Suzaku Discovery of a Hard X-Ray Tail in the Persistent Spectra from the Magnetar 1E 1547.0-5408 during its 2009 Activity

The fastest-rotating magnetar 1E 1547.0-5408 was observed in broad-band X-rays with Suzaku for 33 ks on 2009 January 28-29, 7 days after the onset of its latest bursting activity. After removing burst events, the absorption-uncorrected 2-10 keV flux of the persistent emission was measured with the XIS as 5.7e-11 ergs cm-2 s-1, which is 1-2 orders of magnitude higher than was measured in 2006 and 2007 when the source was less active. The persistent emission was also detected significantly with the HXD in >10 keV up to at least ~110 keV, with an even higher flux of 1.3e-10 ergs cm-2 s-1 in 20-100 keV. The pulsation was detected at least up to 70 keV at a period of 2.072135+/-0.00005 s, with a deeper modulation than was measured in a fainter state. The phase-averaged 0.7-114 keV spectrum was reproduced by an absorbed blackbody emission with a temperature of 0.65+/-0.02 keV, plus a hard power-law with a photon index of ~1.5. At a distance of 9 kpc, the bolometric luminosity of the blackbody and the 2-100 keV luminosity of the hard power-law are estimated as (6.2+/-1.2)e+35 ergs s-1 and 1.9e+36 ergs s-1, respectively, while the blackbody radius becomes ~5 km. Although the source had not been detected significantly in hard X-rays during the past fainter states, a comparison of the present and past spectra in energies below 10 keV suggests that the hard component is more enhanced than the soft X-ray component during the persistent activity.Comment: 12 pages, 7 figures, PASJ Vol.62 No.2 accepte

Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation

Genetic Encoding of 3-Iodo-l-Tyrosine in Escherichia coli for Single-Wavelength Anomalous Dispersion Phasing in Protein Crystallography

SummaryWe developed an Escherichia coli cell-based system to generate proteins containing 3-iodo-l-tyrosine at desired sites, and we used this system for structure determination by single-wavelength anomalous dispersion (SAD) phasing with the strong iodine signal. Tyrosyl-tRNA synthetase from Methanocaldococcus jannaschii was engineered to specifically recognize 3-iodo-l-tyrosine. The 1.7 Å crystal structure of the engineered variant, iodoTyrRS-mj, bound with 3-iodo-l-tyrosine revealed the structural basis underlying the strict specificity for this nonnatural substrate; the iodine moiety makes van der Waals contacts with 5 residues at the binding pocket. E. coli cells expressing iodoTyrRS-mj and the suppressor tRNA were used to incorporate 3-iodo-l-tyrosine site specifically into the ribosomal protein N-acetyltransferase from Thermus thermophilus. The crystal structure of this enzyme with iodotyrosine was determined at 1.8 and 2.2 Å resolutions by SAD phasing at CuKα and CrKα wavelengths, respectively. The native structure, determined by molecular replacement, revealed no significant structural distortion caused by iodotyrosine incorporation

Reviewing E(sub peak) Relations with Swift and Suzaku Data

In recent years several authors have derived correlations between gamma-ray burst (GRB) spectral peak energy (E(sub peak)) and either isotropic-equivalent radiated energy (E(sub iso)) or peak luminosity (L(sub iso)). Since these relationships are controversial, but could provide redshift estimators, it is important to determine whether bursts detected by Swift exhibit the same correlations. Swift has greatly added to the number of GRBs for which redshifts are known and hence E(sub iso) and L(sub iso) could be calculated. However, for most bursts it is not possible to adequately constrain E(sub peak) with Swift data alone since most GRBs have E(sub peak) above the energy range (15-50 keV) of the Swift Burst Alert Telescope (BAT). Therefore we have analyzed the spectra of 78 bursts (31 with redshift) which were detected by both Swift/BAT and the Suzaku Wide-band All-sky Monitor (WAM), which covers the energy range 50-5000 keV. For most bursts in this sample we can precisely determine E(sub peak) and for bursts with known redshift we can compare how the E(sub peak) relations for the Swift/Suzaku sample compare to earlier published results. Keywords: gamma rays: burst

Spectral Properties of Prompt Emission of Four Short Gamma-Ray Bursts Observed by the Suzaku-WAM and the Konus-Wind

We have performed a joint analysis of prompt emission from four bright short gamma-ray bursts (GRBs) with the Suzaku-WAM and the Konus-Wind experiments. This joint analysis allows us to investigate the spectral properties of short-duration bursts over a wider energy band with a higher accuracy. We find that these bursts have a high E$_{\rm peak}$, around 1 MeV and have a harder power-law component than that of long GRBs. However, we can not determine whether these spectra follow the cut-off power-law model or the Band model. We also investigated the spectral lag, hardness ratio, inferred isotropic radiation energy and existence of a soft emission hump, in order to classify them into short or long GRBs using several criteria, in addition to the burst duration. We find that all criteria, except for the existence of the soft hump, support the fact that our four GRB samples are correctly classified as belonging to the short class. In addition, our broad-band analysis revealed that there is no evidence of GRBs with a very large hardness ratio, as seen in the BATSE short GRB sample, and that the spectral lag of our four short GRBs is consistent with zero, even in the MeV energy band, unlike long GRBs. Although our short GRB samples are still limited, these results suggest that the spectral hardness of short GRBs might not differ significantly from that of long GRBs, and also that the spectral lag at high energies could be a strong criterion for burst classification.Comment: 23 pages, 6 figures, accepted for Publications of the Astronomical Society of Japa

Uric acid-lowering and renoprotective effects of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group study (UPWARD study)

金沢大学医薬保健研究域医学系Background: Hyperuricemia is supposed to be an independent risk factor for kidney dysfunction in diabetic patients. We attempted to examine the uric acid-lowering effect and the renoprotective effect of topiroxostat, a selective xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia in this pilot study. Methods: The study design was randomized, double-blind, placebo-controlled, parallel-group study. A total of 65 patients with hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and assigned to either the topiroxostat group or the placebo group. Topiroxostat (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID for 28 weeks. The primary endpoint was a change in the urinary albumin-to-creatinine ratio in the first-morning-void urine sample. Secondary endpoints were changes in the estimated glomerular filtration rate and the serum uric acid level. Results: At 28 weeks, there was no significant difference in the percent change from baseline in the urinary albumin-to-creatinine ratio between the two groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the estimated glomerular filtration rate (− 0.2 vs. − 4.0 mL/min/1.73 m2, p = 0.0303) and the serum uric acid level (− 2.94 vs. − 0.20 mg/dL, p < 0.0001) were significantly different between the topiroxostat and placebo groups. Gouty arthritis occurred in 1 patient in the placebo group and no patients in the topiroxostat group. Conclusion: These findings support that diabetic nephropathy combined with hyperuricemia may be associated with kidney dysfunctions. Topiroxostat provides strict control of the serum uric acid level preventing decline of eGFR in these patients. © 2018 The Author(s)Embargo Period 12 month

Detection of the thermal component in GRB 160107A

We present the detection of a blackbody component in gamma-ray burst GRB 160107A emission by using the combined spectral data of the CALET Gamma-ray Burst Monitor (CGBM) and the MAXI Gas Slit Camera (GSC). MAXI/GSC detected the emission ∼45 s prior to the main burst episode observed by the CGBM. The MAXI/GSC and the CGBM spectrum of this prior emission period is fitted well by a blackbody with temperature 1.0 +0.3-0.2 keV plus a power law with a photon index of -1.6 ± 0.3. We discuss the radius of the photospheric emission and the main burst emission based on the observational properties. We stress the importance of coordinated observations via various instruments collecting high-quality data over a broad energy coverage in order to understand the GRB prompt emission mechanism