The N domain of Smad7 is essential for specific inhibition of transforming growth factor-β signaling

Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-β (TGF-β) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-β and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-β signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-β and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-β signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-β type I receptor (TβR-I) more efficiently, and were more potent in repressing TGF-β signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-β receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-β signaling

A Spectral Study of the Black Hole Candidate XTE J1752-223 in the High/Soft State with MAXI, Suzaku and Swift

We report on the X-ray spectral analysis of the black hole candidate XTE\ J1752--223 in the 2009--2010 outburst, utilizing data obtained with the MAXI/Gas Slit Camera (GSC), the Swift/XRT, and Suzaku, which work complementarily. As already reported by Nakahira et al. (2010) MAXI monitored the source continuously throughout the entire outburst for about eight months. All the MAXI/GSC energy spectra in the high/soft state lasting for 2 months are well represented by a multi-color disk plus power-law model. The innermost disk temperature changed from $\sim$0.7 keV to $\sim$0.4 keV and the disk flux decreased by an order of magnitude. Nevertheless, the innermost radius is constant at $\sim$41 $D_{3.5}(\cos{\it i})^{-1/2}$ km, where $D_{3.5}$ is the source distance in units of 3.5 kpc and $i$ the inclination. The multi-color disk parameters obtained with the MAXI/GSC are consistent with those with the Swift/XRT and Suzaku. The Suzaku data also suggests a possibility that the disk emission is slightly Comptonized, which could account for broad iron-K features reported previously. Assuming that the obtained innermost radius represents the innermost stable circular orbit for a non-rotating black hole, we estimate the mass of the black hole to be 5.51$\pm$0.28 $M_{\odot}$ $D_{3.5}(\cos{\it i})^{-1/2}$, where the correction for the stress-free inner boundary condition and color hardening factor of 1.7 are taken into account. If the inclination is less than 49$^{\circ}$ as suggested from the radio monitoring of transient jets and the soft-to-hard transition in 2010 April occurred at 1--4% of Eddignton luminosity, the fitting of the Suzaku spectra with a relativistic accretion-disk model derives constraints on the mass and the distance to be 3.1--55 $M_{\odot}$ and 2.3--22 {\rm kpc}, respectively. This confirms that the compact object in XTE J1752--223 is a black hole.Comment: 12 pages including 7 figures and 4 tables, accepted for publication in PAS

A Large X-ray Flare from a Single Weak-lined T Tauri Star TWA-7 Detected with MAXI GSC

We present a large X-ray flare from a nearby weak-lined T Tauri star TWA-7 detected with the Gas Slit Camera (GSC) on the Monitor of All-sky X-ray Image (MAXI). The GSC captured X-ray flaring from TWA-7 with a flux of $3\times10^{-9}$ ergs cm$^{-2}$ s$^{-1}$ in 2--20 keV band during the scan transit starting at UT 2010-09-07 18:24:30.The estimated X-ray luminosity at the scan in the energy band is 3$\times10^{32}$ ergs s$^{-1}$,indicating that the event is among the largest X-ray flares fromT Tauri stars.Since MAXI GSC monitors a target only during a scan transit of about a minute per 92 min orbital cycle, the luminosity at the flare peak might have been higher than that detected. At the scan transit, we observed a high X-ray-to-bolometric luminosity ratio, log $L_{\rm X}/L_{\rm bol}$ = $-0.1^{+0.2}_{-0.3}$; i.e., the X-ray luminosity is comparable to the bolometric luminosity. Since TWA-7 has neither an accreting disk nor a binary companion, the observed event implies that none of those are essential to generate such big flares in T Tauri stars.Comment: 4 pages, 2 figures, 1 table accepted for publication in PAS

Do Longer Intervals between Challenges Reduce the Risk of Adverse Reactions in Oral Wheat Challenges?

The use of oral food challenges (OFCs) in clinics is limited because they are complicated and associated with anaphylactic symptoms. To increase their use, it is necessary to develop novel, effective, and safe methods. However, the effectiveness of different OFCs has not been compared.To investigate the effect of ingestion methods on wheat allergy symptoms and treatment during OFCs.Without changing the total challenge dose, we changed the administration method from a 5-installment dose titration every 15 min (15-min interval method) to 3 installments every 30 min (30-min interval method). We retrospectively reviewed and compared the results of 65 positive 15-min interval wheat challenge tests conducted between July 2005 and February 2008 and 87 positive 30-min interval tests conducted between March 2008 and December 2009.A history of immediate symptoms was more common for the 30-min interval method; however, no difference between methods was observed in other background parameters. Switching from the 15-min to the 30-min interval method did not increase symptoms or require treatment. The rate of cardiovascular symptoms (p = 0.032), and adrenaline use (p = 0.017) was significantly lower with the 30-min interval method. The results did not change after adjusting for the effects of immediate symptom history in multivariate analysis.This study suggests that the 30-min interval method reduces the risk of adverse events, compared to the 15-min interval method