Modulation of human cardiac transient outward potassium current by EGFR tyrosine kinase and Src-family kinases

Aims: The human cardiac transient outward K + current Ito (encoded by Kv4.3 or KCND3) plays an important role in phase 1 rapid repolarization of cardiac action potentials in the heart. However, modulation of I to by intracellular signal transduction is not fully understood. The present study was therefore designed to determine whether/how human atrial I to and hKv4.3 channels stably expressed in HEK 293 cells are regulated by protein tyrosine kinases (PTKs). Methods and results: Whole-cell patch voltage-clamp, immunoprecipitation, western blotting, and site-directed mutagenesis approaches were employed in the present study. We found that human atrial I to was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. The inhibitory effect was countered by the protein tyrosine phosphatase inhibitor orthovanadate. In HEK 293 cells stably expressing human KCND3, genistein, AG556, and PP2 significantly reduced the hKv4.3 current, and the reduction was antagonized by orthovanadate. Interestingly, orthovanadate also reversed the reduced tyrosine phosphorylation level of hKv4.3 channels by genistein, AG556, or PP2. Mutagenesis revealed that the hKv4.3 mutant Y136F lost the inhibitory response to AG556, while Y108F lost response to PP2. The double-mutant Y108FY136F hKv4.3 channels showed no response to either AG556 or PP2. Conclusion: Our results demonstrate that human atrial Ito and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue; tyrosine phosphorylation of the channel may be involved in regulating cardiac electrophysiology. © The Author 2011.postprin

Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice.

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Insensitivity of Human iPS Cells-derived Mesenchymal Stem Cells to Interferon-γ -induced HLA Expression Potentiates Repair Efficiency of Hind Limb Ischemia in Immune Humanized NOD Scid Gamma Mice

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Resonances in J/ψ→ϕπ+π−J/\psi \to \phi \pi ^+\pi ^- and ϕK+K−\phi K^+K^-

A partial wave analysis is presented of $J/\psi \to \phi \pi ^+\pi ^-$ and $\phi K^+K^-$ from a sample of 58M $J/\psi$ events in the BES II detector. The $f_0(980)$ is observed clearly in both sets of data, and parameters of the Flatt\' e formula are determined accurately: $M = 965 \pm 8$ (stat) $\pm 6$ (syst) MeV/c$^2$, $g_1 = 165 \pm 10 \pm 15$ MeV/c$^2$, $g_2/g_1 = 4.21 \pm 0.25 \pm 0.21$. The $\phi \pi \pi$ data also exhibit a strong $\pi \pi$ peak centred at $M = 1335$ MeV/c$^2$. It may be fitted with $f_2(1270)$ and a dominant $0^+$ signal made from $f_0(1370)$ interfering with a smaller $f_0(1500)$ component. There is evidence that the $f_0(1370)$ signal is resonant, from interference with $f_2(1270)$. There is also a state in $\pi \pi$ with $M = 1790 ^{+40}_{-30}$ MeV/c$^2$ and $\Gamma = 270 ^{+60}_{-30}$ MeV/c$^2$; spin 0 is preferred over spin 2. This state, $f_0(1790)$, is distinct from $f_0(1710)$. The $\phi K\bar K$ data contain a strong peak due to $f_2'(1525)$. A shoulder on its upper side may be fitted by interference between $f_0(1500)$ and $f_0(1710)$.Comment: 17 pages, 6 figures, 1 table. Submitted to Phys. Lett.

Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

Search for K_S K_L in psi'' decays

K_S K_L from psi'' decays is searched for using the psi'' data collected by BESII at BEPC, the upper limit of the branching fraction is determined to be B(psi''--> K_S K_L) < 2.1\times 10^{-4} at 90% C. L. The measurement is compared with the prediction of the S- and D-wave mixing model of the charmonia, based on the measurements of the branching fractions of J/psi-->K_S K_L and psi'-->K_S K_L.Comment: 5 pages, 1 figur

First Measurements of eta_c Decaying into K^+K^-2(pi^+pi^-) and 3(pi^+pi^-)

The decays of eta_c to K^+K^-2(pi^+pi^-) and 3(pi^+pi^-) are observed for the first time using a sample of 5.8X10^7 J/\psi events collected by the BESII detector. The product branching fractions are determined to be B(J/\psi-->gamma eta_c)*B(eta_c-->K^+K^-pi^+pi^-pi^+pi^-)=(1.21+-0.32+- 0.23)X10^{-4}$,B(J/\psi-->gamma eta_c)*B(eta_c-->K^{*0}\bar{K}^{*0}pi^+pi^-)= (1.29+-0.43+-0.32)X10^{-4}$, and (J/\psi-->gamma eta_c)* B(eta_c-->pi^+pi^-pi^+pi^-pi^+pi^-)= (2.59+-0.32+-0.48)X10^{-4}. The upper limit for eta_c-->phi pi^+pi^-pi^+pi^- is also obtained as B(J/\psi-->gamma eta_c)*B(eta_c--> phi pi^+pi^-pi^+pi^-)< 6.03 X10^{-5} at the 90% confidence level.Comment: 11 pages, 4 figure

First observation of psi(2S)-->K_S K_L

The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Study of psi(2S) decays to X J/psi

Using J/psi -> mu^+ mu^- decays from a sample of approximately 4 million psi(2S) events collected with the BESI detector, the branching fractions of psi(2S) -> eta J/psi, pi^0 pi^0 J/psi, and anything J/psi normalized to that of psi(2S) -> pi^+ pi^- J/psi are measured. The results are B(psi(2S) -> eta J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.098 \pm 0.005 \pm 0.010, B(psi(2S) -> pi^0 pi^0 J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.570 \pm 0.009 \pm 0.026, and B(psi(2S) -> anything J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 1.867 \pm 0.026 \pm 0.055.Comment: 13 pages, 8 figure

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

&lt;b&gt;BACKGROUND:&lt;/b&gt; In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.&lt;p&gt;&lt;/p&gt