Myocardial deletion of Smad4 using a novel alpha skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract

S MAD4 acts as the converging point f or T GF β and BMP signaling in heart development. Here, we investigated the role of S MAD4 in heart development usi ng a novel α skeletal muscle actin Cre recombinase (MuCre) transgenic mouse strain. Lineage tracing using MuCre/ROSA26LacZ reporter mice indicated strong Cre-recombinase expression in developing and adult heart and skeletal muscles. In heart development, significant MuCre expression was noted at E11.5 in the atrial, ventricular, outflow tract and atrioventricular canal myocardium, but not in the endocardial cushions. MuCre-driven conditional deletion of Smad4 in mice caused double outlet right ventricle (DORV), ventricular septal defect (VSD), impaired trabeculation and thinning of ventricular myocardium, and mid-gestational embryonic lethality. In conclusion, MuCre mice effectively delete genes in both heart and skeletal muscles, thus enabling the discovery that myocardial Smad4 deletion causes misalignment of the outflow tract and DORV

Hedgehog signal activation in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy

The zinc finger protein glioma-associated oncogene homologue 1 (Gli-1) is a critical component of the Hedgehog (Hh) signalling pathway, which is essential for morphogenesis and stem-cell renewal, and is dysregulated in many cancer types. As data were not available on the role of Gli-1 expression in oesophageal cancer progression, we analysed whether it could be used to predict disease progression and prognosis in oesophageal cancer patients undergoing neoadjuvant chemoradiotherapy (CRT). Among 69 patients with histologically confirmed oesophageal squamous cell carcinomas (ESCCs), 25 showed a pathological complete response after preoperative CRT. Overall survival (OS) was significantly associated with lymph-node metastasis, distant metastasis, and CRT, and was further correlated with the absence of both Gli-1 nuclear expression and residual tumour. All patients with Gli-1 nuclear expression (10.1%) had distant or lymph-node metastasis, and six out of seven died within 13 months. Furthermore, patients with Gli-1 nuclear-positive cancers showed significantly poorer prognoses than those without (disease-free survival: mean DFS time 250 vs 1738 months, 2-year DFS 0 vs 54.9%, P=0.009; OS: mean OS time 386 vs 1742 months, 2-year OS 16.7 vs 54.9%, P=0.001). Our study provides the first evidence that Gli-1 nuclear expression is a strong and independent predictor of early relapse and poor prognosis in ESCC after CRT. These findings suggest that Hh signal activation might promote cancer regrowth and progression after CRT

Observation of Large CP Violation in the Neutral B Meson System

We present a measurement of the Standard Model CP violation parameter sin 2phi_1 based on a 29.1 fb^{-1} data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. One neutral B meson is fully reconstructed as a J/psi Ks, psi(2S) Ks, chi_c1 Ks, eta_c Ks, J/psi K_L or J/psi K^{*0} decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin 2phi_1 = 0.99 +- 0.14(stat) +- 0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.Comment: 4 figures, to appear in Phys. Rev. Letter

Measurement of B0d - B0d-bar mixing rate from the time evolution of dilepton events at the Upsilon(4S)

We report a determination of the B0d - B0d-bar mixing parameter Delta-m_d based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 /fb data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Delta-m_d as a free parameter. Using both muons and electrons, we obtain Delta-m_d = 0.463 +- 0.008(stat.) +- 0.016(sys.) ps^{-1} This is the first determination of Delta-m_d from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.Comment: 12 pages, 2 figure

Measurement of the CP Violation Parameter sin(2phi_1) in B^0_d Meson Decays

We present a measurement of the Standard Model CP violation parameter sin(2phi_1) based on a 10.5 fb^{-1} data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e+e- collider. One neutral B meson is reconstructed in the J/psi K_S, psi(2S) K_S, chi_{c1} K_S, eta_c K_S, J/psi K_L or J/psi pi^0 CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin(2phi_1) = 0.58 +0.32-0.34 (stat) +0.09-0.10 (syst).Comment: LaTex, 13 pages, 3 figures, submitted to P.R.

Study of CP-Violating Asymmetries in B0 -> pi+pi- Decays

We present a measurement of CP-violating asymmetries in B0 -> pi+pi- decays based on a 41.8 fb-1 data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We fully reconstruct one neutral B meson as a B0 -> pi+pi- CP eigenstate and identify the flavor of the accompanying B meson from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we obtain the CP-violating asymmetry parameters Spipi = -1.21 +0.38/-0.27(stat) +0.16/-0.13(syst) and Apipi = +0.94 +0.25/-0.31(stat) +/- 0.09(syst).Comment: 9 pages, 2 figures, accepted for publication in Physical Review Letter

An Improved Measurement of Mixing-induced CP Violation in the Neutral B Meson System

We present an improved measurement of the standard model CP violation parameter sin2phi_1 (also known as sin2beta) based on a sample of 85 times 10^6 B Bbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. One neutral B meson is reconstructed in a J/psi K_S, psi(2S) K_S, chi_{c1} K_S, eta_c K_S, J/psi K^{*0}, or J/psi K_L CP-eigenstate decay channel and the flavor of accompanying B meson is identified from itsdecay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we obtain sin2phi_1 = 0.719 +/- 0.074(stat) +/- 0.035(syst). We also report measurements of CP violation parameters for the related B^0 -> J/psi pi^0 decay mode and the penguin-dominated processes B^0 -> eta' K_S, phi K_S and K^+K^- K_S.Comment: 11 pages, 4 figures, 4 tables, contributed to ICHEP200