Showing papers by "Takashi Saito published in 2008"
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TL;DR: The results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.
Abstract: Macrophage-inducible C-type lectin (Mincle) is expressed mainly in macrophages and is induced after exposure to various stimuli and stresses. Here we show that Mincle selectively associated with the Fc receptor common gamma-chain and activated macrophages to produce inflammatory cytokines and chemokines. Mincle-expressing cells were activated in the presence of dead cells, and we identified SAP130, a component of small nuclear ribonucloprotein, as a Mincle ligand that is released from dead cells. To investigate whether Mincle is required for normal responses to cell death in vivo, we induced thymocyte death by irradiating mice and found that transient infiltration of neutrophils into the thymus could be blocked by injection of Mincle-specific antibody. Our results suggest that Mincle is a receptor that senses nonhomeostatic cell death and thereby induces the production of inflammatory cytokines to drive the infiltration of neutrophils into damaged tissue.
611 citations
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TL;DR: The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source 3C 279, at a distance of more than 5 billion light-years.
Abstract: The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.
510 citations
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TL;DR: The swift IL-17 response mounted by antigen-naive gammadelta T cells suggests a critical role for these cells at the onset of an acute inflammatory response to novel antigens, and thymic selection determines the effector fate of gammad delta T cells rather than constrains their antigen specificities.
440 citations
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TL;DR: The accumulation of MCs at the cSMAC was accompanied by the segregation of CD28 from the TCR, which resulted in the translocation of both CD28 and PKCtheta to a spatially unique subregion of c SMAC.
311 citations
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TL;DR: In this paper, the MAGIC observations were analyzed for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index similar or equal to 1 + (E/M-QGn)(n), n = 1, 2.71 +/- 2.57) x 10(-6) s/GeV2, respectively.
251 citations
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TL;DR: By developing a new electronic trigger, the threshold of the MAGIC telescope is lowered, revealing a relatively high cutoff energy in the phase-averaged spectrum, which indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of the measurement.
Abstract: One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high- end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase- averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar- cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot- gap scenario.
241 citations
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University of Würzburg1, ETH Zurich2, Complutense University of Madrid3, Autonomous University of Barcelona4, Max Planck Society5, University of Padua6, Technical University of Dortmund7, University of Barcelona8, Yerevan Physics Institute9, Spanish National Research Council10, University of Udine11, University of Siena12, University of California, Davis13, Humboldt University of Berlin14, INAF15, University of Pisa16, Institut de Ciències de l'Espai17
11 Apr 2008-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: In this paper, an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC, is described, and critical issues of the method and its implementation are discussed.
Abstract: The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.
221 citations
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TL;DR: In vivo therapy with 2 KCa3.1 blockers, TRAM-34 and clotrimazole, significantly reduced the development of atherosclerosis in aortas of Apoe(-/-) mice by suppressing VSMC proliferation and migration into plaques, decreasing infiltration of plaques by macrophages and T lymphocytes, and reducing oxidative stress.
Abstract: Atherosclerosis remains a major cause of death in the developed world despite the success of therapies that lower cholesterol and BP. The intermediate-conductance calcium-activated potassium channel KCa3.1 is expressed in multiple cell types implicated in atherogenesis, and pharmacological blockade of this channel inhibits VSMC and lymphocyte activation in rats and mice. We found that coronary vessels from patients with coronary artery disease expressed elevated levels of KCa3.1. In Apoe–/– mice, a genetic model of atherosclerosis, KCa3.1 expression was elevated in the VSMCs, macrophages, and T lymphocytes that infiltrated atherosclerotic lesions. Selective pharmacological blockade and gene silencing of KCa3.1 suppressed proliferation, migration, and oxidative stress of human VSMCs. Furthermore, VSMC proliferation and macrophage activation were reduced in KCa3.1–/– mice. In vivo therapy with 2 KCa3.1 blockers, TRAM-34 and clotrimazole, significantly reduced the development of atherosclerosis in aortas of Apoe–/– mice by suppressing VSMC proliferation and migration into plaques, decreasing infiltration of plaques by macrophages and T lymphocytes, and reducing oxidative stress. Therapeutic concentrations of TRAM-34 in mice caused no discernible toxicity after repeated dosing and did not compromise the immune response to influenza virus. These data suggest that KCa3.1 blockers represent a promising therapeutic strategy for atherosclerosis.
206 citations
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Hirosaki University1, Chinese Academy of Sciences2, Yokohama National University3, Hebei Normal University4, Tibet University5, Shandong University6, Southwest Jiaotong University7, Yunnan University8, Kanagawa University9, Utsunomiya University10, University of Tokyo11, Konan University12, Waseda University13, Shinshu University14, Tsinghua University15, Saitama University16, National Institute of Informatics17, College of Industrial Technology18, Max Planck Society19, Shonan Institute of Technology20
TL;DR: In this paper, the authors presented an updated all-particle energy spectrum of primary cosmic rays in a wide range from 10 14 to 10 17 eVusing 5:5 ; 10 7 events collected from 2000 November through 2004 October by the Tibet-III air-shower array located 4300 m in altitude.
Abstract: We present an updated all-particle energy spectrum of primary cosmic rays in a wide range from 10 14 to 10 17 eVusing 5:5 ; 10 7 events collected from 2000 November through 2004 October by the Tibet-III air-shower array located 4300 m abovesealevel(anatmosphericdepthof 606gcm � 2 ).Thesizespectrumexhibitsasharpkneeatacorrespondingprimary energy around 4 PeV. This work uses increased statistics and new simulation calculations for the analysis. We discuss our extensive Monte Carlo calculations and the model dependencies involved in thefinal result, assuming interaction models QGSJET01c and SIBYLL2.1, and heavy dominant (HD) and proton dominant (PD) primary composition models. Pure protonandpureironprimarymodelsarealsoexaminedasextremecases.A detector simulationwasalsoperformedtoimproveouraccuracyindeterminingthesizeof theairshowersandtheenergyof theprimaryparticle.Weconfirmedthatthe all-particle energy spectra obtained under various plausible model parameters are not significantly different from each other, which was the expected result given the characteristics of the experiment at high altitude, where the air showers of the primary energy around the knee reach near-maximum development, with their features dominated by electromagnetic components,leadingtoaweakdependenceontheinteractionmodel or theprimarymass.Thisisthehighest statistical and the best systematics-controlled measurement covering the widest energy range around the knee energy region.
194 citations
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TL;DR: In this article, the MAGIC telescope detected a rapid flare in very high energy (VHE) gamma-rays from the M87 radio galaxy, which is the only known nonblazar radio galaxy to emit VHE gamma rays and the highest measured flux reached 15% of the Crab Nebula flux.
Abstract: M87 is the only known nonblazar radio galaxy to emit very high energy (VHE) gamma rays. During a monitoring program of M87, a rapid flare in VHE gamma-rays was detected by the MAGIC telescope in early 2008. The flux was found to be variable above 350 GeV on a timescale as short as 1 day at a significance level of 5.6 sigma. The highest measured flux reached 15% of the Crab Nebula flux. We observed several substantial changes of the flux level during the 13 day observing period. The flux at lower energies (150-350 GeV), instead, is compatible with being constant. The energy spectrum can be described by a power law with a photon index of 2.30 +/- 0.11(stat) +/- 0.20(syst). The observed day-scale flux variability at VHE prefers the M87 core as source of the emission and implies that either the emission region is very compact (just a few Schwarzschild radii) or the Doppler factor of the emitting blob is rather large in the case of a nonexpanding emission region.
103 citations
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TL;DR: In this paper, a multi-wavelength campaign on the TeVblazar 1ES 1959+650, performed in 2006May, was presented, with the results from the optical, UV, soft-and hard-X-ray, and very high energy (VHE) gamma-ray (E > 100 GeV) bands obtained with the Suzaku and Swift satellites, the MAGIC telescope, and other ground-based facilities.
Abstract: We present the resultsfroma multiwavelength campaignonthe TeVblazar1ES 1959+650, performed in2006May. Data from the optical, UV, soft- and hard-X-ray, and very high energy (VHE) gamma-ray (E > 100 GeV) bands were obtained with the Suzaku and Swift satellites, the MAGIC telescope, and other ground-based facilities. The source spectral energy distribution (SED), derived from Suzaku and MAGIC observations at the end of 2006 May, shows the usual double hump shape, with the synchrotron peak at a higher flux level than the Compton peak. With respect to historicalvalues,duringourcampaignthe sourceexhibiteda relatively highstateinX-raysand optical, while inthe VHEbanditwasatoneof thelowestlevelsofarrecorded.Wealsomonitoredthesourceforfluxspectralvariability onatimewindowof 10daysintheoptical-UVandX-raybandsand7daysintheVHEband.Thesourcevariesmorein the X-ray than in the optical band, with the 2Y10 keV X-ray flux varying by a factor of � 2. The synchrotron peak is locatedintheX-raybandandmovestohigherenergiesasthesourcegetsbrighter,withtheX-rayfluxesaboveitvarying more rapidly than the X-ray fluxes at lower energies. The variability behavior observed in the X-ray band cannot be
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University of Würzburg1, IFAE2, ETH Zurich3, Complutense University of Madrid4, Autonomous University of Barcelona5, Max Planck Society6, University of Padua7, Technical University of Dortmund8, University of Siena9, University of Barcelona10, Yerevan Physics Institute11, Spanish National Research Council12, University of Udine13, University of California, Davis14, Centre national de la recherche scientifique15, Humboldt University of Berlin16, INAF17, University of Pisa18, Institut de Ciències de l'Espai19
TL;DR: Pantka et al. as mentioned in this paper observed the first known very high energy (VHE) gamma-ray-emitting unidentified source, TeV J2032 + 4130, for 94 hours with the MAGIC telescope.
Abstract: We observed the first known very high energy (VHE) gamma-ray-emitting unidentified source, TeV J2032 + 4130, for 94 hr with the MAGIC telescope. The source was detected with a significance of 5.6 sigma. The flux, position, and angular extension are compatible with the previous ones measured by the HEGRA telescope system 5 years ago. The integral flux amounts to (4.5 +/- 0.3(stat)+/- 0.35(sys)) x 10 (- 13) photons cm(-2) s(-1) above 1 TeV. The source energy spectrum, obtained with the lowest energy threshold to date, is compatible with a single power law with a hard photon index of Gamma= - 2.0 +/- 0.3(stat)+/- 0.2(sys).
Miranda Pantka
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TL;DR: It is suggested that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients and had a safe profile as fluconazole in neutropenic patients.
Abstract: A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, −5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.
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TL;DR: IL‐1β is an anti‐amyloidogenic factor, and that enhancement of its signaling or inhibition of IL‐1Ra activity could represent potential therapeutic strategies against Alzheimer’s disease.
Abstract: The proinflammatory cytokine interleukin (IL)-1beta is up-regulated in microglial cells surrounding amyloid plaques, leading to the hypothesis that IL-1beta is a risk factor for Alzheimer's disease. However, we unexpectedly found that IL-1beta significantly enhanced alpha-cleavage, indicated by increases in sAPPalpha and C83, but reduced beta-cleavage, indicated by decreases in sAPPbeta and Abeta40/42, in human neuroblastoma SK-N-SH cells. IL-1beta did not significantly alter the mRNA levels of BACE1, ADAM-9, and ADAM-10, but up-regulated that of TACE by threefold. The proform and mature form of TACE protein were also significantly up-regulated. A TACE inhibitor (TAPI-2) concomitantly reversed the IL-1beta-dependent increase in sAPPalpha and decrease in sAPPbeta, suggesting that APP consumption in the alpha-cleavage pathway reduced its consumption in the beta-cleavage pathway. IL-1Ra, a physiological antagonist for the IL-1 receptor, reversed the effects of IL-1beta, suggesting that the IL-1beta-dependent up-regulation of alpha-cleavage is mediated by the IL-1 receptor. IL-1beta also induced this concomitant increase in alpha-cleavage and decrease in beta-cleavage in mouse primary cultured neurons. Taken together we conclude that IL-1beta is an anti-amyloidogenic factor, and that enhancement of its signaling or inhibition of IL-1Ra activity could represent potential therapeutic strategies against Alzheimer's disease.
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TL;DR: Differential roles of the three activating FcγR in IgG 2a- and IgG2b-mediated AIHA are indicated, including the development of mild and severe AIHA induced by two different doses of 34-3C anti-RBC monoclonal autoantibody.
Abstract: Murine phagocytes express three different activating IgG FcgammaR: FcgammaRI is specific for IgG2a; FcgammaRIII for IgG1, IgG2a, and IgG2b; and FcgammaRIV for IgG2a and IgG2b. Although the role of FcgammaRIII in IgG1 and IgG2a anti-RBC-induced autoimmune hemolytic anemia (AIHA) is well documented, the contribution of FcgammaRI and FcgammaRIV to the development of IgG2a- and IgG2b-induced anemia has not yet been defined. In the present study, using mice deficient in FcgammaRI, FcgammaRIII, and C3, in combination with an FcgammaRIV-blocking mAb, we assessed the respective roles of these three FcgammaR in the development of mild and severe AIHA induced by two different doses (50 and 200 microg) of the IgG2a and IgG2b subclasses of the 34-3C anti-RBC monoclonal autoantibody. We observed that the development of mild anemia induced by a low dose of 34-3C IgG2a autoantibody was highly dependent on FcgammaRIII, while FcgammaRI and FcgammaRIV additionally contributed to the development of severe anemia induced by a high dose of this subclass. In contrast, the development of both mild and severe anemia induced by 34-3C IgG2b was dependent on FcgammaRIII and FcgammaRIV. Our results indicate differential roles of the three activating FcgammaR in IgG2a- and IgG2b-mediated AIHA.
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University of Würzburg1, IFAE2, ETH Zurich3, Complutense University of Madrid4, Technical University of Dortmund5, Autonomous University of Barcelona6, Max Planck Society7, University of Padua8, University of Barcelona9, Yerevan Physics Institute10, Spanish National Research Council11, University of Udine12, University of Siena13, University of California, Davis14, Humboldt University of Berlin15, INAF16, University of Pisa17, Institut de Ciències de l'Espai18
TL;DR: In this article, an analysis of the data results in a flux upper limit (2 sigma) of 1.1 x 10(-11) photons cm(-2) s(-1) for photon energies above 140 GeV, assuming a pointlike source.
Abstract: The nearby dwarf spheroidal galaxy Draco, with its high mass to light ratio, is one of the most auspicious targets for indirect dark matter (DM) searches. Annihilation of hypothetical DM particles can result in high-energy gamma-rays, e. g., from neutralino annihilation in the supersymmetric framework. A search for a possible DM signal originating from Draco was performed with the MAGIC telescope during 2007. Analysis of the data results in a flux upper limit (2 sigma) of 1.1 x 10(-11) photons cm(-2) s(-1) for photon energies above 140 GeV, assuming a pointlike source. A comparison with predictions from supersymmetric models is also given. While our results do not constrain the mSUGRA phase parameter space, a very high flux enhancement can be ruled out.
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TL;DR: Novel Betaproteobacteria, possibly within the order Rhodocyclales, represented 43% of the clones obtained and may play an important role in denitrification in rice paddy soil.
Abstract: Rice paddy soil has been shown to have strong denitrifying activity However, the microbial populations responsible for the denitrification have not been well characterized In this study, we employed Stable Isotope Probing (SIP) to study succinate-assimilating denitrifiers in soil microcosms amended with nitrate and (13)C-succinate Microbial populations represented in (12)C- and (13)C-DNA fractions were different based on denaturing gradient gel electrophoresis (DGGE) of the PCR-amplified 16S rRNA gene fragment A nearly full-length 16S rRNA gene was also amplified, cloned, and sequenced from (13)C-DNA fraction Both PCR-DGGE and clone library analyses revealed that Burkholderiales and Rhodocyclales dominated the succinate-assimilating population in denitrifying soil after 24 h incubation Among these, novel Betaproteobacteria, possibly within the order Rhodocyclales, represented 43% of the clones obtained Nitrite reductase genes, nirS and nirK, were also amplified and cloned from the (13)C-DNA fraction While most nirK clones in this study were similar to the nirK sequences from Rhizobiales, a majority of the nirS clones were similar to the nirS sequences from Burkholderiales and Rhodocyclales, consistent with the 16S rRNA gene analysis These groups of bacteria, including the novel Betaproteobacteria, may play an important role in denitrification in rice paddy soil
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TL;DR: In this article, the results of the first multi-wavelength observing campaign on the high-mass X-ray binary LS I +61 303 were presented, comprising observations at the TeV regime with the MAGIC telescope, along with Chandra, and radio interferometric observations with the MERLIN, EVN, and VLBA arrays, in 2006 October and November.
Abstract: We present the results of the first multiwavelength observing campaign on the high-mass X-ray binary LS I +61 303, comprising observations at the TeV regime with the MAGIC telescope, along with X-ray observations with Chandra, and radio interferometric observations with the MERLIN, EVN, and VLBA arrays, in 2006 October and November. From our MERLIN observations, we can exclude the existence of large-scale (~100 mas) persistent radio jets. Our 5.0 GHz VLBA observations display morphological similarities to previous 8.4 GHz VLBA observations carried out at the same orbital phase, suggesting a high level of periodicity and stability in the processes behind the radio emission. This makes it unlikely that variability of the radio emission is due to the interaction of an outflow with variable wind clumps. If the radio emission is produced by a milliarcsecond scale jet, it should also show a stable, periodic behavior. It is then difficult to reconcile the absence of a large-scale jet (~100 mas) in our observations with the evidence of a persistent relativistic jet reported previously. We find a possible hint of temporal correlation between the X-ray and TeV emissions and evidence for radio/TeV noncorrelation, which points to the existence of one population of particles producing the radio emission and a different one producing the X-ray and TeV emissions. Finally, we present a quasi-simultaneous energy spectrum including radio, X-ray, and TeV bands.
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TL;DR: The human acquired immune system can be reconstituted from CD34+ cells in NOD/SCID/JAK3null mice, a novel model for the human immune system’s development and a powerful tool for the study of human immunity.
Abstract: An animal model in which the human immune system can be reconstituted is necessary to study acquired immunity in vivo. We report here a novel model, the NOD/SCID/JAK3(null) mouse, for the human immune system's development. Newborn mice transplanted with human cord blood CD34(+) cells intrahepatically, developed human T and B cells, and myeloid and plasmacytoid dendritic cells. The T and B cells had a naive to memory phenotype, and included plasma cells. The human acquired immune system can be reconstituted from CD34(+) cells in NOD/SCID/JAK3(null) mice. This model is a powerful tool for the study of human immunity.
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University of Würzburg1, ETH Zurich2, Complutense University of Madrid3, Max Planck Society4, University of Padua5, Technical University of Dortmund6, University of Barcelona7, Yerevan Physics Institute8, Spanish National Research Council9, University of Udine10, University of Siena11, University of California, Davis12, Autonomous University of Barcelona13, Humboldt University of Berlin14, University of Pisa15, Institut de Ciències de l'Espai16
11 Sep 2008-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: In this paper, different algorithms to reconstruct the signal from the read-out samples (extractors) have been implemented and compared and criteria based on the obtained charge and time resolution/bias are defined and used to judge the different extractors, by applying them to calibration, cosmic and pedestal signals.
Abstract: Until April 2007 the Major Atmospheric Gamma ray Imaging Cherenkov (MAGIC) telescope used a 300 MSamples/s flash analog-to-digital converter (FADC) system to sample the shaped photomultiplier tube (PMT) signals produced by the captured Cherenkov photons of air showers. Different algorithms to reconstruct the signal from the read-out samples (extractors) have been implemented and are described and compared. Criteria based on the obtained charge and time resolution/bias are defined and used to judge the different extractors, by applying them to calibration, cosmic and pedestal signals. The achievable charge and time resolution have been derived as functions of the number of incident photoelectrons. (C) 2008 Elsevier B.V. All rights reserved.
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TL;DR: It is shown that the deficiency of CARMA1 or Bcl10, but not CARD9, resulted in severe impairment of cytokine/chemokine production mediated by activating NK cell receptors due to a selective defect in NF-κB activation, whereas cytotoxicity mediated by the same receptors did not require CarMA1-Bcl10-mediated signaling.
Abstract: Activating NK cell receptors transduce signals through ITAM-containing adaptors, including FcRgamma and DAP12. Although the caspase recruitment domain (CARD)9-Bcl10 complex is essential for FcRgamma/DAP12-mediated NF-kappaB activation in myeloid cells, its involvement in NK cell receptor signaling is unknown. Herein we show that the deficiency of CARMA1 or Bcl10, but not CARD9, resulted in severe impairment of cytokine/chemokine production mediated by activating NK cell receptors due to a selective defect in NF-kappaB activation, whereas cytotoxicity mediated by the same receptors did not require CARMA1-Bcl10-mediated signaling. IkappaB kinase (IKK) activation by direct protein kinase C (PKC) stimulation with PMA plus ionomycin (P/I) was abrogated in CARMA1-deficient NK cells, similar to T and B lymphocytes, whereas CARD9-deficient dendritic cells (DCs) exhibited normal P/I-induced IKK activation. Surprisingly, CARMA1 deficiency also abrogated P/I-induced IKK activation in DCs, indicating that CARMA1 is essential for PKC-mediated NF-kappaB activation in all cell types, although the PKC-CARMA1 axis is not used downstream of myeloid ITAM receptors. Consistently, PKC inhibition abrogated ITAM receptor-mediated activation only in NK cells but not in DCs, suggesting PKC-CARMA1-independent, CARD9-dependent ITAM receptor signaling in myeloid cells. Conversely, the overexpression of CARD9 in CARMA1-deficient cells failed to restore the PKC-mediated NF-kappaB activation. Thus, NF-kappaB activation signaling through ITAM receptors is regulated by a cell type-specific mechanism depending on the usage of adaptors CARMA1 and CARD9, which determines the PKC dependence of the signaling.
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TL;DR: It is demonstrated that the lysosomal protein LAPTM5 negatively regulated surface TCR expression by specifically interacting with the invariant signal-transducing CD3zeta chain and promoting its degradation without affecting other CD3 proteins,CD3epsilon, CD3delta, or CD3gamma.
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TL;DR: It is shown that, although collagen-induced arthritis (CIA) could not be induced by immunization and challenge with a standard amount of type-II collagen in LFA-1-deficient mice, a higher dose of the antigen did induce CIA in the absence of L FA-1, suggesting that LFA -1 decreases the threshold of TCR signal for T cell activation in vivo as well as in vitro.
Abstract: Leukocyte adhesion molecule leukocyte function-associated antigen (LFA)-1 not only mediates intercellular binding but also delivers co-stimulatory signals in T cells. LFA-1 has been shown to decrease the threshold of TCR signal and an antigen dose required for T cell activation and proliferation in vitro. However, physiological significance of the role of LFA-1 in TCR signal has remained unclear. We examined whether LFA-1 decreased the antigen dose for T cell activation in vivo. We showed here that, although collagen-induced arthritis (CIA) could not be induced by immunization and challenge with a standard amount of type-II collagen in LFA-1-deficient mice, a higher dose of the antigen did induce CIA in the absence of LFA-1. We also showed that CD4+ T cells could be primed by immunization with a high, but not low, dose of ovalbumin antigen in LFA-1-deficient mice. These results suggest that LFA-1 decreases the threshold of TCR signal for T cell activation in vivo as well as in vitro. Further studies using TCR-transgenic LFA-1-deficient mice showed that LFA-1 cooperated with TCR in sustained Erk1/2 phosphorylation. Moreover, TCR could induce sustained Erk1/2 phosphorylation in the absence of LFA-1 when T cells were stimulated with a high, but not low, dose of antigen, suggesting that LFA-1 may cooperate with TCR in sustaining Erk1/2 phosphorylation.
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University of Würzburg1, IFAE2, ETH Zurich3, Complutense University of Madrid4, Autonomous University of Barcelona5, Max Planck Society6, University of Padua7, Technical University of Dortmund8, University of Barcelona9, Yerevan Physics Institute10, University of La Laguna11, Spanish National Research Council12, University of Udine13, University of Siena14, University of California, Davis15, Humboldt University of Berlin16, INAF17, University of Pisa18, Institut de Ciències de l'Espai19
TL;DR: In this article, a systematic scan of candidate sources with the MAGIC telescope, based on the Donato et al. compilation of X-ray blazars, was carried out for detecting Xray-bright [F(1 keV) > 2 mu Jy] sources emitting at least the same energy flux at 200 GeV as at 1 keV.
Abstract: All but three (M87, BL Lac, and 3C 279) extragalactic sources detected so far at very high energy gamma-rays belong to the class of high-frequency-peaked BL Lac objects. This suggested to us a systematic scan of candidate sources with the MAGIC telescope, based on the Donato et al. compilation of X-ray blazars. The observations took place from 2004 December to 2006 March and cover northern sky sources visible under small zenith distances zd 30 degrees at culmination, constraining the declination to -2 degrees to +58 degrees. The sensitivity of the search was planned for detecting X-ray-bright [F(1 keV) > 2 mu Jy] sources emitting at least the same energy flux at 200 GeV as at 1 keV. To avoid strong gamma-ray attenuation close to the energy threshold, source redshift was constrained to z < 0.3. Of the 14 sources observed, 1ES 1218+304 (for the first time at VHE) and 1ES 2344+514 (strong detection in a low flux state) were detected in addition to the known bright TeV blazars Mrk 421 and Mrk 501. A marginal excess of 3.5 sigma from the position of 1ES 1011+496 was observed and then confirmed as a VHE gamma-ray source by a second MAGIC observation triggered by a high optical state. For the remaining sources, we present 99% c. l. upper limits on the integral flux greater than or similar to 200 GeV. We characterize the HBL sample (including all HBLs detected at VHE so far) by looking for correlations between their multifrequency spectral indices determined from simultaneous optical, archival X-ray, and radio luminosities, finding that VHE-emitting HBLs do not seem to constitute a unique subclass. The HBLs' absorption-corrected gamma-ray luminosities at 200 GeV are generally not higher than their X-ray luminosities at 1 keV.
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TL;DR: In this article, the authors presented the first bounds on the putative gamma-ray emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope.
Abstract: High-energy gamma-ray emission is theoretically expected to arise in tight binary star systems (with high mass loss and high-velocity winds), although the evidence of this relationship has proven to be elusive so far. Here we present the first bounds on this putative emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope.
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TL;DR: FcRgamma-mediated sustained Erk activation is critical for IgE-induced mast cell survival through autocrine production of IL-3 and Transmembrane adaptors LAT and NTAL contribute to the maintenance of prolonged Erkactivation through membrane retention of the Ras-activating complex, Grb2-Sos.
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TL;DR: Gads is a Grb2-like adaptor protein expressed in hematopoietic cells and has been shown to suppress the IgE-mediated allergic reaction with minimum adverse effects on both innate and acquired immune responses.
Abstract: Gads is a Grb2-like adaptor protein expressed in hematopoietic cells. We demonstrated that mast cells from Gads 2/2 mice have selective functional defects. Bone marrow-derived mast cells from Gads 2/2 mice failed to induce Ca 21 mobilization, degranulation and cytokine production upon crosslinking of FceRI. In vivo passive cutaneous anaphylaxis was also greatly impaired in Gads 2/2 mice. In contrast, Gads was dispensable for Toll-like receptor-mediated cytokine production in mast cells. Accordingly, mast cell-dependent resistance to acute peritoneal bacterial infection is not reduced in Gads 2/2 mice in vivo. Moreover, mature T and B cell responses and antibody production upon immunization were apparently normal in Gads 2/2 mice. Thus, inhibition of Gads in vivo would suppress the IgE-mediated allergic reaction with minimum adverse effects on both innate and acquired immune responses, and Gads could be an ideal target for the control of allergic responses.
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TL;DR: The results suggest that endogenous Rap GTPases downstream of pre-TCR play an essential role in rescuing pre-T cells from the p53-mediated checkpoint response, thus allowing Notch-mediated expansion and differentiation.
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18 Apr 2008
TL;DR: In this paper, the aqueous pigmented ink for use in an inkjet as is capable of suppressing the curling of printing papers and as is excellent in the storage stability and the head leaving performance.
Abstract: PROBLEM TO BE SOLVED: To provide such an aqueous pigmented ink for use in an inkjet as is capable of suppressing the curling of printing papers and as is excellent in the storage stability and the head leaving performance. SOLUTION: The aqueous ink for use in inkjets containing a pigment, a water-soluble organic solvent A, a water-soluble organic solvent B and water, is characterized in that the above water-soluble organic solvent A comprises at least one kind of diglycerin and polyglycerins and the above water-soluble organic solvent B comprises a polyethylene glycol monoalkyl ether expressed by general formula (1): RO-(CH 2 CH 2 O) n -H (wherein, R is a 4-6C alkyl group; and n is an integer of 4 through 6). COPYRIGHT: (C)2009,JPO&INPIT
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TL;DR: In vivo results demonstrate that GC B cells are unique in having an intrinsic propensity to generate A:T mutations during repair of endogenous DNA damage and have important implications in understanding how AID, which can only target C:G base pairs, is able to induce the entire spectrum of mutations observed in immunoglobulin variable region genes in GC B Cells.