-DPF with no noticeable contribution from either the Cu- or Fe-zeolite SCR systems. Furthermore, experiments performed with high chlorine concentration provided no evidence that chlorine content has an impact on the catalytic synthesis of PCDD/Fs for the chlorine levels investigated in this study.

  7. Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

    Science.gov (United States)

    Tong, Dandan; Liang, Ya-Nan; Stepanova, A A; Liu, Yu; Li, Xiaobo; Wang, Letian; Zhang, Fengmin; Vasilyeva, N V

    2017-02-01

    Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis

  8. Molecular and structural characterisation of the human sodium/iodide symporter (h N.I.S.) C-terminus and the implication of this domain in the transporter regulation; Caracterisation moleculaire et structurale de l'extremite C-Terminale du co-transporteur sodium/iode humain (h N.I.S.): Implication de ce domaine dans la regulation du transporteur

    Energy Technology Data Exchange (ETDEWEB)

    Huc, S

    2007-12-15

    The human natrium iodide symporter (h N.I.S.) is an intrinsic membrane protein expressed in thyroid cells where it allows iodide uptake and accumulation. It is composed of thirteen transmembrane helices and its ninety- three amino acids long cytosolic C-terminus presents many potential post-translational regulatory sites. A first part of the PhD work has been dedicated to the expression in a bacterial system and to the purification of the cytosolic C-terminal fragment. Biochemical and structural characterisation have revealed that this C-terminus is very flexible but prone to dimerization. The fragment has also been used as a bait to test the interactions with PDZ domain proteins spotted on a membrane. Several proteins interacting with the (natrium/iodide symporter) N.I.S. C-terminus have thus been identified and the study of their implication in the protein regulation has been initiated. A second part of the work has underlined the existence of a N.I.S. fragment co-purified with the entire protein. This fragment has been found in cells in culture stably expressing N.I.S. and also in human thyroid extracts and in rodent thyroid cells. We observed that this fragment is spontaneously associated with the entire protein. It is composed of the last 131 amino acid of the protein and so comprises the last transmembrane domain and the C-terminal extremity. The expression of a truncated form of h N.I.S., lacking the last 131 amino acids, shows that this protein is not correctly addressed to the cell membrane and cells expressing this mutated symporter cannot accumulate iodide. However, our results show that the co-expression of the two N.I.S. parts, the truncated form lacking the last 131 amino acid, and the complementary C-terminal fragment, leads to cells presenting 10 % of the activity of cells expressing the whole N.I.S.. (author)

  9. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-kappaB as well as cell survival and oncogenesis

    DEFF Research Database (Denmark)

    Gyrd-Hansen, Mads; Darding, Maurice; Miasari, Maria

    2008-01-01

    found that the UBA domain is essential for the oncogenic potential of cIAP1, to maintain endothelial cell survival and to protect cells from TNF-alpha-induced apoptosis. Moreover, the UBA domain is required for XIAP and cIAP2-MALT1 to activate NF-kappaB. Our data suggest that the UBA domain of cIAP2......-MALT1 stimulates NF-kappaB signalling by binding to polyubiquitylated NEMO. Significantly, 98% of all cIAP2-MALT1 fusion proteins retain the UBA domain, suggesting that ubiquitin-binding contributes to the oncogenic potential of cIAP2-MALT1 in MALT lymphoma. Our data identify IAPs as ubiquitin...

  10. The regulation of induced depression during a frustrating situation: benefits of expressive suppression in Chinese individuals.

    Science.gov (United States)

    Yuan, Jiajin; Liu, Yingying; Ding, Nanxiang; Yang, Jiemin

    2014-01-01

    Studies from European-American cultures consistently reported that expressive suppression was associated with worse emotional consequence (e.g. depression) in comparison with acceptance. However, this conclusion may not apply to Chinese, as suppressing emotional displays to maintain relational harmony is culturally valued in East Asian countries. Thus, the present study examined the effects of suppression and acceptance on the depressive mood induced by a frustrating task in a Chinese sample. Sixty-four subjects were randomly assigned to one of three instructions: suppression, acceptance or no-regulation during a frustrating arithmetic task. The experience of depressive emotion and skin conductance response (SCR) were recorded during pre-frustration baseline, frustration induction and post-frustration recovery phases, respectively. Compared with the control and acceptance instructions, suppression instruction was associated with decreased depressive experiences and smaller SCR activity during frustration. There were no significant differences between acceptance and control groups in both subjective depression and SCR activity during frustration. Moreover, the suppression group showed a better emotional recovery after the frustrating task, in comparison with the acceptance and control groups. Correlation analyses verified that SCR reactivity was a reliable index of experienced depression during the frustration. Expressive suppression is effective in reducing depressive experiences and depression-related physiological activity (SCR) when Chinese people are involved. By contrast, the acceptance of depressive emotion in Chinese people does not produce a similar regulation effect. These findings suggest that cultural context should be considered in understanding the emotional consequences of suppression and acceptance strategies.

  11. A method of formal requirements analysis for NPP I and C systems based on object-oriented visual modeling with SCR

    International Nuclear Information System (INIS)

    Koo, S. R.; Seong, P. H.

    1999-01-01

    In this work, a formal requirements analysis method for Nuclear Power Plant (NPP) I and C systems is suggested. This method uses Unified Modeling Language (UML) for modeling systems visually and Software Cost Reduction (SCR) formalism for checking the system models. Since object-oriented method can analyze a document by the objects in a real system, UML models that use object-oriented method are useful for understanding problems and communicating with everyone involved in the project. In order to analyze the requirement more formally, SCR tabular notations is converted from UML models. To help flow-through from UML models to SCR specifications, additional syntactic extensions for UML notation and a converting procedure are defined. The combined method has been applied to Dynamic Safety System (DSS). From this application, three kinds of errors were detected in the existing DSS requirements

  12. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  13. Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

    Science.gov (United States)

    Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

    2008-11-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

  14. Surface Species and Metal Oxidation State during H2-Assisted NH3-SCR of NOx over Alumina-Supported Silver and Indium

    Directory of Open Access Journals (Sweden)

    Linda Ström

    2018-01-01

    Full Text Available Alumina-supported silver and indium catalysts are investigated for the hydrogen-assisted selective catalytic reduction (SCR of NOx with ammonia. Particularly, we focus on the active phase of the catalyst and the formation of surface species, as a function of the gas environment. Diffuse reflectance ultraviolet-visible (UV-vis spectroscopy was used to follow the oxidation state of the silver and indium phases, and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS was used to elucidate the formation of surface species during SCR conditions. In addition, the NOx reduction efficiency of the materials was evaluated using H2-assisted NH3-SCR. The DRIFTS results show that the Ag/Al2O3 sample forms NO-containing surface species during SCR conditions to a higher extent compared to the In/Al2O3 sample. The silver sample also appears to be more reduced by H2 than the indium sample, as revealed by UV-vis spectroscopic experiments. Addition of H2, however, may promote the formation of highly dispersed In2O3 clusters, which previously have been suggested to be important for the SCR reaction. The affinity to adsorb NH3 is confirmed by both temperature programmed desorption (NH3-TPD and in situ DRIFTS to be higher for the In/Al2O3 sample compared to Ag/Al2O3. The strong adsorption of NH3 may inhibit (self-poison the NH3 activation, thereby hindering further reaction over this catalyst, which is also shown by the lower SCR activity compared to Ag/Al2O3.

  15. HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6.

    Directory of Open Access Journals (Sweden)

    Shuangshuang Li

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in almost all patients with acute promyelocytic leukemia (APL via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117. Western blot analysis and quantitative real-time PCR demonstrated that HA117 causes alternative splicing of regulator of G-protein signaling 6 (RGS6 and down-regulation of the expression of the GGL domain of RGS6, which plays an important role in DNA methyltransferase 1 (DNMT1 degradation. Moreover, DNMT1 expression was increased in multi-drug resistance HL60/ATRA cells. Knockdown of HA117 restored expression of the GGL domain and blocked DNMT1 expression. Moreover, resistant cells displayed a putative stem-like signature with increased expression of cancer steam cell markers CD133 and CD123. The stem cell marker, Nanog, was significantly up-regulated. In conclusion, our study shows that HA117 potentially promotes the stem-like signature of the HL60/ATRA cell line by inhibiting by the ubiquitination and degradation of DNMT1 and by down-regulating the expression of the GGL domain of RGS6. These results throw light on the cellular events associated with the ATRA-induced multi-drug resistance phenotype in acute leukemia.

  16. Load-Independent Harmonic Mitigation in SCR-Fed Three-Phase Multiple Adjustable Speed Drive Systems with Deliberately Dispatched Firing Angles

    DEFF Research Database (Denmark)

    Yang, Yongheng; Davari, Pooya; Blaabjerg, Frede

    2018-01-01

    Adjustable speed drives (ASD) are widely used in industry for energy savings, where low-cost diode rectifiers are still employed as the front-ends, also for simplicity in control and reliability in operation. However, significant harmonics appear at the grid, which should be tackled according...... a harmonic mitigation strategy for multiple ASD systems, where silicon-controlled rectifiers (SCR) with boost converters in the dc-link have been adopted to increase the harmonic-current controllability. More specific, the SCR firing angles are deliberately dispatched among the drive units, which results...

  17. Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

    Science.gov (United States)

    Schiffmann, D A; White, J H; Cooper, A; Nutley, M A; Harding, S E; Jumel, K; Solari, R; Ray, K P; Gay, N J

    1999-09-07

    In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

  18. Olfactory receptor signaling is regulated by the post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) scaffold multi-PDZ domain protein 1.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2009-12-01

    The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30% of olfactory receptors possess a classical post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) domain binding motif in their C-termini. PDZ domains have been established as sites for protein-protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 (MUPP1) is expressed in the apical compartment of olfactory sensory neurons. Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 + 2 of MUPP1 with the C-terminus of olfactory receptors in vitro. Moreover, the odorant-elicited calcium response of OR2AG1 showed a prolonged decay in MUPP1 small interfering RNA-treated cells. We have therefore elucidated the first building blocks of the putative \\'olfactosome\\

  19. A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes.

    Science.gov (United States)

    Anosova, Irina; Melnik, Svitlana; Tripsianes, Konstantinos; Kateb, Fatiha; Grummt, Ingrid; Sattler, Michael

    2015-05-26

    The chromatin remodeling complex NoRC, comprising the subunits SNF2h and TIP5/BAZ2A, mediates heterochromatin formation at major clusters of repetitive elements, including rRNA genes, centromeres and telomeres. Association with chromatin requires the interaction of the TAM (TIP5/ARBP/MBD) domain of TIP5 with noncoding RNA, which targets NoRC to specific genomic loci. Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins. However, the TAM domain exhibits an extended MBD fold with unique C-terminal extensions that constitute a novel surface for RNA binding. Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo. Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. KEJAHATAN NAMA DOMAIN BERKAITAN DENGAN MEREK

    Directory of Open Access Journals (Sweden)

    Muhammad Nizar

    2018-02-01

    Full Text Available Indonesia already has an ITE Law governing domain names in general terms and on certain provisions in chapter VI, but the regulation of domain name crimes is not regulated in the ITE Law as mandated in the academic draft of the ITE Bill. The absence of regulation of domain name norm in the ITE Law creates problems with registrant of domain name (registrant which deliberately register the domain name is bad faith. The characteristic of a crime in a domain name relating to the mark is that the registered domain name has an equation in essence with another party’s well-known brand, the act of doing so by exploiting a reputation for well-known or previously commercially valuable names as domain names for addresses for sites (websites it manages. The Prosecutor may include articles of the KUHP in filing his indictment before the Court during the absence of special regulatory provisions concerning domain name crime.

  1. Serine 77 in the PDZ domain of PICK1 is a protein kinase Cα phosphorylation site regulated by lipid membrane binding

    DEFF Research Database (Denmark)

    Ammendrup-Johnsen, Ina; Thorsen, Thor Seneca; Gether, Ulrik

    2012-01-01

    PICK1 (protein interacting with C kinase 1) contains an N-terminal protein binding PDZ domain and a C-terminal lipid binding BAR domain. PICK1 plays a key role in several physiological processes, including synaptic plasticity. However, little is known about the cellular mechanisms governing the a...... lipid binding and/or polymerization capacity. We propose that PICK1 is phosphorylated at Ser77 by PKCα preferentially when bound to membrane vesicles and that this phosphorylation in turn modulates its cellular distribution....

  2. The drug-binding activity of the multidrug-responding transcriptional regulator BmrR resides in its C-terminal domain.

    OpenAIRE

    Markham, P N; Ahmed, M; Neyfakh, A A

    1996-01-01

    Rhodamine and tetraphenylphosphonium, the substrates of the Bacillus subtilis multidrug efflux transporter Bmr, induce the expression of Bmr through direct interaction with its transcriptional activator BmrR. Here we show that the C-terminal domain of BmrR, expressed individually, binds both these compounds and therefore can be used as a model for molecular analysis of the phenomenon of multidrug recognition.

  3. Self-Esteem Is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    Science.gov (United States)

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions,…

  4. Elucidating respective functions of two domains BIR and C-helix of human IAP survivin for precise targeted regulating mitotic cycle, apoptosis and autophagy of cancer cells.

    Science.gov (United States)

    Hu, Fabiao; Pan, Daxia; Zheng, Wenyun; Yan, Ting; He, Xiujuan; Ren, Fuzheng; Lu, Yiming; Ma, Xingyuan

    2017-12-26

    Survivin was the smallest member of the IAP family, which was over expressed in many different cancers, and considered to be a promising hot target for cancer therapy, and our previous study demonstrated that multiple dominant negative mutants from full-length survivin could have many complex effects on cancer cells, such as cell cycle, apoptosis, and autophagy. But it was not yet known what role the two main domains played in those functions, which would be very important for the design of targeted anticancer drugs and for the interpretation of their molecular mechanisms. In this study, based on preparation the two parts (BIR domain and CC domain) of survivin by genetic engineering and cell characterization assay, we discovered that BIR (T34A)-domain peptide could inhibit Bcap-37 cells growth in a dose- and time-dependent manner, increase the proportion of G2/M phase, and induce caspase-dependent apoptosis via the mitochondrial pathway. While CC (T117A)-domain peptide increased the proportion of S-phase cells and increased the level of the autophagy marker protein LC3B significantly. These further experiments confirmed that TAT-BIR (T34A) peptide could be used to inhibit cell proliferation, promote apoptosis, and block mitosis, and TAT-CC (T117A) peptide showed mainly to promote autophagy, process of DNA replication, and mitosis to breast cancer cells. This research will lay the foundation for interpreting the multifunction mechanism of survivin in cell fates, further make senses in developing the anticancer drugs targeting it precisely and efficiently.

  5. Intrinsic, Functional, and Structural Properties of β-Thymosins and β-Thymosin/WH2 Domains in the Regulation and Coordination of Actin Self-Assembly Dynamics and Cytoskeleton Remodeling.

    Science.gov (United States)

    Renault, L

    2016-01-01

    β-Thymosins are a family of heat-stable multifunctional polypeptides that are expressed as small proteins of about 5kDa (~45 amino acids) almost exclusively in multicellular animals. They were first isolated from the thymus. As full-length or truncated polypeptides, they appear to stimulate a broad range of extracellular activities in various signaling pathways, including tissue repair and regeneration, inflammation, cell migration, and immune defense. However, their cell surface receptors and structural mechanisms of regulations in these multiple pathways remain still poorly understood. Besides their extracellular activities, they belong to a larger family of small, intrinsically disordered actin-binding domains called WH2/β-thymosin domains that have been identified in more than 1800 multidomain proteins found in different taxonomic domains of life and involved in various actin-based motile processes including cell morphogenesis, motility, adhesions, tissue development, intracellular trafficking, or pathogen infections. This review briefly surveys the main recent findings to understand how these small, intrinsically disordered but functional domains can interact with many unrelated partners and can thus integrate and coordinate various intracellular activities in actin self-assembly dynamics and cell signaling pathways linked to their cytoskeleton remodeling. © 2016 Elsevier Inc. All rights reserved.

  6. The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains.

    Science.gov (United States)

    Han, Sangyeul; Kim, Sun; Bahl, Samira; Li, Lin; Burande, Clara F; Smith, Nicole; James, Marianne; Beauchamp, Roberta L; Bhide, Pradeep; DiAntonio, Aaron; Ramesh, Vijaya

    2012-08-31

    Pam and its homologs (the PHR protein family) are large E3 ubiquitin ligases that function to regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans. Phr1-deficient mouse models (Phr1(Δ8,9) and Phr1(Magellan), with deletions in the N-terminal putative guanine exchange factor region and the C-terminal ubiquitin ligase region, respectively) exhibit axon guidance/outgrowth defects and striking defects of major axon tracts in the CNS. Our earlier studies identified Pam to be associated with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Here, we examine the potential involvement of the TSC/mTOR complex 1(mTORC1) signaling pathway in Phr1-deficient mouse models. We observed attenuation of mTORC1 signaling in the brains of both Phr1(Δ8,9) and Phr1(Magellan) mouse models. Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains. To further address whether Pam regulates mTORC1 through two functionally independent domains, we undertook heterozygous mutant crossing between Phr1(Δ8,9) and Phr1(Magellan) mice to generate a compound heterozygous model to determine whether these two domains can complement each other. mTORC1 signaling was not attenuated in the brains of double mutants (Phr1(Δ8,9/Mag)), confirming that Pam displays dual regulation of the mTORC1 pathway through two functional domains. Our results also suggest that although dysregulation of mTORC1 signaling may be responsible for the corpus callosum defects, other neurodevelopmental defects observed with Phr1 deficiency are independent of mTORC1 signaling. The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency.

  7. Improved Automotive NO (x) Aftertreatment System: Metal Ammine Complexes as NH3 Source for SCR Using Fe-Containing Zeolite Catalysts

    DEFF Research Database (Denmark)

    Johannessen, Tue; Schmidt, Henning; Frey, Anne Mette

    2009-01-01

    Ammonia storage is a challenge in the selective catalytic reduction of NO (x) in vehicles. We propose a new system, based on metal ammines as the ammonia source. In combination with iron containing zeolites as the SCR catalyst it should be possible to obtain a low temperature system for NO (x...

  8. Oxidation of elemental mercury by modified spent TiO2-based SCR-DeNOx catalysts in simulated coal-fired flue gas.

    Science.gov (United States)

    Zhao, Lingkui; Li, Caiting; Zhang, Xunan; Zeng, Guangming; Zhang, Jie; Xie, Yin'e

    2016-01-01

    In order to reduce the costs, the recycle of spent TiO2-based SCR-DeNOx catalysts were employed as a potential catalytic support material for elemental mercury (Hg(0)) oxidation in simulated coal-fired flue gas. The catalytic mechanism for simultaneous removal of Hg(0) and NO was also investigated. The catalysts were characterized by Brunauer-Emmett-Teller (BET), scanning electron microscope (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) method. Results indicated that spent TiO2-based SCR-DeNOx catalyst supported Ce-Mn mixed oxides catalyst (CeMn/SCR1) was highly active for Hg(0) oxidation at low temperatures. The Ce1.00Mn/SCR1 performed the best catalytic activities, and approximately 92.80% mercury oxidation efficiency was obtained at 150 °C. The inhibition effect of NH3 on Hg(0) oxidation was confirmed in that NH3 consumed the surface oxygen. Moreover, H2O inhibited Hg(0) oxidation while SO2 had a promotional effect with the aid of O2. The XPS results illustrated that the surface oxygen was responsible for Hg(0) oxidation and NO conversion. Besides, the Hg(0) oxidation and NO conversion were thought to be aided by synergistic effect between the manganese and cerium oxides.

  9. Low-temperature SCR of NO with NH{sub 3} over activated semi-coke composite-supported rare earth oxides

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jinping; Yan, Zheng; Liu, Lili; Zhang, Yingyi; Zhang, Zuotai; Wang, Xidong, E-mail: xidong@pku.edu.cn

    2014-08-01

    The catalysts with different rare earth oxides (La, Ce, Pr and Nd) loaded onto activated semi-coke (ASC) via hydrothermal method are prepared for the selective catalytic reduction (SCR) of NO with NH{sub 3} at low temperature (150–300 °C). It is evidenced that CeO{sub 2} loaded catalysts present the best performance, and the optimum loading amount of CeO{sub 2} is about 10 wt%. Composite catalysts by doping La, Pr and Nd into CeO{sub 2} are prepared to obtain further improved catalytic properties. The SCR mechanism is investigated through various characterizations, including XRD, Raman, XPS and FT-IR, the results of which indicate that the oxygen defect plays an important role in SCR process and the doped rare earth elements effectively serve as promoters to increase the concentration of oxygen vacancies. It is also found that the oxygen vacancies in high concentration are favored for the adsorption of O{sub 2} and further oxidation of NO, which facilitates a rapid progressing of the following reduction reactions. The SCR process of NO with NH{sub 3} at low temperature over the catalysts of ASC composite-supported rare earth oxides mainly follows the Langmuir–Hinshlwood mechanism.

  10. Harmonic Distortion Performance of Multi Three-Phase SCR-Fed Drive Systems with Controlled DC-Link Current under Unbalanced Grid

    DEFF Research Database (Denmark)

    Soltani, Hamid; Davari, Pooya; Blaabjerg, Frede

    2017-01-01

    . In this paper, the main aim is to analyze the effects of the grid unbalanced voltage on the multi-unit three-phase ASDs with the Silicon-Controlled Rectifier (SCR)-fed front-end rectifiers, where the DC-link current is controlled utilizing an Electronic Inductor (EI) technique. In this respect, the main...

  11. Effect of the sol-gel conditions on the morphology and SCR performance of electrospun V-W-TiO2 catalysts

    DEFF Research Database (Denmark)

    Marani, Debora; Silva, Rafael Hubert; Dankeaw, Apiwat

    2018-01-01

    V-W-TiO2 catalysts are prepared as nanofibers for the removal of the NOx in exhausts via the NH3 Selective Catalytic Reduction (SCR) method. By combining electrospinning and soft chemistry, materials are processed as nanofibers with the catalytic components (e. g. V2O5-WO3) incorporated as dopant...

  12. A study on synthetic method and material characteristics of magnesium ammine chloride as ammonia transport materials for solid SCR

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jong Kook; Yoon, Cheon Seog [Dept. of Mechanical Engineering, Hannam University, Daejeon (Korea, Republic of); Kim, Hong Suk [Engine Research Center, Korea Institute of Machinery and Materials, Daejeon (Korea, Republic of)

    2015-11-15

    Among various ammonium salts and metal ammine chlorides used as solid materials for the sources of ammonia with solid SCR for lean NOx reduction, magnesium ammine chloride was taken up for study in this paper because of its ease of handling and safety. Lab-scale synthetic method of magnesium ammine chloride were studied for different durations, temperatures, and pressures with proper ammonia gas charged, as a respect of ammonia gas adsorption rate(%). To understand material characteristics for lab-made magnesium ammine chloride, DA, IC, FT-IR, XRD and SDT analyses were performed using the published data available in literature. From the analytical results, the water content in the lab-made magnesium ammine chloride can be determined. A new test procedure for water removal was proposed, by which the adsorption rate of lab-made sample was found to be approximately 100%.

  13. A study on synthetic method and material characteristics of magnesium ammine chloride as ammonia transport materials for solid SCR

    International Nuclear Information System (INIS)

    Shin, Jong Kook; Yoon, Cheon Seog; Kim, Hong Suk

    2015-01-01

    Among various ammonium salts and metal ammine chlorides used as solid materials for the sources of ammonia with solid SCR for lean NOx reduction, magnesium ammine chloride was taken up for study in this paper because of its ease of handling and safety. Lab-scale synthetic method of magnesium ammine chloride were studied for different durations, temperatures, and pressures with proper ammonia gas charged, as a respect of ammonia gas adsorption rate(%). To understand material characteristics for lab-made magnesium ammine chloride, DA, IC, FT-IR, XRD and SDT analyses were performed using the published data available in literature. From the analytical results, the water content in the lab-made magnesium ammine chloride can be determined. A new test procedure for water removal was proposed, by which the adsorption rate of lab-made sample was found to be approximately 100%

  14. Protein phosphatase 2a (PP2A binds within the oligomerization domain of striatin and regulates the phosphorylation and activation of the mammalian Ste20-Like kinase Mst3

    Directory of Open Access Journals (Sweden)

    Jones Candace A

    2011-10-01

    Full Text Available Abstract Background Striatin, a putative protein phosphatase 2A (PP2A B-type regulatory subunit, is a multi-domain scaffolding protein that has recently been linked to several diseases including cerebral cavernous malformation (CCM, which causes symptoms ranging from headaches to stroke. Striatin association with the PP2A A/C (structural subunit/catalytic subunit heterodimer alters PP2A substrate specificity, but targets and roles of striatin-associated PP2A are not known. In addition to binding the PP2A A/C heterodimer to form a PP2A holoenzyme, striatin associates with cerebral cavernous malformation 3 (CCM3 protein, the mammalian Mps one binder (MOB homolog, Mob3/phocein, the mammalian sterile 20-like (Mst kinases, Mst3, Mst4 and STK25, and several other proteins to form a large signaling complex. Little is known about the molecular architecture of the striatin complex and the regulation of these sterile 20-like kinases. Results To help define the molecular organization of striatin complexes and to determine whether Mst3 might be negatively regulated by striatin-associated PP2A, a structure-function analysis of striatin was performed. Two distinct regions of striatin are capable of stably binding directly or indirectly to Mob3--one N-terminal, including the coiled-coil domain, and another more C-terminal, including the WD-repeat domain. In addition, striatin residues 191-344 contain determinants necessary for efficient association of Mst3, Mst4, and CCM3. PP2A associates with the coiled-coil domain of striatin, but unlike Mob3 and Mst3, its binding appears to require striatin oligomerization. Deletion of the caveolin-binding domain on striatin abolishes striatin family oligomerization and PP2A binding. Point mutations in striatin that disrupt PP2A association cause hyperphosphorylation and activation of striatin-associated Mst3. Conclusions Striatin orchestrates the regulation of Mst3 by PP2A. It binds Mst3 likely as a dimer with CCM3 via

  15. Integrated energy & emission management for hybrid electric truck with SCR aftertreatment

    NARCIS (Netherlands)

    Kessels, J.T.B.A.; Willems, F.P.T.; Schoot, W.J.; Bosch, P.P.J. van den

    2010-01-01

    Energy management in hybrid vehicles typically relates to the vehicle powertrain, whereas emission management is associated with the combustion engine and aftertreatment system. To achieve maximum performance in fuel economy and regulated pollutants, the concept of (model-based) Integrated

  16. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  17. The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

    Science.gov (United States)

    Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

    2014-01-01

    The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

  18. A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation

    International Nuclear Information System (INIS)

    Littler, Dene R.; Walker, John R.; Davis, Tara; Wybenga-Groot, Leanne E.; Finerty, Patrick J. Jr; Newman, Elena; Mackenzie, Farell; Dhe-Paganon, Sirano

    2010-01-01

    A 1.9 Å resolution crystal structure of the isolated kinase domain from the α2 subunit of human AMPK, the first from a multicellular organism, is presented. The AMP-activated protein kinase (AMPK) is a highly conserved trimeric protein complex that is responsible for energy homeostasis in eukaryotic cells. Here, a 1.9 Å resolution crystal structure of the isolated kinase domain from the α2 subunit of human AMPK, the first from a multicellular organism, is presented. This human form adopts a catalytically inactive state with distorted ATP-binding and substrate-binding sites. The ATP site is affected by changes in the base of the activation loop, which has moved into an inhibited DFG-out conformation. The substrate-binding site is disturbed by changes within the AMPKα2 catalytic loop that further distort the enzyme from a catalytically active form. Similar structural rearrangements have been observed in a yeast AMPK homologue in response to the binding of its auto-inhibitory domain; restructuring of the kinase catalytic loop is therefore a conserved feature of the AMPK protein family and is likely to represent an inhibitory mechanism that is utilized during function

  19. The Jasmonate-ZIM-domain proteins interact with the WD-Repeat/bHLH/MYB complexes to regulate Jasmonate-mediated anthocyanin accumulation and trichome initiation in Arabidopsis thaliana.

    Science.gov (United States)

    Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

    2011-05-01

    Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)-based SCF(COI1) complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation.

  20. The Jasmonate-ZIM-Domain Proteins Interact with the WD-Repeat/bHLH/MYB Complexes to Regulate Jasmonate-Mediated Anthocyanin Accumulation and Trichome Initiation in Arabidopsis thaliana[C][W

    Science.gov (United States)

    Qi, Tiancong; Song, Susheng; Ren, Qingcuo; Wu, Dewei; Huang, Huang; Chen, Yan; Fan, Meng; Peng, Wen; Ren, Chunmei; Xie, Daoxin

    2011-01-01

    Jasmonates (JAs) mediate plant responses to insect attack, wounding, pathogen infection, stress, and UV damage and regulate plant fertility, anthocyanin accumulation, trichome formation, and many other plant developmental processes. Arabidopsis thaliana Jasmonate ZIM-domain (JAZ) proteins, substrates of the CORONATINE INSENSITIVE1 (COI1)–based SCFCOI1 complex, negatively regulate these plant responses. Little is known about the molecular mechanism for JA regulation of anthocyanin accumulation and trichome initiation. In this study, we revealed that JAZ proteins interact with bHLH (Transparent Testa8, Glabra3 [GL3], and Enhancer of Glabra3 [EGL3]) and R2R3 MYB transcription factors (MYB75 and Glabra1), essential components of WD-repeat/bHLH/MYB transcriptional complexes, to repress JA-regulated anthocyanin accumulation and trichome initiation. Genetic and physiological evidence showed that JA regulates WD-repeat/bHLH/MYB complex-mediated anthocyanin accumulation and trichome initiation in a COI1-dependent manner. Overexpression of the MYB transcription factor MYB75 and bHLH factors (GL3 and EGL3) restored anthocyanin accumulation and trichome initiation in the coi1 mutant, respectively. We speculate that the JA-induced degradation of JAZ proteins abolishes the interactions of JAZ proteins with bHLH and MYB factors, allowing the transcriptional function of WD-repeat/bHLH/MYB complexes, which subsequently activate respective downstream signal cascades to modulate anthocyanin accumulation and trichome initiation. PMID:21551388

  1. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    remote access via IP-based devices such as smartphones. The Trusted Domain platform fits existing legacy technologies by managing their interoperability and access controls, and it seeks to avoid the security issues of relying on third-party servers outside the home. It is a distributed system...... of wireless standards, limited resources of embedded systems, etc. Taking these challenges into account, we present a Trusted Domain home automation platform, which dynamically and securely connects heterogeneous networks of Short-Range Wireless devices via simple non-expert user. interactions, and allows......In the digital age of home automation and with the proliferation of mobile Internet access, the intelligent home and its devices should be accessible at any time from anywhere. There are many challenges such as security, privacy, ease of configuration, incompatible legacy devices, a wealth...

  2. A mutation within the SH2 domain of slp-76 regulates the tissue distribution and cytokine production of iNKT cells in mice

    OpenAIRE

    Danzer, Claudia; Koller, Anna; Baier, Julia; Arnold, Harald; Giessler, Claudia; Opoka, Robert; Schmidt, Stephanie; Willers, Maike; Mihai, Sidonia; Parsch, Hans; Wirtz, Stefan; Daniel, Christoph; Reinhold, Annegret; Engelmann, Swen; Kliche, Stefanie

    2016-01-01

    TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76ace/ace mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduct...

  3. Structure and dimerization of the catalytic domain of the protein phosphatase Cdc14p, a key regulator of mitotic exit in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kobayashi, Junya; Matsuura, Yoshiyuki

    2017-10-01

    In the budding yeast Saccharomyces cerevisiae, the protein phosphatase Cdc14p orchestrates various events essential for mitotic exit. We have determined the X-ray crystal structures at 1.85 Å resolution of the catalytic domain of Cdc14p in both the apo state, and as a complex with S160-phosphorylated Swi6p peptide. Each asymmetric unit contains two Cdc14p chains arranged in an intimately associated homodimer, consistent with its oligomeric state in solution. The dimerization interface is located on the backside of the substrate-binding cleft. Structure-based mutational analyses indicate that the dimerization of Cdc14p is required for normal growth of yeast cells. © 2017 The Protein Society.

  4. Estrogen receptor alpha regulates expression of the breast cancer 1 associated ring domain 1 (BARD1) gene through intronic DNA sequence.

    Science.gov (United States)

    Creekmore, Amy L; Ziegler, Yvonne S; Bonéy, Jamie L; Nardulli, Ann M

    2007-03-15

    We have used a chromatin immunoprecipitation (ChIP)-based cloning strategy to isolate and identify genes associated with estrogen receptor alpha (ERalpha) in MCF-7 human breast cancer cells. One of the gene regions isolated was a 288bp fragment from the ninth intron of the breast cancer 1 associated ring domain (BARD1) gene. We demonstrated that ERalpha associated with this region of the endogenous BARD 1 gene in MCF-7 cells, that ERalpha bound to three of five ERE half sites located in the 288bp BARD1 region, and that this 288bp BARD1 region conferred estrogen responsiveness to a heterologous promoter. Importantly, treatment of MCF-7 cells with estrogen increased BARD1 mRNA and protein levels. These findings demonstrate that ChIP cloning strategies can be utilized to successfully isolate regulatory regions that are far removed from the transcription start site and assist in identifying cis elements involved in conferring estrogen responsiveness.

  5. Multi-domain CGFS-type glutaredoxin Grx4 regulates iron homeostasis via direct interaction with a repressor Fep1 in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung-Dong; Kim, Hyo-Jin; Lee, Kyung-Chang [Laboratory of Molecular Microbiology, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742 (Korea, Republic of); Roe, Jung-Hye, E-mail: jhroe@snu.ac.kr [Laboratory of Molecular Microbiology, School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2011-05-20

    Research highlights: {yields} Monothiol glutaredoxin Grx4 allows Fep1-mediated de-repression of iron uptake genes at low iron. {yields} Grx4 directly interacts with Fep1 in vivo and in vitro. {yields} The Cys172 in the CGFS motif of Grx4 is necessary for cell proliferation and iron regulation. {yields} The Cys172 of Grx4 is required for normal interaction with Fep1. -- Abstract: The fission yeast Schizosaccharomyces pombe contains two CGFS-type monothiol glutaredoxins, Grx4 and Grx5, which are localized primarily in the nucleus and mitochondria, respectively. We observed involvement of Grx4 in regulating iron-responsive gene expression, which is modulated by a repressor Fep1. Lack of Grx4 caused defects not only in growth but also in the expression of both iron-uptake and iron-utilizing genes regardless of iron availability. In order to unravel how Grx4 is involved in Fep1-mediated regulation, interaction between them was investigated. Co-immunoprecipitation and bimolecular fluorescence complementation (BiFC) revealed that Grx4 physically interacts with Fep1 in vivo. BiFC revealed localized nuclear dots produced by interaction of Grx4 with Fep1. Mutation of cysteine-172 in the CGFS motif to serine (C172S) produced effects similarly observed under Grx4 depletion, such as the loss of iron-dependent gene regulation and the absence of nuclear dots in BiFC analysis. These results suggest that the ability of Grx4 to bind iron, most likely Fe-S cofactor, could be critical in interacting with and modulating the activity of Fep1.

  6. New developments of high dust-SCR technology in the cement industry results of pilot tests in Solnhofen and development state of a full scale SCR unit; Nouveaux developpements de la technologie SCR ''High Dust'' dans l'industrie du ciment - resultats de tests pilotes a Solnhoffen et etat de developpement d'une unite pilote a l'echelle

    Energy Technology Data Exchange (ETDEWEB)

    Samant, G. [Lurgi Energie und Entsorgung GmbH, Frankfurt (Germany); Sauter, G. [Soinhofer Portland Zementwerke AG, Solnhofen (Germany); Haug, N. [Agence Federale de l' Environnement, Berlin (Germany)

    2001-07-01

    The production of clinker in the cement industry involve the formation of nitrous oxides, and the emission limits are becoming more stringent from year to year. The added up total NOx emissions from the European cement industry amounts at present approx. 450.000 Mg/year. As such it is high time for the decision to develop and implement a technology to reduce NOx-emissions. At present SCR technology which is implemented in the glass industry, waste incineration and power plants seems to be the best economical and ecological solution for cement industry. In the period time from 1997 to the end of 1999 pilot plant test work was carried out by the companies 'Solnhofer Portland Zementwerke AG' and 'mg Engineering Lurgi' in the cement plant in Solnhofen. The results of pilot plan test work show that NOx reduction rates above 90% with NH{sub 3} slip less then 5 vppm can be achieved. The results of the test work with different type of catalysts are discussed. Based on the results of the test work a suitable SCR-process for cement industry is developed. At present a High-Dust-SCR demonstration plant at 'Solnhofer Portland Zementwerke AG' with the help of German Federal Environmental Agency, UBA-Berlin, is under commissioning and going on stream. (authors)

  7. Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells.

    Science.gov (United States)

    Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin

    2016-01-01

    The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb St

  8. On the Effect of Preparation Methods of PdCe-MOR Catalysts as NOx CH4-SCR System for Natural Gas Vehicles Application

    Directory of Open Access Journals (Sweden)

    Acácio Nobre Mendes

    2015-10-01

    Full Text Available In the present work, the effect of several parameters involved in the preparation of PdCe-HMOR catalysts active for NOx selective catalytic reduction with methane (NOx CH4-SCR was studied. Results show that the catalytic performance of Pd-HMOR is better when palladium is introduced by ion-exchange, namely at room temperature. It was also shown that Pd loading does not influence the formation of cerium species, namely surface Ce4+ (CeO2 species and CeO2 species in interaction with Pd. However, when Ce is introduced before Pd, more surface CeO2 species are stabilized in the support and less CeO2 become in interaction with Pd, which results in a worse NOx CH4-SCR catalytic performance.

  9. The enhanced resistance to K deactivation of Ce/TiO2 catalyst for NH3-SCR reaction by the modification with P

    Science.gov (United States)

    Li, Ming-yuan; Guo, Rui-tang; Hu, Chang-xing; Sun, Peng; Pan, Wei-guo; Liu, Shu-ming; Sun, Xiao; Liu, Shuai-wei; Liu, Jian

    2018-04-01

    The deactivation of SCR catalyst caused by K species contained in the fly ash would suppress its DeNOx performance. In this study, it was manifested that the modification of Ce/TiO2 catalyst with P could enhance its K tolerance. To understand the promotion mechanism, the fresh and poisoned catalyst samples were subjected to the characterization techniques including BET, XRD, XPS, H2-TPR, NH3-TPD and in situ DRIFT. The results elucidated that the introduction of P species could increase the reducibility of Ce species and generate more surface chemisorbed oxygen, along with the strengthened surface acidity for NH3 adsorption. It seemed that the NH3-SCR reaction mechanism over Ce/TiO2 catalyst was a combination of L-H mechanism (reason for its good K resistance.

  10. Design and preliminary results for a fast bipolar resonant discharge pulser using SCR switches for driving the injection bump magnets at the ALS

    International Nuclear Information System (INIS)

    Stover, G.; Reginato, L.

    1993-05-01

    A fast (4.0 us half period) resonant discharge pulser using SCRs has been designed and constructed to drive the injection bump magnet system at the Advanced Light Source (ALS). The pulser employs a series-parallel arrangement of Silicon Controlled Rectifiers (SCRS) that creates a bipolar high voltage (±10 KV), high peak current (6600 amps.) and a high di/dt (6000 amp/us) switch network that discharges a capacitor bank into the magnet load. Fast recovery diodes in series with the SCRs significantly reduces the SCR turn-off time during the negative current cycle of the magnet. The SCR switch provides a very reliable and stable alternative to the gas filled Thyratron. A very low impedance transmission system allows the pulser system to reside completely outside the storage ring shielding wall

  11. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions.

    OpenAIRE

    Pettit, S C; Moody, M D; Wehbie, R S; Kaplan, A H; Nantermet, P V; Klein, C A; Swanstrom, R

    1994-01-01

    The proteolytic processing sites of the human immunodeficiency virus type 1 (HIV-1) Gag precursor are cleaved in a sequential manner by the viral protease. We investigated the factors that regulate sequential processing. When full-length Gag protein was digested with recombinant HIV-1 protease in vitro, four of the five major processing sites in Gag were cleaved at rates that differ by as much as 400-fold. Three of these four processing sites were cleaved independently of the others. The CA/p...

  12. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorgani-Firuzjaee, Sattar [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of); Adeli, Khosrow [Division of Clinical Biochemistry, The Hospital for Sick Children, University of Toronto, Toronto (Canada); Meshkani, Reza, E-mail: rmeshkani@tums.ac.ir [Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran (Iran, Islamic Republic of)

    2015-08-21

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway.

  13. Inhibition of SH2-domain-containing inositol 5-phosphatase (SHIP2) ameliorates palmitate induced-apoptosis through regulating Akt/FOXO1 pathway and ROS production in HepG2 cells

    International Nuclear Information System (INIS)

    Gorgani-Firuzjaee, Sattar; Adeli, Khosrow; Meshkani, Reza

    2015-01-01

    The serine–threonine kinase Akt regulates proliferation and survival by phosphorylating a network of protein substrates; however, the role of a negative regulator of the Akt pathway, the SH2-domain-containing inositol 5-phosphatase (SHIP2) in apoptosis of the hepatocytes, remains unknown. In the present study, we studied the molecular mechanisms linking SHIP2 expression to apoptosis using overexpression or suppression of SHIP2 gene in HepG2 cells exposed to palmitate (0.5 mM). Overexpression of the dominant negative mutant SHIP2 (SHIP2-DN) significantly reduced palmitate-induced apoptosis in HepG2 cells, as these cells had increased cell viability, decreased apoptotic cell death and reduced the activity of caspase-3, cytochrome c and poly (ADP-ribose) polymerase. Overexpression of the wild-type SHIP2 gene led to a massive apoptosis in HepG2 cells. The protection from palmitate-induced apoptosis by SHIP2 inhibition was accompanied by a decrease in the generation of reactive oxygen species (ROS). In addition, SHIP2 inhibition was accompanied by an increased Akt and FOXO-1 phosphorylation, whereas overexpression of the wild-type SHIP2 gene had the opposite effects. Taken together, these findings suggest that SHIP2 expression level is an important determinant of hepatic lipoapotosis and its inhibition can potentially be a target in treatment of hepatic lipoapoptosis in diabetic patients. - Highlights: • Lipoapoptosis is the major contributor to the development of NAFLD. • The PI3-K/Akt pathway regulates apoptosis in different cells. • The role of negative regulator of this pathway, SHIP2 in lipoapoptosis is unknown. • SHIP2 inhibition significantly reduces palmitate-induced apoptosis in HepG2 cells. • SHIP2 inhibition prevents palmitate induced-apoptosis by regulating Akt/FOXO1 pathway

  14. Self-Esteem is Relatively Stable Late in Life: The Role of Resources in the Health, Self-Regulation, and Social Domains

    Science.gov (United States)

    Wagner, Jenny; Hoppmann, Christiane; Ram, Nilam; Gerstorf, Denis

    2015-01-01

    A large body of research has documented changes in self-esteem across adulthood and individual-difference correlates thereof. However, little is known about whether people maintain their self-esteem until the end of life and what role key risk factors in the health, cognitive, self-regulatory, and social domains play. To examine these questions, we apply growth modeling to 13-year longitudinal data obtained from by now deceased participants of the Berlin Aging Study (BASE, N = 462; age 70 – 103, M = 86.3 yrs., SD = 8.3; 51% male). Results revealed that self-esteem, on average, does decline in very old age and close to death, but the amount of typical decline is minor. Health-related constraints and disabilities as well as lower control beliefs and higher loneliness were each associated with lower self-esteem late in life. We obtained initial evidence that some of these associations were stronger among the oldest-old participants. Our results corroborate and extend initial reports that self-esteem is, on average, fairly stable into the last years of life. We discuss possible pathways by which common and often severe late-life challenges may undermine an otherwise relatively robust self-esteem system. PMID:25546600

  15. The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size

    DEFF Research Database (Denmark)

    Christensen, Alex Hørby; Chatelain, Franck C; Huttner, Inken G

    2016-01-01

    distribution with predominant localization in the endosomal compartment. Two-electrode voltage-clamp experiments using Xenopus oocytes showed that both zebrafish and wild-type human TWIK-1 channels produced K(+) currents that are sensitive to external K(+) concentration as well as acidic pH. There were......The two-pore domain potassium (K(+)) channel TWIK-1 (or K2P1.1) contributes to background K(+) conductance in diverse cell types. TWIK-1, encoded by the KCNK1 gene, is present in the human heart with robust expression in the atria, however its physiological significance is unknown. To evaluate......-coding regions in two independent cohorts of patients (373 subjects) and identified three non-synonymous variants, p.R171H, p.I198M and p.G236S, that were all located in highly conserved amino acid residues. In transfected mammalian cells, zebrafish and wild-type human TWIK-1 channels had a similar cellular...

  16. Synthesis of S/Cr doped mesoporous TiO2 with high-active visible light degradation property via solid state reaction route

    International Nuclear Information System (INIS)

    Liu Shaoyou; Tang Qunli; Feng Qingge

    2011-01-01

    S/Cr doped mesoporous TiO 2 (S-TiO 2 , Cr-TiO 2 , S-Cr-TiO 2 ) were successfully synthesized via a simple, effective and environmental benign solid state reaction route. The low angle XRD patterns demonstrated that the resulting samples possess mesostructures. The further characterizations via N 2 adsorption-desorption and XPS showed that the typical S/Cr co-doped mesoporous TiO 2 (S-Cr-TiO 2 (5S-5Cr)) possesses mesopore with the high specific surface area of 118.4 m 2 /g and narrow pore size distribution, and both S and Cr have been incorporated into the lattice of TiO 2 with the amounts of 4.16% sulfur and 7.88% chromium, respectively. And Raman spectroscopy shows that the surface of S-Cr-TiO 2 (5S-5Cr) material possesses stretching vibrational peaks at ∼709, ∼793 cm -1 are assignable to the Ti-O-Cr, O-Cr (Ti)-OH bonds, respectively. Interestingly, the UV-vis displayed that the absorption regions of S/Cr doped mesoporous TiO 2 cover the visible light region. As for the series of S-Cr-TiO 2 samples, the absorption region even extends to near infrared region with strong adsorption. Moreover, compared with the pure titanium dioxide (P25-TiO 2 ), the photodegradation properties of bromocresol green (BCG) on the S/Cr doped mesoporous TiO 2 showed excellent photocatalytic properties under visible light irradiation. Within 50 min visible light irradiation, 82.6% of the initial BCG was degraded for the S-Cr-TiO 2 (6S-4Cr) photocatalyst.

  17. Evaluation of air jet erosion profiles in metal mesh supported SCR plate catalyst based on glass fiber concentrations

    Science.gov (United States)

    Rajath, S.; Nandakishora, Y.; Siddaraju, C.; Roy, Sukumar

    2018-04-01

    This paper explains the evaluation of erosion profiles in metal mesh supported SCR plate catalyst structures in which the glass fibers concentration in the catalyst material is considered as prime factor for erosion resistance and mechanical strength. The samples are prepared and tested at the specified and constant conditions like velocity as 30m/s, sand flow rate as 2g/min, average particle diameter 300 µm and all these samples were tested at different angles at impact preferably 15°,30°,45°,60°,75°,and 90° as per ASTM G76 standards. Say, if 5% glass fibers are present in catalyst material, then erosion resistance increases, but the density of glass fibers is very less because each glass fiber is approximately 20 microns in diameter and weight of individual is negligible. The composition in which 2% fiber is present has slightly higher erosion comparatively, but 3% glass fibers or more foreign inclusion like excessive binders can be eliminated that contributes much for the conversion of NOx. So 2% -3% glass fibers are preferred and optimized based on NOx conversion and erosion resistance property.

  18. Experimental Studies for CPF and SCR Model, Control System, and OBD Development for Engines Using Diesel and Biodiesel Fuels

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, John; Naber, Jeffrey; Parker, Gordon; Yang, Song-Lin; Stevens, Andrews; Pihl, Josh

    2013-04-30

    The research carried out on this project developed experimentally validated Diesel Oxidation Catalyst (DOC), Diesel Particulate Filter (DPF), and Selective Catalytic Reduction (SCR) high‐fidelity models that served as the basis for the reduced order models used for internal state estimation. The high‐fidelity and reduced order/estimator codes were evaluated by the industrial partners with feedback to MTU that improved the codes. Ammonia, particulate matter (PM) mass retained, PM concentration, and NOX sensors were evaluated and used in conjunction with the estimator codes. The data collected from PM experiments were used to develop the PM kinetics using the high‐fidelity DPF code for both NO2 assisted oxidation and thermal oxidation for Ultra Low Sulfur Fuel (ULSF), and B10 and B20 biodiesel fuels. Nine SAE papers were presented and this technology transfer process should provide the basis for industry to improve the OBD and control of urea injection and fuel injection for active regeneration of the PM in the DPF using the computational techniques developed. This knowledge will provide industry the ability to reduce the emissions and fuel consumption from vehicles in the field. Four MS and three PhD Mechanical Engineering students were supported on this project and their thesis research provided them with expertise in experimental, modeling, and controls in aftertreatment systems.

  19. A study on post impingement effects of urea-water solution spray on the heated wall of automotive SCR systems

    Science.gov (United States)

    Shahariar, G. M. H.; Wardana, M. K. A.; Lim, O. T.

    2018-04-01

    The post impingement effects of urea-water solution spray on the heated wall of automotive SCR systems was numerically investigated in a constant volume chamber using STAR CCM+ CFD code. The turbulence flow was modelled by realizable k-ε two-layer model together with standard wall function and all y+ treatment was applied along with two-layer approach. The Eulerian-Lagrangian approach was used for the modelling of multi phase flow. Urea water solution (UWS) was injected onto the heated wall for the wall temperature of 338, 413, 473, 503 & 573 K. Spray development after impinging on the heated wall was visualized and measured. Droplet size distribution and droplet evaporation rates were also measured, which are vital parameters for the system performance but still not well researched. Specially developed user defined functions (UDF) are implemented to simulate the desired conditions and parameters. The investigation reveals that wall temperature has a great impact on spray development after impingement, droplet size distribution and evaporation. Increasing the wall temperature leads to longer spray front projection length, smaller droplet size and faster droplet evaporation which are preconditions for urea crystallization reduction. The numerical model and parameters are validated comparing with experimental data.

  20. The word-family of s.-cr. batati, botati, butati "to hit, beat, push, etc.": Derivation, semantics, etymology

    Directory of Open Access Journals (Sweden)

    Vlajić-Popović Jasna

    2005-01-01

    Full Text Available The paper offers a thorough phonetic discussion, word-formation classification and se­mantic analysis of the word-family of S.-Cr. batati botati, butati "to hit, heat, push, etc.", including the available references to their Slavic counterparts and PS1. prototypes which altogether corroborate the hitherto rarely expressed opinion that they are onomatopoeic by origin, and subsequently "normalized" to various extents, which is obvious from the semantic span of their postverbals: while the primary ones mostly feature meanings of verba instrumenti or verba acti (further developing into verba resultativa, their secondary derivatives include terms for a wide range of specific, concrete realia (sorted in pgfs. 5.2. through 5.2.5.1. Since the entire study is aimed at facilitating the lexicographic treatment of this vast and complicated word-family in the Serbian etymological dictionary (ERSJ, some practical repercussions of such an analysis are il­lustrated by homonymous nouns batl/bafi, bofl/bofi/bot3 and bufl/bufi viewed not only per se, but also as departure points for further derivation.

  1. Influence of flue gas desulfurization (FGD) installations on emission characteristics of PM2.5 from coal-fired power plants equipped with selective catalytic reduction (SCR).

    Science.gov (United States)

    Li, Zhen; Jiang, Jingkun; Ma, Zizhen; Fajardo, Oscar A; Deng, Jianguo; Duan, Lei

    2017-11-01

    Flue gas desulfurization (FGD) and selective catalytic reduction (SCR) technologies have been widely used to control the emissions of sulphur dioxide (SO 2 ) and nitrogen oxides (NO X ) from coal-fired power plants (CFPPs). Field measurements of emission characteristics of four conventional CFPPs indicated a significant increase in particulate ionic species, increasing PM 2.5 emission with FGD and SCR installations. The mean concentrations of PM 2.5 from all CFPPs tested were 3.79 ± 1.37 mg/m 3 and 5.02 ± 1.73 mg/m 3 at the FGD inlet and outlet, respectively, and the corresponding contributions of ionic species were 19.1 ± 7.7% and 38.2 ± 7.8%, respectively. The FGD was found to enhance the conversion of NH 3 slip from the SCR to NH 4 + in the PM 2.5 , together with the conversion of SO 2 to SO 4 2- , and increased the primary NH 4 + and SO 4 2- aerosol emissions by approximately 18.9 and 4.2 times, respectively. This adverse effect should be considered when updating the emission inventory of CFPPs and should draw the attention of policy-makers for future air pollution control. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. NH3-SCR on Cu, Fe and Cu + Fe exchanged beta and SSZ-13 catalysts: Hydrothermal aging and propylene poisoning effects

    International Nuclear Information System (INIS)

    Wang, Aiyong; Wang, Yilin; Walter, Eric D.; Washton, Nancy M.

    2017-01-01

    Cu, Fe and Cu + Fe ion exchanged Beta and SSZ-13 catalysts were prepared by solution ion exchange using commercial NH 4 /Beta, and NH 4 /SSZ-13 that was prepared in-house. To study hydrothermal aging effects, Beta supported catalysts were aged hydrothermally at 700 °C and SSZ-13 supported catalysts were aged at 750 °C. In order to reveal the effects of Fe addition in the co-exchanged catalysts, these catalysts were characterized by means of powder X-ray diffraction (XRD), N 2 adsorption-desorption, electron paramagnetic resonance (EPR), 27 Al-nuclear magnetic resonance ( 27 Al-NMR) and propylene coking followed with temperature programmed reaction (TPR), and further tested with standard NH 3 -SCR with and without the presence of propylene. Collectively, the catalyst characterizations and reaction testing indicated minor beneficial effects of Fe addition in Cu,Fe/Beta, where NH 3 -SCR activity, N 2 selectivity and hydrothermal stability were all slightly improved. In contrast, Fe addition did not show apparent beneficial effects in low-temperature SCR for the Cu,Fe/SSZ-13 case. In conclusion, at elevated reaction temperatures, however, the presence of Fe indeed considerably improved NO conversion and N 2 selectivity for the hydrothermally aged Cu,Fe/SSZ-13 catalyst in the presence of propylene.

  3. Iron loading effects in Fe/SSZ-13 NH3-SCR catalysts: nature of the Fe-ions and structure-function relationships

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Feng; Zheng, Yang; Kukkadapu, Ravi K.; Wang, Yilin; Walter, Eric D.; Schwenzer, Birgit; Szanyi, Janos; Peden, Charles HF

    2016-05-06

    Using a traditional aqueous solution ion-exchange method under a protecting atmosphere of N2, a series of Fe/SSZ-13 catalysts with various Fe loadings were synthesized. UV-Vis, EPR and Mössbauer spectroscopies, coupled with temperature programmed reduction and desorption techniques, were used to probe the nature of the Fe sites. The major monomeric and dimeric Fe species are extra-framework [Fe(OH)2]+ and [HO-Fe-O-Fe-OH]2+. Larger oligomers with unknown nuclearity, poorly crystallized Fe2O3 particles, together with isolated Fe2+ ions, are minor Fe-containing moieties. Reaction rate and Fe loading correlations suggest that isolated Fe3+ ions are the active sites for standard SCR while the dimeric sites are the active centers for NO oxidation. NH3 oxidation, on the other hand, is catalyzed by sites with higher nuclearity. A low-temperature standard SCR reaction network is proposed that includes redox cycling of both monomeric and dimeric Fe species, for SCR and NO2 generation, respectively. The authors gratefully acknowledge the US Department of Energy (DOE), Energy Efficiency and Renewable Energy, Vehicle Technologies Program for the support of this work. The research described in this paper was performed at the Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated for the US DOE by Battelle.

  4. Influence of real-world engine load conditions on nanoparticle emissions from a DPF and SCR equipped heavy-duty diesel engine.

    Science.gov (United States)

    Thiruvengadam, Arvind; Besch, Marc C; Carder, Daniel K; Oshinuga, Adewale; Gautam, Mridul

    2012-02-07

    The experiments aimed at investigating the effect of real-world engine load conditions on nanoparticle emissions from a Diesel Particulate Filter and Selective Catalytic Reduction after-treatment system (DPF-SCR) equipped heavy-duty diesel engine. The results showed the emission of nucleation mode particles in the size range of 6-15 nm at conditions with high exhaust temperatures. A direct result of higher exhaust temperatures (over 380 °C) contributing to higher concentration of nucleation mode nanoparticles is presented in this study. The action of an SCR catalyst with urea injection was found to increase the particle number count by over an order of magnitude in comparison to DPF out particle concentrations. Engine operations resulting in exhaust temperatures below 380 °C did not contribute to significant nucleation mode nanoparticle concentrations. The study further suggests the fact that SCR-equipped engines operating within the Not-To-Exceed (NTE) zone over a critical exhaust temperature and under favorable ambient dilution conditions could contribute to high nanoparticle concentrations to the environment. Also, some of the high temperature modes resulted in DPF out accumulation mode (between 50 and 200 nm) particle concentrations an order of magnitude greater than typical background PM concentrations. This leads to the conclusion that sustained NTE operation could trigger high temperature passive regeneration which in turn would result in lower filtration efficiencies of the DPF that further contributes to the increased solid fraction of the PM number count.

  5. Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro

    Directory of Open Access Journals (Sweden)

    Qian Yu

    2017-11-01

    Full Text Available Background/Aims: ATP-binding cassette transporter E1 (ABCE1, a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. Methods: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1. The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Results: Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. Conclusion: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.

  6. Invasive Streptococcus mutans induces inflammatory cytokine production in human aortic endothelial cells via regulation of intracellular toll-like receptor 2 and nucleotide-binding oligomerization domain 2.

    Science.gov (United States)

    Nagata, E; Oho, T

    2017-04-01

    Streptococcus mutans, the primary etiologic agent of dental caries, can gain access to the bloodstream and has been associated with cardiovascular disease. However, the roles of S. mutans in inflammation in cardiovascular disease remain unclear. The aim of this study was to examine cytokine production induced by S. mutans in human aortic endothelial cells (HAECs) and to evaluate the participation of toll-like receptors (TLRs) and cytoplasmic nucleotide-binding oligomerization domain (NOD) -like receptors in HAECs. Cytokine production by HAECs was determined using enzyme-linked immunosorbent assays, and the expression of TLRs and NOD-like receptors was evaluated by real-time polymerase chain reaction, flow cytometry and immunocytochemistry. The involvement of TLR2 and NOD2 in cytokine production by invaded HAECs was examined using RNA interference. The invasion efficiencies of S. mutans strains were evaluated by means of antibiotic protection assays. Five of six strains of S. mutans of various serotypes induced interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production by HAECs. All S. mutans strains upregulated TLR2 and NOD2 mRNA levels in HAECs. Streptococcus mutans Xc upregulated the intracellular TLR2 and NOD2 protein levels in HAECs. Silencing of the TLR2 and NOD2 genes in HAECs invaded by S. mutans Xc led to a reduction in interleukin-6, interleukin-8 and monocyte chemoattractant protein-1 production. Cytokine production induced by invasive S. mutans via intracellular TLR2 and NOD2 in HAECs may be associated with inflammation in cardiovascular disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. A conserved WW domain-like motif regulates invariant chain-dependent cell-surface transport of the NKG2D ligand ULBP2

    DEFF Research Database (Denmark)

    Uhlenbrock, Franziska Katharina; van Andel, Esther; Andresen, Lars

    2015-01-01

    that the NKG2D ligand ULBP2 traffics over an invariant chain (Ii)-dependent pathway to the cell surface. This study set out to elucidate how Ii regulates ULBP2 cell-surface transport: We discovered conserved tryptophan (Trp) residues in the primary protein sequence of ULBP1-6 but not in the related MICA....../B. Substitution of Trp to alanine resulted in cell-surface inhibition of ULBP2 in different cancer cell lines. Moreover, the mutated ULBP2 constructs were retained and not degraded inside the cell, indicating a crucial role of this conserved Trp-motif in trafficking. Finally, overexpression of Ii increased...... surface expression of wt ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the ULBP2 sequence could counteract...

  8. The BRCT domain is a phospho-protein binding domain.

    Science.gov (United States)

    Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

    2003-10-24

    The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

  9. Crystallization and X-ray diffraction analysis of the HMG domain of the chondrogenesis master regulator Sox9 in complex with a ChIP-Seq-identified DNA element

    Energy Technology Data Exchange (ETDEWEB)

    Vivekanandan, Saravanan; Moovarkumudalvan, Balasubramanian; Lescar, Julien; Kolatkar, Prasanna R.

    2015-10-30

    Sox9 is a fundamental sex-determining gene and the master regulator of chondrogenesis, and is involved in the development of various vital organs such as testes, kidney, heart and brain, and in skeletal development. Similar to other known Sox transcription factors, Sox9 recognizes and binds DNA with the consensus sequence C(T/A)TTG(T/A)(T/A) through the highly conserved HMG domain. Nonetheless, the molecular basis of the functional specificity of Sox9 in key developmental processes is still unclear. As an initial step towards a mechanistic understanding of Sox9 transcriptional regulation, the current work describes the details of the purification of the mouse Sox9 HMG domain (mSox9HMG), its crystallization in complex with a ChIP-Seq-identified FOXP2 promoter DNA element and the X-ray diffraction data analysis of this complex. The mSox9HMG–FOXP2 promoter DNA complex was crystallized by the hanging-drop vapour-diffusion method using 20% PEG 3350 in 200 mMsodium/potassium phosphate with 100 mMbis-tris propane at pH 8.5. The crystals diffracted to 2.7 Å resolution and the complex crystallized in the tetragonal space groupP41212, with unit-cell parametersa=b= 99.49,c= 45.89 Å. Crystal-packing parameters revealed that asymmetric unit contained one mSox9HMG–FOXP2 promoter DNA complex with an estimated solvent content of 64%.

  10. ORA47 (octadecanoid-responsive AP2/ERF-domain transcription factor 47) regulates jasmonic acid and abscisic acid biosynthesis and signaling through binding to a novel cis-element.

    Science.gov (United States)

    Chen, Hsing-Yu; Hsieh, En-Jung; Cheng, Mei-Chun; Chen, Chien-Yu; Hwang, Shih-Ying; Lin, Tsan-Piao

    2016-07-01

    ORA47 (octadecanoid-responsive AP2/ERF-domain transcription factor 47) of Arabidopsis thaliana is an AP2/ERF domain transcription factor that regulates jasmonate (JA) biosynthesis and is induced by methyl JA treatment. The regulatory mechanism of ORA47 remains unclear. ORA47 is shown to bind to the cis-element (NC/GT)CGNCCA, which is referred to as the O-box, in the promoter of ABI2. We proposed that ORA47 acts as a connection between ABA INSENSITIVE1 (ABI1) and ABI2 and mediates an ABI1-ORA47-ABI2 positive feedback loop. PORA47:ORA47-GFP transgenic plants were used in a chromatin immunoprecipitation (ChIP) assay to show that ORA47 participates in the biosynthesis and/or signaling pathways of nine phytohormones. Specifically, many abscisic acid (ABA) and JA biosynthesis and signaling genes were direct targets of ORA47 under stress conditions. The JA content of the P35S:ORA47-GR lines was highly induced under wounding and moderately induced under water stress relative to that of the wild-type plants. The wounding treatment moderately increased ABA accumulation in the transgenic lines, whereas the water stress treatment repressed the ABA content. ORA47 is proposed to play a role in the biosynthesis of JA and ABA and in regulating the biosynthesis and/or signaling of a suite of phytohormone genes when plants are subjected to wounding and water stress. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  11. The Staphylococcus aureus group II biotin protein ligase BirA is an effective regulator of biotin operon transcription and requires the DNA binding domain for full enzymatic activity.

    Science.gov (United States)

    Henke, Sarah K; Cronan, John E

    2016-11-01

    Group II biotin protein ligases (BPLs) are characterized by the presence of an N-terminal DNA binding domain that functions in transcriptional regulation of the genes of biotin biosynthesis and transport. The Staphylococcus aureus Group II BPL which is called BirA has been reported to bind an imperfect inverted repeat located upstream of the biotin synthesis operon. DNA binding by other Group II BPLs requires dimerization of the protein which is triggered by synthesis of biotinoyl-AMP (biotinoyl-adenylate), the intermediate in the ligation of biotin to its cognate target proteins. However, the S. aureus BirA was reported to dimerize and bind DNA in the absence of biotin or biotinoyl-AMP (Soares da Costa et al. (2014) Mol Microbiol 91: 110-120). These in vitro results argued that the protein would be unable to respond to the levels of biotin or acceptor proteins and thus would lack the regulatory properties of the other characterized BirA proteins. We tested the regulatory function of the protein using an in vivo model system and examined its DNA binding properties in vitro using electrophoretic mobility shift and fluorescence anisotropy analyses. We report that the S. aureus BirA is an effective regulator of biotin operon transcription and that the prior data can be attributed to artifacts of mobility shift analyses. We also report that deletion of the DNA binding domain of the S. aureus BirA results in loss of virtually all of its ligation activity. © 2016 John Wiley & Sons Ltd.

  12. Arabidopsis KHZ1 and KHZ2, two novel non-tandem CCCH zinc-finger and K-homolog domain proteins, have redundant roles in the regulation of flowering and senescence.

    Science.gov (United States)

    Yan, Zongyun; Jia, Jianheng; Yan, Xiaoyuan; Shi, Huiying; Han, Yuzhen

    2017-12-01

    The two novel CCCH zinc-finger and K-homolog (KH) proteins, KHZ1 and KHZ2, play important roles in regulating flowering and senescence redundantly in Arabidopsis. The CCCH zinc-finger proteins and K-homolog (KH) proteins play important roles in plant development and stress responses. However, the biological functions of many CCCH zinc-finger proteins and KH proteins remain uncharacterized. In Arabidopsis, KHZ1 and KHZ2 are characterized as two novel CCCH zinc-finger and KH domain proteins which belong to subfamily VII in CCCH family. We obtained khz1, khz2 mutants and khz1 khz2 double mutants, as well as overexpression (OE) lines of KHZ1 and KHZ2. Compared with the wild type (WT), the khz2 mutants displayed no defects in growth and development, and the khz1 mutants were slightly late flowering, whereas the khz1 khz2 double mutants showed a pronounced late flowering phenotype. In contrast, artificially overexpressing KHZ1 and KHZ2 led to the early flowering. Consistent with the late flowering phenotype, the expression of flowering repressor gene FLC was up-regulated, while the expression of flowering integrator and floral meristem identity (FMI) genes were down-regulated significantly in khz1 khz2. In addition, we also observed that the OE plants of KHZ1 and KHZ2 showed early leaf senescence significantly, whereas the khz1 khz2 double mutants showed delayed senescence of leaf and the whole plant. Both KHZ1 and KHZ2 were ubiquitously expressed throughout the tissues of Arabidopsis. KHZ1 and KHZ2 were localized to the nucleus, and possessed both transactivation activities and RNA-binding abilities. Taken together, we conclude that KHZ1 and KHZ2 have redundant roles in the regulation of flowering and senescence in Arabidopsis.

  13. A conserved WW domain-like motif regulates invariant chain-dependent cell-surface transport of the NKG2D ligand ULBP2.

    Science.gov (United States)

    Uhlenbrock, Franziska; van Andel, Esther; Andresen, Lars; Skov, Søren

    2015-08-01

    Malignant cells expressing NKG2D ligands on their cell surface can be directly sensed and killed by NKG2D-bearing lymphocytes. To ensure this immune recognition, accumulating evidence suggests that NKG2D ligands are trafficed via alternative pathways to the cell surface. We have previously shown that the NKG2D ligand ULBP2 traffics over an invariant chain (Ii)-dependent pathway to the cell surface. This study set out to elucidate how Ii regulates ULBP2 cell-surface transport: We discovered conserved tryptophan (Trp) residues in the primary protein sequence of ULBP1-6 but not in the related MICA/B. Substitution of Trp to alanine resulted in cell-surface inhibition of ULBP2 in different cancer cell lines. Moreover, the mutated ULBP2 constructs were retained and not degraded inside the cell, indicating a crucial role of this conserved Trp-motif in trafficking. Finally, overexpression of Ii increased surface expression of wt ULBP2 while Trp-mutants could not be expressed, proposing that this Trp-motif is required for an Ii-dependent cell-surface transport of ULBP2. Aberrant soluble ULBP2 is immunosuppressive. Thus, targeting a distinct protein module on the ULBP2 sequence could counteract this abnormal expression of ULBP2. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Brucella Melitensis 16M Regulates the Effect of AIR Domain on Inflammatory Factors, Autophagy, and Apoptosis in Mouse Macrophage through the ROS Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Tiansen Li

    Full Text Available Brucellosis is a highly contagious zoonosis caused by Brucella. Brucella can invade and persist inside host cells, which results in chronic infection. We constructed AIR interference and overexpression lentiviruses to acquire AIR interference, overexpression, and rescue stable expression cell lines. We also established a Brucella melitensis 16M-infected macrophage model, which was treated with either the vehicle control or NAC (ROS scavenger N-acetylcysteine (NAC for 0, 3, 6, 12, and 24 h. Confocal laser microscopy, transmission electron microscopy, fluorescence quantitative PCR, flow cytometry, ELISA, and Western blot were used to detect inflammation, cell autophagy and apoptosis-related protein expression levels, ROS levels, and the distribution of mitochondria. It was found that after interference and overexpression of AIR, ROS release was significantly changed, and mitochondria became abnormally aggregated. B. melitensis 16M activated the NLRP3/AIM2 inflammatory complex, and induced RAW264.7 cells to secrete IL-1β and IL-18 through the ROS pathway. B. melitensis 16M also altered autophagy-related gene expression, increased autophagy activity, and induced cell apoptosis through the ROS pathway. The results showed that after B. melitensis 16M infection, ROS induced apoptosis, inflammation, and autophagy while AIR inhibited autophagosome maturation and autophagy initiation. Autophagy negatively regulated the activation of inflammasomes and prevented inflammation from occurring. In addition, mitophagy could promote cell apoptosis.

  15. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  16. Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.

    Directory of Open Access Journals (Sweden)

    Nicole C Riddle

    2012-09-01

    Full Text Available Chromatin environments differ greatly within a eukaryotic genome, depending on expression state, chromosomal location, and nuclear position. In genomic regions characterized by high repeat content and high gene density, chromatin structure must silence transposable elements but permit expression of embedded genes. We have investigated one such region, chromosome 4 of Drosophila melanogaster. Using chromatin-immunoprecipitation followed by microarray (ChIP-chip analysis, we examined enrichment patterns of 20 histone modifications and 25 chromosomal proteins in S2 and BG3 cells, as well as the changes in several marks resulting from mutations in key proteins. Active genes on chromosome 4 are distinct from those in euchromatin or pericentric heterochromatin: while there is a depletion of silencing marks at the transcription start sites (TSSs, HP1a and H3K9me3, but not H3K9me2, are enriched strongly over gene bodies. Intriguingly, genes on chromosome 4 are less frequently associated with paused polymerase. However, when the chromatin is altered by depleting HP1a or POF, the RNA pol II enrichment patterns of many chromosome 4 genes shift, showing a significant decrease over gene bodies but not at TSSs, accompanied by lower expression of those genes. Chromosome 4 genes have a low incidence of TRL/GAGA factor binding sites and a low T(m downstream of the TSS, characteristics that could contribute to a low incidence of RNA polymerase pausing. Our data also indicate that EGG and POF jointly regulate H3K9 methylation and promote HP1a binding over gene bodies, while HP1a targeting and H3K9 methylation are maintained at the repeats by an independent mechanism. The HP1a-enriched, POF-associated chromatin structure over the gene bodies may represent one type of adaptation for genes embedded in repetitive DNA.

  17. Mn-Ce-V-WOx/TiO2 SCR Catalysts: Catalytic Activity, Stability and Interaction among Catalytic Oxides

    Directory of Open Access Journals (Sweden)

    Xuteng Zhao

    2018-02-01

    Full Text Available A series of Mn-Ce-V-WOx/TiO2 composite oxide catalysts with different molar ratios (active components/TiO2 = 0.1, 0.2, 0.3, 0.6 have been prepared by wet impregnation method and tested in selective catalytic reduction (SCR of NO by NH3 in a wide temperature range. These catalysts were also characterized by X-ray diffraction (XRD, Transmission Electron Microscope (TEM, in situ Fourier Transform infrared spectroscopy (in situ FTIR, H2-Temperature programmed reduction (H2-TPR and X-ray photoelectron spectroscopy (XPS. The results show the catalyst with a molar ratio of active components/TiO2 = 0.2 exhibits highest NO conversion value between 150 °C to 400 °C and good resistance to H2O and SO2 at 250 °C with a gas hourly space velocity (GHSV value of 40,000 h−1. Different oxides are well dispersed and interact with each other. NH3 and NO are strongly adsorbed on the catalyst surface and the adsorption of the reactant gas leads to a redox cycle with the valence state change among the surface oxides. The adsorption of SO2 on Mn4+ and Ce4+ results in good H2O and SO2 resistance of the catalyst, but the effect of Mn and Ce are more than superior water and sulfur resistance. The diversity of valence states of the four active components and their high oxidation-reduction performance are the main reasons for the high NO conversion in this system.

  18. Excellent durability of DLC film on carburized steel (JIS-SCr420) under a stress of 3.0 GPa

    International Nuclear Information System (INIS)

    Yakabe, F; Kumagai, M; Kuwahara, H; Ochiai, S; Jinbo, Y; Horiuchi, T

    2008-01-01

    To improve durability of transmission gears, Diamond Like Carbon (DLC) film coated on roller was estimated as well as TiN film. These films were coated on JIS-SCr420 steel, which was carburized, quenched, and tempered. DLC and TiN films were deposited by PCVD and PVD process, respectively. These surface modified rollers were estimated by usual metallurgical methods (observation of microstructure by optical microscope, SEM, and TEM, measurement of hardness by Vickers hardness tester and nano-indentator), measurement of friction coefficient by ball-on-disk in dry atmosphere, analysis of carbon by Raman spectroscopy and hydrogen by EDRA, and lifetime of pitting by the roller-pitting test. The hardness values were 21 GPa and 26 GPa, the elasticity coefficients were 192 GPa and 336 GPa, the friction coefficients were 0.1∼0.15 and 0.5∼0.6 for DLC and TiN films, respectively. The present DLC was a typical DLC called as hydrogenated amorphous carbon (a-C: H). The hydrogen content was about 20%. The surface fatigue resistance of DLC-coated specimen had 100 times longer life than that the carburized and quenched one even under Hertzian contact stress of 3.0 GPa. TiN coated specimen was failed at 3.0 GPa by 5.17·10 5 cycles despite that the strength of the surface of the substrate was reduced due to the exposure at higher temperature in the coating process than the temperature for tempering

  19. Demonstration of Selective Catalytic Reduction (SCR) technology for the control of nitrogen oxide (NO{sub x}) emissions from high-sulfur coal-fired boilers. Technical progress report, first and second quarters 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    The objective of this project is to demonstrate and evaluate commercially available Selective Catalytic Reduction (SCR) catalysts from U.S., Japanese and European catalyst suppliers on a high-sulfur U.S. coal-fired boiler. SCR is a post-combustion nitrogen oxide (NO{sub x}) control technology that involve injecting ammonia into the flue gas generated from coal combustion in a boiler. The flue gas containing ammonia is then passed through a reactor that contains a specialized catalyst. In the presence of the catalyst, the ammonia reacts with NO{sub x} to form nitrogen and water vapor. Although SCR is widely practiced in Japan and Europe on gas-, oil-, and low-sulfur coal-fired boilers, there are several technical uncertainties associated with applying SCR to U.S. coals. These uncertainties include: (1) potential catalyst deactivation due to poisoning by trace metal species present in U.S. coals that are not present in other fuels; (2) performance of the technology and effects on the balance-of-plant equipment in the presence of high amounts of SO{sub 2} and SO{sub 3}; and (3) performance of a wide variety of SCR catalyst compositions, geometries and methods of manufacture under typical high-sulfur coal-fired utility operating conditions. These uncertainties are being explored by operating a series of small-scale SCR reactors and simultaneously exposing different SCR catalysts to flue gas derived from the combustion of high sulfur U.S. coal. The project is being conducted in the following three phases: permitting, environmental monitoring plan and preliminary engineering; detailed design engineering and construction; and operation, testing, disposition and final report. The project was in the operation and testing phase during this reporting period. Accomplishments for this period are described.

  20. Innovative Clean Coal Technology (ICCT): Demonstration of selective catalytic reduction (SCR) technology for the control of nitrogen oxide (NO{sub x}) emissions from high-sulfur coal-fired boilers. Technical progress report, third and fourth quarters 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    The objective of this project is to demonstrate and evaluate commercially available selective catalytic reduction (SCR) catalysts from U.S., Japanese, and European catalyst suppliers on a high-sulfur U.S. Coal-fired boiler. SCR is a post-combustion nitrogen oxide (NO{sub x}) control technology that involves injecting ammonia into the flue gas generated from coal combustion in an electric utility boiler. The flue gas containing ammonia is then passed through a reactor that contains a specialized catalyst. In the presence of the catalyst, the ammonia reacts with NO{sub x} to form nitrogen and water vapor. Although SCR is widely practiced in Japan and European gas-, oil-, and low-sulfur coal-fired boilers, there are several technical uncertainties associated with applying SCR to U.S. coals. These uncertainties include: (1) potential catalyst deactivation due to poisoning by trace metal species present in U.S. coals that are not present in other fuels; (2) performance of the technology and effects on the balance-of-plant equipment in the presence of high amounts of SO{sub 2} and SO{sub 3}; performance of a wide variety of SCR catalyst compositions, geometries, and methods of manufacture under typical high-sulfur coal-fired utility operating conditions. These uncertainties are being explored by operating a series of small- scale SCR reactors and simultaneously exposing different SCR catalysts to flue gas derived from the combustion of high sulfur U.S. coal. The demonstration is being performed at Gulf Power Company`s Plant Crist Unit No. 5 (75 MW capacity) near Pensacola, Florida. The project is funded by the U.S. Department of Energy (DOE), Southern Company Services, Inc. (SCS on behalf of the entire Southern electric system), the Electric Power Research Institute (EPRI), and Ontario Hydro. SCS is the participant responsible for managing al aspects of this project. 1 ref., 69 figs., 45 tabs.

  1. The Regulation of Induced Depression during a Frustrating Situation: Benefits of Expressive Suppression in Chinese Individuals

    Science.gov (United States)

    Ding, Nanxiang; Yang, Jiemin

    2014-01-01

    Background Studies from European-American cultures consistently reported that expressive suppression was associated with worse emotional consequence (e.g. depression) in comparison with acceptance. However, this conclusion may not apply to Chinese, as suppressing emotional displays to maintain relational harmony is culturally valued in East Asian countries. Thus, the present study examined the effects of suppression and acceptance on the depressive mood induced by a frustrating task in a Chinese sample. Method Sixty-four subjects were randomly assigned to one of three instructions: suppression, acceptance or no-regulation during a frustrating arithmetic task. The experience of depressive emotion and skin conductance response (SCR) were recorded during pre-frustration baseline, frustration induction and post-frustration recovery phases, respectively. Results Compared with the control and acceptance instructions, suppression instruction was associated with decreased depressive experiences and smaller SCR activity during frustration. There were no significant differences between acceptance and control groups in both subjective depression and SCR activity during frustration. Moreover, the suppression group showed a better emotional recovery after the frustrating task, in comparison with the acceptance and control groups. Correlation analyses verified that SCR reactivity was a reliable index of experienced depression during the frustration. Conclusions Expressive suppression is effective in reducing depressive experiences and depression-related physiological activity (SCR) when Chinese people are involved. By contrast, the acceptance of depressive emotion in Chinese people does not produce a similar regulation effect. These findings suggest that cultural context should be considered in understanding the emotional consequences of suppression and acceptance strategies. PMID:24827934

  2. The regulation of induced depression during a frustrating situation: benefits of expressive suppression in Chinese individuals.

    Directory of Open Access Journals (Sweden)

    Jiajin Yuan

    Full Text Available BACKGROUND: Studies from European-American cultures consistently reported that expressive suppression was associated with worse emotional consequence (e.g. depression in comparison with acceptance. However, this conclusion may not apply to Chinese, as suppressing emotional displays to maintain relational harmony is culturally valued in East Asian countries. Thus, the present study examined the effects of suppression and acceptance on the depressive mood induced by a frustrating task in a Chinese sample. METHOD: Sixty-four subjects were randomly assigned to one of three instructions: suppression, acceptance or no-regulation during a frustrating arithmetic task. The experience of depressive emotion and skin conductance response (SCR were recorded during pre-frustration baseline, frustration induction and post-frustration recovery phases, respectively. RESULTS: Compared with the control and acceptance instructions, suppression instruction was associated with decreased depressive experiences and smaller SCR activity during frustration. There were no significant differences between acceptance and control groups in both subjective depression and SCR activity during frustration. Moreover, the suppression group showed a better emotional recovery after the frustrating task, in comparison with the acceptance and control groups. Correlation analyses verified that SCR reactivity was a reliable index of experienced depression during the frustration. CONCLUSIONS: Expressive suppression is effective in reducing depressive experiences and depression-related physiological activity (SCR when Chinese people are involved. By contrast, the acceptance of depressive emotion in Chinese people does not produce a similar regulation effect. These findings suggest that cultural context should be considered in understanding the emotional consequences of suppression and acceptance strategies.

  3. Molecular and structural characterisation of the human sodium/iodide symporter (h N.I.S.) C-terminus and the implication of this domain in the transporter regulation

    International Nuclear Information System (INIS)

    Huc, S.

    2007-12-01

    The human natrium iodide symporter (h N.I.S.) is an intrinsic membrane protein expressed in thyroid cells where it allows iodide uptake and accumulation. It is composed of thirteen transmembrane helices and its ninety- three amino acids long cytosolic C-terminus presents many potential post-translational regulatory sites. A first part of the PhD work has been dedicated to the expression in a bacterial system and to the purification of the cytosolic C-terminal fragment. Biochemical and structural characterisation have revealed that this C-terminus is very flexible but prone to dimerization. The fragment has also been used as a bait to test the interactions with PDZ domain proteins spotted on a membrane. Several proteins interacting with the (natrium/iodide symporter) N.I.S. C-terminus have thus been identified and the study of their implication in the protein regulation has been initiated. A second part of the work has underlined the existence of a N.I.S. fragment co-purified with the entire protein. This fragment has been found in cells in culture stably expressing N.I.S. and also in human thyroid extracts and in rodent thyroid cells. We observed that this fragment is spontaneously associated with the entire protein. It is composed of the last 131 amino acid of the protein and so comprises the last transmembrane domain and the C-terminal extremity. The expression of a truncated form of h N.I.S., lacking the last 131 amino acids, shows that this protein is not correctly addressed to the cell membrane and cells expressing this mutated symporter cannot accumulate iodide. However, our results show that the co-expression of the two N.I.S. parts, the truncated form lacking the last 131 amino acid, and the complementary C-terminal fragment, leads to cells presenting 10 % of the activity of cells expressing the whole N.I.S.. (author)

  4. ‘’Mapping Self- and Co-regulation Approaches in the EU Context’’ : Explorative Study for the European Commission, DG Connect

    NARCIS (Netherlands)

    Senden, L.A.J.; Kica, E.; Klinger, Kilian; Hiemstra, M.I.

    2015-01-01

    This report presents a first mapping or inventory of the different approaches to self- and co- regulation (SCR) that can be found within the EU context, in a number of Member States (MS) and international organizations. The report consists of four sections. Whereas the first section provides an

  5. Influence of reaction products of K-getter fuel additives on commercial vanadia-based SCR catalysts Part II. Simultaneous addition of KCl, Ca(OH)(2), H3PO4 and H2SO4 in a hot flue gas at a SCR pilot-scale setup

    DEFF Research Database (Denmark)

    Castellino, Francesco; Jensen, Anker Degn; Johnsson, Jan Erik

    2009-01-01

    A commercial V2O5-WO3-TiO2 corrugated-type SCR monolith has been exposed for 1000 h in a pilot-scale setup to a flue gas doped with KCl, Ca(OH)(2), H3PO4 and H2SO4 by spraying a water solution of the components into the hot flue gas. The mixture composition has been adjusted in order to have P...... surface and did not proceed at the fast rates known for KCl. This fact indicates that binding K in P-K-Ca compounds is an effective way to reduce the negative influence of alkali metals on the lifetime of the vanadia-based SCR catalysts. On the other hand, P-deposition was favoured by the formation...

  6. Regeneration of Pt-catalysts deactivated in municipal waste flue gas with H2/N2 and the effect of regeneration step on the SCR catalyst

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Rasmussen, Søren Birk; Kustov, Arkadii

    Municipal waste flue gas was previously found to deactivate the Pt-based CO oxidation catalyst severely. In the specific case studied, siloxanes were found to cause the deactivation. An on-site method for complete regeneration of the catalyst activity was found without shutdown of the flue gas...... stream, i.e. by in situ treatment of the Pt-catalyst by reductive H2-gas. However, introduction of H2 gas in the gas stream could also affect other units in the tail pipe gas cleaning system. Of special interest here, is the effect of hydrogen gas on the performance of the deNOx + SCR catalytic process...

  7. On the activation of Pt/Al2O3 catalysts in HC-SCR by sintering. Determination of redox-active sites using Multitrack

    International Nuclear Information System (INIS)

    Vaccaro, A.R.; Mul, G.; Moulijn, J.A.; Perez-Ramirez, J.

    2003-01-01

    A highly dispersed Pt/Al 2 O 3 catalyst was used for the selective catalytic reduction of NO x using propene (HC-SCR). Contact with the reaction gas mixture led to a significant activation of the catalyst at temperatures above 523K. According to CO chemisorption data and HRTEM analysis, Pt particles on the activated catalyst had sintered. The redox behavior of the fresh and sintered catalysts was investigated using Multitrack, a TAP-like pulse reactor. If Pt particles on the catalyst are highly dispersed (average size below =2nm), only a small part (=10%) of the total number of Pt surface sites as determined by CO chemisorption (Pt surf ) participates in H 2 /O 2 redox cycles (Pt surf,redox ) in Multitrack conditions. For a sintered catalyst, with an average particle size of 2.7nm, the number of Pt surf and Pt surf,redox sites are in good agreement. Similar results were obtained for both catalysts using NO as the oxidant. The low number of Pt surf,redox sites on highly dispersed Pt/Al 2 O 3 is explained by the presence of a kinetically more stable-probably ionic-form of Pt-O bonds on all surface sites of the smaller Pt particles, including corner, edge and terrace sites. When the average particle size shifts to =2.7nm, the kinetic stability of all Pt-O bonds is collectively decreased, enabling the participation of all Pt surface sites in the redox cycles. A linear correlation between the NO x conversion in HC-SCR, and the amount of Pt surf,redox was found. This suggests that redox-active Pt sites are necessary for catalytic activity. In addition, the correlation could be significantly improved by assuming that Pt surf,terrace sites of the particles larger than 2.7nm are mainly responsible for HC-SCR activity in steady state conditions. Implications of these results for the pathway of HC-SCR over Pt catalysts are discussed

  8. Bromine based mercury abatement in waste and coal combustion. Mercury retention in the catalyst bed of a tail-end-SCR

    Energy Technology Data Exchange (ETDEWEB)

    Vosteen, Bernhard W. [Vosteen Consulting GmbH, Koeln (Germany); Kanefke, Rico; Beyer, Joachim; Bonkhofer, Theodor Gerhard [CURRENTA GmbH und Co. OHG, Leverkusen (Germany); Ullrich, Rick [WastePro Engineering Inc., Kennett Square, PA (United States)

    2008-07-01

    Observations and testing at a CURRENTA waste incineration plant and several coal fired power plants has derived the following aspects of mercury behavior in the plant's waste heat boiler and its gas cleaning train: - Hg{sub met} is oxidized to Hg{sub ion} most readily by bromine, and also by chlorine, - sulfur (SO{sub 2}) inhibit the Hg{sub met} chlorination but not the Hg{sub met} bromination, - Hg{sub met} passes through scrubbers and is adsorbed onto the catalyst bed of a tail-end SCR, slowly oxidized and finally elutes off as Hg{sub ion}, - sulfur (SO{sub 2}) impacts the reduction of molecular halogens in different ways; SO{sub 2} reduces Cl{sub 2} at elevated temperatures (boiler range), but reduces Br{sub 2} only at low temperatures (scrubber range) The operational tests and studies performed in the spring and summer of 2000 at this plant led to some specific knowledge about Hg{sub met} adsorption and also Hg{sub ion} desorption at the catalyst bed of a tail-end SCR. This knowledge, which was at that time in many respects novel, has provided more insight into the mercury oxidation behaviour. Today, process options derived from this knowledge could be implemented in hazardous waste incineration plants and also municipal solid waste incineration plants, to achieve complete mercury halogenation in the boiler flue gas, ahead of the scrubber system, at any time. This might prevent penetration of metallic mercury to the tail-end SCR and avoid the corresponding long time mercury elution. For effective prevention to be achieved in practice, it is strongly recommended to also install a continuously measuring (possibly uncalibrated) AAS mercury monitor for immediate detection of any unexpected Hg{sub met} breakthrough, for example caused by ''hidden mercury'' in the waste feed, and to initiate the rapid (preferably automized) injection of some bromine compound before even more mercury is transferred into the tail-end SCR, stored there as Hg

  9. Reversible and irreversible deactivation of Cu-CHA NH3-SCR catalysts by SO2 and SO3

    DEFF Research Database (Denmark)

    Hammershøi, Peter S.; Jangjou, Yasser; Epling, William S.

    2018-01-01

    be divided into two parts: a reversible deactivation that is restored by the regeneration treatment, and an irreversible part. The irreversible deactivation does not affect the activation energy for NH3-SCR and display a 1:1 correlation with the S-content, consistent with deactivation by Cu-sulfate formation...... is always higher when exposed at 200 °C than at 550 °C, and in wet conditions, compared to a dry feed. The deactivation is predominantly reversible, making regeneration at 550 °C a realistic approach to handle S-poisoning in exhaust systems....

  10. SH2 domain-containing inositol 5-phosphatase (SHIP2) regulates de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells.

    Science.gov (United States)

    Gorgani-Firuzjaee, Sattar; Khatami, Shohreh; Adeli, Khosrow; Meshkani, Reza

    2015-09-04

    Hepatic de-novo lipogenesis and production of triglyceride rich VLDL are regulated via the phosphoinositide 3-kinase cascade, however, the role of a negative regulator of this pathway, the SH2 domain-containing inositol 5-phosphatase (SHIP2) in this process, remains unknown. In the present study, we investigated the molecular link between SHIP2 expression and metabolic dyslipidemia using overexpression or suppression of SHIP2 gene in HepG2 cells. The results showed that overexpression of the wild type SHIP2 gene (SHIP2-WT) led to a higher total lipid content (28%) compared to control, whereas overexpression of the dominant negative SHIP2 gene (SHIP2-DN) reduced total lipid content in oleate treated cells by 40%. Overexpression of SHIP2-WT also led to a significant increase in both secretion of apoB100 containing lipoproteins and de-novo lipogenesis, as demonstrated by an enhancement in secreted apoB100 and MTP expression, increased intra and extracellular triglyceride levels and enhanced expression of lipogenic genes such as SREBP1c, FAS and ACC. On the other hand, overexpression of the SHIP2-DN gene prevented oleate-induced de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells. Collectively, these findings suggest that SHIP2 expression level is a key determinant of hepatic lipogenesis and lipoprotein secretion, and its inhibition could be considered as a potential target for treatment of dyslipidemia. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Phylogeny of the TRAF/MATH domain.

    Science.gov (United States)

    Zapata, Juan M; Martínez-García, Vanesa; Lefebvre, Sophie

    2007-01-01

    The TNF-receptor associated factor (TRAF) domain (TD), also known as the meprin and TRAF-C homology (MATH) domain is a fold of seven anti-parallel p-helices that participates in protein-protein interactions. This fold is broadly represented among eukaryotes, where it is found associated with a discrete set of protein-domains. Virtually all protein families encompassing a TRAF/MATH domain seem to be involved in the regulation of protein processing and ubiquitination, strongly suggesting a parallel evolution of the TRAF/MATH domain and certain proteolysis pathways in eukaryotes. The restricted number of living organisms for which we have information of their genetic and protein make-up limits the scope and analysis of the MATH domain in evolution. However, the available information allows us to get a glimpse on the origins, distribution and evolution of the TRAF/MATH domain, which will be overviewed in this chapter.

  12. EH domain of EHD1

    Energy Technology Data Exchange (ETDEWEB)

    Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve, E-mail: scaplan@unmc.edu; Sorgen, Paul L. [University of Nebraska Medical Center, Department of Biochemistry and Molecular Biology and Eppley Cancer Center (United States)], E-mail: psorgen@unmc.edu

    2007-12-15

    EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

  13. EH domain of EHD1

    International Nuclear Information System (INIS)

    Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

    2007-01-01

    EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed

  14. Catalytic activity of Co-Mg-Al, Cu-Mg-Al and Cu-Co-Mg-Al mixed oxides derived from hydrotalcites in SCR of NO with ammonia

    Energy Technology Data Exchange (ETDEWEB)

    Chmielarz, Lucjan; Kustrowski, Piotr; Rafalska-Lasocha, Alicja [Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow (Poland); Majda, Dorota; Dziembaj, Roman [Regional Laboratory for Physicochemical Analyses and Structural Research, Ingardena 3, 30-060 Krakow (Poland)

    2002-01-10

    M-Mg-Al hydrotalcites (where M=Cu{sup 2+}, Co{sup 2+} and Cu{sup 2+}+Co{sup 2+}) with M ranging from 5 to 20% (as atomic ratio) were prepared by co-precipitation method. Obtained samples were characterised by XRD and TGA techniques. The influence of transition metal content on thermal decomposition of hydrotalcites was observed. Calcination of the hydrotalcites at 600C resulted in the formation of mixed oxides with surface areas in the range 71-154m{sup 2}/g. Calcined hydrotalcites were tested as catalysts in the selective reduction of NO with ammonia (NO-SCR). The catalytic activity depends on the kind of transition metal, as well as its content. For the NO-SCR the following reactivity order was found: Cu-Mg-Al>Cu-Co-Mg-Al>Co-Mg-Al. Temperature-programmed methods (TPD, TPSR, stop flow-TPD), as well as FT-IR spectroscopy have been applied to determine interaction of NO and NH{sub 3} molecules with the catalyst surface.

  15. Characterizations of self-combustion reactions (SCR) for the production of nanomaterials used as advanced cathodes in Li-ion batteries

    Energy Technology Data Exchange (ETDEWEB)

    Haik, Ortal; Martha, Surendra K.; Sclar, Hadar; Samuk-Fromovich, Zvi; Zinigrad, Ella; Markovsky, Boris [Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900 (Israel); Kovacheva, Daniela; Saliyski, Nikolay [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Aurbach, Doron, E-mail: aurbach@mail.biu.ac.il [Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900 (Israel)

    2009-09-10

    In this work, self-combustion reactions (SCR) for the preparation of important cathode materials for rechargeable Li-ion batteries were investigated by thermal analytical tools (DSC, ARC, TGA), electron microscopy, XRD, various spectroscopies (MS, Raman, FTIR) and elemental analysis by ICP. The systems studied include solutions containing metal nitrates at the right stoichiometry and sucrose as a fuel, for the preparation of LiMn{sub 0.5}Ni{sub 0.5}O{sub 2} (layered), LiMn{sub 1.5}Ni{sub 0.5}O{sub 4} (spinel), LiMn{sub 0.33}Ni{sub 0.33}Co{sub 0.33}O{sub 2} (layered), and LiMn{sub 0.4}Ni{sub 0.4}Co{sub 0.2}O{sub 2} (layered). Similar products, which do not depend on the atmosphere of the processes (air or inert) were obtained by spontaneous SCR and the gradual heating of the same solutions by DSC, ARC, and TGA. The reactions involve the partial caramelization of sucrose, complicated by red-ox reactions with the nitrates that form solid products, whose organic part is finally decomposed around 400 {sup o}C. The presence of cobalt ions has a stabilizing effect, which is expressed by the low dissolution rates of Li ions from the solid products thus formed, into aqueous solutions. The reaction mechanisms are discussed herein.

  16. Empathy, Einfühlung, and aesthetic experience: the effect of emotion contagion on appreciation of representational and abstract art using fEMG and SCR.

    Science.gov (United States)

    Gernot, Gerger; Pelowski, Matthew; Leder, Helmut

    2017-03-17

    Since the advent of the concept of empathy in the scientific literature, it has been hypothesized, although not necessarily empirically verified, that empathic processes are essential to aesthetic experiences of visual art. We tested how the ability to "feel into" ("Einfühlung") emotional content-a central aspect of art empathy theories-affects the bodily responses to and the subjective judgments of representational and abstract paintings. The ability to feel into was measured by a standardized pre-survey on "emotional contagion"-the ability to pick up and mirror, or in short to "feel into", emotions, which often overlaps with higher general or interpersonal empathetic abilities. Participants evaluated the artworks on several aesthetic dimensions (liking, valence, moving, and interest), while their bodily reactions indicative of empathetic engagement (facial electromyography-EMG, and skin conductance responses-SCR) were recorded. High compared to low emotion contagion participants showed both more congruent and more intense bodily reactions (EMG and SCR) and aesthetic evaluations (higher being moved, valence, and interest) and also liked the art more. This was largely the case for both representational and abstract art, although stronger with the representational category. Our findings provide tentative evidence for recent arguments by art theorists for a close "empathic" mirroring of emotional content. We discuss this interpretation, as well as a potential tie between emotion contagion and a general increase in emotion intensity, both of which may impact, in tandem, the experience and evaluation of art.

  17. Evolution of RLSB, a nuclear-encoded S1 domain RNA binding protein associated with post-transcriptional regulation of plastid-encoded rbcL mRNA in vascular plants.

    Science.gov (United States)

    Yerramsetty, Pradeep; Stata, Matt; Siford, Rebecca; Sage, Tammy L; Sage, Rowan F; Wong, Gane Ka-Shu; Albert, Victor A; Berry, James O

    2016-06-29

    RLSB, an S-1 domain RNA binding protein of Arabidopsis, selectively binds rbcL mRNA and co-localizes with Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) within chloroplasts of C3 and C4 plants. Previous studies using both Arabidopsis (C3) and maize (C4) suggest RLSB homologs are post-transcriptional regulators of plastid-encoded rbcL mRNA. While RLSB accumulates in all Arabidopsis leaf chlorenchyma cells, in C4 leaves RLSB-like proteins accumulate only within Rubisco-containing bundle sheath chloroplasts of Kranz-type species, and only within central compartment chloroplasts in the single cell C4 plant Bienertia. Our recent evidence implicates this mRNA binding protein as a primary determinant of rbcL expression, cellular localization/compartmentalization, and photosynthetic function in all multicellular green plants. This study addresses the hypothesis that RLSB is a highly conserved Rubisco regulatory factor that occurs in the chloroplasts all higher plants. Phylogenetic analysis has identified RLSB orthologs and paralogs in all major plant groups, from ancient liverworts to recent angiosperms. RLSB homologs were also identified in algae of the division Charophyta, a lineage closely related to land plants. RLSB-like sequences were not identified in any other algae, suggesting that it may be specific to the evolutionary line leading to land plants. The RLSB family occurs in single copy across most angiosperms, although a few species with two copies were identified, seemingly randomly distributed throughout the various taxa, although perhaps correlating in some cases with known ancient whole genome duplications. Monocots of the order Poales (Poaceae and Cyperaceae) were found to contain two copies, designated here as RLSB-a and RLSB-b, with only RLSB-a implicated in the regulation of rbcL across the maize developmental gradient. Analysis of microsynteny in angiosperms revealed high levels of conservation across eudicot species and for both paralogs in

  18. Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

    KAUST Repository

    Aleisa, Fajr A

    2017-01-08

    Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.

  19. Short consensus repeat domains extend the E-selectin structure in order to grab cells out of flow

    KAUST Repository

    Aleisa, Fajr A; Sakashita, Kosuke; Lee, Jaeman; Abu Samra, Dina Bashir Kamil; Habuchi, Satoshi; Kusakabe, Takahiro; Merzaban, Jasmeen

    2017-01-01

    Selectins are key adhesion molecules responsible for initiating a multistep process that leads a cell out of the blood circulation and into a tissue or organ. They are composed of an N-terminal extracellular C-type lectin like domain, followed by an Endothelial Growth Factor like domain (EGF), a defined number of short consensus repeats SCR (also called “sushi” domains), a transmembrane domain and a C-terminal cytoplasmic tail. The adhesion of cells (expressing ligands) to the endothelium (expressing the selection i.e., E-selectin) occurs through the interaction between the lectin domain of selectins and sLeX presenting ligands. Structural/function studies to date have mainly focused on investigating the influence of the lectin domain of E-selectin on its ability to bind its ligands while other domains received less atention. We prepared a number of different recombinant E-selectin proteins with changes in the SCR units. Specifically we generated wild-type E-selectin proteins as monomeric or dimeric structures, mutant proteins with varied numbers of SCRs as well as proteins where strategic residues were mutated to change the conformation of the selectin. Using a novel real time immunoprecipitation surface plasmon resonance (SPR)-based in vitro binding study developed in our lab, the interaction of recombinant E-selectin proteins with immunoprecipitated endogenous ligands (i.e. CD44) captured on a CM-5 chip was assessed. These studies provided quantitative binding kinetics with on and off rates of selectin-ligand interactions and suggested that robust binding is dependent on the presence of the SCRs and oligomerization. These results provide significant implications on the functional mechanism of E-selectin binding to its ligands.

  20. Simultaneous removal of NO and Hg{sup 0} over Ce-Cu modified V{sub 2}O{sub 5}/TiO{sub 2} based commercial SCR catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Guilong [School of Energy & Environmental Engineering, Hebei University of Technology, Tianjin 300401 (China); College of Environmental Science & Engineering, Nankai University, Tianjin 300350 (China); Shen, Boxiong, E-mail: shenbx@nankai.edu.cn [School of Energy & Environmental Engineering, Hebei University of Technology, Tianjin 300401 (China); Yu, Ranran [School of Energy & Environmental Engineering, Hebei University of Technology, Tianjin 300401 (China); He, Chuan; Zhang, Xiao [College of Environmental Science & Engineering, Nankai University, Tianjin 300350 (China)

    2017-05-15

    Highlights: • Simultaneous removal of NO and Hg{sup 0} over the novel modified commercial SCR catalysts. • 7% Ce-1% Cu/SCR catalyst exhibited excellent activity of NO conversion and Hg{sup 0} oxidation. • 7% Ce-1% Cu/SCR catalyst showed higher resistance to SO{sub 2} and H{sub 2}O than other catalysts. • The synergistic interaction between Ce and Cu in the catalyst improved the activity greatly. - Abstract: A series of novel Ce-Cu modified V{sub 2}O{sub 5}/TiO{sub 2} based commercial SCR catalysts were prepared via ultrasonic-assisted impregnation method for simultaneous removal of NO and elemental mercury (Hg{sup 0}). Nitrogen adsorption, X-ray diffraction (XRD), temperature programmed reduction of H{sub 2} (H{sub 2}-TPR) and X-ray photoelectron spectroscopy (XPS) were used to characterize the catalysts. 7% Ce-1% Cu/SCR catalyst exhibited the highest NO conversion efficiency (>97%) at 200–400 °C, as well as the best Hg{sup 0} oxidation activity (>75%) at 150–350 °C among all the catalysts. The XPS and H{sub 2}-TPR results indicated that 7% Ce-1% Cu/SCR possess abundant chemisorbed oxygen and good redox ability, which was due to the strong synergy between Ce and Cu in the catalyst. The existence of the redox cycle of Ce{sup 4+} + Cu{sup 1+} ↔ Ce{sup 3+} + Cu{sup 2+} could greatly improve the catalytic activity. 7% Ce-1% Cu/SCR showed higher resistance to SO{sub 2} and H{sub 2}O than other catalysts. NO has a promoting effect on Hg{sup 0} oxidation. The Hg{sup 0} oxidation activity was inhibited by the injection of NH{sub 3}, which was due to the competitive adsorption and oxidized mercury could be reduced by ammonia at temperatures greater than 325 °C. Therefore, Hg{sup 0} oxidation could easily occurred at the outlet of SCR catalyst layer due to the consumption of NH{sub 3}.

  1. Domain-to-domain coupling in voltage-sensing phosphatase.

    Science.gov (United States)

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  2. Nitrous Oxide Formation and Destruction by Industrial No Abatement Techniques Including Scr Emissions des protoxides d'azote par des techniques industrielles d'abattement de NO y compris le SCR

    Directory of Open Access Journals (Sweden)

    De Soete G. G.

    2006-11-01

    Full Text Available Systematic investigations on N2O emission from full scale stationary combustion units, equipped with primary or secondary NO control techniques, are scarce or inexistent. Recent results obtained from laboratory scale studies are presented, from which it appears that fuel staging, selective non catalytic NO reduction with ammonia and selective catalytic NO reduction in the presence of ammonia, should be considered as potential sources of nitrous oxide emission enhancement. For the two mentioned gas phase NO abatement techniques (fuel staging and NCSR, this N2O emission enhancement is clearly linked with a decrease of the temperature, a result that might have been expected from the known gas phase reactions of N2O formation and destruction. Production of N2O from NCSR is more important than from fuel staging, and increases with ammonia concentration; this probably is related to the fact that ammonia yields N2O precursors (NH, NH2 readily by its decomposition. Separate injection of pure NO or NH3 suggests that N2O is a product of the interaction of those two reactants, whereas NO also is formed as a primary ammonia decomposition product in the presence of oxygen. A kinetic investigation of N2O formation from SCR has been made. It is shown that catalytic decomposition of neat ammonia yields both NO and N2O, the former as a primary product (from adsorbed ammonia and solid bound oxygen, the latter as a secondary product (from NO and adsorbed ammonia. Both NO and N2O subsequently undergo catalytic decomposition. In the presence of molecular oxygen, another NO formation (from O2 and adsorbed ammonia manifests itself at somewhat higher temperatures, creating the well known optimum temperature window . Comparative tests conducted on a number of metal oxides, tend to show that high efficiency for NO decomposition is often related to high production of N2O within the temperature window . On ne dispose actuellement pas encore de résultats d

  3. Up-regulated Ectonucleotidases in Fas-Associated Death Domain Protein- and Receptor-Interacting Protein Kinase 1-Deficient Jurkat Leukemia Cells Counteract Extracellular ATP/AMP Accumulation via Pannexin-1 Channels during Chemotherapeutic Drug-Induced Apoptosis.

    Science.gov (United States)

    Boyd-Tressler, Andrea M; Lane, Graham S; Dubyak, George R

    2017-07-01

    Pannexin-1 (Panx1) channels mediate the efflux of ATP and AMP from cancer cells in response to induction of extrinsic apoptosis by death receptors or intrinsic apoptosis by chemotherapeutic agents. We previously described the accumulation of extracellular ATP /AMP during chemotherapy-induced apoptosis in Jurkat human leukemia cells. In this study, we compared how different signaling pathways determine extracellular nucleotide pools in control Jurkat cells versus Jurkat lines that lack the Fas-associated death domain (FADD) or receptor-interacting protein kinase 1 (RIP1) cell death regulatory proteins. Tumor necrosis factor- α induced extrinsic apoptosis in control Jurkat cells and necroptosis in FADD-deficient cells; treatment of both lines with chemotherapeutic drugs elicited similar intrinsic apoptosis. Robust extracellular ATP/AMP accumulation was observed in the FADD-deficient cells during necroptosis, but not during apoptotic activation of Panx1 channels. Accumulation of extracellular ATP/AMP was similarly absent in RIP1-deficient Jurkat cells during apoptotic responses to chemotherapeutic agents. Apoptotic activation triggered equivalent proteolytic gating of Panx1 channels in all three Jurkat cell lines. The differences in extracellular ATP/AMP accumulation correlated with cell-line-specific expression of ectonucleotidases that metabolized the released ATP/AMP. CD73 mRNA, and α β -methylene-ADP-inhibitable ecto-AMPase activity were elevated in the FADD-deficient cells. In contrast, the RIP1-deficient cells were defined by increased expression of tartrate-sensitive prostatic acid phosphatase as a broadly acting ectonucleotidase. Thus, extracellular nucleotide accumulation during regulated tumor cell death involves interplay between ATP/AMP efflux pathways and different cell-autonomous ectonucleotidases. Differential expression of particular ectonucleotidases in tumor cell variants will determine whether chemotherapy-induced activation of Panx1 channels

  4. New insights into Cu/SSZ-13 SCR catalyst acidity. Part I: Nature of acidic sites probed by NH 3 titration

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinyong; Gao, Feng; Kamasamudram, Krishna; Currier, Neal; Peden, Charles H. F.; Yezerets, Aleksey

    2017-04-01

    In this work we investigated an unusual acidity feature of a Cu/SSZ-13 catalyst used in selective catalytic reduction of NOx with NH3 (NH3-SCR). In particular, this catalyst showed two distinct NH3 desorption peaks in NH3-TPD measurements, in contrast to single, unresolved desorption peaks observed for other Cu-exchanged zeolites conventionally used in the SCR studies, including its isostructural but chemically different analogue Cu/SAPO-34. We further observed that the intensities of the two TPD peaks, which represented the amount of stored NH3, changed in opposite directions in response to progressive mild hydrothermal aging, while the total storage capacity was preserved. We proposed an explanation for this remarkable behavior, by using model reference samples and additional characterization techniques. At least three NH3 storage sites were identified: two distinct populations of Cu sites responsible for low-temperature NH3 storage, and Brønsted acid sites responsible for high-temperature NH3 storage. Contrary to the commonly accepted mechanism that Brønsted acid site loss during hydrothermal aging is driven by dealumination, we concluded that the decline in the number of Brønsted acid sites upon mild hydrothermal aging for Cu/SSZ-13 was not due to dealumination, but rather transformation of Cu sites, i.e., gradual conversion of ZCuOH (Cu2+ singly coordinated with Zeolite) to Z2Cu (Cu2+ doubly coordinated with Zeolite). This transformation was responsible for the increased low-temperature desorption peak in NH3-TPD since each ZCuOH adsorbed ~1 NH3 molecule while each Z2Cu adsorbed ~2 NH3 molecules under the conditions used here. These findings were used in Part II of this series of studies to develop a method for quantifying hydrothermal ageing of industrial Cu/SSZ-13 SCR catalysts. Authors would like to thank Randall Jines for his help with collecting the reactor data, Nancy W. Washton for measuring the NMR data and Tamas Varga for in-situ XRD measurements

  5. Low-Temperature NH3–SCR of NO on Mesoporous Mn0.6Fe0.4/TiO2 Prepared by a Hydrothermal Method

    DEFF Research Database (Denmark)

    Schill, Leonhard; Putluru, Siva Sankar Reddy; Fehrmann, Rasmus

    2014-01-01

    higher (NH4)2SO4 tolerance at 150 °C compared to the impregnation preparation method. Regeneration of the (NH4)2SO4 loaded samples by heating to 400 °C was not possible whereas water washing yielded better regeneration. The catalysts are significantly more active than a commercial VWT SCR catalyst...

  6. On the importance of the phase distribution and acidity of VOx-ZrO2-SO4-sepiolite catalysts for the NH3-SCR process in relation to biomass fueled power plants

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Rasmussen, Søren Birk; Riisager, Anders

    A series of V2O5-ZrO2-SO42- - sepiolite mixtures were extruded, calcined and characterized. NH3-SCR activity was related to the phase distribution of the agglomerant and active VOX-ZrO2-SO42- phase, as well as the acidity of the composite material. Electrophoretic migration results showed...

  7. Fabrication of doped Titania (TiO2) nanofibers to serve as catalysts in NH3-Selective CatalyticReduction (SCR)

    DEFF Research Database (Denmark)

    Marani, Debora; Silva, Rafael Hubert; Dankeaw, Apiwat

    2016-01-01

    conversion efficiencies are obtained andassociated with the unique features deriving from the synergism among the doping approach, the nanoscaleconfinement, and the nano-fibrous texture. A novel concept of self-supported, lightweight and ultra-compactdesign SCR reactor is defined....... of either one or moredimensions into the nanoscale level. Among others the large surface-to-volume ratio is a feature that greatlyincreases the reactivity of the nanomaterials towards gaseous species when compared with the non-nanodimensional materials. With this regards, catalysis is one of those...... applications that unquestionable benefitsfrom this novel feature. In addition, when nanofibers (1D nanostructure) are used as catalysts, the furtheradvantage of a self-supported wide open and well-interconnected porous structure is achieved.Herein we demonstrate nanofibers as catalysts for the removal...

  8. Characterization of Co and Fe-MCM-56 catalysts for NH3-SCR and N2O decomposition: An in situ FTIR study

    Science.gov (United States)

    Grzybek, Justyna; Gil, Barbara; Roth, Wieslaw J.; Skoczek, Monika; Kowalczyk, Andrzej; Chmielarz, Lucjan

    2018-05-01

    Two-step preparation of iron and cobalt-containing MCM-56 zeolites has been undertaken to evaluate the influence of their physicochemical properties in the selective catalytic reduction (NH3-SCR or DeNOx) of NO using NH3 as a reductant. Zeolites were prepared by the selective leaching of the framework cations by concentrated HNO3 solution and NH4F/HF mixture and consecutively, introduction of Co and Fe heteroatoms, in quantities below 1 wt%. Further calcination allowed to obtain highly dispersed active species. Their evaluation and speciation was realized by adsorption of pyridine and NO, followed by FTIR spectroscopy. Both Fe-MCM-56 zeolites showed excellent activities (maximum NO conversion 92%) with high selectivity to dinitrogen (above 99%) in the high temperature NH3-SCR process. High catalytic activity of Fe-MCM-56 zeolites was assigned to the formation of stable nitrates, delivering NO to react with NH3 at higher temperatures and suppressing the direct NO oxidation. It was found that more nitrates was formed in Fe-MCM-56 (HNO3) than in Fe-MCM-56 (HF/NH4F) and that could compensate for the lower Fe loading, resulting in very similar catalytic activity of both catalysts. At the same time both Co-and Fe-MCM-56 zeolites were moderately active in direct N2O decomposition, with maximum N2O conversion not higher than 80% and activity window starting at 500 °C. This phenomenon was expected since both types of catalysts contained well dispersed active centers, not beneficial for this reaction.

  9. The addition of bio-butanol to GHGenius and a review of the GHG emissions from diesel engines with urea SCR

    International Nuclear Information System (INIS)

    2007-01-01

    The GHGenius model was developed to analyze the emissions of contaminants associated with the use and production of traditional and alternative transportation fuels. Over 140 vehicle and fuel combinations can be used with the model, which is continuously updated with new information on existing processes, new pathways, and new features. This paper provided details of the addition of a butanol production pathway and a urea system for heavy duty diesel engines. Butanol has recently been proposed as a gasoline additive for use with ethanol or as an alternative to ethanol in low-level gasoline blends. A corn to butanol pathway for low level blends was considered as the most appropriate pathway for North American applications. Estimates of energy required were made based on economic assessments and the estimated cost of energy at the time the estimates were made. In the second approach, an ethanol process model was modified to have the same water and feedstock ratios as a butanol feedstock. Total energy balances for the traditional butanol production system were poor due to the large energy requirement in the butanol production process. Low butanol concentrations were attributed to butanol toxicity to fermentation organisms. However, energy credits from co-products were large compared to many other pathways, and were attributed to the energy intensity of hydrogen and acetone. This report also provided details of selective catalytic reduction (SCR) processes that used ammonia or urea with a catalyst to produce water and gaseous nitrogen. Total energy balances and emissions impacts on the full lifecycle of SCR systems for diesel engines were provided. 13 refs., 17 tabs., 8 figs

  10. SH2 domains: modulators of nonreceptor tyrosine kinase activity

    OpenAIRE

    Filippakopoulos, Panagis; Müller, Susanne; Knapp, Stefan

    2009-01-01

    The Src homology 2 (SH2) domain is a sequence-specific phosphotyrosine-binding module present in many signaling molecules. In cytoplasmic tyrosine kinases, the SH2 domain is located N-terminally to the catalytic kinase domain (SH1) where it mediates cellular localization, substrate recruitment, and regulation of kinase activity. Initially, structural studies established a role of the SH2 domain stabilizing the inactive state of Src family members. However, biochemical characterization showed ...

  11. Cooperative interactions between paired domain and homeodomain.

    Science.gov (United States)

    Jun, S; Desplan, C

    1996-09-01

    The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.

  12. The Private Legal Governance of Domain Names

    DEFF Research Database (Denmark)

    Schovsbo, Jens Hemmingsen

    2016-01-01

    This chapter evaluates the performance of the special private tribunals or panels such as the UDRP which have been developed within complicated systems of self- and co-regulation such as ICANN to decide disputes over domain names. It uses two different dispute resolution models viz. the UDRP (WIP...... trademarks are used as (parts of) domain names to express criticism of the trademark holder or the trademark itself (e.g. “TMsucks.com” / “lorteTM.dk”)....

  13. Barratt Impulsivity and Neural Regulation of Physiological Arousal.

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    Full Text Available Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association.We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11 and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity.Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14 and women (n = 12 were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women.Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

  14. Barratt Impulsivity and Neural Regulation of Physiological Arousal.

    Science.gov (United States)

    Zhang, Sheng; Hu, Sien; Hu, Jianping; Wu, Po-Lun; Chao, Herta H; Li, Chiang-shan R

    2015-01-01

    Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association. We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity. Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women. Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

  15. Tyr721 regulates specific binding of the CSF-1 receptor kinase insert to PI 3'-kinase SH2 domains: a model for SH2-mediated receptor-target interactions.

    Science.gov (United States)

    Reedijk, M; Liu, X; van der Geer, P; Letwin, K; Waterfield, M D; Hunter, T; Pawson, T

    1992-01-01

    Efficient binding of active phosphatidylinositol (PI) 3'-kinase to the autophosphorylated macrophage colony stimulating factor receptor (CSF-1R) requires the noncatalytic kinase insert (KI) region of the receptor. To test whether this region could function independently to bind PI 3'-kinase, the isolated CSF-1R KI was expressed in Escherichia coli, and was inducibly phosphorylated on tyrosine. The tyrosine phosphorylated form of the CSF-1R KI bound PI 3'-kinase in vitro, whereas the unphosphorylated form had no binding activity. The p85 alpha subunit of PI 3'-kinase contains two Src homology (SH)2 domains, which are implicated in the interactions of signalling proteins with activated receptors. Bacterially expressed p85 alpha SH2 domains complexed in vitro with the tyrosine phosphorylated CSF-1R KI. Binding of the CSF-1R KI to PI 3'-kinase activity, and to the p85 alpha SH2 domains, required phosphorylation of Tyr721 within the KI domain, but was independent of phosphorylation at Tyr697 and Tyr706. Tyr721 was also critical for the association of activated CSF-1R with PI 3'-kinase in mammalian cells. Complex formation between the CSF-1R and PI 3'-kinase can therefore be reconstructed in vitro in a specific interaction involving the phosphorylated receptor KI and the SH2 domains of p85 alpha. Images PMID:1314163

  16. O-linked glycosylation of the mucin domain of the herpes simplex virus type 1-specific glycoprotein gC-1 is temporally regulated in a seed-and-spread manner

    DEFF Research Database (Denmark)

    Nordén, Rickard; Halim, Adnan; Nyström, Kristina

    2015-01-01

    The herpes simplex virus type 1 (HSV-1) glycoprotein gC-1, participating in viral receptor interactions and immunity interference, harbors a mucin-like domain with multiple clustered O-linked glycans. Using HSV-1-infected diploid human fibroblasts, an authentic target for HSV-1 infection...... of in all 11 GalNAc residues to selected Ser and Thr residues of the Thr-76-Lys-107 stretch of the mucin domain. The expression patterns of GalNAc transferases in the infected cells suggested that initial additions of GalNAc were carried out by initiating GalNAc transferases, in particular GalNAc-T2...

  17. Membrane-sculpting BAR domains generate stable lipid microdomains

    DEFF Research Database (Denmark)

    Zhao, Hongxia; Michelot, Alphée; Koskela, Essi V.

    2013-01-01

    Bin-Amphiphysin-Rvs (BAR) domain proteins are central regulators of many cellular processes involving membrane dynamics. BAR domains sculpt phosphoinositide-rich membranes to generate membrane protrusions or invaginations. Here, we report that, in addition to regulating membrane geometry, BAR...... domains can generate extremely stable lipid microdomains by "freezing" phosphoinositide dynamics. This is a general feature of BAR domains, because the yeast endocytic BAR and Fes/CIP4 homology BAR (F-BAR) domains, the inverse BAR domain of Pinkbar, and the eisosomal BAR protein Lsp1 induced...... phosphoinositide clustering and halted lipid diffusion, despite differences in mechanisms of membrane interactions. Lsp1 displays comparable low diffusion rates in vitro and in vivo, suggesting that BAR domain proteins also generate stable phosphoinositide microdomains in cells. These results uncover a conserved...

  18. HYBRID SELECTIVE NON-CATALYTIC REDUCTION (SNCR)/SELECTIVE CATALYTIC REDUCTION (SCR) DEMONSTRATION FOR THE REMOVAL OF NOx FROM BOILER FLUE GASES; FINAL

    International Nuclear Information System (INIS)

    Jerry B. Urbas

    1999-01-01

    The U. S. Department of Energy (DOE), Electric Power Research Institute (EPRI), Pennsylvania Electric Energy Research Council, (PEERC), New York State Electric and Gas and GPU Generation, Inc. jointly funded a demonstration to determine the capabilities for Hybrid SNCR/SCR (Selective Non-Catalytic Reduction/Selective Catalytic Reduction) technology. The demonstration site was GPU Generation's Seward Unit No.5 (147MW) located in Seward Pennsylvania. The demonstration began in October of 1997 and ended in December 1998. DOE funding was provided through Grant No. DE-FG22-96PC96256 with T. J. Feeley as the Project Manager. EPRI funding was provided through agreements TC4599-001-26999 and TC4599-002-26999 with E. Hughes as the Project Manager. This project demonstrated the operation of the Hybrid SNCR/SCR NO(sub x) control process on a full-scale coal fired utility boiler. The hybrid technology was expected to provide a cost-effective method of reducing NO(sub x) while balancing capital and operation costs. An existing urea based SNCR system was modified with an expanded-duct catalyst to provide increased NO(sub x) reduction efficiency from the SNCR while producing increased ammonia slip levels to the catalyst. The catalyst was sized to reduce the ammonia slip to the air heaters to less than 2 ppm while providing equivalent NO(sub x) reductions. The project goals were to demonstrate hybrid technology is capable of achieving at least a 55% reduction in NO(sub x) emissions while maintaining less than 2ppm ammonia slip to the air heaters, maintain flyash marketability, verify the cost benefit and applicability of Hybrid post combustion technology, and reduce forced outages due to ammonium bisulfate (ABS) fouling of the air heaters. Early system limitations, due to gas temperature stratification, restricted the Hybrid NO(sub x) reduction capabilities to 48% with an ammonia slip of 6.1 mg/Nm(sup 3) (8 ppm) at the catalyst inlet. After resolving the stratification problem

  19. HYBRID SELECTIVE NON-CATALYTIC REDUCTION (SNCR)/SELECTIVE CATALYTIC REDUCTION (SCR) DEMONSTRATION FOR THE REMOVAL OF NOx FROM BOILER FLUE GASES

    Energy Technology Data Exchange (ETDEWEB)

    Jerry B. Urbas

    1999-05-01

    The U. S. Department of Energy (DOE), Electric Power Research Institute (EPRI), Pennsylvania Electric Energy Research Council, (PEERC), New York State Electric and Gas and GPU Generation, Inc. jointly funded a demonstration to determine the capabilities for Hybrid SNCR/SCR (Selective Non-Catalytic Reduction/Selective Catalytic Reduction) technology. The demonstration site was GPU Generation's Seward Unit No.5 (147MW) located in Seward Pennsylvania. The demonstration began in October of 1997 and ended in December 1998. DOE funding was provided through Grant No. DE-FG22-96PC96256 with T. J. Feeley as the Project Manager. EPRI funding was provided through agreements TC4599-001-26999 and TC4599-002-26999 with E. Hughes as the Project Manager. This project demonstrated the operation of the Hybrid SNCR/SCR NO{sub x} control process on a full-scale coal fired utility boiler. The hybrid technology was expected to provide a cost-effective method of reducing NO{sub x} while balancing capital and operation costs. An existing urea based SNCR system was modified with an expanded-duct catalyst to provide increased NO{sub x} reduction efficiency from the SNCR while producing increased ammonia slip levels to the catalyst. The catalyst was sized to reduce the ammonia slip to the air heaters to less than 2 ppm while providing equivalent NO{sub x} reductions. The project goals were to demonstrate hybrid technology is capable of achieving at least a 55% reduction in NO{sub x} emissions while maintaining less than 2ppm ammonia slip to the air heaters, maintain flyash marketability, verify the cost benefit and applicability of Hybrid post combustion technology, and reduce forced outages due to ammonium bisulfate (ABS) fouling of the air heaters. Early system limitations, due to gas temperature stratification, restricted the Hybrid NO{sub x} reduction capabilities to 48% with an ammonia slip of 6.1 mg/Nm{sup 3} (8 ppm) at the catalyst inlet. After resolving the stratification

  20. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

    Directory of Open Access Journals (Sweden)

    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  1. Supersymmetric domain walls

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Kleinschmidt, Axel; Riccioni, Fabio

    2012-01-01

    We classify the half-supersymmetric "domain walls," i.e., branes of codimension one, in toroidally compactified IIA/IIB string theory and show to which gauged supergravity theory each of these domain walls belong. We use as input the requirement of supersymmetric Wess-Zumino terms, the properties of

  2. SH3 domain tyrosine phosphorylation--sites, role and evolution.

    Directory of Open Access Journals (Sweden)

    Zuzana Tatárová

    Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

  3. The Effect of Temperature, pH and SO/sub 2/ on Ethanol Concentration and Sugar Consumption Rate (SCR) in Apple Wine Process

    International Nuclear Information System (INIS)

    Bozoglu, M. D.; Ertunc, S.; Akay, B.; Vural, N.; Hapoglu, H.; Demirci, Y.

    2015-01-01

    The goal of this study was to examine the effects of operating parameters on ethanol concentration (ethanol) in apple wine production process. Examined parameters were temperature (T), pH and sulphur dioxide concentration (SO/sub 2/). Experiments were planned and executed according to a full two-level factorial experimental design method. The studied levels were 18 degree C and 25 degree C for temperature, 3 and 4 for pH and 50 and 150 ppm for SO/sub 2/. Ethanol concentration of apple wine for each set of experiments was determined by GC/MS. Experimental data were analyzed by using both graphical and quantitative Exploratory Data Analysis (EDA) Techniques. The main effect of each factor on sugar consumption rate (SCR) was also examined. The results show that the effect of examined operating parameters on ethanol was negative. High temperature level caused faster fermentation rate than the one caused by low temperature. Low level of pH and high level of SO/sub 2/ inhibited the activities of both harmful microorganisms and wine yeast. (author)

  4. EMISSION REDUCTION FROM A DIESEL ENGINE FUELED BY CERIUM OXIDE NANO-ADDITIVES USING SCR WITH DIFFERENT METAL OXIDES COATED CATALYTIC CONVERTER

    Directory of Open Access Journals (Sweden)

    B. JOTHI THIRUMAL

    2015-11-01

    Full Text Available This paper reports the results of experimental investigations on the influence of the addition of cerium oxide in nanoparticle form on the major physiochemical properties and the performance of diesel. The fuel is modified by dispersing the catalytic nanoparticle by ultrasonic agitation. The physiochemical properties of sole diesel fuel and modified fuel are tested with ASTM standard procedures. The effects of the additive nanoparticles on the individual fuel properties, the engine performance, and emissions are studied, and the dosing level of the additive is optimized. Cerium oxide acts as an oxygen-donating catalyst and provides oxygen for the oxidation of CO during combustion. The active energy of cerium oxide acts to burn off carbon deposits within the engine cylinder at the wall temperature and prevents the deposition of non-polar compounds on the cylinder wall which results in reduction in HC emission by 56.5%. Furthermore, a low-cost metal oxide coated SCR (selective catalyst reduction, using urea as a reducing agent, along with different types of CC (catalytic converter, has been implemented in the exhaust pipe to reduce NOx. It was observed that a reduction in NOx emission is 50–60%. The tests revealed that cerium oxide nanoparticles can be used as an additive in diesel to improve complete combustion of the fuel and reduce the exhaust emissions significantly.

  5. Ti and Si doping as a way to increase low temperature activity of sulfated Ag/Al2O3 in H2-assisted NH3-SCR of NOx

    DEFF Research Database (Denmark)

    Doronkin, Dmitry E.; Fogel, Sebastian; Gabrielsson, Pär

    2013-01-01

    Ag/Al2O3 catalysts modified by Si, Ti, Mg and W were studied to obtain higher NOx SCR activity and potentially also higher SO2 resistance than the pure silver-based catalyst for automotive applications. Addition of Ti or Si to the alumina support leads to a better NOx removal at low temperature i......-TPR) and temperature-programmed desorption of ammonia (NH3-TPD). The obtained results suggest a better silver dispersion and better regeneration capability in the case of Ti- and Si-modified Ag/Al2O3 catalysts........e. reduces the SCR onset temperature by about 10°C under the applied conditions. However, it does not increase the SO2 resistance. The catalysts and the supports have been characterized by BET, conventional and synchrotron XRD, X-ray absorption spectroscopy during temperature-programmed reduction (XAS......Ag/Al2O3 catalysts modified by Si, Ti, Mg and W were studied to obtain higher NOx SCR activity and potentially also higher SO2 resistance than the pure silver-based catalyst for automotive applications. Addition of Ti or Si to the alumina support leads to a better NOx removal at low temperature i...

  6. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR.

    Science.gov (United States)

    Suzuki, Takuo; Ishii-Watabe, Akiko; Tada, Minoru; Kobayashi, Tetsu; Kanayasu-Toyoda, Toshie; Kawanishi, Toru; Yamaguchi, Teruhide

    2010-02-15

    The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.

  7. Conserved Domain Database (CDD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.