Effect of dominant negative SNAP-23 expression on platelet function.

BACKGROUND: The protein SNAP-23 is part of the secretory pathway in platelets. It is, however, not entirely clear to what extent this protein contributes to the secretory function of platelets. Therefore, we overexpressed a dominant negative mutant with a novel technology that allows the creation of intact transgene-expressing platetets. RESULTS: Overexpression of a dominant negative SNAP-23 mutant that inhibited the binding of the native protein to the docking site within the secretory machinery resulted in significant suppression of the agonist-dependent surface recruitment of P-selectin and CD40L. Simultaneously, release from dense granules was clearly suppressed in the presence of this construct. Also agonist-dependent surface expression of fibrinogen receptor markers CD41 and CD61 was reduced, and agonist-triggered aggregation was inhibited. CONCLUSION: The dominant negative inhibition of SNAP-23 resulted in clear effects on platelet functions. The novel method using recombinant culture-derived platelets allowed the rapid clarification of the functional importance of this protein in intact platelets.

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

Deeply bound 1s and 2p pionic states in 205Pb and determination of the s-wave part of the pion-nucleus interaction.

We observed well-separated 1s and 2p pi(-) states in 205Pb in the 206Pb(d,3He) reaction at T(d) = 604.3 MeV. The binding energies and the widths determined are B(1s) = 6.762+/-0.061 MeV, Gamma(1s) = 0.764(+0.154)(-0.171) MeV, B(2p) = 5.110+/-0.045 MeV, and Gamma(2p) = 0.321(-0.062)(+0.060) MeV. They are used to deduce the real and imaginary strengths of the s-wave part of the pion-nucleus interaction, which translates into a positive mass shift of pi(-) in 205Pb.

Blocking caspase-activated apoptosis improves contractility in failing myocardium.

Cardiac myocyte apoptosis has been demonstrated in end-stage failing human hearts. The therapeutic utility of blocking apoptosis in congestive heart failure (CHF) has not been elucidated. This study investigated the role of caspase activation in cardiac contractility and sarcomere organization in the development of CHF. In a rabbit model of heart failure obtained by rapid ventricular pacing, we demonstrate, using in vivo transcoronary adenovirus-mediated gene delivery of the potent caspase inhibitor p35, that caspase activation is associated with a reduction in contractile force of failing myocytes by destroying sarcomeric structure. In this animal model gene transfer of p35 prevented the rise in caspase 3 activity and DNA-histone formation. Genetically manipulated hearts expressing p35 had a significant improvement in left ventricular pressure rise (+dp/dt), decreased end-diastolic chamber pressure (LVEDP), and the development of heart failure was delayed. To better understand this benefit, we examined the effects of caspase 3 on cardiomyocyte dysfunction in vitro. Microinjection of activated caspase 3 into the cytoplasm of intact myocytes induced sarcomeric disorganization and reduced contractility of the cells. These results demonstrate a direct impact of caspases on cardiac function and may lead to novel therapeutic strategies via antiapoptotic regimens.

Antilambda production in Au+Au collisions at 11.7A GeV/c.

We present results for antilambda and antiproton production in Au+Au collisions at 11.7 A GeV/c including spectra and extracted invariant yields for both species in central and peripheral collisions in the rapidity range 1.0

Baryon rapidity loss in relativistic Au + Au collisions.

An excitation function of proton rapidity distributions for different centralities is reported from AGS Experiment E917 for Au+Au collisions at 6, 8, and 10.8 GeV/nucleon. The rapidity distributions from peripheral collisions have a valley at midrapidity which smoothly change to distributions that display a broad peak at midrapidity for central collisions. The mean rapidity loss increases with increasing beam energy, whereas the fraction of protons consistent with isotropic emission from a stationary source at midrapidity decreases with increasing beam energy. The data suggest that the stopping is substantially less than complete at these energies.