Overexpression of hIGF-1 exclusively in skeletal muscle increases the number of dihydropyridine receptors in adult transgenic mice

AbstractThe number of dihydropyridine receptors (DHPR) and sarcoplasmic reticulum (SR) Ca2+ release channels (RyR1) and their interaction determine the efficacy of the sarcolemmal excitation-SR Ca2+ release-contraction coupling (ECC). Both receptors play a central role in ECC as demonstrated in various animal species and muscle subtypes. In the present work we studied the effect of transgenic overexpression of human insulin-like growth factor 1 (hIGF-1) on the levels of these two Ca2+ channels in extensor digitorum longus (EDL) (fast-twitch), soleus (slow-twitch) and pool of fast- and slow-twitch muscles from adult C57BL/6 mice. Muscles from hIGF-1 transgenic mice showed a significant increase in IGF-1 concentration (20–30-fold) and in the number of DHPR (52% increase) whereas no significant change in RyR1 binding sites was detected. The differential effect on DHPR and RyR1 resulted in a 30% increase in DHPR/RyR1 ratio. Fast- and slow-twitch muscles showed 50 and 70% increase in the number of DHPR and 30 and 80% increase in DHPR/RyR1, respectively. These results support the concept that the increased autocrine/paracrine secretion of hIGF-1 exerts potent stimulatory effects on DHPR α1 subunit expression in adult skeletal muscle

Measurement of hadronic cross section and preliminary results on the pion form factor using the radiative return at DAPHNE

In the fixed energy environment of the $e^{+}e^{-}$ collider DA$\Phi$NE, KLOE can measure the cross section of the process $e^{+}e^{-} \to$ hadrons as a function of the hadronic system energy using the radiative return. At energies below 1 GeV, $e^{+}e^{-} \to \rho \to \pi^{+}\pi^{-}$ is the dominating hadronic process. We report here on the status of the analysis for the e^{+}e^{-} \to \ppg channel, which allows to obtain a preliminary measurement of the pion form factor using an integrated luminosity of $\sim73 pb^{-1}$.Comment: Invited talk at the Seventh International Workshop on Tau Lepton Physics (TAU02-WE07), Santa Cruz, Ca, USA, Sept 2002, 9 pages, LaTeX, 9 eps figure

Measurement of the leptonic decay widths of the phi-meson with the KLOE detector

The phi-meson leptonic widths, Gee and Gmm, are obtained, respectively, from the e+e- forward-backward asymmetry and the muon cross section around the phi-mass energy. We find Gee=1.32⊕0.05⊕0.03 kev and sqrt(GeeGmm)= 1.320⊕0.018⊕0.017 kev. These results, compatible with Gee=Gmm, provide a precise test of lepton universality. Combining the two results gives G_lept=1.320⊕0.023 kev.Comment: 10 pages and 8 figures to be submitted to Phys.Lett.

Upper Limit on the eta to gamma gamma gamma Branching Ratio with the KLOE Detector

We have searched for the C-violating decay eta to gamma gamma gamma in a sample of ~ 18 million eta mesons produced in phi to eta gamma decays, collected with the KLOE detector at the Frascati phi-factory DAFNE. No signal is observed and we obtain the upper limit BR(eta to gamma gamma gamma) less equal than 1.6x10^(-5) at 90 % C.L.Comment: 8 pages, 5 figures Systematic study refined, some figures reordere

Measurement of the branching fraction for the decay KS --> pi e nu

We present a measurement of the branching ratio BR(KS --> pi e nu) performed using the KLOE detector. KS mesons are produced in the reaction e+ e- --> phi --> KS KL at the DAFNE collider. In a sample of about 5 million KS-tagged events we find 624 +- 30 semileptonic KS decays. Normalizing to the KS --> pi+ pi- count in the same data sample, we obtain BR(KS --> pi e nu) = (6.91 +- 0.37) 10^-4, in agreement with the Standard Model expectation.Comment: 9 pages, 5 Encapsulated Postscript figures. Submitted to Phys. Lett.

Measuring the hadronic cross section via radiative return

Recently it has been demonstrated that particle factories, such as DAPHNE and PEP-II, operating at fixed center-of-mass energies, are able to measure hadronic cross sections as a function of the hadronic system energy using the raditive return. This paper is an experimental overview of the progress in this aera. Preliminary results from KLOE for the process e+e- -> \rho \gamma -> \pi+\pi-\gamma and a fit to the pion form factor are presented. Some first results from the BABAR collaboration are also shown.Comment: Invited talk presented at RADCOR/Loops and Legs 2002, Kloster Banz/Germany, September 8-13 2002, 6 pages, 2 Figures; v1: references added, typos correcte

Measurement of Gamma(phi -> eta' gamma)/Gamma(phi -> eta gamma) and the pseudoscalar mixing angle

We have measured the radiative decays phi -> eta gamma, phi ->etaprime gamma selecting pi+ pi- gamma gamma gamma final state in a sample of about 5 times 10^7 phi mesons produced at the Frascati phi factory DAFNE. We obtain Gamma(phi -> etaprime gamma)/Gamma(phi -> eta gamma)=(4.70 +- 0.47 +- 0.31) times 10^-3. From this result we derive new accurate values for the branching ratio BR(phi ->etaprime gamma) = (6.10 +- 0.61 +- 0.43) times 10^-5, and the mixing angle of pseudoscalar mesons in the flavour basis phi_P=(41.8 +1.9 -1.6) degrees.Comment: Submitted to Phys. Lett.

Study of the Decay phi --> eta pi0 gamma with the KLOE detector

In a sample of 5.3x10^7 phi-decays observed with the KLOE detector at the Frascati phi-factory Dafne we find 605 eta pi0 gamma events with eta --> gamma\gamma and 197 eta pi0 gamma events with eta --> pi+ pi- pi0. The decay phi --> eta pi0 gamma is dominated by the process phi --> a0 gamma. From a fit to the eta pi0 mass spectrum we find BR(phi --> ao(980) gamma)= (7.4 +- 0.7)x10^-5.Comment: 12 pages, 6 figures, submitted to Phys.Lett.

Measurement of the ratio Gamma(K_L -> gamma gamma)/Gamma(K_L -> pi^0 pi^0 pi^0) with the KLOE detector

We have measured the ratio R=Gamma(K_L -> gamma gamma)/ \Gamma(K_L -> 3 pi^0) using the KLOE detector. From a sample of ~ 10^9 phi-mesons produced at DAFNE, the Frascati phi-factory, we select ~ 1.6 10^8 K_L-mesons tagged by observing K_S -> pi^+ pi^- following the reaction e^+ e^- -> phi -> K_L K_S. From this sample we select 27,375 K_L -> gamma gamma events and obtain R = (2.79 \pm 0.02_{stat} \pm 0.02_{syst}) \times 10^{-3}. Using the world average value for BR(K_{L} -> 3 pi^0), we obtain BR(K_{L} -> gamma gamma) = (5.89 \pm 0.07 \pm 0.08) \times 10^{-4} where the second error is due to the uncertainty on the 3 pi^0 branching fraction.Comment: 14 page

A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting

Rationale: Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness thatpersists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown. Objectives: To identify the muscle-specific molecular mechanisms responsible for muscle wasting in a mouse model of ALI. Methods:Changes in skeletal muscle weight, fiber size, in vivo contractile performance, and expression of mRNAs and proteins encoding muscle atrophy-associated genes for muscle ring finger-1 (MuRF1) and atrogin1 were measured. Genetic inactivation of MuRF1 or electroporation-mediated transduction of miRNA-based short hairpin RNAs targeting either MuRF1 or atrogin1 were used to identify their role in ALI-associated skeletal muscle wasting. Measurements and Main Results: Mice with ALI developed profound muscle atrophy and preferential loss of muscle contractile proteins associatedwith reducedmuscle function in vivo. Although mRNA expression of the muscle-specific ubiquitin ligases, MuRF1 and atrogin1, was increased in ALI mice, only MuRF1 protein levels were up-regulated. Consistent with these changes, suppression of MuRF1 by genetic or biochemical approaches prevented muscle fiber atrophy, whereas suppression of atrogin1 expression was without effect. Despite resolution of lung injury and down-regulation of MuRF1 and atrogin1, force generation in ALI mice remained suppressed. Conclusions: These data show that MuRF1 is responsible for mediating muscle atrophy that occurs during the period of active lung injury inALI mice and that, as in humans, skeletal muscle dysfunction persists despite resolution of lung injury