Proteins from morphologically differentiated neuroblastoma cells promote tubulin polymerization

Clonal cells (N18) of the mouse neuroblastoma C-1300 can be induced to undergo a morphological differentiation characterized by the outgrowth of very long neurites (> 150 microns) that contain many microtubules. Because the marked increase in the number and length of microtubules is apparently not due to an increase in the concentration of tubulin subunits, the possible role of additional macromolecules in the regulation of tubulin polymerization during neurite formation by N18 cells was examined. Using an in vitro system where the polymerization of low concentrations (< 4 mg/ml) of purified brain tubulin requires microtubule-associated proteins (MAPs), high-speed supernates (250,000 g) from neuroblastoma and glioma cells were assayed for their ability to replace MAPs in the polymerization of brain tubulin. Only the supernates from "differentiated" N18 cells were polymerization competent. Electron microscope observations of these supernates failed to demonstrate the presence of nucleation structures (rings or disks). The active factor(s) sedimented at approximately 7S on sucrose gradient centrifugation and eluted from 4B Sepharose in the region of 170,000 mol wt proteins. Furthermore, the inactive supernates from other cells did not inhibit polymerization when tested in the presence of limiting MAPs. Thus, microtubule formation accompanying neurite outgrowth in neuroblastoma cells appears to be regulated by the presence of additional macromolecular factor(s) that may be functionally equivalent to the MAPs found with brain microtubules

Measuring Gravito-magnetic Effects by Multi Ring-Laser Gyroscope

We propose an under-ground experiment to detect the general relativistic effects due to the curvature of space-time around the Earth (de Sitter effect) and to rotation of the planet (dragging of the inertial frames or Lense-Thirring effect). It is based on the comparison between the IERS value of the Earth rotation vector and corresponding measurements obtained by a tri-axial laser detector of rotation. The proposed detector consists of six large ring-lasers arranged along three orthogonal axes. In about two years of data taking, the 1% sensitivity required for the measurement of the Lense-Thirring drag can be reached with square rings of 6 $m$ side, assuming a shot noise limited sensitivity ($20 prad/s/\sqrt{Hz}$). The multi-gyros system, composed of rings whose planes are perpendicular to one or the other of three orthogonal axes, can be built in several ways. Here, we consider cubic and octahedron structures. The symmetries of the proposed configurations provide mathematical relations that can be used to study the stability of the scale factors, the relative orientations or the ring-laser planes, very important to get rid of systematics in long-term measurements, which are required in order to determine the relativistic effects.Comment: 24 pages, 26 Postscript figure

NEMO: A Project for a km3^3 Underwater Detector for Astrophysical Neutrinos in the Mediterranean Sea

The status of the project is described: the activity on long term characterization of water optical and oceanographic parameters at the Capo Passero site candidate for the Mediterranean km$^3$ neutrino telescope; the feasibility study; the physics performances and underwater technology for the km$^3$; the activity on NEMO Phase 1, a technological demonstrator that has been deployed at 2000 m depth 25 km offshore Catania; the realization of an underwater infrastructure at 3500 m depth at the candidate site (NEMO Phase 2).Comment: Proceeding of ISCRA 2006, Erice 20-27 June 200

Repeated administration of the GABAB receptor positive modulator BHF177 decreased nicotine self-administration, and acute administration decreased cue-induced reinstatement of nicotine seeking in rats

Abstract: Rationale $\gamma$-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain and is implicated in the modulation of central reward processes. Acute or chronic administration of GABA$_B$ receptor agonists or positive modulators decreased self-administration of various drugs of abuse. Furthermore, GABA$_B$ receptor agonists inhibited cue-induced reinstatement of nicotine- and cocaine-seeking behavior. Because of their fewer adverse side effects compared with GABA$_B$ receptor agonists, GABA$_B$ receptor positive modulators are potentially improved therapeutic compounds for the treatment of drug dependence compared with agonists. Objectives and methods: We examined whether the acute effects of the GABA$_B$ receptor positive modulator N-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yl]-2-methyl-5-[4-(trifluoromethyl)phenyl]-4-pyrimidinamine (BHF177) on nicotine self- administration and food-maintained responding under a fixed-ratio 5 schedule of reinforcement were maintained after repeated administration. The effects of acute BHF177 administration on cue-induced nicotine- and food-seeking behavior, a putative animal model of relapse, were also examined. Results: Repeated administration of BHF177 for 14 days decreased nicotine self-administration, with small tolerance observed during the last 7 days of treatment, whereas BHF177 minimally affected food-maintained responding. Acute BHF177 administration dose-dependently blocked cue-induced reinstatement of nicotine-, but not food-, seeking behavior after a 10-day extinction period. Conclusions: These results showed that BHF177 selectively blocked nicotine self-administration and prevented cueinduced reinstatement of nicotine seeking, with minimal effects on responding for food and no effect on cue-induced reinstatement of food seeking. Thus, GABA$_B$ receptor positive modulators could be useful therapeutics for the treatment of different aspects of nicotine dependence by facilitating smoking cessation by decreasing nicotine intake and preventing relapse to smoking in humans

Measuring gravito-magnetic effects by multi ring-laser gyroscope

We propose an under-ground experiment to detect the general relativistic effects due to the curvature of space-time around the Earth (de Sitter effect) and to the rotation of the planet (dragging of the inertial frames or Lense-Thirring effect). It is based on the comparison between the IERS value of the Earth rotation vector and corresponding measurements obtained by a tri-axial laser detector of rotation. The proposed detector consists of six large ring-lasers arranged along three orthogonal axes. In about two years of data taking, the 1% sensitivity required for the measurement of the Lense-Thirring drag can be reached with square rings of 6 m side, assuming a shot noise limited sensitivity (20prad/s/sqrt(Hz). The multi-gyros system, composed of rings whose planes are perpendicular to one or the other of three orthogonal axes, can be built in several ways. Here, we consider cubic and octahedral structures. It is shown that the symmetries of the proposed configurations provide mathematical relations that can be used to ensure the long term stability of the apparatus

Measurement of the atmospheric muon depth intensity relation with the NEMO Phase-2 tower

The results of the analysis of the data collected with the NEMO Phase-2 tower, deployed at 3500 m depth about 80 km off-shore Capo Passero (Italy), are presented. Cherenkov photons detected with the photomultipliers tubes were used to reconstruct the tracks of atmospheric muons. Their zenith-angle distribution was measured and the results compared with Monte Carlo simulations. An evaluation of the systematic effects due to uncertainties on environmental and detector parameters is also included. The associated depth intensity relation was evaluated and compared with previous measurements and theoretical predictions. With the present analysis, the muon depth intensity relation has been measured up to 13 km of water equivalent.Comment: submitted to Astroparticle Physic

Dust in the Small Magellanic Cloud: Interstellar Polarization and Extinction

To elucidate the dust properties in the SMC we have for the first time measured linear polarization in five colors in the optical region of the spectrum for a sample of reddened stars. For two of these stars, for which there were no existing UV spectrophotometric measurements, but for which we measured a relatively large polarization, we have also obtained data from the International Ultraviolet Explorer (IUE) in order to study the extinction. The main results are: (1) the wavelength of maximum polarization, $\lambda_{max}$, in the SMC is typically smaller than that in the Galaxy; (2) however, AZV 456, which shows the UV extinction bump, has a $\lambda_{max}$ typical of that in the Galaxy, its polarization curve is narrower, its bump is shifted to shorter wavelengths as compared to the Galaxy and its UV extinction does not conform to the Galactic analytical interpolation curve based on the ratio of total to selective extinction; (3) the 'typical', monotonic SMC extinction curve can be best fit with amorphous carbon and silicate grains; (4) the extinction towards AZV456 may only be explained by assuming a larger gas-to-dust ratio than the observed N(HI)/A(V) value, with a small amount of the available carbon in graphite form; (5) from an analysis of both the extinction and polarization data and our model fits it appears that the SMC has typically smaller grains than those in the Galaxy.Comment: To appear in the ApJ, 50 pages, latex fil

Sensitivity of an underwater Cerenkov km3 telescope to TeV neutrinos from Galactic Microquasars

In this paper are presented the results of Monte Carlo simulations on the capability of the proposed NEMO-km$^3$ telescope to detect TeV muon neutrinos from Galactic microquasars. For each known microquasar we compute the number of detectable events, together with the atmospheric neutrino and muon background events. We also discuss the detector sensitivity to neutrino fluxes expected from known microquasars, optimizing the event selection also to reject the background; the number of events surviving the event selection are given. The best candidates are the steady microquasars SS433 and GX339-4 for which we estimate a sensitivity of about $5\cdot10^{-11}$ erg/cm$^2$ s; the predicted fluxes are expected to be well above this sensitivity. For bursting microquasars the most interesting candidates are Cygnus X-3, GRO J1655-40 and XTE J1118+480: their analyses are more complicated because of the stochastic nature of the bursts.Comment: 20 pages, 3 figures, accepted by Astroparticle Physic