Biodistribution and function of extracellular miRNA-155 in mice

Circulating miRNAs can be found in extracellular vesicles (EV) and could be involved in intercellular communication. Here, we report the biodistribution of EV associated miR-155 using miR-155 KO mouse model. Administration of exosomes loaded with synthetic miR-155 mimic into miR-155 KO mice resulted in a rapid accumulation and clearance of miR-155 in the plasma with subsequent distribution in the liver, adipose tissue, lung, muscle and kidney (highest to lowest, respectively). miR-155 expression was detected in isolated hepatocytes and liver mononuclear cells of recipient KO mice suggesting its cellular uptake. In vitro, exosome-mediated restoration of miR-155 in Kupffer cells from miR-155 deficient mice augmented their LPS-induced MCP1 mRNA increase. The systemic delivery of wild type plasma to miR-155 KO mice also resulted in a rapid accumulation of miR-155 in the circulation and distribution to the liver and adipose tissue. In summary, our results demonstrate tissue biodistribution and biologic function of EV-associated miR-155

Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via Stimulator of Interferon Genes.

Fibrosis, driven by inflammation, marks the transition from benign to progressive stages of chronic liver diseases. Although inflammation promotes fibrogenesis, it is not known whether other events, such as hepatocyte death, are required for the development of fibrosis. Interferon Regulatory Factor 3 (IRF3) regulates hepatocyte apoptosis and production of Type-I interferons (IFNs). In the liver, IRF3 is activated via Toll-like receptor 4 (TLR4) signaling or the ER adapter, Stimulator of Interferon Genes (STING). We hypothesized that IRF3-mediated hepatocyte death is an independent determinant of chemically-induced liver fibrogenesis. To test this, we performed acute or chronic carbontetrachloride (CCl4) administration to WT, IRF3-, TRAM-, TRIF-, and STING-deficient mice. We report that acute CCl4 administration to WT mice resulted in early ER stress, activation of IRF3 and Type-I IFNs, followed by hepatocyte apoptosis and liver injury, accompanied by liver fibrosis upon repeated administration of CCl4. Deficiency of IRF3 or STING prevented hepatocyte death and fibrosis both in acute or chronic CCl4. In contrast, mice deficient in Type-I IFN receptors or in TLR4-signaling adaptors, TRAM or TRIF, upstream of IRF3, were not protected from hepatocyte death and/or fibrosis suggesting that the pro-apoptotic role of IRF3 is independent of TLR signaling in fibrosis. Hepatocyte death is required for liver fibrosis with causal involvement of STING and IRF3. Thus, our results identify that IRF3, by its association with STING in the presence of ER stress, couples hepatocyte apoptosis with liver fibrosis, and indicate that innate immune signaling modulates outcomes of liver fibrosis via modulation of hepatocyte death in the liver

Measurements of the masses and widths of the Σc(2455)0/++\Sigma_{c}(2455)^{0/++} and Σc(2520)0/++\Sigma_{c}(2520)^{0/++} baryons

We present measurements of the masses and decay widths of the baryonic states $\Sigma_{c}(2455)^{0/++}$ and $\Sigma_{c}(2520)^{0/++}$ using a data sample corresponding to an integrated luminosity of 711 fb$^{-1}$ collected with the Belle detector at the KEKB $e^{+}e^{-}$ asymmetric-energy collider operating at the $\Upsilon(4S)$ resonance. We report the mass differences with respect to the $\Lambda_{c}^{+}$ baryon $M(\Sigma_{c}(2455)^{0})-M(\Lambda_{c}^{+}) = 167.29\pm0.01\pm0.02$ MeV/$c^{2}$, $M(\Sigma_{c}(2455)^{++})-M(\Lambda_{c}^{+}) = 167.51\pm0.01\pm0.02$ MeV/$c^{2}$, $M(\Sigma_{c}(2520)^{0})-M(\Lambda_{c}^{+}) = 231.98\pm0.11\pm0.04$ MeV/$c^{2}$, $M(\Sigma_{c}(2520)^{++})-M(\Lambda_{c}^{+}) = 231.99\pm0.10\pm0.02$ MeV/$c^{2}$, and the decay widths $\Gamma(\Sigma_{c}(2455)^{0}) = 1.76\pm0.04^{+0.09}_{-0.21}$ MeV/$c^{2}$, $\Gamma(\Sigma_{c}(2455)^{++}) = 1.84\pm0.04^{+0.07}_{-0.20}$ MeV/$c^{2}$, $\Gamma(\Sigma_{c}(2520)^{0}) = 15.41\pm0.41^{+0.20}_{-0.32}$ MeV/$c^{2}$, $\Gamma(\Sigma_{c}(2520)^{++}) = 14.77\pm0.25^{+0.18}_{-0.30}$ MeV/$c^{2}$, where the first uncertainties are statistical and the second are systematic. The isospin mass splittings are measured to be $M(\Sigma_{c}(2455)^{++})-M(\Sigma_{c}(2455)^{0})=0.22\pm0.01\pm0.01$ MeV/$c^{2}$ and $M(\Sigma_{c}(2520)^{++})-M(\Sigma_{c}(2520)^{0})=0.01\pm0.15\pm0.03$ MeV/$c^{2}$. These results are the most precise to date.Comment: 13 pages, 4 figures, Submitted to PRD(RC

Search for B+ -> l+ nu gamma decays with hadronic tagging using the full Belle data sample

We search for the decay B+ -> l+ nu gamma with l+ = e+ or mu+ using the full Belle data set of 772 x 10^6 BBbar pairs, collected at the Y(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider. We reconstruct one B meson in a hadronic decay mode and search for the B+ -> l+ nu gamma decay in the remainder of the event. We observe no significant signal within the phase space of E_gamma^sig > 1 GeV and obtain upper limits of BR(B+ -> e+ nu gamma) mu+ nu gamma) l+ nu gamma) < 3.5 x 10^-6 at 90 % credibility level.Comment: Submitted to Phys. Rev.

First Observation of CP Violation in B0->D(*)CP h0 Decays by a Combined Time-Dependent Analysis of BaBar and Belle Data

We report a measurement of the time-dependent CP asymmetry of B0->D(*)CP h0 decays, where the light neutral hadron h0 is a pi0, eta or omega meson, and the neutral D meson is reconstructed in the CP eigenstates K+ K-, K0S pi0 or K0S omega. The measurement is performed combining the final data samples collected at the Y(4S) resonance by the BaBar and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain ( 471 +/- 3 ) x 10^6 BB pairs recorded by the BaBar detector and ( 772 +/- 11 ) x 10^6, BB pairs recorded by the Belle detector. We measure the CP asymmetry parameters -eta_f S = +0.66 +/- 0.10 (stat.) +/- 0.06 (syst.) and C = -0.02 +/- 0.07 (stat.) +/- 0.03 (syst.). These results correspond to the first observation of CP violation in B0->D(*)CP h0 decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.Comment: 9 pages, 2 figures, submitted to Physical Review Letter

The ATLAS SCT grounding and shielding concept and implementation

This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper

Energy scan of the e+e−→hb(nP)π+π−e^+e^- \to h_b(nP)\pi^+\pi^- (n=1,2)(n=1,2) cross sections and evidence for Υ(11020)\Upsilon(11020) decays into charged bottomonium-like states

Using data collected with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider, we measure the energy dependence of the $e^+e^- \to h_b(nP)\pi^+\pi^-$ $(n=1,2)$ cross sections from thresholds up to $11.02\,$GeV. We find clear $\Upsilon(10860)$ and $\Upsilon(11020)$ peaks with little or no continuum contribution. We study the resonant substructure of the $\Upsilon(11020) \to h_b(nP)\pi^+\pi^-$ transitions and find evidence that they proceed entirely via the intermediate isovector states $Z_b(10610)$ and $Z_b(10650)$. The relative fraction of these states is loosely constrained by the current data: the hypothesis that only $Z_b(10610)$ is produced is excluded at the level of 3.3 standard deviations, while the hypothesis that only $Z_b(10650)$ is produced is not excluded at a significant level.Comment: 8 pages, 4 figures, submitted to Physical Review Letter

Evidence of Υ(1S)→J/ψ+χc1\Upsilon(1S) \to J/\psi+\chi_{c1} and search for double-charmonium production in Υ(1S)\Upsilon(1S) and Υ(2S)\Upsilon(2S) decays

Using data samples of $102\times10^6$ $\Upsilon(1S)$ and $158\times10^6$ $\Upsilon(2S)$ events collected with the Belle detector, a first experimental search has been made for double-charmonium production in the exclusive decays $\Upsilon(1S,2S)\rightarrow J/\psi(\psi')+X$, where $X=\eta_c$, $\chi_{cJ} (J=~0,~1,~2)$, $\eta_c(2S)$, $X(3940)$, and $X(4160)$. No significant signal is observed in the spectra of the mass recoiling against the reconstructed $J/\psi$ or $\psi'$ except for the evidence of $\chi_{c1}$ production with a significance of $4.6\sigma$ for $\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}$. The measured branching fraction \BR(\Upsilon(1S)\rightarrow J/\psi+\chi_{c1}) is $(3.90\pm1.21(\rm stat.)\pm0.23 (\rm syst.))\times10^{-6}$. The $90\%$ confidence level upper limits on the branching fractions of the other modes having a significance of less than $3\sigma$ are determined. These results are consistent with theoretical calculations using the nonrelativistic QCD factorization approach.Comment: 12 pages, 4 figures, 1 table. The fit range was extended to include X(4160) signal according to referee's suggestions. Other results unchanged. Paper was accepted for publication as a regular article in Physical Review

Search for the decay B+→K‾∗0K∗+B^+\rightarrow\overline{K}{}^{*0}K^{*+} at Belle

We report a search for the rare charmless decay $B^+\rightarrow\overline{K}{}^{*0}K^{*+}$ using a data sample of $772\times10^6$ $B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. No statistically significant signal is found and a 90% confidence-level upper limit is set on the decay branching fraction as $\mathcal{B}(B^+\rightarrow\overline{K}{}^{*0}K^{*+}) <1.31\times 10^{-6}$.Comment: 8 pages, 3 figures, submitted to PRD(RC

Measurement of the direct CPCP asymmetry in Bˉ→Xs+dγ\bar{B}\rightarrow X_{s+d}\gamma decays with a lepton tag

We report the measurement of the direct $CP$ asymmetry in the radiative $\bar{B}\rightarrow X_{s+d}\gamma$ decay using a data sample of $(772 \pm 11)\times 10^6$ $B\bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. The $CP$ asymmetry is measured as a function of the photon energy threshold. For $E^{\rm{*}}_{\gamma} \geq 2.1~{\rm{GeV}}$, where $E^{\rm{*}}_{\gamma}$ is the photon energy in the center-of-mass frame, we obtain $\mathcal{A}_{CP}(\bar{B}\rightarrow X_{s+d}\gamma)= (2.2 \pm 3.9 \pm 0.9) \%$, consistent with the Standard Model prediction.Comment: Published at PR