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Sample records for ri ja eluhoone

  1. 76 FR 50770 - Submission for Review: Financial Resources Questionnaire (RI 34-1, RI 34-17, and RI 34-18) and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... MANAGEMENT Submission for Review: Financial Resources Questionnaire (RI 34- 1, RI 34-17, and RI 34-18) and Notice of Amount Due Because of Annuity Overpayment (RI 34-3, RI 34-19, and RI 34-20) AGENCY: U.S. Office... Resources Questionnaire (RI 34-1), Financial Resources Questionnaire--Federal Employees' Group...

  2. Mass Measurement with Rare-RI Rin

    NASA Astrophysics Data System (ADS)

    Ozawa, Akira

    2014-09-01

    Mass measurement with Rare-RI Ring in RIKEN RI Beam Factory (RIBF) will be presented. The main purpose of Rare-RI Ring is to measure the mass for very neutron-rich nuclei, the production rate of which is very small (rare RI) and the life-time of which is predicted to be very short (less than 10 ms). In Rare-RI Ring, mass measurements will be performed based on isochronous mass spectrometry. There are two innovative apparatus in Rare-RI Ring: individual injection, which can realize the injection of 200 A MeV rare RI one-by-one, and a cyclotron-like storage ring, which allows high isochronous magnetic fields with large angular and momentum acceptances (~1%). By these apparatus, we will achieve a 10-6 mass resolution, and will be able to access rare RI, the production rate of which is down to 1 event/day/pnA in RIBF. Construction of Rare-RI Ring has started from the 2012 fiscal year. Construction of the storage ring itself was almost completed. In this fiscal year, we succeeded to store alphas from 241Am source and to check the production of isochronous fields in the storage ring. In this talk, present status of Rare-RI Ring and the possible mass measurement there will be presented.

  3. SAMURAI spectrometer for RI beam experiments

    NASA Astrophysics Data System (ADS)

    Kobayashi, T.; Chiga, N.; Isobe, T.; Kondo, Y.; Kubo, T.; Kusaka, K.; Motobayashi, T.; Nakamura, T.; Ohnishi, J.; Okuno, H.; Otsu, H.; Sako, T.; Sato, H.; Shimizu, Y.; Sekiguchi, K.; Takahashi, K.; Tanaka, R.; Yoneda, K.

    2013-12-01

    A large-acceptance multiparticle spectrometer SAMURAI has been constructed at the RIKEN RI Beam Factory (RIBF) for RI beam experiments. It was designed primarily for kinematically complete experiments such as the invariant-mass spectroscopy of particle-unbound states in exotic nuclei, by detecting heavy fragments and projectile-rapidity nucleons in coincidence. The system consists of a superconducting dipole magnet, beam line detectors, heavy fragment detectors, neutron detectors, and proton detectors. The SAMURAI spectrometer was commissioned in March 2012, and a rigidity resolution of about 1/1500 was obtained for RI beams up to 2.4 GeV/c.

  4. RI 1170 advanced strapdown gyro

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The major components of the RI 1170 gyroscope are described. A detailed functional description of the electronics including block diagrams and photographs of output waveshapes within the loop electronics are presented. An electronic data flow diagram is included. Those gyro subassemblies that were originally planned and subsequently changed or modified for one reason or another are discussed in detail. Variations to the original design included the capacitive pickoffs, torquer flexleads, magnetic suspension, gas bearings, electronic design, and packaging. The selection of components and changes from the original design and components selected are discussed. Device failures experienced throughout the program are reported and design corrections to eliminate the failure modes are noted. Major design deficiencies such as those of the MSE electronics are described in detail. Modifications made to the gas bearing parts and design improvements to the wheel are noted. Changes to the gas bearing prints are included as well as a mathematical analysis of the 1170 gas bearing wheel by computer analysis. The mean free-path effects on gas bearing performance is summarized.

  5. Electron-beam-driven RI separator for SCRIT (ERIS) at RIKEN RI beam factory

    NASA Astrophysics Data System (ADS)

    Ohnishi, T.; Ichikawa, S.; Koizumi, K.; Kurita, K.; Miyashita, Y.; Ogawara, R.; Tamaki, S.; Togasaki, M.; Wakasugi, M.

    2013-12-01

    We constructed a radioactive isotope (RI) separator named ERIS (electron-beam-driven RI separator for SCRIT) for the SCRIT (Self-Confinement RI Target) electron scattering facility at RIKEN RI Beam Factory (RIBF). In ERIS, production rate of fission products in the photofission of uranium is estimated to be 2.2 ×1011 fissions/s with 30 g of uranium and a 1-kW electron beam. During the commissioning of ERIS, the mass resolution and overall efficiency, including ionization, extraction, and transmission, were found to be 1660 and 21%, respectively, using natural xenon gas. The preparation of uranium carbide (UC2) RI production targets is described from which a 132Sn beam was successfully separated in our first attempt at RI production.

  6. Genetics Home Reference: Léri-Weill dyschondrosteosis

    MedlinePlus

    ... health and development? More about Mutations and Health Inheritance Pattern Léri-Weill dyschondrosteosis has a pseudoautosomal dominant pattern ... of the SHOX gene in each cell. The inheritance pattern of Léri-Weill dyschondrosteosis is described as dominant ...

  7. 34. Boston switch interlocking tower. Central Falls, Providence Co., RI. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Boston switch interlocking tower. Central Falls, Providence Co., RI. Sec. 4116, mp 190.40. - Northeast Railroad Corridor, Amtrak route between CT & MA state lines, Providence, Providence County, RI

  8. 77 FR 33007 - Submission for Review: Rollover Election (RI 38-117), Rollover Information (RI 38-118), and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ... MANAGEMENT Submission for Review: Rollover Election (RI 38-117), Rollover Information (RI 38-118), and... change, of a currently approved collection information request (ICR) 3206-0212, Rollover Election (RI 38... other forms of information technology, e.g., permitting electronic submissions of responses....

  9. 77 FR 66187 - Submission for Review: Rollover Election (RI 38-117), Rollover Information (RI 38-118), and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-02

    ... MANAGEMENT Submission for Review: Rollover Election (RI 38-117), Rollover Information (RI 38-118), and... change, of a currently approved information collection request (ICR) 3206-0212, Rollover Election (RI 38... information technology, e.g., permitting electronic submissions of responses. DATES: Comments are...

  10. Streamlining the RI/FS process

    SciTech Connect

    Dumas, L.; Doss, R.C.

    1998-07-01

    In 1994, Pacific Gas and Electric Company (PG and E) contracted with CH2M HILL to manage remedial investigations and feasibility studies (RI/FS) at its former manufactured gas plant (MGP) sites in Chico, Willows, and Marysville, California. These three sites had similar histories, MGP-related contaminants, similar geologic settings, and geographically were close together. Recognizing the advantages that may be gained, both in time and money, by streamlining the RI/FS process, PG and E and CH2M HILL combined the sites into one project. From the start of the project, PG and E and CH2M HILL looked for an implemented changes to the RI/FS process to streamline the project. These changes included combining deliverables, linking field programs at the three sites, and negotiating bulk discounts on laboratory and other services by combining the work to be done at the three sites under one contract. CH2M HILL later proposed additional measures to streamline the project that were eventually adopted by both PG and E and the regulatory agencies. PG and E and CH2M HILL are currently working with the regulatory agencies to negotiate realistic measures to address contaminants in soil and groundwater, and are jointly preparing the FS with the regulatory agencies using a unique means of documentation.

  11. Outreach and Education with Europlanet 2020 RI

    NASA Astrophysics Data System (ADS)

    Heward, Anita R.; Barrosa, Mariana; Europlanet 2020 RI

    2016-10-01

    Since 2005, Europlanet has provided a framework to bring together Europe's widespread planetary science community. The project has evolved through a number of phases, and currently comprises a Research Infrastructure (RI) funded through the European Commission's Horizon 2020 program, as well as a self-sustaining membership organization. Launched in September 2015, Europlanet 2020 RI provides support, services, access to facilities, new research tools and a virtual planetary observatory. Europlanet 2020 RI's outreach and education program aims to engage members of the public, schools, teachers, policy makers and industrial partners across Europe with planetary science and the opportunities that it provides for innovation, inspiration and job creation. Europlanet's outreach and education activities are led by Science Office Ltd, a Portuguese-based SME, and a network of partners spread across nine countries including University College London, the University of Leiden, University of Latvia, Vilnius University, the Institute of Accelerating Systems and Applications, the Observatoire de Paris, CAB-INTA and the Austrian Space Forum.Europlanet supports educators and outreach providers within the planetary science community by organizing meetings, best practice workshops and communication training sessions, offering a seed-funding scheme for outreach activities, and awarding an annual prize for public engagement. Europlanet is also developing its own education and outreach resources, including an animation on 'Jupiter and its Icy Moons' (the first in a series of video "shorts") and kits for hands-on comparative planetology activities. The Europlanet Media Centre uses traditional and social media channels to communicate newsworthy results and activities to diverse audiences in Europe and worldwide. Using tools like Google Hangouts, the project connects planetary researchers directly with the public and school groups. In addition, Europlanet engages with policy makers in the

  12. Radio Meteors Observations Techniques at RI NAO

    NASA Astrophysics Data System (ADS)

    Vovk, Vasyl; Kaliuzhnyi, Mykola

    2016-07-01

    The Solar system is inhabited with large number of celestial bodies. Some of them are well studied, such as planets and vast majority of big asteroids and comets. There is one group of objects which has received little attention. That is meteoroids with related to them meteors. Nowadays enough low-technology high-efficiency radio-technical solutions are appeared which allow to observe meteors daily. At RI NAO three methodologies for meteor observation are developed: single-station method using FM-receiver, correlation method using FM-receiver and Internet resources, and single-station method using low-cost SDR-receiver.

  13. Construction of rare-RI ring at RIKEN RI Beam Factory

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Y.; Wakasugi, M.; Uesaka, T.; Ozawa, A.; Abe, Y.; Fujinawa, T.; Kase, M.; Komiyama, M.; Kubo, T.; Kumagai, K.; Maie, T.; Nagae, D.; Ohnishi, J.; Suzaki, F.; Tokuchi, A.; Watanabe, Y.; Yoshida, K.; Yamada, K.; Yamaguchi, T.; Yamasawa, H.; Yanagisawa, Y.; Zenihiro, J.; Yano, Y.

    2013-12-01

    An isochronous mass spectroscopy system using a newly constructed storage ring named the “rare-RI ring” is expected to be implemented at the RIKEN Nishina Center to determine the masses of short-lived rare nuclei including those in the r-process region with a relative precision of the order of 10-6 even for only one particle. In an isochronous storage ring, the mass is determined by measuring the revolution time of each nucleus. Our rare-RI ring consists of six magnetic sectors, and each sector consists of four bending magnets. To precisely optimize the isochronous conditions of the circulating particles for large acceptance, we install ten trim coils to half of the bending magnets. A fast-response and fast-charging kicker system enables selective and efficient injection of the produced rare nuclei into the ring one by one, along with facilitating efficient extraction of the circulating particles for time-of-flight measurement. Construction of the rare-RI ring was begun in the middle of the fiscal year 2012 at the RIKEN RI Beam Factory, and the ring is expected to be fully functional by 2015.

  14. Rare-RI ring for mass measurements at RIBF

    SciTech Connect

    Ozawa, Akira

    2014-05-02

    The rare-RI (radioactive isotope) ring at the RIKEN RI Beam Factory is described. The main purpose of the rare-RI ring is to measure the mass of short-lived rare RI. In the rare-RI ring, the mass is determined by measuring the revolution time of each nucleus based on isochronous mass spectrometry. The rare-RI ring consists of six magnetic sectors, and each sector consists of four dipole magnets. To precisely optimize the isochronous conditions of the circulating particles for large acceptance, we install 10 trim coils to half of the dipole magnets. Individual injection system enables efficient injection of the produced rare RI into the ring one by one. With facilitating efficient extraction of the circulating particles, time-of-flight measurements can be performed to the each rare RI. Construction of the rare-RI ring was begun in the middle of the fiscal year 2012, and the ring is expected to be fully functional by 2015, when we can start the mass measurements for unknown masses.

  15. Rare-RI ring for mass measurements at RIBF

    NASA Astrophysics Data System (ADS)

    Ozawa, Akira

    2014-05-01

    The rare-RI (radioactive isotope) ring at the RIKEN RI Beam Factory is described. The main purpose of the rare-RI ring is to measure the mass of short-lived rare RI. In the rare-RI ring, the mass is determined by measuring the revolution time of each nucleus based on isochronous mass spectrometry. The rare-RI ring consists of six magnetic sectors, and each sector consists of four dipole magnets. To precisely optimize the isochronous conditions of the circulating particles for large acceptance, we install 10 trim coils to half of the dipole magnets. Individual injection system enables efficient injection of the produced rare RI into the ring one by one. With facilitating efficient extraction of the circulating particles, time-of-flight measurements can be performed to the each rare RI. Construction of the rare-RI ring was begun in the middle of the fiscal year 2012, and the ring is expected to be fully functional by 2015, when we can start the mass measurements for unknown masses.

  16. Evaluation of the Hanford RI/FS cost projections

    SciTech Connect

    Not Available

    1991-06-01

    The US Department of Energy-Richland Operations (DOE-RL) tasked the Environmental Management Operations (EMO) to review the cost estimates and implementation process for the Hanford Remedial Investigation/Feasibility Study (RI/FS) Program as defined by the Hanford RCRA/CERLA Past Practices Cost Models. The purpose of the review was to determine if there were opportunities to reduce the RI/FS costs at Hanford, with a focus on the approach being taken at Hanford to implement and complete the RI/FS process. This volume contains 4 appendices for the evaluation of the Hanford RI/FS Cost Projections.

  17. 33 CFR 80.150 - Block Island, RI.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Block Island, RI. 80.150 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.150 Block Island, RI. The 72 COLREGS shall apply on the harbors of Block Island. ...

  18. 33 CFR 80.150 - Block Island, RI.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Block Island, RI. 80.150 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.150 Block Island, RI. The 72 COLREGS shall apply on the harbors of Block Island. ...

  19. 33 CFR 80.150 - Block Island, RI.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Block Island, RI. 80.150 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.150 Block Island, RI. The 72 COLREGS shall apply on the harbors of Block Island. ...

  20. 33 CFR 80.150 - Block Island, RI.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Block Island, RI. 80.150 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.150 Block Island, RI. The 72 COLREGS shall apply on the harbors of Block Island. ...

  1. 33 CFR 80.150 - Block Island, RI.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Block Island, RI. 80.150 Section... NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.150 Block Island, RI. The 72 COLREGS shall apply on the harbors of Block Island. ...

  2. Characterization of Three New Glutaredoxin Genes in the Arbuscular Mycorrhizal Fungus Rhizophagus irregularis: Putative Role of RiGRX4 and RiGRX5 in Iron Homeostasis.

    PubMed

    Tamayo, Elisabeth; Benabdellah, Karim; Ferrol, Nuria

    2016-01-01

    Glutaredoxins (GRXs) are small ubiquitous oxidoreductases involved in the regulation of the redox state in living cells. In an attempt to identify the full complement of GRXs in the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis, three additional GRX homologs, besides the formerly characterized GintGRX1 (renamed here as RiGRX1), were identified. The three new GRXs (RiGRX4, RiGRX5 and RiGRX6) contain the CXXS domain of monothiol GRXs, but whereas RiGRX4 and RiGRX5 belong to class II GRXs, RiGRX6 belongs to class I together with RiGRX1. By using a yeast expression system, we observed that the newly identified homologs partially reverted sensitivity of the GRX deletion yeast strains to external oxidants. Furthermore, our results indicated that RiGRX4 and RiGRX5 play a role in iron homeostasis in yeast. Gene expression analyses revealed that RiGRX1 and RiGRX6 were more highly expressed in the intraradical (IRM) than in the extraradical mycelium (ERM). Exposure of the ERM to hydrogen peroxide induced up-regulation of RiGRX1, RiGRX4 and RiGRX5 gene expression. RiGRX4 expression was also up-regulated in the ERM when the fungus was grown in media supplemented with a high iron concentration. These data indicate the two monothiol class II GRXs, RiGRX4 and RiGRX5, might be involved in oxidative stress protection and in the regulation of fungal iron homeostasis. Increased expression of RiGRX1 and RiGRX6 in the IRM suggests that these GRXs should play a key role in oxidative stress protection of R. irregularis during its in planta phase.

  3. Characterization of Three New Glutaredoxin Genes in the Arbuscular Mycorrhizal Fungus Rhizophagus irregularis: Putative Role of RiGRX4 and RiGRX5 in Iron Homeostasis

    PubMed Central

    Tamayo, Elisabeth; Benabdellah, Karim; Ferrol, Nuria

    2016-01-01

    Glutaredoxins (GRXs) are small ubiquitous oxidoreductases involved in the regulation of the redox state in living cells. In an attempt to identify the full complement of GRXs in the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis, three additional GRX homologs, besides the formerly characterized GintGRX1 (renamed here as RiGRX1), were identified. The three new GRXs (RiGRX4, RiGRX5 and RiGRX6) contain the CXXS domain of monothiol GRXs, but whereas RiGRX4 and RiGRX5 belong to class II GRXs, RiGRX6 belongs to class I together with RiGRX1. By using a yeast expression system, we observed that the newly identified homologs partially reverted sensitivity of the GRX deletion yeast strains to external oxidants. Furthermore, our results indicated that RiGRX4 and RiGRX5 play a role in iron homeostasis in yeast. Gene expression analyses revealed that RiGRX1 and RiGRX6 were more highly expressed in the intraradical (IRM) than in the extraradical mycelium (ERM). Exposure of the ERM to hydrogen peroxide induced up-regulation of RiGRX1, RiGRX4 and RiGRX5 gene expression. RiGRX4 expression was also up-regulated in the ERM when the fungus was grown in media supplemented with a high iron concentration. These data indicate the two monothiol class II GRXs, RiGRX4 and RiGRX5, might be involved in oxidative stress protection and in the regulation of fungal iron homeostasis. Increased expression of RiGRX1 and RiGRX6 in the IRM suggests that these GRXs should play a key role in oxidative stress protection of R. irregularis during its in planta phase. PMID:26900849

  4. Narragansett, RI Lab--Office of Research and Development

    EPA Pesticide Factsheets

    The EPA-ORD laboratory in Narragansett, RI is a recognized leader in scientific knowledge and expertise concerning the ecology of oceans, estuaries, and water-sheds, and the effects of human activities on that ecology.

  5. 75 FR 19666 - Rhode Island Disaster #RI-00007

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-15

    ... Island Disaster RI-00007 AGENCY: Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice... Island (FEMA-1894-DR), dated 04/08/2010. Incident: Severe Storms and Flooding. Incident Period: 03/12...

  6. Present status of Rare-RI Ring facility at RIBF

    NASA Astrophysics Data System (ADS)

    T Yamaguchithe Rare-RI Ring Collaboration

    2015-11-01

    A new storage ring facility called the Rare-RI Ring is currently under preparation at the RI Beam Factory (RIBF) in RIKEN. The storage ring is dedicated to the single-ion precision mass spectrometry of neutron-rich exotic nuclei. The masses are essential to elucidate the evolution of the nuclear shell structure far from the β stability and to determine the pathway of astrophysical nucleosynthesis. Such exotic nuclei are provided by the large-acceptance superconducting fragment separator, BigRIPS, at the RIBF accelerator complex. The experimental principle of the Rare-RI Ring mass measurements is based on isochronous mass spectrometry combined with the individual injection technique. This novel technique enables exotic species of interest to be produced randomly, in time to be sequentially stored in the storage ring. The Rare-RI Ring facility realizes the most efficient measurements for rare isotopes. An overview of the project is presented, along with its present status.

  7. RadNet Air Data From Providence, RI

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Providence, RI from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  8. Defining A-Kinase Anchoring Protein (AKAP) Specificity for the Protein Kinase A Subunit RI (PKA-RI).

    PubMed

    Autenrieth, Karolin; Bendzunas, N George; Bertinetti, Daniela; Herberg, Friedrich W; Kennedy, Eileen J

    2016-04-15

    A-Kinase anchoring proteins (AKAPs) act as spatial and temporal regulators of protein kinase A (PKA) by localizing PKA along with multiple proteins into discrete signaling complexes. AKAPs interact with the PKA holoenzyme through an α-helix that docks into a groove formed on the dimerization/docking domain of PKA-R in an isoform-dependent fashion. In an effort to understand isoform selectivity at the molecular level, a library of protein-protein interaction (PPI) disruptors was designed to systematically probe the significance of an aromatic residue on the AKAP docking sequence for RI selectivity. The stapled peptide library was designed based on a high affinity, RI-selective disruptor of AKAP binding, RI-STAD-2. Phe, Trp and Leu were all found to maintain RI selectivity, whereas multiple intermediate-sized hydrophobic substitutions at this position either resulted in loss of isoform selectivity (Ile) or a reversal of selectivity (Val). As a limited number of RI-selective sequences are currently known, this study aids in our understanding of isoform selectivity and establishing parameters for discovering additional RI-selective AKAPs.

  9. Regulation of FcεRI signaling by lipid phosphatases.

    PubMed

    Kuhny, Marcel; Zorn, Carolin N; Huber, Michael

    2014-01-01

    Mast cells (MCs) are tissue-resident sentinels of hematopoietic origin that play a prominent role in allergic diseases. They express the high-affinity receptor for IgE (FcεRI), which when cross-linked by multivalent antigens triggers the release of preformed mediators, generation of arachidonic acid metabolites, and the synthesis of cytokines and chemokines. Stimulation of the FcεRI with increasing antigen concentrations follows a characteristic bell-shaped dose-responses curve. At high antigen concentrations, the so-called supra-optimal conditions, repression of FcεRI-induced responses is facilitated by activation and incorporation of negative signaling regulators. In this context, the SH2-containing inositol-5'-phosphatase, SHIP1, has been demonstrated to be of particular importance. SHIP1 with its catalytic and multiple protein interaction sites provides several layers of control for FcεRI signaling. Regulation of SHIP1 function occurs on various levels, e.g., protein expression, receptor and membrane recruitment, competition for protein-protein interaction sites, and activating modifications enhancing the phosphatase function. Apart from FcεRI-mediated signaling, SHIP1 can be activated by diverse unrelated receptor systems indicating its involvement in the regulation of antigen-dependent cellular responses by autocrine feedback mechanisms or tissue-specific and/or (patho-) physiologically determined factors. Thus, pharmacologic engagement of SHIP1 may represent a beneficial strategy for patients suffering from acute or chronic inflammation or allergies.

  10. Structure of RiVax: a recombinant ricin vaccine

    PubMed Central

    Legler, Patricia M.; Brey, Robert N.; Smallshaw, Joan E.; Vitetta, Ellen S.; Millard, Charles B.

    2011-01-01

    RiVax is a recombinant protein that is currently under clinical development as part of a human vaccine to protect against ricin poisoning. RiVax includes ricin A-chain (RTA) residues 1–267 with two intentional amino-acid substitutions, V76M and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was solved to 2.1 Å resolution and it was shown that it is superposable with that of the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation of 0.6 Å over 258 Cα atoms. The RiVax structure is also compared with the recently determined structure of another potential ricin-vaccine immunogen, RTA 1–33/44–198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin-neutralizing B-cell epitopes were examined and it was found that these epitopes are within or near regions predicted to be involved in catalysis. The results demonstrate the composition of the RiVax clinical material and will guide ongoing protein-engineering strategies to develop improved immunogens. PMID:21904036

  11. In vivo specificity of EcoRI DNA methyltransferase.

    PubMed Central

    Smith, D W; Crowder, S W; Reich, N O

    1992-01-01

    The EcoRI adenine DNA methyltransferase forms part of a bacterial restriction/modification system; the methyltransferase modifies the second adenine within the canonical site GAATTC, thereby preventing the EcoRI endonuclease from cleaving this site. We show that five noncanonical EcoRI sites (TAATTC, CAATTC, GTATTC, GGATTC and GAGTTC) are not methylated in vivo under conditions when the canonical site is methylated. Only when the methyltransferase is overexpressed is partial in vivo methylation of the five sites detected. Our results suggest that the methyltransferase does not protect host DNA against potential endonuclease-mediated cleavage at noncanonical sites. Our related in vitro analysis of the methyltransferase reveals a low level of sequence-discrimination. We propose that the high in vivo specificity may be due to the active removal of methylated sequences by DNA repair enzymes (J. Bacteriology (1987), 169 3243-3250). Images PMID:1461739

  12. Schedule Optimization Study, Hanford RI/FS Program

    SciTech Connect

    Not Available

    1992-12-01

    A Schedule Optimization Study (SOS) of the US Department of Energy (DOE) Hanford Site Remedial Investigation/Feasibility Study (RI/FS) Program was conducted by an independent team of professionals from other federal agencies and the private sector experienced in environmental restoration. This team spent two weeks at Hanford in September 1992 examining the reasons for the lengthy RI/FS process at Hanford and developing recommendations to expedite the process. The need for the study arose out of a schedule dispute regarding the submission of the 1100-EM-1 Operable Unit RI/FS Work Plan. This report documents the study called for in the August 29, 1991, Dispute Resolution Committee Decision Statement. Battelle's Environmental Management Operations (EMO) coordinated the effort for DOE's Richland Field Office (RL).

  13. AKAP7gamma is a nuclear RI-binding AKAP.

    PubMed

    Brown, Rebecca L; August, Shelley L; Williams, Carmen J; Moss, Stuart B

    2003-06-27

    Spatial regulation of protein kinase A (PKA) is accomplished by its sequestration via A-kinase anchor proteins (AKAPs). PKA activity is critical for mammalian oocyte development, suggesting that PKA must be appropriately positioned in these large cells. A screen for AKAPs in oocytes identified AKAP7gamma, an AKAP originally found in pancreas. Yeast two-hybrid analysis and co-immunoprecipitation studies showed that AKAP7gamma bound the type I PKA regulatory subunit (RI) and that the RI-binding domain overlapped the previously identified type II PKA regulatory subunit (RII) binding domain. Overexpressed AKAP7gamma localized to the nuclei of HEK 293 cells via a nuclear localization signal. In addition, endogenous AKAP7gamma protein was found in both the nucleus and cytoplasm of oocytes. This work identifies AKAP7gamma as the first nuclear AKAP to bind RI and suggests that AKAP7gamma may be responsible for positioning PKA via RI and/or RII to regulate PKA-mediated gene transcription in both somatic cells and oocytes.

  14. 78 FR 21492 - Rhode Island Disaster #RI-00012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-10

    ... From the Federal Register Online via the Government Publishing Office ] SMALL BUSINESS ADMINISTRATION Rhode Island Disaster RI-00012 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of Rhode Island (FEMA-4107-DR), dated 03/22/2013. Incident: Severe winter storm and snowstorm...

  15. 75 FR 18554 - Rhode Island Disaster Number RI-00006

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... ADMINISTRATION Rhode Island Disaster Number RI-00006 AGENCY: U.S. Small Business Administration. ACTION... of Rhode Island (FEMA-1894-DR), dated 03/ 29/2010. Incident: Severe storms and flooding. Incident... INFORMATION: The notice of the Presidential disaster declaration for the State of Rhode Island, dated 03/29...

  16. 78 FR 4967 - Rhode Island Disaster #RI-00010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... ADMINISTRATION Rhode Island Disaster RI-00010 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1... Island (FEMA-4089-DR), dated 11/ 14/2012. Incident: Hurricane Sandy. Incident Period: 10/26/2012 through... the President's major disaster declaration for the State of Rhode Island, dated 11/14/2012 is hereby...

  17. 75 FR 22872 - Rhode Island Disaster Number RI-00006

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... ADMINISTRATION Rhode Island Disaster Number RI-00006 AGENCY: U.S. Small Business Administration. ACTION... of Rhode Island (FEMA-1894-DR), dated 03/ 29/2010. Incident: Severe storms and flooding. Incident... of Rhode Island, dated 03/29/2010 is hereby amended to establish the incident period for this...

  18. 76 FR 61131 - Rhode Island Disaster #RI-00008

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-03

    ... ADMINISTRATION Rhode Island Disaster RI-00008 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of Rhode Island dated 09... Island: Bristol, Kent. Connecticut: Windham. Massachusetts: Bristol, Norfolk, Worcester. The Interest...

  19. 77 FR 67857 - Rhode Island Disaster #RI-00011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-14

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Rhode Island Disaster RI-00011 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... State of Rhode Island (FEMA-4089-DR), dated 11/03/2012. Incident: Hurricane Sandy. Incident Period: 10...

  20. 75 FR 17178 - Rhode Island Disaster #RI-00006

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... ADMINISTRATION Rhode Island Disaster RI-00006 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice of the Presidential declaration of a major disaster for the State of Rhode Island.... Contiguous Counties (Economic Injury Loans Only): Rhode Island: Bristol. Connecticut: New London, Windham...

  1. 77 FR 69915 - Rhode Island Disaster Number RI-00011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-21

    ... ADMINISTRATION Rhode Island Disaster Number RI-00011 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of Rhode Island (FEMA-4089-DR), dated 11/03/2012. Incident: Hurricane Sandy... Private Non-Profit organizations in the State of RHODE ISLAND, dated 11/03/2012, is hereby amended to...

  2. 75 FR 22873 - Rhode Island Disaster Number RI-00007

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... ADMINISTRATION Rhode Island Disaster Number RI-00007 AGENCY: U.S. Small Business Administration. ACTION... Assistance Only for the State of Rhode Island (FEMA-1894-DR), dated 04/08/2010. Incident: Severe storms and... Private Non-Profit organizations in the State of Rhode Island, dated 04/08/2010, is hereby amended to...

  3. 77 FR 70203 - Rhode Island Disaster #RI-00010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-23

    ... ADMINISTRATION Rhode Island Disaster RI-00010 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a Notice of the Presidential declaration of a major disaster for the State of Rhode Island...): Rhode Island: Kent. Connecticut: New London. Massachusetts: Bristol. The Interest Rates are: Percent For...

  4. ZeroDegree spectrometer at RIKEN RI Beam Factory

    NASA Astrophysics Data System (ADS)

    Kubo, Toshiyuki; Ohnishi, Tetsuya; Takeda, Hiroyuki; Fukuda, Naoki; Kameda, Daisuke; Kusaka, Kensuke; Yoshida, Atsushi; Yoshida, Koichi; Ohtake, Masao; Inabe, Naohito; Yanagisawa, Yoshiyuki; Tanaka, Kanenobu

    2009-10-01

    At RI Beam Factory (RIBF) [1] at RIKEN Nishina Center, a variety of fast rare isotope (RI) beams are produced using the BigRIPS in-flight separator [2] for studies of exotic nuclei. The beam line following BigRIPS is designed to work as a forward spectrometer named ZeroDegree, so that it can be used for reaction studies with RI beams. The ZeroDegree spectrometer consists of two dipoles and six superconducting quadrupole triplets, of which designs are essentially the same as those of BigRIPS. It analyzes and indentifies projectile reaction residues, often in coincidence with gamma rays, and can be operated in different optics modes, depending on experimental requirements. The ZeroDegree spectrometer has recently been commissioned and used for a series of full-dress RI-beam experiments. Overview and status of the ZeroDegree spectrometer will be reported.[4pt] [1] Y. Yano: Nucl. Instr. and Meth. B 261 (2007) 1009. [0pt] [2] T. Kubo: Nucl. Instr. and Meth. B 204 (2003) 97 and T. Ohnishi et al.: J. Phys. Soc. Japan, 77 (2008) 083201.

  5. Evaluation of the Hanford RI/FS cost projections

    SciTech Connect

    Not Available

    1991-06-01

    The US Department of Energy-Richland Operations (DOE-RL) tasked the Environmental Management Operations (EMO) to review the cost estimates and implementation process for the Hanford Remedial Investigation/Feasibility Study (RI/FS) Program as defined by the Hanford RCRA/CERCLA Past Particles Cost Model. The purpose of the review was to determine if there were opportunities to reduce the RI/FS costs at Hanford, with a focus on the approach being taken at Hanford to implement and complete the RI/FS process. Three specific tasks comprised the review. The first focused on the cost model assumptions to assess whether the assumptions and resulting estimates were representative of the cost of performing work at Hanford. The second involved a detailed review of the regulatory and other driving forces that define the scope and approach to be taken at Hanford. The purpose of the review was to develop recommendations on changes what would help streamline the past practices process and reduce the cost and schedule. The third (Task 1C) provided a review of the scope and approach planned for two operable units (OUs), 100-HR-1 and 100-HR-3, as contained in their detailed draft RI/FS work plans. These work plans were reviewed for appropriate application of and conformance to the regulations and other requirements examined in the first two tasks. 4 refs.

  6. Structure of RiVax: a recombinant ricin vaccine

    SciTech Connect

    Legler, Patricia M.; Brey, Robert N.; Smallshaw, Joan E.; Vitetta, Ellen S.; Millard, Charles B.

    2011-09-01

    The X-ray crystal structure (at 2.1 Å resolution) of an immunogen under development as part of a ricin vaccine for humans is presented and structure-based analysis of the results was conducted with respect to related proteins and the known determinants for inducing or suppressing the protective immune response. RiVax is a recombinant protein that is currently under clinical development as part of a human vaccine to protect against ricin poisoning. RiVax includes ricin A-chain (RTA) residues 1–267 with two intentional amino-acid substitutions, V76M and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was solved to 2.1 Å resolution and it was shown that it is superposable with that of the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation of 0.6 Å over 258 C{sup α} atoms. The RiVax structure is also compared with the recently determined structure of another potential ricin-vaccine immunogen, RTA 1–33/44–198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin-neutralizing B-cell epitopes were examined and it was found that these epitopes are within or near regions predicted to be involved in catalysis. The results demonstrate the composition of the RiVax clinical material and will guide ongoing protein-engineering strategies to develop improved immunogens.

  7. The GPU-enabled divide-expand-consolidate RI-MP2 method (DEC-RI-MP2).

    PubMed

    Bykov, Dmytro; Kjaergaard, Thomas

    2017-02-05

    We report porting of the Divide-Expand-Consolidate Resolution of the Identity second-order Møller-Plesset perturbation (DEC-RI-MP2) method to the graphic processing units (GPUs) using OpenACC compiler directives. It is shown that the OpenACC compiler directives implementation efficiently accelerates the rate-determining step of the DEC-RI-MP2 method with minor implementation effort. Moreover, the GPU acceleration results in a better load balance and thus in an overall scaling improvement of the DEC algorithm. The resulting cross-platform hybrid MPI/OpenMP/OpenACC implementation has scalable and portable performance on heterogeneous HPC architectures. The GPU-enabled code was benchmarked using a reduced version of the S12L test set of Stefan Grimme (Grimme, Chem. Eur. J. 2012, 18, 9955) consisting of supramolecular complexes up to 158 atoms and 4292 contracted basis functions (cc-pVTZ). The test set results demonstrate the general applicability of the DEC-RI-MP2 method showing results consistent with the DEC-RI-MP2 introductory paper (Baudin et al., J. Chem. Phys. 2016, 144, 054102) on molecules of complicated electronic structures. © 2016 Wiley Periodicals, Inc.

  8. Spin-Isospin responses via charge exchange reactions of RI beams at SHARAQ

    SciTech Connect

    Shimoura, Susumu

    2012-11-12

    Nuclear spectroscopy via direct reactions of RI beams is discussed focusing on characteristics of charge-exchange reactions of RI beams. Recent experiments using the SHARAQ spectrometer at the RIBF are presented, where isovector spin monopole and spin-non-flip monopole responses are studied by charge exchange reaction of RI beams. Some experimental plans and perspectives are also presented.

  9. Genetic transformation of Begonia tuberhybrida by Ri rol genes.

    PubMed

    Kiyokawa, S; Kikuchi, Y; Kamada, H; Harada, H

    1996-04-01

    We have developed an Agrobacterium -mediated transformation system for commercial Begonia species. The leaf explants of Begonia semperflorens, Begonia x hiemalis and B. tuberhybrida were inoculated with Agrobacterium tumefaciens LBA4404 harboring a binary vector pBI121 which contains rolA, B and C genes of an agropine type Ri plasmid (pRiA4b). Kanamycin resistant shoots of B. tuberhybrida were obtained on MS agar medium supplemented with 0.1 mg/l NAA, 0.5 mg/l BA, 500 mg/l claforan and 100 mg/l kanamycin. These shoots exhibited GUS activity and Southern analysis showed a single copy insertion into the genome. When the transgenic plants were transferred to soil, they displayed the phenotype specific to the transgenic plants by A. rhizogenes such as dwarfness, delay of flowering, and wrinkled leaves and petals.

  10. FAT: Fully Automated TiRiFiC

    NASA Astrophysics Data System (ADS)

    Kamphuis, P.; Józsa, G. I. G.; Oh, S.-. H.; Spekkens, K.; Urbancic, N.; Serra, P.; Koribalski, B. S.; Dettmar, R.-J.

    2015-07-01

    FAT (Fully Automated TiRiFiC) is an automated procedure that fits tilted-ring models to Hi data cubes of individual, well-resolved galaxies. The method builds on the 3D Tilted Ring Fitting Code (TiRiFiC, ascl:1208.008). FAT accurately models the kinematics and the morphologies of galaxies with an extent of eight beams across the major axis in the inclination range 20°-90° without the need for priors such as disc inclination. FAT's performance allows us to model the gas kinematics of many thousands of well-resolved galaxies, which is essential for future HI surveys, with the Square Kilometre Array and its pathfinders.

  11. Quarry residuals RI/FS scoping document. [Weldon Spring quarry

    SciTech Connect

    Not Available

    1991-10-01

    The purpose of this document is to serve as a planning tool for the implementation of the Quarry Residual Remedial Investigation/Feasibility Study (RI/FS) process and to provide direct input to revising and updating the 1988 Work Plan for the Weldon Spring Site Remedial Action Project (WSSRAP) Remedial Investigation/Feasibility Study-Environmental Impact Statement for the Weldon Spring Site (RI/FS-EIS) (Peterson et al. 1988) for this effort. The scoping process is intended to outline the tasks necessary to develop and implement activities in compliance with the Comprehensive Environmental Response, Compensation and Liability Act-National Environmental Policy Act (CERCLA-NEPA) process from detailed planning through the appropriate decision document. In addition to scoping the entire process, this document will serve as the primary tool for planning and accomplishing all activities to be developed in the Quarry Residual RI/FS Work Plan. Subsequent tasks are difficult to plan at this time. 10 refs., 5 figs., 5 tabs.

  12. Standards for Reporting Implementation Studies (StaRI) Statement.

    PubMed

    Pinnock, Hilary; Barwick, Melanie; Carpenter, Christopher R; Eldridge, Sandra; Grandes, Gonzalo; Griffiths, Chris J; Rycroft-Malone, Jo; Meissner, Paul; Murray, Elizabeth; Patel, Anita; Sheikh, Aziz; Taylor, Stephanie J C

    2017-03-06

    Implementation studies are often poorly reported and indexed, reducing their potential to inform initiatives to improve healthcare services. The Standards for Reporting Implementation Studies (StaRI) initiative aimed to develop guidelines for transparent and accurate reporting of implementation studies. Informed by the findings of a systematic review and a consensus-building e-Delphi exercise, an international working group of implementation science experts discussed and agreed the StaRI Checklist comprising 27 items. It prompts researchers to describe both the implementation strategy (techniques used to promote implementation of an underused evidence-based intervention) and the effectiveness of the intervention that was being implemented. An accompanying Explanation and Elaboration document (published in BMJ Open, doi:10.1136/bmjopen-2016-013318) details each of the items, explains the rationale, and provides examples of good reporting practice. Adoption of StaRI will improve the reporting of implementation studies, potentially facilitating translation of research into practice and improving the health of individuals and populations.

  13. 77 FR 5581 - Submission for Review: Financial Resources Questionnaire (RI 34-1, RI 34-17) and Notice of Amount...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Due Because of Annuity Overpayment (RI 34-3, RI 34-19) AGENCY: U.S. Office of Personnel Management... Street NW., Washington, DC 20503, Attention: Desk Officer for the Office of Personnel Management or sent...., Washington, DC 20503, Attention: Desk Officer for the Office of Personnel Management or sent via...

  14. 76 FR 18811 - Submission for Review: Letter Reply To Request for Information (RI 20-64), Former Spouse Survivor...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... Annuity Election (RI 20-64A), Information on Electing a Survivor Annuity for Your Former Spouse (RI 20-64B... Reply to Request for Information, RI 20-64, and Former Spouse Survivor Annuity Election, RI 20-64A. As... information technology, e.g., permitting electronic submissions of responses. DATES: Comments are...

  15. Improving Forecast Skill by Assimilation of AIRS Cloud Cleared Radiances RiCC

    NASA Technical Reports Server (NTRS)

    Susskind, Joel; Rosenberg, Robert I.; Iredell, Lena

    2015-01-01

    ECMWF, NCEP, and GMAO routinely assimilate radiosonde and other in-situ observations along with satellite IR and MW Sounder radiance observations. NCEP and GMAO use the NCEP GSI Data Assimilation System (DAS).GSI DAS assimilates AIRS, CrIS, IASI channel radiances Ri on a channel-by-channel, case-by-case basis, only for those channels i thought to be unaffected by cloud cover. This test excludes Ri for most tropospheric sounding channels under partial cloud cover conditions. AIRS Version-6 RiCC is a derived quantity representative of what AIRS channel i would have seen if the AIRS FOR were cloud free. All values of RiCC have case-by-case error estimates RiCC associated with them. Our experiments present to the GSI QCd values of AIRS RiCC in place of AIRS Ri observations. GSI DAS assimilates only those values of RiCC it thinks are cloud free. This potentially allows for better coverage of assimilated QCd values of RiCC as compared to Ri.

  16. THE UBV(RI){sub C} COLORS OF THE SUN

    SciTech Connect

    Ramirez, I.; Michel, R.; Schuster, W. J.; Sefako, R.; Van Wyk, F.; Tucci Maia, M.; Melendez, J.; Castilho, B. V.

    2012-06-10

    Photometric data in the UBV(RI){sub C} system have been acquired for 80 solar analog stars for which we have previously derived highly precise atmospheric parameters T{sub eff}, log g, and [Fe/H] using high-resolution, high signal-to-noise ratio spectra. UBV and (RI){sub C} data for 46 and 76 of these stars, respectively, are published for the first time. Combining our data with those from the literature, colors in the UBV(RI){sub C} system, with {approx_equal} 0.01 mag precision, are now available for 112 solar analogs. Multiple linear regression is used to derive the solar colors from these photometric data and the spectroscopically derived T{sub eff}, log g, and [Fe/H] values. To minimize the impact of systematic errors in the model-dependent atmospheric parameters, we use only the data for the 10 stars that most closely resemble our Sun, i.e., the solar twins, and derive the following solar colors: (B - V){sub Sun} = 0.653 {+-} 0.005, (U - B){sub Sun} = 0.166 {+-} 0.022, (V - R){sub Sun} = 0.352 {+-} 0.007, and (V - I){sub Sun} = 0.702 {+-} 0.010. These colors are consistent, within the 1{sigma} errors, with those derived using the entire sample of 112 solar analogs. We also derive the solar colors using the relation between spectral-line-depth ratios and observed stellar colors, i.e., with a completely model-independent approach, and without restricting the analysis to solar twins. We find (B - V){sub Sun} = 0.653 {+-} 0.003, (U - B){sub Sun} = 0.158 {+-} 0.009, (V - R){sub Sun} = 0.356 {+-} 0.003, and (V - I){sub Sun} = 0.701 {+-} 0.003, in excellent agreement with the model-dependent analysis.

  17. Study on astrophysical reactions using low-energy RI beams

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Hidetoshi

    2009-10-01

    In recent years, low-energy RI beams can be produced in a good intensity and they have been used for studying many astrophysical reactions. One of the facilities producing low-energy RI beams is CRIB (CNS Radio-Isotope Beam separator) [1,2], an RI-beam separator of Center for Nuclear Study, University of Tokyo. Taking CRIB as an example, recent improvements on the RI-beam production and experimental results on astrophysical studies are presented. Several experimental approaches have been taken for the studies on astrophysical reactions.The feature of each method are discussed based on real measurements performed at CRIB. One is the direct method, applied for measurements of reactions such as (α,p) [3]. Another is the measurement of proton/alpha resonance scattering using the thick target method in inverse kinematics, by which we can obtain information on the resonances relevant in astrophysical reactions [4,5]. A recent fruitful result was from a measurement of proton resonance scattering using a ^7Be beam [5]. The energy level structure of ^8B, revealed by the experiment, is especially of interest as it is related with the ^7Be(p,γ) ^8B reaction, responsible for the production of ^8B neutrinos in the sun. We successfully determined parameters of resonances in ^8B below 6.7 MeV, which may affect the ^7Be(p,γ)^8B reaction rate at the solar temparature. Indirect methods, such as ANC and the Trojan Horse Method, were also used in some of the measurements.[4pt] [1] S. Kubono et al., Eur. Phys. J. A13 (2002) 217.[0pt] [2] Y. Yanagisawa et al., Nucl. Instrum. Meth. Phys. Res., Sect. A 539 (2005) 74.[0pt] [3] M. Notani et al., Nucl. Phys. A 764 (2004) 113c.[0pt] [4] T. Teranishi et al., Phys. Lett. B 650 (2007) 129.[0pt] [5] H. Yamaguchi et al., Phys. Lett. B 672 (2009) 230.

  18. Coordinates and RI photometry of Large Magellanic Cloud carbon stars

    SciTech Connect

    Costa, E. )

    1990-07-01

    Coordinates and photoelectric RI magnitudes are given for 86 carbon stars discovered by Blanco et al. in four selected 0.12 deg sq areas of the LMC. A comparison with the photometry of Blanco et al. for carbon stars in three different fields of the LMC suggests that the luminosity distribution of the carbon stars may change from center to center in the LMC. This possibility is supported by the differences in the mean I magnitude of the carbon stars detected between the four areas studied. 16 refs.

  19. RiBAC: Role Interaction Based Access Control Model for Community Computing

    NASA Astrophysics Data System (ADS)

    Jung, Youna; Masoumzadeh, Amirreza; Joshi, James B. D.; Kim, Minkoo

    Community computing is an agent-based development paradigm for ubiquitous computing systems. In a community computing system, ubiquitous services are provided by cooperation among agents. While agents cooperate, they interact with each other continuously to access data of other agents and/or to execute other agent’s actions. However, in cases of security-critical ubiquitous services such as medical or military services, an access control mechanism is necessary to prevent unauthorized access to critical data or action. In this paper, we propose a family of Role interaction Based Access Control (RiBAC) models for Community Computing, by extending the existing RBAC model to consider role interactions. As a basic model, we propose the core RiBAC model. For the convenience of management and to provide more fine-grained access control, we propose Hierarchical RiBAC (H-RiBAC), Constrained RiBAC (C-RiBAC), and Constrained Hierarchical RiBAC (CH-RiBAC) models. Finally, we extend the existing community computing framework to accommodate the specification and enforcement of RiBAC policies.

  20. Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome

    PubMed Central

    Draberova, Lubica; Paulenda, Tomas; Halova, Ivana; Potuckova, Lucie; Bugajev, Viktor; Bambouskova, Monika; Tumova, Magda; Draber, Petr

    2015-01-01

    Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of FcεRI

  1. Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (FcεRI) Signaling in Mast Cells by Suppressing the Function of FcεRI-Cholesterol Signalosome.

    PubMed

    Draberova, Lubica; Paulenda, Tomas; Halova, Ivana; Potuckova, Lucie; Bugajev, Viktor; Bambouskova, Monika; Tumova, Magda; Draber, Petr

    2015-01-01

    Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentrations of ethanol on FcεRI signaling events in mouse bone marrow-derived mast cells. We found that 15 min exposure to ethanol inhibited antigen-induced degranulation, calcium mobilization, expression of proinflammatory cytokine genes (tumor necrosis factor-α, interleukin-6, and interleukin-13), and formation of reactive oxygen species in a dose-dependent manner. Removal of cellular cholesterol with methyl-β-cyclodextrin had a similar effect and potentiated some of the inhibitory effects of ethanol. In contrast, exposure of the cells to cholesterol-saturated methyl-β-cyclodextrin abolished in part the inhibitory effect of ethanol on calcium response and production of reactive oxygen species, supporting lipid-centric theories of ethanol action on the earliest stages of mast cell signaling. Further studies showed that exposure to ethanol and/or removal of cholesterol inhibited early FcεRI activation events, including tyrosine phosphorylation of the FcεRI β and γ subunits, SYK kinases, LAT adaptor protein, phospholipase Cγ, STAT5, and AKT and internalization of aggregated FcεRI. Interestingly, ethanol alone, and particularly in combination with methyl-β-cyclodextrin, enhanced phosphorylation of negative regulatory tyrosine 507 of LYN kinase. Finally, we found that ethanol reduced passive cutaneous anaphylactic reaction in mice, suggesting that ethanol also inhibits FcεRI signaling under in vivo conditions. The combined data indicate that ethanol interferes with early antigen-induced signaling events in mast cells by suppressing the function of FcεRI

  2. Anti-Ri-associated paraneoplastic cerebellar and brainstem degenerative syndrome.

    PubMed

    Tay, J K; Miller, J; Joshi, A; Athey, R J

    2012-01-01

    We present the case of a female patient with a subacute paraneoplastic brainstem neurological syndrome associated with breast cancer and the development of anti-Ri antineuronal antibodies (ANNAs). It is an important syndrome to identify because of the need for urgent investigation and management to reduce progressive and irreversible neurological deterioration and to recognise the associated risks of bulbar and central respiratory failure. Diagnosis can be confounded if the anticipated normality of imaging and cerebrospinal fluid (CSF) studies is not appreciated. Positive antineuronal screening can provide rapid support for a paraneoplastic aetiology. Urgent and extensive investigation to identify the underlying tumour is imperative since neurological outcome is dependent on the rapidity of commencement and efficacy of tumour therapy. We discuss the symptoms, pathophysiology, diagnosis, treatment and prognosis of paraneoplastic neurological syndromes.

  3. The Birth Satisfaction Scale-Revised Indicator (BSS-RI).

    PubMed

    Martin, Colin R; Hollins Martin, Caroline; Redshaw, Maggie

    2017-08-29

    The current study sought to develop a short birth satisfaction indicator utilising items from the Birth Satisfaction Scale-Revised (BSS-R) for use as a brief measure of birth satisfaction and as a possible key performance indicator for perinatal service delivery evaluation. Building on the recently developed BSS-R, the study aimed to develop a simplified version of the instrument to assess birth satisfaction easily that could work as a short evaluative measure of clinical service delivery for labour and birth that is consistent with policy documents, placing women at the centre of the birth experience. The six item Birth Satisfaction Scale-Revised Indicator (BSS-RI) was embedded within the 2014 National Maternity Survey for England. A random selection of mothers who had given birth in a two week period in England were surveyed three months after the birth. Using a two-stage design and split-half dataset, exploratory factor analysis, confirmatory factor analysis, internal consistency, convergent, divergent and known-groups discriminant validity evaluation were conducted in a secondary analysis of the survey data. Using this large population based survey of recent mothers the short revised measure was found to comprise two distinct domains of birth satisfaction, 'stress and emotional response to labour and birth' and 'quality of care'. The psychometric qualities of the tool were robust as were the indices of validity and reliability evaluated. The BSS-RI represents a short easily administered and scored measure of women's satisfaction with care and the experience of labour and birth. The instrument is potentially useful for researchers, service evaluation and policy makers.

  4. 76 FR 82001 - Submission for Review: Alternative Annuity Election, RI 20-80

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... MANAGEMENT Submission for Review: Alternative Annuity Election, RI 20-80 AGENCY: U.S. Office of Personnel... on a revised information collection request (ICR) 3206-0168, Alternative Annuity Election, RI 20-80... other forms of information technology, e.g., permitting electronic submissions of responses....

  5. 76 FR 18812 - Submission for Review: RI 30-10, Disabled Dependent Questionnaire

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office OFFICE OF PERSONNEL MANAGEMENT Submission for Review: RI 30-10, Disabled Dependent Questionnaire AGENCY: U.S. Office of Personnel... INFORMATION: The RI 30-10, Disabled Dependent Questionnaire, is used to collect sufficient information...

  6. 76 FR 82000 - Submission for Review: Marital Status Certification Survey, RI 25-7

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... MANAGEMENT Submission for Review: Marital Status Certification Survey, RI 25-7 AGENCY: U.S. Office of... Survey, RI 25-7. As required by the Paperwork Reduction Act of 1995, (Pub. L. 104-13, 44 U.S.C. chapter... collection. The information collection was previously published in the Federal Register on July 7, 2011...

  7. 76 FR 39927 - Submission for Review: Marital Status Certification Survey, RI 25-7

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... From the Federal Register Online via the Government Publishing Office OFFICE OF PERSONNEL MANAGEMENT Submission for Review: Marital Status Certification Survey, RI 25-7 AGENCY: U.S. Office of... to (202) 606-0910. SUPPLEMENTARY INFORMATION: RI 25-7, Marital Status Certification Survey, is...

  8. 33 CFR 110.47 - Little Narragansett Bay, Watch Hill, R.I.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Hill, R.I. 110.47 Section 110.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Hill, R.I. All of the navigable waters of Watch Hill Cove southeasterly of a line beginning at the shore end of the United States project groin on the southerly shore of the cove and running 41°30′...

  9. 33 CFR 110.47 - Little Narragansett Bay, Watch Hill, R.I.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Hill, R.I. 110.47 Section 110.47 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Hill, R.I. All of the navigable waters of Watch Hill Cove southeasterly of a line beginning at the shore end of the United States project groin on the southerly shore of the cove and running 41°30′...

  10. 78 FR 55124 - Submission for Review: Death Benefit Payment Rollover Election, RI 94-7

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-09

    ... MANAGEMENT Submission for Review: Death Benefit Payment Rollover Election, RI 94-7 AGENCY: U.S. Office of... (ICR) 3206-0218, Death Benefit Payment Rollover Election, RI 94-7. As required by the Paperwork... Services, Office of Personnel Management. Title: Death Benefit Payment Rollover Election. OMB: 3206-0218...

  11. 33 CFR 100.119 - Newport-Bermuda Regatta, Narragansett Bay, Newport, RI

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Newport-Bermuda Regatta, Narragansett Bay, Newport, RI 100.119 Section 100.119 Navigation and Navigable Waters COAST GUARD, DEPARTMENT...-Bermuda Regatta, Narragansett Bay, Newport, RI (a) Regulated area. The regulated area includes all...

  12. The Humanities and Interrater Reliability: A Response to R. Stephen RiCharde

    ERIC Educational Resources Information Center

    Flick, Arend

    2009-01-01

    This article presents the author's critique of R. Stephen RiCharde's argument in his essay on the humanities and interrater reliability in the July-August 2008 issue of "Assessment Update." RiCharde suggests that the humanities' historical commitment to a dialectical pedagogy, a "nonlinear" process that values disagreement and debate, is at odds…

  13. Nanoporous Silicon Ignition of JA2 Propellant

    DTIC Science & Technology

    2014-06-01

    Nanoporous Silicon Ignition of JA2 Propellant Stephen L. Howard Weapons and Materials Research Directorate, ARL Wayne A. Churaman Sensors and... Nanoporous Silicon Ignition of JA2 Propellant by Stephen L. Howard, Wayne A. Churaman, and Luke J. Currano ARL-TR-6950 June 2014...2014 2. REPORT TYPE Final 3. DATES COVERED (From - To) June 2010 4. TITLE AND SUBTITLE Nanoporous Silicon Ignition of JA2 Propellant 5a

  14. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells

    PubMed Central

    Budke, Brian; Logan, Hillary L.; Kalin, Jay H.; Zelivianskaia, Anna S.; Cameron McGuire, William; Miller, Luke L.; Stark, Jeremy M.; Kozikowski, Alan P.; Bishop, Douglas K.; Connell, Philip P.

    2012-01-01

    Homologous recombination serves multiple roles in DNA repair that are essential for maintaining genomic stability. We here describe RI-1, a small molecule that inhibits the central recombination protein RAD51. RI-1 specifically reduces gene conversion in human cells while stimulating single strand annealing. RI-1 binds covalently to the surface of RAD51 protein at cysteine 319 that likely destabilizes an interface used by RAD51 monomers to oligomerize into filaments on DNA. Correspondingly, the molecule inhibits the formation of subnuclear RAD51 foci in cells following DNA damage, while leaving replication protein A focus formation unaffected. Finally, it potentiates the lethal effects of a DNA cross-linking drug in human cells. Given that this inhibitory activity is seen in multiple human tumor cell lines, RI-1 holds promise as an oncologic drug. Furthermore, RI-1 represents a unique tool to dissect the network of reaction pathways that contribute to DNA repair in cells. PMID:22573178

  15. On the sequences ri, si, ti ∈ ℤ related to extended Euclidean algorithm and continued fractions

    NASA Astrophysics Data System (ADS)

    Muhammad, Khairun Nisak; Kamarulhaili, Hailiza

    2016-06-01

    The extended Euclidean Algorithm is a practical technique used in many cryptographic applications, where it computes the sequences ri, si, ti ∈ ℤ that always satisfy ri = si a+ tib. The integer ri is the remainder in the ith sequences. The sequences si and ti arising from the extended Euclidean algorithm are equal, up to sign, to the convergents of the continued fraction expansion of a/b. The values of (ri, si, ti) satisfy various properties which are used to solve the shortest vector problem in representing point multiplications in elliptic curves cryptography, namely the GLV (Gallant, Lambert & Vanstone) integer decomposition method and the ISD (integer sub decomposition) method. This paper is to extend the proof for each of the existing properties on (ri, si, ti). We also generate new properties which are relevant to the sequences ri, si, ti ∈ ℤ. The concepts of Euclidean algorithm, extended Euclidean algorithm and continued fractions are intertwined and the properties related to these concepts are proved. These properties together with the existing properties of the sequence (ri, si, ti) are regarded as part and parcel of the building blocks of a new generation of an efficient cryptographic protocol.

  16. Remedial Investigation/Feasibility Study (RI/FS) process, elements and techniques guidance

    SciTech Connect

    Not Available

    1993-12-01

    This manual provides detailed guidance on Remedial Investigation/Feasibility Studies (RI/FSs) conducted pursuant to the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) at Department of Energy (DOE) facilities. The purpose of the RI/FS, to assess the risk posed by a hazardous waste site and to determine the best way to reduce that risk, and its structure (site characterization, risk assessment, screening and detailed analysis of alternatives, etc.) is defined in the National Oil and Hazardous Substances Pollution Contingency Plan (NCP) and further explained in the Environmental Protection Agency`s (EPA`s) Guidance for Conducting Remedial Investigations and Feasibility Studies Under CERCLA (Interim Final) 540/G-89/004, OSWER Directive 9355.3-01, October 1988. Though issued in 1988, the EPA guidance remains an excellent source of information on the conduct and structure of an RI/FS. This document makes use of supplemental RI/FS-related guidance that EPA has developed since its initial document was issued in 1988, incorporates practical lessons learned in more than 12 years of experience in CERCLA hazardous site remediation, and drawing on those lessons, introduces the Streamlined Approach For Environmental Restoration (SAFER), developed by DOE as a way to proceed quickly and efficiently through the RI/FS process at DOE facilities. Thus as its title implies, this guidance is intended to describe in detail the process and component elements of an RI/FS, as well as techniques to manage the RI/FS effectively.

  17. Stability of EcoRI restriction-modification enzymes in vivo differentiates the EcoRI restriction-modification system from other postsegregational cell killing systems.

    PubMed

    Ichige, Asao; Kobayashi, Ichizo

    2005-10-01

    Certain type II restriction modification gene systems can kill host cells when these gene systems are eliminated from the host cells. Such ability to cause postsegregational killing of host cells is the feature of bacterial addiction modules, each of which consists of toxin and antitoxin genes. With these addiction modules, the differential stability of toxin and antitoxin molecules in cells plays an essential role in the execution of postsegregational killing. We here examined in vivo stability of the EcoRI restriction enzyme (toxin) and modification enzyme (antitoxin), the gene system of which has previously been shown to cause postsegregational host killing in Escherichia coli. Using two different methods, namely, quantitative Western blot analysis and pulse-chase immunoprecipitation analysis, we demonstrated that both the EcoRI restriction enzyme and modification enzyme are as stable as bulk cellular proteins and that there is no marked difference in their stability. The numbers of EcoRI restriction and modification enzyme molecules present in a host cell during the steady-state growth were estimated. We monitored changes in cellular levels of the EcoRI restriction and modification enzymes during the postsegregational killing. Results from these analyses together suggest that the EcoRI gene system does not rely on differential stability between the toxin and the antitoxin molecules for execution of postsegregational cell killing. Our results provide insights into the mechanism of postsegregational killing by restriction-modification systems, which seems to be distinct from mechanisms of postsegregational killing by other bacterial addiction modules.

  18. Effect of nanoparticles on the RII -RI -RV rotator phase transitions of alkanes

    NASA Astrophysics Data System (ADS)

    Mukherjee, Prabir K.

    2017-08-01

    Experimental studies have shown that nanoparticles play an important role on the rotator phase transitions of n-alkanes. A phenomenological model for predicting the RII -RI -RV phase transitions in mixtures of alkanes and nanoparticles has been proposed by combining Flory-Huggins free energy of isotropic mixing and Landau free energy. The impact of nanoparticles on the RII -RI -RV phase transitions and their transition temperatures is discussed by means of phenomenological theory. The possibility of the tricritical behavior of the RI -RV phase transition in the mixtures of alkanes and nanoparticles is discussed. The theoretical predictions are in good qualitative agreement with available experimental results.

  19. Optical observations of meteors in RI Nikolaev Astronomical Observatory

    NASA Astrophysics Data System (ADS)

    Shulga, Alexander; Sybiryakova, Yevgeniya; Kulichenko, Nikolay; Vovk, Vasyl

    2015-08-01

    Video observations of meteors at the RI NAO are conducted using meteor patrol, which includes 6 optical telescopes (4 lenses: f = 85 mm, f/1.8; 2 lenses: f = 100 mm, f/2.0) equipped with a TV CCD cameras WAT-902H2 (768×576, 8.6×8.3µ). The field of view of 4 telescopes is 3.2°×4.2° and 2.7°×3.6° for 2 telescopes. System doesn't have any intensifier. Each video system is contained in a hermetic capsule to prevent it from rain and other aggressive meteorological conditions. Cameras work in the interlace mode with rate 50 half-frames per second.During 2011-2014 4135 single station meteors were observed. The mean duration of observed meteor trajectories are in 0.05-0.6 s. Double station observation campaigns has been started in September 2013 and it is still working with baseline 11.8 km. During September 2013 - September 2014 total number of observed meteor trajectories was 1757. Number of double station meteors - 328. The mean accuracy of visible radiant determination is less than 0.5 arc sec, more than 80% of radiates have standard deviation less than 0.2 arc sec.

  20. Radiation protection system at the RIKEN RI beam factory.

    PubMed

    Uwamino, Y; Fujita, S; Sakamoto, H; Ito, S; Fukunishi, N; Yabutani, T; Yamano, T; Fukumura, A

    2005-01-01

    The RIKEN RI (radioactive isotope) Beam Factory is scheduled to commence operations in 2006, and its maximum energy will be 400 MeV u(-1) for ions lighter than Ar and 350 MeV u(-1) for uranium. The beam intensity will be 1 pmicroA (6 x 10(12) particles s(-1)) for any element at the goal. For the hands-on-maintenance and the rational shield thickness of the building, the beam loss must be controlled with several kinds of monitors. Three types of radiation monitors will be installed. The first one consists of a neutron dose equivalent monitor and an ionisation chamber, which are commercially available area monitors. The second one is a conventional hand-held dose equivalent monitor wherein the logarithmic signal is read by a programmable logic controller based on the radiation safety interlock system (HIS). The third one is a simple plastic scintillator called a beam loss monitor. All the monitors have threshold levels for alarm and beam stop, and HIS reads all these signals.

  1. Initial Measurements of Radiocarbon In Atmospheric Formaldehyde at Narragansett, RI

    NASA Astrophysics Data System (ADS)

    Shen, H.; Heikes, B. G.; Xu, L.; McNichol, A. P.; Olson, J. R.

    2008-12-01

    Formaldehyde is an intermediate in the atmospheric oxidation of nearly every volatile organic compound (VOC) and is important to odd-hydrogen radicals and ozone chemistry. It is directly observed from space and its distributions are used to constrain biogenic emissions of VOCs, specifically isoprene. The relative contribution of fossil VOCs and biogenic VOCs to formaldehyde, to isoprene emission estimates and subsequently to ozone and oxidant chemistry is expected to vary seasonally and spatially due to VOC speciation, emission patterns, and reactivity. The radiocarbon, 14C, content of formaldehyde is useful in assessing the relative contributions of fossil and biogenic VOC groups to formaldehyde. We report a compound specific radiocarbon analysis (CSRA) method for formaldehyde based upon gaseous formaldehyde collection, derivatization to thiazolidine, preparative capillary gas chromatography separation, and AMS analysis. Ambient measurements from Narragansett, RI, made in winter and summer 2007 are presented. On 11 of 13 samples, we find 80 to >95% of the collected formaldehyde is of fossil origin and, contrary to our initial hypothesis, we see no seasonal shift in proportion. The remaining 2 samples, one each from winter and summer, are 30-40% biogenic carbon. The measurements are interpreted considering fossil-biogenic source attribution and local transport conditions and contrasted with prior measurements from Nova Scotia. Further, CSRA measurement of acetaldehyde is feasible with the method.

  2. CCD UBV(RI)C photometry of twenty open clusters

    NASA Astrophysics Data System (ADS)

    Oralhan, İnci Akkaya; Karataş, Yüksel; Schuster, William J.; Michel, Raúl; Chavarría, Carlos

    2015-01-01

    Fundamental astrophysical parameters have been derived for 20 open clusters (OCs) using CCD UBV(RI)C photometric data observed with the 84 cm telescope at the San Pedro Mártir National Astronomical Observatory, México. The interstellar reddenings, metallicities, distances, and ages have been compared to the literature values. Significant differences are usually due to the usage of diverse empirical calibrations and differing assumptions, such as concerning cluster metallicity, as well as distinct isochrones which correspond to differing element-abundance ratios, internal stellar physics, and photometric systems. Different interstellar reddenings, as well as varying reduction and cluster-membership techniques, are also responsible for these kinds of systematic differences and errors. The morphological ages, which are derived from the morphological indices (δV and δ1) in the CM diagrams, are in good agreement with the isochrone ages of 12 OCs, those with good red clump (RC) and red giant (RG) star candidates. No metal abundance gradient is detected for the range 6.82⩽RGC⩽15.37 kpc, nor any correlation between the cluster ages and metal abundances for these 20 OCs. Young, metal-poor OCs, observed here in the third Galactic quadrant, may be associated with stellar over-densities, such as that in Canis Major (Martin et al.) and the Monoceros Ring (Newberg et al.), or signatures of past accretion events, as discussed by Yong et al. and Carraro et al.

  3. A Soluble Form of the High Affinity IgE Receptor, Fc-Epsilon-RI, Circulates in Human Serum

    PubMed Central

    Dehlink, Eleonora; Platzer, Barbara; Baker, Alexandra H.; LaRosa, Jessica; Pardo, Michael; Dwyer, Peter; Yen, Elizabeth H.; Szépfalusi, Zsolt

    2011-01-01

    Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum. PMID:21544204

  4. R.I. Officials, EPA Celebrate Successful Climate Showcase Communities Partnership

    EPA Pesticide Factsheets

    RI's Congressional delegation today joined the EPA, elected officials, & community leaders to celebrate innovative work accomplished by 4 Ocean State communities to reduce energy consumption & greenhouse gas emissions in municipal & residential buildings.

  5. City of Newport, R.I. Industrial Pretreatment Program Recognized for Excellence

    EPA Pesticide Factsheets

    The Newport, R.I. Water Pollution Control Plant was recently selected by EPA for a 2014 Regional Industrial Pretreatment Program Excellence Award. The pretreatment program staff at the Newport facility, led by Industrial Pretreatment

  6. Agreement Ensures Groundwater Study at No. Smithfield, R.I. Superfund Site

    EPA Pesticide Factsheets

    The owner/operators & parties responsible for hazardous substance disposal at the Landfill & Resource Recovery Superfund Site in N. Smithfield, RI, have agreed to perform & pay for an investigation & study to evaluate the extent of, & cleanup options...

  7. 77 FR 49029 - Submission for Review: Annuity Supplement Earnings Report, RI 92-22

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Personnel Management, 1900 E Street NW., Room 4332, Washington, DC 20415, Attention: Cyrus S. Benson or sent via electronic mail to Cyrus.Benson@opm.gov or faxed to (202) 606-0910. SUPPLEMENTARY INFORMATION: RI...

  8. 33 CFR 100.119 - Newport-Bermuda Regatta, Narragansett Bay, Newport, RI

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of Narragansett Bay, Newport, RI, within the following points (NAD 83): Latitude Longitude 41°27′51... will begin offshore and the following regulated area applies (NAD 83): Latitude Longitude 41°26′04″...

  9. 33 CFR 100.119 - Newport-Bermuda Regatta, Narragansett Bay, Newport, RI

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of Narragansett Bay, Newport, RI, within the following points (NAD 83): Latitude Longitude 41°27′51... will begin offshore and the following regulated area applies (NAD 83): Latitude Longitude 41°26′04″...

  10. VizieR Online Data Catalog: RR Gem BV(RI)c differential photometry (Jurcsik+, 2005)

    NASA Astrophysics Data System (ADS)

    Jurcsik, J.; Sodor, A.; Varadi, M.; Szeidl, B.; Washuettl, A.; Weber, M.; Dekany, I.; Hurta, Zs.; Lakatos, B.; Posztobanyi, K.; Szing, A.; Vida, K.

    2004-10-01

    The observations were obtained with the automated 60cm telescope of Konkoly Observatory, Svabhegy, Budapest equiped with a Wright 750x1100 CCD using BV(RI)c filters, between 14 January and 4 May 2004. (4 data files).

  11. Nuclear Astrophysics and Structure Studies Using Low-energy RI Beams at CRIB

    SciTech Connect

    Yamaguchi, H.; Hashimoto, T.; Hayakawa, S.; Binh, D. N.; Kahl, D.; Kubono, S.

    2010-05-12

    CRIB (CNS Radioactive Ion Beam separator) is a low-energy RI beam separator at the Center for Nuclear Study (CNS) of the University of Tokyo. Using the RI beams at CRIB, Many measurements on proton and alpha resonance scatterings, (alpha,p) reactions, and others were peformed in recent years, mainly for studying astrophysical reactions and exotic nuclear structure. Among them, the results on the {sup 7}Be+p and {sup 7}Li+alpha resonance scatterings are presented.

  12. Europlanet-RI IDIS - A Data Network in Support of Planetary Research

    NASA Astrophysics Data System (ADS)

    Schmidt, Walter; Capria, Maria Teresa; Chanteur, Gérard

    2010-05-01

    The "Europlanet Research Infrastructure - Europlanet RI", supported by the European Commission's Framework Program 7, aims at integrating major parts of the distributed European Planetary Research infrastructure with as diverse components as space exploration, ground-based observations, laboratory experiments and numerical modeling teams. A central part of Europlanet RI is the "Integrated and Distributed Information Service" (IDIS), a network of data and information access facilities in Europe via which information relevant for planetary research can be easily found and retrieved. This covers the wide range from contact addresses of possible research partners, laboratories and test facilities to the access of data collected with space missions or during laboratory or simulation tests and to model software useful for their interpretation. During the following three years the capabilities of the network will be extended to allow the combination of many different data sources for comperative studies including the results of modeling calculations and simulations of instrument observations. Together with the access to complex databases for spectra of atmospheric molecules and planetary surface material IDIS will offer a versatile working environment for making the scientific exploitation of the resources put into planetary research in the past and future more effective. Many of the mentioned capabilities are already available now. List of contact web-sites: Technical node for support and management aspects: http://www.idis.europlanet-ri.eu/ Planetary Surfaces and Interiors node: http://www.idis-interiors.europlanet-ri.eu/ Planetary Plasma node: http://www.idis-plasma.europlanet-ri.eu/ Planetary Atmospheres node: http://www.idis-atmos.europlanet-ri.eu/ Small Bodies and Dust node: http://www.idis-sbdn.europlanet-ri.eu/ Planetary Dynamics and Extraterrestrial Matter node: http://www.idis-dyn.europlanet-ri.eu/

  13. Planetary GIS and EuroPlanet-RI H2020

    NASA Astrophysics Data System (ADS)

    Rossi, A. P.; Cecconi, B.; Manaud, N.; Erard, S.; Marmo, C.

    2015-10-01

    Geographic Information System (GIS) practice and applications within Planetary Science became in the last decade a major component for studying solid surfaces of Solar System bodies [e.g. 1,2,3]: from earlier mainly Mars-focused efforts limited to few datasets, the availability of high-quality spatial data grew enormously and its accessibility is also enhanced by the use of OGC web standards. Higher-level, calibrated georeferenced datasets are the prime target for geologic and related thematic mapping [e.g. 4], although the communities potentially benefiting from a GIS-based approach are beyond and they include most closely Atmospheric science, as well as Magnetospheric and Plasma Physics, to quote only few. In the upcoming EuroPlanet-RI H2020 project Planetary GIS efforts are embedded within the VESPA activity [5] and they allow for a tight integration of OGC and VO-based tools and interfaces [6]. Nowadays GIS-based analyses are used for carrying out research tasks and systematic mapping on planetary bodies, but also for a wide range of analyses related [e.g. 7] to landing site selection, ranging from scientific merit to safety [e.g.8] Community building is a key part of VESPA [5], but also independently followed by other actors like ESA PSA [9]. Recently a workshop on Planetary GIS in broad sense and with particular reference to ESA data archives has been organized [10]. Such workshop has been strongly supported by ESA and the broad planetary community, both directly and through its official channel for Planetary Science archive science access and exploitation-related needs, the PSA User Group [11]. Its outcomes, also in terms of use case development, might be instrumental to VESPA GIS/VO future activities

  14. Fast, accurate evaluation of exact exchange: The occ-RI-K algorithm

    SciTech Connect

    Manzer, Samuel; Horn, Paul R.; Mardirossian, Narbe; Head-Gordon, Martin

    2015-07-14

    Construction of the exact exchange matrix, K, is typically the rate-determining step in hybrid density functional theory, and therefore, new approaches with increased efficiency are highly desirable. We present a framework with potential for greatly improved efficiency by computing a compressed exchange matrix that yields the exact exchange energy, gradient, and direct inversion of the iterative subspace (DIIS) error vector. The compressed exchange matrix is constructed with one index in the compact molecular orbital basis and the other index in the full atomic orbital basis. To illustrate the advantages, we present a practical algorithm that uses this framework in conjunction with the resolution of the identity (RI) approximation. We demonstrate that convergence using this method, referred to hereafter as occupied orbital RI-K (occ-RI-K), in combination with the DIIS algorithm is well-behaved, that the accuracy of computed energetics is excellent (identical to conventional RI-K), and that significant speedups can be obtained over existing integral-direct and RI-K methods. For a 4400 basis function C{sub 68}H{sub 22} hydrogen-terminated graphene fragment, our algorithm yields a 14 × speedup over the conventional algorithm and a speedup of 3.3 × over RI-K.

  15. Fast, accurate evaluation of exact exchange: The occ-RI-K algorithm

    PubMed Central

    Manzer, Samuel; Horn, Paul R.; Mardirossian, Narbe; Head-Gordon, Martin

    2015-01-01

    Construction of the exact exchange matrix, K, is typically the rate-determining step in hybrid density functional theory, and therefore, new approaches with increased efficiency are highly desirable. We present a framework with potential for greatly improved efficiency by computing a compressed exchange matrix that yields the exact exchange energy, gradient, and direct inversion of the iterative subspace (DIIS) error vector. The compressed exchange matrix is constructed with one index in the compact molecular orbital basis and the other index in the full atomic orbital basis. To illustrate the advantages, we present a practical algorithm that uses this framework in conjunction with the resolution of the identity (RI) approximation. We demonstrate that convergence using this method, referred to hereafter as occupied orbital RI-K (occ-RI-K), in combination with the DIIS algorithm is well-behaved, that the accuracy of computed energetics is excellent (identical to conventional RI-K), and that significant speedups can be obtained over existing integral-direct and RI-K methods. For a 4400 basis function C68H22 hydrogen-terminated graphene fragment, our algorithm yields a 14 × speedup over the conventional algorithm and a speedup of 3.3 × over RI-K. PMID:26178096

  16. IL-1RI participates in normal growth plate development and bone modeling.

    PubMed

    Simsa-Maziel, Stav; Zaretsky, Janna; Reich, Adi; Koren, Yoav; Shahar, Ron; Monsonego-Ornan, Efrat

    2013-07-01

    The proinflammatory cytokine interleukin-1 (IL-1) signals through IL-1 receptor type I (IL-1RI) and induces osteoclastogenesis and bone resorption mainly during pathological conditions. Little is known about the effect of excess or absence of IL-1 signaling on the physiological development of the growth plate and bone. In this study, we examine growth plate morphology, bone structure, and mechanical properties as well as osteoclast number in IL-1RI knockout mice to evaluate the role of IL-1RI in the normal development of the growth plate and bone. We show for the first time that IL-1RI knockout mice have narrower growth plates due to a smaller hypertrophic zone, suggesting a role for this cytokine in hypertrophic differentiation, together with higher proteoglycan content. The bones of theses mice exhibit higher trabecular and cortical mass, increased mineral density, and superior mechanical properties. In addition, IL-1RI knockout mice have significantly reduced osteoclast numbers in the chondro-osseous junction, trabecular bone, and cortical bone. These results suggest that IL-1RI is involved in normal growth plate development and ECM homeostasis and that it is significant in the physiological process of bone modeling.

  17. Emdogain-regulated gene expression in palatal fibroblasts requires TGF-βRI kinase signaling.

    PubMed

    Stähli, Alexandra; Bosshardt, Dieter; Sculean, Anton; Gruber, Reinhard

    2014-01-01

    Genome-wide microarrays have suggested that Emdogain regulates TGF-β target genes in gingival and palatal fibroblasts. However, definitive support for this contention and the extent to which TGF-β signaling contributes to the effects of Emdogain has remained elusive. We therefore studied the role of the TGF-β receptor I (TGF-βRI) kinase to mediate the effect of Emdogain on palatal fibroblasts. Palatal fibroblasts were exposed to Emdogain with and without the inhibitor for TGF-βRI kinase, SB431542. Emdogain caused 39 coding genes to be differentially expressed in palatal fibroblasts by microarray analysis (p<0.05; >10-fold). Importantly, in the presence of the TGF-βRI kinase inhibitor SB431542, Emdogain failed to cause any significant changes in gene expression. Consistent with this mechanism, three independent TGF-βRI kinase inhibitors and a TGF-β neutralizing antibody abrogated the increased expression of IL-11, a selected Emdogain target gene. The MAPK inhibitors SB203580 and U0126 lowered the impact of Emdogain on IL-11 expression. The data support that TGF-βRI kinase activity is necessary to mediate the effects of Emdogain on gene expression in vitro.

  18. [Bacteria and viruses modulate FcεRI-dependent mast cell activity].

    PubMed

    Słodka, Aleksandra; Brzezińska-Błaszczyk, Ewa

    2013-03-08

    Undoubtedly, mast cells play a central role in allergic processes. Specific allergen cross-linking of IgE bound to the high affinity receptors (FcεRI) on the mast cell surface leads to the release of preformed mediators and newly synthesized mediators, i.e. metabolites of arachidonic acid and cytokines. More and more data indicate that bacteria and viruses can influence FcεRI-dependent mast cell activation. Some bacterial and viral components can reduce the surface expression of FcεRI. There are also findings that ligation of Toll-like receptors (TLRs) by bacterial or viral antigens can affect IgE-dependent mast cell degranulation and preformed mediator release as well as eicosanoid production. The synergistic interaction of TLR ligands and allergen can also modify cytokine synthesis by mast cells stimulated via FcεRI. Moreover, data suggest that specific IgE for bacterial or viral antigens can influence mast cell activity. What is more, some bacterial and viral components or some endogenous proteins produced during viral infection can act as superantigens by interacting with the VH3 domain of IgE. All these observations indicate that bacterial and viral infections modify the course of allergic diseases by affecting FcεRI-dependent mast cell activation. 

  19. BspRI restriction endonuclease: cloning, expression in Escherichia coli and sequential cleavage mechanism.

    PubMed

    Raskó, Tamás; Dér, András; Klement, Eva; Slaska-Kiss, Krystyna; Pósfai, Eszter; Medzihradszky, Katalin F; Marshak, Daniel R; Roberts, Richard J; Kiss, Antal

    2010-11-01

    The GGCC-specific restriction endonuclease BspRI is one of the few Type IIP restriction endonucleases, which were suggested to be a monomer. Amino acid sequence information obtained by Edman sequencing and mass spectrometry analysis was used to clone the gene encoding BspRI. The bspRIR gene is located adjacently to the gene of the cognate modification methyltransferase and encodes a 304 aa protein. Expression of the bspRIR gene in Escherichia coli was dependent on the replacement of the native TTG initiation codon with an ATG codon, explaining previous failures in cloning the gene using functional selection. A plasmid containing a single BspRI recognition site was used to analyze kinetically nicking and second-strand cleavage under steady-state conditions. Cleavage of the supercoiled plasmid went through a relaxed intermediate indicating sequential hydrolysis of the two strands. Results of the kinetic analysis of the first- and second-strand cleavage are consistent with cutting the double-stranded substrate site in two independent binding events. A database search identified eight putative restriction-modification systems in which the predicted endonucleases as well as the methyltransferases share high sequence similarity with the corresponding protein of the BspRI system. BspRI and the related putative restriction endonucleases belong to the PD-(D/E)XK nuclease superfamily.

  20. SWAP-70 regulates mast cell FcεRI-mediated signaling and anaphylaxis

    PubMed Central

    Sivalenka, Raja Rajeswari; Sinha, Manoj; Jessberger, Rolf

    2010-01-01

    Mast cells, perhaps best known by their ability to trigger allergic reactions after stimulation through the FcεRI, express the unusual phosphatidylinositol-3-kinase (PI3K)-dependent, Rac-binding protein SWAP-70. Here we show that the IgE-mediated passive cutaneous and the systemic anaphylactic responses are strongly reduced in SWAP-70−/− mice. Cultured SWAP-70−/− immature bone marrow mast cells (BMMC) are also impaired in FcεRI-mediated degranulation, which can be restored by expression of exogenous wild-type SWAP-70, but less so if a phosphatidylinositol trisphosphate (PIP3) binding mutant is expressed. SWAP-70 itself supports inositol-3-phosphate and PIP3 production, the latter indicating a potential feedback from SWAP-70 towards PI3K. FcεRI-stimulated transcription and release of cytokines is controlled by SWAP-70. Key FcεRI signal transduction events like activation of LAT by phosphorylation, activation of Akt/PKB and of p38 MAPKinase are reduced in SWAP-70−/− BMMC, but ERK is strongly hyperactivated. Some requirements for SWAP-70 were apparent only under limited-strength signaling conditions. We suggest that SWAP-70 defines a new element of efficient mast cell activation upon FcεRI signaling, important for the control of mast cell dependent anaphylaxis. PMID:18236401

  1. RI-induced reaction studies by new energy-degrading beam line, OEDO

    NASA Astrophysics Data System (ADS)

    Michimasa, Shin'ichiro

    2014-09-01

    The RI beam factory (RIBF) has expanded variety of accessible nuclei, and provides very intense RI beams. However, the beams are energy range of above 100 MeV/u, and are not necessarily suitable to some kinds of nuclear reactions. Therefore, deceleration of intense RI beams from RIBF open potentially new scientific opportunities to access various states in exotic nuclei by using characteristics probes, such as transfer reactions at several ten MeV/u and fusion reactions at several MeV/u. For energy degrading of nuclear beams, the degrader is generally used. This method easily controls beam energy, while multiple scattering effect and energy straggling in the material broaden the beam spot size at the downstream foci. Therefore, a key issue for reaction measurements is achievement of ion transport to reduce the beam emittance at the secondary target. For this purpose, CNS has set up OEDO (Optimized Energy Degrading Optics for RI beam) project for production of high-quality low energy RI beams. The OEDO beam line scheme is planned to be achieved by re-arrangement of magnets of the high-resolution beam line, where the SHARAQ spectrometer is useful as a spectrograph for low-energy reaction spectroscopy. In this presentation, I will discuss scientific opportunities in the OEDO beam line and the SHARAQ spectrometer.

  2. RI in central retinal artery as assessed by CDI does not correspond to retinal vascular resistance.

    PubMed

    Polska, E; Kircher, K; Ehrlich, P; Vecsei, P V; Schmetterer, L

    2001-04-01

    The aim of the present study was to investigate the association between ultrasound Doppler measurements of resistive index (RI) in the central retinal artery and retinal vascular resistance (R) assessed with laser Doppler velocimetry, vessel size measurement, and calculation of ocular perfusion pressure (PP) in healthy subjects. An increase in vascular resistance was induced by inhalation of 100% O(2). During hyperoxia no significant changes in PP were observed. Mean flow velocity in main retinal veins was reduced by -27.5 +/- 2.0%. The average decrease in diameter was -11.5 +/- 1.0%. R, which was calculated as the ratio of PP to flow rate, increased by 97.6 +/- 7.7%. RI increased as well, but the effect was much smaller (6.6 +/- 2.2%). In addition, a negative correlation was found between baseline values of R and RI (r = -0.83). During hyperoxia R and RI were not associated. In conclusion, our data indicate that RI as assessed with color Doppler imaging in the central retinal artery is not an adequate measure of R.

  3. RiPPAS: A Ring-Based Privacy-Preserving Aggregation Scheme in Wireless Sensor Networks.

    PubMed

    Zhang, Kejia; Han, Qilong; Cai, Zhipeng; Yin, Guisheng

    2017-02-07

    Recently, data privacy in wireless sensor networks (WSNs) has been paid increased attention. The characteristics of WSNs determine that users' queries are mainly aggregation queries. In this paper, the problem of processing aggregation queries in WSNs with data privacy preservation is investigated. A Ring-based Privacy-Preserving Aggregation Scheme (RiPPAS) is proposed. RiPPAS adopts ring structure to perform aggregation. It uses pseudonym mechanism for anonymous communication and uses homomorphic encryption technique to add noise to the data easily to be disclosed. RiPPAS can handle both s u m ( ) queries and m i n ( ) / m a x ( ) queries, while the existing privacy-preserving aggregation methods can only deal with s u m ( ) queries. For processing s u m ( ) queries, compared with the existing methods, RiPPAS has advantages in the aspects of privacy preservation and communication efficiency, which can be proved by theoretical analysis and simulation results. For processing m i n ( ) / m a x ( ) queries, RiPPAS provides effective privacy preservation and has low communication overhead.

  4. RiPPAS: A Ring-Based Privacy-Preserving Aggregation Scheme in Wireless Sensor Networks

    PubMed Central

    Zhang, Kejia; Han, Qilong; Cai, Zhipeng; Yin, Guisheng

    2017-01-01

    Recently, data privacy in wireless sensor networks (WSNs) has been paid increased attention. The characteristics of WSNs determine that users’ queries are mainly aggregation queries. In this paper, the problem of processing aggregation queries in WSNs with data privacy preservation is investigated. A Ring-based Privacy-Preserving Aggregation Scheme (RiPPAS) is proposed. RiPPAS adopts ring structure to perform aggregation. It uses pseudonym mechanism for anonymous communication and uses homomorphic encryption technique to add noise to the data easily to be disclosed. RiPPAS can handle both sum() queries and min()/max() queries, while the existing privacy-preserving aggregation methods can only deal with sum() queries. For processing sum() queries, compared with the existing methods, RiPPAS has advantages in the aspects of privacy preservation and communication efficiency, which can be proved by theoretical analysis and simulation results. For processing min()/max() queries, RiPPAS provides effective privacy preservation and has low communication overhead. PMID:28178197

  5. The erudite humility of the historian: The 'critical epistemology' of Georges Lantéri-Laura.

    PubMed

    Basso Lorini, Elisabetta

    2017-02-01

    This paper analyses the historical and epistemological work of the French psychiatrist Georges Lantéri-Laura (1930-2004) within the context of the French 'tradition' of history and philosophy of sciences, with special reference to Georges Canguilhem and Michel Foucault. After an introduction devoted to a critical survey of the most recent works on the history and historiography of psychiatry in French, the paper outlines Lantéri-Laura's approach by focusing especially on the role played by the methodological concept of 'semiology' as regards the relation between medicine and psychiatry. The last part of the paper draws attention to the relation between the history and philosophy of psychiatry in light of Lantéri-Laura's 'critical epistemology'.

  6. Schedule Optimization Study, Hanford RI/FS Program. Volume 2, Final report

    SciTech Connect

    Not Available

    1992-12-01

    A Schedule Optimization Study (SOS) of the US Department of Energy (DOE) Hanford Site Remedial Investigation/Feasibility Study (RI/FS) Program was conducted by an independent team of professionals from other federal agencies and the private sector experienced in environmental restoration. This team spent two weeks at Hanford in September 1992 examining the reasons for the lengthy RI/FS process at Hanford and developing recommendations to expedite the process. The need for the study arose out of a schedule dispute regarding the submission of the 1100-EM-1 Operable Unit RI/FS Work Plan. This report documents the study called for in the August 29, 1991, Dispute Resolution Committee Decision Statement. Battelle`s Environmental Management Operations (EMO) coordinated the effort for DOE`s Richland Field Office (RL).

  7. RFI/RI work plan for the Road A Chemical Basin 904-111G

    SciTech Connect

    Kmetz, T.F.

    2000-03-07

    This Resource Conservation and Recovery Act (RCRA) Facility Investigation (RFI)/Remedial Investigation (RI) Work Plan has been prepared for the Road A Chemical Basin Operable Unit (RdACB OU) (904-111G). This unit is subject to the requirements of both RCRA and the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). This Work Plan presents the initial evaluation of existing unit data, applicable background data, the regulatory framework for the unit investigation, and the evaluations and decisions made during the determination of the scope and objectives of the planned Remedial Investigation/Feasibility Study (RI/FS) activities.

  8. Alpha-induced reaction studies using low-energy RI beams at CRIB

    SciTech Connect

    Yamaguchi, H.; Kahl, D.; Hu, J.; Kubono, S.; Hayakawa, S.; Hashimoto, T.

    2012-11-12

    CRIB (CNS Radioactive Ion Beam separator) is a low-energy RI beam separator at the Center for Nuclear Study (CNS) of the University of Tokyo. Studies on proton and alpha resonance scatterings, ({alpha}, p) reactions, and other types of measurements ({beta}-decay lifetimes etc.) have been performed using RI beams at CRIB, motivated by interests on astrophysical reactions and exotic nuclear structure. Among the studies at CRIB, the measurement of {sup 7}Li+{alpha}/{sup 7}Be+{alpha} resonant scatterings are presented.

  9. Studies on Nuclear Astrophysics and Exotic Structure at the Low-Energy RI Beam Facility CRIB

    NASA Astrophysics Data System (ADS)

    Yamaguchi, H.; Kahl, D.; Hayakawa, S.; Sakaguchi, Y.; Nakao, T.; Wakabayashi, Y.; Hashimoto, T.; Teranishi, T.; Kubono, S.; Cherubini, S.; Mazzocco, M.; Signorini, C.; Gulino, M.; Di Pietro, A.; Figuera, P.; La Cognata, M.; Lattuada, M.; Spitaleri, C.; Torresi, D.; Lee, P. S.; Lee, C. S.; Komatsubara, T.; Iwasa, N.; Okoda, Y.; Pierroutsakou, D.; Parascandolo, C.; La Commara, M.; Strano, E.; Boiano, C.; Boiano, A.; Manea, C.; Sánchez-Benítez, A. M.; Miyatake, H.; Watanabe, Y. X.; Ishiyama, H.; Jeong, S. C.; Imai, N.; Hirayama, Y.; Kimura, S.; Mukai, M.; Kim, Y. H.; Lin, C. J.; Jia, H. M.; Yan, L.; Yang, Y. Y.; Kawabata, T.; Kwon, Y. K.; Binh, D. N.; Khiem, L. H.; Duy, N. N.

    Studies on nuclear astrophysics, resonant structure, and nuclear reaction are going on at CRIB (CNS Radioactive Ion Beam separator), a low-energy RI beam separator operated by Center for Nuclear Study (CNS), the University of Tokyo. Two major methods used at CRIB to study nuclear reactions of astrophysical relevance are the resonant scattering, and direct measurements of (α,p) reactions using a thick-gas target. Several experiments for decay measurements and reaction mechanism are also performed using low-energy RI beams at CRIB. Some of the results from recent experiments at CRIB are discussed.

  10. BV RI CCD photometry of 361,281 objects in the field of M 31

    NASA Technical Reports Server (NTRS)

    Magnier, E. A.; Lewin, W. H. G.; Van Paradijs, J.; Hasinger, G.; Jain, A.; Pietsch, W.; Truemper, J.

    1992-01-01

    Deep BV RI CCD photometry was performed on a 1 sq deg region of M 31. A catalog of photometry and astrometry of a total of 361,281 stars is presented, with typical completion limits of BV RI = (22.3, 22.2, 22.2, 20.9). Photometric accuracy is about 2 percent at V = 19. This catalog allows detailed studies of stellar populations and reddening. The data are currently being used to assist in finding the optical counterparts of Einstein and ROSAT X-ray sources.

  11. BV RI CCD photometry of 361,281 objects in the field of M 31

    NASA Technical Reports Server (NTRS)

    Magnier, E. A.; Lewin, W. H. G.; Van Paradijs, J.; Hasinger, G.; Jain, A.; Pietsch, W.; Truemper, J.

    1992-01-01

    Deep BV RI CCD photometry was performed on a 1 sq deg region of M 31. A catalog of photometry and astrometry of a total of 361,281 stars is presented, with typical completion limits of BV RI = (22.3, 22.2, 22.2, 20.9). Photometric accuracy is about 2 percent at V = 19. This catalog allows detailed studies of stellar populations and reddening. The data are currently being used to assist in finding the optical counterparts of Einstein and ROSAT X-ray sources.

  12. DoRiNA 2.0--upgrading the doRiNA database of RNA interactions in post-transcriptional regulation.

    PubMed

    Blin, Kai; Dieterich, Christoph; Wurmus, Ricardo; Rajewsky, Nikolaus; Landthaler, Markus; Akalin, Altuna

    2015-01-01

    The expression of almost all genes in animals is subject to post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs (miRNAs). The interactions between both RBPs and miRNAs with mRNA can be mapped on a whole-transcriptome level using experimental and computational techniques established in the past years. The combined action of RBPs and miRNAs is thought to form a post-transcriptional regulatory code. Here we present doRiNA 2.0, available at http://dorina.mdc-berlin.de. In this highly improved new version, we have completely reworked the user interface and expanded the database to improve the usability of the website. Taking into account user feedback over the past years, the input forms for both the simple and the combinatorial search function have been streamlined and combined into a single web page that will also display the search results. Especially, custom uploads is one of the key new features in doRiNA 2.0. To enable the inclusion of doRiNA into third-party analysis pipelines, all operations are accessible via a REST API. Alternatively, local installations can be queried using a Python API. Both the web application and the APIs are available under an OSI-approved Open Source license that allows research and commercial access and re-use. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. DoRiNA 2.0—upgrading the doRiNA database of RNA interactions in post-transcriptional regulation

    PubMed Central

    Blin, Kai; Dieterich, Christoph; Wurmus, Ricardo; Rajewsky, Nikolaus; Landthaler, Markus; Akalin, Altuna

    2015-01-01

    The expression of almost all genes in animals is subject to post-transcriptional regulation by RNA binding proteins (RBPs) and microRNAs (miRNAs). The interactions between both RBPs and miRNAs with mRNA can be mapped on a whole-transcriptome level using experimental and computational techniques established in the past years. The combined action of RBPs and miRNAs is thought to form a post-transcriptional regulatory code. Here we present doRiNA 2.0, available at http://dorina.mdc-berlin.de. In this highly improved new version, we have completely reworked the user interface and expanded the database to improve the usability of the website. Taking into account user feedback over the past years, the input forms for both the simple and the combinatorial search function have been streamlined and combined into a single web page that will also display the search results. Especially, custom uploads is one of the key new features in doRiNA 2.0. To enable the inclusion of doRiNA into third-party analysis pipelines, all operations are accessible via a REST API. Alternatively, local installations can be queried using a Python API. Both the web application and the APIs are available under an OSI-approved Open Source license that allows research and commercial access and re-use. PMID:25416797

  14. Quantitative analysis and QTL mapping for agronomic and fiber traits in an RI population of Upland cotton

    USDA-ARS?s Scientific Manuscript database

    In this present study, we evaluated a RI population including 188 RI lines developed from 94 F2-derived families and their two parental lines, ‘HS 46’ and MARCABUCAG8US-1-88 (Gossypium hirsutum L.), at Mississippi State, MS, for two years. Fourteen agronomic and fiber traits were measured. One hundr...

  15. 78 FR 55121 - Submission for Review: Self-Certification of Full-Time School Attendance for the School Year, RI...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-09

    ... MANAGEMENT Submission for Review: Self-Certification of Full-Time School Attendance for the School Year, RI 25-14 and Information; and Instructions for Completing the Self-Certification of Full-Time School Attendance for the School Year, RI 25-14A AGENCY: U.S. Office of Personnel Management. ACTION: 60-Day Notice...

  16. 77 FR 71200 - Submission for Review: 3206-0140, Representative Payee Application (RI 20-7) and Information...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... Necessary for a Competency Determination (RI 30-3) AGENCY: U.S. Office of Personnel Management. ACTION: 60... Necessary for a Competency Determination (RI 30-3). As required by the Paperwork Reduction Act of 1995 (Pub... other technological collection techniques or other forms of information technology, e.g., permitting...

  17. 76 FR 29805 - Submission for Review: Verification of Full-Time School Attendance, RI 25-49

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-23

    ... MANAGEMENT Submission for Review: Verification of Full-Time School Attendance, RI 25-49 AGENCY: U.S. Office... opportunity to comment on a revised information collection request (ICR) 3206-0215, Verification of Full-Time...@opm.gov or faxed to (202) 606-0910. SUPPLEMENTARY INFORMATION: RI 25-49, Verification of Full-Time...

  18. 77 FR 71200 - Submission for Review: Initial Certification of Full-Time School Attendance, RI 25-41

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... MANAGEMENT Submission for Review: Initial Certification of Full-Time School Attendance, RI 25-41 AGENCY: U.S... Full-Time School Attendance. As required by the Paperwork Reduction Act of 1995, (Pub. L. 104-13, 44 U... to (202) 395-6974. SUPPLEMENTARY INFORMATION: RI 25-41, Initial Certification of Full-Time School...

  19. 78 FR 55123 - Submission for Review: We Need Information About Your Missing Payment, RI 38-31

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-09

    ... MANAGEMENT Submission for Review: We Need Information About Your Missing Payment, RI 38-31 AGENCY: U.S... (ICR) 3206-0187, We Need Information About Your Missing Payment, RI 38-31. As required by the Paperwork... Services, Office of Personnel Management. Title: We Need Information About Your Missing Payment. OMB:...

  20. Treatment Plan Adherence for Your Child With JA

    MedlinePlus

    ... Juvenile Arthritis Camps Juvenile Arthritis Conference Resources JA Power Pack Educational Rights Kit JA Transition Toolkit Print ... Drevlow Family: Coping Through Community Tiffany Family Nora Powers: Taking Charge Jodi Van Emmerik: Happy Campers Bridget ...

  1. 33 CFR 100.112 - Swim the Bay, Narragansett Bay, Narragansett, RI.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Swim the Bay, Narragansett Bay, Narragansett, RI. 100.112 Section 100.112 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.112 Swim the Bay...

  2. Membrane nanoclusters of FcγRI segregate from inhibitory SIRPα upon activation of human macrophages

    PubMed Central

    Valvo, Salvatore; Felce, James H.

    2017-01-01

    Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton. Upon Fc receptor activation, Src-family kinase signaling leads to segregation of FcγRI and SIRPα nanoclusters to be 197 ± 3 nm apart. Co-ligation of SIRPα with CD47 abrogates nanocluster segregation. If the balance of signals favors activation, FcγRI nanoclusters reorganize into periodically spaced concentric rings. Thus, a nanometer- and micron-scale reorganization of activating and inhibitory receptors occurs at the surface of human macrophages concurrent with signal integration. PMID:28289091

  3. 75 FR 47881 - Noise Exposure Map Notice, T.F.Green Airport, Warwick, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-09

    ... Federal Aviation Administration Noise Exposure Map Notice, T.F.Green Airport, Warwick, RI AGENCY: Federal... its determination that the noise exposure maps for T.F.Green Airport as submitted by the Rhode Island... INFORMATION: This notice announces that the FAA finds that the noise exposure maps submitted for...

  4. 77 FR 20330 - Disestablishment of Restricted Area; Rhode Island Sound off Newport, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... Sound off Newport, RI AGENCY: U.S. Army Corps of Engineers, DoD. ACTION: Proposed rule. SUMMARY: The U.S... located in the waters of Rhode Island Sound, 4 nautical miles due south of Lands End in Newport, Rhode... area in Rhode Island Sound, 4 nautical miles due south of Lands End in Newport, Rhode Island....

  5. 76 FR 15246 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ... Sound, RI AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard... an offshore anchorage in Rhode Island Sound south of Brenton Point, Rhode Island, for use by vessels... Sound that under current informal practice is routinely used by mariners as an anchorage while...

  6. MaRiMba: a software application for spectral library-based MRM transition list assembly.

    PubMed

    Sherwood, Carly A; Eastham, Ashley; Lee, Lik Wee; Peterson, Amelia; Eng, Jimmy K; Shteynberg, David; Mendoza, Luis; Deutsch, Eric W; Risler, Jenni; Tasman, Natalie; Aebersold, Ruedi; Lam, Henry; Martin, Daniel B

    2009-10-01

    Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis method that has been increasingly viewed as an avenue to explore proteomes with unprecedented sensitivity and throughput. We have developed a software tool, called MaRiMba, to automate the creation of explicitly defined MRM transition lists required to program triple quadrupole mass spectrometers in such analyses. MaRiMba creates MRM transition lists from downloaded or custom-built spectral libraries, restricts output to specified proteins or peptides, and filters based on precursor peptide and product ion properties. MaRiMba can also create MRM lists containing corresponding transitions for isotopically heavy peptides, for which the precursor and product ions are adjusted according to user specifications. This open-source application is operated through a graphical user interface incorporated into the Trans-Proteomic Pipeline, and it outputs the final MRM list to a text file for upload to MS instruments. To illustrate the use of MaRiMba, we used the tool to design and execute an MRM-MS experiment in which we targeted the proteins of a well-defined and previously published standard mixture.

  7. MaRiMba: A Software Application for Spectral Library-Based MRM Transition List Assembly

    PubMed Central

    Sherwood, Carly A.; Eastham, Ashley; Lee, Lik Wee; Peterson, Amelia; Eng, Jimmy K.; Shteynberg, David; Mendoza, Luis; Deutsch, Eric W.; Risler, Jenni; Tasman, Natalie; Aebersold, Ruedi; Lam, Henry; Martin, Daniel B.

    2009-01-01

    Multiple reaction monitoring mass spectrometry (MRM-MS) is a targeted analysis method that has been increasingly viewed as an avenue to explore proteomes with unprecedented sensitivity and throughput. We have developed a software tool, called MaRiMba, to automate the creation of explicitly defined MRM transition lists required to program triple quadrupole mass spectrometers in such analyses. MaRiMba creates MRM transition lists from downloaded or custom-built spectral libraries, restricts output to specified proteins or peptides, and filters based on precursor peptide and product ion properties. MaRiMba can also create MRM lists containing corresponding transitions for isotopically heavy peptides, for which the precursor and product ions are adjusted according to user specifications. This open-source application is operated through a graphical user interface incorporated into the Trans-Proteomic Pipeline, and it outputs the final MRM list to a text file for upload to MS instruments. To illustrate the use of MaRiMba, we used the tool to design and execute an MRM-MS experiment in which we targeted the proteins of a well-defined and previously published standard mixture. PMID:19603829

  8. 33 CFR 80.145 - Race Point, MA, to Watch Hill, RI.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Race Point, MA, to Watch Hill, RI... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Atlantic Coast § 80.145 Race Point, MA, to Watch Hill... and Rhode Island from Race Point to Watch Hill. (b) A line drawn from Nobska Point Light to Tarpaulin...

  9. 76 FR 34108 - Submission for Review: Alternative Annuity Election (RI 20-80)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... MANAGEMENT Submission for Review: Alternative Annuity Election (RI 20-80) AGENCY: U.S. Office of Personnel... on a revised information collection request (ICR) 3206-0168, Alternative Annuity Election. As... other forms of information technology, e.g., permitting electronic submissions of responses....

  10. Measuring and Monitoring in the South African "Kha Ri Gude" Mass Literacy Campaign

    ERIC Educational Resources Information Center

    McKay, Veronica

    2015-01-01

    After many previous failed attempts to reach illiterate adults, the award-winning South African "Kha Ri Gude" mass literacy campaign, launched in 2008, undertook to ensure that learners seized the opportunity to learn--for many adults, this was a "last chance". Written from an insider perspective by the campaign's founding…

  11. 77 FR 34414 - Submission for Review: Annuitant's Report of Earned Income, RI 30-2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... MANAGEMENT Submission for Review: Annuitant's Report of Earned Income, RI 30-2 AGENCY: Office of Personnel Management. ACTION: 60-Day Notice and request for comments. SUMMARY: The Retirement Services, Office of Personnel Management (OPM) offers the general public and other federal agencies the opportunity to...

  12. 77 FR 7025 - Safety Zones; America's Cup World Series, East Passage, Narragansett Bay, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; America's Cup World Series, East Passage... Bay, Rhode Island, during the America's Cup World Series sailing vessel racing event. This safety zone... and spectators involved with the America's Cup World Series in the vicinity of Newport, RI. Discussion...

  13. Quantifying aggregation of IgE-FcepsilonRI by multivalent antigen.

    PubMed Central

    Hlavacek, W S; Perelson, A S; Sulzer, B; Bold, J; Paar, J; Gorman, W; Posner, R G

    1999-01-01

    Aggregation of cell surface receptors by multivalent ligand can trigger a variety of cellular responses. A well-studied receptor that responds to aggregation is the high affinity receptor for IgE (FcepsilonRI), which is responsible for initiating allergic reactions. To quantify antigen-induced aggregation of IgE-FcepsilonRI complexes, we have developed a method based on multiparameter flow cytometry to monitor both occupancy of surface IgE combining sites and association of antigen with the cell surface. The number of bound IgE combining sites in excess of the number of bound antigens, the number of bridges between receptors, provides a quantitative measure of IgE-FcepsilonRI aggregation. We demonstrate our method by using it to study the equilibrium binding of a haptenated fluorescent protein, 2,4-dinitrophenol-coupled B-phycoerythrin (DNP25-PE), to fluorescein isothiocyanate-labeled anti-DNP IgE on the surface of rat basophilic leukemia cells. The results, which we analyze with the aid of a mathematical model, indicate how IgE-FcepsilonRI aggregation depends on the total concentrations of DNP25-PE and surface IgE. As expected, we find that maximal aggregation occurs at an optimal antigen concentration. We also find that aggregation varies qualitatively with the total concentration of surface IgE as predicted by an earlier theoretical analysis. PMID:10233059

  14. Measuring and Monitoring in the South African "Kha Ri Gude" Mass Literacy Campaign

    ERIC Educational Resources Information Center

    McKay, Veronica

    2015-01-01

    After many previous failed attempts to reach illiterate adults, the award-winning South African "Kha Ri Gude" mass literacy campaign, launched in 2008, undertook to ensure that learners seized the opportunity to learn--for many adults, this was a "last chance". Written from an insider perspective by the campaign's founding…

  15. 33 CFR 100.112 - Swim the Bay, Narragansett Bay, Narragansett, RI.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Swim the Bay, Narragansett Bay, Narragansett, RI. 100.112 Section 100.112 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.112 Swim the...

  16. A new EcoRI polymorphism for the insulin receptor gene

    SciTech Connect

    Accili, D.; Elbein, S.; McKeon, C.; Taylor, S.I. )

    1989-01-25

    A 550 bp BamHI-Pst I fragment encompassing bp 1,926-2,476 of the human insulin receptor cDNA was obtained. EcoRI identifies a two allele polymorphism, with bands of 5.8 and 5.5 kb. Co-dominant segregation was demonstrated in one Venezuelan pedigree.

  17. 77 FR 27115 - Newport to Bermuda Regatta, Narragansett Bay, Newport, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ... SECURITY Coast Guard 33 CFR Part 100 Newport to Bermuda Regatta, Narragansett Bay, Newport, RI AGENCY... Special Local Regulation for the biennial Newport to Bermuda Regatta, Narragansett Bay, Rhode Island, from... Guard will enforce the special local regulation for the biennial Newport/Bermuda Regatta,...

  18. Assessing the Kha Ri Gude Mass Literacy Campaign: A Developmental Evaluation

    ERIC Educational Resources Information Center

    Romm, Norma R. A.; Dichaba, Mpho M.

    2015-01-01

    In this article we explicate our way of assessing the South African Kha Ri Gude Mass Literacy Campaign, and in particular its impact in the Eastern Cape. We provide an account primarily of focus group sessions conducted in 2013 and again in 2014 with volunteer educators and past learners in the campaign. We concentrate on the way in which…

  19. Dual-wavelength Digital Holography for quantification of cell volume and integral refractive index (RI)

    NASA Astrophysics Data System (ADS)

    Boss, Daniel; Kuehn, Jonas; Depeursinge, Christian; Magistretti, Pierre J.; Marquet, Pierre

    2011-07-01

    Quantitative Phase Imaging techniques such as DHM have emerged recently in life sciences and can be aimed at monitoring and quantifying non-invasively dynamic cellular processes modifying cell morphology and/or content. Concretely, the DHM phase signal depends on two cell parameters: cell thickness and integral refractive index. Consequently, due to its dual origin, the interpretation of the phase signal variations remain difficult. Since a net water flux across the cell membrane causes a variation of both parameters, the phase signal cannot be related directly to cellular RI or thickness variations, but must be understood as a coupled signal of these two parameters. We have developped a Dual-wavelength Digital Holographic Microscopy (DHM) setup to separately measure in a single shot fashion cellular thickness and integral RI of living cells. The method is based on the use of an absorbing dye that causes a high RI dispersion in the extracellular medium at the two recording wavelength. Consequently, the phase signals measured at the two wavelengths, differ significantly from each other. Practically, both cell RI and thickness can be univocally determined from the two phase measurements. Important biophysical parameters of living cells, including dry mass concentrations and water membrane permeability can be deduced.

  20. 33 CFR 110.47 - Little Narragansett Bay, Watch Hill, R.I.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Little Narragansett Bay, Watch... SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.47 Little Narragansett Bay, Watch Hill, R.I. All of the navigable waters of Watch Hill Cove southeasterly of a line beginning at...

  1. 33 CFR 110.47 - Little Narragansett Bay, Watch Hill, R.I.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Little Narragansett Bay, Watch... SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.47 Little Narragansett Bay, Watch Hill, R.I. All of the navigable waters of Watch Hill Cove southeasterly of a line beginning at...

  2. 33 CFR 110.47 - Little Narragansett Bay, Watch Hill, R.I.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Little Narragansett Bay, Watch... SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.47 Little Narragansett Bay, Watch Hill, R.I. All of the navigable waters of Watch Hill Cove southeasterly of a line beginning at...

  3. 76 FR 14696 - Ananke, Inc., Providence, RI; Notice of Negative Determination on Reconsideration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-17

    ... Employment and Training Administration Ananke, Inc., Providence, RI; Notice of Negative Determination on... initial negative determination was based on the findings that neither the subject firm nor a declining..., I affirm the original notice of negative determination of eligibility to apply for worker...

  4. RiBOMS: RFID-based object management system for home environments.

    PubMed

    Iraola, Hodei; Schafer, James; Yu, Xunyi; Mullett, Gary; Ganz, Aura

    2011-01-01

    In this paper we introduce a RFID-based object management system, RiBOMS, for home environments. The system has an easy to use pictorial user interface aimed at older adults with associative memory impairments. The system technical correctness was successfully tested in a lab environment.

  5. 76 FR 15350 - Submission for Review: Representative Payee Survey, RI 38-115

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-21

    ... MANAGEMENT Submission for Review: Representative Payee Survey, RI 38-115 AGENCY: U.S. Office of Personnel... Personnel Management (OPM) offers the general public and other Federal agencies the opportunity to comment... information collection to U.S. Office of Personnel Management, Linda Bradford (Acting), Deputy...

  6. 76 FR 36582 - Submission for Review: Disabled Dependent Questionnaire, RI 30-10

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ... MANAGEMENT Submission for Review: Disabled Dependent Questionnaire, RI 30-10 AGENCY: U.S. Office of Personnel... Personnel Management (OPM) offers the general public and other Federal agencies the opportunity to comment..., NW., Washington, DC 20503, Attention: Desk Officer for the Office of Personnel Management or sent...

  7. Tetraspanin CD151 Is a Negative Regulator of FcεRI-Mediated Mast Cell Activation.

    PubMed

    Abdala-Valencia, Hiam; Bryce, Paul J; Schleimer, Robert P; Wechsler, Joshua B; Loffredo, Lucas F; Cook-Mills, Joan M; Hsu, Chia-Lin; Berdnikovs, Sergejs

    2015-08-15

    Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow-derived mast cells from CD151(-/-) mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-α compared with wild-type controls. However, FcεRI-induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cγ1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells.

  8. 33 CFR 100.119 - Newport-Bermuda Regatta, Narragansett Bay, Newport, RI

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Newport-Bermuda Regatta, Narragansett Bay, Newport, RI 100.119 Section 100.119 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.119...

  9. Effects of MeJA on Arabidopsis metabolome under endogenous JA deficiency

    NASA Astrophysics Data System (ADS)

    Cao, Jingjing; Li, Mengya; Chen, Jian; Liu, Pei; Li, Zhen

    2016-11-01

    Jasmonates (JAs) play important roles in plant growth, development and defense. Comprehensive metabolomics profiling of plants under JA treatment provides insights into the interaction and regulation network of plant hormones. Here we applied high resolution mass spectrometry based metabolomics approach on Arabidopsis wild type and JA synthesis deficiency mutant opr3. The effects of exogenous MeJA treatment on the metabolites of opr3 were investigated. More than 10000 ion signals were detected and more than 2000 signals showed significant variation in different genotypes and treatment groups. Multivariate statistic analyses (PCA and PLS-DA) were performed and a differential compound library containing 174 metabolites with high resolution precursor ion-product ions pairs was obtained. Classification and pathway analysis of 109 identified compounds in this library showed that glucosinolates and tryptophan metabolism, amino acids and small peptides metabolism, lipid metabolism, especially fatty acyls metabolism, were impacted by endogenous JA deficiency and exogenous MeJA treatment. These results were further verified by quantitative reverse transcription PCR (RT-qPCR) analysis of 21 related genes involved in the metabolism of glucosinolates, tryptophan and α-linolenic acid pathways. The results would greatly enhance our understanding of the biological functions of JA.

  10. Effects of MeJA on Arabidopsis metabolome under endogenous JA deficiency.

    PubMed

    Cao, Jingjing; Li, Mengya; Chen, Jian; Liu, Pei; Li, Zhen

    2016-11-24

    Jasmonates (JAs) play important roles in plant growth, development and defense. Comprehensive metabolomics profiling of plants under JA treatment provides insights into the interaction and regulation network of plant hormones. Here we applied high resolution mass spectrometry based metabolomics approach on Arabidopsis wild type and JA synthesis deficiency mutant opr3. The effects of exogenous MeJA treatment on the metabolites of opr3 were investigated. More than 10000 ion signals were detected and more than 2000 signals showed significant variation in different genotypes and treatment groups. Multivariate statistic analyses (PCA and PLS-DA) were performed and a differential compound library containing 174 metabolites with high resolution precursor ion-product ions pairs was obtained. Classification and pathway analysis of 109 identified compounds in this library showed that glucosinolates and tryptophan metabolism, amino acids and small peptides metabolism, lipid metabolism, especially fatty acyls metabolism, were impacted by endogenous JA deficiency and exogenous MeJA treatment. These results were further verified by quantitative reverse transcription PCR (RT-qPCR) analysis of 21 related genes involved in the metabolism of glucosinolates, tryptophan and α-linolenic acid pathways. The results would greatly enhance our understanding of the biological functions of JA.

  11. Effects of MeJA on Arabidopsis metabolome under endogenous JA deficiency

    PubMed Central

    Cao, Jingjing; Li, Mengya; Chen, Jian; Liu, Pei; Li, Zhen

    2016-01-01

    Jasmonates (JAs) play important roles in plant growth, development and defense. Comprehensive metabolomics profiling of plants under JA treatment provides insights into the interaction and regulation network of plant hormones. Here we applied high resolution mass spectrometry based metabolomics approach on Arabidopsis wild type and JA synthesis deficiency mutant opr3. The effects of exogenous MeJA treatment on the metabolites of opr3 were investigated. More than 10000 ion signals were detected and more than 2000 signals showed significant variation in different genotypes and treatment groups. Multivariate statistic analyses (PCA and PLS-DA) were performed and a differential compound library containing 174 metabolites with high resolution precursor ion-product ions pairs was obtained. Classification and pathway analysis of 109 identified compounds in this library showed that glucosinolates and tryptophan metabolism, amino acids and small peptides metabolism, lipid metabolism, especially fatty acyls metabolism, were impacted by endogenous JA deficiency and exogenous MeJA treatment. These results were further verified by quantitative reverse transcription PCR (RT-qPCR) analysis of 21 related genes involved in the metabolism of glucosinolates, tryptophan and α-linolenic acid pathways. The results would greatly enhance our understanding of the biological functions of JA. PMID:27883040

  12. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer.

    PubMed

    Luque, F A; Furneaux, H M; Ferziger, R; Rosenblum, M K; Wray, S H; Schold, S C; Glantz, M J; Jaeckle, K A; Biran, H; Lesser, M

    1991-03-01

    The serum and cerebrospinal fluid (CSF) of 8 women with ataxia, 6 of whom also had eye movement abnormalities believed to be opsoclonus, were found to contain a highly specific antineuronal antibody we call anti-Ri. Seven of the 8 women also had or developed cancer: carcinoma of the breast in 5, adenocarcinoma in an axillary lymph node in 1, and carcinoma of the fallopian tube in 1. Four patients presented with the neurological disorder; the cancer was diagnosed first in the other 4. Immunohistochemical studies using serum or CSF from all 8 patients revealed a highly specific antibody interaction with central nervous system neuronal nuclei but not with glial or other cells; the titer ranged from 1:5,000 to 1:320,000 in serum and from 1:2,000 to 1:16,000 in CSF. Biotinylated IgG from the patients' serum reacted with the tumors of 3 of 4 patients with anti-Ri antibody but not with breast cancers from patients without anti-Ri antibody. Immunoblots against cerebral cortex neuronal extracts identified protein antigens of 55-kd and 80-kd relative molecular mass. Serum titers by immunoblot ranged from 1:500 to more than 1:40,000 and CSF titers, from 1:10 to 1:2,000. The relative amount of anti-Ri was always higher in CSF than in serum. The antibody was not present in sera from normal individuals; patients with breast cancer without opsoclonus; other patients with opsoclonus; or patients with other paraneoplastic syndromes related to breast, ovarian, or small-cell lung cancer. We conclude that the presence of anti-Ri antibody identifies a subset of patients with paraneoplastic ataxia and eye movement disorders (opsoclonus) who usually suffer from breast or other gynecological cancer; the antibody when present is a useful marker for an underlying malignancy.

  13. Sugar exchanges in arbuscular mycorrhiza: RiMST5 and RiMST6, two novel Rhizophagus irregularis monosaccharide transporters, are involved in both sugar uptake from the soil and from the plant partner.

    PubMed

    Ait Lahmidi, Nassima; Courty, Pierre-Emmanuel; Brulé, Daphnée; Chatagnier, Odile; Arnould, Christine; Doidy, Joan; Berta, Graziella; Lingua, Guido; Wipf, Daniel; Bonneau, Laurent

    2016-10-01

    Arbuscular mycorrhizal (AM) fungi are associated with about 80% of land plants. AM fungi provide inorganic nutrients to plants and in return up to 20% of the plant-fixed CO2 is transferred to the fungal symbionts. Since AM fungi are obligate biotrophs, unraveling how sugars are provided to the fungus partner is a key for understanding the functioning of the symbiosis. In this study, we identified two new monosaccharide transporters from Rhizophagus irregularis (RiMST5 and RiMST6) that we characterized as functional high affinity monosaccharide transporters. RiMST6 was characterized as a glucose specific, high affinity H(+) co-transporter. We provide experimental support for a primary role of both RiMST5 and RiMST6 in sugar uptake directly from the soil. The expression patterns of RiMSTs in response to partial light deprivation and to interaction with different host plants were investigated. Expression of genes coding for RiMSTs was transiently enhanced after 48 h of shading and was unambiguously dependent on the host plant species. These results cast doubt on the 'fair trade' principle under carbon-limiting conditions. Therefore, in light of these findings, the possible mechanisms involved in the modulation between mutualism and parasitism in plant-AM fungus interactions are discussed.

  14. The Transcription Factor Ehf Is Involved in TGF-β-Induced Suppression of FcεRI and c-Kit Expression and FcεRI-Mediated Activation in Mast Cells.

    PubMed

    Yamazaki, Susumu; Nakano, Nobuhiro; Honjo, Asuka; Hara, Mutsuko; Maeda, Keiko; Nishiyama, Chiharu; Kitaura, Jiro; Ohtsuka, Yoshikazu; Okumura, Ko; Ogawa, Hideoki; Shimizu, Toshiaki

    2015-10-01

    FcεRI, which is composed of α, β, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-β1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-β1 remains unclear. In this study, we found that the expression of Ets homologous factor (Ehf), a member of the Ets family transcriptional factors, is upregulated by TGF-β/Smad signaling in mouse bone marrow-derived mast cells (BMMCs). Forced expression of Ehf in BMMCs repressed the transcription of genes encoding FcεRIα, FcεRIβ, and c-Kit, resulting in a reduction in cell surface FcεRI and c-Kit expression. Additionally, forced expression of Ehf suppressed FcεRI-mediated degranulation and cytokine production. Ehf inhibited the promoter activity of genes encoding FcεRIα, FcεRIβ, and c-Kit by binding to these gene promoters. Furthermore, the mRNA levels of Gata1, Gata2, and Stat5b were lower in BMMCs stably expressing Ehf compared with control cells. Because GATA-1 and GATA-2 are positive regulators of FcεRI and c-Kit expression, decreased expression of GATAs may be also involved in the reduction of FcεRI and c-Kit expression. Decreased expression of Stat5 may contribute to the suppression of cytokine production by BMMCs. In part, mast cell response to TGF-β1 was mimicked by forced expression of Ehf, suggesting that TGF-β1 suppresses FcεRI and c-Kit expression and suppresses FcεRI-mediated activation through upregulation of Ehf.

  15. JA but not JA-Ile is the cell-nonautonomous signal activating JA mediated systemic defenses to herbivory in Nicotiana attenuata.

    PubMed

    Bozorov, Tohir A; Dinh, Son Truong; Baldwin, Ian T

    2017-08-01

    The whole-plant activation of defense responses to wounding and herbivory requires systemic signaling in which jasmonates (JAs) play a pivotal role. To examine the nature of the slower cell-nonautonomous as compared to the rapid cell-autonomous signal in mediating systemic defenses in Nicotiana attenuata, reciprocal stem grafting-experiments were used with plants silenced for the JA biosynthetic gene ALLENE OXIDE CYCLASE (irAOC) or plants transformed to create JA sinks by ectopically expressing Arabidopsis JA-O-methyltransferase (ovJMT). JA-impaired irAOC plants were defective in the cell-nonautonomous signaling pathway but not in JA transport. Conversely, ovJMT plants abrogated the production of a graft-transmissible JA signal. Both genotypes displayed unaltered cell-autonomous signaling. Defense responses (17-hydroxygeranyllinalool diterpene glycosides, nicotine, and proteinase inhibitors) and metabolite profiles were differently induced in irAOC and ovJMT scions in response to graft-transmissible signals from elicited wild type stocks. The performance of Manduca sexta larvae on the scions of different graft combinations was consistent with the patterns of systemic defense metabolite elicitations. Taken together, we conclude that JA and possibly MeJA, but not JA-Ile, either directly functions as a long-distance transmissible signal or indirectly interacts with long distance signal(s) to activate systemic defense responses. © 2017 Institute of Botany, Chinese Academy of Sciences.

  16. Achyranthes japonica Nakai Water Extract Suppresses Binding of IgE Antibody to Cell Surface FcɛRI

    PubMed Central

    Shim, Sun Yup; Lee, Mina; Lee, Kyung Dong

    2016-01-01

    Achyranthes japonica Nakai (AJN) water extract has a variety of physiological properties, including anti-diabetic, anti-cancer, anti-inflammatory, anti-microbial, and anti-oxidative activities. In the present study, the inhibitory effects of AJN extract were investigated in high affinity immunoglobulin E receptor (FcɛRI)-mediated KU812F cells activation. AJN extract showed suppressive effects on histamine release and intracellular calcium [Ca2+]i elevation from anti-FcɛRI antibody (CRA-1)-stimulated cells in a dose-dependent manner. Flow cytometric analysis showed that AJN extract treatment caused a dose-dependent decrease in the cell surface FcɛRI expression and the binding between the cell surface FcɛRI and the IgE antibody. Moreover, reverse transcription-polymerase chain reaction analysis showed that levels of the mRNA for the FcɛRI α chain was decreased by treatment with AJN extract. These results indicate that AJN extract may exert anti-allergic effects via the inhibition of calcium influx and histamine release, which occurs as a result from the down-regulation of the binding of IgE antibody to cell surface FcɛRI. This mechanism may occur through FcɛRI expression inhibition. PMID:28078254

  17. Quorum sensing in Aeromonas hydrophila and Aeromonas salmonicida: identification of the LuxRI homologs AhyRI and AsaRI and their cognate N-acylhomoserine lactone signal molecules.

    PubMed Central

    Swift, S; Karlyshev, A V; Fish, L; Durant, E L; Winson, M K; Chhabra, S R; Williams, P; Macintyre, S; Stewart, G S

    1997-01-01

    Spent culture supernatants from both Aeromonas hydrophila and Aeromonas salmonicida activate a range of biosensors responsive to N-acylhomoserine lactones (AHLs). The genes for a quorum sensing signal generator and a response regulator were cloned from each Aeromonas species and termed ahyRI and asaRI, respectively. Protein sequence homology analysis places the gene products within the growing family of LuxRI homologs. ahyR and asaR are transcribed divergently from ahyI and asaI, respectively, and in both Aeromonas species, the genes downstream have been identified by DNA sequence and PCR analysis. Downstream of both ahyI and asaI is a gene with close homology to iciA, an inhibitor of chromosome replication in Escherichia coli, a finding which implies that in Aeromonas, cell division may be linked to quorum sensing. The major signal molecule synthesized via both AhyI and AsaI was purified from spent culture supernatants and identified as N-(butanoyl)-L-homoserine lactone (BHL) by thin-layer chromatography, high-pressure liquid chromatography analysis, and mass spectrometry. In addition, a second, minor AHL, N-hexanoyl-L-homoserine lactone, was identified. Transcriptional reporter studies with ahyI::luxCDABE fusions indicate that AhyR and BHL are both required for ahyI transcription. For A. salmonicida, although the addition of exogenous BHL gives only a small stimulation of the production of serine protease with comparison to the control culture, the incorporation of a longer-chain AHL, N-(3-oxodecanoyl)-L-homoserine lactone, reduced the final level (by approximately 50%) and delayed the appearance (from an A650 of 0.9 in the control to an A650 of 1.2 in the test) of protease in the culture supernatant. These data add A. hydrophila and A. salmonicida to the growing family of gram-negative bacteria now known to control gene expression through quorum sensing. PMID:9286976

  18. RiSA: A Science Festival for the Bilingual and Bicultural Rio Grande Valley

    NASA Astrophysics Data System (ADS)

    Key, Joey Shapiro; Torres, Cristina; Stone, Robert

    2014-03-01

    The Rio Grande Science and Arts (RiSA) Festival organized by the Center for Gravitational Wave Astronomy (CGWA) at the University of Texas at Brownsville (UTB) will use a wide variety of artforms to bring physics and science topics to the bilingual and bicultural population of the Rio Grande Valley of South Texas. The science and art faculty at UTB will partner with art and education professionals to create an annual community event celebrating science though art. Music, dance, poetry, and visual arts will headline the festival activities. Festival events and products will be produced in both English and Spanish to attract and inform the bilingual local community. The RiSA Festival is supported by the Science Festival Alliance and the Sloan Foundation. Supported by the Science Festival Alliance and the Sloan Foundation.

  19. Cryogenic gas target system for intense RI beam productions in nuclear astrophysics

    NASA Astrophysics Data System (ADS)

    Wakabayashi, Y.; Yamaguchi, H.; Hayakawa, S.; Kurihara, Y.; Amadio, G.; Fujikawa, H.; Binh, D. N.; He, J. J.; Kim, A.; Kubono, S.

    2008-05-01

    A cryogenic gas target system was newly developed to produce intense RI beams at the low-energy in-flight radio-isotope beam separator (CRIB) of the University of Tokyo. The main features of the cryogenic gas target system are the direct cooling of the target cell by a liquid N2 finger and the circulation of the target gas that goes through the liquid N2 tank. Hydrogen gas was cooled down to 85-90 K by liquid nitrogen and used as a secondary beam production target which has a thickness of 2.3 mg/cm2 at the gas pressure of 760 Torr. Intense RI beams, such as a 7Be beam of 2×108 particles per second, were successfully produced using the target.

  20. Construction of the SCRIT electron scattering facility at the RIKEN RI Beam Factory

    NASA Astrophysics Data System (ADS)

    Wakasugi, M.; Ohnishi, T.; Wang, S.; Miyashita, Y.; Adachi, T.; Amagai, T.; Enokizono, A.; Enomoto, A.; Haraguchi, Y.; Hara, M.; Hori, T.; Ichikawa, S.; Kikuchi, T.; Kitazawa, R.; Koizumi, K.; Kurita, K.; Miyamoto, T.; Ogawara, R.; Shimakura, Y.; Takehara, H.; Tamae, T.; Tamaki, S.; Togasaki, M.; Yamaguchi, T.; Yanagi, K.; Suda, T.

    2013-12-01

    The SCRIT electron scattering facility, aiming at electron scattering off short-lived unstable nuclei, has been constructed at the RIKEN RI Beam Factory. This facility consists of a racetrack microtron (RTM), an electron storage ring (SR2) equipped with the SCRIT system, and a low-energy RI separator (ERIS). SCRIT (self-confining radioactive isotope ion targeting) is a novel technique to form internal targets in an electron storage ring. Experiments for evaluating performance of the SCRIT system have been carried out using the stable 133Cs1+ beam and the 132Xe1+ beam supplied from ERIS. Target ions were successfully trapped in the SCRIT system with 90% efficiency at a 250 mA electron beam current, and luminosity exceeding 1026/(cm2 s) was maintained for more than 1 s. Electrons elastically scattered from the target ions were successfully measured. Applicability of the SCRIT system to electron scattering for unstable nuclei has been established in experiments.

  1. CCD UBV(RI)C and 2MASS photometry of seven open clusters

    NASA Astrophysics Data System (ADS)

    Akkaya Oralhan, {İ.; Michel, R.

    Fundamental astrophysical parameters have been derived for Be 45, Be 55, Di 07, Feib 01, Ki 02, NGC 457 and NGC 1548 open clusters (OCs) using CCD U BV (RI)_C photometric data and PPMXL database. CCD U BV (RI)_C photometric data observed with the 84 cm telescope at the San Pedro Mártir National Astronomical Observatory (SPMO), México. The cluster members and field stars in the cluster regions have separated through their Proper Motion (PM) vector point diagrams. We have used JH{Ks} photometry of 2MASS data taken from PPMXL catalogue to have stellar Radial Density Profile (RDP) and determine limit radius of these seven clusters. Five different Color-Magnitude diagrams ane one color-color diagram have been used together with Padova isochrones and intrinsic-colour calibrations to obtain reddenings, metallicities, distance moduli, and ages for these seven clusters.

  2. Cryogenic gas target system for intense RI beam productions in nuclear astrophysics

    SciTech Connect

    Wakabayashi, Y.; Yamaguchi, H.; Hayakawa, S.; Kurihara, Y.; Amadio, G.; Fujikawa, H.; Kubono, S.; Binh, D. N.; He, J. J.; Kim, A.

    2008-05-21

    A cryogenic gas target system was newly developed to produce intense RI beams at the low-energy in-flight radio-isotope beam separator (CRIB) of the University of Tokyo. The main features of the cryogenic gas target system are the direct cooling of the target cell by a liquid N{sub 2} finger and the circulation of the target gas that goes through the liquid N{sub 2} tank. Hydrogen gas was cooled down to 85-90 K by liquid nitrogen and used as a secondary beam production target which has a thickness of 2.3 mg/cm{sup 2} at the gas pressure of 760 Torr. Intense RI beams, such as a {sup 7}Be beam of 2x10{sup 8} particles per second, were successfully produced using the target.

  3. Nuclear Astrophysical studies using low-energy RI beams at CRIB

    SciTech Connect

    Yamaguchi, H.; Wakabayashi, Y.; Hayakawa, S.; Binh, D. N.; Kahl, D.; Kurihara, Y.; Kubono, S.; Niikura, M.; Teranishi, T.; He, J. J.; Kwon, Y. K.; Nishimura, S.; Togano, Y.; Iwasa, N.; Khiem, L. H.

    2009-05-04

    CRIB (CNS Radioactive Ion Beam separator) is a low-energy RI beam separator at the Center for Nuclear Study (CNS) of the University of Tokyo, used for various studies covering nuclear-astrophysical topics. An application of the RI beam at CRIB for the astrophysical studies is a new measurement of the proton resonance scattering on {sup 7}Be. The measurement was performed up to the excitation energy of 6.8 MeV, ans the excitation function above 3.5 MeV was successfully measured for the first time, providing important information about the reaction rate of {sup 7}Be(p,{gamma}){sup 8}B, which is the key reaction in the solar {sup 8}B neutrino production. A preliminary result of the {sup 7}Be+p experiment is presented.

  4. Nuclear Astrophysics Programs with Low-Energy RI Beams at CRIB

    SciTech Connect

    Kubono, S.; Binh, Dam N.; Hayakawa, S.; Hashimoto, T.; Kahl, D. M.; Yamaguchi, H.; Wakabayashi, Y.; Teranishi, T.; Iwasa, N.; Komatsubara, T.; Kato, S.; Khiem, Le H.

    2010-04-30

    Nuclear astrophysics activities with CNS RI beam separator (CRIB) are reported together with the present status of the CRIB facility which is supported by the AVF upgrade project for the total development of the low-energy RIB facility. The activities include direct and indirect measurements of stellar reactions especially relevant to explosive burning processes such as nova and supernovae. Some recent results are discussed together with a scope of the facility.

  5. Structural and Thermodynamic Basis for Enhanced DNA Binding by a Promiscuous Mutant EcoRI Endonuclease

    PubMed Central

    Sapienza, Paul J.; Rosenberg, John M.; Jen-Jacobson, Linda

    2008-01-01

    SUMMARY Promiscuous mutant EcoRI endonucleases bind to the canonical site GAATTC more tightly than does the wild-type endonuclease, yet cleave variant (EcoRI*) sites more rapidly than does wild-type. The crystal structure of the A138T promiscuous mutant homodimer in complex with a GAATTC site is nearly identical to that of the wild-type complex, except that the Thr138 side chains make novel packing interactions with bases in the 5′-flanking regions outside the recognition hexanucleotide, while excluding two bound water molecules seen in the wild-type complex. Molecular dynamics simulations confirm exclusion of these waters. The structure and simulations suggest multiple possible reasons why binding of A138T protein to the GAATTC site has ΔS° more favorable and ΔH° less favorable than for wild-type endonuclease binding. The novel interactions of Thr138 with flanking bases may permit A138T, unlike wild-type enzyme, to form complexes with EcoRI* sites that structurally resemble the specific wild-type complex with GAATTC. PMID:17997963

  6. Gene Ontology density estimation and discourse analysis for automatic GeneRiF extraction.

    PubMed

    Gobeill, Julien; Tbahriti, Imad; Ehrler, Frédéric; Mottaz, Anaïs; Veuthey, Anne-Lise; Ruch, Patrick

    2008-04-11

    This paper describes and evaluates a sentence selection engine that extracts a GeneRiF (Gene Reference into Functions) as defined in ENTREZ-Gene based on a MEDLINE record. Inputs for this task include both a gene and a pointer to a MEDLINE reference. In the suggested approach we merge two independent sentence extraction strategies. The first proposed strategy (LASt) uses argumentative features, inspired by discourse-analysis models. The second extraction scheme (GOEx) uses an automatic text categorizer to estimate the density of Gene Ontology categories in every sentence; thus providing a full ranking of all possible candidate GeneRiFs. A combination of the two approaches is proposed, which also aims at reducing the size of the selected segment by filtering out non-content bearing rhetorical phrases. Based on the TREC-2003 Genomics collection for GeneRiF identification, the LASt extraction strategy is already competitive (52.78%). When used in a combined approach, the extraction task clearly shows improvement, achieving a Dice score of over 57% (+10%). Argumentative representation levels and conceptual density estimation using Gene Ontology contents appear complementary for functional annotation in proteomics.

  7. Gene Ontology density estimation and discourse analysis for automatic GeneRiF extraction

    PubMed Central

    Gobeill, Julien; Tbahriti, Imad; Ehrler, Frédéric; Mottaz, Anaïs; Veuthey, Anne-Lise; Ruch, Patrick

    2008-01-01

    Background This paper describes and evaluates a sentence selection engine that extracts a GeneRiF (Gene Reference into Functions) as defined in ENTREZ-Gene based on a MEDLINE record. Inputs for this task include both a gene and a pointer to a MEDLINE reference. In the suggested approach we merge two independent sentence extraction strategies. The first proposed strategy (LASt) uses argumentative features, inspired by discourse-analysis models. The second extraction scheme (GOEx) uses an automatic text categorizer to estimate the density of Gene Ontology categories in every sentence; thus providing a full ranking of all possible candidate GeneRiFs. A combination of the two approaches is proposed, which also aims at reducing the size of the selected segment by filtering out non-content bearing rhetorical phrases. Results Based on the TREC-2003 Genomics collection for GeneRiF identification, the LASt extraction strategy is already competitive (52.78%). When used in a combined approach, the extraction task clearly shows improvement, achieving a Dice score of over 57% (+10%). Conclusions Argumentative representation levels and conceptual density estimation using Gene Ontology contents appear complementary for functional annotation in proteomics. PMID:18426554

  8. Production of drip-line nuclei at RIKEN RI Beam Factory

    NASA Astrophysics Data System (ADS)

    Saito, Atsumi

    2014-09-01

    Production cross-sections and secondary-beam yields of very neutron rich nuclei near neutron drip-line at 200--250 MeV/u have been investigated at RIKEN RI Beam Factory (RIBF). RIBF is the next generation RI beam facility, which can produce a variety of exotic nuclei with high intensity. The measurement of production yields of 19B, 22C, which are located on the neutron drip-line, and neighboring isotopes was made on the occasion of the Coulomb and nuclear breakup experiments of these halo nuclei at SAMURAI (Superconducting Analyzer for MUlti-particle from RAdioIsotope beams) facility at RIBF. We used 345 MeV/u 48Ca beam as primary beam, which impinged on 30 mm-thick Be target, to obtain secondary beams by projectile fragmentation. The projectile fragments were then separated through Superconducting RI beam separator BigRIPS, and were identified by measuring time of flight (TOF), energy loss (ΔE), and magnetic rigidity (Bρ) by the standard detectors at 2nd stage of BigRIPS. We thus obtained production cross-sections and yields of carbon and boron isotopes. The production cross-sections and yields extracted were compared with the simulation code LISE using EPAX. We discuss these results and comparisons in this poster presentation.

  9. Studying astrophysical reactions with low-energy RI beams at CRIB

    NASA Astrophysics Data System (ADS)

    Yamaguchi, H.; Kahl, D.; Hayakawa, S.; Sakaguchi, Y.; Wakabayashi, Y.; Hashimoto, T.; Cherubini, S.; Gulino, M.; Spitaleri, C.; Rapisarda, G. G.; La Cognata, M.; Lamia, L.; Romano, S.; Kubono, S.; Iwasa, N.; Teranishi, T.; Kawabata, T.; Kwon, Y. K.; Binh, D. N.; Khiem, L. H.; Duy, N. N.; Kato, S.; Komatsubara, T.; Coc, A.; De Sereville, N.; Hammache, F.; Kiss, G.; Bishop, S.

    2016-05-01

    Studies on nuclear astrophysics, nuclear structure, and other interests have been performed using the radioactive-isotope (RI) beams at the low-energy RI beam separator CRIB, operated by Center for Nuclear Study (CNS), the University of Tokyo. A typical measurement performed at CRIB is the elastic resonant scattering with the inverse kinematics. One recent experiment was on the α resonant scattering with 7Li and 7Be beams. This study is related to the astrophysical 7Li/7Be(α,γ) reactions, important at hot p-p chain and νp-process in supernovae. There have also been measurements based on other experimental methods. The first THM measurement using an RI beam has been performed at CRIB, to study the 18F(p, α)15O reaction at astrophysical energies via the three body reaction 2H(18F, α15O)n. The 18F(p, α) 15O reaction rate is crucial to understand the 511-keV γ-ray production in nova explosion phenomena, and we successfully evaluated the reaction cross section at novae temperature and below experimentally for the first time.

  10. Temperature effect on IgE binding to CD23 versus Fc epsilon RI.

    PubMed

    Chen, Bing-Hung; Kilmon, Michelle A; Ma, Check; Caven, Timothy H; Chan-Li, Yee; Shelburne, Anne E; Tombes, Robert M; Roush, Eric; Conrad, Daniel H

    2003-02-15

    A chimeric soluble CD23, consisting of the extracellular domain of mouse CD23 and a modified leucine zipper (lz-CD23), has been shown to inhibit IgE binding to the FcepsilonRI. A similar human CD23 construct was also shown to inhibit binding of human IgE to human FcepsilonRI. In both systems, the inhibition was found to be temperature dependent; a 10-fold molar excess of lz-CD23 gave 90-98% inhibition at 4 degrees C, dropping to 20-30% inhibition at 37 degrees C. Surface plasmon resonance analysis of lz-CD23 binding to an IgE-coated sensor chip suggested that the effective concentration of lz-CD23 was lower at the higher temperatures. Analysis of (125)I-IgE binding to CD23(+)-Chinese hamster ovary cells also indicated that increased temperature resulted in a lower percentage of IgE capable of interacting with CD23. In contrast, IgE interacts more effectively with FcepsilonRI(+)-rat basophilic leukemia cells at 37 degrees C compared with 4 degrees C. The results support the concept that the open and closed IgE structures found by crystallography interact differently with the two IgE receptors and suggest that temperature influences the relative percentage of IgE in the respective structural forms. Changes in CD23 oligomerization also plays a role in the decreased binding seen at physiological temperatures.

  11. [Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma].

    PubMed

    Launay, M; Bozzolo, E; Venissac, N; Delmont, E; Fredenrich, A; Thomas, P

    2008-01-01

    We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.

  12. Experimental Studies of Light-Ion Nuclear Reactions Using Low-Energy RI Beams

    NASA Astrophysics Data System (ADS)

    Yamaguchi, H.; Kahl, D.; Hayakawa, S.; Sakaguchi, Y.; Abe, K.; Shimuzu, H.; Wakabayashi, Y.; Hashimoto, T.; Cherubini, S.; Gulino, M.; Spitaleri, C.; Rapisarda, G. G.; La Cognata, M.; Lamia, L.; Romano, S.; Kubono, S.; Iwasa, N.; Teranishi, T.; Kawabata, T.; Kwon, Y. K.; Binh, D. N.; Khiem, L. H.; Duy, N. N.; Kato, S.; Komatsubara, T.; Coc, A.; de Sereville, N.; Hammache, F.; Kiss, G.; Bishop, S.

    CRIB (CNS Radio-Isotope Beam separator) is a low-energy RI beam separator of Center for Nuclear Study (CNS), the University of Tokyo. Studies on nuclear astrophysics, nuclear structure, and other interests have been performed using the RI beams at CRIB, forming international collaborations. A striking method to study astrophyiscal reactions involving radioactive nuclei is the thick-target method in inverse kinematics. Several astrophysical alpha-induced reactions have been be studied with that method at CRIB. A recent example is on the α resonant scattering with a radioactive 7Be beam. This study is related to the astrophysical 7Be(α , γ ) reactions, important at hot p-p chain and ν p-process in supernovae. There have been measurements based on several indirect methods, such as the asymptotic normalization coefficient (ANC) and Trojan horse method (THM). The first THM measurement using an RI beam has been performed at CRIB, to study the 18F(p, α )15O reaction at astrophysical energies via the three body reaction 2H(18F, α 15O)n. The 18F(p, α )15O reaction rate is crucial to understand the 511-keV γ -ray production in nova explosion phenomena, and we successfully evaluated the reaction cross section at novae temperature and below experimentally for the first time.

  13. Structure of D-AKAP2:PKA RI Complex: Insights into AKAP Specificity and Selectivity

    SciTech Connect

    Sarma, Ganapathy N.; Kinderman, Francis S.; Kim, Choel; von Daake, Sventja; Chen, Lirong; Wang, Bi-Cheng; Taylor, Susan S.

    2010-11-22

    A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RI{alpha} D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RII{alpha}:D-AKAP2 complex structure makes the mode of binding to RI{alpha} novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

  14. Characterization of highly and moderately repetitive 500 bp Eco RI fragments from Xenopus laevis DNA.

    PubMed Central

    Hummel, S; Meyerhof, W; Korge, E; Knöchel, W

    1984-01-01

    Three different types of repetitive Eco RI fragments, which comigrate within a visible band of approximately 500 bp at gel electrophoresis of Xenopus laevis DNA Eco RI digests have been cloned and sequenced. These sequences are designated as Repetitive Eco RI Monomers: REM 1, REM 2 and REM 3. The sequences contain direct repeats, inverted repeats and palindromic elements. Genomic organization of the most abundant sequence (REM 1; 0.4% of total DNA) is that of an interspersed sequence. REM 2 (0.08%) is partly organized as an interspersed element and partly found in tandem arrangement, whereas REM 3 (0.02%) represents the tandemly repeated monomeric unit of a satellite DNA. In situ hybridization has shown that REM 1 and REM 2 sequences are found on most chromosomes, REM 1 being preferentially located on specific chromosomal loci. REM 3 is located near the centromere region of only one chromosome pair (presumably number 1). Hybridization of Northern blots from RNAs of different developmental stages revealed that REM 1, REM 2 and REM 3 sequences are transcribed and that transcription is under developmental control. Images PMID:6330690

  15. Cellular trafficking of the IL-1RI-associated kinase-1 requires intact kinase activity

    SciTech Connect

    Boel, Gaby-Fleur . E-mail: boel@mail.dife.de; Jurrmann, Nadine; Brigelius-Flohe, Regina

    2005-06-24

    Upon stimulation of cells with interleukin-1 (IL-1) the IL-1 receptor type I (IL-1RI) associated kinase-1 (IRAK-1) transiently associates to and dissociates from the IL-1RI and thereafter translocates into the nucleus. Here we show that nuclear translocation of IRAK-1 depends on its kinase activity since translocation was not observed in EL-4 cells overexpressing a kinase negative IRAK-1 mutant (EL-4{sup IRAK-1-K239S}). IRAK-1 itself, an endogenous substrate with an apparent molecular weight of 24 kDa (p24), and exogenous substrates like histone and myelin basic protein are phosphorylated by nuclear located IRAK-1. Phosphorylation of p24 cannot be detected in EL-4{sup IRAK-1-K239S} cells. IL-1-dependent recruitment of IRAK-1 to the IL-1RI and subsequent phosphorylation of IRAK-1 is a prerequisite for nuclear translocation of IRAK-1. It is therefore concluded that intracellular localization of IRAK-1 depends on its kinase activity and that IRAK-1 may also function as a kinase in the nucleus as shown by a new putative endogenous substrate.

  16. Actin restricts FcεRI diffusion and facilitates antigen-induced receptor immobilisation

    PubMed Central

    Andrews, Nicholas L.; Lidke, Keith A.; Pfeiffer, Janet R.; Burns, Alan R.; Wilson, Bridget S.; Oliver, Janet M.; Lidke, Diane S.

    2010-01-01

    The actin cytoskeleton has been implicated in restricting diffusion of plasma membrane components. Here, simultaneous observations of quantum dot-labelled FcεRI motion and GFP-tagged actin dynamics provide direct evidence that actin filament bundles define micron-sized domains that confine mobile receptors. Dynamic reorganisation of actin structures occurs over seconds, making the location and dimensions of actin-defined domains time dependent. Multiple FcεRI often maintain extended close proximity without detectable correlated motion, suggesting that they are co-confined within membrane domains. FcεRI signalling is activated by cross-linking with multivalent antigen. We show that receptors become immobilised within seconds of cross-linking. Disruption of the actin cytoskeleton results in delayed immobilisation kinetics and increased diffusion of cross-linked clusters. These results implicate actin in membrane partitioning that not only restricts diffusion of membrane proteins, but also dynamically influences their long-range mobility, sequestration, and response to ligand binding. PMID:18641640

  17. Uncertainties in NDE Reliability and Assessing the Impact on RI-ISI

    SciTech Connect

    Doctor, Steven R.; Anderson, Michael T.

    2010-08-01

    A major thrust in the past 20 years has been to upgrade nondestructive examinations (NDE) for use in inservice inspection (ISI) programs to more effectively manage degradation at operating nuclear power plants. Risk-informed ISI (RI-ISI) is one of the outcomes of this work, and this approach relies heavily on the reliability of NDE, when properly applied, to detect sources of expected degradation. There have been a number of improvements in the reliability of NDE, specifically in ultrasonic testing (UT), through training of examiners, and improved equipment and procedure development. However, the most significant improvements in UT were derived by moving from prescriptive requirements to performance based requirements. Even with these substantial improvements, NDE contains significant uncertainties and RI-ISI programs need to address and accommodate this factor. As part of the work that PNNL is conducting for the U. S. Nuclear Regulatory Commission, Office of Nuclear Regulatory Research, we are examining the impact of these uncertainties on the effectiveness of RI-ISI programs.

  18. Dating the Bibong-ri Neolithic site in Korea: Excavating the oldest ancient boat

    NASA Astrophysics Data System (ADS)

    Park, Gyujun; Kim, Jong-Chan; Youn, Minyoung; Yun, Chongcheol; Kang, Jin; Song, Yong-Mi; Song, Su-Jin; Noh, Hye-Jin; Kim, Do-Kyun; Im, Hack-Jong

    2010-04-01

    The remains of an ancient wooden boat were unearthed at the Bibong-ri shell mound site. The site was located at Bibong-ri, Bugog-myeon, Changnyeong-gun, Gyeongsangnam-do in South Korea. A substantial fragment of the vessel was discovered in the lowest layer of the site. We collected 17 samples of charcoal and wood from pebble, sand, and shell layers. Sample preparation extracted the carbon from each sample material and converted it into graphite for AMS radiocarbon dating. Radiocarbon dates of the samples indicate that they belong to the Neolithic period and that the boat dates from ca. 5700 BC. To this point, the oldest known boat in the world has been a wooden boat dating from ca. 5500 BC in China. Other ancient boats from around the world include a logboat dating from ca. 3600 BC in Japan and a fleet of wooden boats dating from ca. 3000 BC in Egypt. The Bibong-ri boat is the first boat from the Neolithic period ever found in South Korea and must represent one of the world's oldest known boats.

  19. Some Challenges of an “Upside Down” Nitrogen Budget – Science and Management in Greenwich Bay, RI (USA)

    EPA Science Inventory

    When nutrients impact estuarine water quality, scientists and managers instinctively focus on quantifying and controlling land-based sources. However, in Greenwich Bay, RI, the estuary opens onto a larger and more intensively fertilized coastal water body (Narragansett Bay). Prev...

  20. Some Challenges of an “Upside Down” Nitrogen Budget – Science and Management in Greenwich Bay, RI (USA)

    EPA Science Inventory

    When nutrients impact estuarine water quality, scientists and managers instinctively focus on quantifying and controlling land-based sources. However, in Greenwich Bay, RI, the estuary opens onto a larger and more intensively fertilized coastal water body (Narragansett Bay). Prev...

  1. 78 FR 52580 - Submission for Review: Request for Case Review for Enhanced Disability Annuity Benefit, RI 20-123

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-23

    ... Publications Team, 1900 E Street NW., Room 4445, Washington, DC 20415, Attention: Cyrus S. Benson, or sent by email to Cyrus.Benson@opm.gov or faxed to (202) 606- 0910. SUPPLEMENTARY INFORMATION: RI 20-123 is...

  2. A comment on the paper by R.I. Khrapko 'On the possibility of an experiment on 'nonlocality' of electrodynamics'

    SciTech Connect

    Venediktov, V Yu

    2015-04-30

    This methodological note is dedicated to the analysis of the imaginary experiment proposed in the paper by R.I. Khrapko 'On the possibility of an experiment on 'nonlocality' of electrodynamics' [Quantum Electronics, 42, 1133 (2012)]. (discussion)

  3. VizieR Online Data Catalog: V823 Cas BV(RI)c differential photometry (Jurcsik+, 2006)

    NASA Astrophysics Data System (ADS)

    Jurcsik, J.; Szeidl, B.; Varadi, M.; Henden, A.; Hurta, Zs.; Lakatos, B.; Posztobanyi, K.; Klagyivik, P.; Sodor, A.

    2005-09-01

    The observations were obtained with the automated 60cm telescope of Konkoly Observatory, Svabhegy, Budapest equiped with a Wright 750x1100 CCD using BV(RI)c filters, between 25 September and 14 December in 2003. (5 data files).

  4. Peanut-induced intestinal allergy is mediated through a mast cell-IgE-FcepsilonRI-IL-13 pathway.

    PubMed

    Wang, Meiqin; Takeda, Katsuyuki; Shiraishi, Yoshiki; Okamoto, Masakazu; Dakhama, Azzeddine; Joetham, Anthony; Gelfand, Erwin W

    2010-08-01

    Although implicated in the disease, the specific contributions of FcepsilonRI and IL-13 to the pathogenesis of peanut-induced intestinal allergy are not well defined. We sought to determine the contributions of FcepsilonRI, IL-13, and mast cells to the development of intestinal mucosal responses in a murine model of peanut-induced intestinal allergy. Sensitized wild-type (WT), FcepsilonRI-deficient (FcepsilonRI(-/-)), and mast cell-deficient (Kit(W-sh/W-sh)) mice received peanut orally every day for 1 week. Bone marrow-derived mast cells (BMMCs) from WT, FcepsilonRI(-/-), IL-4(-/-), IL-13(-/-), and IL-4/IL-13(-/-) mice were differentiated and transferred into WT, FcepsilonRI(-/-), and Kit(W-sh/W-sh) recipients. BMMCs from WT and UBI-GFP/BL6 mice were differentiated and transferred into WT and Kit(W-sh/W-sh) mice. Blockade of IL-13 was achieved by using IL-13 receptor alpha2 (IL-13Ralpha2)-IgG fusion protein. FcepsilonRI(-/-) mice showed decreased intestinal inflammation (mast cell and eosinophil numbers) and goblet cell metaplasia and reduced levels of IL4, IL6, IL13, and IL17A mRNA expression in the jejunum. Transfer of WT BMMCs to FcepsilonRI(-/-) recipients restored their ability to develop intestinal allergic responses unlike transfer of FcepsilonRI(-/-), IL-13(-/-), or IL-4/IL-13(-/-) BMMCs. FcepsilonRI(-/-) mice exhibited lower IL-13 levels and treatment of WT mice with IL-13 receptor alpha2 prevented peanut-induced intestinal allergy and inflammation. These data indicate that the development of peanut-induced intestinal allergy is mediated through a mast cell-dependent IgE-FcepsilonRI-IL-13 pathway. Targeting IL-13 might be a potential treatment for IgE-mediated peanut-induced allergic responses in the intestine. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  5. Orai and TRPC channel characterization in FcεRI-mediated calcium signaling and mediator secretion in human mast cells.

    PubMed

    Wajdner, Hannah E; Farrington, Jasmine; Barnard, Claire; Peachell, Peter T; Schnackenberg, Christine G; Marino, Joseph P; Xu, Xiaoping; Affleck, Karen; Begg, Malcolm; Seward, Elizabeth P

    2017-03-01

    Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published. Here, we show evidence for the expression of Orai 1,2, and 3 and TRPC1 and 6 in primary human lung mast cells and the LAD2 human mast cell line but, we only find evidence of functional contribution of Orai and not TRPC channels to FcεRI-mediated calcium entry. Calcium imaging experiments, utilizing an Orai selective antagonist (Synta66) showed the contribution of Orai to FcεRI-mediated signaling in human mast cells. Although, the use of a TRPC3/6 selective antagonist and agonist (GSK-3503A and GSK-2934A, respectively) did not reveal evidence for TRPC6 contribution to FcεRI-mediated calcium signaling in human mast cells. Similarly, inactivation of STIM1-regulated TRPC1 in human mast cells (as tested by transfecting cells with STIM1-KK(684-685)EE - TRPC1 gating mutant) failed to alter FcεRI-mediated calcium signaling in LAD2 human mast cells. Mediator release assays confirm that FcεRI-mediated calcium influx through Orai is necessary for histamine and TNFα release but is differentially involved in the generation of cytokines and eicosanoids.

  6. Suppressive effect of Elf-1 on FcepsilonRI alpha-chain expression in primary mast cells.

    PubMed

    Wang, Qing-Hui; Nishiyama, Chiharu; Nakano, Nobuhiro; Shimokawa, Naomi; Hara, Mutsuko; Kanada, Shunsuke; Ogawa, Hideoki; Okumura, Ko

    2008-10-01

    The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, is specifically expressed in mast cells and basophils and plays a key role in IgE-mediated allergic reactions. The transcription factor Elf-1 has been previously identified to bind to the promoter of the human FcepsilonRI alpha-chain, which is essential for the function and expression of FcepsilonRI. In the present study, Elf-1 siRNA was conducted to evaluate the effects of Elf-1 on FcepsilonRI alpha-chain expression in the primary mouse mast cells, bone marrow-derived mast cells (BMMC). Introduction of Elf-1 siRNA effectively reduced expression levels of Elf-1 mRNA and protein in BMMC. Transient reporter assay showed that the knockdown of Elf-1 by siRNA resulted in increased FcepsilonRI alpha-chain promoter activity, while overexpression of Elf-1 suppressed alpha-chain promoter activity in BMMC. Elf-1 siRNA-treated BMMC exhibited marked upregulation of FcepsilonRI alpha-chain transcription, whereas beta-chain mRNA was not affected by Elf-1 siRNA. Chromatin immunoprecipitation assay showed that the amount of transcription factor PU.1, recognizing the cis-element close to the Elf-1-site on the FcepsilonRI alpha-chain promoter, was significantly increased by introduction of Elf-1 siRNA. These results indicate that Elf-1 negatively regulates FcepsilonRI alpha-chain expression by suppressing PU.1-mediated transcription of the alpha-chain in BMMC.

  7. Homology mapping of T-DNA regions on three Agrobacterium rhizogenes Ri plasmids by electron microscope heteroduplex studies.

    PubMed

    Brevet, J; Tempé, J

    1988-03-01

    Recombinant plasmids carrying segments of the Agrobacterium rhizogenes T-DNA regions of the three Ri plasmids 1855 (TL-DNA only), 8196, and 2659 were used for establishing homology maps by electron microscope examination of heteroduplexes. Plasmid DNA was linearized by digestion with suitable restriction endonucleases in order to generate large T-DNA segments. Heteroduplexes were prepared in 50% formamide and spread under standard conditions. Measurements of double and single strands allowed the drawing of homology maps. The three T-DNAs share mainly two homologous sequences of respectively about 2.5 and 1.5 kb, bracketing a largely nonhomologous central part which is about 5.5 kb long. The T-DNAs from pRi1855 and pRi2659 appear to be more related to each other than to that of pRi8196. With reference to the published nucleotide sequence of the TL-DNA of pRiA4 (probably identical to that of pRi1855), ORFs 8 and 14 seem to be the most conserved sequences of the three T-DNAs. The significance of these conserved sequences is unclear since the genetic loci involved in rhizogenicity of agropine strains identified previously are located in nonhomologous regions.

  8. Asia Rice Crop Estimation and Monitoring (Asia-RiCE) for GEOGLAM

    NASA Astrophysics Data System (ADS)

    Oyoshi, K.; Tomiyama, N.; Okumura, T.; Sobue, S.

    2013-12-01

    Food security is a critical issue for the international community because of rapid population and economic growth, and climate change. In June 2011, the meeting of G20 agriculture ministers was held to discuss food security and food price volatility, and they agreed on an 'Action Plan on Food Price Volatility and Agriculture'. This plan includes a GEO Global Agricultural Monitoring (GEOGLAM) initiative. The aim of GEOGLAM is to reinforce the international community's ability to produce and disseminate relevant, timely, and accurate forecasts of agricultural production on regional, national, and global scales by utilizing remote sensing technology. GEOGLAM focused on four major grain crops, wheat, maize, soybeans and rice. In particular, Asian countries are responsible for approximately 90% of the world rice production and consumption, rice is the most significant cereal crop in Asian region. Hence, Asian space and agricultural agencies with an interest in the development of rice crop monitoring technology launched an Asia-Rice Crop Estimation & Monitoring (Asia-RiCE) component for the GEOGLAM initiative. In Asian region, rice is mainly cultivated in rainy season, and a large amount of cloud limits rice crop monitoring with optical sensors. But, Synthetic Aperture RADAR (SAR) is all-weather sensor and can observe land surface even if the area is covered by cloud. Therefore, SAR technology would be powerful tool to monitor rice crop in Asian region. Asia-RiCE team required mainly SAR observation data including ALOS-2, RISAT-1, Sentinel-1 and RADARSAT, TerraSAR-X, COSMO-SkyMed for Asia-RiCE GEOGLAM Phase 1 implementation (2013-2015) to the Committee on Earth Observations (CEOS) in the GEOGLAM-CEOS Global Agricultural Monitoring Co-community Meeting held in June 2013. And also, rice crop has complicated cropping systems such as rein-fed or irrigated cultivation, single, double or sometimes triple cropping. In addition, each agricultural field is smaller than that of

  9. Accelerated dissociation of IgE:FcεRI complexes by disruptive inhibitors actively desensitizes allergic effector cells

    PubMed Central

    Eggel, Alexander; Baravalle, Günther; Hobi, Gabriel; Kim, Beomkyu; Buschor, Patrick; Forrer, Patrik; Shin, Jeoung-Sook; Vogel, Monique; Stadler, Beda M.; Dahinden, Clemens A.; Jardetzky, Theodore S.

    2014-01-01

    Background The remarkably stable interaction of immunoglobulin E (IgE) with its high-affinity receptor FcεRI on basophils and mast cells is critical for the induction of allergic hypersensitivity reactions. Due to the exceptionally slow dissociation rate of IgE:FcεRI complexes such allergic effector cells permanently display allergen-specific IgE on their surface and immediately respond to allergen challenge by releasing inflammatory mediators. We have recently described a novel macromolecular inhibitor that actively promotes the dissociation of IgE from FcεRI through a molecular mechanism termed facilitated dissociation. Objective Here, we assessed the therapeutic potential of this non-immunoglobulin based IgE inhibitor DARPin E2_79 as well as a novel engineered biparatopic DARPin bi53_79 and directly compared them to the established anti-IgE antibody omalizumab. Methods: IgE:FcεRI complex dissociation was analyzed in vitro using recombinant proteins in ELISA and surface plasmon resonance, ex vivo using human primary basophils with flow cytometry and in vivo using human FcεRI transgenic mice in a functional passive cutaneous anaphylaxis test. Results We show that E2_79 mediated removal of IgE from primary human basophils fully abrogates IgE-dependent cell activation and release of pro-inflammatory mediators ex vivo. Furthermore, we report that omalizumab also accelerates the dissociation of IgE from FcεRI albeit much less efficiently than E2_79. Using the biparatopic IgE targeting approach we further improved the disruptive potency of E2_79 by ~100 fold and show that disruptive IgE inhibitors efficiently prevent passive cutaneous anaphylaxis in mice expressing the human FcεRI alpha chain. Conclusion Our findings highlight the potential of such novel IgE inhibitors as important diagnostic and therapeutic tools to managing allergic diseases. PMID:24642143

  10. Fyn kinase controls Fc{epsilon}RI receptor-operated calcium entry necessary for full degranulation in mast cells

    SciTech Connect

    Sanchez-Miranda, Elizabeth; Ibarra-Sanchez, Alfredo; Gonzalez-Espinosa, Claudia

    2010-01-22

    IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc{epsilon}RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca{sup 2+}) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc{epsilon}RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc{epsilon}RI-dependent Ca{sup 2+} mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca{sup 2+} influx after Fc{epsilon}RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd{sup 3+}) partially blocked Fc{epsilon}RI-induced Ca{sup 2+} influx in WT cells but, in contrast, completely inhibited Ca{sup 2+} mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca{sup 2+} channels (2-aminoethoxyphenyl-borane, 2-APB) blocked Fc{epsilon}RI-induced maximal Ca{sup 2+} rise in WT but not in Fyn -/- cells. Ca{sup 2+} entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc{epsilon}RI-stimulated mast cells.

  11. t-Darpp stimulates protein kinase A activity by forming a complex with its RI regulatory subunit.

    PubMed

    Theile, Dirk; Geng, Shuhui; Denny, Erin C; Momand, Jamil; Kane, Susan E

    2017-09-01

    t-Darpp is the truncated form of the dopamine- and cAMP-regulated phosphoprotein of 32kDa (Darpp-32) and has been demonstrated to confer resistance to trastuzumab, a Her2-targeted anticancer agent, via sustained signaling through the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway and activation of protein kinase A (PKA). The mechanism of t-Darpp-mediated PKA activation is poorly understood. In the PKA holoenzyme, when the catalytic subunits are bound to regulatory subunits RI or RII, kinase activity is inhibited. We investigated PKA activity and holoenzyme composition in cell lines overexpressing t-Darpp (SK.tDp) or a T39A phosphorylation mutant (SK.tDp(T39A)), as well as an empty vector control cell line (SK.empty). We also evaluated protein-protein interactions between t-Darpp and PKA catalytic (PKAc) or regulatory subunits RI and RII in those cell lines. SK.tDp cells had elevated PKA activity and showed diminished association of RI with PKAc, whereas SK.tDp(T39A) cells did not have these properties. Moreover, wild type t-Darpp associates with RI. Concurrent expression of Darpp-32 reversed t-Darrp's effects on PKA holoenzyme state, consistent with earlier observations that Darpp-32 reverses t-Darpp's activation of PKA. Together, t-Darpp phosphorylation at T39 seems to be crucial for t-Darpp-mediated PKA activation and this activation appears to occur through an association with RI and sequestering of RI away from PKAc. The t-Darpp-RI interaction could be a druggable target to reduce PKA activity in drug-resistant cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Monoclonal antibodies and synthetic peptides define the active site of FcepsilonRI and a potential receptor antagonist.

    PubMed

    Rigby, L J; Trist, H; Snider, J; Hulett, M D; Hogarth, P M; Rigby, L J; Epa, V C

    2000-07-01

    Defining the structure of the human high-affinity receptor for IgE, Fc,RI, is crucial to understand the receptor:ligand interaction, and to develop drugs to prevent IgE-dependent allergic diseases. To this end, a series of four anti-FcepsilonRI monoclonal antibodies (mAbs), including three new mAbs, 47, 54, and 3B4, were used in conjunction with synthetic FcepsilonRI peptides to define functional regions of the Fc IgE-binding site and identify an antagonist of IgE binding. The spatial orientation of the epitopes detected by these antibodies and their relationship to the IgE-binding region of FcepsilonRI was defined by a homology model based on the closely related FcepsilonRIIa. Using recombinant soluble FcRI-alpha as well as FcepsilonRI-alpha expressed on the cell surface, a series of direct and competitive binding experiments indicated that the mAbs detected nonoverlapping epitopes. One antibody (15-1), previously thought to be located close to the IgE-binding site, was precisely mapped to a single loop within the IgE-binding site by both mutagenesis and overlapping synthetic peptides encompassing the entire extracellular domain. A synthetic peptide epsilonRI-11, containing the amino acids 101-120 and the mAb 15-1 epitope, inhibited IgE binding and may form the basis for the development of a useful receptor-based therapy.

  13. TRAF6 specifically contributes to FcepsilonRI-mediated cytokine production but not mast cell degranulation.

    PubMed

    Yang, Yong Jun; Chen, Wei; Carrigan, Svetlana O; Chen, Wei-Min; Roth, Kristy; Akiyama, Taishin; Inoue, Jun-ichiro; Marshall, Jean S; Berman, Jason N; Lin, Tong-Jun

    2008-11-14

    TRAF6 (tumor necrosis factor-associated factor 6) is an essential adaptor downstream from the tumor necrosis factor (TNF) receptor and Toll-like receptor superfamily members. This molecule is critical for dendritic cell maturation and T cell homeostasis. Here we show that TRAF6 is important in high affinity IgE receptor, FcepsilonRI-mediated mast cell activation. In contrast to dendritic cells and T cells, TRAF6-deficient mast cells matured normally and showed normal IgE-dependent degranulation. Importantly, TRAF6-deficient mast cells showed impaired production of cytokine interleukin-6, CCL-9, interleukin-13, and TNF following FcepsilonRI aggregation. Chromatin immunoprecipitation assay showed decreased NF-kappaB p65 binding to CCL-9 and TNF promoters in TRAF6-deficient mast cells. Antigen and IgE-induced IkappaB phosphorylation and NF-kappaB p65 translocation to the nucleus were diminished in TRAF6-deficient mast cells. NF-kappaB luciferase activity in response to antigen and IgE stimulation was severely impaired in TRAF6-deficient mast cells. In addition, antigen and IgE-induced phosphorylation of mitogen-activated protein kinase p38 and JNK, but not ERK1/2, was significantly reduced in TRAF6-deficient mast cells. These results identified TRAF6 as an important signal transducer in FcepsilonRI-mediated signaling in mast cells. Our findings implicate TRAF6 as a new adaptor/regulator molecule for allergen-mediated inflammation in allergy.

  14. Transcriptome networks in the mouse retina: An exon level BXD RI database

    PubMed Central

    King, Rebecca; Lu, Lu; Williams, Robert W.

    2015-01-01

    Purpose Differences in gene expression provide diverse retina phenotypes and may also contribute to susceptibility to injury and disease. The present study defines the transcriptome of the retina in the BXD RI strain set, using the Affymetrix Mouse Gene 2.0 ST array to investigate all exons of traditional protein coding genes, non-coding RNAs, and microRNAs. These data are presented in a highly interactive database on the GeneNetwork website. Methods In the Normal Retina Database, the mRNA levels of the transcriptome from retinas was quantified using the Affymetrix Mouse Gene 2.0 ST array. This database consists of data from male and female mice. The data set includes a total of 52 BXD RI strains, the parental strains (C57BL/6J and DBA/2J), and a reciprocal cross. Results In combination with GeneNetwork, the Department of Defense (DoD) Congressionally Directed Medical Research Programs (CDMRP) Normal Retina Database provides a large resource for mapping, graphing, analyzing, and testing complex genetic networks. Protein-coding and non-coding RNAs can be used to map quantitative trait loci (QTLs) that contribute to expression differences among the BXD strains and to establish links between classical ocular phenotypes associated with differences in the genomic sequence. Using this resource, we extracted transcriptome signatures for retinal cells and defined genetic networks associated with the maintenance of the normal retina. Furthermore, we examined differentially expressed exons within a single gene. Conclusions The high level of variation in mRNA levels found among the BXD RI strains makes it possible to identify expression networks that underline differences in retina structure and function. Ultimately, we will use this database to define changes that occur following blast injury to the retina. PMID:26604663

  15. U BV RI PHOTOMETRIC STANDARD STARS AROUND THE SKY AT +50 deg DECLINATION

    SciTech Connect

    Landolt, Arlo U.

    2013-11-01

    U BV RI photoelectric observations have been made of 335 stars around the sky, and centered approximately at +50 deg declination. The majority of the stars fall in the magnitude range 9 < V < 16, and in the color range –0.3 < (B – V) < +1.8. Those 243 stars best suited as new broadband photometric standard stars average 12.5 measures each from data taken on 98 different nights over a period of 17 years at the Kitt Peak National and Lowell Observatories.

  16. Polymer nanocomposite films with extremely high nanoparticle loadings via capillary rise infiltration (CaRI)

    NASA Astrophysics Data System (ADS)

    Huang, Yun-Ru; Jiang, Yijie; Hor, Jyo Lyn; Gupta, Rohini; Zhang, Lei; Stebe, Kathleen J.; Feng, Gang; Turner, Kevin T.; Lee, Daeyeon

    2014-12-01

    Polymer nanocomposite films (PNCFs) with extremely high concentrations of nanoparticles are important components in energy storage and conversion devices and also find use as protective coatings in various applications. PNCFs with high loadings of nanoparticles, however, are difficult to prepare because of the poor processability of polymer-nanoparticle mixtures with high concentrations of nanoparticles even at an elevated temperature. This problem is exacerbated when anisotropic nanoparticles are the desired filler materials. Here we report a straightforward method for generating PNCFs with extremely high loadings of nanoparticles. Our method is based on what we call capillary rise infiltration (CaRI) of polymer into a dense packing of nanoparticles. CaRI consists of two simple steps: (1) the preparation of a two-layer film, consisting of a porous layer of nanoparticles and a layer of polymer and (2) annealing of the bilayer structure above the temperature that imparts mobility to the polymer (e.g., glass transition of the polymer). The second step leads to polymer infiltration into the interstices of the nanoparticle layer, reminiscent of the capillary rise of simple fluid into a narrow capillary or a packing of granules. We use in situ spectroscopic ellipsometry and a three-layer Cauchy model to follow the capillary rise of polystyrene into the random network of nanoparticles. The infiltration of polystyrene into a densely packed TiO2 nanoparticle layer is shown to follow the classical Lucas-Washburn type of behaviour. We also demonstrate that PNCFs with densely packed anisotropic TiO2 nanoparticles can be readily generated by spin coating anisotropic TiO2 nanoparticles atop a polystyrene film and subsequently thermally annealing the bilayer film. We show that CaRI leads to PNCFs with modulus, hardness and scratch resistance that are far superior to the properties of films of the component materials. In addition, CaRI fills in cracks that may exist in the

  17. VizieR Online Data Catalog: UBV(RI)c photometry of Stock 16 (Vazquez+, 2005)

    NASA Astrophysics Data System (ADS)

    Vazquez, R. A.; Baume, G. L.; Feinstein, C.; Nunez, J. A.; Vergne, M. M.

    2005-02-01

    CCD UBV(RI)c imaging photometry was carried out in the field of Stock 16 along two observational runs at the University of Toronto Southern Observatory, Las Campanas, Chile, using the Hellen Sawyer Hogg 60-cm telescope: on the nights of 1994 April 13, 14 and 16, we obtained UBVRI photometry for four frames with the nitrogen-cooled detector PM METHACROME UV coated (0.45"/pix) covering 4' on a side; three more frames were exposed on the nights of 1996 February 25 and 26 in the UBV(I)c bands (this time, the detector was glycol-refrigerated). (1 data file).

  18. Endogenous Bioactive Jasmonate Is Composed of a Set of (+)-7-iso-JA-Amino Acid Conjugates.

    PubMed

    Yan, Jianbin; Li, Suhua; Gu, Min; Yao, Ruifeng; Li, Yuwen; Chen, Juan; Yang, Mai; Tong, Jianhua; Xiao, Langtao; Nan, Fajun; Xie, Daoxin

    2016-12-01

    Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently derepress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. So far, (+)-7-iso-JA-l-Ile has been the only identified endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met, and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules. Furthermore, our studies uncover the general characteristics for all the bioactive JA molecules, and provide a new strategy to synthetically generate novel active JA molecules.

  19. Ion-optical studies of BigRIPS separator and ZeroDegree spectrometer at RIKEN RI Beam Factory

    NASA Astrophysics Data System (ADS)

    Takeda, Hiroyuki; Kubo, Toshiyuki; Ohnishi, Tetsuya; Fukuda, Naoki; Kameda, Daisuke; Kusaka, Kensuke; Yoshida, Atsushi; Yoshida, Koichi; Ohtake, Masao; Inabe, Naohito; Yanagisawa, Yoshiyuki; Tanaka, Kanenobu; Matsushita, Masafumi

    2009-10-01

    The BigRIPS in-flight separator[1] and the ZeroDegree spectrometer (ZDS) have been commissioned at RIKEN RI Beam Factory (RIBF) recently. Intense radioactive isotope (RI) beams are produced, separated and analyzed by the BigRIPS and the ZDS. Both of them are operated in several optical modes according to experimental conditions. For particle identifications of RI beams, it is essentially important to achieve high resolutions in A/Q ratio because RI beams are produced in several charge states in our energy region especially for heavy RI beams. Ion optical calculation with realistic magnetic field maps is indispensable for our purpose and we use COSY INFINITY[2] for that. Measured field maps are incorporated in the COSY calculations. In 2008, the ZDS was commissioned for the first time in three different modes. Experimental results and comparison with the COSY calculations will be presented in this report. [1]T. Kubo: Nucl. Instr. Meth. B204, 97 (2003). [2]K. Makino, M. Berz: Nucl. Instr. Meth. A558, 346 (2006).

  20. An Interaction Library for the FcεRI Signaling Network

    DOE PAGES

    Chylek, Lily A.; Holowka, David A.; Baird, Barbara A.; ...

    2014-04-15

    Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein–protein and protein–lipid interactions.more » This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP3 at the plasma membrane and the soluble second messenger IP3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs.« less

  1. Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation.

    PubMed

    Phong, Binh L; Avery, Lyndsay; Sumpter, Tina L; Gorman, Jacob V; Watkins, Simon C; Colgan, John D; Kane, Lawrence P

    2015-12-14

    T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

  2. Differences between EcoRI nonspecific and "star" sequence complexes revealed by osmotic stress.

    PubMed

    Sidorova, Nina Y; Rau, Donald C

    2004-10-01

    The binding of the restriction endonuclease EcoRI to DNA is exceptionally specific. Even a single basepair change ("star" sequence) from the recognition sequence, GAATTC, decreases the binding free energy of EcoRI to values nearly indistinguishable from nonspecific binding. The difference in the number of waters sequestered by the protein-DNA complexes of the "star" sequences TAATTC and CAATTC and by the specific sequence complex determined from the dependence of binding free energy on water activity is also practically indistinguishable at low osmotic pressures from the 110 water molecules sequestered by nonspecific sequence complexes. Novel measurements of the dissociation rates of noncognate sequence complexes and competition equilibrium show that sequestered water can be removed from "star" sequence complexes by high osmotic pressure, but not from a nonspecific complex. By 5 Osm, the TAATTC "star" sequence complex has lost almost 90 of the approximately 110 waters initially present. It is more difficult to remove water from the CAATTC "star" sequence complex. The sequence dependence of water loss correlates with the known sequence dependence of "star" cleavage activity.

  3. Structural consequences of aglycosylated IgG Fc variants evolved for FcγRI binding.

    PubMed

    Ju, Man-Seok; Na, Jung-Hyun; Yu, Yeon Gyu; Kim, Jae-Yeol; Jeong, Cherlhyun; Jung, Sang Taek

    2015-10-01

    In contrast to the glycosylated IgG antibodies secreted by human plasma cells, the aglycosylated IgG antibodies produced by bacteria are unable to bind FcγRs expressed on the surface of immune effector cells and cannot trigger immune effector functions. To avoid glycan heterogeneity problems, elicit novel effector functions, and produce therapeutic antibodies with effector function using a simple bacterial expression system, FcγRI-specific Fc-engineered aglycosylated antibodies, Fc11 (E382V) and Fc (E382V/M428I), containing mutations in the CH3 region, were isolated in a previous study. To elucidate the relationship between FcγRI binding affinity and the structural dynamics of the upper CH2 region of Fc induced by the CH3 mutations, the conformational variation of Fc variants was observed by single-molecule Förster resonance energy transfer (FRET) analysis using alternating-laser excitation (ALEX). In sharp contrast to wild-type Fc, which exhibits a highly dynamic upper CH2 region, the mutations in the CH3 region significantly stabilized the upper CH2 region. The results indicate that conformational plasticity, as well as the openness of the upper CH2 region, is critical for FcγR binding and therapeutic effector functions of IgG antibodies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. An Interaction Library for the FcεRI Signaling Network

    PubMed Central

    Chylek, Lily A.; Holowka, David A.; Baird, Barbara A.; Hlavacek, William S.

    2014-01-01

    Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein–protein and protein–lipid interactions. This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP3 at the plasma membrane and the soluble second messenger IP3. We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs. PMID:24782869

  5. Assessing the Combinatorial Potential of the RiPP Cyanobactin tru Pathway

    PubMed Central

    2015-01-01

    Ribosomally produced natural products, the RiPPs, exhibit features that are potentially useful in the creation of large chemical libraries using simple mutagenesis. RiPPs are encoded on ribosomal precursor peptides, but they are extensively posttranslationally modified, endowing them with properties that are useful in drug discovery and biotechnology. In order to determine which mutations are acceptable, strategies are required to determine sequence selectivity independently of the context of flanking amino acids. Here, we examined the absolute sequence selectivity of the trunkamide cyanobactin pathway, tru. A series of random double and quadruple simultaneous mutants were synthesized and produced in Escherichia coli. Out of a total of 763 mutated amino acids examined in 325 unique sequences, 323 amino acids were successfully incorporated in 159 sequences, leading to >300 new compounds. Rules for tru sequence selectivity were determined, which will be useful for the design and synthesis of combinatorial biosynthetic libraries. The results are also interpreted in comparison to the known natural products of tru and pat cyanobactin pathways. PMID:25140729

  6. Streamlining the RI/FS for CERCLA municipal landfill sites. Fact sheet

    SciTech Connect

    Not Available

    1990-09-01

    Approximately 20 percent of the sites on the National Priorities List (NPL) are municipal landfills which typically share similar characteristics. Because of the similarity the Superfund Program anticipates that their remediation will involve similar waste management approaches. As stated in the National Contingency Plan, EPA expects that containment technologies will generally be appropriate for waste that poses a relatively low long-term threat or where treatment is impracticable (Sec. 300.430(a)(1)(iii)(B),55FR8846(March 8, 1990)). In addition, EPA expects treatment to be considered for identifiable areas of highly toxic and/or mobile material that constitute the principal threat(s) posed by the site (Sec. 300.430(a)(1)(iii)(A)). The similarity in landfill characteristics and the NCP expectations make it possible to streamline the RI/FS for municipal landfills with respect to site characterization, risk assessment, and the development of remedial action alternatives. The fact sheet outlines available streamlining techniques for each of these three phases of an RI/FS. Additional information, including tools to assist in scoping activities, will be included in the document Conducting Remedial Investigations/Feasibility Studies for CERCLA Municipal Landfill Sites (November 1990, Directive No. 9355.3-11). The document will be available from the Center for Environmental Research Information (FTS 684-7562 or 513-569-7562).

  7. Standards for Reporting Implementation Studies (StaRI): explanation and elaboration document

    PubMed Central

    Pinnock, Hilary; Barwick, Melanie; Carpenter, Christopher R; Eldridge, Sandra; Grandes, Gonzalo; Griffiths, Chris J; Rycroft-Malone, Jo; Meissner, Paul; Murray, Elizabeth; Patel, Anita; Sheikh, Aziz; Taylor, Stephanie J C

    2017-01-01

    Objectives Implementation studies are often poorly reported and indexed, reducing their potential to inform the provision of healthcare services. The Standards for Reporting Implementation Studies (StaRI) initiative aims to develop guidelines for transparent and accurate reporting of implementation studies. Methods An international working group developed the StaRI guideline informed by a systematic literature review and e-Delphi prioritisation exercise. Following a face-to-face meeting, the checklist was developed iteratively by email discussion and critical review by international experts. Results The 27 items of the checklist are applicable to the broad range of study designs employed in implementation science. A key concept is the dual strands, represented as 2 columns in the checklist, describing, on the one hand, the implementation strategy and, on the other, the clinical, healthcare or public health intervention being implemented. This explanation and elaboration document details each of the items, explains the rationale and provides examples of good reporting practice. Conclusions Previously published reporting statements have been instrumental in improving reporting standards; adoption by journals and authors may achieve a similar improvement in the reporting of implementation strategies that will facilitate translation of effective interventions into routine practice. PMID:28373250

  8. Functional nanoscale coupling of Lyn kinase with IgE-FcεRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling

    PubMed Central

    Shelby, Sarah A.; Veatch, Sarah L.; Holowka, David A.; Baird, Barbara A.

    2016-01-01

    The allergic response is initiated on the plasma membrane of mast cells by phosphorylation of the receptor for immunoglobulin E (IgE), FcεRI, by Lyn kinase after IgE-FcεRI complexes are cross-linked by multivalent antigen. Signal transduction requires reorganization of receptors and membrane signaling proteins, but this spatial regulation is not well defined. We used fluorescence localization microscopy (FLM) and pair-correlation analysis to measure the codistribution of IgE-FcεRI and Lyn on the plasma membrane of fixed cells with 20- to 25-nm resolution. We directly visualized Lyn recruitment to IgE-FcεRI within 1 min of antigen stimulation. Parallel FLM experiments captured stimulation-induced FcεRI phosphorylation and colocalization of a saturated lipid-anchor probe derived from Lyn’s membrane anchorage. We used cytochalasin and latrunculin to investigate participation of the actin cytoskeleton in regulating functional interactions of FcεRI. Inhibition of actin polymerization by these agents enhanced colocalization of IgE-FcεRI with Lyn and its saturated lipid anchor at early stimulation times, accompanied by augmented phosphorylation within FcεRI clusters. Ising model simulations provide a simplified model consistent with our results. These findings extend previous evidence that IgE-FcεRI signaling is initiated by colocalization with Lyn in ordered lipid regions and that the actin cytoskeleton regulates this functional interaction by influencing the organization of membrane lipids. PMID:27682583

  9. High-resolution abundance analysis of very metal-poor r-I stars

    NASA Astrophysics Data System (ADS)

    Siqueira Mello, C.; Hill, V.; Barbuy, B.; Spite, M.; Spite, F.; Beers, T. C.; Caffau, E.; Bonifacio, P.; Cayrel, R.; François, P.; Schatz, H.; Wanajo, S.

    2014-05-01

    Context. Moderately r-process-enriched stars (r-I; +0.3 ≤ [Eu/Fe] ≤ +1.0) are at least four times as common as those that are greatly enriched in r-process elements (r-II; [Eu/Fe] > +1.0), and the abundances in their atmospheres are important tools for obtaining a better understanding of the nucleosynthesis processes responsible for the origin of the elements beyond the iron peak. Aims: The main aim of this work is to derive abundances for a sample of seven metal-poor stars with -3.4 ≤ [Fe/H] ≤ -2.4 classified as r-I stars, to understand the role of these stars for constraining the astrophysical nucleosynthesis event(s) that is (are) responsible for the production of the r-process, and to investigate whether they differ, in any significant way, from the r-II stars. Methods: We carried out a detailed abundance analysis based on high-resolution spectra obtained with the VLT/UVES spectrograph, using spectra in the wavelength ranges 3400-4500 Å, 6800-8200 Å, and 8700-10 000 Å, with resolving power R ~ 40 000 (blue arm) and R ~ 55 000 (red arm). The OSMARCS LTE 1D model atmosphere grid was employed, along with the spectrum synthesis code Turbospectrum. Results: We have derived abundances of the light elements Li, C, and N, the α-elements Mg, Si, S, Ca, and Ti, the odd-Z elements Al, K, and Sc, the iron-peak elements V, Cr, Mn, Fe, Co, and Ni, and the trans-iron elements from the first peak (Sr, Y, Zr, Mo, Ru, and Pd), the second peak (Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb), the third peak (Os and Ir, as upper limits), and the actinides (Th) regions. The results are compared with values for these elements for r-II and "normal" very and extremely metal-poor stars reported in the literature, ages based on radioactive chronometry are explored using different models, and a number of conclusions about the r-process and the r-I stars are presented. Hydrodynamical models were used for some elements, and general behaviors for the 3D corrections

  10. RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol

    PubMed Central

    Smallshaw, Joan E.; Richardson, James A.; Vitetta, Ellen S.

    2007-01-01

    Ricin is a plant toxin that is a CDC level B biothreat. Our recombinant ricin A chain vaccine (RiVax), which contains mutations in both known toxic sites, has no residual toxicity at doses at least 800 times the immunogenic dose. RiVax without adjuvant given intramuscularly (i.m.) protected mice against intraperitoneally administered ricin. Furthermore the vaccine without alum was safe and immunogenic in human volunteers. Here we describe the development of gavage and aerosol ricin challenge models in mice and demonstrate that i.m. vaccination protects mice against ricin delivered by either route. Also RiVax protects against aerosol-induced lung damage as determined by histology and lung function tests. PMID:17875350

  11. Effector-Mediated Interaction of CbbRI and CbbRII Regulators with Target Sequences in Rhodobacter capsulatus

    PubMed Central

    Dubbs, Padungsri; Dubbs, James M.; Tabita, F. Robert

    2004-01-01

    In Rhodobacter capsulatus, genes encoding enzymes of the Calvin-Benson-Bassham reductive pentose phosphate pathway are located in the cbbI and cbbII operons. Each operon contains a divergently transcribed LysR-type transcriptional activator (CbbRI and CbbRII) that regulates the expression of its cognate cbb promoter in response to an as yet unidentified effector molecule(s). Both CbbRI and CbbRII were purified, and the ability of a variety of potential effector molecules to induce changes in their DNA binding properties at their target promoters was assessed. The responses of CbbRI and CbbRII to potential effectors were not identical. In gel mobility shift assays, the affinity of both CbbRI and CbbRII for their target promoters was enhanced in the presence of ribulose-1,5-bisphosphate (RuBP), phosphoenolpyruvate, 3-phosphoglycerate, 2-phosphoglycolate. ATP, 2-phosphoglycerate, and KH2PO4 were found to enhance only CbbRI binding, while fructose-1,6-bisphosphate enhanced the binding of only CbbRII. The DNase I footprint of CbbRI was reduced in the presence of RuBP, while reductions in the CbbRII DNase I footprint were induced by fructose-1,6-bisphosphate, 3-phosphoglycerate, and KH2PO4. The current in vitro results plus recent in vivo studies suggest that CbbR-mediated regulation of cbb transcription is controlled by multiple metabolic signals in R. capsulatus. This control reflects not only intracellular levels of Calvin-Benson-Bassham cycle metabolic intermediates but also the fixed (organic) carbon status and energy charge of the cell. PMID:15547275

  12. The Rhode Island Consortium for Autism Research and Treatment (RI-CART): a new statewide autism collaborative.

    PubMed

    Gerber, Alan; Morrow, Eric; Sheinkopf, Stephen J; Anders, Thomas

    2014-05-01

    Autism is a neurodevelopmental disorder characterized by core deficits in social interaction, language and repetitive behaviors. The need for services is rising sharply as the number of children identified with autism increases. The Rhode Island Consortium for Autism Research and Treatment (RI-CART) was founded in 2009 with the goal of increasing communication among autism researchers throughout the state and improving treatment for children with autism. RI-CART members have several exciting projects in progress, with its larger aim being the creation of a statewide research registry. A statewide registry would benefit research in Rhode Island and allow for larger collaborations nationally.

  13. Coordinate expression of AOS genes and JA accumulation: JA is not required for initiation of closing layer in wound healing tubers.

    PubMed

    Lulai, Edward; Huckle, Linda; Neubauer, Jonathan; Suttle, Jeffrey

    2011-06-15

    Wounding induces a series of coordinated physiological responses essential for protection and healing of the damaged tissue. Wound-induced formation of jasmonic acid (JA) is important in defense responses in leaves, but comparatively little is known about the induction of JA biosynthesis and its role(s) in tuber wound-healing. In this study, the effects of wounding on JA content, expression of JA biosynthetic genes, and the involvement of JA in the initiation of closing layer formation in potato tubers were determined. In addition, the role of abscisic acid (ABA) in wound-induced JA accumulation was examined. The basal JA content in non-wounded tuber tissues was low (< 3 ng g⁻¹ FW). Two hours after wounding, the JA content increased by > 5-fold, reached a maximum between 4 and 6h after wounding, and declined to near-basal levels thereafter. Tuber age (storage duration) had little effect on the pattern of JA accumulation. The expressions of the JA biosynthetic genes (StAOS2, StAOC, and StOPR3) were greatly increased by wounding reaching a maximum 2-4 h after wounding and declining thereafter. A 1-h aqueous wash of tuber discs immediately after wounding resulted in a 94% inhibition of wound-induced JA accumulation. Neither JA treatment nor inhibition of JA accumulation affected suberin polyphenolic accumulation during closing layer development indicating that JA was not essential for the initiation of primary suberization. ABA treatment did not restore JA accumulation in washed tuber tissues suggesting that leaching of endogenous ABA was either not involved or not solely involved in this loss of JA accumulation by washing. Collectively, these results indicate that JA is not required for the induction of processes essential to the initiation of suberization during closing layer development, but do not exclude the possibility that JA may be involved in other wound related responses. Published by Elsevier GmbH.

  14. Activity measurements of the radionuclides 18F and 99mTc for the NMISA, South Africa in the ongoing comparisons BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Tc-99m

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Nonis, M.; Van Rooy, M. W.; Van Staden, M. J.; Lubbe, J.

    2017-01-01

    In 2015, comparisons of activity measurements of 18F and 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Metrology Institute of South Africa (NMISA, South Africa). Ampoules containing about 25 kBq of 18F and 99mTc solutions were measured in the SIRTI for more than two half-lives. The NMISA standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)β-γ coincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Tc-99m, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Tc-99m comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Development of new auxiliary basis functions of the Karlsruhe segmented contracted basis sets including diffuse basis functions (def2-SVPD, def2-TZVPPD, and def2-QVPPD) for RI-MP2 and RI-CC calculations.

    PubMed

    Hellweg, Arnim; Rappoport, Dmitrij

    2015-01-14

    We report optimized auxiliary basis sets for use with the Karlsruhe segmented contracted basis sets including moderately diffuse basis functions (Rappoport and Furche, J. Chem. Phys., 2010, 133, 134105) in resolution-of-the-identity (RI) post-self-consistent field (post-SCF) computations for the elements H-Rn (except lanthanides). The errors of the RI approximation using optimized auxiliary basis sets are analyzed on a comprehensive test set of molecules containing the most common oxidation states of each element and do not exceed those of the corresponding unaugmented basis sets. During these studies an unsatisfying performance of the def2-SVP and def2-QZVPP auxiliary basis sets for Barium was found and improved sets are provided. We establish the versatility of the def2-SVPD, def2-TZVPPD, and def2-QZVPPD basis sets for RI-MP2 and RI-CC (coupled-cluster) energy and property calculations. The influence of diffuse basis functions on correlation energy, basis set superposition error, atomic electron affinity, dipole moments, and computational timings is evaluated at different levels of theory using benchmark sets and showcase examples.

  16. NEW BV(RI){sub C} PHOTOMETRY FOR PRAESEPE: FURTHER TESTS OF BROADBAND PHOTOMETRIC CONSISTENCY

    SciTech Connect

    Joner, Michael D.; Taylor, Benjamin J.; Laney, C. David; Van Wyk, Francois

    2011-11-15

    New BV(RI){sub C} measurements of Praesepe made at the South African Astronomical Observatory (SAAO) are presented. When those measurements are combined with those reported in previous papers in this series, it is found that they support previously determined V zero points for Praesepe, M67, and the Hyades. Support is also found for joint (V - R){sub C} and (R - I){sub C} zero points established previously for Praesepe and NGC 752. For the SAAO system of standard stars, a B - V correction to the Johnson system of about -9 mmag appears to be reasonably well established. The preferred (though not definitive) V correction is about +7 mmag. For the Landolt V system, zero-point identity with the Johnson system at a 2{sigma} level of 4.8 mmag is found, and no color term as large as 4 mmag (mag){sup -1} is detected. Updated CDS data files for Praesepe are briefly described.

  17. Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia.

    PubMed

    Marjon, Kristopher D; Marnell, Lorraine L; Mold, Carolyn; Du Clos, Terry W

    2009-02-01

    C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP-treated splenocytes also provided protection from ITP in adoptive transfer. Splenocytes from C57BL/6 mice were treated with 200 microg/ml CRP for 30 min, washed, and injected into mice 24 h before induction of ITP. Injection of 10(6) CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig-treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was found to be a macrophage by depletion, enrichment, and the use of purified bone marrow-derived macrophages. The induction of protection by CRP-treated cells was dependent on FcRgamma-chain and Syk activation, indicating an activating effect of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required Fc gamma RI on the donor cell and Fc gamma RIIb in the recipient mice. These findings suggest that CRP generates suppressive macrophages through Fc gamma RI, which then act through an Fc gamma RIIb-dependent pathway in the recipient to decrease platelet clearance. These results provide insight into the mechanism of CRP regulatory activity in autoimmunity and suggest a potential new therapeutic approach to ITP.

  18. Efficient linear-scaling second-order Møller-Plesset perturbation theory: The divide-expand-consolidate RI-MP2 model.

    PubMed

    Baudin, Pablo; Ettenhuber, Patrick; Reine, Simen; Kristensen, Kasper; Kjærgaard, Thomas

    2016-02-07

    The Resolution of the Identity second-order Møller-Plesset perturbation theory (RI-MP2) method is implemented within the linear-scaling Divide-Expand-Consolidate (DEC) framework. In a DEC calculation, the full molecular correlated calculation is replaced by a set of independent fragment calculations each using a subset of the total orbital space. The number of independent fragment calculations scales linearly with the system size, rendering the method linear-scaling and massively parallel. The DEC-RI-MP2 method can be viewed as an approximation to the DEC-MP2 method where the RI approximation is utilized in each fragment calculation. The individual fragment calculations scale with the fifth power of the fragment size for both methods. However, the DEC-RI-MP2 method has a reduced prefactor compared to DEC-MP2 and is well-suited for implementation on massively parallel supercomputers, as demonstrated by test calculations on a set of medium-sized molecules. The DEC error control ensures that the standard RI-MP2 energy can be obtained to the predefined precision. The errors associated with the RI and DEC approximations are compared, and it is shown that the DEC-RI-MP2 method can be applied to systems far beyond the ones that can be treated with a conventional RI-MP2 implementation.

  19. Efficient linear-scaling second-order Møller-Plesset perturbation theory: The divide-expand-consolidate RI-MP2 model

    NASA Astrophysics Data System (ADS)

    Baudin, Pablo; Ettenhuber, Patrick; Reine, Simen; Kristensen, Kasper; Kjærgaard, Thomas

    2016-02-01

    The Resolution of the Identity second-order Møller-Plesset perturbation theory (RI-MP2) method is implemented within the linear-scaling Divide-Expand-Consolidate (DEC) framework. In a DEC calculation, the full molecular correlated calculation is replaced by a set of independent fragment calculations each using a subset of the total orbital space. The number of independent fragment calculations scales linearly with the system size, rendering the method linear-scaling and massively parallel. The DEC-RI-MP2 method can be viewed as an approximation to the DEC-MP2 method where the RI approximation is utilized in each fragment calculation. The individual fragment calculations scale with the fifth power of the fragment size for both methods. However, the DEC-RI-MP2 method has a reduced prefactor compared to DEC-MP2 and is well-suited for implementation on massively parallel supercomputers, as demonstrated by test calculations on a set of medium-sized molecules. The DEC error control ensures that the standard RI-MP2 energy can be obtained to the predefined precision. The errors associated with the RI and DEC approximations are compared, and it is shown that the DEC-RI-MP2 method can be applied to systems far beyond the ones that can be treated with a conventional RI-MP2 implementation.

  20. RuBPCase activase mediates growth-defense tradeoffs: Silencing RCA redirects JA flux from JA-Ile to MeJA to attenuate induced defense responses in Nicotiana attenuata

    PubMed Central

    Mitra, Sirsha; Baldwin, Ian T.

    2014-01-01

    Summary RuBPCase activase (RCA), an abundant photosynthetic protein is strongly down-regulated in response to Manduca sexta’s oral secretion (OS) in Nicotiana attenuata. RCA-silenced plants are impaired not only in photosynthetic capacity and growth, but also in jasmonic acid (JA)-isoleucine (Ile) signaling, and herbivore resistance mediated by JA-Ile dependent defense traits. These responses are consistent with a resource-based growth-defense trade-off. Since JA+Ile-supplementation of OS restored WT levels of JA-Ile, defenses and resistance to M. sexta, but OS supplemented individually with JA- or Ile did not, the JA-Ile deficiency of RCA-silenced plants could not be attributed to lower JA or Ile pools or JAR4/6 conjugating activity. Similar levels of JA-Ile derivatives after OS elicitation indicated unaltered JA-Ile turnover and lower levels of other JA-conjugates ruled out competition from other conjugation reactions. RCA-silenced plants accumulated more methyl jasmonate (MeJA) after OS elicitation, which corresponded with increased jasmonate methyltransferase (JMT) activity. RCA-silencing phenocopies JMT over-expression, wherein elevated JMT activity redirects OS-elicited JA flux towards inactive MeJA, creating a JA sink which depletes JA-Ile and its associated defense responses. Hence RCA plays an additional non-photosynthetic role in attenuating JA-mediated defenses and their associated costs potentially allowing plants to anticipate resource-based constraints on growth before they actually occur. PMID:24491116

  1. Characterization of Temperate Bacteriophages of Bacillus subtilis by the Restriction Endonuclease EcoRI: Evidence for Three Different Temperate Bacteriophages

    PubMed Central

    Wilson, G. A.; Williams, M. T.; Baney, H. W.; Young, F. E.

    1974-01-01

    Temperate bacteriophages of Bacillus subtilis were characterized according to host range and digestion of the bacteriophage genome by endonuclease EcoRI. The three bacteriophages, φ3T, SPO2, and φ105, were all heteroimmune, and the DNA digests showed dissimilar patterns by agarose-ethidium bromide gel electrophoresis. Images PMID:4213607

  2. The high-affinity receptor for IgG, FcγRI, of humans and non-human primates.

    PubMed

    Chenoweth, Alicia M; Trist, Halina M; Tan, Peck-Szee; Wines, Bruce D; Hogarth, P Mark

    2015-11-01

    Non-human primate (NHP) models, especially involving macaques, are considered important models of human immunity and have been essential in preclinical testing for vaccines and therapeutics. Despite this, much less characterization of macaque Fc receptors has occurred compared to humans or mice. Much of the characterization of macaque Fc receptors so far has focused on the low-affinity Fc receptors, particularly FcγRIIIa. From these studies, it is clear that there are distinct differences between the human and macaque low-affinity receptors and their interaction with human IgG. Relatively little work has been performed on the high-affinity IgG receptor, FcγRI, especially in NHPs. This review will focus on what is currently known of how FcγRI interacts with IgG, from mutation studies and recent crystallographic studies of human FcγRI, and how amino acid sequence differences in the macaque FcγRI may affect this interaction. Additionally, this review will look at the functional consequences of differences in the amino acid sequences between humans and macaques. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. 78 FR 13914 - Submission for Review: Survivor Annuity Election for a Spouse, RI 20-63; Cover Letter Giving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-01

    ... MANAGEMENT Submission for Review: Survivor Annuity Election for a Spouse, RI 20-63; Cover Letter Giving... Management. ACTION: 60-Day Notice and request for comments. SUMMARY: The Retirement Services, Office of Personnel Management (OPM), is offering the general public and other Federal agencies the opportunity...

  4. Scituate R.I. High School Teacher Recognized by President Obama and EPA, Yarmouth, Maine teacher received honorable mention

    EPA Pesticide Factsheets

    BOSTON - A teacher at the Ponaganset High School in Scituate, R.I., was recognized by the federal government for his work that has energized environmental education for students, as well as the school system and community. Teacher Ross McCurdy recei

  5. Narratives of Agency: The Experiences of Braille Literacy Practitioners in the "Kha Ri Gude" South African Mass Literacy Campaign

    ERIC Educational Resources Information Center

    McKay, Veronica I.; Romm, Norma R. A.

    2015-01-01

    In this article, we locate the "Kha Ri Gude" South African Mass Literacy Campaign within the context of the problem of illiteracy and exclusion in South Africa, while concentrating on various post-apartheid initiatives designed to give visually challenged adults the opportunity to become literate. We shall provide a detailed account of…

  6. Narratives of Agency: The Experiences of Braille Literacy Practitioners in the "Kha Ri Gude" South African Mass Literacy Campaign

    ERIC Educational Resources Information Center

    McKay, Veronica I.; Romm, Norma R. A.

    2015-01-01

    In this article, we locate the "Kha Ri Gude" South African Mass Literacy Campaign within the context of the problem of illiteracy and exclusion in South Africa, while concentrating on various post-apartheid initiatives designed to give visually challenged adults the opportunity to become literate. We shall provide a detailed account of…

  7. Effect of particle size on conformation and enzymatic activity of EcoRI adsorbed on CdS nanoparticles.

    PubMed

    Song, Yonghai; Zhong, Dandan; Luo, Dan; Huang, Mei; Huang, Zhenzhong; Tan, Hongliang; Sun, Lanlan; Wang, Li

    2014-02-01

    Better understanding of the interaction between nanoparticles (NPs) and protein is the basis for biological and biomedical applications of NPs. Water-soluble fluorescent CdS NPs have been widely used in the biological and biomedical fields and the study on effect of CdS NPs size on conformation and enzymatic activity of protein might be very important in its application. In this work, the interaction of CdS NPs with different size with type II restriction endonuclease (EcoRI) were investigated by atomic force microscopy, transmission electron microscopy, UV-vis spectroscopy, fluorescence quenching method, CD spectra, laser scanning confocal microscopy and gel electrophoresis. It was found that the equilibrium constant (kD) as well as the cooperativity degree of CdS NPs-EcoRI binding (Hill constant, n) strongly depended on the CdS NPs size. The different curvature of CdS NPs surface could result in different changes of EcoRI conformation. The gel electrophoresis indicated that the decrease in α-helix content more or less affected the activity of EcoRI. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 76 FR 50771 - Submission for Review: RI 25-37, Evidence To Prove Dependency of a Child, 3206-0206

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-16

    ... MANAGEMENT Submission for Review: RI 25-37, Evidence To Prove Dependency of a Child, 3206-0206 AGENCY: U.S... Dependency of a Child. As required by the Paperwork Reduction Act of 1995 (Pub. L. 104-13, 44 U.S.C. chapter... techniques or other forms of information technology, e.g., permitting electronic submissions of...

  9. VizieR Online Data Catalog: LDN 1570 BV(RI)c polarisation and photometry (Eswaraiah+, 2013)

    NASA Astrophysics Data System (ADS)

    Eswaraiah, C.; Maheswar, G.; Pandey, A. K.; Jose, J.; Ramaprakash, A. N.; Bhatt, H. C.

    2013-05-01

    Polarimetric observations of the field containing L1570 were carried out on ten nights; namely, 23, 24, 25, 26 November 2009; 23, 24, 27, 28 December 2009 and 27, 31 December 2010 using the ARIES Imaging Polarimeter (AIMPOL) mounted at the Cassegrain focus of the 1.04-m Sampurnanand telescope (ST) of the Aryabhatta Research Institute of Observational sciences (ARIES), Manora Peak, India. The CCD optical photometric observations of the central region (RA=06:07:33.043; DE=+19:30:52.70, 2000) of L1570 were carried out in BVRI-bands using the 1.04-m ST on 27 November 2010. Results based on optical broad-band (BV(RI)c) photometric and polarimetric observations are presented. The polarization results of various polarized standard stars (taken from Schmidt et al. 1992AJ....104.1563S) are presented along with their standard values (Table 1). Rc-band polarization data of 127 stars along with their 2MASS data (JHKs) is presented (Table 2). Polarization and Serkowski fit parameters for the 42 stars with V(RI)c pass-band data is presented (Table 3). Polarization and Serkowski fit parameters for the 15 stars with BV(RI)c pass-band data is presented (Table 4). Photometric data of 144 stars with good signal-noise-ratio (with BV(RI)c and 2MASS JHKs-photometric errors <0.1mag) is also presented (Table 6). (6 data files).

  10. Quantitative measurement of absolute cell volume and intracellular integral refractive index (RI) with dual-wavelength digital holographic microscopy (DHM)

    NASA Astrophysics Data System (ADS)

    Boss, Daniel; Kühn, Jonas; Depeursinge, Christian; Magistretti, Pierre J.; Marquet, Pierre

    2012-06-01

    Quantitative Phase Imaging techniques including DHM have been applied recently in the field of cell imaging to monitor and quantify non-invasively dynamic cellular processes modifying cell morphology and/or content . Concretely, the DHM phase signal is highly sensitive to cell thickness and intracellular integral RI variations associated with transmembrane water movements. As net water flow across the cell membrane leads at the same time to changes in cell thickness and intracellular RI, the interpretation of phase signal variations remains difficult. To overcome this drawback, we have developed a Dual-wavelength Digital Holographic Microscopy (DHM) setup allowing to separately measure, with a single CCD camera acquisition, thickness and integral RI of living cells. The method is based on the use of an absorbing dye that enhances the refractive index dispersion of the extracellular medium. Practically, two significantly different phase signals can be obtained when measuring at two appropriate wavelengths. From the two phase measurements, both cell RI and thickness can be univocally determined.

  11. 77 FR 33007 - Submission for Review: Initial Certification of Full-Time School Attendance, RI 25-41

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ... MANAGEMENT Submission for Review: Initial Certification of Full-Time School Attendance, RI 25-41 AGENCY: U.S... Full-Time School Attendance. As required by the Paperwork Reduction Act of 1995, (Pub. L. 104-13, 44 U... other technological collection techniques or other forms of information technology, e.g.,...

  12. 76 FR 54810 - Submission for Review: 3206-0215, Verification of Full-Time School Attendance, RI 25-49

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-02

    ... MANAGEMENT Submission for Review: 3206-0215, Verification of Full-Time School Attendance, RI 25-49 AGENCY: U..., Verification of Full-Time School Attendance. As required by the Paperwork Reduction Act of 1995 (Pub. L. 104-13... technological collection techniques or other forms of information technology, e.g., permitting...

  13. EPA Awards $91,000 Environmental Education Grant to Woonasquatucket River Watershed Council in Providence, R.I.

    EPA Pesticide Factsheets

    The U.S. Environmental Protection Agency has awarded a $91,000 environmental education grant to the Woonasquatucket River Watershed Council in Providence, R.I. to work on a two-year effort to educate K-12 students in greater Providence about environmental

  14. 78 FR 28007 - Submission for Review: Representative Payee Application (RI 20-7) and Information Necessary for a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... Competency Determination (RI 30-3) AGENCY: U.S. Office of Personnel Management. ACTION: 30-Day Notice and request for comments. SUMMARY: The Retirement Services, Office of Personnel Management (OPM) offers the... Office of Personnel Management or sent via email to oira_submission@omb.eop.gov or faxed to (202)...

  15. 77 FR 73114 - Draft Written Re-Evaluation for Environmental Impact Statement: T.F. Green Airport, Warwick, RI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-07

    ... January 7, 2013. Issued on: November 26, 2012. Richard Doucette, Environmental Program Manager, Airports... Federal Aviation Administration Draft Written Re-Evaluation for Environmental Impact Statement: T.F. Green Airport, Warwick, RI AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of...

  16. Accelerated dissociation of IgE-FcεRI complexes by disruptive inhibitors actively desensitizes allergic effector cells.

    PubMed

    Eggel, Alexander; Baravalle, Günther; Hobi, Gabriel; Kim, Beomkyu; Buschor, Patrick; Forrer, Patrik; Shin, Jeoung-Sook; Vogel, Monique; Stadler, Beda M; Dahinden, Clemens A; Jardetzky, Theodore S

    2014-06-01

    The remarkably stable interaction of IgE with its high-affinity receptor FcεRI on basophils and mast cells is critical for the induction of allergic hypersensitivity reactions. Because of the exceptionally slow dissociation rate of IgE-FcεRI complexes, such allergic effector cells permanently display allergen-specific IgE on their surface and immediately respond to allergen challenge by releasing inflammatory mediators. We have recently described a novel macromolecular inhibitor that actively promotes the dissociation of IgE from FcεRI through a molecular mechanism termed facilitated dissociation. Here we assessed the therapeutic potential of this non-immunoglobulin-based IgE inhibitor E2_79, a designed ankyrin repeat protein (DARPin), as well as a novel engineered biparatopic DARPin bi53_79, and directly compared them with the established anti-IgE antibody omalizumab. IgE-FcεRI complex dissociation was analyzed in vitro by using recombinant proteins in ELISA and surface plasmon resonance, ex vivo by using human primary basophils with flow cytometry, and in vivo by using human FcεRI α-chain transgenic mice in a functional passive cutaneous anaphylaxis test. We show that E2_79-mediated removal of IgE from primary human basophils fully abrogates IgE-dependent cell activation and release of proinflammatory mediators ex vivo. Furthermore, we report that omalizumab also accelerates the dissociation of IgE from FcεRI, although much less efficiently than E2_79. Using the biparatopic IgE targeting approach, we further improved the disruptive potency of E2_79 by approximately 100-fold and show that disruptive IgE inhibitors efficiently prevent passive cutaneous anaphylaxis in mice expressing the human FcεRI α-chain. Our findings highlight the potential of such novel IgE inhibitors as important diagnostic and therapeutic tools for management of allergic diseases. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights

  17. Structure of FcγRI in complex with Fc reveals the importance of glycan recognition for high-affinity IgG binding

    PubMed Central

    Lu, Jinghua; Chu, Jonathan; Zou, Zhongcheng; Hamacher, Nels B.; Rixon, Mark W.; Sun, Peter D.

    2015-01-01

    Fc gamma receptor I (FcγRI) contributes to protective immunity against bacterial infections, but exacerbates certain autoimmune diseases. The sole high-affinity IgG receptor, FcγRI plays a significant role in immunotherapy. To elucidate the molecular mechanism of its high-affinity IgG binding, we determined the crystal structure of the extracellular domains of human FcγRI in complex with the Fc domain of human IgG1. FcγRI binds to the Fc in a similar mode as the low-affinity FcγRII and FcγRIII receptors. In addition to many conserved contacts, FcγRI forms additional hydrogen bonds and salt bridges with the lower hinge region of Fc. Unique to the high-affinity receptor-Fc complex, however, is the conformation of the receptor D2 domain FG loop, which enables a charged KHR motif to interact with proximal carbohydrate units of the Fc glycans. Both the length and the charge of the FcγRI FG loop are well conserved among mammalian species. Ala and Glu mutations of the FG loop KHR residues showed significant contributions of His-174 and Arg-175 to antibody binding, and the loss of the FG loop–glycan interaction resulted in an ∼20- to 30-fold decrease in FcγRI affinity to all three subclasses of IgGs. Furthermore, deglycosylation of IgG1 resulted in a 40-fold loss in FcγRI binding, demonstrating involvement of the receptor FG loop in glycan recognition. These results highlight a unique glycan recognition in FcγRI function and open potential therapeutic avenues based on antibody glycan engineering or small molecular glycan mimics to target FcγRI for certain autoimmune diseases. PMID:25561553

  18. Vaccinium angustifolium Root Extract Suppresses FcɛRI Expression in Human Basophilic KU812F Cells

    PubMed Central

    Shim, Sun Yup; Lee, Kyung Dong; Lee, Mina

    2017-01-01

    Vaccinium angustifolium, commonly known as the lowbush blueberry, is a rich source of flavonoids, with which various human physiological activities have been associated. The present study focuses on the investigation of the effect of the methanolic extract of V. angustifolium root extract (VAE) on high affinity immunoglobulin E receptor (FcɛRI) α chain antibody (CRA-1)-induced allergic reaction in human basophilic KU812F cells. The total phenolic content of VAE was found to be 170±1.9 mg gallic acid equivalents/g. Flow cytometry analysis revealed that the cell surface expression of FcɛRI was suppressed in a concentration-dependent manner upon culture with VAE. Reverse-transcriptase polymerase chain reaction analysis showed that the mRNA level of the FcɛRI α chain was reduced in a concentration-dependent manner as a result of VAE treatment. Western blot analysis revealed that the protein expression of FcɛRI and the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 were concentration-dependently inhibited by VAE. We determined that VAE inhibited anti-CRA-1-induced histamine release, in addition to the elevation of intracellular calcium concentration ([Ca2+]i), in a concentration-dependent manner. These results indicate that VAE may exert an anti-allergic effect via the inhibition of calcium influx and histamine release, which occurs as a result of the down-regulation of FcɛRI expression through inhibition of ERK 1/2 activation. PMID:28401082

  19. Vaccinium angustifolium Root Extract Suppresses FcɛRI Expression in Human Basophilic KU812F Cells.

    PubMed

    Shim, Sun Yup; Lee, Kyung Dong; Lee, Mina

    2017-03-01

    Vaccinium angustifolium, commonly known as the lowbush blueberry, is a rich source of flavonoids, with which various human physiological activities have been associated. The present study focuses on the investigation of the effect of the methanolic extract of V. angustifolium root extract (VAE) on high affinity immunoglobulin E receptor (FcɛRI) α chain antibody (CRA-1)-induced allergic reaction in human basophilic KU812F cells. The total phenolic content of VAE was found to be 170±1.9 mg gallic acid equivalents/g. Flow cytometry analysis revealed that the cell surface expression of FcɛRI was suppressed in a concentration-dependent manner upon culture with VAE. Reverse-transcriptase polymerase chain reaction analysis showed that the mRNA level of the FcɛRI α chain was reduced in a concentration-dependent manner as a result of VAE treatment. Western blot analysis revealed that the protein expression of FcɛRI and the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 were concentration-dependently inhibited by VAE. We determined that VAE inhibited anti-CRA-1-induced histamine release, in addition to the elevation of intracellular calcium concentration ([Ca(2+)]i), in a concentration-dependent manner. These results indicate that VAE may exert an anti-allergic effect via the inhibition of calcium influx and histamine release, which occurs as a result of the down-regulation of FcɛRI expression through inhibition of ERK 1/2 activation.

  20. The Tla protein of Porphyromonas gingivalis W50: a homolog of the RI protease precursor (PrpRI) is an outer membrane receptor required for growth on low levels of hemin.

    PubMed

    Aduse-Opoku, J; Slaney, J M; Rangarajan, M; Muir, J; Young, K A; Curtis, M A

    1997-08-01

    The prpR1 gene of Porphyromonas gingivalis W50 encodes the polyprotein precursor (PrpRI) of an extracellular arginine-specific protease. PrpRI is organized into four distinct domains (pro, alpha, beta, and gamma) and is processed to a heterodimeric protease (RI) which comprises the alpha and beta components in a noncovalent association. The alpha component contains the protease active site, whereas the beta component appears to have a role in adherence and hemagglutination processes. DNA sequences homologous to the coding region for the RI beta component are present at multiple loci on the P. gingivalis chromosome and may represent a family of related genes. In this report, we describe the cloning, sequence analysis, and characterization of one of these homologous loci isolated in plasmid pJM7. The 6,041-bp P. gingivalis DNA fragment in pJM7 contains a major open reading frame of 3,291 bp with coding potential for a protein with an Mr 118,700. An internal region of the deduced sequence (V304 to N768) shows 98% identity to the beta domain of PrpRI, and the recombinant product of pJM7 is immunoreactive with an antibody specific to the RI beta component. The N terminus of the deduced sequence has regional similarity to TonB-linked receptors which are frequently involved in periplasmic translocation of hemin, iron, colicins, or vitamin B12 in other bacteria. We have therefore designated this gene tla (TonB-linked adhesin). In contrast to the parent strain, an isogenic mutant of P. gingivalis W50 in which the tla was insertionally inactivated was unable to grow in medium containing low concentrations of hemin (<2.5 mg liter(-1)), and hemin-depleted cells of this mutant failed to respond to hemin in an agar diffusion plate assay. These data suggest a role for this gene product in hemin acquisition and utilization. Furthermore, the mutant produced significantly less arginine- and lysine-specific protease activities than the parent strain, indicating that there may be a

  1. Europlanet-RI: Access to Planetary Data, Tools, Models and Support Information

    NASA Astrophysics Data System (ADS)

    Schmidt, W.; Capria, M. T.; Chanteur, G.

    2012-04-01

    information is collected in the data access system of IDIS. By the end of the project in 2012 data from most planetary missions can be accessed, combined and correlated with spectral data bases for atmospheric gases and solids, laboratory measurements related to space observations and the results of model runs simulating the observations of different parameters around and at planets under various boundary conditions. The VO-structure will allow the access to these data through graphical interfaces including optimized visualization tools or alternatively through a command interface for further integration into other applications. Reference: [1] Details to IDIS and the Europlanet-RI via Web-site: http://www.idis.europlanet-ri.eu/ [2] Demonstrator implementation for Plasma-VO AMDA: http://cdpp-amda.cesr.fr/DDHTML/index.html [3] Demonstrator implementation for the IDIS-VO: http://www.idis-dyn.europlanet-ri.eu/vodev.shtml

  2. Molecular hydrogen suppresses FcepsilonRI-mediated signal transduction and prevents degranulation of mast cells.

    PubMed

    Itoh, Tomohiro; Fujita, Yasunori; Ito, Mikako; Masuda, Akio; Ohno, Kinji; Ichihara, Masatoshi; Kojima, Toshio; Nozawa, Yoshinori; Ito, Masafumi

    2009-11-27

    Molecular hydrogen ameliorates oxidative stress-associated diseases in animal models. We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the FcepsilonRI-associated Lyn and its downstream signal transduction, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide. We also found that inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells, indicating the presence of a feed-forward loop that potentiates the allergic responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial effect not by its radical scavenging activity but by modulating a specific signaling pathway. Effects of hydrogen in other diseases are possibly mediated by modulation of yet unidentified signaling pathways. Our studies also suggest that hydrogen is a gaseous signaling molecule like nitric oxide.

  3. Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity.

    PubMed

    Sarma, Ganapathy N; Kinderman, Francis S; Kim, Choel; von Daake, Sventja; Chen, Lirong; Wang, Bi-Cheng; Taylor, Susan S

    2010-02-10

    A-kinase anchoring proteins (AKAPs) regulate cyclic AMP-dependent protein kinase (PKA) signaling in space and time. Dual-specific AKAP 2 (D-AKAP2) binds to the dimerization/docking (D/D) domain of both RI and RII regulatory subunits of PKA with high affinity. Here we have determined the structures of the RIalpha D/D domain alone and in complex with D-AKAP2. The D/D domain presents an extensive surface for binding through a well-formed N-terminal helix, and this surface restricts the diversity of AKAPs that can interact. The structures also underscore the importance of a redox-sensitive disulfide in affecting AKAP binding. An unexpected shift in the helical register of D-AKAP2 compared to the RIIalpha:D-AKAP2 complex structure makes the mode of binding to RIalpha novel. Finally, the comparison allows us to deduce a molecular explanation for the sequence and spatial determinants of AKAP specificity.

  4. The R.I. Pimenov unified gravitation and electromagnetism field theory as semi-Riemannian geometry

    SciTech Connect

    Gromov, N. A.

    2009-05-15

    More than forty years ago R.I. Pimenov introduced a new geometry-semi-Riemannian one-as a set of geometrical objects consistent with a fibering pr: M{sub n} {yields} M{sub m}. He suggested the heuristic principle according to which the physically different quantities (meter, second, Coulomb, etc.) are geometrically modelled as space coordinates that are not superposed by automorphisms. As there is only one type of coordinates in Riemannian geometry and only three types of coordinates in pseudo-Riemannian one, a multiple-fibered semi-Riemannian geometry is the most appropriate one for the treatment of more than three different physical quantities as unified geometrical field theory. Semi-Euclidean geometry {sup 3}R{sub 5}{sup 4} with 1-dimensional fiber x{sup 5} and 4-dimensional Minkowski space-time as a base is naturally interpreted as classical electrodynamics. Semi-Riemannian geometry {sup 3}V{sub 5}{sup 4} with the general relativity pseudo-Riemannian space-time {sup 3}V{sub 4}, and 1-dimensional fiber x{sup 5}, responsible for the electromagnetism, provides the unified field theory of gravitation and electromagnetism. Unlike Kaluza-Klein theories, where the fifth coordinate appears in nondegenerate Riemannian or pseudo-Riemannian geometry, the theory based on semi-Riemannian geometry is free from defects of the former. In particular, scalar field does not arise.

  5. The EnRiCH Community Resilience Framework for High-Risk Populations

    PubMed Central

    O'Sullivan, Tracey L.; Kuziemsky, Craig E.; Corneil, Wayne; Lemyre, Louise; Franco, Zeno

    2014-01-01

    Introduction: Resilience has been described in many ways and is inherently complex. In essence, it refers to the capacity to face and do well when adversity is encountered. There is a need for empirical research on community level initiatives designed to enhance resilience for high-risk groups as part of an upstream approach to disaster management. In this study, we address this issue, presenting the EnRiCH Community Resilience Framework for High-Risk Populations. Methods: The framework presented in this paper is empirically-based, using qualitative data from focus groups conducted as part of an asset-mapping intervention in five communities in Canada, and builds on extant literature in the fields of disaster and emergency management, health promotion, and community development. Results: Adaptive capacity is placed at the centre of the framework as a focal point, surrounded by four strategic areas for intervention (awareness/communication, asset/resource management, upstream-oriented leadership, and connectedness/engagement). Three drivers of adaptive capacity (empowerment, innovation, and collaboration) cross-cut the strategic areas and represent levers for action which can influence systems, people and institutions through expansion of asset literacy. Each component of the framework is embedded within the complexity and culture of a community. Discussion: We present recommendations for how this framework can be used to guide the design of future resilience-oriented initiatives with particular emphasis on inclusive engagement across a range of functional capabilities. PMID:25642373

  6. 76 FR 82000 - Submission for Review: Request for Change to Unreduced Annuity, RI 20-120

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ...The Retirement Services, Office of Personnel Management (OPM) offers the general public and other federal agencies the opportunity to comment on a revised information collection request (ICR) 3206-0245, Request for Change to Unreduced Annuity, RI 20-120. As required by the Paperwork Reduction Act of 1995, (Pub. L. 104-13, 44 U.S.C. chapter 35) as amended by the Clinger-Cohen Act (Pub. L. 104-106), OPM is soliciting comments for this collection. The information collection was previously published in the Federal Register on June 7, 2011 at Volume 76 FR 32997 allowing for a 60-day public comment period. No comments were received for this information collection. The purpose of this notice is to allow an additional 30 days for public comments. The Office of Management and Budget is particularly interested in comments that: 1. Evaluate whether the proposed collection of information is necessary for the proper performance of functions of the agency, including whether the information will have practical utility; 2. Evaluate the accuracy of the agency's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; 3. Enhance the quality, utility, and clarity of the information to be collected; and 4. Minimize the burden of the collection of information on those who are to respond, including through the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology, e.g., permitting electronic submissions of responses.

  7. Microwave-optical study of an As(III) derivative of Eco RI methylase

    NASA Astrophysics Data System (ADS)

    Maki, August H.; Tsao, Desiree H. H.

    1991-06-01

    The authors report on the formation of an unusually stable As(III)-thiolate with a single 'high- affinity' cysteine (Cys) of E. coli RI methylase, monitored via its influence on a neighboring tryptophan (Trp) residue in the enzyme structure. The binding was studied by Trp fluorescence quenching, low temperature phosphorescence and triplet state optically detected magnetic resonance (ODMR) of the intrinsic Trp residue(s). The affected Trp is subject to an external heavy atom effect (HAE) from arsenic, quenching its fluorescence and reducing its phosphorescence lifetime from 6 sec to ca. 70 msec. The enzyme high affinity binding site has at least 27 times the affinity for As(III) as does a typical sulfhydryl reagent, HSCH2CONH2. The accessibility of the arsenical to this Cys site was reduced upon formation of the ternary complex methylase-DNA-sinefungin, suggesting a local conformational change in the enzyme when DNA is bound. The enzymatic activity assay of methylase is not affected by the addition of a 1:1 molar ratio of the arsenical to the methylase, but incubation with an excess of As(III) causes complete loss of enzymatic activity. This suggests that the high- affinity Cys residue is not a part of the active site of the enzyme, but the addition of a molar excess of arsenical to the enzyme derivatizes the Cys residue known to be located in the active site.

  8. Performance of ion surfing rf-carpets for RI beam gas catcher

    NASA Astrophysics Data System (ADS)

    Arai, Fumiya; Ito, Yuta; Katayama, Ichirou; Schury, Peter; Sonoda, Tetsu; Wada, Michiharu; Wollnik, Hermann

    2014-09-01

    High-energy RI beams produced in-flight by fragmentation or fission are used in ion trap-based precision experiments after being stopped in a gas catcher. The stopped ions can be extracted from the gas catcher as a low energy ion beam. In order to transport and extract ions quickly and efficiently, an rf-carpet (RFC) method utilizing a dc potential gradient has been the standard technique. However, such a method is restricted by the transport time to longer half-life isotopes due to the maximum dc gradient that can be supported before electric discharges occur in the gas catcher. To avoid that limitation, a hybrid technique wherein the dc gradient is replaced by a traveling potential wave was proposed, called ``ion surfing''. Recently, we have demonstrated ion extraction using a circular RFC under low and intermediate pressures. For the first time we demonstrated the ion extraction using an rf-carpet in high-pressure He gas. An efficiency of nearly 100% was obtained at 200 mbar He gas pressure for K+ ions.

  9. The University of Jaén Astronomical Observatory

    NASA Astrophysics Data System (ADS)

    Martí, Josep; Luque-Escamilla, Pedro L.; García-Hernández, María T.

    2017-01-01

    We present a description and instrumental characterization of the photometric equipment of the Astronomical Observatory of the University of Jaén. The observatory hosts a 41 cm automated telescope inside a 4 m dome located at the university main campus, in the outskirts of the city of Jaén (Spain). This facility is used for educational, outreach and occasional scientific research on bright stellar objects. Despite the observatory location in a light polluted urban area, its performance for differential photometry studies has proven to be very acceptable. The discovery of the Be star LS I +5979 as a peculiar eclipsing binary system is so far the most relevant achievement.

  10. A gas circulation and purification system for gas-cell-based low-energy RI-beam production

    SciTech Connect

    Sonoda, T.; Wada, M.; Katayama, I.; Kojima, T. M.; Reponen, M.; Tsubota, T.

    2016-06-15

    A gas circulation and purification system was developed at the RIKEN Radioactive Isotope Beam Factory that can be used for gas-cell-based low-energy RI-beam production. A high-flow-rate gas cell filled with one atmosphere of buffer gas (argon or helium) is used for the deceleration and thermalization of high-energy RI-beams. The exhausted buffer gas is efficiently collected using a compact dry pump and returned to the gas cell with a recovery efficiency of >97%. The buffer gas is efficiently purified using two gas purifiers as well as collision cleaning, which eliminates impurities in the gas. An impurity level of one part per billion is achieved with this method.

  11. A gas circulation and purification system for gas-cell-based low-energy RI-beam production

    NASA Astrophysics Data System (ADS)

    Sonoda, T.; Tsubota, T.; Wada, M.; Katayama, I.; Kojima, T. M.; Reponen, M.

    2016-06-01

    A gas circulation and purification system was developed at the RIKEN Radioactive Isotope Beam Factory that can be used for gas-cell-based low-energy RI-beam production. A high-flow-rate gas cell filled with one atmosphere of buffer gas (argon or helium) is used for the deceleration and thermalization of high-energy RI-beams. The exhausted buffer gas is efficiently collected using a compact dry pump and returned to the gas cell with a recovery efficiency of >97%. The buffer gas is efficiently purified using two gas purifiers as well as collision cleaning, which eliminates impurities in the gas. An impurity level of one part per billion is achieved with this method.

  12. Photochemistry of a dual-bacteriorhodopsin system in Haloarcula marismortui: HmbRI and HmbRII.

    PubMed

    Tsai, Fu-Kuo; Fu, Hsu-Yuan; Yang, Chii-Shen; Chu, Li-Kang

    2014-07-03

    Recently, a dual-bacteriorhodopsin system, containing HmbRI and HmbRII, has been found in Haloarcula marismortui (Mol. Microbiol. 2013, 88, 551-561), and the light-driven proton pump activities were intrinsically different in a wide pH range. Compared with bacteriorhodopsin in H. salinarum (HsbR), the identical steady-state absorption contours of HsbR and HmbRs in the visible range indicated similarities in the retinal pocket. In addition, other reactive residues, including the proton relay channel, proton release group, and proton collecting funnel at the cytoplasm, were mostly conserved. We employed transient absorption spectroscopy and global analysis to characterize the photocycle intermediates and kinetics of HmbRI and HmbRII in the pH range of 4-8. The features of the time-resolved difference spectra of HmbRI indicated that the photocycle of HmbRI mainly followed the conventional pathway, including intermediates M, N, and O. A minute bypassed pathway from intermediate M needed to be included to better match the experimental data. The corresponding intermediate M' is attributed to the all-trans deprotonated Schiff base retinal, indicating the occurrence of retinal reisomerization prior to the reprotonation of the deprotonated Schiff base following the decay of intermediate M. Regarding HmbRII, its photocycle only followed the intermediates M and N, without intermediate O. The plausible molecular mechanisms, including the effects of the lengths of the loops and the distribution of the charged residues in the bacterio-opsin interior, were proposed to explain the differences in the photocycles. The pH-dependent photocycles were also investigated, and the results supported our proposed mechanism. Unravelling the photocycles of the HmbRs in the Haloarcula marismortui provided evidence that not only expanding the functional pH ranges but also the turnover kinetics are the strategies of the dual-bR system in the evolution of microbes in extreme environments.

  13. Repeated FcεRI triggering reveals modified mast cell function related to chronic allergic responses in tissue.

    PubMed

    Suurmond, Jolien; Habets, Kim L L; Tatum, Zuotian; Schonkeren, Joris J; Hoen, Peter A C 't; Huizinga, Tom W J; Laros, Jeroen F J; Toes, René E M; Kurreeman, Fina

    2016-09-01

    Activation of mast cells through FcεRI plays an important role in acute allergic reactions. However, little is known about the function of mast cells in patients with chronic allergic inflammation or the effect of repeated FcεRI triggering occurring in such responses. We aimed to identify changes in mast cell function after repeated FcεRI triggering and to correlate these changes to chronic allergic responses in tissue. Human cord blood-derived mast cells were treated for 2 weeks with anti-IgE. The function of naive or treated mast cells was analyzed by means of RNA sequencing, quantitative RT-PCR, flow cytometry, and functional assays. Protein secretion was measured with ELISAs and multiplex assays. We observed several changes in mast cell function after repeated anti-IgE triggering. Although the acute response was dampened, we identified 289 genes significantly upregulated after repeated anti-IgE. Most of these genes (84%) were not upregulated after a single anti-IgE stimulus, indicating a significantly different response mode characterized by increased antigen presentation, response to bacteria, and chemotaxis. Changes in mast cell function were related to changes in expression of the transcription factors RXRA and BATF and others. Importantly, we found a substantial overlap between genes upregulated after repeated anti-IgE triggering and genes upregulated in tissue from patients with chronic allergy, in particular those of patients with chronic rhinosinusitis. Our study provides evidence for intrinsic modulation of mast cell function on repeated FcεRI-mediated activation. The overlap with gene expression in tissues is suggestive of a direct link between repeated IgE-mediated activation of mast cells and chronic allergy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL.

    PubMed

    Zhu, Minghua; Liu, Yan; Koonpaew, Surapong; Granillo, Olivia; Zhang, Weiguo

    2004-10-18

    Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcepsilonRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcepsilonRI-mediated signaling than LAT(-/-) mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcepsilonRI-mediated signaling.

  15. Parasitic production of slow RI-beam from a projectile fragment separator by ion guide Laser Ion Source (PALIS)

    NASA Astrophysics Data System (ADS)

    Sonoda, Tetsu

    2009-10-01

    The projectile fragment separator BigRIPS of RIBF at RIKEN provides a wide variety of short-lived radioactive isotope (RI) ions without restrictions on their lifetime or chemical properties. A universal slow RI-beam facility (SLOWRI) to decelerate the beams from BigRIPS using an RF-carpet ion guide has been proposed as a principal facility of RIBF. However, beam time at such a modern accelerator facility is always limited and operational costs are high. We therefore propose an additional scheme as a complementary option to SLOWRI to drastically enhance the usability of such an expensive facility. In BigRIPS, a single primary beam produces thousands of isotopes but only one isotope is used for an experiment while the other >99.99% of isotopes are simply dumped in the slits or elsewhere in the fragment separator. We plan to locate a compact gas cell with 1 bar Ar at the slits. The thermalized ions in the cell will be quickly neutralized and transported to the exit by gas flow and resonantly re-ionized by lasers. Such low energy RI-beams will always be provided without any restriction to the main experiment. It will allow us to run parasitic experiments for precision atomic or decay spectroscopy, mass measurements. Furthermore, the resonance ionization in the cell itself can be used for high-sensitive laser spectroscopy, which will expand our knowledge of the ground state property of unstable nuclei.

  16. Integration of human health and ecological risk assessments in the RI/FS process. Part A: Overview and methods

    SciTech Connect

    Pueuler, E.A.; Clarkson, J.R.; Mazzera, D.M.; Cura, J.K.; Menzie, C.A.; Morrisey, D.; Sarmiento, R.

    1995-12-31

    In the US, human health and ecological risk assessments are required components of remedial investigation/feasibility study (RI/FS) efforts at Superfund sites. However, these assessments are often conducted as independent evaluations rather than being optimally integrated into the RI/FS process. The purpose of this presentation is to describe how these independent assessments can be coordinated and ultimately used together in remedial action decision-making. Part A of this presentation will provide an overview of the approach and the methods used to integrate the human health and ecological risk assessments. An RI/FS conducted at a coastal Superfund site will be used to illustrate this integrated evaluation of potential human and ecological risk. Initial investigation of soils, sediment, water, and fish tissue data at the site indicated potential for adverse effects to human health and potential ecological receptors. A multi-component field investigation was designed to allow qualitative and quantitative evaluation of the potential for adverse impacts to biota at the site. The field investigation elements were primarily focused on acquiring data to support the ecological assessment. However, additional consideration was given to the concurrent collection of data to supplement human health risk decision-making. This included analyses of fish samples analyzed for whole-body and edible portions. The results were combined with site-specific field observations on the use and activities at the site by local human and ecological populations in order to support conservative, yet realistic site-specific exposure assumptions.

  17. Model of interaction of the IL-1 receptor accessory protein IL-1RAcP with the IL-1beta/IL-1R(I) complex.

    PubMed

    Casadio, R; Frigimelica, E; Bossù, P; Neumann, D; Martin, M U; Tagliabue, A; Boraschi, D

    2001-06-15

    A preliminary model has been calculated for the activating interaction of the interleukin 1 receptor (IL-1R) accessory protein IL-1RAcP with the ligand/receptor complex IL-1beta/IL-1R(I). First, IL-1RAcP was modeled on the crystal structure of IL-1R(I) bound to IL-1beta. Then, the IL-1RAcP model was docked using specific programs to the crystal structure of the IL-1beta/IL-1R(I) complex. Two types of models were predicted, with comparable probability. Experimental data obtained with the use of IL-1beta peptides and antibodies, and with mutated IL-1beta proteins, support the BACK model, in which IL-1RAcP establishes contacts with the back of IL-1R(I) wrapped around IL-1beta.

  18. Human eosinophils express the high affinity IgE receptor, FcεRI, in bullous pemphigoid.

    PubMed

    Messingham, Kelly N; Holahan, Heather M; Frydman, Alexandra S; Fullenkamp, Colleen; Srikantha, Rupasree; Fairley, Janet A

    2014-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease mediated by autoantibodies targeting BP180 (type XVII collagen). Patient sera and tissues typically have IgG and IgE autoantibodies and elevated eosinophil numbers. Although the pathogenicity of the IgE autoantibodies is established in BP, their contribution to the disease process is not well understood. Our aims were two-fold: 1) To establish the clinical relationships between total and BP180-specific IgE, eosinophilia and other markers of disease activity; and 2) To determine if eosinophils from BP patients express the high affinity IgE receptor, FcεRI, as a potential mechanism of action for IgE in BP. Our analysis of 48 untreated BP patients revealed a correlation between BP180 IgG and both BP180 IgE and peripheral eosinophil count. Additionally, we established a correlation between total IgE concentration and both BP180 IgE levels and eosinophil count. When only sera from patients (n = 16) with total IgE ≥ 400 IU/ml were analyzed, BP180 IgG levels correlated with disease severity, BP230 IgG, total circulating IgE and BP180 IgE. Finally, peripheral eosinophil count correlated more strongly with levels of BP180 IgE then with BP180 IgG. Next, eosinophil FcεRI expression was investigated in the blood and skin using several methods. Peripheral eosinophils from BP patients expressed mRNA for all three chains (α, β and γ) of the FcεRI. Surface expression of the FcεRIα was confirmed on both peripheral and tissue eosinophils from most BP patients by immunostaining. Furthermore, using a proximity ligation assay, interaction of the α- and β-chains of the FcεRI was observed in some biopsy specimens, suggesting tissue expression of the trimeric receptor form in some patients. These studies provide clinical support for the relevance of IgE in BP disease and provide one mechanism of action of these antibodies, via binding to the FcεRI on eosinophils.

  19. The efficacy of an IL-1alpha vaccine depends on IL-1RI availability and concomitant myeloid-derived suppressor cell reduction.

    PubMed

    Weiss, Tobias; Vitacolonna, Mario; Zöller, Margot

    2009-01-01

    We recently reported that tumor-derived interleukin (IL)-1beta strongly promotes tumor growth by inducing myeloid-derived suppressor cell (MDSC) and regulatory T-cell (T(reg)) expansion. To see whether redirection of an immune response can be achieved through immune response-supporting IL-1alpha application, IL-1RI competent (IL-1RI(comp)) and IL-1RI-deficient (IL-1RI(-/-)) mice received IL-1alpha cDNA-transformed attenuated Salmonella typhimurium (SL-IL-1alpha) and/or lysates from methycholanthrene-induced IL-1(comp) or IL-1(-/-) fibrosarcoma cells. Vaccination with SL-IL-1alpha and/or tumor lysate exerted only a minor effect on the survival of IL-1alpha/beta(-/-) and none on IL-1alpha(comp) tumor-bearing mice despite induction of a potent antitumor response, that was overridden by intratumoral and systemic expansion of MDSC. Application of all-trans-retinoic acid together with anti-CD25 efficiently coped with MDSC and T(reg) expansion. Vaccination concomitantly with application of all-trans-retinoic acid and anti-CD25 treatment significantly increased the survival time and rate of IL-1alpha/beta(comp), but even of IL-1alpha(-/-)beta(comp) IL-1RI(comp) tumor-bearing mice. Instead, in IL-1RI(-/-) mice, though MDSC expansion was weaker, SL-IL-1alpha application hardly displayed any therapeutic efficacy, which implies signal transduction through IL-1alpha binding to the IL-1RI as an essential component for immune response induction. Taken together, IL-1alpha can efficiently support tumor vaccination, as far as expansion of MDSC and T(reg) is controlled. However, care should be taken to interfere with MDSC expansion/activation not through a blockade of the IL-1RI, which is the preferential target of IL-1alpha.

  20. Genetic variability to diet-induced hippocampal dysfunction in BXD recombinant inbred (RI) mouse strains

    PubMed Central

    Xue, Yueqiang; Li, JingJing; Yan, Lei; Lu, Lu; Liao, Francesca-Fang

    2016-01-01

    Evidence has emerged suggesting that diet-induced obesity can have a negative effect on cognitive function. Here, we exploited a mouse genetic reference population to look for the linkage between these two processes on a genome-wide scale. The focus of this report is to determine whether the various BXD RI strains exhibited different behavioral performance and hippocampal function under high fat dietary (HFD) condition. We quantified genetic variation in body weight gain and consequent influences on behavioral tests in a cohort of 14 BXD strains of mice (8–12 mice/strain, n=153), for which we have matched data on gene expression and neuroanatomical changes in the hippocampus. It showed that BXD66 was the most susceptible, whereas BXD77 was the least susceptible strain to dietary influences. The performance of spatial reference memory tasks was strongly correlated with body weight gain (P<0.05). The obesity-prone strains displayed more pronounced spatial memory defects compared to the obesity-resistant strains. These abnormalities were associated with neuro inflammation, synaptic dysfunction, and neuronal loss in the hippocampus. The biological relevance of DSCAM gene polymorphism was assessed using the trait correlation analysis tool in Genenet work. Further more, a significant strain-dependent gene expression difference of DSCAM was detected in the hippocampus of obese BXD strains by real-time quantitative PCR. In conclusion, a variety of across-strain hippocampal alterations and genetic predispositions to diet-induced obesity were found in a set of BXD strains. The obesity-prone and obesity-resistant lines we have identified should be highly useful to study the molecular genetics of diet-induced cognitive decline. PMID:26092713

  1. Measuring and monitoring in the South African Kha Ri Gude mass literacy campaign

    NASA Astrophysics Data System (ADS)

    McKay, Veronica

    2015-06-01

    After many previous failed attempts to reach illiterate adults, the award-winning South African Kha Ri Gude mass literacy campaign, launched in 2008, undertook to ensure that learners seized the opportunity to learn - for many adults, this was a "last chance". Written from an insider perspective by the campaign's founding Chief Executive Officer, this article outlines the features which contributed to its success despite the many challenges it initially faced. The author outlines the social and legislative backdrop, notably the South African National Qualifications Framework (NQF) providing the scaffold for the continuum of adult learning and the assessment of learning outcomes, and examines the various components which influenced the design of the campaign. She focuses, in particular, on the learning outcomes measurement model tailored to the campaign's specific context, namely a structured and standardised learner assessment portfolio (LAP). Designed as a tool to be administered universally for both formative and diagnostic purposes, the portfolio enables continuous assessment, forming an integral part of the process of learning and teaching. After many initial challenges encountered in introducing this mode of learner assessment, it was eventually institutionalised and found to be a non-threatening way of assessing learning outcomes while also functioning as a tool for monitoring and ensuring accountability in the campaign. This article gives an account of the development considerations and explains the role of the assessment process within the broader context of the campaign. It also refers to ways in which the mass-based assessments were administered under difficult campaign conditions with a view to assessing for learning.

  2. Molecular and morphological diversity of Narragansett Bay (RI, USA) Ulva (Ulvales, Chlorophyta) populations.

    PubMed

    Guidone, Michele; Thornber, Carol; Wysor, Brian; O'Kelly, Charles J

    2013-10-01

    Macroalgal bloom-forming species occur in coastal systems worldwide. However, due to overlapping morphologies in some taxa, accurate taxonomic assessment and classification of these species can be quite challenging. We investigated the molecular and morphological characteristics of 153 specimens of bloom-forming Ulva located in and around Narragansett Bay, RI, USA. We analyzed sequences of the nuclear internal transcribed spacer 1 region (ITS1) and the chloroplast-encoded rbcL; based on the ITS1 data, we grouped the specimens into nine operational taxonomic units (OTUs). Eight of these OTUs have been previously reported to exist, while one is novel. Of the eight OTUs, all shared sequence identity with previously published sequences or differed by less than 1.5% sequence divergence for two molecular markers. Previously, 10 species names were reported for Ulva in Rhode Island (one blade and nine tube-forming species) based upon morphological classification alone. Of our nine OTUs, three contained blade-forming specimens (U. lactuca, U. compressa, U. rigida), one OTU had a blade with a tubular stipe, and six contained unbranched and/or branched tubular morphologies (one of these six, U. compressa, had both a blade and a tube morphology). While the three blade-forming OTUs in Narragansett Bay can frequently be distinguished by careful observations of morphological characteristics, and spatial/temporal distribution, it is much more difficult to distinguish among the tube-forming specimens based upon morphology or distribution alone. Our data support the molecular species concept for Ulva, and indicate that molecular-based classifications of Ulva species are critical for proper species identification, and subsequent ecological assessment or mitigation of Ulva blooms.

  3. In vivo effector functions of high-affinity mouse IgG receptor FcγRI in disease and therapy models.

    PubMed

    Gillis, Caitlin M; Zenatti, Priscila P; Mancardi, David A; Beutier, Héloïse; Fiette, Laurence; Macdonald, Lynn E; Murphy, Andrew J; Celli, Susanna; Bousso, Philippe; Jönsson, Friederike; Bruhns, Pierre

    2016-10-10

    Two activating mouse IgG receptors (FcγRs) have the ability to bind monomeric IgG, the high-affinity mouse FcγRI and FcγRIV. Despite high circulating levels of IgG, reports using FcγRI(-/-) or FcγRIV(-/-) mice or FcγRIV-blocking antibodies implicate these receptors in IgG-induced disease severity or therapeutic Ab efficacy. From these studies, however, one cannot conclude on the effector capabilities of a given receptor, because different activating FcγRs possess redundant properties in vivo, and cooperation between FcγRs may occur, or priming phenomena. To help resolve these uncertainties, we used mice expressing only FcγRI to determine its intrinsic properties in vivo. FcγRI(only) mice were sensitive to IgG-induced autoimmune thrombocytopenia and anti-CD20 and anti-tumour immunotherapy, but resistant to IgG-induced autoimmune arthritis, anaphylaxis and airway inflammation. Our results show that the in vivo roles of FcγRI are more restricted than initially reported using FcγRI(-/-) mice, but confirm effector capabilities for this high-affinity IgG receptor in vivo.

  4. Activated IL-1RI Signaling Pathway Induces Th17 Cell Differentiation via Interferon Regulatory Factor 4 Signaling in Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Sha, Yonggang; Markovic-Plese, Silva

    2016-01-01

    IL-1β plays a crucial role in the differentiation of human Th17 cells. We report here that IL-1RI expression is significantly increased in both naive and memory CD4+ T cells derived from relapsing-remitting multiple sclerosis (RR MS) patients in comparison to healthy controls. Interleukin 1 receptor (IL-1R)I expression is upregulated in the in vitro-differentiated Th17 cells from RR MS patients in comparison to the Th1 and Th2 cell subsets, indicating the role of IL-1R signaling in the Th17 cell differentiation in RR MS. When IL-1RI gene expression was silenced using siRNA, human naive CD4+ T cells cultured in the presence of Th17-polarizing cytokines had a significantly decreased expression of interleukin regulatory factor 4 (IRF4), RORc, IL-17A, IL-17F, IL-21, IL-22, and IL-23R genes, confirming that IL-1RI signaling induces Th17 cell differentiation. Since IL-1R gene expression silencing inhibited IRF4 expression and Th17 differentiation, and IRF4 gene expression silencing inhibited Th17 cell differentiation, our results indicate that IL-1RI induces human Th17 cell differentiation in an IRF4-dependant manner. Our study has identified that IL-1RI-mediated signaling pathway is constitutively activated, leading to an increased Th17 cell differentiation in IRF4-dependent manner in patients with RR MS. PMID:27965670

  5. Cloning and characterization of a cDNA of cro rI from the white pine blister rust fungus Cronartium ribicola.

    PubMed

    Yu, Xueshu; Ekramoddoullah, Abul K M; Taylor, Doug W; Piggott, Nina

    2002-02-01

    White pine blister rust (WPBR) is caused by the fungus Cronartium ribicola which has five spore stages on two unrelated hosts, the five-needle pines and Ribes spp. Recently, during the molecular analysis of the proteins and genes involved in host-pathogen interaction, the WPBR fungal protein Cro rI was identified in infected white pine tissues. To further characterize Cro rI, an expression cDNA library from poly(A)(+) mRNA of C. ribicola axenic mycelial culture was constructed and immunoscreened and the cDNA was cloned. Sequence analysis indicated an open reading frame of 462 bases, which encodes a protein of 153 amino acid residues with a molecular mass of 16.7 kDa and a predicted isoelectric point (pI) of 8.93. Based on the N-terminal amino acid sequences of Cro rI, the secreted portion of Cro rI protein should be 136 amino acids long with several putative posttranslational modification sites and a molecular mass of 14.8 kDa. The predicted pI for the secreted portion was 9.34. The predicted N-terminal signal peptide was 17 amino acids long. The N-terminal 42-amino acid sequence of the predicted mature protein (secreted portion) was identical to the amino terminal sequence of Cro rI that was previously determined. Southern blot hybridizations indicated that the C. ribicola genome contained at least two copies of the cro rI gene. Isolation of the genomic PCR fragment, which was approximately 400 bp longer than the cDNA, and subsequent cloning and sequencing analyses confirmed that there were three introns within the coding regions. Western immunoblot analyses revealed that Cro rI protein accumulated in large amounts only in the infected white pine tissues while no trace was detectable in the alternate Ribes stage or the five different spores, suggesting a critical role of Cro rI in the haploid stage of the fungus (in pine). The translocation of Cro rI was only found to occur in cankered trees, and not in the young infected seedlings. The implications of Cro rI in

  6. Increased SA in NPR1-silenced plants antagonizes JA and JA-dependent direct and indirect defenses in herbivore-attacked Nicotiana attenuata in nature.

    PubMed

    Rayapuram, Cbgowda; Baldwin, Ian T

    2007-11-01

    The phytohormone jasmonic acid (JA) is known to mediate herbivore resistance, while salicylic acid (SA) and non-expressor of PR-1 (NPR1) mediate pathogen resistance in many plants. Herbivore attack on Nicotiana attenuata elicits increases in JA and JA-mediated defenses, but also increases SA levels and Na-NPR1 transcripts from the plant's single genomic copy. SA treatment of wild-type plants increases Na-NPR1 and Na-PR1 transcripts. Plants silenced in NPR1 accumulation by RNAi (ir-npr1) are highly susceptible to herbivore and pathogen attack when planted in their native habitat in Utah. They are also impaired in their ability to attract Geocorus pallens predators, due to their decreased ability to release cis-alpha-bergamotene, a JA-elicited volatile 'alarm call'. In the glasshouse, Spodoptera exigua larvae grew better on ir-npr1 plants, which had low levels of JA, JA-isoleucine/leucine, lipoxygenase-3 (LOX3) transcripts and JA-elicited direct defense metabolites (nicotine, caffeoyl putrescine and rutin), but high levels of SA and isochorismate synthase (ICS) transcripts, suggesting de novo biosynthesis of SA. A microarray analysis revealed downregulation of many JA-elicited genes and upregulation of SA biosynthetic genes. JA treatment restored nicotine levels and resistance to S. exigua in ir-npr1 plants. We conclude that, during herbivore attack, NPR1 negatively regulates SA production, allowing the unfettered elicitation of JA-mediated defenses; when NPR1 is silenced, the elicited increases in SA production antagonize JA and JA-related defenses, making the plants susceptible to herbivores.

  7. Free Energy Analysis of Protein-DNA Binding: The EcoRI Endonuclease-DNA Complex

    NASA Astrophysics Data System (ADS)

    Jayaram, B.; McConnell, K. J.; Dixit, Surjit B.; Beveridge, D. L.

    1999-05-01

    A detailed theoretical analysis of the thermodynamics and functional energetics of protein-DNA binding in the EcoRI endonuclease-DNA complex is presented. The standard free energy of complexation is considered in terms of a thermodynamic cycle of seven distinct steps decomposed into a total of 24 well-defined components. The model we employ involves explicit all-atom accounts of the energetics of structural adaptation of the protein and the DNA upon complex formation; the van der Waals and electrostatic interactions between the protein and the DNA; and the electrostatic polarization and screening effects, van der Waals components, and cavitation effects of solvation. The ion atmosphere of the DNA is described in terms of a counterion condensation model combined with a Debye-Huckel treatment of added salt effects. Estimates of entropy loss due to decreased translational and rotational degrees of freedom in the complex relative to the unbound species based on classical statistical mechanics are included, as well as corresponding changes in the vibrational and configurational entropy. The magnitudes and signs of the various components are estimated from the AMBER parm94 force field, generalized Born theory, solvent accessibility measures, and empirical estimates of quantities related to ion release. The calculated standard free energy of formation, -11.5 kcal/mol, agrees with experiment to within 5 kcal/mol. This net binding free energy is discerned to be the resultant of a balance of several competing contributions associated with chemical forces as conventionally defined, with 10 out of 24 terms favoring complexation. Contributions to binding compounded from subsets of the 24 components provide a basis for advancing a molecular perspective of binding in terms of structural adaptation, electrostatics, van der Waals interactions, hydrophobic effects, and small ion reorganization and release upon complexation. The van der Waals interactions and water release favor

  8. First flight of SMASH, the SwRI Miniature Assembly for Solar Hard X-rays

    NASA Astrophysics Data System (ADS)

    Caspi, Amir; Laurent, Glenn Thomas; Shoffner, Michael; Higuera Caubilla, David; Meurisse, Jeremie; Smith, Kelly; Shih, Albert Y.; Saint-Hilaire, Pascal; DeForest, Craig; Mansour, Nagi N.; Hathaway, David H.

    2016-05-01

    The SwRI Miniature Assembly for Solar Hard X-rays (SMASH) was successfully flown from Antarctica in January (19-30) 2016, as a piggy-back instrument on the Gamma-Ray Imager/Polarimeter for Solar flares (GRIPS) high altitude balloon payload. SMASH is a technological demonstration of a new miniaturized hard X-ray (HXR) detector for use on CubeSats and other small spacecraft, including the proposed CubeSat Imaging X-ray Solar Spectrometer (CubIXSS).HXRs are the observational signatures of energetic processes on the Sun, including plasma heating and particle acceleration. One of the goals of CubIXSS will be to address the question of how plasma is heated during solar flares, including the relationship between thermal plasma and non-thermal particles. SMASH demonstrated the space-borne application of the commercial off-the-shelf Amptek X123-CdTe, a miniature cadmium telluride photon-counting HXR spectrometer. The CdTe detector has a physical area of 25 mm^2 and 1 mm fully-depleted thickness, with a ~100 micron Be window; with on-board thermoelectric cooling and pulse pile-up rejection, it is sensitive to solar photons from ~5 to ~100 keV with ~0.5-1.0 keV FWHM resolution. Photons are accumulated into histogram spectra with customizable energy binning and integration time. With modest resource requirements (~1/8 U, ~200 g, ~2.5 W) and low cost (~$10K), the X123-CdTe is an attractive solution for HXR measurements from budget- and resource-limited platforms such as CubeSats. SMASH flew two identical X123-CdTe detectors for redundancy and increased collecting area; the supporting electronics (power, CPU) were largely build-to-print using the Miniature X-ray Solar Spectrometer (MinXSS) CubeSat design.We review the SMASH mission, design, and detector performance during the 12-day Antarctic flight. We present current progress on our data analysis of observed solar flares, and discuss future applications of the space-qualified X123-CdTe detector, including the CubIXSS mission

  9. MeRiT repair verification using in-die phase metrology Phame

    NASA Astrophysics Data System (ADS)

    Buttgereit, Ute; Birkner, Robert; Stelzner, Robert

    2009-01-01

    With the transition of lithography into 45nm node and beyond the industry faces the challenge that mask complexity increases steadily, mask specifications tighten and process control becomes extremely important. The use of Phase Shifting Masks (PSM), combined with off-axis illumination schemes, is essential to print feature sizes going beyond the lithographic wavelength. In conjunction with the shrinking feature size the tolerable defect size shrinks as well. This goes along with rising mask costs and therefore a high first pass yield becomes more important than ever. Repair strategies are required which have the potential to support the trend of decreasing tolerable defect sizes for both clear and opaque defects. In case of PSM it is not only important to remove material, of special interest is the capability to repair phase defects. This requires material deposition and etching accounting for transmission and phase as well. The ebeam repair system MeRiT(R) MG 45 is based on the GEMINI(R) column and allows etching and deposition to repair both clear and opaque defects with high resolution and edge placement precision. In this paper we focus on repair of phase defects on 6% att. PSM. We concentrate on 45nm lines/spaces looking into different defect dimensions. At feature sizes of 45nm CD, corresponding to 180nm CD at mask, feature topography already impacts the phase shift. Therefore a base line investigation is performed evaluating the correlation between deposited PSM layer height and phase shift covering also the impact of 3D mask effects on phase shift. The deposited layer height is measured using AFM. For phase evaluation the newly developed phase metrology system Phame® was used. Phame(R) enables optical phase shift measurement with high spatial resolution down to 120nm half pitch on mask. On-axis and off-axis illumination can be applied according to the required scanner settings during wafer printing. Phame(R) captures imaging effects as well as 3D mask

  10. RiPEIP1, a gene from the arbuscular mycorrhizal fungus Rhizophagus irregularis, is preferentially expressed in planta and may be involved in root colonization.

    PubMed

    Fiorilli, Valentina; Belmondo, Simone; Khouja, Hassine Radhouane; Abbà, Simona; Faccio, Antonella; Daghino, Stefania; Lanfranco, Luisa

    2016-08-01

    Transcriptomics and genomics data recently obtained from the arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis have offered new opportunities to decipher the contribution of the fungal partner to the establishment of the symbiotic association. The large number of genes which do not show similarity to known proteins witnesses the uniqueness of this group of plant-associated fungi. In this work, we characterize a gene that was called RiPEIP1 (Preferentially Expressed In Planta). Its expression is strongly induced in the intraradical phase, including arbuscules, and follows the expression profile of the Medicago truncatula phosphate transporter MtPT4, a molecular marker of a functional symbiosis. Indeed, mtpt4 mutant plants, which exhibit low mycorrhizal colonization and an accelerated arbuscule turnover, also show a reduced RiPEIP1 mRNA abundance. To further characterize RiPEIP1, in the absence of genetic transformation protocols for AM fungi, we took advantage of two different fungal heterologous systems. When expressed as a GFP fusion in yeast cells, RiPEIP1 localizes in the endomembrane system, in particular to the endoplasmic reticulum, which is consistent with the in silico prediction of four transmembrane domains. We then generated RiPEIP1-expressing strains of the fungus Oidiodendron maius, ericoid endomycorrhizal fungus for which transformation protocols are available. Roots of Vaccinium myrtillus colonized by RiPEIP1-expressing transgenic strains showed a higher mycorrhization level compared to roots colonized by the O. maius wild-type strain, suggesting that RiPEIP1 may regulate the root colonization process.

  11. Application of STORMTOOLS's simplified flood inundation model with sea level rise to assess impacts to RI coastal areas

    NASA Astrophysics Data System (ADS)

    Spaulding, M. L.

    2015-12-01

    The vision for STORMTOOLS is to provide access to a suite of coastal planning tools (numerical models et al), available as a web service, that allows wide spread accessibly and applicability at high resolution for user selected coastal areas of interest. The first product developed under this framework were flood inundation maps, with and without sea level rise, for varying return periods for RI coastal waters. The flood mapping methodology is based on using the water level vs return periods at a primary NOAA water level gauging station and then spatially scaling the values, based on the predictions of high resolution, storm and wave simulations performed by Army Corp of Engineers, North Atlantic Comprehensive Coastal Study (NACCS) for tropical and extratropical storms on an unstructured grid, to estimate inundation levels for varying return periods. The scaling for the RI application used Newport, RI water levels as the reference point. Predictions are provided for once in 25, 50, and 100 yr return periods (at the upper 95% confidence level), with sea level rises of 1, 2, 3, and 5 ft. Simulations have also been performed for historical hurricane events including 1938, Carol (1954), Bob (1991), and Sandy (2012) and nuisance flooding events with return periods of 1, 3, 5, and 10 yr. Access to the flooding maps is via a web based, map viewer that seamlessly covers all coastal waters of the state at one meter resolution. The GIS structure of the map viewer allows overlays of additional relevant data sets (roads and highways, wastewater treatment facilities, schools, hospitals, emergency evacuation routes, etc.) as desired by the user. The simplified flooding maps are publically available and are now being implemented for state and community resilience planning and vulnerability assessment activities in response to climate change impacts.

  12. Engineered selective plant male sterility through pollen-specific expression of the EcoRI restriction endonuclease.

    PubMed

    Millwood, Reginald J; Moon, Hong S; Poovaiah, Charleson R; Muthukumar, Balasubramaniam; Rice, John Hollis; Abercrombie, Jason M; Abercrombie, Laura L; Green, William Derek; Stewart, Charles Neal

    2016-05-01

    Unintended gene flow from transgenic plants via pollen, seed and vegetative propagation is a regulatory concern because of potential admixture in food and crop systems, as well as hybridization and introgression to wild and weedy relatives. Bioconfinement of transgenic pollen would help address some of these concerns and enable transgenic plant production for several crops where gene flow is an issue. Here, we demonstrate the expression of the restriction endonuclease EcoRI under the control of the tomato pollen-specific LAT52 promoter is an effective method for generating selective male sterility in Nicotiana tabacum (tobacco). Of nine transgenic events recovered, four events had very high bioconfinement with tightly controlled EcoRI expression in pollen and negligible-to-no expression other plant tissues. Transgenic plants had normal morphology wherein vegetative growth and reproductivity were similar to nontransgenic controls. In glasshouse experiments, transgenic lines were hand-crossed to both male-sterile and emasculated nontransgenic tobacco varieties. Progeny analysis of 16 000-40 000 seeds per transgenic line demonstrated five lines approached (>99.7%) or attained 100% bioconfinement for one or more generations. Bioconfinement was again demonstrated at or near 100% under field conditions where four transgenic lines were grown in close proximity to male-sterile tobacco, and 900-2100 seeds per male-sterile line were analysed for transgenes. Based upon these results, we conclude EcoRI-driven selective male sterility holds practical potential as a safe and reliable transgene bioconfinement strategy. Given the mechanism of male sterility, this method could be applicable to any plant species. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  13. Low-energy RI beam technology and nuclear clusters in the explosive pp-chain breakout process

    SciTech Connect

    Kubono, S.; Yamaguchi, H.; Kahl, D. M.; Ohshiro, Y.; Watanabe, S.; Yamazaki, N.; Teranishi, T.; Yanagisawa, Y.; Wakabayashi, Y.; Kase, M.; Hayakawa, S.; Kwon, Y. K.; Hashimoto, T.; Fukuda, Y.; He, J. J.; Goto, A.; Muto, H.

    2014-05-09

    The lecture includes two parts: One is a discussion on the technology for developing RIB beam facility based on the in-flight method and relevant experimental technology. The second part is a discussion on experimental efforts for studying the breakout process from the pp-chain region based on recent works with low energy RI beams. The discussion of the second part specifically covers the problem of the vp-process in type II supernovae in terms of alpha cluster nature for the reactions.

  14. Population trends and flight behavior of the American burying beetle, Nicrophorus americanus (Coleoptera: Silphidae), on Block Island, RI

    USGS Publications Warehouse

    Raithel, C.J.; Ginsberg, H.S.; Prospero, M.L.

    2006-01-01

    The endangered American burying beetle, Nicrophorus americanus, was monitored on Block Island, RI, USA, from 1991-2003 using mark-recapture population estimates of adults collected in pitfall traps. Populations increased through time, especially after 1994 when a program was initiated that provided carrion for beetle production. Beetle captures increased with increasing temperature and dew point, and decreased with increasing wind speed. Short distance movement was not related to wind direction, while longer distance flights tended to be downwind. Although many individuals flew considerable distances along transects, most recaptures were in traps near the point of release. These behaviors probably have counterbalancing effects on population estimates.

  15. Constraint on Nuclear Symmetry Energy through Heavy RI Collision Experiment by Using SπRIT Device at RIBF-SAMURAI

    NASA Astrophysics Data System (ADS)

    Isobe, Tadaaki

    The symmetry energy of the nuclear Equation of State (EoS) is essential in many aspects of the astrophysics. However it has large ambiguity mainly for the dense region of ρ > ρ0. In order to give a constraint on the dencity dependent nuclear symmetry energy, an international experimental project at RIKEN-RIBF: SπRIT was launched. By using newly developed Time Projection Chamber (TPC) as a main device of SπRIT experiment, first heavy RI collision experiment was performed in the spring of 2016. In this experiment, charged π meson was measured as main observable as it is expected to be most sensitive to the symmetry energy.

  16. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Yb-169 of activity measurements of the radionuclide 169Yb and links for the 1997 regional comparison EUROMET.RI(II)-K2.Yb-169

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Coursol, N.; Morel, J.

    2004-01-01

    Since 1978, six national metrology institutes (NMI) have submitted eleven samples of known activity of 169Yb to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Yb-169. The activities ranged from about 200 kBq to 46 MBq. The degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated and the results are given in the form of a matrix for four NMIs. A graphical presentation is also given. The results of a EUROMET regional comparison, comparison identifier EUROMET.RI(II)-K2.Yb-169, completed in 1997 for this radionuclide have been linked to the SIR results through those of the BNM-LNHB and the IRA. This has enabled five other NMIs and an international laboratory to have degrees of equivalence in the KCDB and two other NMIs to update their earlier results in the SIR. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  17. Two-loop matching factors for light quark masses and three-loop mass anomalous dimensions in the RI/SMOM schemes

    SciTech Connect

    Sturm, C.; Almeida, L.

    2010-04-26

    Light quark masses can be determined through lattice simulations in regularization invariant momentum-subtraction (RI/MOM) schemes. Subsequently, matching factors, computed in continuum perturbation theory, are used in order to convert these quark masses from a RI/MOM scheme to the {ovr MS} scheme. We calculate the two-loop corrections in QCD to these matching factors as well as the three-loop mass anomalous dimensions for the RI/SMOM and RI/SMOM{sub {gamma}{mu}} schemes. These two schemes are characterized by a symmetric subtraction point. Providing the conversion factors in the two different schemes allows for a better understanding of the systematic uncertainties. The two-loop expansion coefficients of the matching factors for both schemes turn out to be small compared to the traditional RI/MOM schemes. For n{sub f} = 3 quark flavors they are about 0.6%-0.7% and 2%, respectively, of the leading order result at scales of about 2 GeV. Therefore, they will allow for a significant reduction of the systematic uncertainty of light quark mass determinations obtained through this approach. The determination of these matching factors requires the computation of amputated Green's functions with the insertions of quark bilinear operators. As a by-product of our calculation we also provide the corresponding results for the tensor operator.

  18. Computational modeling of the Fc αRI receptor binding in the Fc α domain of the human antibody IgA: Normal Modes Analysis (NMA) study

    NASA Astrophysics Data System (ADS)

    Jayasinghe, Manori; Posgai, Monica; Tonddast-Navaei, Sam; Ibrahim, George; Stan, George; Herr, Andrew; George Stan Group Collaboration; Herr's Group Team

    2014-03-01

    Fc αRI receptor binding in the Fc α domain of the antibody IgA triggers immune effector responses such as phagocytosis and antibody-dependent cell-mediated cytotoxicity in eukaryotic cells. Fc α is a dimer of heavy chains of the IgA antibody and each Fc α heavy chain which consisted of two immunoglobulin constant domains, CH2 and CH3, can bind one Fc αRI molecule at the CH2-CH3 interface forming a 2:1 stoichiometry. Experimental evidences confirmed that Fc αRI binding to the Fc α CH2-CH3 junction altered the kinetics of HAA lectin binding at the distant IgA1 hinge. Our focus in this research was to understand the conformational changes and the network of residues which co-ordinate the receptor binding dynamics of the Fc α dimer complex. Structure-based elastic network modeling was used to compute normal modes of distinct Fc α configurations. Asymmetric and un-liganded Fc α configurations were obtained from the high resolution crystal structure of Fc α-Fc αRI 2:1 symmetric complex of PDB ID 1OW0. Our findings confirmed that Fc αRI binding, either in asymmetric or symmetric complex with Fc α, propagated long-range conformational changes across the Fc domains, potentially also impacting the distant IgA1 hinge.

  19. Anti-Ri-associated paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis in a patient with mixed large cell neuroendocrine lung carcinoma.

    PubMed

    Mitchell, Amber N; Bakhos, Charles T; Zimmerman, Earl A

    2015-02-01

    Paraneoplastic neurologic syndromes (PNS) can be the first manifestations of occult malignancies. If left untreated, PNS often lead to significant morbidity and mortality. Anti-Ri (anti-neuronal nuclear antibody type 2 [ANNA-2]) autoantibodies are commonly associated with breast and small cell lung cancers. Cases of anti-Ri paraneoplastic cerebellar degeneration are reported, but few describe severe nausea and coexisting limbic encephalitis as the major presenting features. We report a 75-year-old woman with medically-intractable emesis, encephalopathy, diplopia, vertigo, and gait ataxia for 3 months. Examination revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Anti-Ri antibodies were positive in serum only. CT scan identified a 2.0 cm left lung mass, and histopathology revealed large cell neuroendocrine carcinoma with admixed adenocarcinoma non-small cell lung carcinoma (NCSLC). Though the patient achieved nearly complete clinical recovery after tumor resection, anti-Ri levels remained high at 20 months post-resection. To our knowledge this is the first report of a paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis involving anti-Ri positivity and associated mixed neuroendocrine/NSCLC of the lung with marked improvement after tumor resection.

  20. Coordinate expression of AOS genes and JA accumulation: JA is not required for initiation of closing layer in wound healing tubers

    USDA-ARS?s Scientific Manuscript database

    Wounding induces a series of coordinated physiological responses essential for protection and healing of the damaged tissue. Wound-induced formation of jasmonic acid (JA) is important in defense responses in leaves, but comparatively little is known about the induction of JA biosynthesis and its ro...

  1. Contribution of FcɛRI-associated vesicles to mast cell-macrophage communication following Francisella tularensis infection.

    PubMed

    Rodriguez, Annette R; Yu, Jieh-Juen; Navara, Christopher; Chambers, James P; Guentzel, M Neal; Arulanandam, Bernard P

    2016-10-01

    Understanding innate immune intercellular communication following microbial infection remains a key biological issue. Using live cell imaging, we demonstrate that mast cells actively extend cellular projections to sample the macrophage periphery during Francisella tularensis LVS infection. Mast cell MHCII(hi) expression was elevated from less than 1% to 13% during LVS infection. Direct contact during co-culture with macrophages further increased mast cell MHCII(hi) expression to approximately 87%. Confocal analyses of the cellular perimeter revealed mast cell caspase-1 was localized in close proximity with FcɛRI in uninfected mast cells, and repositioned to clustered regions upon LVS infection. Importantly, mast cell FcɛRI-encompassed vesicles are transferred to macrophages by trogocytosis, and macrophage caspase-1 expression is further up-regulated upon direct contact with mast cells. Our study reveals direct cellular interactions between innate cells that may impact the function of caspase-1, a known sensor of microbial danger and requirement for innate defense against many pathogenic microbes including F. tularensis.

  2. Activation of Fc gamma RI on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses.

    PubMed

    Tanaka, Motoyuki; Krutzik, Stephan R; Sieling, Peter A; Lee, Delphine J; Rea, Thomas H; Modlin, Robert L

    2009-08-15

    The formation of immune complexes results in activation of the innate immune system and subsequent induction of host inflammatory responses. In particular, the binding of IgG immune complexes to FcgammaR on monocytes triggers potent inflammatory responses leading to tissue injury in disease. We investigated whether activation of monocytes via FcgammaR induced cell differentiation, imparting specific inflammatory functions of the innate immune response. Human IgG alone induced monocytes to differentiate into cells with an immature dendritic cell (iDC) phenotype, including up-regulation of CD1b, CD80, CD86, and CD206. Differentiation into CD1b(+) iDC was dependent on activation via CD64 (FcgammaRI) and induction of GM-CSF. The human IgG-differentiated iDC were phenotypically different from GM-CSF-derived iDC at the same level of CD1b expression, with higher cell surface CD86, but lower MHC class II, CD32, CD206, and CD14. Finally, in comparison to GM-CSF-derived iDC, IgG-differentiated iDC were more efficient in activating T cells in both autologous and allogeneic mixed lymphocyte reactions but less efficient at presenting microbial Ag to T cells. Therefore, activation of FcgammaRI on monocytes triggers differentiation into specialized iDC with the capacity to expand autoreactive T cells that may contribute to the pathogenesis of immune complex-mediated tissue injury.

  3. BIPM comparison BIPM.RI(II)-K1.Th-228 of activity measurements of the radionuclide 228Th

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Lucas, L.; Kossert, K.; Nähle, O.; Ott, O.

    2016-01-01

    Since 1986, two national metrology institutes (NMI) have submitted two samples of known activity of 228Th to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Th-228. The values of the activity submitted were about 300 kBq and 2 MBq. A key comparison reference value (KCRV) has been evaluated for the first time for 228Th. There is only one result remaining in the BIPM.RI(II)-K1.Th-228 comparison, the 1986 NIST result being outdated. The degrees of equivalence between each equivalent activity measured in the SIR and the KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  4. 8-Oxoguanine Affects DNA Backbone Conformation in the EcoRI Recognition Site and Inhibits Its Cleavage by the Enzyme

    PubMed Central

    Kiryutin, Alexey S.; Kasymov, Rustem D.; Petrova, Darya V.; Endutkin, Anton V.; Popov, Alexander V.; Yurkovskaya, Alexandra V.; Fedechkin, Stanislav O.; Brockerman, Jacob A.; Zharkov, Dmitry O.; Smirnov, Serge L.

    2016-01-01

    8-oxoguanine is one of the most abundant and impactful oxidative DNA lesions. However, the reasons underlying its effects, especially those not directly explained by the altered base pairing ability, are poorly understood. We report the effect of the lesion on the action of EcoRI, a widely used restriction endonuclease. Introduction of 8-oxoguanine inside, or adjacent to, the GAATTC recognition site embedded within the Drew—Dickerson dodecamer sequence notably reduced the EcoRI activity. Solution NMR revealed that 8-oxoguanine in the DNA duplex causes substantial alterations in the sugar—phosphate backbone conformation, inducing a BI→BII transition. Moreover, molecular dynamics of the complex suggested that 8-oxoguanine, although does not disrupt the sequence-specific contacts formed by the enzyme with DNA, shifts the distribution of BI/BII backbone conformers. Based on our data, we propose that the disruption of enzymatic cleavage can be linked with the altered backbone conformation and dynamics in the free oxidized DNA substrate and, possibly, at the protein—DNA interface. PMID:27749894

  5. A new fission-fragment detector to complement the CACTUS-SiRi setup at the Oslo Cyclotron Laboratory

    NASA Astrophysics Data System (ADS)

    Tornyi, T. G.; Görgen, A.; Guttormsen, M.; Larsen, A. C.; Siem, S.; Krasznahorkay, A.; Csige, L.

    2014-02-01

    An array of Parallel Plate Avalanche Counters (PPAC) for the detection of heavy ions has been developed. The new device, NIFF (Nuclear Instrument for Fission Fragments), consists of four individual detectors and covers 60% of 2π. It was designed to be used in conjunction with the SiRi array of ΔE-E silicon telescopes for light charged particles and fits into the CACTUS array of 28 large-volume NaI scintillation detectors at the Oslo Cyclotron Laboratory. The low-pressure gas-filled PPACs are sensitive for the detection of fission fragments, but are insensitive to scattered beam particles of light ions or light-ion ejectiles. The PPAC detectors of NIFF have good time resolution and can be used either to select or to veto fission events in in-beam experiments with light-ion beams and actinide targets. The powerful combination of SiRi, CACTUS, and NIFF provides new research opportunities for the study of nuclear structure and nuclear reactions in the actinide region. The new setup is particularly well suited to study the competition of fission and γ decay as a function of excitation energy.

  6. Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform

    SciTech Connect

    Liu, Yanli; Barua, Dipak; Liu, Peng; Wilson, Bridget S.; Oliver, Janet M.; Hlavacek, William S.; Singh, Anup K.

    2013-03-27

    Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. In this paper, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry and optical imaging. The device seamlessly integrates cell culture, stimulation, and preparation with downstream measurements permitting hands-free, automated analysis to minimize experimental variability. The platform was used to interrogate IgE receptor (FcεRI) signaling, which is responsible for triggering allergic reactions, in RBL-2H3 cells. Following on-chip crosslinking of IgE-FcεRI complexes by multivalent antigen, we monitored signaling events including protein phosphorylation, calcium mobilization and the release of inflammatory mediators. The results demonstrate the ability of our platform to produce quantitative measurements on a cell-by-cell basis from just a few hundred cells. Finally, model-based analysis of the Syk phosphorylation data suggests that heterogeneity in Syk phosphorylation can be attributed to protein copy number variations, with the level of Syk phosphorylation being particularly sensitive to the copy number of Lyn.

  7. Single-cell measurements of IgE-mediated FcεRI signaling using an integrated microfluidic platform.

    PubMed

    Liu, Yanli; Barua, Dipak; Liu, Peng; Wilson, Bridget S; Oliver, Janet M; Hlavacek, William S; Singh, Anup K

    2013-01-01

    Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry and optical imaging. The device seamlessly integrates cell culture, stimulation, and preparation with downstream measurements permitting hands-free, automated analysis to minimize experimental variability. The platform was used to interrogate IgE receptor (FcεRI) signaling, which is responsible for triggering allergic reactions, in RBL-2H3 cells. Following on-chip crosslinking of IgE-FcεRI complexes by multivalent antigen, we monitored signaling events including protein phosphorylation, calcium mobilization and the release of inflammatory mediators. The results demonstrate the ability of our platform to produce quantitative measurements on a cell-by-cell basis from just a few hundred cells. Model-based analysis of the Syk phosphorylation data suggests that heterogeneity in Syk phosphorylation can be attributed to protein copy number variations, with the level of Syk phosphorylation being particularly sensitive to the copy number of Lyn.

  8. IgE/FcεRI-Mediated Antigen Cross-Presentation by Dendritic Cells Enhances Anti-Tumor Immune Responses.

    PubMed

    Platzer, Barbara; Elpek, Kutlu G; Cremasco, Viviana; Baker, Kristi; Stout, Madeleine M; Schultz, Cornelia; Dehlink, Eleonora; Shade, Kai-Ting C; Anthony, Robert M; Blumberg, Richard S; Turley, Shannon J; Fiebiger, Edda

    2015-03-03

    Epidemiologic studies discovered an inverse association between immunoglobulin E (IgE)-mediated allergies and cancer, implying tumor-protective properties of IgE. However, the underlying immunologic mechanisms remain poorly understood. Antigen cross-presentation by dendritic cells (DCs) is of key importance for anti-tumor immunity because it induces the generation of cytotoxic CD8(+) T lymphocytes (CTLs) with specificity for tumor antigens. We demonstrate that DCs use IgE and FcεRI, the high-affinity IgE receptor, for cross-presentation and priming of CTLs in response to free soluble antigen at low doses. Importantly, IgE/FcεRI-mediated cross-presentation is a distinct receptor-mediated pathway because it does not require MyD88 signals or IL-12 induction in DCs. Using passive immunization with tumor antigen-specific IgE and DC-based vaccination experiments, we demonstrate that IgE-mediated cross-presentation significantly improves anti-tumor immunity and induces memory responses in vivo. Our findings suggest a cellular mechanism for the tumor-protective features of IgE and expand the known physiological functions of this immunoglobulin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. A Lanthipeptide-like N-Terminal Leader Region Guides Peptide Epimerization by Radical SAM Epimerases: Implications for RiPP Evolution.

    PubMed

    Fuchs, Sebastian W; Lackner, Gerald; Morinaka, Brandon I; Morishita, Yohei; Asai, Teigo; Riniker, Sereina; Piel, Jörn

    2016-09-26

    Ribosomally synthesized and posttranslationally modified peptide natural products (RiPPs) exhibit diverse structures and bioactivities and are classified into distinct biosynthetic families. A recently reported family is the proteusins, with the prototype members polytheonamides being generated by almost 50 maturation steps, including introduction of d-residues at multiple positions by an unusual radical SAM epimerase. A region in the protein-like N-terminal leader of proteusin precursors is identified that is crucial for epimerization. It resembles a precursor motif previously shown to mediate interaction in thioether bridge-formation in class I lanthipeptide biosynthesis. Beyond this region, similarities were identified between proteusin and further RiPP families, including class I lanthipeptides. The data suggest that common leader features guide distinct maturation types and that nitrile hydratase-like enzymes are ancestors of several RiPP classes.

  10. N-Formyl-Methionyl-Leucyl-Phenylalanine Inhibits both Gamma Interferon- and Interleukin-10-Induced Expression of FcγRI on Human Monocytes

    PubMed Central

    Beigier-Bompadre, Macarena; Barrionuevo, Paula; Alves-Rosa, Fernanda; Rubel, Carolina J.; Palermo, Marina S.; Isturiz, Martín A.

    2001-01-01

    Three different classes of receptors for the Fc portion of immunoglobulin G (FcγRs), FcγRI, FcγRII, and FcγRIII, have been identified on human leukocytes. One of them, FcγRI, is a high-affinity receptor capable of induction of functions that include phagocytosis, respiratory burst, antibody-dependent cell-mediated cytotoxicity (ADCC), and secretion of cytokines. This receptor is expressed on mononuclear phagocytes, and this expression is regulated by cytokines and hormones such as gamma interferon (IFN-γ), IFN-β, interleukin-10 (IL-10), and glucocorticoids. We have recently demonstrated that the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) is capable of inducing a time-dependent downregulation of both FcγRIIIB and FcγRII in human neutrophils, altering FcγR-dependent functions. Considering the biological relevance of the regulation of FcγRI, we investigated the effect of FMLP on the overexpression of FcγRI induced by both IFN-γ and IL-10 on human monocytes. We demonstrate that FMLP significantly abrogated IFN-γ- and IL-10-induced FcγRI expression, although its basal level of expression was not altered. However, other IFN-γ-mediated effects such as the overexpression of the major histocompatibility complex class II antigens and the enhancement of lipopolysaccharide-induced secretion of tumor necrosis factor alpha were not affected by FMLP treatment. The formyl peptide completely inhibited the IFN-γ- and IL-10-induced enhancement of ADCC and phagocytosis carried out by adherent cells. The inhibitory effect of FMLP on FcγRI upregulation could exert an important regulatory effect during the evolution of bacterial infections. PMID:11238229

  11. Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human FcγRI

    PubMed Central

    Bonetto, Stephane; Spadola, Loredana; Buchanan, Andrew G.; Jermutus, Lutz; Lund, John

    2009-01-01

    Identification of short, structured peptides able to mimic potently protein-protein interfaces remains a challenge in drug discovery. We report here the use of a naive cyclic peptide phage display library to identify peptide ligands able to recognize and mimic IgG1-Fc functions with FcγRI. Selection by competing off binders to FcγRI with IgG1 allowed the isolation of a family of peptides sharing the common consensus sequence TX2CXXθPXLLGCΦXE (θ represents a hydrophobic residue, Φ is usually an acidic residue, and X is any residue) and able to inhibit IgG1 binding to FcγRI. In soluble form, these peptides antagonize superoxide generation mediated by IgG1. In complexed form, they trigger phagocytosis and a superoxide burst. Unlike IgG, these peptides are strictly FcγRI-specific among the FcγRs. Molecular modeling studies suggest that these peptides can adopt 2 distinct and complementary conformers, each able to mimic the discontinuous interface contacts constituted by the Cγ2-A and -B chains of Fc for FcγRI. In addition, by covalent homodimerization, we engineered a synthetic bivalent 37-mer peptide that retains the ability to trigger effector functions. We demonstrate here that it is feasible to maintain IgG-Fc function within a small structured peptide. These peptides represent a new format for modulation of effector functions.—Bonetto, S., Spadola, L., Buchanan, A. G., Jermutus, L. Lund, J. Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human FcγRI. PMID:18957574

  12. IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection

    PubMed Central

    Xiong, Juan; Burkovetskaya, Maria; Karpuk, Nikolay; Kielian, Tammy

    2012-01-01

    Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood–brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared with WT (wild-type) animals. Loss of IL-1RI signalling also dampened the expression of select cytokines and chemokines, concomitant with significant reductions in neutrophil and macrophage infiltrates into the brain. In addition, the opening of astrocyte hemichannels during acute infection was shown to be dependent on IL-1RI activity. Collectively, these results demonstrate that IL-1RI signalling plays a pivotal role in the genesis of immune responses during the acute stage of brain abscess development through S. aureus containment, inflammatory mediator production, peripheral immune cell recruitment, and regulation of astrocyte hemichannel activity. Taken in the context of previous studies with MyD88 (myeloid differentiation primary response gene 88) and TLR2 (Toll-like receptor 2) KO animals, the current report advances our understanding of MyD88-dependent cascades and implicates IL-1RI signalling as a major antimicrobial effector pathway during acute brain-abscess formation. PMID:22414156

  13. Allergen Valency, Dose, and FcεRI Occupancy Set Thresholds for Secretory Responses to Pen a 1 and Motivate Design of Hypoallergens.

    PubMed

    Mahajan, Avanika; Youssef, Lama A; Cleyrat, Cédric; Grattan, Rachel; Lucero, Shayna R; Mattison, Christopher P; Erasmus, M Frank; Jacobson, Bruna; Tapia, Lydia; Hlavacek, William S; Schuyler, Mark; Wilson, Bridget S

    2017-02-01

    Ag-mediated crosslinking of IgE-FcεRI complexes activates mast cells and basophils, initiating the allergic response. Of 34 donors recruited having self-reported shrimp allergy, only 35% had significant levels of shrimp-specific IgE in serum and measurable basophil secretory responses to rPen a 1 (shrimp tropomyosin). We report that degranulation is linked to the number of FcεRI occupied with allergen-specific IgE, as well as the dose and valency of Pen a 1. Using clustered regularly interspaced palindromic repeat-based gene editing, human RBL(rαKO) cells were created that exclusively express the human FcεRIα subunit. Pen a 1-specific IgE was affinity purified from shrimp-positive plasma. Cells primed with a range of Pen a 1-specific IgE and challenged with Pen a 1 showed a bell-shaped dose response for secretion, with optimal Pen a 1 doses of 0.1-10 ng/ml. Mathematical modeling provided estimates of receptor aggregation kinetics based on FcεRI occupancy with IgE and allergen dose. Maximal degranulation was elicited when ∼2700 IgE-FcεRI complexes were occupied with specific IgE and challenged with Pen a 1 (IgE epitope valency of ≥8), although measurable responses were achieved when only a few hundred FcεRI were occupied. Prolonged periods of pepsin-mediated Pen a 1 proteolysis, which simulates gastric digestion, were required to diminish secretory responses. Recombinant fragments (60-79 aa), which together span the entire length of tropomyosin, were weak secretagogues. These fragments have reduced dimerization capacity, compete with intact Pen a 1 for binding to IgE-FcεRI complexes, and represent a starting point for the design of promising hypoallergens for immunotherapy. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Negative regulation of inflammatory responses by immunoglobulin A receptor (FcαRI) inhibits the development of Toll-like receptor-9 signalling-accelerated glomerulonephritis.

    PubMed

    Watanabe, T; Kanamaru, Y; Liu, C; Suzuki, Y; Tada, N; Okumura, K; Horikoshi, S; Tomino, Y

    2011-11-01

    Myeloid FcαRI, a receptor for immunoglobulin (Ig)A, mediates cell activation or inhibition depending on the type of ligand interaction, which can be either multivalent or monovalent. Anti-inflammatory signalling is triggered by monomeric targeting using anti-FcαRI Fab or IgA ligand binding, which inhibits immune and non-immune-mediated renal inflammation. The participation of Toll-like receptors (TLRs) in kidney pathology in experimental models and various forms of human glomerular nephritis has been discussed. However, little is known about negative regulation of innate-immune activation. In the present study, we generated new transgenic mice that express FcαRI(R209L) /FcRγ chimeric protein and showed that the monovalent targeting of FcαRI exhibited inhibitory effects in an in vivo model of TLR-9 signalling-accelerated nephritis. Mouse monoclonal anti-FcαRI MIP8a Fab improved urinary protein levels and reduced the number of macrophages and immunoglobulin deposition in the glomeruli. Monovalent targeting using MIP8a Fab attenuates the TLR-9 signalling pathway and is associated with phosphorylation of extracellular signal-related protein kinases [extracellular signal-regulated kinase (ERK), P38, c-Jun N-terminal kinase (JNK)] and the activation of nuclear factor (NF)-κB. The inhibitory mechanism involves recruitment of tyrosine phosphatase Src homology 2 domain-containing phosphatase-1 (SHP-1) to FcαRI. Furthermore, cell transfer studies with macrophages pretreated with MIP8a Fab showed that blockade of FcαRI signalling in macrophages prevents the development of TLR-9 signalling-accelerated nephritis. These results suggest a role of anti-FcαRI Fab as a negative regulator in controlling the magnitude of the innate immune response and a new type of anti-inflammatory drug for treatment of kidney disease. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  15. Effect of MeJA treatment on polyamine, energy status and anthracnose rot of loquat fruit.

    PubMed

    Cao, Shifeng; Cai, Yuting; Yang, Zhenfeng; Joyce, Daryl C; Zheng, Yonghua

    2014-02-15

    The effect of methyl jasmonate (MeJA) on changes in polyamines content and energy status and their relation to disease resistance was investigated. Freshly harvested loquat fruit were treated with 10 μmol l(-1) MeJA and wound inoculated with Colletotrichum acutatum spore suspension (1.0 × 10(5) spores ml(-1)) after 24h, and then stored at 20 °C for 6 days. MeJA treatment significantly reduced decay incidence. MeJA treated fruit manifested higher contents of polyamines (putrescine, spermidine and spermine) compared with the control fruit, during storage. MeJA treatment also maintained higher levels of adenosine triphosphate, and suppressed an increase in adenosine monophosphate content in loquat fruit. These results suggest that MeJA treatment may inhibit anthracnose rot by increasing polyamine content and maintaining the energy status. Copyright © 2013. Published by Elsevier Ltd.

  16. Mitochondrial chaperone DnaJA3 induces Drp1-dependent mitochondrial fragmentation.

    PubMed

    Elwi, Adam N; Lee, Byoungchun; Meijndert, H Christopher; Braun, Janice E A; Kim, Sung-Woo

    2012-08-01

    Mitochondrial morphology is dynamic and controlled by coordinated fusion and fission pathways. The role of mitochondrial chaperones in mitochondrial morphological changes and pathology is currently unclear. Here we report that altered levels of DnaJA3 (Tid1/mtHsp40) a mitochondrial member of the DnaJ protein family, and heat shock protein (Hsp) co-chaperone of matrix 70 kDa Hsp70 (mtHsp70/mortalin/HSPA9), induces mitochondrial fragmentation. Suppression of DnaJA3 induced mitochondrial fragmentation in HeLa cells. Elevated levels of DnaJA3 in normal Hs68 fibroblast cells and HeLa, SKN-SH, U87 and U251 cancer cell lines induces mitochondrial fragmentation. Mitochondrial fragmentation induction was not observed in HeLa cells when other DnaJA family members, or mitochondrial DnaJ protein HSC20, were ectopically expressed, indicating that the effects on mitochondrial morphology were specific to DnaJA3. We show that the DnaJ domain (amino acids 88-168) of DnaJA3 is sufficient for the induction of mitochondrial fragmentation. Furthermore, an H121Q point mutation of the DnaJ domain, which abrogates interaction and activation of mtHsp70 ATPase, eliminates fragmentation induced by DnaJA3. This suggests that DnaJA3 interaction with mtHsp70 may be critical in mitochondrial morphological changes. DnaJA3-induced mitochondrial fragmentation was dependent on fission factor dynamin-related protein 1 (Drp1). Ectopic expression of the mitofusins (Mfn1 and Mfn2), however, does not rescue DnaJA3-induced mitochondrial fragmentation. Lastly, elevated levels of DnaJA3 inducing mitochondrial fragmentation were associated with reduction in cell viability. Taken together, elevated DnaJA3 induces Drp1-depedendent mitochondrial fragmentation and decreased cell viability.

  17. Synthesis, structural characterization and biological activity of two diastereomeric JA-Ile macrolactones.

    PubMed

    Jimenez-Aleman, Guillermo H; Machado, Ricardo A R; Görls, Helmar; Baldwin, Ian T; Boland, Wilhelm

    2015-06-07

    Jasmonates are phytohormones involved in a wide range of plant processes, including growth, development, senescence, and defense. Jasmonoyl-L-isoleucine (JA-Ile, 2), an amino acid conjugate of jasmonic acid (JA, 1), has been identified as a bioactive endogenous jasmonate. However, JA-Ile (2) analogues trigger different responses in the plant. ω-Hydroxylation of the pentenyl side chain leads to the inactive 12-OH-JA-Ile (3) acting as a “stop” signal. On the other hand, a lactone derivative of 12-OH-JA (5) (jasmine ketolactone, JKL) occurs in nature, although with no known biological function. Inspired by the chemical structure of JKL (6) and in order to further explore the potential biological activities of 12-modified JA-Ile derivatives, we synthesized two macrolactones (JA-Ile-lactones (4a) and (4b)) derived from 12-OH-JA-Ile (3). The biological activity of (4a) and (4b) was tested for their ability to elicit nicotine production, a well-known jasmonate dependent secondary metabolite. Both macrolactones showed strong biological activity, inducing nicotine accumulation to a similar extent as methyl jasmonate does in Nicotiana attenuata leaves. Surprisingly, the highest nicotine contents were found in plants treated with the JA-Ile-lactone (4b), which has (3S,7S) configuration at the cyclopentanone not known from natural jasmonates. Macrolactone (4a) is a valuable standard to explore for its occurrence in nature.

  18. The mealybug Phenacoccus solenopsis suppresses plant defense responses by manipulating JA-SA crosstalk

    PubMed Central

    Zhang, Peng-Jun; Huang, Fang; Zhang, Jin-Ming; Wei, Jia-Ning; Lu, Yao-Bin

    2015-01-01

    Induced plant defenses against herbivores are modulated by jasmonic acid-, salicylic acid-, and ethylene-signaling pathways. Although there is evidence that some pathogens suppress plant defenses by interfering with the crosstalk between different signaling pathways, such evidence is scarce for herbivores. Here, we demonstrate that the mealybug Phenacoccus solenopsis suppresses the induced defenses in tomato. We found that exogenous JA, but not SA, significantly decreased mealybug feeding time and reduced nymphal performance. In addition, constitutive activation of JA signaling in 35s::prosys plants reduced mealybug survival. These data indicate that the JA signaling pathway plays a key role in mediating the defense responses against P. solenopsis. We also found that mealybug feeding decreased JA production and JA-dependent defense gene expression, but increased SA accumulation and SA-dependent gene expression. In SA-deficient plants, mealybug feeding did not suppress but activated JA accumulation, indicating that the suppression of JA-regulated defenses depends on the SA signaling pathway. Mealybugs benefit from suppression of JA-regulated defenses by exhibiting enhanced nymphal performance. These findings confirm that P. solenopsis manipulates plants for its own benefits by modulating the JA-SA crosstalk and thereby suppressing induced defenses. PMID:25790868

  19. MoRiBS-PIMC: A program to simulate molecular rotors in bosonic solvents using path-integral Monte Carlo

    NASA Astrophysics Data System (ADS)

    Zeng, Tao; Blinov, Nicholas; Guillon, Grégoire; Li, Hui; Bishop, Kevin P.; Roy, Pierre-Nicholas

    2016-07-01

    We provide the source code of our in-house program MoRiBS-PIMC. This program was developed to simulate rigid molecules rotating in bosonic clusters composed of helium atoms, parahydrogen molecules or any other bosonic point solvent particles. The program can be employed to obtain superfluid response, structural and energetic properties as well as imaginary time correlation functions of dipole operators. These quantities can be used to interpret and predict the results of spectroscopic Andronikashvili experiments. The software is based on the latest advances in the simulation of the quantum rotation of non-linear rigid rotors and in the sampling of bosonic permutations. The program has been parallelized to improve its performance and new techniques have been implemented to obtain symmetry-adapted simulation results. The usage and robustness of the program is demonstrated with some illustrative examples.

  20. ANTIOXIDANT PROPERTIES OF METHANOLIC EXTRACTS FROM THE SHOOTS AND ROOTS OF pRi-TRANSFORMED PLANTS OF REHMANNIA GLUTINOSA LIBOSCH.

    PubMed

    Piatczak, Ewelina; Dfbska, Marta; Kontek, Bogdan; Olas, Beata; Wysokinskai, Halina

    2016-01-01

    The antioxidant activity of methanolic extracts derived from shoots (HR-shoots) and roots (HR-roots) of pRi-transformed Rehmannia glutinosa plants were determined. The activity was indicated by the ability of the plant extracts to inhibit superoxide anion (O2(-·)) generation and thiobarbituric acid reactive substances (TBARS) production in resting blood platelets and platelets activated by thrombin. The strongest activity was exhibited by the HR-shoot extract (50 μg/mL). The present study also examines the antioxidant properties of the plant extracts against human plasma lipid peroxidation induced by strong biological oxidants: hydrogen peroxide (H2O2) and H2O2/Fe. The study shows that extracts from transformed R. glutinosa plants may be a promising source of natural antioxidants, which would be valuable in various cardiovascular diseases. The extracts may also protect lipids against oxidative modifications.

  1. Malachite green bioremoval by a newly isolated strain Citrobacter sedlakii RI11; enhancement of the treatment by biosurfactant addition.

    PubMed

    Mnif, Inès; Fendri, Raouia; Ghribi, Dhouha

    2015-01-01

    Citrobacter sedlackii RI11, isolated from acclimated textile effluent after selective enrichment on synthetic dyes, was assessed for malachite green (MG) biotreatment potency. Results indicate that this bacterium has potential for use in effective treatment of MG contaminated wastewaters under shaking conditions at neutral and alkaline pH value, characteristic of typical textile effluents. Also, the newly isolated strain can tolerate higher doses of dye and decolorize up to 1,000 mg/l of dye. When used as microbial surfactant to enhance MG biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that MG removal by this strain could be due to biodegradation and/or adsorption. Results on germination potencies of different seeds using the treated dyes under different conditions favor the use of SPB1 biosurfactant for the treatment of MG.

  2. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Rn-222 of activity measurements of the radionuclide 222Rn

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Bochud, F. O.

    2004-01-01

    Since 2001, a national metrology institute, the Institut de Radiophysique Appliquée (IRA), Switzerland, has submitted two samples of known activity of 222Rn to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM). The activities ranged from about 13 kBq to 370 kBq. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), with comparison identifier BIPM.RI(II)-K1.Rn-222, according to the provisions of the Mutual Recognition Arrangement (MRA).

  3. The First Results of the Photometric Observation of Selected Asteroids on KT-50 Telescope of Mobitel Complex of RI MAO

    NASA Astrophysics Data System (ADS)

    Pomazan, A. V.; Maigurova, N. V.

    2017-02-01

    The first results of the photometric observations of asteroids performed on the telescope KT-50 of Mobitel complex (RI "MAO") during 2016 are presented in the paper. Asteroids were selected based on the infrared survey NEOWISE, moving objects catalog SDSS MOC-3 and MPC database. Selected asteroids have a relatively high albedo (pV > 0.2) and are located in the Outer Main Belt (semi-major axis a >0.28 a.u.). The observations were made using filter close to the Rc standard band of Cousins system. Standard deviations of the instrumental differential magnitude measurements were in the range of 0.01m-0.03m for a 10m-15.5m reference stars. The light curve based on the results of the differential aperture photometry was obtained from long series of observations of the asteroid (2144) Marietta.

  4. SIM.RI(I)-K3 comparison of calibration coefficients at radiotherapy level for orthovoltage x-ray beams

    NASA Astrophysics Data System (ADS)

    O'Brien, M.; McCaffrey, J.; Shen, H.; Saraví, M.; Stefanic, A.; Montaño Ortiz, G.; Carlos, M.; da Silva, C.; Álvarez, J.; Tovar, V.

    2015-01-01

    Air-kerma calibration coefficients were compared at the radiotherapy level for orthovoltage x ray beams in the SIM.RI(I)-K3 comparison for members of the Sistema Interamericano de Metrología (SIM). Five SIM laboratories participated in the comparison: NIST, NRC, ININ, CNEA and LNMRI, the NIST being the pilot laboratory. Results from the comparison are linked to the BIPM.RI(I)-K3 key comparison reference value through the NIST-BIPM comparison made in 2003 and will meet requirements of the Mutual Recognition Arrangement (MRA) to support several CMCs (calibration and measurement capability claims) of the participants. The comparison began in October of 2007 and the measurements were completed in September 2008. The results reveal the degree to which the participating calibration facility can demonstrate proficiency in transferring air-kerma calibrations under the conditions of the said facility at the time of the measurements. The evaluation of the degrees of equivalence was performed as described in the comparison protocol. The comparison of the calibration coefficients for the four chambers is based on the average ratios of the calibration coefficients measured at the NIST and at each participating laboratory. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  5. Single-Cell Measurements of IgE-Mediated FcεRI Signaling Using an Integrated Microfluidic Platform

    DOE PAGES

    Liu, Yanli; Barua, Dipak; Liu, Peng; ...

    2013-03-27

    Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. In this paper, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chipmore » flow cytometry and optical imaging. The device seamlessly integrates cell culture, stimulation, and preparation with downstream measurements permitting hands-free, automated analysis to minimize experimental variability. The platform was used to interrogate IgE receptor (FcεRI) signaling, which is responsible for triggering allergic reactions, in RBL-2H3 cells. Following on-chip crosslinking of IgE-FcεRI complexes by multivalent antigen, we monitored signaling events including protein phosphorylation, calcium mobilization and the release of inflammatory mediators. The results demonstrate the ability of our platform to produce quantitative measurements on a cell-by-cell basis from just a few hundred cells. Finally, model-based analysis of the Syk phosphorylation data suggests that heterogeneity in Syk phosphorylation can be attributed to protein copy number variations, with the level of Syk phosphorylation being particularly sensitive to the copy number of Lyn.« less

  6. A small novel A-kinase anchoring protein (AKAP) that localizes specifically protein kinase A-regulatory subunit I (PKA-RI) to the plasma membrane.

    PubMed

    Burgers, Pepijn P; Ma, Yuliang; Margarucci, Luigi; Mackey, Mason; van der Heyden, Marcel A G; Ellisman, Mark; Scholten, Arjen; Taylor, Susan S; Heck, Albert J R

    2012-12-21

    Protein kinase A-anchoring proteins (AKAPs) provide spatio-temporal specificity for the omnipotent cAMP-dependent protein kinase (PKA) via high affinity interactions with PKA regulatory subunits (PKA-RI, RII). Many PKA-RII-AKAP complexes are heavily tethered to cellular substructures, whereas PKA-RI-AKAP complexes have remained largely undiscovered. Here, using a cAMP affinity-based chemical proteomics strategy in human heart and platelets, we uncovered a novel, ubiquitously expressed AKAP, termed small membrane (sm)AKAP due to its specific localization at the plasma membrane via potential myristoylation/palmitoylation anchors. In vitro binding studies revealed specificity of smAKAP for PKA-RI (K(d) = 7 nM) over PKA-RII (K(d) = 53 nM) subunits, co-expression of smAKAP with the four PKA R subunits revealed an even more exclusive specificity of smAKAP for PKA-RIα/β in the cellular context. Applying the singlet oxygen-generating electron microscopy probe miniSOG indicated that smAKAP is tethered to the plasma membrane and is particularly dense at cell-cell junctions and within filopodia. Our preliminary functional characterization of smAKAP provides evidence that, like PKA-RII, PKA-RI can be tightly tethered by a novel repertoire of AKAPs, providing a new perspective on spatio-temporal control of cAMP signaling.

  7. Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice.

    PubMed

    Morine, Melissa J; Toomey, Sinead; McGillicuddy, Fiona C; Reynolds, Clare M; Power, Karen A; Browne, John A; Loscher, Christine; Mills, Kingston H G; Roche, Helen M

    2013-05-01

    A subacute inflammatory phenotype is implicated in the pathology of insulin resistance (IR) and type 2 diabetes mellitus. Interleukin (IL)-1α and IL-1β are produced by innate immune cells, including macrophages, and mediate their inflammatory response through the IL-1 type I receptor (IL-IRI). This study sought to understand the transcriptomic signature of adipose tissue in obese IL-1RI(-/-) mice. Following dietary intervention, markers of insulin sensitivity and inflammation in adipose tissue were determined, and gene expression was assessed with microarrays. IL-1RI(-/-) mice fed a high-fat diet (HFD) had significantly lower plasma inflammatory cytokine concentrations than wild-type mice. Metabolic network analysis of transcriptomic effects identified up-regulation and co-expression of genes involved in lipolysis, lipogenesis and tricarboxylic acid (TCA) cycle. Further assessment of gene expression in a network of protein interactions related to innate immunity highlighted Stat3 as a potential transcriptional regulator of IL-1 signalling. The complex, downstream effects of IL-1 signalling through the IL-1RI receptor remain poorly defined. Using network-based analyses of transcriptomic signatures in IL-1RI(-/-) mice, we have identified expression changes in genes involved in lipid cycling and TCA cycle, which may be more broadly indicative of a restoration of mitochondrial function in the context of HFD. Our results also highlight a potential role for Stat3 in linking IL-1 signalling to adipogenesis and IR. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Structural insights into the interaction of human IgG1 with FcγRI: no direct role of glycans in binding

    SciTech Connect

    Oganesyan, Vaheh Mazor, Yariv; Yang, Chunning; Cook, Kimberly E.; Woods, Robert M.; Ferguson, Andrew; Bowen, Michael A.; Martin, Tom; Zhu, Jie; Wu, Herren; Dall’Acqua, William F.

    2015-10-31

    In an effort to identify the critical structural features responsible for the high-affinity interaction of IgG1 Fc with FcγRI, the structure of the corresponding complex was solved at a resolution of 2.4 Å. The three-dimensional structure of a human IgG1 Fc fragment bound to wild-type human FcγRI is reported. The structure of the corresponding complex was solved at a resolution of 2.4 Å using molecular replacement; this is the highest resolution achieved for an unmutated FcγRI molecule. This study highlights the critical structural and functional role played by the second extracellular subdomain of FcγRI. It also explains the long-known major energetic contribution of the Fc ‘LLGG’ motif at positions 234–237, and particularly of Leu235, via a ‘lock-and-key’ mechanism. Finally, a previously held belief is corrected and a differing view is offered on the recently proposed direct role of Fc carbohydrates in the corresponding interaction. Structural evidence is provided that such glycan-related effects are strictly indirect.

  9. 78 FR 19024 - Submission for Review: It's Time to Sign Up for Direct Deposit or Direct Express, RI 38-128

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... MANAGEMENT Submission for Review: It's Time to Sign Up for Direct Deposit or Direct Express, RI 38-128 AGENCY... agencies the opportunity to comment on revised information collection request (ICR) 3206-0226, It's Time to...: Retirement Operations, Retirement Services, Office of Personnel Management. Title: It's Time to Sign Up for...

  10. 77 FR 66190 - Submission for Review: It's Time To Sign Up for Direct Deposit or Direct Express, RI 38-128

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-02

    ... MANAGEMENT Submission for Review: It's Time To Sign Up for Direct Deposit or Direct Express, RI 38-128 AGENCY... agencies the opportunity to comment on a revised information collection request (ICR) 3206-0226, It's Time... Management. Title: It's Time To Sign Up for Direct Deposit or Direct Express. OMB Number: 3206-0226...

  11. Allergic FcεRI- and pseudo-allergic MRGPRX2-triggered mast cell activation routes are independent and inversely regulated by SCF.

    PubMed

    Babina, M; Guhl, S; Artuc, M; Zuberbier, T

    2017-08-31

    While allergic mast cell (MC) degranulation occurs by FcεRI aggregation and varies in strength among subjects, the analogous pseudo-allergic route was recently uncovered to proceed via MRGPRX2. Here, we examine interindividual variability in skin MC responses to FcεRI triggering vs those evoked by MRGPRX2. While population-based variability is comparable between the routes, FcεRI- and MRGPRX2-stimulated pathways are completely independent from each other, and responsiveness to one has therefore no predictive value for the other. Conversely, degranulation triggered by compound 48/80 is highly correlated to the process elicited by substance P. MRGPRX2 mRNA shows pronounced population-based variability (coefficient of variation 102.9%). Surprisingly, stem cell factor (SCF) as the MC-supportive mediator par excellence potently inhibits pseudo-allergic degranulation, while it simultaneously promotes allergic stimulation via FcεRI. We conclude that SCF can have selective MC-dampening functions. Clinically, the data imply that subjects highly reactive in one pathway are not automatically hyper-responsive in terms of the alternative route. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  12. FcɛRI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane

    PubMed Central

    Nishida, Keigo; Yamasaki, Satoru; Ito, Yukitaka; Kabu, Koki; Hattori, Kotaro; Tezuka, Tohru; Nishizumi, Hirofumi; Kitamura, Daisuke; Goitsuka, Ryo; Geha, Raif S.; Yamamoto, Tadashi; Yagi, Takeshi; Hirano, Toshio

    2005-01-01

    The aggregation of high affinity IgE receptors (Fcɛ receptor I [FcɛRI]) on mast cells is potent stimulus for the release of inflammatory and allergic mediators from cytoplasmic granules. However, the molecular mechanism of degranulation has not yet been established. It is still unclear how FcɛRI-mediated signal transduction ultimately regulates the reorganization of the cytoskeleton and how these events lead to degranulation. Here, we show that FcɛRI stimulation triggers the formation of microtubules in a manner independent of calcium. Drugs affecting microtubule dynamics effectively suppressed the FcɛRI-mediated translocation of granules to the plasma membrane and degranulation. Furthermore, the translocation of granules to the plasma membrane occurred in a calcium-independent manner, but the release of mediators and granule–plasma membrane fusion were completely dependent on calcium. Thus, the degranulation process can be dissected into two events: the calcium-independent microtubule-dependent translocation of granules to the plasma membrane and calcium-dependent membrane fusion and exocytosis. Finally, we show that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical role in the calcium-independent microtubule-dependent pathway. PMID:15998803

  13. Instability structures during periods of large Richardson number (Ri > 14): Evidence of parametric instability

    NASA Astrophysics Data System (ADS)

    Walterscheid, R. L.; Gelinas, L. J.; Hecht, J. H.; Liu, A. Z.

    2013-07-01

    commonly used criteria for shear and convective instabilities were developed for steady horizontally uniform background flows. However, the formalism that rigorously addresses the instability of waves on a basic state modulated by a primary wave is Floquet theory in which the basic state includes a wave. A Floquet system supports parametric instabilities when conventional Richardson number (Ri) criteria indicate that the system is stable. In a study of small-scale instability structures during the Maui MALT campaign, Hecht et al. (2005) noted that there were occurrences of ripple (instability) structure when the conventional criteria indicated stable conditions. We have followed up this work with a detailed survey of the occurrence of ripple structure over Maui during periods that were both stable and unstable according to conventional criteria. Values of Ri were calculated from lidar data. We have found frequent occurrence of ripple structure when Ri > 14. We have focused on a period when there are clear indications of waves and ripple structure exhibiting two-dimensional instability structure when Ri 1 or greater. These results are analyzed in terms of Floquet theory and interpreted as parametric instabilities occurring for modest primary wave amplitudes.

  14. 76 FR 18812 - Submission for Review: We Need the Social Security Number of the Person Named Below, RI 38-45

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... MANAGEMENT Submission for Review: We Need the Social Security Number of the Person Named Below, RI 38-45... agencies the opportunity to comment on a revised information collection request (ICR) 3206-0144, We Need..._submission@omb.eop.gov or faxed to (202) 395-6974. SUPPLEMENTARY INFORMATION: We Need the Social...

  15. Interaction between activated chemokine receptor 1 and FcεRI at membrane rafts promotes communication and F-actin-rich cytoneme extensions between mast cells

    PubMed Central

    Beer, Freddy; Ono, Shoichiro; Ono, Santa J.

    2010-01-01

    Chemokines play important regulatory roles in immunity, but their contributions to mast cell function remain poorly understood. We examined the effects of FcεRI–chemokine receptor (CCR) 1 co-stimulation on receptor localization and cellular morphology of bone marrow-derived mast cells. Whereas FcεRI and CCR1 co-localized at the plasma membrane in unsensitized cells, sensitization with IgE promoted internalization of CCR1 molecules. Co-stimulation of FcεRI and CCR1 with antigen and macrophage inflammatory protein-1α was more effective than FcεRI stimulation alone in causing leading edge formation, flattened morphology, membrane ruffles and ganglioside (GM1+) lipid mediator release. Co-stimulation resulted in phalloidin-positive cytoneme-like cellular extensions, also known as tunneling nanotubes, which originated at points of calcium accumulation. This is the first report of cytoneme formation by mast cells. To determine the importance of lipid rafts for mast cell function, the cells were cholesterol depleted. Cholesterol depletion enhanced degranulation in resting, sensitized and co-stimulated cells, but not in FcεRI-cross-linked cells, and inhibited formation of filamentous actin+ cytonemes but not GM1+ cytonemes. Treatment with latrunculin A to sequester globular-actin abolished cytoneme formation. The cytonemes may participate in intercellular communication during allergic and inflammatory responses, and their presence in the co-stimulated mast cells suggests new roles for CCRs in immunopathology. PMID:20173038

  16. Absence of Tec Family Kinases Interleukin-2 Inducible T cell Kinase (Itk) and Bruton's Tyrosine Kinase (Btk) Severely Impairs FcϵRI-dependent Mast Cell Responses*

    PubMed Central

    Iyer, Archana S.; Morales, J. Luis; Huang, Weishan; Ojo, Folake; Ning, Gang; Wills, Elizabeth; Baines, Joel D.; August, Avery

    2011-01-01

    Mast cells are critical effector cells in the pathophysiology of allergic asthma and other IgE-mediated diseases. The Tec family of tyrosine kinases Itk and Btk serve as critical signal amplifiers downstream of antigen receptors. Although both kinases are expressed and activated in mast cells following FcϵRI stimulation, their individual contributions are not clear. To determine whether these kinases play unique and/or complementary roles in FcϵRI signaling and mast cell function, we generated Itk and Btk double knock-out mice. Analyses of these mice show decreased mast cell granularity and impaired passive systemic anaphylaxis responses. This impaired response is accompanied by a significant elevation in serum IgE in Itk/Btk double knock-out mice. In vitro analyses of bone marrow-derived mast cells (BMMCs) indicated that Itk/Btk double knock-out BMMCs are defective in degranulation and cytokine secretion responses downstream to FcϵRI activation. These responses were accompanied by a significant reduction in PLCγ2 phosphorylation and severely impaired calcium responses in these cells. This defect also results in altered NFAT1 nuclear localization in double knock-out BMMCs. Network analysis suggests that although they may share substrates, Itk plays both positive and negative roles, while Btk primarily plays a positive role in mast cell FcϵRI-induced cytokine secretion. PMID:21212279

  17. EPA Will Host Community Visioning Session for Superfund Site in Cumberland, R.I. Wednesday, May 11 at 6:30 p.m.

    EPA Pesticide Factsheets

    EPA invites members of the Cumberland, R.I. community to attend a presentation and community visioning session, which is designed and intended to gather community input on the future reuse of the Peterson/Puritan, Inc. OU2 Superfund Site in Cumberland an

  18. Activity measurements of the radionuclide 99mTc for the VNIIM, Russian Federation and ENEA-INMRI, Italy, in the ongoing comparison BIPM.RI(II)-K4.Tc-99m and KCRV update in the BIPM.RI(II)-K1.Tc-99m comparison

    NASA Astrophysics Data System (ADS)

    Michottea, C.; Nonisa, M.; Alekseevb, I. V.; Kharitonovb, I. A.; Tereshchenkob, E. E.; Zanevskiyb, A. V.; Capognic, M.; De Felicec, P.; Fazioc, A.; Carconic, P.

    2016-01-01

    In 2014, comparisons of activity measurements of 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the VNIIM (Russian Federation) and at the ENEA-INMRI (Italy), with comparison identifier BIPM.RI(II)-K4.Tc-99m. Ampoules containing about 32 kBq of 99mTc solutions were measured in the SIRTI for three half-lives. There are now nine results in the BIPM.RI(II)-K4.Tc-99m comparison. This comparison is linked to the BIPM.RI(II)-K1.Tc-99m comparison and the key comparison reference value (KCRV) of the BIPM.RI(II)-K1.Tc-99m has been updated to include eligible results from BIPM.RI(II)-K4.Tc-99m. The degrees of equivalence between each equivalent activity measured in the SIR or the SIRTI and the KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

    PubMed

    Heineke, Marieke H; van der Steen, Lydia P E; Korthouwer, Rianne M; Hage, J Joris; Langedijk, Johannes P M; Benschop, Joris J; Bakema, Jantine E; Slootstra, Jerry W; van Egmond, Marjolein

    2017-07-24

    The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. IgE enhances Fc epsilon RI expression and IgE-dependent TNF-alpha release from canine skin mast cells.

    PubMed

    Brazís, P; De Mora, F; Ferrer, L; Puigdemont, A

    2002-03-01

    The role of IgE on mast cell (MC) activation is well known. Recent studies have demonstrated that IgE also has the ability to up-regulate the high affinity IgE receptor (Fc epsilon RI) on the surface of human and murine MC, leading to an increased production of cytokines and chemokines. In the present study, we have examined the influence of IgE levels on Fc epsilon RI expression, and its consequences on TNF-alpha production from canine skin MC. Mature MC were enzymatically dispersed from the skin biopsies of 6-8 dogs and were cultured for up to 5 days in medium supplemented with recombinant canine stem cell factor (SCF) (6 ng/ml), in the presence of increasing serum IgE concentrations (ranging from 0 to 80 microg/ml). Subsequently, skin MC were activated with anti-IgE, and TNF-alpha concentration was assessed 5h post-activation by a cytotoxic bioassay. Fc epsilon RI receptors were identified in MC surface by flow cytometry. MC cultured for up to 5 days in the presence of high serum IgE concentration (8 microg/ml) produced twice the quantity of TNF-alpha than MC cultured in the absence of serum IgE, in response to stimulation with anti-IgE. Moreover, the percentage of Fc epsilon RI-positive skin cells was found to be approximately double in cells cultured with serum IgE compared to that cultured in the absence of IgE, following saturation of IgE receptors. These results suggest that, as found in human and murine MC, IgE may induce an up-regulation of the Fc epsilon RI density and an enhancement in the secretory activity of canine skin MC. This study could be of great interest in designing new therapeutic strategies for controlling MC activation in inflammatory and allergic processes.

  1. Promoter sequences in the RI beta subunit gene of cAMP-dependent protein kinase required for transgene expression in mouse brain.

    PubMed

    Clegg, C H; Haugen, H S; Boring, L F

    1996-01-19

    Neural-specific expression of the mouse regulatory type-I beta (RI beta) subunit gene of cAMP-dependent protein kinase is controlled by a fragment of genomic DNA comprised of a TATA-less promoter flanked by 1.5 kilobases of 5'-upstream sequence and a 1.8-kilobase intron. This DNA contains a complex arrangement of transcription factor binding motifs, and previous experiments have shown that many of these are recognized by proteins found in brain nuclear extract. To identify sequences critical for RI beta expression in functional neurons, we performed a deletion analysis in transgenic mice. Evidence is presented that the GC-rich proximal promoter is responsible for cell type-specific expression in vivo because RI beta DNA containing as little as 17 base pairs (bp) of 5'-upstream sequence was functional in mouse brain. One likely regulatory element coincides with the start of transcription and includes an EGR-1 motif and 3 consecutive SP1 sites within a 21-bp interval. Maximal RI beta promoter activity required the adjacent 663 bp of 5'-upstream DNA where most, but not all, of the regulatory activity was localized between position -663 and -333. A 37-bp direct repeat lies within this region that contains 2 basic helix-loop-helix binding sites, each of which are overlapped by two steroid hormone receptor half-sites, and a shared AP1 consensus sequence. Intron I sequences were also tested, and deletion of a 388-bp region containing numerous Sp1-like sequences lowered transgene activity significantly. These results have identified specific regions of the RI beta promoter that are required for the expression of this signal transduction protein in mouse neurons.

  2. Leukocyte immunoglobulin-like receptor B4 regulates key signalling molecules involved in FcγRI-mediated clathrin-dependent endocytosis and phagocytosis

    PubMed Central

    Park, Mijeong; Raftery, Mark J.; Thomas, Paul S.; Geczy, Carolyn L.; Bryant, Katherine; Tedla, Nicodemus

    2016-01-01

    FcγRI cross-linking on monocytes may trigger clathrin-mediated endocytosis, likely through interaction of multiple intracellular molecules that are controlled by phosphorylation and dephosphorylation events. However, the identity of phospho-proteins and their regulation are unknown. We proposed the leukocyte immunoglobulin-like receptor B4 (LILRB4) that inhibits FcγRI-mediated cytokine production via Tyr dephosphorylation of multiple kinases, may also regulate endocytosis/phagocytosis through similar mechanisms. FcγRI and/or LILRB4 were antibody-ligated on THP-1 cells, lysates immunoprecipitated using anti-pTyr antibody and peptides sequenced by mass spectrometry. Mascot Search identified 25 Tyr phosphorylated peptides with high confidence. Ingenuity Pathway Analysis revealed that the most significantly affected pathways were clathrin-mediated endocytosis and Fc-receptor dependent phagocytosis. Tyr phosphorylation of key candidate proteins in these pathways included common γ-chain of the Fc receptors, Syk, clathrin, E3 ubiquitin protein ligase Cbl, hepatocyte growth factor-regulated tyrosine kinase substrate, tripartite motif-containing 21 and heat shock protein 70. Importantly, co-ligation of LILRB4 with FcγRI caused significant dephosphorylation of these proteins and was associated with suppression of Fc receptor-dependent uptake of antibody-opsonised bacterial particles, indicating that LILRB4. These results suggest that Tyr phosphorylation may be critical in FcγRI-dependent endocytosis/phagocytosis that may be regulated by LILRB4 by triggering dephosphorylation of key signalling proteins. PMID:27725776

  3. Domain one of the high affinity IgE receptor, FcepsilonRI, regulates binding to IgE through its interface with domain two.

    PubMed

    Rigby, L J; Epa, V C; Mackay, G A; Hulett, M D; Sutton, B J; Gould, H J; Hogarth, P M

    2000-03-31

    The high affinity receptor for IgE, FcepsilonRI, binds IgE through the second Ig-like domain of the alpha subunit. The role of the first Ig-like domain is not well understood, but it is required for optimal binding of IgE to FcepsilonRI, either through a minor contact interaction or in a supporting structural capacity. The results reported here demonstrate that domain one of FcepsilonRI plays a major structural role supporting the presentation of the ligand-binding site, by interactions generated within the interdomain interface. Analysis of a series of chimeric receptors and point mutants indicated that specific residues within the A' strand of domain one are crucial to the maintenance of the interdomain interface, and IgE binding. Mutation of the Arg(15) and Phe(17) residues caused loss in ligand binding, and utilizing a homology model of FcepsilonRI-alpha based on the solved structure of FcgammaRIIa, it appears likely that this decrease is brought about by collapse of the interface and consequently the IgE-binding site. In addition discrepancies in results of previous studies using chimeric IgE receptors comprising FcepsilonRIalpha with either FcgammaRIIa or FcgammaRIIIA can be explained by the presence or absence of Arg(15) and its influence on the IgE-binding site. The data presented here suggest that the second domain of FcepsilonRI-alpha is the only domain involved in direct contact with the IgE ligand and that domain one has a structural function of great importance in maintaining the integrity of the interdomain interface and, through it, the ligand-binding site.

  4. Novel bioactive oxazolomycin isomers produced by Streptomyces albus JA3453.

    PubMed

    Kanzaki, H; Wada, K; Nitoda, T; Kawazu, K

    1998-03-01

    Two novel oxazolomycin isomers, oxazolomycins B (2) and C (3), were isolated from the fermentation broth of an oxazolomycin-producing strain, Streptomyces albus JA3453. Both compounds are geometrical isomers of oxazolomycin (1), the configurations of their triene moieties being (4'E, 6'E, 8'E) (2) and (4'Z, 6'E, 8'E) (3) while that of oxazolomycin (1) is (4'Z, 6'Z, 8'E). Compounds 2 and 3 exhibited potent inhibitory activity against crown gall formation with the same MIC (0.8 microgram/disk) as oxazolomycin. Compounds 2 and 3 showed no antibacterial activity against Agrobacterium tumefaciens, in contrast to oxazolomycin which has specific anti-A. tumefaciens activity.

  5. Subthreshold desensitization of human basophils re-capitulates the loss of Syk and FcεRI expression characterized by other methods of desensitization.

    PubMed

    MacGlashan, D

    2012-07-01

    Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 h. In prior studies, this method was re-capitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signalling studies of human basophils have identified changes in signalling by using other methods of inducing cellular desensitization. This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. The loss of FcεRI and syk was examined in human basophils. It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/mL IL-3, the concentration-dependence of histamine release shifted to 100-fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100-fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signalling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100-fold. These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signalling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signalling elements that are downstream of syk activation. © 2012 Blackwell Publishing Ltd.

  6. Subthreshold Desensitization of Human Basophils Re-capitulates the Loss of syk and FcεRI expression Characterized by Other Methods of Desensitization

    PubMed Central

    MacGlashan, Donald

    2012-01-01

    Background Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 hours. In prior studies, this method was recapitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signaling studies of human basophils have identified changes in signaling by using other methods of inducing cellular desensitization. Objective This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. Methods The loss of FceRI and syk was examined in human basophils. Results It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/ml IL-3, the concentration-dependence of histamine release shifted to 100 fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100 fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signaling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100 fold. Conclusions These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signaling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signaling elements that are downstream of syk activation. PMID:22702505

  7. Interaction of berenil with the EcoRI dodecamer d(CGCGAATTCGCG) sub 2 in solution studied by NMR

    SciTech Connect

    Lane, A.N. ); Jenkins, T.C.; Neidle, S. ); Brown, T. )

    1991-02-05

    The conformation of the EcoRI dodecamer d(CGCGAATTCGCG){sub 2} has been examined in solution by {sup 1}H and {sup 31}P NMR. Spin-spin coupling constants and nuclear Overhauser (NOE) enhancement spectroscopy show that all deoxyriboses lie in the south domain, with a small admixture of the north conformation (0-20%). The time dependence of the nuclear Overhauser enhancements also reveals a relatively uniform conformation at the glycosidic bonds. The average helical twist is 36.5. Tilt angles are small, and roll angles are poorly determined. Both the NOE intensities and {sup 31}P relaxation data imply conformational anomalies at the C3-G4/C9-G10 and the A5-A6/T7-T8 steps. Berenil binds in 1:1 stoichiometry to the dodecamer with high affinity and causes substantial changes in chemical shifts of the sugar protons of nucleotides Ado 5-Cyt 9 and of the H2 resonances of the two Ado residues. NOEs are observed between the aromatic protons of berenil and the H1{prime} of both Thy 7 and Thy 8, as well as to Ado 5 and Ado 6 H2. These results firmly establish that berenil binds via the minor groove and closely approaches the nucleotides Ado 6, Thy 7, and Thy 8. Using the observed NOEs between the ligand and the DNA together with the derived glycosidic torsion angles, the authors have built models that satisfy all of the available solution data.

  8. Distribution and Dynamics of Rat Basophilic Leukemia Immunoglobulin E Receptors (FcɛRI) on Planar Ligand-Presenting Surfaces

    PubMed Central

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A.; Wilson, Bridget S.; Timlin, Jerilyn A.; Thomas, James L.

    2010-01-01

    Abstract There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcɛRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (±50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D ∼10−1μm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes. PMID:20643056

  9. Effects of catastrophic draining of Wisconsinian glacial lakes on the continental shelf; an example from Block Island Sound, RI

    NASA Astrophysics Data System (ADS)

    Klotsko, S.; Driscoll, N. W.

    2013-12-01

    After the last glacial maximum (~21 kya) runoff from the Laurentide ice sheet was trapped behind terminal moraines, creating large glacial lakes along the New York-southern New England coast. These lakes drained catastrophically from east to west, with Lake Block Island Sound (occupying current Block Island Sound, RI; BIS) draining ~ 16 kya. Glacial Lake Connecticut, located in current Long Island Sound just south of BIS, drained through Block Island Sound approximately 500 years later. This catastrophic draining created large, 100-meter deep depressions on the shelf as waters flowed through a low in the moraine called ';The Race'. These depressions have remained open through the transgression, with exposure to swift modern tidal currents in the region. In 1999, the two easternmost, more circular features were mapped using high-resolution seismic CHIRP data. These data show several geologic units, including bedrock, glacial lake varved deposits, and modern sediment. The modern sediment can be seen prograding towards the eastern depression, but is hindered by a local topographic high, preventing the depression from being filled. We postulate that the depressions were not filled in with sediment during the transgression because they were filled with ice and are now drowned kettle holes. Another possibility is the transgression across the shelf was too rapid for sediment to fill in such large depressions.

  10. Zebrafish mast cells possess an FcɛRI-like receptor and participate in innate and adaptive immune responses.

    PubMed

    Da'as, Sahar; Teh, Evelyn M; Dobson, J Tristan; Nasrallah, Gheyath K; McBride, Eileen R; Wang, Hao; Neuberg, Donna S; Marshall, Jean S; Lin, Tong-Jun; Berman, Jason N

    2011-01-01

    We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p=0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p=0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FcɛRIγ) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish FcɛRI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p=0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells.

    PubMed

    Kamide, Yosuke; Ishizuka, Tamotsu; Tobo, Masayuki; Tsurumaki, Hiroaki; Aoki, Haruka; Mogi, Chihiro; Nakakura, Takashi; Yatomi, Masakiyo; Ono, Akihiro; Koga, Yasuhiko; Sato, Koichi; Hisada, Takeshi; Dobashi, Kunio; Yamada, Masanobu; Okajima, Fumikazu

    2015-08-28

    Although blood pH is maintained in a narrow range of around pH 7.4 in living organisms, inflammatory loci are characterized by acidic conditions. Mast cells tend to reside close to the surface of the body in areas such as the mucosa and skin where they may be exposed to exogenous acids, and they play an important role in immune responses. However, little is known about the effects of extracellular acidification on the functions of mast cell. Here, we found that extracellular acidification increased the dinitrophenyl-conjugated human serum albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9 cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE. Extracellular acidification also inhibited migration of MC/9 cells toward DNP-HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt). These findings suggest that extracellular acidification augmented antigen/IgE-induced and FcεRI-mediated production of IL-6 and IL-13 in mast cells, and that this was associated with the enhancement of p38 MAPK and Akt activation.

  12. Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains

    PubMed Central

    Huang, Yue; Zhu, Xiaodong; Wang, Lishi; Liu, Xiaoyun; Lu, Lu; Jiao, Yan

    2014-01-01

    The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference. PMID:25133246

  13. Massively parallel algorithm and implementation of RI-MP2 energy calculation for peta-scale many-core supercomputers.

    PubMed

    Katouda, Michio; Naruse, Akira; Hirano, Yukihiko; Nakajima, Takahito

    2016-11-15

    A new parallel algorithm and its implementation for the RI-MP2 energy calculation utilizing peta-flop-class many-core supercomputers are presented. Some improvements from the previous algorithm (J. Chem. Theory Comput. 2013, 9, 5373) have been performed: (1) a dual-level hierarchical parallelization scheme that enables the use of more than 10,000 Message Passing Interface (MPI) processes and (2) a new data communication scheme that reduces network communication overhead. A multi-node and multi-GPU implementation of the present algorithm is presented for calculations on a central processing unit (CPU)/graphics processing unit (GPU) hybrid supercomputer. Benchmark results of the new algorithm and its implementation using the K computer (CPU clustering system) and TSUBAME 2.5 (CPU/GPU hybrid system) demonstrate high efficiency. The peak performance of 3.1 PFLOPS is attained using 80,199 nodes of the K computer. The peak performance of the multi-node and multi-GPU implementation is 514 TFLOPS using 1349 nodes and 4047 GPUs of TSUBAME 2.5. © 2016 Wiley Periodicals, Inc.

  14. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Tl-201 of activity measurements of the radionuclide 201Tl

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.

    2004-01-01

    Since 1979, six national metrology institutes (NMI) and another laboratory have submitted 16 samples of known activity of 201Tl to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Tl-201. The activities ranged from about 3.5 MBq to 207 MBq. The degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated and the results are given in the form of a matrix for six NMIs. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  15. Characterization of an EcoRI family of satellite DNA from two species of the genus Eptesicus (Vespertilionidae; Chiroptera).

    PubMed

    Marchal, J A; Martínez, S; Acosta, M J; Bullejos, M; Díaz de la Guardia, R; Sánchez, A

    2004-11-01

    We have cloned and sequenced a 321 bp band of repetitive DNA from Eptesicus fuscus and E. serotinus observed after gel electrophoresis of EcoRI digested genomic DNA in both species. Southern blot analysis of genomic DNA (from both species) digested with the same enzyme showed the existence of a ladder pattern indicating that the repetitive DNA is arrayed in tandem. The repetitive sequences have a monomer unit of 321 bp which is composed of two subunits of 160 bp, suggested by the existence of a 160 bp band in the ladder of E. fuscus and by the presence of some direct repeats found in the analysis of the consensus sequence. Analysis of the methylation status demonstrated that cytosines in CCGG sequences in this satellite DNA are methylated in E. fuscus but not in the E. serotinus. Alignment of the sequenced clones showed that several nucleotide positions are diagnostic species-specific and consequently the phylogenetic analysis grouped the monomer units from both species in two clearly separated groups.

  16. Cigarette smoke suppresses the surface expression of c-kit and FcεRI on mast cells.

    PubMed

    Givi, M E; Blokhuis, B R; Da Silva, C A; Adcock, I; Garssen, J; Folkerts, G; Redegeld, F A; Mortaz, E

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a multicomponent disease characterized by emphysema and/or chronic bronchitis. COPD is mostly associated with cigarette smoking. Cigarette smoke contains over 4,700 chemical compounds, including free radicals and LPS (a Toll-Like Receptor 4 agonist) at concentrations which may contribute to the pathogenesis of diseases like COPD. We have previously shown that short-term exposure to cigarette smoke medium (CSM) can stimulate several inflammatory cells via TLR4 and that CSM reduces the degranulation of bone-marrow-derived mast cells (BMMCs). In the current study, the effect of CSM on mast cells maturation and function was investigated. Coculturing of BMMC with CSM during the development of bone marrow progenitor cells suppressed the granularity and the surface expression of c-kit and Fc ε RI receptors. Stimulation with IgE/antigen resulted in decreased degranulation and release of Th1 and Th2 cytokines. The effects of CSM exposure could not be mimicked by the addition of LPS to the culture medium. In conclusion, this study shows that CSM may affect mast cell development and subsequent response to allergic activation in a TLR4-independent manner.

  17. Three-dimensional transition of a water flow around a heated cylinder at {{Re {=} 85}} and {{Ri {=} 1.0}}

    NASA Astrophysics Data System (ADS)

    Ren, Maosheng; Rindt, Camilo C. M.; van Steenhoven, Anton A.

    2006-11-01

    The three-dimensional flow transition behind a heated cylinder subjected to a horizontal flow (water is used as the working fluid; Pr {≃} 7) at a Reynolds number Re {=} 85 and a Richardson number Ri {=} 1.0, manifests itself in the far wake as escaping mushroom-type structures from the upper vortices. The origin of the escaping mushroom-type structures lies in the generation of streamwise vorticity in the near wake, which is described as a cyclic process. In the presence of a spanwise temperature gradient in the near wake, streamwise vorticity is generated, which results from baroclinic vorticity production. Owing to these streamwise vorticity regions, low-speed flow will move upwards at so-called in-plume positions resulting in high- and low-speed streaks in the upper half of the wake. Next, ‘transverse’ vorticity is generated by the spanwise gradients in the streamwise velocity component, resulting in counter-rotating vortices directly behind the cylinder. These vortices lead to high- and low-temperature regions in the spanwise direction and the process repeats itself.

  18. Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

    PubMed

    Fadakar, Puran; Akbari, Abolfazl; Ghassemi, Fariba; Mobini, Gholam Reza; Mohebi, Masoumeh; Bolhassani, Manzar; Abed Khojasteh, Hoda; Heidari, Mansour

    2016-06-01

    Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment.

  19. Btk-dependent Rac activation and actin rearrangement following FcepsilonRI aggregation promotes enhanced chemotactic responses of mast cells.

    PubMed

    Kuehn, Hye Sun; Rådinger, Madeleine; Brown, Jared M; Ali, Khaled; Vanhaesebroeck, Bart; Beaven, Michael A; Metcalfe, Dean D; Gilfillan, Alasdair M

    2010-08-01

    Mast cells infiltrate the sites of inflammation associated with chronic atopic disease and during helminth and bacterial infection. This process requires receptor-mediated cell chemotaxis across a concentration gradient of their chemotactic ligands. In vivo, mast cells are likely to be exposed to several such agents, which can cooperate in a synergistic manner to regulate mast cell homing. Here, we report that chemotaxis of mouse bone-marrow-derived mast cells (BMMCs) in response to the chemoattractants stem-cell factor (SCF) and prostaglandin (PG)E(2), is substantially enhanced following antigen-dependent ligation of the high-affinity receptor for IgE (FcεRI). These responses were associated with enhanced activation of phosphoinositide 3-kinase (PI3K), and downstream activation of the tyrosine protein kinase Btk, with subsequent enhanced phospholipase (PL)Cγ-mediated Ca(2+) mobilization, Rac activation and F-actin rearrangement. Antigen-induced chemotaxis, and the ability of antigen to amplify responses mediated by SCF, adenosine and PGE(2) were suppressed following inhibition of PI3K, and were impaired in BMMCs derived from Btk(-/-) mice. There were corresponding decreases in the PLCγ-mediated Ca(2+) signal, Rac activation and F-actin rearrangement, which, as they are essential for BMMC chemotaxis, accounts for the impaired migration of Btk-deficient cells. Taken together, these data demonstrate that, by regulating signaling pathways that control F-actin rearrangement, Btk is crucial for the ability of antigen to amplify mast-cell chemotactic responses.

  20. Chemical composition of the essential oil from Corsican Mentha aquatica--combined analysis by GC(RI), GC-MS and 13C NMR spectroscopy.

    PubMed

    Sutour, Sylvain; Tomi, Félix; Bradesi, Pascale; Casanova, Joseph

    2011-10-01

    The essential oil (EO) of M. aquatica L. growing wild in Corsica was isolated by dry vapor distillation and submitted to combined analysis by column chromatography over silica gel, GC(RI), GC-MS and 13C NMR spectroscopy. The composition was dominated byoxygenated monoterpenes and characterized by the occurrence of menthofuran (50.7%) as the major component. In parallel, seven laboratory-distilled oil samples isolated from individual plants collected in Corsica were analyzed by GC(RI) and 13C NMR spectroscopy. Onlyquantitative differences were observed between the samples. Beside the usual terpenes, various p-menthane lactones (mintlactone, isomintlactone, hydroxymintlactone, menthofurolactone and epimenthofurolactone) have been identified in all the oil samples.

  1. Palindromic oligonucleotides containing 7-deaza-2'-deoxyguanosine: solid-phase synthesis of d[(p)GG*AATTCC] octamers and recognition by the endodeoxyribonuclease EcoRI.

    PubMed Central

    Seela, F; Driller, H

    1986-01-01

    Octadeoxynucleotides with the sequence d[(p)GG*AATTCC] have been prepared by solid-phase synthesis employing regular and base-modified phosphoramidites. These oligomers which contain an isosterically altered recognition sequence of the endodeoxyribonuclease Eco RI form duplexes under appropriate salt conditions. Since G* can represent 7-deaza-2'-deoxyguanosine the oligomers were used as probes to study their cleavage by the endodeoxyribonuclease Eco RI. The enzymatic hydrolysis of the modified octamer was strongly decreased compared to the regular DNA-fragment. This shows that guanine N-7 located at the cleavage site is important for the recognition process by the enzyme. The residual enzymatic activity is discussed on the basis of reduced specificity towards the recognition fragment. The fact that this cleavage occurs already under regular conditions indicates that the process described here bases on an intrinsic property of the oligomer and is different from the star activity. PMID:3008089

  2. Detailed analysis of the essential oil from Cistus albidus L. by combination of GC/RI, GC/MS and 13C-NMR spectroscopy.

    PubMed

    Paolini, Julien; Tomi, Pierre; Bernardini, Antoine-François; Bradesi, Pascale; Casanova, Joseph; Kaloustian, Jacques

    2008-01-01

    The composition of the essential oil of Cistus albidus (L.) obtained from plants growing wild in Provence (France) has been investigated using GC-RI (RI = retention indices), GC/MS and (13)C-NMR. Eighty-eight components were reported accounting for 81.8% of the essential oil. This essential oil was characterized by a high content of sesquiterpenes with alpha-zingiberene (12.8%), alpha-curcumene (7.7%), (E)-beta-caryophyllene (5.9%), alpha-cadinol (5.4%), alpha-bisabolol (4.1%), caryophyllene oxide (3.8%), allo-aromadendrene (3.4%), delta-cadinene (3.4%), and germacrene D (3.1%) being the main components.

  3. Carrier phases for iodine in the Allende meteorite and their associated Xe-129(r)/I-127 ratios - A laser microprobe study

    NASA Technical Reports Server (NTRS)

    Kirschbaum, C.

    1988-01-01

    This paper presents the results of a study of the carrier phases of iodine in the Allende meteorite and their associated Xe-129(r)/I-127 ratios, obtained using a new high-sensitivity low-blank mass spectrometer coupled with a low-blank laser extraction system. Two types of experiments were performed: a survey of the Xe-129(r) amounts in unirradiated specimens of fine-grained assemblages and individual coarse mineral grains, and a study of the relationship between chlorine and iodine in irradiated samples of the inclusions, in which the Xe-129(r)/I-127 ratios were determined for various minerals. As a by-product of these measurements, the Ar-40/Ar-39 ages were obtained along with some results on trapped Xe components. A schematic diagram of the new mass spectrometer system is included.

  4. Modeling tools for an Integrated River-Delta-Sea system investigation: the Pan-European Research Infrastructure DANUBIUS-RI philosophy

    NASA Astrophysics Data System (ADS)

    Umgiesser, Georg; Bellafiore, Debora; De Pascalis, Francesca; Icke, Joost; Stanica, Adrian

    2017-04-01

    The DANUBIUS Research Infrastructure (DANUBIUS-RI) is a new initiative to address the challenges and opportunities of research on large river- sea (RS) systems. DANUBIUS-RI is a distributed pan-European RI that will provide a platform for interdisciplinary research. It will deal with RS investigation through facilities and expertise from a large number of European institutions becoming a 'one-stop shop' for knowledge exchange in managing RS systems, ranging from freshwater to marine research. Globally, RS systems are complex and dynamic, with huge environmental, social and economic value. They are poorly understood but under increasing pressure through pollution, hydraulic engineering, water supply, energy, flood control and erosion. RS systems in Europe are among the most impacted globally, after centuries of industrialisation, urbanisation and agricultural intensification. Improved understanding is essential to avoid irreversible degradation and for restoration. DANUBIUS-RI will provide, among a number of other facilities concerning observations, analyses, impacts' evaluation, a modeling node that will provide integrated up-to-date tools, at locations of high scientific importance and opportunity, covering the RS systems - from source (upper parts of rivers - mountain lakes) to the transition with coastal seas. Modeling will be one of the major services provided by DANUBIUS-RI, relying on the inputs from the whole RI. RS systems are challenging from a modelling point of view, because of the complex morphology and the wide temporal and spatial range of processes occurring. Scale interaction plays a central role, considering the different hydro-eco-morphological processes on the large (basin) and small (local, coast, rivers, lagoons) scale. Currently, different model applications are made for the different geographical domains, and also for subsets of the processes. For instance there are separate models for rainfall runoff in the catchment, a sewer model for the

  5. Lin− CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors

    PubMed Central

    Dahlin, Joakim S.; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell

    2016-01-01

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow–derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34+ progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin−) CD34hi CD117int/hi FcεRI+ progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell–like phenotype, although with a slow cell division capacity in vitro. Isolated Lin− CD34hi CD117int/hi FcεRI+ blood cells had an immature mast cell–like appearance and expressed high levels of many mast cell–related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription–polymerase chain reaction. Altogether, we propose that the Lin− CD34hi CD117int/hi FcεRI+ blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin− CD34hi CD117int/hi FcεRI+ blood mast cell progenitors than asthmatics with normal lung function. PMID:26626992

  6. IgA Complexes in Plasma and Synovial Fluid of Patients with Rheumatoid Arthritis Induce Neutrophil Extracellular Traps via FcαRI.

    PubMed

    Aleyd, Esil; Al, Marjon; Tuk, Cornelis W; van der Laken, Conny J; van Egmond, Marjolein

    2016-12-15

    Autoantibodies, including rheumatoid factor (RF), are an important characteristic of rheumatoid arthritis (RA). Interestingly, several studies reported a correlation between the presence of IgA autoantibodies and worse disease course. We demonstrated previously that triggering the IgA Fc receptor (FcαRI) on neutrophils results in neutrophil recruitment and the release of neutrophil extracellular traps (NETs). Because this can lead to tissue damage, we investigated whether IgA immune complexes in plasma and synovial fluid of RA patients activate neutrophils. RF isotypes were measured with ELISA, and immune complexes were precipitated using polyethylene glycol 6000. Isolated neutrophils were incubated with immune complexes, and activation and release of NETs were determined in the presence or absence of FcαRI-blocking Abs. Plasma and SF of RA patients contained IgM, IgG, and IgA RFs. Patient plasma IgA RF and IgM RF showed a strong correlation. No uptake of IgM and minimal endocytosis of IgG immune complexes by neutrophils was observed, in contrast to avid uptake of IgA complexes. Incubation of neutrophils with immune complexes resulted in the production of reactive oxygen species, as well as the release of NETs, lactoferrin, and chemotactic stimuli. Importantly, activation of neutrophils was reduced when FcαRI was blocked. Neutrophils were activated by IgA immune complexes, which suggests that neutrophils play a role in inducing joint damage in RA patients who have IgA autoantibody complexes, thereby increasing the severity of disease. Blocking FcαRI inhibited neutrophil activation and, as such, may represent an additional attractive novel therapeutic strategy for the treatment of RA. Copyright © 2016 by The American Association of Immunologists, Inc.

  7. Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

    PubMed

    Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

    2016-01-28

    Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function.

  8. Determination of surface-bound hydroxypropylcellulose (HPC) on drug particles in colloidal dispersions using size exclusion chromatography: a comparison of ELS and RI detection.

    PubMed

    Zhu, Limin; Seburg, Randal A; Tsai, Eric W

    2006-03-18

    Evaporative light scattering (ELS) and refractive index (RI) detection methods were evaluated for the determination of surface-bound hydroxypropylcellulose (HPC) on drug particles in colloidal dispersions. Size exclusion chromatography (SEC) was used to separate HPC from other components of the dispersions. The instrumental parameters of the ELS detector were optimized to obtain maximum peak intensity, adequate peak shape and minimal baseline noise by varying the mobile phase flow rate, nebulizer temperature, and evaporation temperature. The chromatographic method was validated using both detectors. The ELS detector response exhibited second order polynomial and linear double logarithmic correlation with concentration over a 10-300% range while the RI response was linear. The double logarithmic correlation simplified the calculation compared to using the polynomial fit, and it provided more accurate results compared to the linear fit approach. Total HPC was obtained by solubilizing all components of the dispersion and analyzing for HPC. Non-bound HPC was obtained by ultracentrifuging the dispersion and analyzing the supernatant for HPC concentration. Analysis for total- and non-bound HPC in a representative colloidal dispersion gave method precisions with R.S.D.s of 2.5 and 2.2% for ELS, and 4.5 and 2.4% for RI (n=4). HPC bound to the surface of the drug particles was determined by difference: % bound HPC=100%-% non-bound HPC. Resultant % bound HPC values ranged from 22.1 to 25.4% of available HPC. Both ELS and RI are satisfactory detection techniques for HPC quantitation and for determination of the proportion of HPC bound to drug colloid particles, and the assay results are comparable.

  9. Continuous Dust Formation in SNe 2010jl and 2011ja

    NASA Astrophysics Data System (ADS)

    Krafton, Kelsie; Clayton, Geoffrey; Andrews, Jennifer; Barlow, Michael; De Looze, Ilse

    2016-08-01

    Studies in the last 10 years of dust formation in core-collapse supernovae (CCSNe) have found only small amounts, ~0.001 solar masses. This is far less than the amount needed to account for the large masses of dust seen in some high redshift galaxies. However, the recent discovery of ~1 solar mass of cold dust in the ejecta of SN 1987A has has caused a complete re-evaluation of dust formation in CCSNe. It has been suggested that the CCSNe are continuously forming dust so that by the time they are about 25 years old they will have dust masses similar to SN 1987A. However, there is a wide time gap between the CCSNe that have been studied recently and SN 1987A. We plan to use the sensitivity of Spitzer to detect dust emission from CCSNe 5 or more years after explosion. Radiative transfer models will be used to estimate the dust masses. This proposal is to continue our study of two interesting SNe 2010jl and 2011ja. These observations are part of a long term study requiring multiple epochs of Spitzer observations to look for evidence of continuous dust formation. These observations will help shed light on the mystery of dust in SN 1987A.

  10. THE PROGENITOR OF SN 2011ja: CLUES FROM CIRCUMSTELLAR INTERACTION

    SciTech Connect

    Chakraborti, Sayan; Ray, Alak; Yadav, Naveen; Smith, Randall; Ryder, Stuart; Sutaria, Firoza; Dwarkadas, Vikram V.; Chandra, Poonam; Pooley, David; Roy, Rupak

    2013-09-01

    Massive stars, possibly red supergiants, which retain extended hydrogen envelopes until core collapse, produce Type II plateau (IIP) supernovae. The ejecta from these explosions shocks the circumstellar matter originating from the mass loss of the progenitor during the final phases of its life. This interaction accelerates particles to relativistic energies which then lose energy via synchrotron radiation in the shock-amplified magnetic fields and inverse Compton scattering against optical photons from the supernova. These processes produce different signatures in the radio and X-ray parts of the electromagnetic spectrum. Observed together, they allow us to break the degeneracy between shock acceleration and magnetic field amplification. In this work, we use X-rays observations from the Chandra and radio observations from the Australia Telescope Compact Array to study the relative importance of processes which accelerate particles and those which amplify magnetic fields in producing the non-thermal radiation from SN 2011ja. We use radio observations to constrain the explosion date. Multiple Chandra observations allow us to probe the history of variable mass loss from the progenitor. The ejecta expands into a low-density bubble followed by interaction with a higher density wind from a red supergiant consistent with M{sub ZAMS} {approx}> 12 M{sub Sun }. Our results suggest that a fraction of Type IIP supernovae may interact with circumstellar media set up by non-steady winds.

  11. Regulation of FcϵRI Signaling in Mast Cells by G Protein-coupled Receptor Kinase 2 and Its RH Domain*

    PubMed Central

    Subramanian, Hariharan; Gupta, Kshitij; Parameswaran, Narayanan; Ali, Hydar

    2014-01-01

    Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) promotes their desensitization and internalization. Here, we sought to determine the role of GRK2 on FcϵRI signaling and mediator release in mast cells. The strategies utilized included lentiviral shRNA-mediated GRK2 knockdown, GRK2 gene deletion (GRK2flox/flox/cre recombinase) and overexpression of GRK2 and its regulator of G protein signaling homology (RH) domain (GRK2-RH). We found that silencing GRK2 expression caused ∼50% decrease in antigen-induced Ca2+ mobilization and degranulation but resulted in ablation of cytokine (IL-6 and IL-13) generation. The effect of GRK2 on cytokine generation does not require its catalytic activity but is mediated via the phosphorylation of p38 and Akt. Overexpression of GRK2 or its RH domain (GRK2-RH) enhanced antigen-induced mast cell degranulation and cytokine generation without affecting the expression levels of any of the FcϵRI subunits (α, β, and γ). GRK2 or GRK2-RH had no effect on antigen-induced phosphorylation of FcϵRIγ or Src but enhanced tyrosine phosphorylation of Syk. These data demonstrate that GRK2 modulates FcϵRI signaling in mast cells via at least two mechanisms. One involves GRK2-RH and modulates tyrosine phosphorylation of Syk, and the other is mediated via the phosphorylation of p38 and Akt. PMID:24904059

  12. Isoflavones suppress the expression of the FcεRI high-affinity immunoglobulin E receptor independent of the estrogen receptor.

    PubMed

    Yamashita, Shuya; Tsukamoto, Shuntaro; Kumazoe, Motofumi; Kim, Yoon-hee; Yamada, Koji; Tachibana, Hirofumi

    2012-08-29

    Isoflavones found in soybeans and soy products possess clinically relevant properties. However, the anti-allergic effect of isoflavones has been poorly studied. We examined the effects of isoflavones, genistein, daidzein, and equol, on the expression of the high-affinity immunoglobulin E (IgE) receptor, FcεRI, which plays a central role in IgE-mediated allergic response. Flow cytometric analysis showed that all of these isoflavones reduced the cell surface expression of FcεRI on mouse bone-marrow-derived mast cells and human basophilic KU812 cells. All isoflavones decreased the levels of the FcεRIα mRNA in the cells. Genistein reduced the mRNA expression of the β chain, and daidzein and equol downregulated that of the γ chain. The suppressive effects of isoflavones on FcεRI expression were unaffected by ICI 182,780, an estrogen receptor antagonist, suggesting that these effects were independent of estrogen receptors.

  13. A comparison of the use of refractive index (RI) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for the provenance establishment of glass bottles.

    PubMed

    May, Christopher D; Watling, R John

    2009-01-01

    The use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been compared with the traditional method of refractive index (RI) measurement for the establishment of the provenance of glass bottles. Using the RI method alone, it is not possible to discriminate between certain glass bottles produced up to 18 days apart from a single manufacturing plant. Furthermore, variations in RI within a single bottle can be large enough to invalidate co-provenance establishment using this technique alone. Determination of the trace elemental composition of bottles collected over a 1-month period confirmed that minimal variation of trace metal distribution occurred within individual bottles made during this period. Therefore, the trace element composition of any fragment of glass from a broken bottle may be considered representative of the elemental composition of the entire bottle. In addition, statistical comparison of the distribution of approximately 38 of the 56 analytes that were determined established that it was possible to discriminate between two glass bottles manufactured in the same plant two hours apart. Using this methodology it has been possible to develop an analytical protocol to significantly improve the accurate comparison and provenance establishment of forensic glass evidence.

  14. Focal adhesion molecule Kindlin-1 mediates activation of TGF-β signaling by interacting with TGF-βRI, SARA and Smad3 in colorectal cancer cells

    PubMed Central

    Wang, Yunling; Yang, Mingzi; Gao, Jianchao; Wei, Xiaofan; Fang, Weigang; Zhan, Jun; Zhang, Hongquan

    2016-01-01

    Kindlin-1, an integrin-interacting protein, has been implicated in TGF-β/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-β/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-β/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-β receptor I (TβRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TβRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-β/Smad3 signaling pathway. Functionally, Kindlin-1 promoted colorectal cancer (CRC) cell proliferation in vitro and tumor growth in vivo, and was also required for CRC cell migration and invasion via an epithelial to mesenchymal transition. Kindlin-1 was found to be increased with the CRC progression from stages I to IV. Importantly, raised expression level of Kindlin-1 correlates with poor outcome in CRC patients. Taken together, we demonstrated that Kindlin-1 promotes CRC progression by recruiting SARA and Smad3 to TβRI and thereby activates TGF-β/Smad3 signaling. Thus, Kindlin-1 is a novel regulator of TGF-β/Smad3 signaling and may also be a potential target for CRC therapeutics. PMID:27776350

  15. Formation of a Mast Cell Synapse: FcεRI Membrane Dynamics upon Binding Mobile or Immobilized Ligands on Surfaces1

    PubMed Central

    Carroll-Portillo, Amanda; Spendier, Kathrin; Pfeiffer, Janet; Griffiths, Gary; Li, Haitao; Lidke, Keith A.; Oliver, Janet M.; Lidke, Diane S.; Thomas, James L.; Wilson, Bridget S.; Timlin, Jerilyn A.

    2011-01-01

    High affinity IgE receptors (FcεRI) on mast cells form a “synapse” when presented with mobile, bilayer incorporated antigen. Here, we show that receptor reorganization within the contacting mast cell membrane is markedly different upon binding of mobile and immobilized ligands. Rat basophilic leukemia mast cells (RBL-2H3) primed with fluorescent anti-DNP IgE were engaged by surfaces presenting either bilayer-incorporated, monovalent DNP-lipid (mobile ligand) or chemically crosslinked, multivalent DNP (immobilized ligand). Total internal reflection fluorescence imaging and electron microscopy methods were used to visualize receptor reorganization at the contact site. The spatial relationships of FcεRI to other cellular components at the synapse, such as actin, cholesterol and LAT, were also analyzed. Stimulation of mast cells with immobilized polyvalent ligand resulted in typical levels of degranulation. Remarkably, degranulation also followed interaction of mast cells with bilayers presenting mobile, monovalent ligand. Receptors engaged with mobile ligand coalesce into large, cholesterol-rich clusters that occupy the central portion of the contacting membrane. These data indicate that FcεRI crosslinking is not an obligatory step in triggering mast cell signaling and suggest that dense populations of mobile receptors are capable of initiating low level degranulation upon ligand recognition. PMID:20042583

  16. Physical map and strand polarity of specific fragments of adenovirus-associated virus DNA produced by endonuclease R-EcoRI.

    PubMed Central

    Carter, B J; Khoury, G; Denhardt, D T

    1975-01-01

    Cleavage of adenovirus-associated virus type 2 (AAV2) DNA linear duplex monomers with the restriction endonuclease R-EcoRI yielded three fragments, A, B, and C, having approximate mol wt of 1.6 X 10(6), 1.1 X 10(6), and 1.3 X 10(5), respectively. Radioactive labeling the 5' termini of AAV DNA before cleavage with R-EcoRI showed that A and B were terminal fragments and C was internal. Separation of the complementary strands of fragments A and B showed that A contained the 5' terminus of the minus strand and the 3' terminus of the plus strand, and conversely for fragment B. The physical map of the AAV R-EcoRI fragments can thus be unambiguously determined and is drawn with B at the left-hand and A at the right-hand end. On this map, transcription of stable AAV mRNA from the minus strand proceeds from left to right, beginning in fragment B and terminating in fragment A. The asymmetry in distribution of thymidine between the AAV DNA plus and minus strands is preferentially located in fragment A, which represents the right-hand half of the duplex molecule. These experiments enable preparative separation of all four single-strand termini of AAV DNA and provide a basis for orientation of fragment maps derived by cleavage with other restriction enzymes. PMID:1159894

  17. The leukocyte receptor CD84 inhibits Fc epsilon RI-mediated signaling through homophilic interaction in transfected RBL-2H3 cells.

    PubMed

    Oliver-Vila, Irene; Saborit-Villarroya, Ifigènia; Engel, Pablo; Martin, Margarita

    2008-04-01

    Signaling through the high-affinity receptor for immunoglobulin E (Fc epsilon RI) results in the coordinated activation of tyrosine kinases, thus leading to calcium mobilization, degranulation, and leukotriene and cytokine synthesis. Here, we show that CD84, a member of the CD150 family of leukocyte receptors, inhibits Fc epsilon RI-mediated mast cell degranulation in CD84-transfected rat basophilic leukaemia-2H3 mast cell line cells (RBL-2H3) through homophilic interaction. There was no reduction in overall protein phosphorylation following IgE triggering in CD84 RBL-2H3 cells. Indeed, phosphorylation of Dok-1 and c-Cbl increased in CD84 RBL-2H3, suggesting that inhibition is mediated by these molecules. MAP kinase phosphorylation (ERK1/2, JNK and p38) and cytokine synthesis were impaired in CD84 RBL-2H3. This inhibitory mechanism was independent of SAP and SHP-2 recruitment. Interestingly, CD84 mutants in tyrosines (Y279F and DeltaY324) reversed this inhibitory profile. These data suggest that CD84 may play a role in modulating Fc epsilon RI-mediated signaling in mast cells. Thus, CD84 could play a protective role against undesired allergic and inflammatory responses.

  18. Focal adhesion molecule Kindlin-1 mediates activation of TGF-β signaling by interacting with TGF-βRI, SARA and Smad3 in colorectal cancer cells.

    PubMed

    Kong, Jinfeng; Du, Juan; Wang, Yunling; Yang, Mingzi; Gao, Jianchao; Wei, Xiaofan; Fang, Weigang; Zhan, Jun; Zhang, Hongquan

    2016-11-15

    Kindlin-1, an integrin-interacting protein, has been implicated in TGF-β/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-β/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-β/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-β receptor I (TβRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TβRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-β/Smad3 signaling pathway. Functionally, Kindlin-1 promoted colorectal cancer (CRC) cell proliferation in vitro and tumor growth in vivo, and was also required for CRC cell migration and invasion via an epithelial to mesenchymal transition. Kindlin-1 was found to be increased with the CRC progression from stages I to IV. Importantly, raised expression level of Kindlin-1 correlates with poor outcome in CRC patients. Taken together, we demonstrated that Kindlin-1 promotes CRC progression by recruiting SARA and Smad3 to TβRI and thereby activates TGF-β/Smad3 signaling. Thus, Kindlin-1 is a novel regulator of TGF-β/Smad3 signaling and may also be a potential target for CRC therapeutics.

  19. Update of the BIPM comparison BIPM.RI(II)-K1.Ho-166m activity measurements of the radionuclide 166mHo for the PTB (Germany), with linked results for the EURAMET.RI(II)-K2.Ho-166m comparison

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Courte, S.; Kossert, K.

    2015-01-01

    The PTB submitted directly to the SIR one ampoule of 166mHo prepared from a dilution of the solution distributed to four laboratories participating in the EURAMET.RI(II)-K2.Ho-166m comparison in 2013. No attempt to evaluate a new KCRV has been made and the usual procedure was applied to link the results of the comparison to the usual SIR entries through the PTB. One NMI used this K2 comparison to update its previous degree of equivalence which is older than 20 years. The degrees of equivalence between each equivalent activity measured in the International Reference System (SIR) and the KCRV have been calculated and the results are given in the form of a table for the four remaining laboratories in the BIPM.RI(II)-K1.Ho166m comparison, the six laboratories in the regional comparison APMP.RI(II)-K2.Ho166m and the four laboratories in the regional EURAMET.RI(II)-K2.Ho-166m comparison. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. EUROPLANET-RI modelling service for the planetary science community: European Modelling and Data Analysis Facility (EMDAF)

    NASA Astrophysics Data System (ADS)

    Khodachenko, Maxim; Miller, Steven; Stoeckler, Robert; Topf, Florian

    2010-05-01

    Computational modeling and observational data analysis are two major aspects of the modern scientific research. Both appear nowadays under extensive development and application. Many of the scientific goals of planetary space missions require robust models of planetary objects and environments as well as efficient data analysis algorithms, to predict conditions for mission planning and to interpret the experimental data. Europe has great strength in these areas, but it is insufficiently coordinated; individual groups, models, techniques and algorithms need to be coupled and integrated. Existing level of scientific cooperation and the technical capabilities for operative communication, allow considerable progress in the development of a distributed international Research Infrastructure (RI) which is based on the existing in Europe computational modelling and data analysis centers, providing the scientific community with dedicated services in the fields of their computational and data analysis expertise. These services will appear as a product of the collaborative communication and joint research efforts of the numerical and data analysis experts together with planetary scientists. The major goal of the EUROPLANET-RI / EMDAF is to make computational models and data analysis algorithms associated with particular national RIs and teams, as well as their outputs, more readily available to their potential user community and more tailored to scientific user requirements, without compromising front-line specialized research on model and data analysis algorithms development and software implementation. This objective will be met through four keys subdivisions/tasks of EMAF: 1) an Interactive Catalogue of Planetary Models; 2) a Distributed Planetary Modelling Laboratory; 3) a Distributed Data Analysis Laboratory, and 4) enabling Models and Routines for High Performance Computing Grids. Using the advantages of the coordinated operation and efficient communication between the

  1. Mutations in jasmonoyl-L-isoleucine-12-hydroxylases suppress multiple JA-dependent wound responses in Arabidopsis thaliana.

    PubMed

    Poudel, Arati N; Zhang, Tong; Kwasniewski, Misha; Nakabayashi, Ryo; Saito, Kazuki; Koo, Abraham J

    2016-09-01

    Plants rapidly perceive tissue damage, such as that inflicted by insects, and activate several key defense responses. The importance of the fatty acid-derived hormone jasmonates (JA) in dictating these wound responses has been recognized for many years. However, important features pertaining to the regulation of the JA pathway are still not well understood. One key unknown is the inactivation mechanism of the JA pathway and its relationship with plant response to wounding. Arabidopsis cytochrome P450 enzymes in the CYP94 clade metabolize jasmonoyl-L-isoleucine (JA-Ile), a major metabolite of JA responsible for many biological effects attributed to the JA signaling pathway; thus, CYP94s are expected to contribute to the attenuation of JA-Ile-dependent wound responses. To directly test this, we created the double and triple knock-out mutants of three CYP94 genes, CYP94B1, CYP94B3, and CYP94C1. The mutations blocked the oxidation steps and caused JA-Ile to accumulate 3-4-fold the WT levels in the wounded leaves. Surprisingly, over accumulation of JA-Ile did not lead to a stronger wound response. On the contrary, the mutants displayed a series of symptoms reminiscent of JA-Ile deficiency, including resistance to wound-induced growth inhibition, decreased anthocyanin and trichomes, and increased susceptibility to insects. The mutants, however, responded normally to exogenous JA treatments, indicating that JA perception or signaling pathways were intact. Untargeted metabolite analyses revealed >40% reduction in wound-inducible metabolites in the mutants. These observations raise questions about the current JA signaling model and point toward a more complex model perhaps involving JA derivatives and/or feedback mechanisms. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI.

    PubMed Central

    Shiue, L; Green, J; Green, O M; Karas, J L; Morgenstern, J P; Ram, M K; Taylor, M K; Zoller, M J; Zydowsky, L D; Bolen, J B

    1995-01-01

    Activation of protein tyrosine kinases is one of the initial events following aggregation of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on RBL-2H3 cells, a model mast cell line. The protein tyrosine kinase p72syk (Syk), which contains two Src homology 2 (SH2) domains, is activated and associates with phosphorylated Fc epsilon RI subunits after receptor aggregation. In this report, we used Syk SH2 domains, expressed in tandem or individually, as fusion proteins to identify Syk-binding proteins in RBL-2H3 lysates. We show that the tandem Syk SH2 domains selectively associate with tyrosine-phosphorylated forms of the gamma and beta subunits of Fc epsilon RI. The isolated carboxy-proximal SH2 domain exhibited a significantly higher affinity for the Fc epsilon RI subunits than did the amino-proximal domain. When in tandem, the Syk SH2 domains showed enhanced binding to phosphorylated gamma and beta subunits. The conserved tyrosine-based activation motifs contained in the cytoplasmic domains of the gamma and beta subunits, characterized by two YXXL/I sequences in tandem, represent potential high-affinity binding sites for the dual SH2 domains of Syk. Peptide competition studies indicated that Syk exhibits a higher affinity for the phosphorylated tyrosine activation motif of the gamma subunit than for that of the beta subunit. In addition, we show that Syk is the major protein in RBL-2H3 cells that is affinity isolated with phosphorylated peptides corresponding to the phosphorylated gamma subunit motif. These data suggest that Syk associates with the gamma subunit of the high-affinity receptor for immunoglobulin E through an interaction between the tandem SH2 domains of SH2 domains of Syk and the phosphorylated tyrosine activation motif of the gamma subunit and that Syk may be the major signaling protein that binds to Fc epsilon RI tyrosine activation motif of the gamma subunit and that Syk may be the major signaling protein that binds to Dc epsilon

  3. N-termini of EcoRI restriction endonuclease dimer are in close proximity on the protein surface.

    PubMed

    Liu, W; Chen, Y; Watrob, H; Bartlett, S G; Jen-Jacobson, L; Barkley, M D

    1998-11-03

    The N-terminal region of EcoRI endonuclease is essential for cleavage yet is invisible in the 2.5 A crystal structure of endonuclease-DNA complex [Kim, Y., Grable, J. C., Love, R., Greene, P. J., Rosenberg, J. M. (1990) Science 249, 1307-1309]. We used site-directed fluorescence spectroscopy and chemical cross-linking to locate the N-terminal region and assess its flexibility in the absence and presence of DNA substrate. The second amino acid in each subunit of the homodimer was replaced with cysteine and labeled with pyrene or reacted with bifunctional cross-linkers. The broad absorption spectra and characteristic excimer emission bands of pyrene-labeled muteins indicated stacking of the two pyrene rings in the homodimer. Proximity of N-terminal cysteines was confirmed by disulfide bond formation and chemical cross-linking. The dynamics of the N-terminal region were determined from time-resolved emission anisotropy measurements. The anisotropy decay had two components: a fast component with rotational correlation time of 0.3-3 ns representing probe internal motions and a slow component with 50-100 ns correlation time representing overall tumbling of the protein conjugate. We conclude that the N-termini are close together at the dimer interface with limited flexibility. Binding of Mg2+ cofactor or DNA substrate did not affect the location or flexibility of the N-terminal region as sensed by pyrene fluorescence and cross-linking, indicating that substrate binding is not accompanied by folding or unfolding of the N-terminus.

  4. Acidic environment augments FcεRI-mediated production of IL-6 and IL-13 in mast cells

    SciTech Connect

    Kamide, Yosuke; Ishizuka, Tamotsu; Tobo, Masayuki; Tsurumaki, Hiroaki; Aoki, Haruka; Mogi, Chihiro; Nakakura, Takashi; Yatomi, Masakiyo; Ono, Akihiro; Koga, Yasuhiko; Sato, Koichi; Hisada, Takeshi; Dobashi, Kunio; Yamada, Masanobu; Okajima, Fumikazu

    2015-08-28

    Although blood pH is maintained in a narrow range of around pH 7.4 in living organisms, inflammatory loci are characterized by acidic conditions. Mast cells tend to reside close to the surface of the body in areas such as the mucosa and skin where they may be exposed to exogenous acids, and they play an important role in immune responses. However, little is known about the effects of extracellular acidification on the functions of mast cell. Here, we found that extracellular acidification increased the dinitrophenyl-conjugated human serum albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9 cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE. Extracellular acidification also inhibited migration of MC/9 cells toward DNP-HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt). These findings suggest that extracellular acidification augmented antigen/IgE-induced and FcεRI-mediated production of IL-6 and IL-13 in mast cells, and that this was associated with the enhancement of p38 MAPK and Akt activation. - Highlights: • Antigen-induced IL-6 and IL-13 production was augmented by acidic pH in mast cells. • Acidic pH-induced actions were associated with activation of p38 MAPK and Akt. • Inhibition of p38 MAPK and Akt attenuated cytokine responses to acidic pH. • Acidic pH effects are not attributable to actions of known proton-sensing GPCRs.

  5. Analysis of TRPV channel activation by stimulation of FCεRI and MRGPR receptors in mouse peritoneal mast cells.

    PubMed

    Solís-López, A; Kriebs, U; Marx, A; Mannebach, S; Liedtke, W B; Caterina, M J; Freichel, M; Tsvilovskyy, V V

    2017-01-01

    The activation of mast cells (MC) is part of the innate and adaptive immune responses and depends on Ca2+ entry across the plasma membrane, leading to the release of preformed inflammatory mediators by degranulation or by de novo synthesis. The calcium conducting channels of the TRPV family, known by their thermo and osmotic sensitivity, have been proposed to be involved in the MC activation in murine, rat, and human mast cell models. So far, immortalized mast cell lines and nonspecific TRPV blockers have been employed to characterize the role of TRPV channels in MC. The aim of this work was to elucidate the physiological role of TRPV channels by using primary peritoneal mast cells (PMCs), a model of connective tissue type mast cells. Our RT-PCR and NanoString analysis identified the expression of TRPV1, TRPV2, and TRPV4 channels in PMCs. For determination of the functional role of the expressed TRPV channels we performed measurements of intracellular free Ca2+ concentrations and beta-hexosaminidase release in PMCs obtained from wild type and mice deficient for corresponding TRPV1, TRPV2 and TRPV4 in response to various receptor-mediated and physical stimuli. Furthermore, substances known as activators of corresponding TRPV-channels were also tested using these assays. Our results demonstrate that TRPV1, TRPV2, and TRPV4 do not participate in activation pathways triggered by activation of the high-affinity receptors for IgE (FcεRI), Mrgprb2 receptor, or Endothelin-1 receptor nor by heat or osmotic stimulation in mouse PMCs.

  6. A Novel Class of Pseudoautosomal Region 1 Deletions Downstream of SHOX Is Associated with Léri-Weill Dyschondrosteosis

    PubMed Central

    Benito-Sanz, Sara; Thomas, N. Simon; Huber, Céline; del Blanco, Darya Gorbenko; Aza-Carmona, Miriam; Crolla, John A.; Maloney, Vivienne; Argente, Jesús; Campos-Barros, Ángel; Cormier-Daire, Valérie; Heath, Karen E.

    2005-01-01

    ri-Weill dyschondrosteosis (LWD) is a pseudoautosomal dominant disorder characterized by disproportionate short stature and a characteristic curving of the radius, known as the “Madelung deformity.” SHOX mutations resulting in SHOX haploinsufficiency have been found in LWD and in a variable proportion of patients with idiopathic short stature (ISS), whereas homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia (LMD). Defects in SHOX have been identified in ∼60% of LWD cases, whereas, in the remaining ∼40%, the molecular basis is unknown. This suggests either genetic heterogeneity or the presence of mutations in unanalyzed regions of SHOX, such as the upstream, intragenic, or downstream regulatory sequences. Therefore, the pseudoautosomal region 1 (PAR1) of 80 patients with LWD, in whom SHOX deletions and mutations had been excluded, was screened for deletions by use of a new panel of microsatellite markers. We identified 12 patients with LWD who presented with a novel class of PAR1 deletions that did not include SHOX. The deletions were of variable size and mapped at least ∼30–530 kb downstream of SHOX. In our cohort, this type of deletion accounted for 15% of cases. In all cases, the deletions cosegregated with the phenotype. No apparent phenotypic differences were observed between patients with SHOX deletions and those with this new class of PAR1 deletions. Thus, we present here the identification of a second PAR1 region implicated in the etiopathogenesis of LWD. Our findings suggest the presence of distal regulatory elements of SHOX transcription in PAR1 or, alternatively, the existence of an additional locus apparently involved in the control of skeletal development. Deletion analysis of this newly identified region should be included in the mutation screening of patients with LWD, LMD, and ISS. PMID:16175500

  7. Analysis of TRPV channel activation by stimulation of FCεRI and MRGPR receptors in mouse peritoneal mast cells

    PubMed Central

    Solís-López, A.; Kriebs, U.; Marx, A.; Mannebach, S.; Liedtke, W. B.; Caterina, M. J.; Freichel, M.; Tsvilovskyy, V. V.

    2017-01-01

    The activation of mast cells (MC) is part of the innate and adaptive immune responses and depends on Ca2+ entry across the plasma membrane, leading to the release of preformed inflammatory mediators by degranulation or by de novo synthesis. The calcium conducting channels of the TRPV family, known by their thermo and osmotic sensitivity, have been proposed to be involved in the MC activation in murine, rat, and human mast cell models. So far, immortalized mast cell lines and nonspecific TRPV blockers have been employed to characterize the role of TRPV channels in MC. The aim of this work was to elucidate the physiological role of TRPV channels by using primary peritoneal mast cells (PMCs), a model of connective tissue type mast cells. Our RT-PCR and NanoString analysis identified the expression of TRPV1, TRPV2, and TRPV4 channels in PMCs. For determination of the functional role of the expressed TRPV channels we performed measurements of intracellular free Ca2+ concentrations and beta-hexosaminidase release in PMCs obtained from wild type and mice deficient for corresponding TRPV1, TRPV2 and TRPV4 in response to various receptor-mediated and physical stimuli. Furthermore, substances known as activators of corresponding TRPV-channels were also tested using these assays. Our results demonstrate that TRPV1, TRPV2, and TRPV4 do not participate in activation pathways triggered by activation of the high-affinity receptors for IgE (FcεRI), Mrgprb2 receptor, or Endothelin-1 receptor nor by heat or osmotic stimulation in mouse PMCs. PMID:28158279

  8. Sugars profiles of different chestnut (Castanea sativa Mill.) and almond (Prunus dulcis) cultivars by HPLC-RI.

    PubMed

    Barreira, João C M; Pereira, José Alberto; Oliveira, M Beatriz P P; Ferreira, Isabel C F R

    2010-03-01

    Sugar profiles of different almond and chestnut cultivars were obtained by high-performance liquid chromatography (HPLC), by means of a refractive index (RI) detector. A solid-liquid extraction procedure was used in defatted and dried samples. The chromatographic separation was achieved using a Eurospher 100-5 NH(2) column using an isocratic elution with acetonitrile/water (70:30, v/v) at a flow rate of 1.0 ml/min. All the compounds were separated in 16 min. The method was optimized and proved to be reproducible and accurate. Generally, more than 95% of sugars were identified for both matrixes. Sugars profiles were quite homogeneous for almond cultivars; sucrose was the main sugar (11.46 +/- 0.14 in Marcona to 22.23 +/- 0.59 in Ferragnes g/100 g of dried weight), followed by raffinose (0.71 +/- 0.05 in Ferraduel to 2.11 +/- 0.29 in Duro Italiano), glucose (0.42 +/- 0.12 in Pegarinhos two seeded to 1.47 +/- 0.19 in Ferragnes) and fructose (0.11 +/- 0.02 in Pegarinhos two seeded to 0.59 +/- 0.05 in Gloriette). Commercial cultivars proved to have higher sucrose contents, except in the case of Marcona. Nevertheless, chestnut cultivars revealed a high heterogeneity. Sucrose was the main sugar in Aveleira (22.05 +/- 1.48), Judia (23.30 +/- 0.83) and Longal (9.56 +/- 0.91), while glucose was slightly prevalent in Boa Ventura (6.63 +/- 0.49). The observed variance could serve for inter-cultivar discrimination.

  9. Impact of Stratification on Summer Hypoxia in Narragansett Bay, RI: Time-Series Observations and Numerical Modeling

    NASA Astrophysics Data System (ADS)

    Bergondo, D. L.; Kincaid, C. R.; Kester, D. R.

    2003-12-01

    Determining water column structure in a partially-mixed estuary, such as Narragansett Bay, is important for understanding the impact stratification has on phytoplankton productivity and dissolved oxygen concentrations. Stratification reduces vertical mixing and influences the vertical flux of ecologically important variables such as phytoplankton, heat, oxygen, and nutrients. We utilize a combination of buoy data and numerical modeling to better understand processes surrounding the evolution and breakdown in stratification in Narragansett Bay for a range of environmental conditions. Autonomous sensors have been deployed in Narragansett Bay to collect continuous high temporal resolution chemical and hydrographic data. Data were collected every fifteen minutes 0.5 m below the surface and 1 m from the bottom from July 2001 to December 2001 and from July 2002 to December 2002 at two locations in Narragansett Bay and the Providence River, RI. The suite of water column variables measured were surface and bottom temperature, salinity, dissolved oxygen and pH, and surface chlorophyll. Results show that stratification events occur intermittently in the Providence River and Narragansett Bay and that increased phytoplankton productivity and hypoxia were associated with summertime stratification events. The Regional Ocean Modeling System (ROMS) model, a three-dimensional hydrodynamic model developed by Rutgers University, New Jersey, has been applied to Narragansett Bay to determine how the basic layered flow can be perturbed by runoff events and variable winds. For instance, in the basic stratified flow pattern in Narragansett Bay there is an outward flow of fresher water at the surface and an inward flow of deep denser water within the channel, however, strong south winds shutdown the deep return flow. Time series observations combined with model relationships have been able to enhance the understanding of the development and breakdown of stratification and the impact

  10. EURAMET supplementary comparison of the personal dose equivalent quantity for photon radiation: EURAMET.RI(I)-S5

    NASA Astrophysics Data System (ADS)

    Ankerhold, U.; Hupe, O.

    2012-01-01

    Comparison measurements among primary standard facilities are required to achieve quality assurance in the realization and transfer of the quantity of personal dose equivalent, Hp(10), for photon radiation by national standards laboratories. Although some bilateral comparisons for this quantity had already taken place, in May 2003 the Consultative Committee for Ionizing Radiation [CCRI(I)] decided that a EUROMET supplementary comparison would be appropriate and that primary standards laboratories from other Regional Metrology Organizations could participate. The first comparison of the radiation protection quantity Hp(10) with low energy x-rays started in January 2004 and was completed in December 2007. The comparison was piloted by the PTB as EUROMET project No. 738 known also as EUROMET.RI(I)-S5. The operation and results of the comparison are reported here. The transfer instrument consisted of a secondary standard ionization chamber and a complete electronic measuring device. The response of this transfer instrument in various photon reference fields (N-15 and 0°, N-20 and 45°, N-30 and 75°, N-60 and 0°, N-120 and 0°, radiation quality according to ISO 4037-1:1996 [1]) was compared. Measurements were made by participants in 17 countries: Austria, France, Czech Republic, Finland, Germany, Greece, Hungary, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland, the Netherlands, the United Kingdom and by one international organization. The results obtained by most of the participants are consistent with the stated uncertainties. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  11. Seasonality of the copepods Acartia hudsonica and Acartia tonsa in Narragansett Bay, RI, USA during a period of climate change

    NASA Astrophysics Data System (ADS)

    Sullivan, Barbara K.; Costello, John H.; Van Keuren, D.

    2007-06-01

    Seasonality of species living at the boundaries of biogeographic zones may be more sensitive to climate change than in other regions. This is apparently the case for the ctenophore, Mnemiopsis leidyi, in Narragansett Bay, RI, which is the historical northern boundary of its distribution in the Northwest Atlantic. Seasonal advancement of population pulses of this ctenophore correlates with an increase in average annual temperatures of 1.2 °C over the last ˜50 years. Do other zooplankton in Narragansett Bay show evidence of altered phenologies? Here we examine patterns of seasonal succession of the copepod congeners, Acartia tonsa and Acartia hudsonica, for evidence of alteration over the period 1950-2004. A warming trend might be expected to limit springtime abundance of A. hudsonica, a temperate-boreal species that produces resting eggs in response to warm weather. Conversely, increasing temperatures could favor the summer dominant, A. tonsa, over its congener, allowing a shift to earlier appearance in spring, thus preserving the predator-free window that has previously allowed it a period of high production prior to ctenophore population pulses in late summer. Contrary to these predictions we found that A. hudsonica has become the dominant copepod of the congener pair. There has been no seasonal advancement of populations of A. tonsa, whose numbers have plummeted due to intensification of the predator-prey interaction with M. leidyi. In contrast, advancement of seasonal appearance of A. hudsonica is evident in sustained population increases earlier in spring (March rather than in May), although, as predicted, there is curtailment of its distribution in late spring. This latter shift is likely exacerbated by ctenophore predation. This study demonstrates the complexity of predicting individual species responses to climatic warming, even for species with well-known patterns of seasonal and geographic distribution.

  12. Structure, interaction, dynamics and solvent effects on the DNA-EcoRI complex in aqueous solution from molecular dynamics simulation.

    PubMed Central

    Sen, S; Nilsson, L

    1999-01-01

    A 0.7-ns molecular dynamics simulation of the DNA-EcoRI complex in a 7.0-A solvent shell indicated a stable behavior of the system. No significant evaporation or smearing of the solvent's outer boundary occurred. The structure and the intermolecular interactions were found to be well maintained during the simulation. The interaction pattern in the simulation was found to be very similar to that in the crystal structure. Most of the specific interactions between the DNA and the protein were found to be enhanced in the simulation compared to that in the crystal structure as a result of improved interaction geometry. The nonspecific interactions were found to be stronger than the specific ones. The specific interactions between the N7 atoms of Gua(4) or Ade(5) or Ade(6) and the protein were found to be present over almost the entire time of the simulation, whereas hydrogen bonds involving the amino groups of the Ade(5) and Ade(6) with the protein were found to be relatively weaker, with lower probability and shorter lifetime. The time evolution of the root mean square deviations of the DNA and the protein were highly correlated even at the later part of the simulation, showing the tight binding between them. Several long-lived water bridges were found between the DNA backbone atoms and the protein and also between the two protein monomers, which increased the overall stability of the complex. The two protein monomers were found to interact strongly with each other. The energy of the DNA kink deformation was estimated as approximately 31 kcal/mol. PMID:10512803

  13. Update from the Japanese Center for the Validation of Alternative Methods (JaCVAM).

    PubMed

    Kojima, Hajime

    2013-12-01

    The Japanese Center for the Validation of Alternative Methods (JaCVAM) was established in 2005 to promote the use of alternatives to animal testing in regulatory studies, thereby replacing, reducing, or refining the use of animals, according to the Three Rs principles. JaCVAM assesses the utility, limitations and suitability for use in regulatory studies, of test methods needed to determine the safety of chemicals and other materials. JaCVAM also organises and performs validation studies of new test methods, when necessary. In addition, JaCVAM co-operates and collaborates with similar organisations in related fields, both in Japan and internationally, which also enables JaCVAM to provide input during the establishment of guidelines for new alternative experimental methods. These activities help facilitate application and approval processes for the manufacture and sale of pharmaceuticals, chemicals, pesticides, and other products, as well as for revisions to standards for cosmetic products. In this manner, JaCVAM plays a leadership role in the introduction of new alternative experimental methods for regulatory acceptance in Japan.

  14. Shared binding sites in Lepidoptera for Bacillus thuringiensis Cry1Ja and Cry1A toxins.

    PubMed

    Herrero, S; González-Cabrera, J; Tabashnik, B E; Ferré, J

    2001-12-01

    Bacillus thuringiensis toxins act by binding to specific target sites in the insect midgut epithelial membrane. The best-known mechanism of resistance to B. thuringiensis toxins is reduced binding to target sites. Because alteration of a binding site shared by several toxins may cause resistance to all of them, knowledge of which toxins share binding sites is useful for predicting cross-resistance. Conversely, cross-resistance among toxins suggests that the toxins share a binding site. At least two strains of diamondback moth (Plutella xylostella) with resistance to Cry1A toxins and reduced binding of Cry1A toxins have strong cross-resistance to Cry1Ja. Thus, we hypothesized that Cry1Ja shares binding sites with Cry1A toxins. We tested this hypothesis in six moth and butterfly species, each from a different family: Cacyreus marshalli (Lycaenidae), Lobesia botrana (Tortricidae), Manduca sexta (Sphingidae), Pectinophora gossypiella (Gelechiidae), P. xylostella (Plutellidae), and Spodoptera exigua (Noctuidae). Although the extent of competition varied among species, experiments with biotinylated Cry1Ja and radiolabeled Cry1Ac showed that Cry1Ja and Cry1Ac competed for binding sites in all six species. A recent report also indicates shared binding sites for Cry1Ja and Cry1A toxins in Heliothis virescens (Noctuidae). Thus, shared binding sites for Cry1Ja and Cry1A occur in all lepidopteran species tested so far.

  15. The molecular gradient using the divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation theory: The DEC-RI-MP2 gradient

    NASA Astrophysics Data System (ADS)

    Bykov, Dmytro; Kristensen, Kasper; Kjærgaard, Thomas

    2016-07-01

    We report an implementation of the molecular gradient using the divide-expand-consolidate resolution of the identity second-order Møller-Plesset perturbation theory (DEC-RI-MP2). The new DEC-RI-MP2 gradient method combines the precision control as well as the linear-scaling and massively parallel features of the DEC scheme with efficient evaluations of the gradient contributions using the RI approximation. We further demonstrate that the DEC-RI-MP2 gradient method is capable of calculating molecular gradients for very large molecular systems. A test set of supramolecular complexes containing up to 158 atoms and 1960 contracted basis functions has been employed to demonstrate the general applicability of the DEC-RI-MP2 method and to analyze the errors of the DEC approximation. Moreover, the test set contains molecules of complicated electronic structures and is thus deliberately chosen to stress test the DEC-RI-MP2 gradient implementation. Additionally, as a showcase example the full molecular gradient for insulin (787 atoms and 7604 contracted basis functions) has been evaluated.

  16. IgE and IgA produced by OX40-OX40L or CD40-CD40L interaction in B cells-mast cells re-activate FcεRI or FcαRI on mast cells in mouse allergic asthma.

    PubMed

    Hong, Gwan Ui; Lim, Ji Yeun; Kim, Nam Goo; Shin, Joo-Ho; Ro, Jai Youl

    2015-05-05

    Mast cells are major effector cells of allergic diseases related to IgE. This study was undertaken to determine whether IgE or IgA, produced by CD40-CD40L or OX40-OX40L interactions between B cells and mast cells, re-activate FcεRI or FcαRI on mast cell surface. C57BL mice were sensitized and subjected to OVA challenge to induce asthma. Bone marrow-derived mast cells (BMMCs) and primary B cells were co-cultured. Mast cell recruitment into airways was stained by May-Grünwald Giemsa, the expression of markers or signaling molecules were determined by immunohistochemistry or Western blotting, and co-localization of B cells and mast cells by immunofluorescence. Anti-CD40 plus anti-OX40L Abs synergistically reduced IgE and IgA production, and mediators (histamine, LTs and cytokines) released in mast cells, and additively reduced other responses, such as, numbers of mast cells, the expression of markers (tryptase, mMCP5, B220 and CD19), surface molecules (CD40, CD40L, OX40 and OX40L), FcεRI or FcαRI and the co-localization of BMMCs and B cells, and IgE- or IgA-producing cells, as compared with individual blocking Ab treatment which reducedresponses in BAL cells or lung tissues of OVA-challenged mice or in co-culture of B and mast cells. The data suggest that IgE and IgA, produced by OX40-OX40L or CD40-CD40L interaction between B cells and mast cells, may re-activate receptors of FCεRI and FcαRI on mast cell surfaces, followed by more mediator release, and furthermore, that treatment with anti-CD40 plus anti-OX40L Abs offers a potential treatment for allergic asthma.

  17. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial

    PubMed Central

    Parry, Selina M; Berney, Sue; Koopman, René; Bryant, Adam; El-Ansary, Doa; Puthucheary, Zudin; Hart, Nicholas; Warrillow, Stephen; Denehy, Linda

    2012-01-01

    Introduction Intensive care-acquired weakness is a common problem, leads to significant impairment in physical functioning and muscle strength, and is prevalent in individuals with sepsis. Early rehabilitation has been shown to be safe and feasible; however, commencement is often delayed due to a patient's inability to co-operate. An intervention that begins early in an intensive care unit (ICU) admission without the need for patient volition may be beneficial in attenuating muscle wasting. The eRiCC (early rehabilitation in critical care) trial will investigate the effectiveness of functional electrical stimulation-assisted cycling and cycling alone, compared to standard care, in individuals with sepsis. Methods and analysis This is a single centre randomised controlled trial. Participants (n=80) aged ≥18 years, with a diagnosis of sepsis or severe sepsis, who are expected to be mechanically ventilated for ≥48 h and remain in the intensive care ≥4 days will be randomised within 72 h of admission to (1) standard care or (2) intervention where participants will receive functional electrical muscle stimulation-assisted supine cycling on one leg while the other leg undergoes cycling alone. Primary outcome measures include: muscle mass (quadriceps ultrasonography; bioelectrical impedance spectroscopy); muscle strength (Medical Research Council Scale; hand-held dynamometry) and physical function (Physical Function in Intensive Care Test; Functional Status Score in intensive care; 6 min walk test). Blinded outcome assessors will assess measures at baseline, weekly, at ICU discharge and acute hospital discharge. Secondary measures will be evaluated in a nested subgroup (n=20) and will consist of biochemical/histological analyses of collected muscle, urine and blood samples at baseline and at ICU discharge. Ethics and dissemination Ethics approval has been obtained from the relevant institution, and results will be published to inform clinical practice in

  18. Expression of a Flax Allene Oxide Synthase cDNA Leads to Increased Endogenous Jasmonic Acid (JA) Levels in Transgenic Potato Plants but Not to a Corresponding Activation of JA-Responding Genes.

    PubMed Central

    Harms, K.; Atzorn, R.; Brash, A.; Kuhn, H.; Wasternack, C.; Willmitzer, L.; Pena-Cortes, H.

    1995-01-01

    Both jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA), are thought to be significant components of the signaling pathway regulating the expression of plant defense genes in response to various stresses. JA and MeJA are plant lipid derivatives synthesized from [alpha]-linolenic acid by a lipoxygenase-mediated oxygenation leading to 13-hydroperoxylinolenic acid, which is subsequently transformed by the action of allene oxide synthase (AOS) and additional modification steps. AOS converts lipoxygenase-derived fatty acid hydroperoxide to allene epoxide, which is the precursor for JA formation. Overexpression of flax AOS cDNA under the regulation of the cauliflower mosaic virus 35S promoter in transgenic potato plants led to an increase in the endogenous level of JA. Transgenic plants had six- to 12-fold higher levels of JA than the nontransformed plants. Increased levels of JA have been observed when potato and tomato plants are mechanically wounded. Under these conditions, the proteinase inhibitor II (pin2) genes are expressed in the leaves. Despite the fact that the transgenic plants had levels of JA similar to those found in nontransgenic wounded plants, pin2 genes were not constitutively expressed in the leaves of these plants. Transgenic plants with increased levels of JA did not show changes in water state or in the expression of water stress-responsive genes. Furthermore, the transgenic plants overexpressing the flax AOS gene, and containing elevated levels of JA, responded to wounding or water stress by a further increase in JA and by activating the expression of either wound- or water stress-inducible genes. Protein gel blot analysis demonstrated that the flax-derived AOS protein accumulated in the chloroplasts of the transgenic plants. PMID:12242357

  19. Down-Regulation of FcεRI-Mediated CD63 Basophil Response during Short-Term VIT Determined Venom-Nonspecific Desensitization

    PubMed Central

    Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

    2014-01-01

    Background We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. Methods In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. Results We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Conclusions Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific. PMID:24733549

  20. Development of the Italian version of the revised Scoliosis Research Society-22 Patient Questionnaire, SRS-22r-I: cross-cultural adaptation, factor analysis, reliability, and validity.

    PubMed

    Monticone, Marco; Baiardi, Paola; Calabrò, David; Calabrò, Fabio; Foti, Calogero

    2010-11-15

    Evaluation of the psychometric properties of a translated and culturally adapted questionnaire. Translating, culturally adapting, and validating the Italian version of the revised Scoliosis Research Society-22 Patient Questionnaire (SRS-22r-I) in order to allow its use with Italian-speaking patients with adolescent idiopathic scoliosis (AIS). Increasing attention is being given to health-related quality of life measures as a means of adding information about the evaluation of AIS. A translated form of the revised SRS-22 has never been validated in Italian patients with AIS. The development of the SRS-22 questionnaire involved its translation and back-translation, a final review by an Expert Committee, and testing of the prefinal version to establish its correspondence to the original English version. Psychometric testing included factor analysis, reliability by internal consistency (Cronbach alpha) and test-retest repeatability (Intraclass Coefficient Correlation), and concurrent validity (Pearson correlation) by comparing the SRS-22r-I domains with the Short-Form Health Survey (SF-36) subscales. It took 4 months to develop a shared version of the SRS-22r-I, which proved to be satisfactorily acceptable when administered to 223 subjects with AIS. Factor analysis indicated a 4-factor solution (54% of the explained variance), and the questionnaire had an acceptable level of internal consistency (α = 0.77) and a high level of test-retest reliability (intraclass correlation coefficient = 0.957). In terms of concurrent validity, the correlations with the related Short-Form-36 subscales were moderate to good in the case of the Pain and Mental Health domains, and moderate in the case of the Function and Self-Image domains. The Italian translation of the SRS-22r has a good factorial structure and psychometric properties, and replicates the results of existing English versions of the questionnaire. Its use for research purposes can therefore be recommended.

  1. [Individual risk screening and visualization as a central element of health days through the interactive electronic GloRiA program].

    PubMed

    Reuter, H-M; Bierwirth, R A; Jecht, M; Cassens, S; Brosz, M; Prien, M; Pels, K; Pittrow, D; Geller, J C

    2011-12-15

    Health days are an established forum for prevention and health promotion for different groups in the general population. Through the use of modular questionnaires "Global Risk Assessment" (GloRiA) on computers (handheld and desktop), the recording of patient data and presentation of the results can be optimized. Possible applications include identification of risk factors, early detection of patients at risk, epidemiology and health services research, promotion of patient adherence by visualizations (e.g. risk scores). Up to 12 different question modules are available (e.g. risk for the occurrence of cardiovascularevents by Framingham score, forfuture riskof diabetes mellitus using FindRisk score, smoking, COPD, pain, comorbidities). During 57 health days in 2010 and 2011, data were collected from 3451 persons (53% women, mean age 59.6 +/- 15.4 years) using GloRiA. The percentage of former smokers was 32.7%, while that of current smokers was 14.7%. The average 10-year risk based on the Framingham score (calculated with 1739 persons) in 53.7% of respondents was at <10%, in 37.0% at 10-20%, and in 9.3% at > 20%. In men risk was higher than in women. Smoking cessation would theoretically reduce the mean 10-year risk from 10.9 +/- 9.2% to 7.4 +/- 6.6%. In 50.5% of participants blood pressure measurement revealed elevated values, and in 10% or 2%, respectively, a moderately high or high 10-year riskof incident diabetes mellitus according to FindRisk. The use of GloRiA for the consolidation of health data under the framework of health days provides new and sustained possibilities in early detection of cardiovascular disease. The calculation and visualization of risks and the impact of treatment decisions, e.g. reduction of cardiovascular risk by smoking cessation, were communicated directly to the participants. The individual health report facilitates the diagnostic procedures bya physician.

  2. Inhibitory Effects of Cytosolic Ca2+ Concentration by Ginsenoside Ro Are Dependent on Phosphorylation of IP3RI and Dephosphorylation of ERK in Human Platelets

    PubMed Central

    Kwon, Hyuk-Woo; Shin, Jung-Hae; Lee, Dong-Ha; Park, Hwa-Jin

    2015-01-01

    Intracellular Ca2+ ([Ca2+]i) is platelet aggregation-inducing molecule and is involved in activation of aggregation associated molecules. This study was carried out to understand the Ca2+-antagonistic effect of ginsenoside Ro (G-Ro), an oleanane-type saponin in Panax ginseng. G-Ro, without affecting leakage of lactate dehydrogenase, dose-dependently inhibited thrombin-induced platelet aggregation, and the half maximal inhibitory concentration was approximately 155 μM. G-Ro inhibited strongly thrombin-elevated [Ca2+]i, which was strongly increased by A-kinase inhibitor Rp-8-Br-cAMPS compared to G-kinase inhibitor Rp-8-Br-cGMPS. G-Ro increased the level of cAMP and subsequently elevated the phosphorylation of inositol 1, 4, 5-triphosphate receptor I (IP3RI) (Ser1756) to inhibit [Ca2+]i mobilization in thrombin-induced platelet aggregation. Phosphorylation of IP3RI (Ser1756) by G-Ro was decreased by PKA inhibitor Rp-8-Br-cAMPS. In addition, G-Ro inhibited thrombin-induced phosphorylation of ERK 2 (42 kDa), indicating inhibition of Ca2+ influx across plasma membrane. We demonstrate that G-Ro upregulates cAMP-dependent IP3RI (Ser1756) phosphorylation and downregulates phosphorylation of ERK 2 (42 kDa) to decrease thrombin-elevated [Ca2+]i, which contributes to inhibition of ATP and serotonin release, and p-selectin expression. These results indicate that G-Ro in Panax ginseng is a beneficial novel Ca2+-antagonistic compound and may prevent platelet aggregation-mediated thrombotic disease. PMID:26355658

  3. SuMoToRI, an Ecophysiological Model to Predict Growth and Sulfur Allocation and Partitioning in Oilseed Rape (Brassica napus L.) Until the Onset of Pod Formation.

    PubMed

    Brunel-Muguet, Sophie; Mollier, Alain; Kauffmann, François; Avice, Jean-Christophe; Goudier, Damien; Sénécal, Emmanuelle; Etienne, Philippe

    2015-01-01

    Sulfur (S) nutrition in rapeseed (Brassica napus L.) is a major concern for this high S-demanding crop, especially in the context of soil S oligotrophy. Therefore, predicting plant growth, S plant allocation (between the plant's compartments) and S pool partitioning (repartition of the mobile-S vs. non-mobile-S fractions) until the onset of reproductive phase could help in the diagnosis of S deficiencies during the early stages. For this purpose, a process-based model, SuMoToRI (Sulfur Model Toward Rapeseed Improvement), was developed up to the onset of pod formation. The key features rely on (i) the determination of the S requirements used for growth (structural and metabolic functions) through critical S dilution curves and (ii) the estimation of a mobile pool of S that is regenerated by daily S uptake and remobilization from senescing leaves. This study describes the functioning of the model and presents the model's calibration and evaluation. SuMoToRI was calibrated and evaluated with independent datasets from greenhouse experiments under contrasting S supply conditions. It is run with a small number of parameters with generic values, except in the case of the radiation use efficiency, which was shown to be modulated by S supply. The model gave satisfying predictions of the dynamics of growth, S allocation between compartments and S partitioning, such as the mobile-S fraction in the leaves, which is an indicator of the remobilization potential toward growing sinks. The mechanistic features of SuMoToRI provide a process-based framework that has enabled the description of the S remobilizing process in a species characterized by senescence during the vegetative phase. We believe that this model structure could be useful for modeling S dynamics in other arable crops that have similar senescence-related characteristics.

  4. SuMoToRI, an Ecophysiological Model to Predict Growth and Sulfur Allocation and Partitioning in Oilseed Rape (Brassica napus L.) Until the Onset of Pod Formation

    PubMed Central

    Brunel-Muguet, Sophie; Mollier, Alain; Kauffmann, François; Avice, Jean-Christophe; Goudier, Damien; Sénécal, Emmanuelle; Etienne, Philippe

    2015-01-01

    Sulfur (S) nutrition in rapeseed (Brassica napus L.) is a major concern for this high S-demanding crop, especially in the context of soil S oligotrophy. Therefore, predicting plant growth, S plant allocation (between the plant’s compartments) and S pool partitioning (repartition of the mobile-S vs. non-mobile-S fractions) until the onset of reproductive phase could help in the diagnosis of S deficiencies during the early stages. For this purpose, a process-based model, SuMoToRI (Sulfur Model Toward Rapeseed Improvement), was developed up to the onset of pod formation. The key features rely on (i) the determination of the S requirements used for growth (structural and metabolic functions) through critical S dilution curves and (ii) the estimation of a mobile pool of S that is regenerated by daily S uptake and remobilization from senescing leaves. This study describes the functioning of the model and presents the model’s calibration and evaluation. SuMoToRI was calibrated and evaluated with independent datasets from greenhouse experiments under contrasting S supply conditions. It is run with a small number of parameters with generic values, except in the case of the radiation use efficiency, which was shown to be modulated by S supply. The model gave satisfying predictions of the dynamics of growth, S allocation between compartments and S partitioning, such as the mobile-S fraction in the leaves, which is an indicator of the remobilization potential toward growing sinks. The mechanistic features of SuMoToRI provide a process-based framework that has enabled the description of the S remobilizing process in a species characterized by senescence during the vegetative phase. We believe that this model structure could be useful for modeling S dynamics in other arable crops that have similar senescence-related characteristics. PMID:26635825

  5. Alterations in Fc[epsilon]RI induced by protoporphyrin plus long-wavelength ultraviolet light in mouse bone marrow-derived mast cells

    SciTech Connect

    Yen, A.; Barrett, K.E.; Gigli, I. ); Liu, F.T. )

    1993-07-15

    As previously reported, protoporphyrin plus long-wavelength UV light (PP/UVA) inhibits IgE-mediated degranulation of mouse bone marrow-derived mast cells, as assessed by measurement of the release of [beta]-hexosaminidase. This inhibitory effect was seen with cells sensitized with IgE either before or after PP/UVA treatment (57.8 and 55.35 inhibition, respectively). PP/UVA did not dissociate IgE already bound to cells as assessed either by measure of release of bound [sup 125]I-IgE or by flow cytometric analysis. Results from immunoadsorption followed by SDS-PAGE analysis suggested that PP/UVA treatment may cause stable conjugation of IgE to its receptor. In unsensitized cells, PP/UVA did not cause conjugation of the unoccupied Fc[epsilon]RI to other proteins in the plasma membrane. Nevertheless, Scatchard analysis revealed that PP/UVA decreased the number of Fc[epsilon]Ri per cell by 37% (0.95 [times] 10[sup 5] vs 1.51 [times] 10[sup 5] cell), whereas affinity of the receptor for IgE was comparable between PP/UVA-treated and untreated cells (3.40 nM vs 3.27 nM). Flow cytometric analysis also confirmed the decrease in Fc[epsilon]RI number in PP/UVA-treated unsensitized mouse bone marrow-derived mast cells. Although 84% of PP/UVA-treated and 82% of untreated cells expressed positive fluorescence when stained with FITC-conjugated IgE, fluorescence intensity was reduced by 40% after PP/UVA treatment. The authors conclude that PP/UVA alters the conformational structure and/or number of Fc[epsilon]RI expressed on the mast cell surface. This effect could potentially explain the ability of PP/UVA to inhibit mast cell secretory function and may be related to an ability of PP/UVA to alter the properties of the plasma membrane. 29 refs., 8 figs.

  6. The Immunotherapeutics & Vaccine Summit--CHI's fourth annual meeting. Preclinical/clinical development of immunotherapies and vaccines. 17-19 August 2009, Providence, RI, USA.

    PubMed

    Butterfield, Lisa H

    2009-10-01

    The Immunotherapeutics & Vaccine Summit held in Providence, RI, USA included topics covering new preclinical and clinical developments in the field of immunotherapies and vaccines. This conference report highlights selected presentations on the iSBTc-FDA-NCI taskforce findings on immunotherapy biomarkers, clinical assay development and optimization, and bioassays to measure immune responses. Investigational vaccines discussed include a fusion protein adjuvant vaccine (Research by Discovery), a novel intradermal particle delivery device (Université de Sherbrooke) and a Hsp-based vaccine for meningitis (ImmunoBiology Ltd).

  7. Efficient parallel algorithm of second-order Møller-Plesset perturbation theory with resolution-of-identity approximation (RI-MP2)

    NASA Astrophysics Data System (ADS)

    Katouda, Michio; Nagase, Shigeru

    An efficient parallel algorithm is developed for second-order Møller-Plesset perturbation theory with the resolution-of-identity approximation of two-electron repulsion integrals (RI-MP2) to perform MP2 energy calculations of large molecules on distributed memory processors. Benchmark calculations are carried out for taxol (C47H51NO14), valinomycin (C54H90N6O18), and two-layer nanographene sheets (C96H24)2, which show the high parallel efficiency of the developed algorithm.

  8. National Program for Inspection of Non-Federal Dams. Georgiaville Pond Dam (RI 03108), Woonasquatucket River Basin, Smithfield, Rhode Island. Phase I Inspection Report.

    DTIC Science & Technology

    1979-04-01

    with concrete and the structure is abandoned. - 0 0 A0 5 -7 7 07.71 PERIODIC INSPECTION CHECK LIST *PROJECT Georgi avilIlIe Pond Dam DATE November 30...VISUAL INSPECTION CHiECK LIST * PARTY ORGANIZATiON PROJECT Georgi avil11e Pond flam DATE November 30. 1978 * Smithfield, RI* 6 TIME 8AM to 3PM wEATHER...Deow Hr. Bloyd: fot ihode Island. I visited the Georiaville Dm an October 4, 1968 in company with you, Hr. Howard and Mr. Chawles Rap linger of the

  9. Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1

    PubMed Central

    Orthwein, Alexandre; Zahn, Astrid; Methot, Stephen P; Godin, David; Conticello, Silvestro G; Terada, Kazutoyo; Di Noia, Javier M

    2012-01-01

    The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1-deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID. PMID:22085931

  10. A balanced JA/ABA status may correlate with adaptation to osmotic stress in Vitis cells.

    PubMed

    Ismail, Ahmed; Seo, Mitsunori; Takebayashi, Yumiko; Kamiya, Yuji; Nick, Peter

    2015-08-01

    Water-related stress is considered a major type of plant stress. Osmotic stress, in particular, represents the common part of all water-related stresses. Therefore, plants have evolved different adaptive mechanisms to cope with osmotic-related disturbances. In the current work, two grapevine cell lines that differ in their osmotic adaptability, Vitis rupestris and Vitis riparia, were investigated under mannitol-induced osmotic stress. To dissect signals that lead to adaptability from those related to sensitivity, osmotic-triggered responses with respect to jasmonic acid (JA) and its active form JA-Ile, abscisic acid (ABA), and stilbene compounds, as well as the expression of their related genes were observed. In addition, the transcript levels of the cellular homeostasis gene NHX1 were examined. The data are discussed with a hypothesis suggesting that a balance of JA and ABA status might correlate with cellular responses, either guiding cells to sensitivity or to progress toward adaptation.

  11. APMP supplementary comparison report of absorbed dose rate in tissue for beta radiation (BIPM KCDB: APMP.RI(I)-S2)

    NASA Astrophysics Data System (ADS)

    Kato, M.; Kurosawa, T.; Saito, N.; Kadni, T. B.; Kim, I. J.; Kim, B. C.; Yi, C.-Y.; Pungkun, V.; Chu, C.-H.

    2017-01-01

    The supplementary comparison of absorbed dose rate in tissue for beta radiation (APMP.RI(I)-S2) was performed with five national metrology institutes in 2013 and 2014. Two commercial thin window ionization chambers were used as transfer instruments and circulated among the participants. Two of the NMIs measured the calibration coefficients of the chambers in reference fields produced from Pm-147, Kr-85 and Sr-90/Y-90, while the other three measured those only in Sr-90/Y-90 beta-particle field. The degree of equivalence for the participants was determined and this comparison verifies the calibration capabilities of the participating laboratories. In addition, most of the results of this comparison are consistent with another international comparison (EUROMET.RI(I)-S2) reported before this work. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  12. Gender-related effects of sex steroids on histamine release and FcεRI expression in rat peritoneal mast cells.

    PubMed

    Muñoz-Cruz, Samira; Mendoza-Rodríguez, Yolanda; Nava-Castro, Karen E; Yepez-Mulia, Lilián; Morales-Montor, Jorge

    2015-01-01

    Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

  13. Gender-Related Effects of Sex Steroids on Histamine Release and FcεRI Expression in Rat Peritoneal Mast Cells

    PubMed Central

    Muñoz-Cruz, Samira; Mendoza-Rodríguez, Yolanda; Nava-Castro, Karen E.; Yepez-Mulia, Lilián; Morales-Montor, Jorge

    2015-01-01

    Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids. PMID:25973435

  14. Development and application of HPLC-RI and HPLC-MS/MS based methods for quantification of residual deoxycholate levels in pneumococcal polysaccharides.

    PubMed

    Gairola, Sunil; Gautam, Manish; Patil, Dada; Manoj Kumar, Krishna; Shinde, Pravin; Jana, S K; Dhere, Rajeev; Jadhav, Suresh

    2016-11-01

    The analysis of residual sodium deoxycholate (DOC); a detergent of biological origin used in manufacturing of polysaccharide vaccines is challenging due to complex sample matrices and the lack of suitable methods. Here we report, rapid and sensitive high-performance liquid chromatography-refractive index (HPLC-RI) and tandem mass spectrometry (HPLC-MS/MS) methods for estimation of residual DOC in pneumococcal polysaccharides. For HPLC-RI method, separation was achieved using Luna C18 column and mobile phase compositions of acetonitrile: methanol: 20 mM sodium acetate (60:05:35% v/v). For HPLC-MS/MS method, separation was achieved using a Hypersil BDS C18 column with gradient elution of methanol and water (0.1% formic acid). MS/MS method showed linearity (r(2) = 0.997) over the range of 10-320 ng/mL with limits of detection (LOD) and lower limit of quantitation (LOQ) of 3 and 10 ng/mL respectively. Precision (% RSD) and accuracy (% recovery) for both methods were in the range of 0.74-8.29% and 82.33-117.86% respectively. Sample matrices interferences were addressed following novel sample clean-up method based on liquid-liquid extraction. Both methods enabled traceable quantitation of DOC in intermediate and purified pneumococcal polysaccharides of serotypes: 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F and 23F.

  15. Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes (RI) in the Multi-Provincial Boundary Region of the Taihu Basin, China.

    PubMed

    Yao, Hong; Li, Weixin; Qian, Xin

    2015-08-21

    Environmental safety in multi-district boundary regions has been one of the focuses in China and is mentioned many times in the Environmental Protection Act of 2014. Five types were categorized concerning the risk sources for surface water pollution in the multi-provincial boundary region of the Taihu basin: production enterprises, waste disposal sites, chemical storage sites, agricultural non-point sources and waterway transportations. Considering the hazard of risk sources, the purification property of environmental medium and the vulnerability of risk receptors, 52 specific attributes on the risk levels of each type of risk source were screened out. Continuous piecewise linear function model, expert consultation method and fuzzy integral model were used to calculate the integrated risk indexes (RI) to characterize the risk levels of pollution sources. In the studied area, 2716 pollution sources were characterized by RI values. There were 56 high-risk sources screened out as major risk sources, accounting for about 2% of the total. The numbers of sources with high-moderate, moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124, respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure proposed could be included in the integrated risk management systems of the multi-district boundary region of the Taihu basin. It could help decision makers to identify major risk sources in the risk prevention and reduction of surface water pollution.

  16. IgG4 can induce an M2-like phenotype in human monocyte-derived macrophages through FcγRI.

    PubMed

    Swisher, Jennifer F A; Haddad, Devin A; McGrath, Anna G; Boekhoudt, Gunther H; Feldman, Gerald M

    2014-01-01

    Antibodies evoke cellular responses through the binding of their Fc region to Fc receptors, most of which contain immunoreceptor tyrosine-based activation motif domains and are thus considered "activating." However, there is a growing appreciation of these receptors for their ability to deliver an inhibitory signal as well. We previously described one such phenomenon whereby interferon (IFN)γ signaling is inhibited by immune complex signaling through FcγRI. To understand the implications of this in the context of therapeutic antibodies, we assessed individual IgG subclasses to determine their ability to deliver this anti-inflammatory signal in monocyte-derived macrophages. Like IgG1, we found that IgG4 is fully capable of inhibiting IFNγ-mediated events. In addition, F(ab')2 fragments that interfere with FcγRI signaling reversed this effect. For mAbs developed with either an IgG1 or an IgG4 constant region for indications where inflammation is undesirable, further examination of a potential Fc-dependent contribution to their mechanism of action is warranted.

  17. The EcoRI centromeric satellite DNA of the Sparidae family (Pisces, Perciformes) contains a sequence motive common to other vertebrate centromeric satellite DNAs.

    PubMed

    Garrido-Ramos, M A; Jamilena, M; Lozano, R; Ruiz Rejón, C; Ruiz Rejón, M

    1995-01-01

    By means of cloning, sequencing, and fluorescence in situ hybridization, we have determined that the EcoRI satellite DNA family is conserved in the 10 sparid species analyzed here. Its conservation, its chromosomal location at the centromere of each chromosome, and its structural features could make this satellite DNA family an important structural and/or functional element of the centromeres of these species. Monomeric units of this satellite DNA have a consensus length of 187 bp. Its sequence is characterized by a high AT content and the presence of short runs of consecutive AT base pairs. These monomeric EcoRI repeats also contain three to four copies, depending on the species, of a short sequence reflecting the repetitive duplication and subsequent divergence of an ancestral 9-bp sequence in this family. This sequence motive is conserved in some parts of the monomeric units of the different species studied at the same positions, and, precisely, surrounding the area in which the curvature of the monomeric molecule is greatest. The 9-bp sequence motive is similar to other direct-repeat sequences of the centromeric satellite DNAs of other vertebrates, including those of amphibians and mammals.

  18. Activity measurements of the radionuclide 99mTc for the IFIN-HH, Romania in the ongoing comparison BIPM.RI(II)-K4.Tc-99m

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Sahagia, M.; Ioan, M. R.; Antohe, A.; Luca, A.

    2014-01-01

    In 2013, a comparison of activity measurements of 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the Institutul National de Cercetare - Dezvoltare in Fizica si Inginerie Nucleara - 'Horia Hulubei' (IFIN-HH, Romania). Ampoules containing about 21 kBq and 40 kBq of a 99mTc solution were measured in the SIRTI for, respectively, one and three half-lives. The comparison, identifier BIPM.RI(II)-K4.Tc-99m, is linked to the BIPM.RI(II)-K1.Tc-99m comparison and the degrees of equivalence with the key comparison reference value and between the present IFIN-HH result, the other K4 participants and the six participants in the K1 comparison have been evaluated. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. Activity measurements of the radionuclide 99mTc for the NIM, China in the ongoing comparison BIPM.RI(II)-K4.Tc-99m

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Nonis, M.; Liang, J. C.; Chen, J.; Liu, H. R.; Zhang, M.; Zhao, Q.; Yang, Y. D.

    2013-01-01

    In 2012, the fourth comparison of activity measurements of 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the Chinese National Institute of Metrology (NIM). An ampoule containing about 70 kBq of 99mTc traceable to the NIM primary standard was measured in the SIRTI for more than three half-lives. The comparison, identifier BIPM.RI(II)-K4.Tc-99m, is linked to the BIPM.RI(II)-K1.Tc-99m comparison and the degrees of equivalence with the key comparison reference value and between the present NIM result, the other K4 participant and the six participants in the K1 comparison have been evaluated. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Participation of the NPL in 2008 in the BIPM.RI(II)-K1.Mn-56 comparison of activity measurements of the radionuclide 56Mn

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Keightley, J.

    2015-01-01

    In 2008, the National Physical Laboratory (NPL) submitted one sample of known activity of 56Mn to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Mn-56. The value of the activity submitted was about 290 kBq. There is now one result in the BIPM.RI(II)-K1.Mn-56 comparison. The key comparison reference value (KCRV) has been evaluated for the first time using the NPL result and a BIPM result dating November 1978. The degree of equivalence between the NPL equivalent activity measured in the SIR and the KCRV has been calculated and is reported. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  1. TRPM4-mediated control of FcεRI-evoked Ca2+ elevation comprises enhanced plasmalemmal trafficking of TRPM4 channels in connective tissue type mast cells

    PubMed Central

    Rixecker, Torben; Mathar, Ilka; Medert, Rebekka; Mannebach, Stefanie; Pfeifer, Alexander; Lipp, Peter; Tsvilovskyy, Volodymyr; Freichel, Marc

    2016-01-01

    TRPM4 proteins form Ca2+-activated non selective cation (CAN) channels that affect transmembrane Ca2+-influx by determining the membrane potential. Tight control of the intracellular Ca2+ concentration is essential for mast cell responses. In this study, we analyzed the expression of TRPM4 in peritoneal mast cells (PCMC) as a model for connective tissue type mast cells with respect to FcεRI-evoked calcium changes and the subcellular localization of fluorescently labeled TRPM4 using two viral transduction systems before and following antigen stimulation. Our results show that TRPM4 is expressed in PCMCs, is an essential constituent of the endogenous CAN channels in PCMCs and regulates antigen-evoked increases in intracellular calcium that are significantly enhanced in TRPM4-deficient PCMCs. Compared to PCMCs analyzed before antigen stimulation, the cells depict a substantially increased localization of TRPM4 proteins towards the plasma membrane after FcεRI stimulation. Thus, TRPM4 functions as a limiting factor for antigen evoked calcium rise in connective tissue type mast cells and concurrent translocation of TRPM4 into the plasma membrane is part of this mechanism. PMID:27624684

  2. Identification of Major Risk Sources for Surface Water Pollution by Risk Indexes (RI) in the Multi-Provincial Boundary Region of the Taihu Basin, China

    PubMed Central

    Yao, Hong; Li, Weixin; Qian, Xin

    2015-01-01

    Environmental safety in multi-district boundary regions has been one of the focuses in China and is mentioned many times in the Environmental Protection Act of 2014. Five types were categorized concerning the risk sources for surface water pollution in the multi-provincial boundary region of the Taihu basin: production enterprises, waste disposal sites, chemical storage sites, agricultural non-point sources and waterway transportations. Considering the hazard of risk sources, the purification property of environmental medium and the vulnerability of risk receptors, 52 specific attributes on the risk levels of each type of risk source were screened out. Continuous piecewise linear function model, expert consultation method and fuzzy integral model were used to calculate the integrated risk indexes (RI) to characterize the risk levels of pollution sources. In the studied area, 2716 pollution sources were characterized by RI values. There were 56 high-risk sources screened out as major risk sources, accounting for about 2% of the total. The numbers of sources with high-moderate, moderate, moderate-low and low pollution risk were 376, 1059, 101 and 1124, respectively, accounting for 14%, 38%, 5% and 41% of the total. The procedure proposed could be included in the integrated risk management systems of the multi-district boundary region of the Taihu basin. It could help decision makers to identify major risk sources in the risk prevention and reduction of surface water pollution. PMID:26308032

  3. Dermal sensitization potential of ja-2 solid propellant in guinea pigs. Report for 4 April-9 May 1986

    SciTech Connect

    Lewis, C.M.; Brown, L.D.; Korte, D.W.

    1989-11-01

    JA-2 Solid Propellant was evaluated for its potential to produce dermal sensitization in male guinea pigs. The Buehler test, which utilizes repeated closed patch inductions with the test compound, was used for this evaluation. No evidence that JA-2 Solid Propellant induced sensitization was obtained in the study.

  4. Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI).

    PubMed

    Kyono, W T; de Jong, R; Park, R K; Liu, Y; Heisterkamp, N; Groffen, J; Durden, D L

    1998-11-15

    Cbl-Crkl and Crkl-C3G interactions have been implicated in T cell and B cell receptor signaling and in the regulation of the small GTPase, Rap1. Recent evidence suggests that Rap1 plays a prominent role in the regulation of immunoreceptor tyrosine-based activation motif (ITAM) signaling. To gain insight into the role of Crkl in myeloid ITAM signaling, we investigated Cbl-Crkl and Crkl-C3G interactions following Fc gamma RI aggregation in U937IF cells. Fc gamma RI cross-linking of U937IF cells results in the tyrosine phosphorylation of Cbl, Crkl, and Hef-1, an increase in the association of Crkl with Cbl via direct SH2 domain interaction and increased Crkl-Hef-1 binding. Crkl constitutively binds to the guanine nucleotide-releasing protein, C3G, via direct SH3 domain binding. Our data show that distinct Cbl-Crkl and Crkl-C3G complexes exist in myeloid cells, suggesting that these complexes may modulate distinct signaling events. Anti-Crkl immunoprecipitations demonstrate that the ITAM-containing gamma subunit of Fc gamma RI is induced to form a complex with the Crkl protein, and Crkl binds to the cytoskeletal protein, Hef-1. The induced association of Crkl with Cbl, Hef-1, and Fc gamma RI gamma after Fc gamma RI activation and the constitutive association between C3G and Crkl provide the first evidence that a Fc gamma RI gamma-Crkl-C3G complex may link ITAM receptors to the activation of Rap1 in myeloid cells.

  5. Integrated metabolomic and proteomic analysis reveals systemic responses of Rubrivivax benzoatilyticus JA2 to aniline stress.

    PubMed

    Mujahid, Md; Prasuna, M Lakshmi; Sasikala, Ch; Ramana, Ch Venkata

    2015-02-06

    Aromatic amines are widely distributed in the environment and are major environmental pollutants. Although degradation of aromatic amines is well studied in bacteria, physiological adaptations and stress response to these toxic compounds is not yet fully understood. In the present study, systemic responses of Rubrivivax benzoatilyticus JA2 to aniline stress were deciphered using metabolite and iTRAQ-labeled protein profiling. Strain JA2 tolerated high concentrations of aniline (30 mM) with trace amounts of aniline being transformed to acetanilide. GC-MS metabolite profiling revealed aniline stress phenotype wherein amino acid, carbohydrate, fatty acid, nitrogen metabolisms, and TCA (tricarboxylic acid cycle) were modulated. Strain JA2 responded to aniline by remodeling the proteome, and cellular functions, such as signaling, transcription, translation, stress tolerance, transport and carbohydrate metabolism, were highly modulated. Key adaptive responses, such as transcription/translational changes, molecular chaperones to control protein folding, and efflux pumps implicated in solvent extrusion, were induced in response to aniline stress. Proteo-metabolomics indicated extensive rewiring of metabolism to aniline. TCA cycle and amino acid catabolism were down-regulated while gluconeogenesis and pentose phosphate pathways were up-regulated, leading to the synthesis of extracellular polymeric substances. Furthermore, increased saturated fatty acid ratios in membranes due to aniline stress suggest membrane adaptation. The present study thus indicates that strain JA2 employs multilayered responses: stress response, toxic compound tolerance, energy conservation, and metabolic rearrangements to aniline.

  6. Transcriptome Analysis in Haematococcus pluvialis: Astaxanthin Induction by Salicylic Acid (SA) and Jasmonic Acid (JA).

    PubMed

    Gao, Zhengquan; Li, Yan; Wu, Guanxun; Li, Guoqiang; Sun, Haifeng; Deng, Suzhen; Shen, Yicheng; Chen, Guoqiang; Zhang, Ruihao; Meng, Chunxiao; Zhang, Xiaowen

    2015-01-01

    Haematococcus pluvialis is an astaxanthin-rich microalga that can increase its astaxanthin production by salicylic acid (SA) or jasmonic acid (JA) induction. The genetic transcriptome details of astaxanthin biosynthesis were analyzed by exposing the algal cells to 25 mg/L of SA and JA for 1, 6 and 24 hours, plus to the control (no stress). Based on the RNA-seq analysis, 56,077 unigenes (51.7%) were identified with functions in response to the hormone stress. The top five identified subcategories were cell, cellular process, intracellular, catalytic activity and cytoplasm, which possessed 5600 (~9.99%), 5302 (~9.45%), 5242 (~9.35%), 4407 (~7.86%) and 4195 (~7.48%) unigenes, respectively. Furthermore, 59 unigenes were identified and assigned to 26 putative transcription factors (TFs), including 12 plant-specific TFs. They were likely associated with astaxanthin biosynthesis in Haematococcus upon SA and JA stress. In comparison, the up-regulation of differential expressed genes occurred much earlier, with higher transcript levels in the JA treatment (about 6 h later) than in the SA treatment (beyond 24 h). These results provide valuable information for directing metabolic engineering efforts to improve astaxanthin biosynthesis in H. pluvialis.

  7. Risk-Informed Monitoring, Verification and Accounting (RI-MVA). An NRAP White Paper Documenting Methods and a Demonstration Model for Risk-Informed MVA System Design and Operations in Geologic Carbon Sequestration

    SciTech Connect

    Unwin, Stephen D.; Sadovsky, Artyom; Sullivan, E. C.; Anderson, Richard M.

    2011-09-30

    This white paper accompanies a demonstration model that implements methods for the risk-informed design of monitoring, verification and accounting (RI-MVA) systems in geologic carbon sequestration projects. The intent is that this model will ultimately be integrated with, or interfaced with, the National Risk Assessment Partnership (NRAP) integrated assessment model (IAM). The RI-MVA methods described here apply optimization techniques in the analytical environment of NRAP risk profiles to allow systematic identification and comparison of the risk and cost attributes of MVA design options.

  8. Effects of Human Alterations on Global River Basins and their Associated Coastal Zones: focus on River-dominated Ocean Margins (RiOMars)

    NASA Astrophysics Data System (ADS)

    Dürr, H. H.; Van Cappellen, P.; Meybeck, M.; Laruelle, G. G.; Mayorga, E.; Hartmann, J.; Maavara, T.; Bouwman, L.; Seitzinger, S.

    2013-12-01

    Coastal systems connected to large rivers, mostly major delta systems or river-dominated ocean margins (RiOMars), make up <1% of the worldwide shoreline. Yet, they comprise 28% of the exorheic terrestrial river basins area, and host 26.4% of the population connected via rivers to coastal systems (Dürr et al. 2011). These systems receive 41.6% of the discharge delivered to oceans. 25.7% of the suspended sediment load is processed, with comparable amounts for the total nitrogen (N) and phosphorus (P) loads. The filter function for incoming riverine nutrients (N, P, C, Si) in these coastal environments is very different from other near-shore environments such as macro-tidal estuaries, lagoons or fjords. In this type, the major biogeochemical transformation of incoming river fluxes takes place in a plume on the continental margins (RiOMars). This effect is even more pronounced at high flow stages when the highest volumes of water and material are delivered. The filtering efficiency of delta systems is highest during low flows, and some of the systems may be influenced by tides when ebb and flood might flow through different channels, creating a braided network of streams and many islands (Dürr et al. 2011). Here, we discuss controls on the different nutrient forms delivered to different coastal environments, and how they are assessed (Global-NEWS and other approaches), with a special focus on large deltas and RiOMars. Drivers and impacts of global change will be explored through the Millenium Assessment Scenarios and how the fluxes to these different coastal systems might change. An increasing role is also played by aquaculture in different coastal types as a non-insignificant source of nutrients. World-wide distribution of coastal types and their related river basins (Dürr et al. 2011). Characteristics of types of near-shore coastal areas and their associated river basins Greenland and Antarctica excepted. Data from Dürr et al. (2011) and the Global-NEWS program

  9. Resveratrol Suppresses Cytokine Production Linked to FcεRI-MAPK Activation in IgE-Antigen Complex-Exposed Basophilic Mast Cells and Mice.

    PubMed

    Han, Seon-Young; Choi, Yean-Jung; Kang, Min-Kyung; Park, Jung Han Yoon; Kang, Young-Hee

    2015-01-01

    A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the

  10. IL-1β increases necrotic neuronal cell death in the developing rat hippocampus after status epilepticus by activating type I IL-1 receptor (IL-1RI).

    PubMed

    Medel-Matus, Jesús-Servando; Álvarez-Croda, Dulce-Mariely; Martínez-Quiroz, Joel; Beltrán-Parrazal, Luis; Morgado-Valle, Consuelo; López-Meraz, María-Leonor

    2014-11-01

    Interleukin-1β (IL-1β) is associated with seizure-induced neuronal cell death in the adult brain. The contribution of IL-1β to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. In the present study, we investigated the effects of IL-1β administration on hippocampal neuronal cell death associated with SE in the immature brain, and the role of the type I receptor of IL-1β (IL-1RI). SE was induced with lithium-pilocarpine in 14-days-old (P14) rat pups. Six hours after SE onset, pups were i.c.v. injected in the right ventricle with IL-1β (0, 0.3, 3, 30, or 300 ng), 30 ng of IL-1RI antagonist (IL-1Ra) alone, or 30 ng of IL-1Ra plus 3ng of IL-1β. As control groups, pups without seizures were injected with 3 ng of IL-1β or vehicle. Twenty-four hours after SE onset, neuronal cell death in the CA1 field of dorsal hippocampus was assessed by hematoxylin-eosin, Fluoro-Jade B and in vivo propidium iodide (PI) staining; expression of active caspase-3 (aCas-3) was also determined, using immunohistochemistry. The concentration-response curve of IL-1β showed a bell-shape. Only pups injected with 3 ng of IL-1β after SE showed a significant increase in the number of cells with eosinophilic cytoplasm and pyknotic nuclei, as well as F-JB positive cells with respect to the vehicle group. This effect was prevented when IL-1β was injected with IL-1Ra. Injection of 3 ng of IL-1β increased the number of PI-positive cells in CA1 area after SE. Injection of 3 ng of IL-1β did not produce hippocampal cell death in rats without seizures. Active caspase-3 expression was not observed after treatments in hippocampus. The activation of the IL-1β/IL-1RI system increases necrotic neuronal cell death caused by SE in rat pups.

  11. Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction

    PubMed Central

    Amil-Ruiz, Francisco; Garrido-Gala, José; Gadea, José; Blanco-Portales, Rosario; Muñoz-Mérida, Antonio; Trelles, Oswaldo; de los Santos, Berta; Arroyo, Francisco T.; Aguado-Puig, Ana; Romero, Fernando; Mercado, José-Ángel; Pliego-Alfaro, Fernando; Muñoz-Blanco, Juan; Caballero, José L.

    2016-01-01

    Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria × ananassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutatum spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen. PMID:27471515

  12. Partial Activation of SA- and JA-Defensive Pathways in Strawberry upon Colletotrichum acutatum Interaction.

    PubMed

    Amil-Ruiz, Francisco; Garrido-Gala, José; Gadea, José; Blanco-Portales, Rosario; Muñoz-Mérida, Antonio; Trelles, Oswaldo; de Los Santos, Berta; Arroyo, Francisco T; Aguado-Puig, Ana; Romero, Fernando; Mercado, José-Ángel; Pliego-Alfaro, Fernando; Muñoz-Blanco, Juan; Caballero, José L

    2016-01-01

    Understanding the nature of pathogen host interaction may help improve strawberry (Fragaria × ananassa) cultivars. Plant resistance to pathogenic agents usually operates through a complex network of defense mechanisms mediated by a diverse array of signaling molecules. In strawberry, resistance to a variety of pathogens has been reported to be mostly polygenic and quantitatively inherited, making it difficult to associate molecular markers with disease resistance genes. Colletotrichum acutatum spp. is a major strawberry pathogen, and completely resistant cultivars have not been reported. Moreover, strawberry defense network components and mechanisms remain largely unknown and poorly understood. Assessment of the strawberry response to C. acutatum included a global transcript analysis, and acidic hormones SA and JA measurements were analyzed after challenge with the pathogen. Induction of transcripts corresponding to the SA and JA signaling pathways and key genes controlling major steps within these defense pathways was detected. Accordingly, SA and JA accumulated in strawberry after infection. Contrastingly, induction of several important SA, JA, and oxidative stress-responsive defense genes, including FaPR1-1, FaLOX2, FaJAR1, FaPDF1, and FaGST1, was not detected, which suggests that specific branches in these defense pathways (those leading to FaPR1-2, FaPR2-1, FaPR2-2, FaAOS, FaPR5, and FaPR10) were activated. Our results reveal that specific aspects in SA and JA dependent signaling pathways are activated in strawberry upon interaction with C. acutatum. Certain described defense-associated transcripts related to these two known signaling pathways do not increase in abundance following infection. This finding suggests new insight into a specific putative molecular strategy for defense against this pathogen.

  13. Combined analysis by GC (RI), GC-MS and 13C NMR of the supercritical fluid extract of Abies alba twigs.

    PubMed

    Duquesnoy, Emilie; Marongiu, Bruno; Castola, Vincent; Piras, Alessandra; Porcedda, Silvia; Casanova, Joseph

    2010-12-01

    Two samples (leaves and twigs) of Abies alba Miller from Corsica were extracted using supercritical CO2 and their chemical compositions were compared with those of the essential oils obtained from the same batch of plant material. In total 45 components were identified using combined analysis by GC (RI), GC-MS and 13C NMR. It was observed that the contents of monoterpenes (mainly represented by limonene, alpha-pinene and camphene) were significantly lower in the supercritical fluid extract (SFE) than in the essential oil (EO). Conversely, the proportions of sesquiterpenes were much higher in CO2 extracts than in essential oils (around 30% vs 4%). Cis-abienol, a diterpene alcohol, was identified only in SFE, and the proportions of this constituent (7.5% and 17.3%) were determined using quantitative 13C NMR since it was under estimated using the standard conditions of GC.

  14. Status of Beam Line Detectors for the BigRIPS Fragment Separator at RIKEN RI Beam Factory: Issues on High Rates and Resolution

    NASA Astrophysics Data System (ADS)

    Sato, Yuki; Fukuda, Naoki; Takeda, Hiroyuki; Kameda, Daisuke; Suzuki, Hiroshi; Shimizu, Yohei; Ahn, DeukSoon; Murai, Daichi; Inabe, Naohito; Shimaoka, Takehiro; Tsubota, Masakatsu; Kaneko, Junichi H.; Chayahara, Akiyoshi; Umezawa, Hitoshi; Shikata, Shinichi; Kumagai, Hidekazu; Murakami, Hiroyuki; Sato, Hiromi; Yoshida, Koichi; Kubo, Toshiyuki

    A multiple sampling ionization chamber (MUSIC) and parallel-plate avalanche counters (PPACs) were installed within the superconducting in-flight separator, named BigRIPS, at the RIKEN Nishina Center for particle identification of RI beams. The MUSIC detector showed negligible charge collection inefficiency from recombination of electrons and ions, up to a 99-kcps incidence rate for high-energy heavy ions. For the PPAC detectors, the electrical discharge durability for incident heavy ions was improved by changing the electrode material. Finally, we designed a single crystal diamond detector, which is under development for TOF measurements of high-energy heavy ions, that has a very fast response time (pulse width <1 ns).

  15. Presence of an allelic EcoRI restriction fragment of the c-mos locus in leukocyte and tumor cell DNAs of breast cancer patients.

    PubMed Central

    Lidereau, R; Mathieu-Mahul, D; Theillet, C; Renaud, M; Mauchauffé, M; Gest, J; Larsen, C J

    1985-01-01

    Structure of the human c-mos protooncogene in DNAs from breast tumors, leukemic cells, and lymphocytes from normal individuals was analyzed by restriction enzyme digestion and Southern blot. In 6 of 75 breast tumor DNAs, we found an EcoRI 5-kilobase extra band hybridizing with a human c-mos probe containing all of the sequences homologous to v-mos oncogene. This band was also found in lymphocyte DNA from 3 of these patients, indicating a restriction fragment length polymorphism. This polymorphism was not found in a series of 69 lymphocyte DNAs from the unaffected population. Moreover, 1 of 73 leukemic cell DNAs exhibited the 5-kilobase band. These results indicate that this rare polymorphism is significantly more frequently found in patients with breast cancer than in the rest of the population (P less than 0.05, by a chi 2 test with Yates correction. Images PMID:2996003

  16. KEY COMPARISON: Activity measurements of the radionuclide 153Sm for the ANSTO, Australia in the ongoing comparison BIPM.RI(II)-K1.Sm-153

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Reinhard, M.; Alexiev, D.; Mo, L.

    2005-01-01

    In 2004, the Australian Nuclear Science and Technology Organisation (ANSTO) submitted two samples of known activity of 153Sm to the International Reference System (SIR). The value of the activity submitted was about 920 MBq. This key comparison result has been added to the matrix of degrees of equivalence in the key comparison database that now contains five results, identifier BIPM.RI(II)-K1.Sm-153. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  17. Physical Map of the Channel Catfish Virus Genome: Location of Sites for Restriction Endonucleases EcoRI, HindIII, HpaI, and XbaI

    PubMed Central

    Chousterman, Suzanne; Lacasa, Michel; Sheldrick, Peter

    1979-01-01

    The overall arrangement of nucleotide sequences in the DNA of channel catfish virus has been studied by cleavage with four restriction endonucleases. Physical maps have been developed for the location of sites for EcoRI, HindIII, HpaI, and XbaI. The sum of the molecular weights of fragments generated by each restriction enzyme indicates a molecular weight of approximately 86 × 106 for the channel catfish virus genome. Fragments corresponding to the molecular ends of channel catfish virus DNA have been identified by their sensitivity to exonuclease treatment. The distribution of restriction sites in the genome shows that sequences included in a 12 × 106-molecular weight region at one end are repeated with direct polarity at the other end, and that the overall genomic sequence order is nonpermuted. Images PMID:16789182

  18. HPLC separation and determination of 12 cholesterol oxidation products in fish: comparative study of RI, UV, and APCI-MS detectors.

    PubMed

    Saldanha, Tatiana; Sawaya, Alexandra Christine Helena Frankland; Eberlin, Marcos Nogueira; Bragagnolo, Neura

    2006-06-14

    A simple, fast, and sensitive method for the extraction through direct saponification, separation, quantification, and identification of 12 cholesterol oxidation products (COPs) and cholesterol in a single isocratic, normal-phase, high-performance liquid chromatography (HPLC) was developed. Three detectors were compared for determination of COPs and cholesterol in fish samples: refractive index (RI), ultraviolet (UV), and atmospheric pressure chemical ionization mass spectrometry (APCI-MS). The results did not show significant differences (p > 0.05) between the concentration of the cholesterol oxides and cholesterol obtained with these detectors. The present study demonstrated the presence of 19-hydroxycholesterol, 22"R"-hydroxycholesterol, 22"S"-hydroxycholesterol, 24"S"-hydroxycholesterol, and 25"R"-hydroxycholesterol for the first time in fish samples.

  19. Suppression of IgE B cells and IgE binding to Fc(epsilon)RI by gene therapy with single-chain anti-IgE.

    PubMed

    Ota, Takayuki; Aoki-Ota, Miyo; Duong, Bao Hoa; Nemazee, David

    2009-06-15

    IgE plays a pivotal role in allergic reactions and asthma through its ability to bind to the mast cell FcR for IgE (FcepsilonRI). Current therapies to suppress such reactions include passive treatment with neutralizing Abs to IgE that block its binding to FcepsilonRI. In theory, induction of immune tolerance in the B lymphocytes that carry IgE Ag receptors and give rise to IgE-secreting cells should provide longer term efficacy. However, recent data have suggested that such memory cells may lack cell surface IgE. Using a gene therapy approach, we show that a recombinant single-chain neutralizing anti-IgE could not only neutralize circulating IgE, but also reduce IgE(+) B cell numbers and H chain transcripts. Therapeutic anti-IgE stimulated a calcium response in primary B cells or in a B cell line expressing membrane IgE and suppressed IgE secretion in vitro, suggesting that active signaling through membrane IgE likely promoted tolerance. Interestingly, upon subsequent challenge of anti-IgE-treated mice with an IgE cross-linking reagent capable of inducing activation of IgE-decorated mast cells, an anaphylaxis reaction was induced, apparently via a FcgammaRIII pathway involving recognition of anti-IgE Ab itself. These studies have important implications for the optimal design of safe and effective anti-IgE therapies and suggest that the IgE memory B cells may be targeted by such genetic Ab therapies.

  20. Crosstalk between the p38 and TGF-β signaling pathways through TβRI, TβRII and Smad3 expression in plancental choriocarcinoma JEG-3 cells.

    PubMed

    Tan, Yusi; Xu, Qian; Li, Yuhong; Mao, Xiaodan; Zhang, Kongyan

    2014-09-01

    Choriocarcinoma is a highly aggressive tumor that develops from germ cells. Some choriocarcinomas originate in the testes or ovaries, while others may develop in the uterus after a normal pregnancy or after miscarriage. The tumor is characterized by early hematogenous spread to distal organs, such as the lung and brain. Transforming growth factor β1 (TGF-β1) is key in regulating tumor cell proliferation and invasion through a variety of Smad-dependent and -independent pathways, including the p38 mitogen-activated protein kinase (MAPK) pathway. There appears to be crosstalk between the TGF-β/Smad and p38 MAPK pathways; however, the molecular mechanisms underlying the crosstalk are not fully understood. The present study validated the role of TGF-β signaling in cancer progression and explored the interaction between Smad and p38 MAPK signaling on transduction mediators in choriocarcinoma using the JEG-3 cell line. MTT assay was used to detect the effect of TGF-β1 on JEG-3 cell proliferation. Cells were treated with p38 MAPK inhibitor and TGF-β receptor inhibitor, followed by TGF-β1, and reverse transcription quantitative real-time polymerase chain reaction was used to examine the transcriptional levels of Smad3 and TGF-β receptors. The data demonstrated that TGF-β can enhance the viability of JEG-3 cells. Blockade of the TGF-β and p38 MAPK pathways attenuated the expression of Smad3, TGF-β receptor type I (TβRI) and TβRII, and inhibited their expression in a dose-dependent manner. Analysis revealed that p38 MAPK is involved in and contributes to the TGF-β pathway, dependent on the regulation of TβRI, TβRII and Smad3. Further investigation of the interactions between the TGF-β and p38 MAPK pathways may offer potential venues for therapeutic intervention for choriocarcinoma.

  1. Monomeric Immunoglobulin A from Plasma Inhibits Human Th17 Responses In Vitro Independent of FcαRI and DC-SIGN

    PubMed Central

    Saha, Chaitrali; Das, Mrinmoy; Patil, Veerupaxagouda; Stephen-Victor, Emmanuel; Sharma, Meenu; Wymann, Sandra; Jordi, Monika; Vonarburg, Cédric; Kaveri, Srini V.; Bayry, Jagadeesh

    2017-01-01

    Circulating immunoglobulins including immunoglobulin G (IgG) and IgM play a critical role in the immune homeostasis by modulating functions of immune cells. These functions are mediated in part by natural antibodies. However, despite being second most abundant antibody in the circulation, the immunoregulatory function of IgA is relatively unexplored. As Th17 cells are the key mediators of a variety of autoimmune, inflammatory, and allergic diseases, we investigated the ability of monomeric IgA (mIgA) isolated from pooled plasma of healthy donors to modulate human Th17 cells. We show that mIgA inhibits differentiation and amplification of human Th17 cells and the production of their effector cytokine IL-17A. mIgA also suppresses IFN-γ responses under these experimental conditions. Suppressive effect of mIgA on Th17 responses is associated with reciprocal expansion of FoxP3-positive regulatory T cells. The effect of mIgA on Th17 cells is dependent on F(ab′)2 fragments and independent of FcαRI (CD89) and DC-SIGN. Mechanistically, the modulatory effect of mIgA on Th17 cells implicates suppression of phosphorylation of signal transducer and activator of transcription 3. Furthermore, mIgA binds to CD4+ T cells and recognizes in a dose-dependent manner the receptors for cytokines (IL-6Rα and IL-1RI) that mediate Th17 responses. Our findings thus reveal novel anti-inflammatory functions of IgA and suggest potential therapeutic utility of mIgA in autoimmune and inflammatory diseases that implicate Th17 cells. PMID:28352269

  2. Enhancement of antibody-dependent cell-mediated cytotoxicity by endowing IgG with FcαRI (CD89) binding.

    PubMed

    Borrok, M Jack; Luheshi, Nadia M; Beyaz, Nurten; Davies, Gareth C; Legg, James W; Wu, Herren; Dall'Acqua, William F; Tsui, Ping

    2015-01-01

    Fc effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) are crucial to the efficacy of many antibody therapeutics. In addition to IgG, antibodies of the IgA isotype can also promote cell killing through engagement of myeloid lineage cells via interactions between the IgA-Fc and FcαRI (CD89). Herein, we describe a unique, tandem IgG1/IgA2 antibody format in the context of a trastuzumab variable domain that exhibits enhanced ADCC and ADCP capabilities. The IgG1/IgA2 tandem Fc format retains IgG1 FcγR binding as well as FcRn-mediated serum persistence, yet is augmented with myeloid cell-mediated effector functions via FcαRI/IgA Fc interactions. In this work, we demonstrate anti-human epidermal growth factor receptor-2 antibodies with the unique tandem IgG1/IgA2 Fc can better recruit and engage cytotoxic polymorphonuclear (PMN) cells than either the parental IgG1 or IgA2. Pharmacokinetics of IgG1/IgA2 in BALB/c mice are similar to the parental IgG, and far surpass the poor serum persistence of IgA2. The IgG1/IgA2 format is expressed at similar levels and with similar thermal stability to IgG1, and can be purified via standard protein A chromatography. The tandem IgG1/IgA2 format could potentially augment IgG-based immunotherapeutics with enhanced PMN-mediated cytotoxicity while avoiding many of the problems associated with developing IgAs.

  3. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood

    PubMed Central

    Lim, Sang-Dong

    2014-01-01

    Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain 9.03μg/mL of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was 37℃, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products. PMID:26760752

  4. Expansion and methylation status at FRAXE can be detected on EcoRI blots used for FRAXA diagnosis: Analysis of four FRAXE families with mild mental retardation in males

    SciTech Connect

    Biancalana, V.; Bouix, J.C.; Mandel, J.L.

    1996-10-01

    The original test for the analysis of the CCG expansion at the FRAXE locus involves Southern blot analysis of HindIII digests. We show that, by using a different probe, the FRAXE mutation can be detected easily on the same EcoRI or EagI+EcoRI blots as are used for detection of FRAXA. Unexpectedly, we found that both the expansion and methylation status can be determined on a single EcoRI digest, because of the presence of a methylation-sensitive EcoRI site very close to the CCG repeat. We thus detected in a series of mentally retarded individuals previously tested for FRAXA expansion a FRAXE proband who led to the identification of a large sibship (7 of 10 children carrying a mutation). We also show that two fragile X families without FRAXA mutation that previously have been described by Oberle et al. have the FRAXE expansion. In another family also ascertained initially by cytogenetic finding of a fragile X site, we performed the combined cytogenetic and molecular prenatal diagnosis of a mutated male fetus. All nine males (>3 years old) in whom we found a methylated mutation had mild mental retardation. Our results suggest that the threshold of repeat length for abnormal methylation and fragile-site expression may be smaller at FRAXE than at FRAXA. 20 refs., 5 figs., 1 tab.

  5. Role of CC chemokines and their receptors in multiple aspects of mast cell biology: comparative protein profiling of FcepsilonRI- and/or CCR1-engaged mast cells using protein chip technology.

    PubMed

    Toda, Masako; Nakamura, Takao; Ohbayashi, Masaharu; Ikeda, Yoshifumi; Dawson, Maria; Richardson, Ricardo Micheler; Alban, Andrew; Leed, Benjamin; Miyazaki, Dai; Ono, Santa Jeremy

    2005-01-01

    Apart from the FcepsilonRI-mediated mechanism, mast cells are activated by chemokines. Evidence has accumulated indicating that there is cross-talk between the FcepsilonRI-mediated signalling pathway and CC chemokine receptor (CCR)-mediated signalling pathways in mast cells. We have found that costimulation with IgE/antigen and CC chemokine ligand 3 (CCL3) enhances degranulation but inhibits chemotaxis of rat basophilic leukaemia (RBL)-2H3 cells expressing human CCR1 (RBL-CCR1 cells). We hypothesize that this signalling cross-talk in mast cells may play important roles in the orchestration and focusing of the allergic response. In this study, we have sought information about global protein networks either enhanced or inhibited following cross-talk between the FcepsilonRI-mediated and CCR-mediated signalling pathways in mast cells. We believe this information may be useful for providing an understanding of mast cell function and in the establishment of new anti-inflammatory drugs for allergic diseases. Proteomics is a promising tool for studying protein profiles within biological samples and facilitates an understanding of the complex responses of an organism to a stimulus. Here, we show comparative data of protein profiles derived from FcepsilonRI-engaged and/or CCR1-engaged RBL-CCR1 cells using protein chip array technology, a proteomic technology. We also discuss our view of the role of CC chemokines and CCRs in regulating multiple aspects of mast cell biology.

  6. Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.

    PubMed Central

    Pawankar, R; Okuda, M; Yssel, H; Okumura, K; Ra, C

    1997-01-01

    Cross-linking of allergen specific IgE bound to the high affinity IgE receptor (FC epsilonRI) on the surface of mast cells with multivalent allergens results in the release of both pre-formed and newly generated mediators, and in the manifestation of allergic symptoms. The expression of Fc epsilonRI, and the synthesis of IgE are therefore critical for the development of allergic diseases. In this study, we report that nasal mast cells (NMC) from patients with perennial allergic rhinitis (PAR) expressed significantly greater levels of the Fc epsilonRI, CD40L, IL-4, and IL-13 as compared to NMC from patients with chronic infective rhinitis (CIR). The level of Fc epsilonRI expression in NMC of PAR patients strongly correlated with the levels of serum total (r = 0.8, P < 0.003) and specific IgE (r = 0.89, P < 0.0004) antibodies. In addition, stimulation of NMC with IL-4, upregulated the Fc epsilonRIalpha chain expression both at the protein and mRNA levels, as detected by flow cytometry and reverse transcriptase-polymerase chain reaction. Furthermore, NMC from PAR, but not CIR, patients induced IgE synthesis by purified B cells in the presence of Der fII (mite antigen). These results suggest novel and critical roles for mast cells in promoting the allergic reaction through the increased expression of Fc epsilonRI and by enhancing and amplifying the IgE production, within the local microenvironment. PMID:9119992

  7. Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation.

    PubMed

    Udell, Christian M; Samayawardhena, Lionel A; Kawakami, Yuko; Kawakami, Toshiaki; Craig, Andrew W B

    2006-07-28

    Mast cells express the high affinity IgE receptor FcepsilonRI, which upon aggregation by multivalent antigens elicits signals that cause rapid changes within the mast cell and in the surrounding tissue. We previously showed that FcepsilonRI aggregation caused a rapid increase in phosphorylation of both Fer and Fps/Fes kinases in bone marrow-derived mast cells. In this study, we report that FcepsilonRI aggregation leads to increased Fer/Fps kinase activities and that Fer phosphorylation downstream of FcepsilonRI is independent of Syk, Fyn, and Gab2 but requires Lyn. Activated Fer/Fps readily phosphorylate the C terminus of platelet-endothelial cell adhesion molecule 1 (Pecam-1) on immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a non-ITIM residue (Tyr(700)) in vitro and in transfected cells. Mast cells devoid of Fer/Fps kinase activities display a reduction in FcepsilonRI aggregation-induced tyrosine phosphorylation of Pecam-1, with no defects in recruitment of Shp1/Shp2 phosphatases observed. Lyn-deficient mast cells display a dramatic reduction in Pecam-1 phosphorylation at Tyr(685) and a complete loss of Shp2 recruitment, suggesting a role as an initiator kinase for Pecam-1. Consistent with previous studies of Pecam-1-deficient mast cells, we observe an exaggerated degranulation response in mast cells lacking Fer/Fps kinases at low antigen dosages. Thus, Lyn and Fer/Fps kinases cooperate to phosphorylate Pecam-1 and activate Shp1/Shp2 phosphatases that function in part to limit mast cell activation.

  8. Total and partial sleep deprivation: Effects on plasma TNF-αRI, TNF-αRII, and IL-6, and reversal by caffeine operating through adenosine A2 receptor

    NASA Astrophysics Data System (ADS)

    Shearer, William T.; Reuben, James M.; Lee, Bang-Ning; Mullington, Janet; Price, Nicholas; Dinges, David F.

    2000-01-01

    Plasma levels of IL-6 and TNF-α are elevated in individuals who are deprived of sleep. TNF-α regulates expression of its soluble receptors, sTNF-αRI and sTNF-αRII. Sleep deprivation (SD) also increases extracellular adenosine that induces sedation and sleep. An antagonist of adenosine, caffeine, raises exogenous adenosine levels, stimulates the expression of IL-6 and inhibits the release of TNF-α. Our objective was to determine the effect of total SD (TSD) or partial SD (PSD) on the levels of these sleep regulatory molecules in volunteers who experienced SD with or without the consumption of caffeine. Plasma levels of IL-6, sTNF-αRI and sTNF-αRII were assayed by ELISA in samples collected at 90-min intervals from each subject over an 88-hour period. The results were analyzed by the repeated measures ANOVA. Whereas only TSD significantly increased sTNF-αRI over time, caffeine suppressed both sTNF-α receptors in TSD and PSD subjects. The selective increase in the expression of sTNF-αRI and not sTNF-αRII in subjects experiencing TSD with caffeine compared with others experiencing PSD with caffeine has not been previously reported. Moreover, caffeine significantly increased IL-6 in TSD subjects compared with those who did not receive caffeine. However, subjects who were permitted intermittent naps (PSD) ablated the effects of caffeine and reduced their level of IL-6 to that of the TSD group. These data further lend support to the hypothesis that the sTNF-αRI and not the sTNF-αRII plays a significant role in sleep regulation by TNF-α. .

  9. New Enhanced Artificial Bee Colony (JA-ABC5) Algorithm with Application for Reactive Power Optimization

    PubMed Central

    2015-01-01

    The standard artificial bee colony (ABC) algorithm involves exploration and exploitation processes which need to be balanced for enhanced performance. This paper proposes a new modified ABC algorithm named JA-ABC5 to enhance convergence speed and improve the ability to reach the global optimum by balancing exploration and exploitation processes. New stages have been proposed at the earlier stages of the algorithm to increase the exploitation process. Besides that, modified mutation equations have also been introduced in the employed and onlooker-bees phases to balance the two processes. The performance of JA-ABC5 has been analyzed on 27 commonly used benchmark functions and tested to optimize the reactive power optimization problem. The performance results have clearly shown that the newly proposed algorithm has outperformed other compared algorithms in terms of convergence speed and global optimum achievement. PMID:25879054

  10. KEY COMPARISON: Comparisons CCRI(II)-K3.F-18 and APMP.RI(II)-K3.F-18 of activity measurements of the radionuclide 18F and links to the key comparison reference value of the BIPM.RI(II)-K1.F-18 comparison

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Woods, M. J.

    2005-01-01

    In 2003, the CCRI(II) decided that an indirect comparison of 18F measurements piloted by the National Physical Laboratory (NPL), UK in 2001 was sufficiently well constructed that it could be converted into a CCRI(II) comparison, with comparison identifier CCRI(II)-K3.F-18. At the same time, the pilot laboratory made a bilateral comparison with the institute in Chinese Taipei, comparison identifier APMP.RI(II)-K3.F-18. The results of the comparisons have been reported and the key comparison working group (KCWG) of the CCRI(II) has approved the mechanism to link all the results to the key comparison reference value (KCRV) of 18F. The KCRV has been determined through the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.F-18. These comparisons have enabled a further four results to be added to the matrix of degrees of equivalence for 18F activity measurements. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  11. Aniline is an inducer, and not a precursor, for indole derivatives in Rubrivivax benzoatilyticus JA2.

    PubMed

    Mujahid, Mohammed; Sasikala, Ch; Ramana, Ch V

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway.

  12. Aniline Is an Inducer, and Not a Precursor, for Indole Derivatives in Rubrivivax benzoatilyticus JA2

    PubMed Central

    Mohammed, Mujahid; Ch, Sasikala; Ch, Ramana V.

    2014-01-01

    Rubrivivax benzoatilyticus JA2 and other anoxygenic photosynthetic bacteria produce indole derivatives when exposed to aniline, a xenobiotic compound. Though this phenomenon has been reported previously, the role of aniline in the production of indoles is still a biochemical riddle. The present study aims at understanding the specific role of aniline (as precursor or stimulator) in the production of indoles and elucidating the biochemical pathway of indoles in aniline-exposed cells by using stable isotope approaches. Metabolic profiling revealed tryptophan accumulation only in aniline exposed cells along with indole 3-acetic acid (IAA) and indole 3-aldehyde (IAld), the two major catabolites of tryptophan. Deuterium labelled aniline feeding studies revealed that aniline is not a precursor of indoles in strain JA2. Further, production of indoles only in aniline-exposed cells suggests that aniline is an indoles stimulator. In addition, production of indoles depended on the presence of a carbon source, and production enhanced when carbon sources were added to the culture. Isotope labelled fumarate feeding identified, fumarate as the precursor of indole, indicating de novo synthesis of indoles. Glyphosate (shikimate pathway inhibitor) inhibited the indoles production, accumulation of tryptophan, IAA and IAld indicating that indoles synthesis in strain JA2 occurs via the de novo shikimate pathway. The up-regulation of anthranilate synthase gene and induction of anthranilate synthase activity correlated well with tryptophan production in strain JA2. Induction of tryptophan aminotransferase and tryptophan 2-monooxygenase activities corroborated well with IAA levels, suggesting that tryptophan catabolism occurs simultaneously in aniline exposed cells. Our study demonstrates that aniline (stress) stimulates tryptophan/indoles synthesis via the shikimate pathway by possibly modulating the metabolic pathway. PMID:24533057

  13. Resistance of Fusarium poae in Arabidopsis leaves requires mainly functional JA and ET signaling pathways.

    PubMed

    Dinolfo, María Inés; Castañares, Eliana; Stenglein, Sebastián A

    2017-10-01

    Fusarium poae has been considered as a minor species among those that cause the FHB disease but in recent years several researchers have documented a high frequency of occurrence in several crops. We evaluated the ability of F. poae to produce symptoms in A. thaliana leaves. Moreover, we analyzed the defense of A. thaliana against F. poae using SA, JA, and ET mutants and we monitored the expression level of genes involved in the main signaling pathways related to plant defense. Symptoms were observed in the inoculated leaves demonstrating the ability of F. poae to infect A. thaliana leaves. Moreover, the npr1-1 mutants presented low symptoms compared to Col-0, etr2-1, and coi1-1 and that the coi1-1 mutant was the most susceptible genotypes followed by etr2-1 genotypes. The RT-PCR revealed that PDF1.2, CHI/PR3, and ERF1, three important JA-ET responsive genes and NPR1 and PR1, which are regulated by SA signaling, were expressed upon F. poae inoculation. Our results suggest that JA and ET could play a key role in Arabidopsis leaves defense against F. poae representing the first evaluation of the response of the main A. thaliana phytohormones involved in plant defense in the presence of F. poae. Copyright © 2017 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  14. Biosynthesis of silver and zinc oxide nanoparticles using Pichia fermentans JA2 and their antimicrobial property

    NASA Astrophysics Data System (ADS)

    Chauhan, Ritika; Reddy, Arpita; Abraham, Jayanthi

    2015-01-01

    The development of eco-friendly alternative to chemical synthesis of metal nanoparticles is of great challenge among researchers. The present study aimed to investigate the biological synthesis, characterization, antimicrobial study and synergistic effect of silver and zinc oxide nanoparticles against clinical pathogens using Pichia fermentans JA2. The extracellular biosynthesis of silver and zinc oxide nanoparticles was investigated using Pichia fermentans JA2 isolated from spoiled fruit pulp bought in Vellore local market. The crystalline and stable metallic nanoparticles were characterized evolving several analytical techniques including UV-visible spectrophotometer, X-ray diffraction pattern analysis and FE-scanning electron microscope with EDX-analysis. The biosynthesized metallic nanoparticles were tested for their antimicrobial property against medically important Gram positive, Gram negative and fungal pathogenic microorganisms. Furthermore, the biosynthesized nanoparticles were also evaluated for their increased antimicrobial activities with various commercially available antibiotics against clinical pathogens. The biosynthesized silver nanoparticles inhibited most of the Gram negative clinical pathogens, whereas zinc oxide nanoparticles were able to inhibit only Pseudomonas aeruginosa. The combined effect of standard antibiotic disc and biosynthesized metallic nanoparticles enhanced the inhibitory effect against clinical pathogens. The biological synthesis of silver and zinc oxide nanoparticles is a novel and cost-effective approach over harmful chemical synthesis techniques. The metallic nanoparticles synthesized using Pichia fermentans JA2 possess potent inhibitory effect that offers valuable contribution to pharmaceutical associations.

  15. High-Rate Mechanical Properties of JA2 Propellant at Temperatures from -50 to 80 deg C

    DTIC Science & Technology

    2015-07-01

    Proving Ground (MD): Army Research Laboratory (US); 2005 Jul. Report No.: ARL-TR-3546. 11. Hoffman HJ. Uniaxial compressive gun propellant test. In: Solid ...ARL-MR-0894 ● JULY 2015 US Army Research Laboratory High-Rate Mechanical Properties of JA2 Propellant at Temperatures from –50...Research Laboratory High-Rate Mechanical Properties of JA2 Propellant at Temperatures from –50 to 80 °C by Stephen L Howard, Michael G Leadore

  16. The crosstalk between Target of Rapamycin (TOR) and Jasmonic Acid (JA) signaling existing in Arabidopsis and cotton

    PubMed Central

    Song, Yun; Zhao, Ge; Zhang, Xueyan; Li, Linxuan; Xiong, Fangjie; Zhuo, Fengping; Zhang, Chaojun; Yang, Zuoren; Datla, Raju; Ren, Maozhi; Li, Fuguang

    2017-01-01

    Target of rapamycin (TOR) acts as an important regulator of cell growth, development and stress responses in most examined diploid eukaryotes. However, little is known about TOR in tetraploid species such as cotton. Here, we show that TORC1-S6K-RPS6, the major signaling components, are conserved and further expanded in cotton genome. Though the cotton seedlings are insensitive to rapamycin, AZD8055, the second-generation inhibitor of TOR, can significantly suppress the growth in cotton. Global transcriptome analysis revealed that genes associated with jasmonic acid (JA) biosynthesis and transduction were significantly altered in AZD8055 treated cotton seedlings, suggesting the potential crosstalk between TOR and JA signaling. Pharmacological and genetic approaches have been employed to get further insights into the molecular mechanism of the crosstalk between TOR and JA. Combination of AZD8055 with methyl jasmonate can synergistically inhibit cotton growth, and additionally JA levels were significantly increased when cotton seedlings were subjected to AZD8055. JA biosynthetic and signaling mutants including jar1, coi1-2 and myc2-2 displayed TOR inhibitor-resistant phenotypes, whereas COI1 overexpression transgenic lines and jaz10 exhibited sensitivity to AZD8055. Consistently, cotton JAZ can partially rescue TOR-suppressed phenotypes in Arabidopsis. These evidences revealed that the crosstalk between TOR and JA pathway operates in cotton and Arabidopsis. PMID:28374843

  17. The crosstalk between Target of Rapamycin (TOR) and Jasmonic Acid (JA) signaling existing in Arabidopsis and cotton.

    PubMed

    Song, Yun; Zhao, Ge; Zhang, Xueyan; Li, Linxuan; Xiong, Fangjie; Zhuo, Fengping; Zhang, Chaojun; Yang, Zuoren; Datla, Raju; Ren, Maozhi; Li, Fuguang

    2017-04-04

    Target of rapamycin (TOR) acts as an important regulator of cell growth, development and stress responses in most examined diploid eukaryotes. However, little is known about TOR in tetraploid species such as cotton. Here, we show that TORC1-S6K-RPS6, the major signaling components, are conserved and further expanded in cotton genome. Though the cotton seedlings are insensitive to rapamycin, AZD8055, the second-generation inhibitor of TOR, can significantly suppress the growth in cotton. Global transcriptome analysis revealed that genes associated with jasmonic acid (JA) biosynthesis and transduction were significantly altered in AZD8055 treated cotton seedlings, suggesting the potential crosstalk between TOR and JA signaling. Pharmacological and genetic approaches have been employed to get further insights into the molecular mechanism of the crosstalk between TOR and JA. Combination of AZD8055 with methyl jasmonate can synergistically inhibit cotton growth, and additionally JA levels were significantly increased when cotton seedlings were subjected to AZD8055. JA biosynthetic and signaling mutants including jar1, coi1-2 and myc2-2 displayed TOR inhibitor-resistant phenotypes, whereas COI1 overexpression transgenic lines and jaz10 exhibited sensitivity to AZD8055. Consistently, cotton JAZ can partially rescue TOR-suppressed phenotypes in Arabidopsis. These evidences revealed that the crosstalk between TOR and JA pathway operates in cotton and Arabidopsis.

  18. Differential Expression of Carotenogenic Genes, Associated Changes on Astaxanthin Production and Photosynthesis Features Induced by JA in H. pluvialis

    PubMed Central

    Zhang, Xiaowen; Xu, Dong; Zhao, Yuefeng; Wang, Yitao; Lv, Hongxin; Liming Yang; Chen, Lingling; Ye, Naihao

    2012-01-01

    Haematococcus pluvialis is an organism that under certain conditions can produce astaxanthin, an economically important carotenoid. In this study, the transcriptional expression patterns of eight carotenogenic genes of H. pluvialis in response to jasmonic acid (JA) were evaluated using real-time PCR. Astaxanthin accumulation action and photosynthesis flourescence were monitored at the same time. The results showed all eight genes exhibited higher transcriptional expression significantly under JA treatments. JA25 (25 mg/L) induction had greater effect (>10-fold up-regulation) on the transcriptional expression of pds, crtR-B and lyc than on ipi-1, ipi-2, psy, bkt2, and crtO. JA50 (50 mg/L) treatment had greater impact on the transcriptional expression of ipi-1, ipi-2, psy, crtR-B and crtO than on pds, lyc and bkt2. Astaxanthin biosynthesis in the presence of JA appeared to be up-regulated mainly by psy, pds, crtR-B, lyc, bkt2 and crtO at the transcriptional level and ipi-1, ipi-2 at both transcriptional and post-transcriptional levels. Under JA induction, the photosynthetic efficiency [Y (II)] and the maximum quantum efficiency of PS II (Fv/Fm) decreased significantly, but the non-photochemical quenching of chlorophyll fluorescence (NPQ) increased drastically with the accumulation of astaxanthin. PMID:22870309

  19. AN EXAMINATION OF RECENT TRANSFORMATIONS TO THE BV(RI){sub C} PHOTOMETRIC SYSTEM FROM THE PERSPECTIVE OF STELLAR MODELS FOR OLD STARS

    SciTech Connect

    VandenBerg, Don A.; Casagrande, L.; Stetson, Peter B. E-mail: Luca@MPA-Garching.mpg.d

    2010-10-15

    Isochrones for ages {approx}>4 Gyr and metallicities in the range -2.5{approx}< [Fe/H] {approx}<+0.3 that take the diffusion of helium and recent advances in stellar physics into account are compared with observations in the Johnson-Cousins BV(RI){sub C} photometric system for several open and globular star clusters. The adopted color-T{sub eff} relations include those which we have derived from the latest MARCS model atmospheres and the empirical transformations for dwarf and subgiant stars given by Casagrande et al. (CRMBA). Those reported by VandenBerg and Clem have also been considered, mainly to resolve some outstanding questions concerning them. Indeed, for the latter, V - I{sub C} colors should be corrected by {approx}-0.02 mag, for all metal abundances, in order to obtain consistent interpretations of the observed (B - V, V), (V - R{sub C} , V), and (V - I{sub C} , V) diagrams for M 67 and the Hyades as well as for local subdwarfs. Remarkably, when the subdwarfs in the CRMBA data set that have {sigma}{sub {pi}/{pi}} {<=} 0.15 are superimposed on a set of 12 Gyr isochrones spanning a wide range in [Fe/H], the inferred metallicities and effective temperatures agree, in the mean, with those given by CRMBA to within {+-}0.05 dex and {+-}10 K, respectively. Thus, the hot T{sub eff} scale derived by CRMBA is nearly identical with that predicted by stellar models; and consequently, there is excellent consistency between theory and observations on the Hertzsprung-Russell diagram and the different color-magnitude diagrams considered in this investigation. To obtain similar consistency, the colors obtained from the MARCS and VandenBerg and Clem (B - V)-T{sub eff} relations for metal-poor dwarf stars should be adjusted to the red by 0.02-0.03 mag. In general, isochrones that employ the CRMBA transformations provide reasonably consistent fits to our BV(RI){sub C} photometry for main-sequence stars in the globular clusters 47 Tuc, M 3, M 5, M 92, and NGC 1851-but not

  20. SPiRIT-TPC with GET readout electronics for the study of density dependent symmetry energy of high dense matter with Heavy RI collisions

    NASA Astrophysics Data System (ADS)

    Isobe, Tadaaki; SPiRIT Collaboration

    2014-09-01

    The nuclear Equation of State (EoS) is a fundamental property of nuclear matter that describes the relationships between the parameters for a nuclear system, such as energy, density and temperature. An international collaboration, named SPiRIT, to study the nuclear EoS has been formed recently. One of the main devices of experimental setup is a Time Projection Chamber (TPC) which will be installed into the SAMURAI dipole magnet at RIKEN-RIBF. The TPC can measure charged pions, protons and light ions simultaneously in heavy RI collisions, and those will be used as probes to study the asymmetric dense nuclear matter. In addition to the status of the SPiRIT project, testing of SPiRIT-TPC with GET electronics will be presented in this talk. GET, general electronics for TPC, is a project for the development of novel electronics for TPC supported by NSF and ANR. This work is supported in part by the Japan Grant-in-Aide award and the US DOE grant DE-SC0004835 and JUSEIPEN.

  1. Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation.

    PubMed

    Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S; Pucillo, Carlo E

    2011-10-01

    Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.

  2. Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation

    PubMed Central

    Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S.; Pucillo, Carlo E.

    2011-01-01

    Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease. PMID:21653238

  3. Colonization pattern of primary tomato roots by Pseudomonas fluorescens A6RI characterized by dilution plating, flow cytometry, fluorescence, confocal and scanning electron microscopy.

    PubMed

    Gamalero, Elisa; Lingua, Guido; Giusy Caprì, Flavia; Fusconi, Anna; Berta, Graziella; Lemanceau, Philippe

    2004-04-01

    Early colonization of primary tomato roots, grown in vitro, by Pseudomonas fluorescens A6RI, introduced by seed bacterization, was monitored for 7 days in three different root zones (zone A, apex+elongation+young hairy zone; zone B, hairy zone; zone C, old hairy zone+collar). Bacterial quantification was assessed by enumeration of (i) colony forming units (cfu) after dilution plating and of (ii) total bacterial cells by flow cytometry. Bacterial distribution and organization in the root zones were analyzed by fluorescence, confocal and scanning electron microscopy. For all sampling dates and zones, the densities of total bacterial cells were significantly higher than those of the cfu. The kinetics of cfu densities varied according to the root zone. Their density decreased with time in zone A, while no variation with time was recorded in zones B and C. Densities of total bacterial cells did not show any significant temporal variation for any of the root zones. Microscopic analyses allowed the characterization of the distribution and organizational patterns of the bacterial cells according to time and space. In 3-day-old plants, bacteria were mostly present as single cells and were evenly distributed in the two root zones analyzed (A and B). In 5- and 7-day-old plants, distribution and organization differed according to the root zone. In zone A, only few single cells were observed, whereas zones B and C were mostly covered by cells localized between epidermal root cells and organized in pairs and strings, respectively.

  4. Evaluation of anti-inflammatory activity of Solanum xanthocarpum Schrad and Wendl (Kaṇṭakāri) extract in laboratory animals

    PubMed Central

    More, Shraddha K.; Lande, Anirudha A.; Jagdale, Priti G.; Adkar, Prafulla P.; Ambavade, Shirishkumar D.

    2013-01-01

    Context: Solanum xanthocarpum Schrad and Wendl (Kaṇṭakāri) is a diffuse herb with prickly stem, traditionally used for the treatment of inflammation and one in the group of daśamūla (group of ten herbs) herbs commonly used drug in Ayurveda. Aims: In continuation of search for potent natural anti-inflammatory agents, the present research work was planned to evaluate the anti-inflammatory activity of ethanol extract of S. xanthocarpum whole plant. Settings and Design: The ethanol extract was evaluated at dose 10, 30 and 100 mg/kg p.o. in rats. Materials and Methods: Using pharmacological screening models carrageenan induced rat paw edema, histamine induced rat paw edema and cotton pellet granuloma in rats. Statistical Analysis Used: Data obtained was analyzed statistically using analysis of variance followed by post-hoc Dunnett test, P < 0.05 is considered as statistically significant. Results: Acute treatment didn’t show anti-inflammatory activity against carrageenan and histamine induced paw edema. However, administration of 100 mg/kg p.o for 7 day reduced the granuloma formation in cotton pellet granuloma model. Conclusions: Present results support the traditional use of plant for anti-inflammatory activity. In brief, the results provide scientific pharmacological basis for the therapeutic use of S. xanthocarpum. PMID:24991071

  5. Structural similarity between Fc receptors and T cell receptors. Expression of the gamma-subunit of Fc epsilon RI in human T cells, natural killer cells and thymocytes.

    PubMed

    Vivier, E; Rochet, N; Kochan, J P; Presky, D H; Schlossman, S F; Anderson, P

    1991-12-15

    The TCR complex is composed of a clonotypic heterodimer (Ti alpha:beta or gamma:delta) noncovalently associated with the CD3 complex (gamma, delta, and epsilon), and with one or more disulfide-linked dimers whose components are designated zeta and eta. zeta and eta are alternative transcripts of a common gene and are structurally related to the gamma-subunit of the FcR for IgE expressed on mast cells and basophils (Fc epsilon RI). Recent evidence suggests that gamma can also be expressed in natural killer cells and in a murine cytotoxic T cell line, CTLL. Because zeta, eta, and gamma have the potential to join together to form disulfide linked homo- and heterodimers, it has been postulated that alternative dimeric forms composed of these zeta-related subunits might subserve unique signal transducing functions in hematopoietic cells. We have used mAb reactive with zeta and gamma to systematically examine the expression of these zeta-related dimers in human T cells, NK cells, and thymocytes. Our results show that each cell type expresses characteristic combinations of zeta-related homo- and hetero-dimers, and are therefore consistent with the possibility that these subunits contribute to the functional heterogeneity of lymphocyte subsets.

  6. Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

    PubMed

    Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

    2011-08-01

    Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

  7. Simultaneous determination of glucose, fructose, sucrose and sorbitol in the leaf and fruit peel of different apple cultivars by the HPLC-RI optimized method.

    PubMed

    Filip, Miuţa; Vlassa, Mihaela; Coman, Virginia; Halmagyi, Adela

    2016-05-15

    A high performance liquid chromatography method with refractive index detection (HPLC-RI), for simultaneous determination of glucose, fructose, sucrose and sorbitol in leaf and/or apple peel samples from nine apple (Malus domestica Borkh.) cultivars and rootstocks, originating from a germplasm collection, has been developed and validated. Box-Behnken design of response surface methodology was applied for the method optimization. The Carbosep Coregel 87H3 column was used under the optimum conditions predicted: mobile phase of H2SO4 0.005 mol L(-1) solution, flow rate of 0.3 mL min(-1) and column temperature of 35°C. The method was validated for linearity (R(2)>0.99), limits of detection (2.67-4.83 μg mL(-1)) and quantification (8.9-16.1 μg mL(-1)), precision (%RSD<5.05) and recovery (93.94-103.06%) and satisfactory results obtained. The sugars content varied across micropropagated plants in vitro, plants regenerated after cryostorage, growing trees in vivo, and fruit peel.

  8. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the NPL

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Woods, M. J.

    2003-01-01

    Since 2001, four national metrology institutes (NMIs) have submitted four samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures, the most recent being that of the NPL (UK). The activities ranged from about 1 MBq to 8 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value and the degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated and the results are given in the form of a matrix. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), comparison identifier BIPM.RI(II)-K1.F-18, according to the provisions of the Mutual Recognition Arrangement (MRA).

  9. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the CIEMAT

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; García-Toraño, E.; Los Arcos, J.-M.

    2004-01-01

    Since 2001, five national metrology institutes (NMIs) have submitted five samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), the most recent being that of the CIEMAT (Spain). The activities ranged from about 1 MBq to 18 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value and the degrees of equivalence between each equivalent activity measured in the SIR have been calculated and the results are given in the form of a matrix. A graphical presentation is also given for this key comparison with identifier BIPM.RI(II)-K1.F-18. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  10. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the PTB

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Kossert, K.; Janßen, H.

    2006-01-01

    Since 2001, six national metrology institutes (NMIs) have submitted six samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), the most recent being that of the PTB (Germany). The activities ranged from about 1 MBq to 18 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value, with the agreement of the CCRI(II). The degrees of equivalence between each equivalent activity measured in the SIR have been recalculated and the results are given in the form of a matrix. A graphical presentation is also given for this key comparison with identifier BIPM.RI(II)-K1.F-18. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  11. Biosorption of Congo Red from aqueous solution by Bacillus weihenstephanensis RI12; effect of SPB1 biosurfactant addition on biodecolorization potency.

    PubMed

    Mnif, Inès; Fendri, Raouia; Ghribi, Dhouha

    2015-01-01

    Bacillus weihenstephanensis RI12, isolated from hydrocarbon contaminated soil, was assessed for Congo Red bio-treatment potency. Results suggested the potential of this bacterium for use in effective treatment of Congo Red contaminated wastewaters under shaking conditions at acidic and neutral pH value. The strain could tolerate higher doses of dyes as it could decolorize up to 1,000 mg/l of Congo Red. When used as microbial surfactant to enhance Congo Red biodecolorization, Bacillus subtilis SPB1-derived lipopeptide accelerated the decolorization rate and maximized the decolorization efficiency at an optimal concentration of biosurfactant of about 0.075%. Studies ensured that Congo Red removal by this strain could be due to an adsorption phenomena. Germination potencies of tomato seeds using the treated dyes under different conditions showed the efficient biotreatment of the azo dye Congo Red especially with the addition of SPB1 biosurfactant. To conclude, the addition of SPB1 bioemulsifier reduced energy costs by reducing the effective decolorization period; the biosurfactant stimulated bacterial decolorization method may provide a highly efficient, inexpensive and time-saving procedure in the treatment of textile effluents.

  12. KEY COMPARISON: APMP/TCRI key comparison report of measurement of air kerma for medium-energy x-rays (APMP.RI(I)-K3)

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Hwang, W. S.; Kotler, L. H.; Webb, D. V.; Büermann, L.; Burns, D. T.; Takeyeddin, M.; Shaha, V. V.; Srimanoroth, S.; Meghzifene, A.; Hah, S. H.; Chun, K. J.; Kadni, T. B.; Takata, N.; Msimang, Z.

    2008-01-01

    The APMP/TCRI Dosimetry Working Group performed the APMP.RI(I)-K3 key comparison of measurement of air kerma for medium-energy x-rays (100 kV to 250 kV) between 2000 and 2003. In total, 11 institutes took part in the comparison, among which 8 were APMP member laboratories. Two commercial cavity ionization chambers were used as transfer instruments and circulated among the participants. All the participants established the 100 kV, 135 kV, 180 kV and 250 kV x-ray beam qualities equivalent to those of the BIPM. The results showed that the maximum difference between the participants and the BIPM in the medium-energy x ray range, evaluated using the comparison data of the linking laboratories ARPANSA and PTB, is less than 1.4%. The degrees of equivalence between the participants are presented and this comparison confirms the calibration capabilities of the participating laboratories. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section I, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  13. Analysis for measuring the interaction of groundwater and river water by using Radon-222: A case study in Yangsu-ri, Korea

    NASA Astrophysics Data System (ADS)

    Kim, J.; Lee, K. K.

    2014-12-01

    The water cycle is essential for the maintenance of ecosystems. Above all, water exchange between groundwater and river water has a significant impact on the water quality and hydrological zones. The natural radiogenic tracers such as Radon-222 can be used as good indicator for measuring the interaction between groundwater and river water even though the conventional methods of analysis are direct measurements of water flux, heat tracer methods, mass balance approaches and methods based on Darcy's law. The object of this study is to know the change of water environment and to do water resource management effectively by studying the interaction between groundwater and river water in Yangsu-ri of Korea. This paper used methods using temperature profiles, EC values, DO values and radon tracer. In this study, diurnal and seasonal variation of radon value was measured with other values. The result values proved that the more the region was influenced by river water, the closer to the values of river water the result values are. The radon value indicated a similar pattern with other values. The analysis also applied river water stage change by dam discharge. In addition, the mixing modeling of groundwater and river water was conducted to confirm the difference between the calculated value and the measured value. It turned out that radon tracer can be used as environmental tracer for analysis of the interaction between groundwater and river water.

  14. Identification of a Gypsy SHOX mutation (p.A170P) in Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia

    PubMed Central

    Barca-Tierno, Verónica; Aza-Carmona, Miriam; Barroso, Eva; Heine-Suner, Damia; Azmanov, Dimitar; Rosell, Jordi; Ezquieta, Begoña; Montané, Lucia Sentchordi; Vendrell, Teresa; Cruz, Jaime; Santos, Fernando; Rodríguez, José Ignacio; Pozo, Jesús; Argente, Jesús; Kalaydjieva, Luba; Gracía, Ricardo; Campos-Barros, Ángel; Benito-Sanz, Sara; Heath, Karen E

    2011-01-01

    We report the clinical and molecular characteristics of 12 Spanish families with multiple members affected with Léri-Weill dyschondrosteosis (LWD) or Langer mesomelic dysplasia (LMD), who present the SHOX (short stature homeobox gene) mutation p.A170P (c.508G>C) in heterozygosity or homozygosity, respectively. In all studied families, the A170P mutation co-segregated with the fully penetrant phenotype of mesomelic limb shortening and Madelung deformity. A shared haplotype around SHOX was observed by microsatellite analysis, confirming the presence of a common ancestor, probably of Gypsy origin, as 11 of the families were of this ethnic group. Mutation screening in 359 Eastern-European Gypsies failed to identify any carriers. For the first time, we have shown SHOX expression in the human growth plate of a 22-week LMD fetus, homozygous for the A170P mutation. Although the mutant SHOX protein was expressed in all zones of the growth plate, the chondrocyte columns in the proliferative zone were disorganized with the chondrocytes occurring in smaller columnal clusters. We have also identified a novel mutation at the same residue, c. 509C>A (p.A170D), in two unrelated Spanish LWD families, which similar to A170P mutation impedes nuclear localization of SHOX. In conclusion, we have identified A170P as the first frequent SHOX mutation in Gypsy LWD and LMD individuals. PMID:21712857

  15. Over-expression of SlJA2 decreased heat tolerance of transgenic tobacco plants via salicylic acid pathway.

    PubMed

    Liu, Zhong-Ming; Yue, Meng-Meng; Yang, Dong-Yue; Zhu, Shao-Bo; Ma, Na-Na; Meng, Qing-Wei

    2017-04-01

    Over-expression of SlJA2 decreased the accumulation of SA, which resulted in significant physiological and gene expression changes in transgenic tobacco plants, leading to the decreased heat tolerance of transgenic tobacco. NAC family, the largest transcription factors in plants, responses to different environmental stimuli. Here, we isolated a typical NAC transcription factor (SlJA2) from tomato and got transgenic tobacco with SlJA2 over-expression. Expression of SlJA2 was induced by heat stress (42 °C), chilling stress (4 °C), drought stress, osmotic stress, abscisic acid, and salicylic acid. Over-expression of SlJA2 decreased the accumulation of salicylic acid by regulating expression of salicylic acid degradation gene under heat stress. Compared to WT plants, stomatal apertures and water loss increased in transgenic plants, and the damage of photosynthetic apparatus and chlorophyll breakdown were more serious in transgenic plants under heat stress. Meanwhile, more H2O2 and O2(·-) were accumulated transgenic plants and proline synthesis was restricted, which resulted in more serious oxidative damage compared to WT. qRT-PCR analysis showed that over-expression of SlJA2 could down-regulate genes involved in reactive oxygen species scavenging, proline biosynthesis, and response to heat stress. All the above results indicated that SlJA2 may be a negative regulator responded to plant's heat tolerance. Thus, this study provides new insight into roles of NAC family member in plant response to abiotic stress.

  16. Priming for JA-dependent defenses using hexanoic acid is an effective mechanism to protect Arabidopsis against B. cinerea.

    PubMed

    Kravchuk, Zhana; Vicedo, Begonya; Flors, Víctor; Camañes, Gemma; González-Bosch, Carmen; García-Agustín, Pilar

    2011-03-01

    Soil drench treatments with hexanoic acid can effectively protect Arabidopsis plants against Botrytis cinerea through a mechanism based on a stronger and faster accumulation of JA-dependent defenses. Plants impaired in ethylene, salicylic acid, abscisic acid or glutathion pathways showed intact protection by hexanoic acid upon B. cinerea infection. Accordingly, no significant changes in the SA marker gene PR-1 in either the SA or ABA hormone balance were observed in the infected and treated plants. In contrast, the JA signaling pathway showed dramatic changes after hexanoic acid treatment, mainly when the pathogen was present. The impaired JA mutants, jin1-2 and jar1, were unable to display hexanoic acid priming against the necrotroph. In addition, hexanoic acid-treated plants infected with B. cinerea showed priming in the expression of the PDF1.2, PR-4 and VSP1 genes implicated in the JA pathways. Moreover, JA and OPDA levels were primed at early stages by hexanoic acid. Treatments also stimulated increased callose accumulation in response to the pathogen. Although callose accumulation has proved an effective IR mechanism against B. cinerea, it is apparently not essential to express hexanoic acid-induced resistance (HxAc-IR) because the mutant pmr4.1 (callose synthesis defective mutant) is protected by treatment. We recently described how hexanoic acid treatments can protect tomato plants against B. cinerea by stimulating ABA-dependent callose deposition and by priming OPDA and JA-Ile production. We clearly demonstrate here that Hx-IR is a dependent plant species, since this acid protects Arabidopsis plants against the same necrotroph by priming JA-dependent defenses without enhancing callose accumulation.

  17. Roles for the High Affinity IgE Receptor, FcεRI, of Human Basophils in the Pathogenesis and Therapy of Allergic Asthma: Disease Promotion, Protection or Both?

    PubMed

    Youssef, Lama A; Schuyler, Mark; Wilson, Bridget S; Oliver, Janet M

    2010-01-01

    The role of basophils, the rarest of blood granulocytes, in the pathophysiology of allergic asthma is still incompletely understood. Indirect evidence generated over many decades is consistent with a role for basophils in disease promotion. Recent improvements in procedures to purify and analyze very small numbers of human cells have generally supported this view, but have also revealed new complexities. This chapter focuses on our analyses of Fcε R1 function in basophils in the context of understanding and treating human allergic asthma. In long-term studies, we demonstrated that asthmatic subjects have higher circulating numbers of basophils than non-atopic non-asthmatic subjects and that their basophils show higher rates of both basal and anti-IgE or antigen-stimulated histamine release. These results hint at a direct role for basophils in promoting asthma. Supporting this interpretation, the non-releaser phenotype that we linked to the excessive proteolysis of Syk via the ubiquitin/proteasomal pathway is less common in basophils from asthmatic than non-asthmatic donors. The discovery of a basophil-specific pathway regulating Syk levels presents a clear opportunity for therapy. Another route to therapy was revealed by evidence that basophil FcεRI signaling can be downregulated by co-crosslinking the ITAM-containing IgE receptor, FcγRI, to the ITIM-containing IgG receptor, FcγRIIB. Based on this discovery, hybrid co-crosslinking fusion proteins are being engineered as potential therapies targeting basophils. A third distinguishing property of human basophils is their high dependence on IgE binding to stabilize membrane FcεRI. The circulating IgE scavenging mAb, Omalizumab, reduces FcεRI expression in basophils from asthmatics by over 95% and produces a substantial impairment of IL-4, IL-8 and IL-13 production in response to the crosslinking of residual cell surface IgE-FcεRI. A search for small molecule inhibitors that similarly impair high affinity Ig

  18. Type I (RI) and type II (RII) receptors for transforming growth factor-beta isoforms are expressed subsequent to transforming growth factor-beta ligands during excisional wound repair.

    PubMed Central

    Gold, L. I.; Sung, J. J.; Siebert, J. W.; Longaker, M. T.

    1997-01-01

    Transforming growth factor (TGF)-beta isoforms (TGF-beta 1, -beta 2, and -beta 3) regulate cell growth and differentiation and have critical regulatory roles in the process of tissue repair and remodeling. Signal transduction for TGF-beta function is transmitted by a heteromeric complex of receptors consisting of two serine/threonine kinase transmembrane proteins (RI and RII). We have previously shown that each TGF-beta isoform is widely expressed in a distinct spatial and temporal pattern throughout the processes of excisional and incisional wound repair. As the presence of TGF-beta receptors determines cellular responsiveness, we have currently examined, by immunohistochemistry, the localization of RI (ALK-1, ALK-5) and RII throughout repair of full-thickness excisional wounds up to 21 days after wounding. The expression of RI (ALK-5) and RII co-localized in both the unwounded and wounded skin and was present in the same cell types as TGF-beta ligands. However, immunoreactivity for TGF-beta receptors, throughout repair, occurred 1 to 5 days later than TGF-beta isoform immunostaining. This implies that the presence of TGF-beta ligands may up-regulate TGF-beta receptors for function and/or may reflect a lag due to local processing of latent TGF-beta. As observed for the immunohistochemical localization of TGF-beta isoforms in unwounded skin, RI and RII were expressed throughout the four layers of the epidermis, showing a wavy pattern of slight to moderate immunostaining, and hair follicles, sweat glands, and sebaceous glands were moderately immunoreactive. The extracellular matrix, fibroblasts, and blood vessels in the dermis were not immunoreactive. After injury, as observed for TGF-beta ligands, RI and RII expression was increased in the epidermis adjacent to the wound and the epithelium migrating over the wound was completely devoid of TGF-beta receptor immunoreactivity until re-epithelialization was completed by day 7 after wounding. The dermis was only

  19. Rice Rab11 is required for JA-mediated defense signaling

    SciTech Connect

    Hong, Min Ji; Lee, Yun mi; Son, Young Sim; Im, Chak Han; Yi, Young Byung; Rim, Yeong Gil; Bahk, Jeong Dong; Heo, Jae Bok

    2013-05-17

    Highlights: •OsRab11 interacts with OsOPR8. •OsOPR8 is localized in the cytosol and peroxisome. •OsRab11 enhances the NADPH consumption by OsOPR8. •Transgenic Arabidopsis overexpressing OsRab11 represents a pathogen-resistant phenotype. -- Abstract: Rab proteins play an essential role in regulating vesicular transport in eukaryotic cells. Previously, we characterized OsRab11, which in concert with OsGAP1 and OsGDI3 regulates vesicular trafficking from the trans-Golgi network (TGN) to the plasma membrane or vacuole. To further elucidate the physiological function of OsRab11 in plants, we performed yeast two-hybrid screens using OsRab11 as bait. OsOPR8 was isolated and shown to interact with OsRab11. A co-immunoprecipitation assay confirmed this interaction. The green fluorescent protein-OsOPR8 fusion product was targeted to the cytoplasm and peroxisomes of protoplasts from Arabidopsis thaliana. OsOPR8 exhibited NADPH-dependent reduction activity when 2-cyclohexen-1-one (CyHE) and 12-oxo-phytodienoic acid (OPDA) were supplied as possible substrates. Interestingly, NADPH oxidation by OsOPR8 was increased when wild-type OsRab11 or the constitutively active form of OsRab11 (Q78L) were included in the reaction mix, but not when the dominant negative form of OsRab11 (S28N) was included. OsRab11 was expressed broadly in plants and both OsRab11 and OsOPR8 were induced by jasmonic acid (JA) and elicitor treatments. Overexpressed OsRab11 transgenic plants showed resistance to pathogens through induced expression of JA-responsive genes. In conclusion, OsRab11 may be required for JA-mediated defense signaling by activating the reducing activity of OsOPR8.

  20. Visualization and Measurement of the Deflagration of Metal-Foil Bounded JA2

    DTIC Science & Technology

    2015-06-01

    ARL‐TR‐7322 ● JUNE 2015          US Army Research Laboratory      Visualization and  Measurement  of the  Deflagration of Metal‐Foil Bounded...Visualization and  Measurement  of the  Deflagration of Metal‐Foil Bounded JA2    John J Ritter and Anthony Canami  Weapons and Materials Research...

  1. Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the 2010 result of the LNE-LNHB (France)

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Cassette, P.; Moune, M.

    2016-01-01

    Since 2001, six national metrology institutes (NMI) have submitted seven samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.F-18. The values of the activity submitted were between about 1 MBq and 18 MBq. The primary standardization result for the LNE-LNHB, France, replaces their earlier result of 2002 and the key comparison reference value (KCRV) has been recalculated. In the frame of the BIPM.RI(II)-K4.F18 comparison, the NPL updated their result in the KCDB. Consequently there are now five results in the BIPM.RI(II)-K1.F-18 comparison. The degrees of equivalence between each equivalent activity measured in the SIR and the updated KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  2. MAPK-dependent JA and SA signalling in Nicotiana attenuata affects plant growth and fitness during competition with conspecifics.

    PubMed

    Meldau, Stefan; Ullman-Zeunert, Lynn; Govind, Geetha; Bartram, Stefan; Baldwin, Ian T

    2012-11-13

    Induced defense responses to herbivores are generally believed to have evolved as cost-saving strategies that defer the fitness costs of defense metabolism until these defenses are needed. The fitness costs of jasmonate (JA)-mediated defenses have been well documented. Those of the early signaling units mediating induced resistance to herbivores have yet to be examined. Early signaling components that mediate herbivore-induced defense responses in Nicotiana attenuata, have been well characterized and here we examine their growth and fitness costs during competition with conspecifics. Two mitogen-activated protein kinases (MAPKs), salicylic acid (SA)-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK) are rapidly activated after perception of herbivory and both kinases regulate herbivory-induced JA levels and JA-mediated defense metabolite accumulations. Since JA-induced defenses result in resource-based trade-offs that compromise plant productivity, we evaluated if silencing SIPK (irSIPK) and WIPK (irWIPK) benefits the growth and fitness of plants competiting with wild type (WT) plants, as has been shown for plants silenced in JA-signaling by the reduction of Lipoxygenase 3 (LOX3) levels. As expected, irWIPK and LOX3-silenced plants out-performed their competing WT plants. Surprisingly, irSIPK plants, which have the largest reductions in JA signaling, did not. Phytohormone profiling of leaves revealed that irSIPK plants accumulated higher levels of SA compared to WT. To test the hypothesis that these high levels of SA, and their presumed associated fitness costs of pathogen associated defenses in irSIPK plants had nullified the JA-deficiency-mediated growth benefits in these plants, we genetically reduced SA levels in irSIPK plants. Reducing SA levels partially recovered the biomass and fitness deficits of irSIPK plants. We also evaluated whether the increased fitness of plants with reduced SA or JA levels resulted from increased nitrogen or CO

  3. MAPK-dependent JA and SA signalling in Nicotiana attenuata affects plant growth and fitness during competition with conspecifics

    PubMed Central

    2012-01-01

    Background Induced defense responses to herbivores are generally believed to have evolved as cost-saving strategies that defer the fitness costs of defense metabolism until these defenses are needed. The fitness costs of jasmonate (JA)-mediated defenses have been well documented. Those of the early signaling units mediating induced resistance to herbivores have yet to be examined. Early signaling components that mediate herbivore-induced defense responses in Nicotiana attenuata, have been well characterized and here we examine their growth and fitness costs during competition with conspecifics. Two mitogen-activated protein kinases (MAPKs), salicylic acid (SA)-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK) are rapidly activated after perception of herbivory and both kinases regulate herbivory-induced JA levels and JA-mediated defense metabolite accumulations. Since JA-induced defenses result in resource-based trade-offs that compromise plant productivity, we evaluated if silencing SIPK (irSIPK) and WIPK (irWIPK) benefits the growth and fitness of plants competiting with wild type (WT) plants, as has been shown for plants silenced in JA-signaling by the reduction of Lipoxygenase 3 (LOX3) levels. Results As expected, irWIPK and LOX3-silenced plants out-performed their competing WT plants. Surprisingly, irSIPK plants, which have the largest reductions in JA signaling, did not. Phytohormone profiling of leaves revealed that irSIPK plants accumulated higher levels of SA compared to WT. To test the hypothesis that these high levels of SA, and their presumed associated fitness costs of pathogen associated defenses in irSIPK plants had nullified the JA-deficiency-mediated growth benefits in these plants, we genetically reduced SA levels in irSIPK plants. Reducing SA levels partially recovered the biomass and fitness deficits of irSIPK plants. We also evaluated whether the increased fitness of plants with reduced SA or JA levels resulted from

  4. Carbon catabolite repression-independent and pH-dependent production of indoles by Rubrivivax benzoatilyticus JA2.

    PubMed

    Mujahid, Md; Sasikala, Ch; Ramana, Ch V

    2013-10-01

    Rubrivivax benzoatilyticus JA2 produces indole derivatives (indoles) from aniline, anthranilate or L-tryptophan. Glucose repressed indole production in R. benzoatilyticus JA2, while malate had no effect. Growth of R. benzoatilyticus JA2 on glucose resulted in decrease in culture pH (6.4) compared with malate (8.4). Growth of R. benzoatilyticus JA2 on sugar carbon sources decreased culture pH (6.4-6.6) and indole production. Further, culture pH of 6.4 repressed the indole production, and pH 8.4 promoted the production irrespective of carbon sources used for growth. Moreover, correlation between indole production and culture pH was observed, where acidic pH inhibited indole production, while alkaline pH promoted the production, suggesting the role of pH in indole production. Tryptophan-catabolizing enzyme activities are significantly high in malate-grown cultures (pH 8.4) compared with that of the glucose (pH 6.4)-grown cultures and corroborated well with indole production, indicating their role in indole production. These results confirm that indole production in R. benzoatilyticus JA2 is pH dependent rather than carbon catabolite repression.

  5. OsJAR1 is required for JA-regulated floret opening and anther dehiscence in rice.

    PubMed

    Xiao, Yuguo; Chen, Yi; Charnikhova, Tatsiana; Mulder, Patrick P J; Heijmans, Jeroen; Hoogenboom, Angela; Agalou, Adamantia; Michel, Corinne; Morel, Jean-Benoit; Dreni, Ludovico; Kater, Martin M; Bouwmeester, Harro; Wang, Mei; Zhu, Zhen; Ouwerkerk, Pieter B F

    2014-09-01

    Jasmonates are important phytohormones regulating reproductive development. We used two recessive rice Tos17 alleles of OsJAR1, osjar1-2 and osjar1-3, to study the biological function of jasmonates in rice anthesis. The florets of both osjar1 alleles stayed open during anthesis because the lodicules, which control flower opening in rice, were not withering on time. Furthermore, dehiscence of the anthers filled with viable pollen, was impaired, resulting in lower fertility. In situ hybridization and promoter GUS transgenic analysis confirmed OsJAR1 expression in these floral tissues. Flower opening induced by exogenous applied methyl jasmonate was impaired in osjar1 plants and was restored in a complementation experiment with transgenics expressing a wild type copy of OsJAR1 controlled by a rice actin promoter. Biochemical analysis showed that OsJAR1 encoded an enzyme conjugating jasmonic acid (JA) to at least Ile, Leu, Met, Phe, Trp and Val and both osjar1 alleles had substantial reduction in content of JA-Ile, JA-Leu and JA-Val in florets. We conclude that OsJAR1 is a JA-amino acid synthetase that is required for optimal flower opening and closing and anther dehiscence in rice.

  6. The tomato res mutant which accumulates JA in roots in non-stressed conditions restores cell structure alterations under salinity.

    PubMed

    Garcia-Abellan, José O; Fernandez-Garcia, Nieves; Lopez-Berenguer, Carmen; Egea, Isabel; Flores, Francisco B; Angosto, Trinidad; Capel, Juan; Lozano, Rafael; Pineda, Benito; Moreno, Vicente; Olmos, Enrique; Bolarin, Maria C

    2015-11-01

    Jasmonic acid (JA) regulates a wide spectrum of plant biological processes, from plant development to stress defense responses. The role of JA in plant response to salt stress is scarcely known, and even less known is the specific response in root, the main plant organ responsible for ionic uptake and transport to the shoot. Here we report the characterization of the first tomato (Solanum lycopersicum) mutant, named res (restored cell structure by salinity), that accumulates JA in roots prior to exposure to stress. The res tomato mutant presented remarkable growth inhibition and displayed important morphological alterations and cellular disorganization in roots and leaves under control conditions, while these alterations disappeared when the res mutant plants were grown under salt stress. Reciprocal grafting between res and wild type (WT) (tomato cv. Moneymaker) indicated that the main organ responsible for the development of alterations was the root. The JA-signaling pathway is activated in res roots prior to stress, with transcripts levels being even higher in control condition than in salinity. Future studies on this mutant will provide significant advances in the knowledge of JA role in root in salt-stress tolerance response, as well as in the energy trade-off between plant growth and response to stress.

  7. Draft genome sequence of Rhodomicrobium udaipurense JA643T with special reference to hopanoid biosynthesis.

    PubMed

    Tushar, L; Sasikala, Ch; Ramana, Ch V

    2014-12-01

    Hopanoids are present in vast amounts as integral components of bacteria and plants with their primary function to strengthen rigidity of the plasma membrane. To establish their roles more precisely, we conducted sequencing of the whole genome of Rhodomicrobium udaipurense JA643(T) isolated from a fresh water stream of Udaipur in Himachal Pradesh, India, by using the Illumina HiSeq pair end chemistry of 2 × 100 bp platform. Determined genome showed a high degree of similarity to the genome of R. vannielii ATCC17100(T) and the 13.7 million reads generated a sequence of 3,649,277 bp possessing 3,611 putative genes. The genomic data were subsequently investigated with respect to genes involved in various features. The machinery required for the degradation of aromatic compounds and resistance to solvents as well as all that required for photosynthesis are present in this organism. Also, through extensive functional annotation, 18 genes involved in the biosynthesis of hopanoids are predicted, namely those responsible for the synthesis of diploptene, diplopterol, adenosylhopane, ribosylhopane, aminobacteriohopanetriol, glycosyl group containing hopanoids and unsaturated hopanoids. The hopanoid biosynthetic pathway was then inferred based on the genes identified and through experimental validation of individual hopanoid molecules. The genome data of R. udaipurense JA643(T) will be useful in understanding the functional features of hopanoids in this bacterium.

  8. Early dust formation and a massive progenitor for SN 2011ja?

    NASA Astrophysics Data System (ADS)

    Andrews, J. E.; Krafton, Kelsie M.; Clayton, Geoffrey C.; Montiel, E.; Wesson, R.; Sugerman, Ben E. K.; Barlow, M. J.; Matsuura, M.; Drass, H.

    2016-04-01

    SN 2011ja was a bright (I = -18.3) Type II supernova occurring in the nearby edge on spiral galaxy NGC 4945. Flat-topped and multipeaked H α and H β spectral emission lines appear between 64 and 84 d post-explosion, indicating interaction with a disc-like circumstellar medium inclined ˜45° from edge-on. After day 84, an increase in the H- and K-band flux along with heavy attenuation of the red wing of the emission lines are strong indications of early dust formation, likely located in the cool dense shell created between the forward shock of the SN ejecta and the reverse shock created as the ejecta plows into the existing circumstellar material. Radiative transfer modelling reveals both ≈1 × 10-5 M⊙ of pre-existing dust located ˜1016.7 cm away and up to ≈6 × 10-4 M⊙ of newly formed dust. Spectral observations after 1.5 yr reveal the possibility that the fading SN is located within a young (3-6 Myr) massive stellar cluster, which when combined with tentative 56Ni mass estimates of 0.2 M⊙ may indicate a massive (≥25 M⊙) progenitor for SN 2011ja.

  9. Kinetics and regulation of lactose transport and metabolism in Kluyveromyces lactis JA6.

    PubMed

    Santos, A M; Silveira, W B; Fietto, L G; Brandão, R L; Castro, I M

    2014-07-01

    Kluyveromyces lactis strains are able to assimilate lactose. They have been used industrially to eliminate this sugar from cheese whey and in other industrial products. In this study, we investigated specific features and the kinetic parameters of the lactose transport system in K. lactis JA6. In lactose grown cells, lactose was transported by a system transport with a half-saturation constant (K s) of 1.49 ± 0.38 mM and a maximum velocity (V max) of 0.96 ± 0.12 mmol. (g dry weight)(-1) h(-1) for lactose. The transport system was constitutive and energy-dependent. Results obtained by different approaches showed that the lactose transport system was regulated by glucose at the transcriptional level and by glucose and other sugars at a post-translational level. In K. lactis JA6, galactose metabolization was under glucose control. These findings indicated that the regulation of lactose-galactose regulon in K. lactis was similar to the regulation of galactose regulon in Saccharomyces cerevisiae.

  10. Sustainable management of river oases along the Tarim River (SuMaRiO) in Northwest China under conditions of climate change

    NASA Astrophysics Data System (ADS)

    Rumbaur, C.; Thevs, N.; Disse, M.; Ahlheim, M.; Brieden, A.; Cyffka, B.; Duethmann, D.; Feike, T.; Frör, O.; Gärtner, P.; Halik, Ü.; Hill, J.; Hinnenthal, M.; Keilholz, P.; Kleinschmit, B.; Krysanova, V.; Kuba, M.; Mader, S.; Menz, C.; Othmanli, H.; Pelz, S.; Schroeder, M.; Siew, T. F.; Stender, V.; Stahr, K.; Thomas, F. M.; Welp, M.; Wortmann, M.; Zhao, X.; Chen, X.; Jiang, T.; Luo, J.; Yimit, H.; Yu, R.; Zhang, X.; Zhao, C.

    2015-03-01

    The Tarim River basin, located in Xinjiang, NW China, is the largest endorheic river basin in China and one of the largest in all of Central Asia. Due to the extremely arid climate, with an annual precipitation of less than 100 mm, the water supply along the Aksu and Tarim rivers solely depends on river water. This is linked to anthropogenic activities (e.g., agriculture) and natural and semi-natural ecosystems as both compete for water. The ongoing increase in water consumption by agriculture and other human activities in this region has been enhancing the competition for water between human needs and nature. Against this background, 11 German and 6 Chinese universities and research institutes have formed the consortium SuMaRiO (Sustainable Management of River Oases along the Tarim River; http://www.sumario.de), which aims to create a holistic picture of the availability of water resources in the Tarim River basin and the impacts on anthropogenic activities and natural ecosystems caused by the water distribution within the Tarim River basin. On the basis of the results from field studies and modeling approaches as well as from suggestions by the relevant regional stakeholders, a decision support tool (DST) will be implemented that will then assist stakeholders in balancing the competition for water, acknowledging the major external effects of water allocation to agriculture and to natural ecosystems. This consortium was formed in 2011 and is funded by the German Federal Ministry of Education and Research. As the data collection phase was finished this year, the paper presented here brings together the results from the fields from the disciplines of climate modeling, cryology, hydrology, agricultural sciences, ecology, geoinformatics, and social sciences in order to present a comprehensive picture of the effects of different water availability schemes on anthropogenic activities and natural ecosystems along the

  11. Modulation of FcεRI-dependent mast cell response by OX40L via Fyn, PI3K, and RhoA.

    PubMed

    Sibilano, Riccardo; Frossi, Barbara; Suzuki, Ryo; D'Incà, Federica; Gri, Giorgia; Piconese, Silvia; Colombo, Mario P; Rivera, Juan; Pucillo, Carlo E

    2012-09-01

    The interaction of mast cells (MCs) with regulatory T cells through the OX40 ligand (OX40L):OX40 axis downregulates FcεRI-dependent immediate hypersensitivity responses both in vitro and in vivo. Little is known on OX40L-mediated intracellular signaling or on the mechanism by which OX40L engagement suppresses MC degranulation. We explored the role of OX40L engagement on IgE/antigen-triggered MCs both in vitro and in vivo. The soluble form of OX40 molecule was used to selectively trigger OX40L on MCs in vitro and was used to dissect OX40L contribution in an in vivo model of systemic anaphylaxis. OX40L:OX40 interaction led to the recruitment of C-terminal src kinase into lipid rafts, causing a preferential suppression of Fyn kinase activity and subsequent reduction in the phosphorylation of Gab2, the phosphatidylinositol 3-OH kinase regulatory subunit p85, and Akt, without affecting the Lyn pathway. Dampening of Fyn kinase activity also inhibited RhoA activation and microtubule nucleation, key regulators of MC degranulation. The in vivo administration of a blocking antibody to OX40L in wild-type mice caused enhanced immediate hypersensitivity, whereas the administration of soluble OX40 to regulatory T-cell-depleted or OX40-deficient mice reduced MC degranulation. The engagement of OX40L selectively suppresses Fyn-initiated signals required for MC degranulation and serves to limit immediate hypersensitivity. Our data suggest that soluble OX40 can restore the aberrant or absent regulatory T-cell activity, revealing a previously unappreciated homeostatic role for OX40L in setting the basal threshold of MC response. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  12. Protein Kinase A RI-{alpha} Predicts for Prostate Cancer Outcome: Analysis of Radiation Therapy Oncology Group Trial 86-10

    SciTech Connect

    Khor, Li-Yan; Bae, Kyounghwa; Al-Saleem, Tahseen; Hammond, Elizabeth H.; Grignon, David J.; Sause, William T.; Pilepich, Miljenko V.; Okunieff, Paul P.; Sandler, Howard M.; Pollack, Alan

    2008-08-01

    Purpose: The RI-{alpha} regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable, p = 0.022), LF (image analysis, dichotomized variable, p = 0.011), CSM (manual analysis, p = 0.037; image analysis, continuous, p = 0.014), and DM (manual analysis, p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy.

  13. 2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway

    PubMed Central

    Kim, Yeon-Yong; Je, In-Gyu; Kim, Min Jong; Kang, Byeong-Cheol; Choi, Young-Ae; Baek, Moon-Chang; Lee, Byungheon; Choi, Jin Kyeong; Park, Hae Ran; Shin, Tae-Yong; Lee, Soyoung; Yoon, Seung-Bin; Lee, Sang-Rae; Khang, Dongwoo; Kim, Sang-Hyun

    2017-01-01

    Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1–100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells. PMID:27890918

  14. Nicotine inhibits Fc epsilon RI-induced cysteinyl leukotrienes and cytokine production without affecting mast cell degranulation through alpha 7/alpha 9/alpha 10-nicotinic receptors.

    PubMed

    Mishra, Neerad C; Rir-sima-ah, Jules; Boyd, R Thomas; Singh, Shashi P; Gundavarapu, Sravanthi; Langley, Raymond J; Razani-Boroujerdi, Seddigheh; Sopori, Mohan L

    2010-07-01

    Smokers are less likely to develop some inflammatory and allergic diseases. In Brown-Norway rats, nicotine inhibits several parameters of allergic asthma, including the production of Th2 cytokines and the cysteinyl leukotriene LTC(4). Cysteinyl leukotrienes are primarily produced by mast cells, and these cells play a central role in allergic asthma. Mast cells express a high-affinity receptor for IgE (FcepsilonRI). Following its cross-linking, cells degranulate and release preformed inflammatory mediators (early phase) and synthesize and secrete cytokines/chemokines and leukotrienes (late phase). The mechanism by which nicotine modulates mast cell activation is unclear. Using alpha-bungarotoxin binding and quantitative PCR and PCR product sequencing, we showed that the rat mast/basophil cell line RBL-2H3 expresses nicotinic acetylcholine receptors (nAChRs) alpha7, alpha9, and alpha10; exposure to exceedingly low concentrations of nicotine (nanomolar), but not the biologically inactive metabolite cotinine, for > or = 8 h suppressed the late phase (leukotriene/cytokine production) but not degranulation (histamine and hexosaminidase release). These effects were unrelated to those of nicotine on intracellular free calcium concentration but were causally associated with the inhibition of cytosolic phospholipase A(2) activity and the PI3K/ERK/NF-kappaB pathway, including phosphorylation of Akt and ERK and nuclear translocation of NF-kappaB. The suppressive effect of nicotine on the late-phase response was blocked by the alpha7/alpha9-nAChR antagonists methyllycaconitine and alpha-bungarotoxin, as well as by small interfering RNA knockdown of alpha7-, alpha9-, or alpha10-nAChRs, suggesting a functional interaction between alpha7-, alpha9-, and alpha10-nAChRs that might explain the response of RBL cells to nanomolar concentrations of nicotine. This "hybrid" receptor might serve as a target for novel antiallergic/antiasthmatic therapies.

  15. Temperature profile analysis for Amargosa Valley wells LWS-A, ASH-B, and MSH-C. DOE UGTA RI/FS geothermal gradient study results FY 1995

    SciTech Connect

    Gillespie, D.

    1995-09-01

    The purpose of this investigation is to estimate vertical fluid flux rates in saturated units penetrated by selected wells at the Nevada Test Site (NTS) using geothermal gradient data. Estimates of vertical fluid flux rates are critical in developing models for contaminate flow within, recharge potential to, and discharge from the groundwater system at the NTS. If temperature in the well is in equilibrium with the surrounding rocks, it is possible to detect the vertical flow of groundwater from the well`s thermal profile. Heat in the subsurface is transported by conduction through the rock and by advection caused by subsurface water movement. Units in which vertical flow is occurring will produce a curve in the thermal profile within the well. Prior to the implementation of the Underground Test Area Remedial Investigation/Feasibility Study (UGTA RI/FS), investigation of thermal data from wells at the NTS was hindered by the completion of wells as open holes or without casing cemented in place. The open-hole type of completion allows cross-flow within the wellbore which can yield information about relative pressures between connected aquifers, but which renders thermal gradient data essentially useless, or at best highly suspect for interpreting in situ groundwater movement. Wells recently completed in the Department of Energy (DOE) Environmental Restoration (ER) Program have been completed with casing cemented to the surface (to prohibit cross-flow between units in the annular space between the casing and the wellbore) and with completion zones open to a single hydrologic horizon. This type of completion results in temperature gradient profiles more representative of actual thermal conditions in the units penetrated by the well. Results are presented of temperature profiles of 3 wells located in the Death Valley Groundwater Basin, outside the southern border of the NTS.

  16. Acute oral toxicity of JA-2 solid propellant in icr mice. Report for 17 December 1985-17 January 1986

    SciTech Connect

    Morgan, E.W.; Frost, D.F.; Wheller, C.R.; Korte, D.W.

    1989-12-01

    The acute oral toxicity of JA-2 Solid Propellant was determined in male and female ICR mice by using an oral gavage, split-dose method. The MLD was 3774.6 + or - 150.5 mg/kg for male mice and 3528.8 + or - 133.8 mg/kg for female mice. JA-2 produced component, diethyleneglycol dinitrate and nitroglycerin. These signs included tremors, inactivity, depression of reflexes, loss of equilibrium, opisthotonus, and increased respiratory activity. Other clinical signs observed were associated with the general malaise of the animals following dosing and included perianal staining, hunched posture, squinting, and rough coat. Most animals exhibited signs by 2 hours after dosing and either had died or the signs had cleared within 5 days of dosing. According to the classification scheme of Hodge and Sterner, these results place JA-2 in the slightly toxic class.

  17. Acute oral toxicity of ja-2 solid propellant in sprague-dawley rats. Report for 12 November-19 December 1985

    SciTech Connect

    Brown, L.D.; Justus, J.D.; Wheeler, C.R.; Korte, D.W.

    1989-12-01

    The acute oral toxicity of JA-2 Solid Propellant was determined in male and female Sprague-Dawley rats by using an oral gavage split-dose method. The MLD was 3990.6 + or - 349.7 mg/kg for male rats and 2545.9 + or - 421.1 mg/kg for female rats. JA-2 produced clinical signs that were attributed to its nitrate ester components, diethyleneglycol dinitrate and nitroglycerin. These signs included tremors and twitching, cyanosis, and increases in respiratory rate and depth. Other clinical signs observed were associated with the general malaise of the animals following dosing and included hunched posture, rough coat, reddish stains around the eyes and nose, and perianal staining. Most animals exhibited signs by 4 hours after dosing and either had died or the signs had cleared by 96 hours after dosing. According to the classification scheme of Hodge and Sterner, these results place JA-2 in the slightly toxic class.

  18. Transcriptome sequencing and de novo analysis of cytoplasmic male sterility and maintenance in JA-CMS cotton.

    PubMed

    Yang, Peng; Han, Jinfeng; Huang, Jinling

    2014-01-01

    Cytoplasmic male sterility (CMS) is the failure to produce functional pollen, which is inherited maternally. And it is known that anther development is modulated through complicated interactions between nuclear and mitochondrial genes in sporophytic and gametophytic tissues. However, an unbiased transcriptome sequencing analysis of CMS in cotton is currently lacking in the literature. This study compared differentially expressed (DE) genes of floral buds at the sporogenous cells stage (SS) and microsporocyte stage (MS) (the two most important stages for pollen abortion in JA-CMS) between JA-CMS and its fertile maintainer line JB cotton plants, using the Illumina HiSeq 2000 sequencing platform. A total of 709 (1.8%) DE genes including 293 up-regulated and 416 down-regulated genes were identified in JA-CMS line comparing with its maintainer line at the SS stage, and 644 (1.6%) DE genes with 263 up-regulated and 381 down-regulated genes were detected at the MS stage. By comparing the two stages in the same material, there were 8 up-regulated and 9 down-regulated DE genes in JA-CMS line and 29 up-regulated and 9 down-regulated DE genes in JB maintainer line at the MS stage. Quantitative RT-PCR was used to validate 7 randomly selected DE genes. Bioinformatics analysis revealed that genes involved in reduction-oxidation reactions and alpha-linolenic acid metabolism were down-regulated, while genes pertaining to photosynthesis and flavonoid biosynthesis were up-regulated in JA-CMS floral buds compared with their JB counterparts at the SS and/or MS stages. All these four biological processes play important roles in reactive oxygen species (ROS) homeostasis, which may be an important factor contributing to the sterile trait of JA-CMS. Further experiments are warranted to elucidate molecular mechanisms of these genes that lead to CMS.

  19. Banana fruit VQ motif-containing protein5 represses cold-responsive transcription factor MaWRKY26 involved in the regulation of JA biosynthetic genes

    PubMed Central

    Ye, Yu-Jie; Xiao, Yun-Yi; Han, Yan-Chao; Shan, Wei; Fan, Zhong-Qi; Xu, Qun-Gang; Kuang, Jian-Fei; Lu, Wang-Jin; Lakshmanan, Prakash; Chen, Jian-Ye

    2016-01-01

    Most harvested fruits and vegetables are stored at low temperature but many of them are highly sensitive to chilling injury. Jasmonic acid (JA), a plant hormone associated with various stress responses, is known to reduce chilling injury in fruits. However, little is known about the transcriptional regulation of JA biosynthesis in relation to cold response of fruits. Here, we show the involvement of a Group I WRKY transcription factor (TF) from banana fruit, MaWRKY26, in regulating JA biosynthesis. MaWRKY26 was found to be nuclear-localized with transcriptional activation property. MaWRKY26 was induced by cold stress or by methyl jasmonate (MeJA), which enhances cold tolerance in banana fruit. More importantly, MaWRKY26 transactivated JA biosynthetic genes MaLOX2, MaAOS3 and MaOPR3 via binding to their promoters. Further, MaWRKY26 physically interacted with a VQ motif-containing protein MaVQ5, and the interaction attenuated MaWRKY26-induced transactivation of JA biosynthetic genes. These results strongly suggest that MaVQ5 might act as a repressor of MaWRKY26 in activating JA biosynthesis. Taken together, our findings provide new insights into the transcriptional regulation of JA biosynthesis in response to cold stress and a better understanding of the molecular aspects of chilling injury in banana fruit. PMID:27004441

  20. HiJaK: the high-resolution J, H and K spectrometer

    NASA Astrophysics Data System (ADS)

    Muirhead, Philip S.; Hall, Zachary J.; Veyette, Mark J.

    2014-08-01

    We present the science drivers, design requirements and a preliminary design for a high-resolution, broad- bandwidth, slit-fed cross-dispersed near-infrared spectrometer for 5-meter-class telescopes. Our concept, called the High-Resolution J, H and K Spectrometer, or HiJaK, utilizes an R6 echelle in a white-pupil design to achieve high resolution in a compact configuration with a 2048 x 2048 pixel infrared detector. We present a preliminary ray-traced optical design matched to the new 4.3-meter Discovery Channel Telescope in Happy Jack, Arizona. We also discuss mechanical and cryogenic options to house our optical design.

  1. EURAMET.RI(I)-S7 comparison of alanine dosimetry systems for absorbed dose to water measurements in gamma- and x-radiation at radiotherapy levels

    NASA Astrophysics Data System (ADS)

    Garcia, Tristan; Anton, Mathias; Sharpe, Peter

    2012-01-01

    The National Physical Laboratory (NPL), the Physikalisch-Technische Bundesanstalt (PTB) and the Laboratoire National Henri Becquerel (LNE-LNHB) are involved in the European project 'External Beam Cancer Therapy', a project of the European Metrology Research Programme. Within this project, the electron paramagnetic resonance (EPR)/alanine dosimetric method has been chosen for performing measurements in small fields such as those used in IMRT (intensity modulated radiation therapy). In this context, these three National Metrology Institutes (NMI) wished to compare the result of their alanine dosimetric systems (detector, modus operandi etc) at radiotherapy dose levels to check their consistency. This EURAMET.RI(I)-S7 comparison has been performed with the support of the Bureau International des Poids et Mesures (BIPM) which collected and distributed the results as a neutral organization, to ensure the comparison was 'blind'. Irradiations have been made under reference conditions by each laboratory in a 60Co beam and in an accelerator beam (10 MV or 12 MV) in a water phantom of 30 cm × 30 cm × 30 cm in a square field of 10 cm × 10 cm at the reference depth. Irradiations have been performed at known values of absorbed dose to water (Dw) within 10% of nominal doses of 5 Gy and 10 Gy, i.e. between 4.5 Gy and 5.5 Gy and between 9 Gy and 11 Gy, respectively. Each participant read out their dosimeters and assessed the doses using their own protocol (calibration curve, positioning device etc) as this comparison aims at comparing the complete dosimetric process. The results demonstrate the effectiveness of the EPR/alanine dosimetry systems operated by National Metrology Institutes as a method of assuring therapy level doses with the accuracy required. The maximum deviation in the ratio of measured to applied dose is less than 1%. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key

  2. Final report on APMP.RI(I)-K1: APMP/TCRI key comparison report of measurement of air kerma for 60Co gamma-rays

    NASA Astrophysics Data System (ADS)

    Chun, K. J.; Butler, D. J.; Webb, D.; Mahant, A. K.; Meghzifene, A.; Lee, J. H.; Hah, S. H.; Kadni, T. B.; Zhang, Y.; Kurosawa, T.; Msimang, Z. L. M.; Caseria, E. S.

    2013-01-01

    The APMP.RI(I)-K1 key comparison of the measurement standards of air kerma for 60Co gamma-rays was undertaken by the APMP/TCRI Dosimetry Working Group between 2004 and 2006, coordinated by the Korean Research Institute of Standards and Science (KRISS). In total, 10 institutes took part in the comparison, among which 7 were APMP member laboratories. Three Farmer-type commercial cavity chambers were used as transfer chambers and circulated among the participants. All the participants carried out their measurements according to the guidelines for the comparison established by the KRISS with the cooperation of the ARPANSA. For each transfer chamber, an NMI calibration coefficient was obtained and a ratio derived by dividing by the average result from the linking laboratories, ARPANSA and NMIJ. The APMP comparison reference value for each chamber was calculated as the mean of the NMI-determined calibration coefficients divided by the average result from the linking laboratories. The results showed that the maximum difference between the APMP linked ratio of a participating NMI and the APMP reference value was 1.76%. The measured ratios of the calibration coefficient RNMI, BIPM between the participating NMI and the BIPM via the link laboratories for the transfer chambers were obtained. The maximum expanded uncertainty of RNMI, BIPM for any participating laboratory was 2.0%. The degree of equivalence of each participating laboratory with respect to the key comparison reference value was also evaluated. The expanded uncertainty of the difference between the results ranged from 0.5% to 1.2%. The pair-wise degree of equivalence between each pair of laboratories was also obtained and the largest difference of the expanded uncertainty of the difference for any pair-wise degree of equivalence was within the expanded uncertainty of the measurement for the pair of laboratories. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that

  3. High Temperature Induces Expression of Tobacco Transcription Factor NtMYC2a to Regulate Nicotine and JA Biosynthesis

    PubMed Central

    Yang, Liming; Li, Junying; Ji, Jianhui; Li, Ping; Yu, Liangliang; Abd_Allah, Elsayed F.; Luo, Yuming; Hu, Liwei; Hu, Xiangyang

    2016-01-01

    Environmental stress elevates the level of jasmonic acid (JA) and activates the biosynthesis of nicotine and related pyridine alkaloids in tobacco (Nicotiana tabacum L.) by up-regulating the expression of putrescine N-methyltransferase 1 (NtPMT1), which encodes a putrescine N-methyl transferase that catalyzes nicotine formation. The JA signal suppressor JASMONATE ZIM DOMAIN 1 (NtJAZ1) and its target protein, NtMYC2a, also regulate nicotine biosynthesis; however, how these proteins interact to regulate abiotic-induced nicotine biosynthesis is poorly understood. In this study, we found that high-temperature (HT) treatment activated transcription of NtMYC2a, which subsequently stimulated the transcription of genes associated with JA biosynthesis, including Lipoxygenase (LOX), Allene oxide synthase (AOS), Allene oxide cyclase (AOC), and 12-oxophytodienodate reductase (OPR). Overexpression of NtMYC2a increased nicotine biosynthesis by enhancing its binding to the promoter of NtPMT1. Overexpression of either NtJAZ1 or proteasome-resistant NtJAZ1ΔC suppressed nicotine production under normal conditions, but overexpression only of the former resulted in low levels of nicotine under HT treatment. These data suggest that HT induces NtMYC2a accumulation through increased transcription to activate nicotine synthesis; meanwhile, HT-induced NtMYC2a can activate JA synthesis to promote additional NtMYC2a activity by degrading NtJAZ1 at the post-transcriptional level. PMID:27833561

  4. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.Ho-166m activity measurements to include the IRA and the NPL and a re-evaluation of the degrees of equivalence for the APMP.RI(II)-K2.Ho-166m comparison

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Nedjadi, Y.; Bailat, C.; Johansson, L.; Hino, Y.

    2009-01-01

    The IRA and the NPL have submitted ampoules of 166Hom to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures, thus becoming the third and fourth participants since 1989. The five samples of known activity of 166Hom now recorded in the SIR have activities between about 70 kBq and 500 kBq. The new results have enabled a re-evaluation of the key comparison reference value, and the degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated. The results are given in the form of a matrix for these four NMIs together with the recalculated degrees of equivalence of an APMP regional comparison held in 2000, comparison identifier APMP.RI(II)-K2.Ho-166m for six other NMIs. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  5. The high-affinity immunoglobulin E receptor (FcepsilonRI) regulates mitochondrial calcium uptake and a dihydropyridine receptor-mediated calcium influx in mast cells: Role of the FcepsilonRIbeta chain immunoreceptor tyrosine-based activation motif.

    PubMed

    Suzuki, Yoshihiro; Yoshimaru, Tetsuro; Inoue, Toshio; Nunomura, Satoshi; Ra, Chisei

    2008-04-01

    A growing body of evidence suggests that mitochondria take up calcium upon receptor (agonist) stimulation and that this contributes to the dynamics of spatiotemporal calcium signaling. We have previously shown that engagement of the high-affinity receptor for immunoglobulin E (FcepsilonRI) stimulates mitochondrial calcium ([Ca2+]m) uptake in mast cells. The present study was undertaken to investigate the mechanisms and biological significance of FcepsilonRI regulation of [Ca2+]m. Antigen stimulated [Ca2+]m uptake in a dose-dependent manner with a minimal effective dose of 0.03-3 ng/ml. This [Ca2+]m uptake took place immediately, reaching its peak within minutes and was inhibited by the src family kinase inhibitor PP1 and phosphatidylinositol-3-kinase inhibitor wortmannin. Analyses using mast cells expressing the wild-type or the mutated type of the FcepsilonRIbeta immunoreceptor tyrosine-based activation motif (ITAM) in which all tyrosine residues were replaced by phenylalanine revealed that the FcepsilonRIbeta ITAM is essential for a sustained [Ca2+]m uptake. The FcepsilonRIbeta ITAM was essential for overall calcium response upon weak FcepsilonRI stimulation (at low antigen concentration), while upon strong stimulation (at high antigen concentration) it appeared necessary selectively to an immediate calcium response that was sensitive to the dihydropyridine receptor (DHPR) antagonist nifedipine and wortmannin but not to the store-operated calcium entry (SOCE) antagonists such as 2-aminoethoxyphenyl borate and SK&F96365. These data demonstrate that the FcepsilonRIbeta regulates [Ca2+]m uptake in mast cells via the ITAM and suggest that this plays a key role in regulating calcium influx especially that induced via a DHPR-mediated calcium channel.

  6. Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study

    PubMed Central

    Koram, Kwadwo A.; Ocran, Josephine; Karikari, Yaa S.; Adu-Amankwah, Susan; Ntiri, Michael; Abuaku, Benjamin; Dodoo, Daniel; Gyan, Ben; Kronmann, Karl C.; Nkrumah, Francis

    2016-01-01

    The erythrocyte binding antigen region II (EBA-175 RII) is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended. Trial registration ClinicalTrials.gov. Identifier: NCT01026246 PMID:27644034

  7. Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcϵRI/CC Chemokine Receptor 1 Cross-talk*

    PubMed Central

    Toda, Masako; Kuo, Chuan-Hui; Borman, Satty K.; Richardson, Ricardo Micheler; Inoko, Akihito; Inagaki, Masaki; Collins, Andrea; Schneider, Klaus; Ono, Santa Jeremy

    2012-01-01

    Accumulating evidence points to cross-talk between FcϵRI and CC chemokine receptor (CCR)-mediated signaling pathways in mast cells. Here, we propose that vimentin, a protein comprising type III intermediate filament, participates in such cross-talk for CCL2/monocyte chemotactic protein 1 (MCP-1) production in mast cells, which is a mechanism for allergic inflammation. Co-stimulation via FcϵRI, using IgE/antigen, and CCR1, using recombinant CCL3/macrophage inflammatory protein-1α (MIP-1α), increased expression of phosphorylated, disassembled, and soluble vimentin in rat basophilic leukemia (RBL)-2H3 cells expressing human CCR1 (RBL-CCR1 cells) and bone marrow-derived murine mast cells, both models of mucosal type mast cells. Furthermore, co-stimulation enhanced production of CCL2 as well as phosphorylation of MAPK. Treating the cells with p38 MAPK inhibitor SB203580, but not with MEK inhibitor PD98058, reduced CCL2 production, suggesting that p38 MAPK, but not ERK1/2, plays a critical role in the chemokine production. Immunoprecipitation analysis showed that vimentin interacts with phosphorylated ERK1/2 and p38 MAPKs in the co-simulated cells. Preventing disassembly of the vimentin by aggregating vimentin filaments using β,β′-iminodipropionitrile reduced the interaction of vimentin with phosphorylated MAPKs as well as CCL2 production in the cells. Taken together, disassembled vimentin interacting with phosphorylated p38 MAPK could mediate CCL2 production in mast cells upon FcϵRI and CCR1 activation. PMID:22613718

  8. Polymorphisms XbaI (rs693) and EcoRI (rs1042031) of the ApoB gene are associated with carotid plaques but not with carotid intima-media thickness in patients with diabetes mellitus type 2.

    PubMed

    Nikolajevic Starcevic, Jovana; Santl Letonja, Marija; Praznikar, Zala J; Makuc, Jana; Vujkovac, Andreja C; Petrovic, Daniel

    2014-05-01

    Hintergrund: Apolipoprotein B ist eine wichtige strukturelle Komponente der atherogenetischen Lipoproteine (LDL, VLDL und IDL). Genetische Variationen des ApoB-Gens können verschiedene Effekte auf Plasmakonzentrationen des ApoB und auf den Lipidspiegel haben, was dann die Atherogenese beeinflusst. Primäres Ziel der Studie war die Analyse der Assoziation der Polymorphismen XbaI (rs693) und EcoRI (rs1042031) mit Plasmakonzentrationen von ApoB, dem Lipidspiegel und verschiedenen atherosklerotischen Phänotypen bei Patienten mit Diabetes mellitus Typ 2. Patienten und Methoden: 595 Patienten mit Diabetes mellitus Typ 2 (399 mit Statin-Therapie und 196 Patienten ohne Statin-Therapie) und 200 Personen ohne Diabetes mellitus Typ 2 (Kontrollgruppe). Die Intima-Media-Dicke (IMD) der A. carotis und die Charakteristika der atherosklerotischen Plaques wurden mit Ultraschall analysiert. Biochemische Untersuchungen wurden mit standardmäßigen biochemischen Methoden durchgeführt. Die XbaI (rs693) und EcoRI (rs1042031) Genotypen wurden mittels Real-Time PCR analysiert. Ergebnisse: Die Genotyp-Verteilung und die allelische Häufigkeit von XbaI und EcoRI Polymorphismen unterschieden sich nicht zwischen Patienten mit und ohne Diabetes mellitus. Es wurden keine signifikanten Unterschiede der Plasmakonzentrationen von ApoA1, ApoB, Cholesterinspiegel, hs-CRP, Fibrinogen und der IMD bei Patienten mit Diabetes mellitus Typ 2 mit verschiedenen Genotypen festgestellt, auch unter Berücksichtigung der Statintherapie. Das Risiko der Atherosklerose der Karotiden wird bei Patienten mit X + X + Genotyp im Vergleich zu Patienten ohne diesen Genotyp (OR = 1.74, p = 0.03)höher und bei Diabetiker mit E-Allelen (OR = 0.48, p = 0.02) niedriger. Es gab keine Assoziation zwischen XbaI / EcoRI Polymorphismen und IMD oder instabilen atherosklerotischen Plaques bei Patienten mit Diabetes mellitus Typ 2. Schlussfolgerungen: Das Risiko der Atherosklerose der Karotiden wird höher bei Patienten mit

  9. Isolation and characterization of the specialized transducing bacteriophages phi80dargF and lambdah80cI857 dargF: specific cleavage of arginine transducing deoxyribonucleic acid by the endonucleases EcoRI and SmaR.

    PubMed Central

    James, P M; Sens, D; Natter, W; Moore, S K; James, E

    1976-01-01

    The directed transposition of argF to the tonB locus of the Escherichia coli chromosome and the subsequent isolation of the specialized transducing phage phi80dargF is described. The structure of this phage has been has been determined. A hybrid lambdah80cI857dargF phage has been constructed. Deoxyribonucleic acid isolated from these and their parent bacteriophages has been specifically cleaved by the endonucleases EcoRI and SmaR; the unique deoxyribonucleic acid fragments thus obtained have been resolved and analyzed by electrophoresis in agarose gel. Images PMID:770435

  10. Overexpression of OsMYC2 Results in the Up-Regulation of Early JA-Rresponsive Genes and Bacterial Blight Resistance in Rice.

    PubMed

    Uji, Yuya; Taniguchi, Shiduku; Tamaoki, Daisuke; Shishido, Hodaka; Akimitsu, Kazuya; Gomi, Kenji

    2016-09-01

    JASMONATE ZIM-domain (JAZ) proteins act as transcriptional repressors of jasmonic acid (JA) responses and play a crucial role in the regulation of host immunity in plants. Here, we report that OsMYC2, a JAZ-interacting transcription factor in rice (Oryza sativa L.), plays an important role in the resistance response against rice bacterial blight, which is one of the most serious diseases in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). The results showed that OsMYC2 interacted with some OsJAZ proteins in a JAZ-interacting domain (JID)-dependent manner. The up-regulation of OsMYC2 in response to JA was regulated by OsJAZ8. Transgenic rice plants overexpressing OsMYC2 exhibited a JA-hypersensitive phenotype and were more resistant to Xoo. A large-scale microarray analysis revealed that OsMYC2 up-regulated OsJAZ10 as well as many other defense-related genes. OsMYC2 selectively bound to the G-box-like motif of the OsJAZ10 promoter in vivo and regulated the expression of early JA-responsive genes, but not of late JA-responsive genes. The nuclear localization of OsMYC2 depended on a nuclear localization signal within JID. Overall, we conclude that OsMYC2 acts as a positive regulator of early JA signals in the JA-induced resistance against Xoo in rice.

  11. bHLH003, bHLH013 and bHLH017 Are New Targets of JAZ Repressors Negatively Regulating JA Responses

    PubMed Central

    Fonseca, Sandra; Fernández-Calvo, Patricia; Fernández, Guillermo M.; Díez-Díaz, Monica; Gimenez-Ibanez, Selena; López-Vidriero, Irene; Godoy, Marta; Fernández-Barbero, Gemma; Van Leene, Jelle; De Jaeger, Geert; Franco-Zorrilla, José Manuel; Solano, Roberto

    2014-01-01

    Cell reprogramming in response to jasmonates requires a tight control of transcription that is achieved by the activity of JA-related transcription factors (TFs). Among them, MYC2, MYC3 and MYC4 have been described as activators of JA responses. Here we characterized the function of bHLH003, bHLH013 and bHLH017 that conform a phylogenetic clade closely related to MYC2, MYC3 and MYC4. We found that these bHLHs form homo- and heterodimers and also interact with JAZ repressors in vitro and in vivo. Phenotypic analysis of JA-regulated processes, including root and rosette growth, anthocyanin accumulation, chlorophyll loss and resistance to Pseudomonas syringae, on mutants and overexpression lines, suggested that these bHLHs are repressors of JA responses. bHLH003, bHLH013 and bHLH017 are mainly nuclear proteins and bind DNA with similar specificity to that of MYC2, MYC3 and MYC4, but lack a conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Moreover, expression of bHLH017 is induced by JA and depends on MYC2, suggesting a negative feed-back regulation of the activity of positive JA-related TFs. Our results suggest that the competition between positive and negative TFs determines the output of JA-dependent transcriptional activation. PMID:24465948

  12. JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells.

    PubMed

    Gao, Xiu-Li; Lin, Hua; Zhao, Wei; Hou, Ya-Qin; Bao, Yong-Li; Song, Zhen-Bo; Sun, Lu-Guo; Tian, Shang-Yi; Liu, Biao; Li, Yu-Xin

    2016-03-01

    Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.

  13. Development and performance evaluation of Time-over-Threshold based digital PET (TODPET2) scanner using SiPM/Ce:GAGG-arrays for non-invasive measurement of blood RI concentrations

    NASA Astrophysics Data System (ADS)

    Yoshino, M.; Kamada, K.; Shoji, Y.; Yoshikawa, A.; Shimazoe, K.; Lipovec, A.; Takahashi, H.; Fujiwara, K.; Takahashi, M.; Momose, T.; Ito, S.; Tsutsumi, K.; Endo, T.; Sato, H.; Usuki, Y.

    2017-02-01

    We developed Time-over-Threshold based digital PET (TODPET2) tomograph using silicon photomultipliers (SiPM) arrays coupled with pixelized Ce:Gd3(Ga, Al)5O12 (Ce:GAGG) scintillators dedicated for non-invasive measurement of blood RI concentrations. The detector consists of 1.57 × 1.57 mm2 SiPM chips and 1.6 × 1.6 × 15 mm3 Ce:GAGG scintillators arranged on a 12 × 12 channel, both working as individual readout systems. After the development of the detector, we fabricated the PET gantry composed of 8 pieces of SiPM/Ce:GAGG detector array which signals were sent to the current-comparing type time-over-threshold (TOT) ASIC for individual readout of pixels. The PET scanner which we developed has 25 mm axial field-of-view (FOV) and 60 mm transaxial FOV. The spatial resolution reconstructed with maximum likelihood estimation method (MLEM) is 0.98 mm (FWHM) at the center of FOV. The sensitivity of the system is measured to be 1.31% using 22Na point source. Finally, timing response to changes in RI concentration was also measured using 5 mm diameter syringe injected with several concentrations of 18FDG.

  14. Key Comparison APMP.RI(I)-K2 of air kerma standards for the CCRI reference radiation qualities for low-energy x-rays, including a supplementary comparison for the ISO 4037 narrow spectrum series

    NASA Astrophysics Data System (ADS)

    Tanaka, T.; Saito, N.; Bero, M.; Butler, D.; Mahant, A. K.; Meghzifene, A.; Chu, C. H.; Kadni, T. B.; Jinjie, WU; Soodprasert, T.

    2014-01-01

    An indirect comparison was performed between nine national standards for air kerma for the CCRI radiation qualities from 10 kV to 50 kV (APMP.RI(I)-K2) and for the ISO 4037 narrow spectrum series (15 kV and 40 kV). Among the nine institutes that participated in the comparison, seven institutes were APMP member laboratories. Three commercially available thin window parallel plate ionization chambers were used as transfer instruments and circulated among the participants. The pilot laboratory, the NMIJ/AIST, served also as the link to the corresponding BIPM.RI(I)-K2 comparison. The results show general agreement within the combined uncertainties, although certain results for Nuclear Malaysia, the BARC and the OAP show larger differences. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Activity measurements of the radionuclide 99mTc for the CNEA, Argentina and the LNMRI/IRD, Brazil in the ongoing comparison BIPM.RI(II)-K4.Tc-99m

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Nonis, M.; Arenillas, P.; Cerutti, G.; José da Silva, Carlos; Lima da Cruz, Paulo Alberto; Simões Moreira, Denise; Iwahara, Akira; Ubiratan Delgado, José; Poledna, Roberto; Lins da Silva, Ronaldo; de Oliveira, Antônio Eduardo; dos Santos Gomes, Régio

    2013-01-01

    In 2012 and 2013, comparisons of activity measurements of 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place, respectively, at the Comisión Nacional de Energía Atómica (CNEA, Argentina) and at the Laboratório Nacional de Metrologia das Radiações Ionizantes, Instituto de Radioproteção e Dosimetria (LNMRI/IRD, Brazil). Ampoules containing about 21 kBq (CNEA) and 66 kBq (LNMRI/IRD) of a 99mTc solution were measured in the SIRTI for more than two half-lives. The comparison, identifier BIPM.RI(II)-K4.Tc-99m, is linked to the BIPM.RI(II)-K1.Tc-99m comparison and the degrees of equivalence with the key comparison reference value and between the present CNEA and LNMRI/IRD results, the other K4 participants and the six participants in the K1 comparison have been evaluated. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  16. BIPM comparison BIPM.RI(II)-K1.Zn-65 of activity measurements of the radionuclide 65Zn for the BARC (India) with linked results for the CCRI(II)-K2.Zn-65 comparison

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Joseph, L.

    2015-01-01

    A new participation in the BIPM.RI(II)-K1.Zn-65 comparison has been added to the previous results. A link has been made to the CCRI(II)-K2.Zn-65 comparison held in 2003 through the measurement of all ampoules of the K2 comparison in the International Reference System (SIR) at the BIPM before dispatch to the participants. This has produced a revised value for the key comparison reference value (KCRV), calculated using the power-moderated weighted mean. Six NMIs used the K2 comparison to update their degrees of equivalence. The degrees of equivalence between each equivalent activity measured in the SIR and the KCRV have been calculated and the results are given in the form of a table for the remaining two NMIs in the BIPM.RI(II)-K1.Zn-65 comparison and the 17 other participants in the CCRI(II)-K2.Zn-65 comparison. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. Update of the BIPM comparison BIPM.RI(II)-K1.Sr-85 of activity measurements of the radionuclide 85Sr to include the 2009 result of the POLATOM (Poland)

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Dziel, T.; Listkowska, A.

    2015-01-01

    Since 1975, ten laboratories have submitted 27 samples of known activity of 85Sr to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Sr-85. The values of the activity submitted were between about 0.2 MBq and 19 MBq. The key comparison reference value (KCRV) has been recalculated to include the primary standardization result for the POLATOM, Poland. There are now four results in the BIPM.RI(II)-K1.Sr-85 comparison. The degrees of equivalence between each equivalent activity measured in the SIR and the updated KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  18. BIPM comparison BIPM.RI(II)-K1.Lu-177 of activity measurements of the radionuclide 177Lu for the NPL (UK) and the IRMM (EU), with linked results for the comparison CCRI(II)-K2.Lu-177

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Johansson, L.; Keightley, J.; Arinc, A.; Bakhshandeiar, E.; Pommé, S.; Altzitzoglou, T.; Paepen, J.; Van Ammel, R.

    2014-01-01

    Two new participations in the comparison BIPM.RI(II)-K1.Lu-177 have been added to the previous results and this has produced a revised value for the key comparison reference value (KCRV), calculated using the power-moderated weighted mean. A link has been made to the comparison CCRI(II)-K2.Lu-177 held in 2009 through the NPL and IRMM who participated in both comparisons. Two NMIs used the K2 comparison to update their degree of equivalence. The degrees of equivalence between each equivalent activity measured in the International Reference System (SIR) and the KCRV have been calculated and the results are given in the form of a table for the remaining two NMIs in the comparison BIPM.RI(II)-K1.Lu-177 and the nine other participants in the comparison CCRI(II)-K2.Lu-177. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  19. Quantification and simultaneous evaluation of the bioactivity of antibody produced in CHO cell culture-The use of the ectodomain of FcγRI and surface plasmon resonance-based biosensor.

    PubMed

    Dorion-Thibaudeau, July; Durocher, Yves; De Crescenzo, Gregory

    2017-02-01

    A surface plasmon resonance (SPR)-based assay has been developed in order to quantify the monoclonal antibody (Mab) Trastuzumab within the supernatant of a mammalian cell culture using the ectodomain of FcγRI (CD64) and confirm Mab bioactivity, i.e. binding to its antigen Her2, in a single biosensing experiment. Under partial mass transport limitation, we were able to quantify Mab present in unpurified samples taken throughout the cell culture. While Mab capture on the biosensor surface confirmed the ability of its Fc region to bind to FcγRI, the binding activity of its Fab region was also tested by injecting increasing concentrations of the Mab antigen (Her2). The kinetics of the interactions we recorded from 48h post transfection until the end of the culture, were superimposable, which highly suggested that the quality attributes of the antibody were conserved throughout the process. This SPR methodology is thus of great interest for atline quality control analysis during Mab production campaign.

  20. Seed germination ecology of feather lovegrass [Eragrostis tenella (L.) Beauv. Ex Roemer & J.A. Schultes].

    PubMed

    Chauhan, Bhagirath S

    2013-01-01

    Feather lovegrass [Eragrostis tenella (L.) Beauv. Ex Roemer & J.A. Schultes] is a C4 grass weed that has the ability to grow in both lowland and upland conditions. Experiments were conducted in the laboratory and screenhouse to evaluate the effect of environmental factors on germination, emergence, and growth of this weed species. Germination in the light/dark regime was higher at alternating day/night temperatures of 30/20 °C (98%) than at 35/25 °C (83%) or 25/15 °C (62%). Germination was completely inhibited by darkness. The osmotic potential and sodium chloride concentrations required for 50% inhibition of maximum germination were -0.7 MPa and 76 mM, respectively. The highest seedling emergence (69%) was observed from the seeds sown on the soil surface and no seedlings emerged from seeds buried at depths of 0.5 cm or more. The use of residue as mulches significantly reduced the emergence and biomass of feather lovegrass seedlings. A residue amount of 0.5 t ha(-1) was needed to suppress 50% of the maximum seedlings. Because germination was strongly stimulated by light and seedling emergence was the highest for the seeds sown on the soil surface, feather lovegrass is likely to become a problematic weed in zero-till systems. The knowledge gained from this study could help in developing effective and sustainable weed management strategies.