Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP

Protein misfolding is linked to different neurodegenerative disorders like Alzheimer’s disease, polyglutamine, and prion diseases. We investigated the cytotoxic effects of aberrant conformers of the prion protein (PrP) and show that toxicity is specifically linked to misfolding of PrP in the cytosolic compartment and involves binding of PrP to the anti-apoptotic protein Bcl-2. PrP targeted to different cellular compartments, including the cytosol, nucleus, and mitochondria, adopted a misfolded and partially proteinase K–resistant conformation. However, only in the cytosol did the accumulation of misfolded PrP induce apoptosis. Apoptotic cell death was also induced by two pathogenic mutants of PrP, which are partially localized in the cytosol. A mechanistic analysis revealed that the toxic potential is linked to an internal domain of PrP (amino acids 115–156) and involves coaggregation of cytosolic PrP with Bcl-2. Increased expression of the chaperones Hsp70 and Hsp40 prevented the formation of PrP/Bcl-2 coaggregates and interfered with PrP-induced apoptosis. Our study reveals a compartment-specific toxicity of PrP misfolding that involves coaggregation of Bcl-2 and indicates a protective role of molecular chaperones

CASTOR: Centauro and Strange Object Research in nucleus-nucleus collisions at LHC

We describe the CASTOR detector designed to probe the very forward, baryon-rich rapidity region in nucleus-nucleus collisions at the LHC. We present a phenomenological model describing the formation of a QGP fireball in a high baryochemical potential environment, and its subsequent decay into baryons and strangelets. The model explains Centauros and the long-penetrating component and makes predictions for the LHC. Simulations of Centauro-type events were done. To study the response of the apparatus to new effects different exotic species (DCC, Centauros, strangelets etc.) were passed through the deep calorimeter. The energy deposition pattern in the calorimeter appears to be a new clear signature of the QGP.Comment: Talk given by E. Gladysz-Dziadus for the CASTOR group, Intern. Workshop on Nuclear Theory, 10-15 June, 2002, Bulgaria, Rila Mountains, 15 pages, 14 figure

Particle abundances and spectra in the hydrodynamical description of relativistic nuclear collisions with light projectiles

We show that a hydrodynamical model with continuous particle emission instead of sudden freeze out may explain both the observed strange particle and pion abundances and transverse mass spectra for light projectile at SPS energy. We found that the observed enhancement of pion production corresponds, within the context of continuous emission, to the maximal entropy production.Comment: 11 pages, 2 figure

Thermal Hadron Production in High Energy Heavy Ion Collisions

We provide a method to test if hadrons produced in high energy heavy ion collisions were emitted at freeze-out from an equilibrium hadron gas. Our considerations are based on an ideal gas at fixed temperature $T_f$, baryon number density $n_B$, and vanishing total strangeness. The constituents of this gas are all hadron resonances up to a mass of 2 GeV; they are taken to decay according to the experimentally observed branching ratios. The ratios of the various resulting hadron production rates are tabulated as functions of $T_f$ and $n_B$. These tables can be used for the equilibration analysis of any heavy ion data; we illustrate this for some specific cases.Comment: 12 pages (not included :13 figures + tables) report CERN-TH 6523/92 and Bielefeld preprint BI-TP 92/0

Characterization of ovarian follicle reserve depletion in Ames dwarf mice.

Publicado: Proceedings of the 29th Annual Meeting of the Brazilian Embryo Technology Society (SBTE); Gramado, RS, Brazil, August 20th to 23rd, 2015, and 31st Meeting of the European Embryo Transfer Association (AETE); Ghent, Belgium, September 11th and 12th, 2015. Abstracts

Disruption of Growth Hormone Receptor Prevents Calorie Restriction from Improving Insulin Action and Longevity

Most mutations that delay aging and prolong lifespan in the mouse are related to somatotropic and/or insulin signaling. Calorie restriction (CR) is the only intervention that reliably increases mouse longevity. There is considerable phenotypic overlap between long-lived mutant mice and normal mice on chronic CR. Therefore, we investigated the interactive effects of CR and targeted disruption or knock out of the growth hormone receptor (GHRKO) in mice on longevity and the insulin signaling cascade. Every other day feeding corresponds to a mild (i.e. 15%) CR which increased median lifespan in normal mice but not in GHRKO mice corroborating our previous findings on the effects of moderate (30%) CR on the longevity of these animals. To determine why insulin sensitivity improves in normal but not GHRKO mice in response to 30% CR, we conducted insulin stimulation experiments after one year of CR. In normal mice, CR increased the insulin stimulated activation of the insulin signaling cascade (IR/IRS/PI3K/AKT) in liver and muscle. Livers of GHRKO mice responded to insulin by increased activation of the early steps of insulin signaling, which was dissipated by altered PI3K subunit abundance which putatively inhibited AKT activation. In the muscle of GHRKO mice, there was elevated downstream activation of the insulin signaling cascade (IRS/PI3K/AKT) in the absence of elevated IR activation. Further, we found a major reduction of inhibitory Ser phosphorylation of IRS-1 seen exclusively in GHRKO muscle which may underpin their elevated insulin sensitivity. Chronic CR failed to further modify the alterations in insulin signaling in GHRKO mice as compared to normal mice, likely explaining or contributing to the absence of CR effects on insulin sensitivity and longevity in these long-lived mice

Remnants of Initial Anisotropic High Energy Density Domains in Nucleus-Nucleus Collisions

Anisotropic high energy density domains may be formed at early stages of ultrarelativistic heavy ion collisions, e.g. due to phase transition dynamics or non-equilibrium phenomena like (mini-)jets. Here we investigate hadronic observables resulting from an initially created anisotropic high energy density domain. Based on our studies using a transport model we find that the initial anisotropies are reflected in the freeze-out multiplicity distribution of both pions and kaons due to secondary hadronic rescattering. The anisotropy appears to be stronger for particles at high transverse momenta. The overall kaon multiplicity increases with large fluctuations of local energy densities, while no change has been found in the pion multiplicity.Comment: Submitted to PR

Enhancement of singly and multiply strangeness in p-Pb and Pb-Pb collisions at 158A GeV/c

The idea that the reduction of the strange quark suppression in string fragmentation leads to the enhancement of strange particle yield in nucleus-nucleus collisions is applied to study the singly and multiply strange particle production in p-Pb and Pb-Pb collisions at 158A GeV/c. In this mechanism the strange quark suppression factor is related to the effective string tension, which increases in turn with the increase of the energy, of the centrality and of the mass of colliding system. The WA97 observation that the strange particle enhancement increases with the increasing of centrality and of strange quark content in multiply strange particles in Pb-Pb collisions with respect to p-Pb collisions was accounted reasonably.Comment: 8 pages, 3 PostScript figures, in Latex form. submitted to PR

Thermal phenomenology of hadrons from 200 AGeV S+S collisions

We develop a complete and consistent description for the hadron spectra from heavy ion collisions in terms of a few collective variables, in particular temperature, longitudinal and transverse flow. To achieve a meaningful comparison with presently available data, we also include the resonance decays into our picture. To disentangle the influences of transverse flow and resonance decays in the $m_T$-spectra, we analyse in detail the shape of the $m_T$-spectra.Comment: 31 pages, 13 figs in seperate uuencoded file, for LaTeX, epsf.sty and dvips, TPR-93-16 and BNL-(no number yet