Cell-autonomous inhibition of alpha 7-containing nicotinic acetylcholine receptors prevents death of parasympathetic neurons during development

Neurotrophic molecules are key retrograde influences of cell survival in the developing nervous system, but other influences such as activity are also emerging as important factors. In the avian ciliary ganglion, half the neurons are eliminated between embryonic day 8 (E8) and E14, but it is not known how cell death is initiated. Because systemic application of alpha7-nicotinic acetylcholine receptor (nAChR) antagonists prevents this cell loss, we examined differences in receptor densities and responses of intracellular calcium to nicotine using the calcium-sensitive dye fura-2. In addition, we determined whether cell-autonomous inhibition of alpha7 activation in neurons prevented cell death. E8 neurons are heterogeneous with respect to alpha7-nAChR density, which leads to large increases in [Ca2+]i in some neurons; E8 neurons also exhibit a slower rate of Ca2+ decay after nicotinic stimulation than E13 neurons. Expressing alpha-bungarotoxin that is tethered to the membrane by a glycosylphosphatidylinositol linkage (GPIalpha btx) in ciliary ganglion neurons with the retroviral vector RCASBP(A) blocks increases in intracellular calcium induced by nicotine through alpha7-nAChRs and prevents neurons from dying. Expression of GPIalpha btx in surrounding non-neural tissues, but not in neurons, does not prevent cell loss. Furthermore, the GPIalpha btx is not efficiently expressed in the accessory oculomotor neurons, eliminating preganglionic inputs as another site for action of the antagonist. These results support the hypothesis that cholinergic inputs facilitate cell death in the developing autonomic nervous system by activating alpha7-nAChRs, possibly by leading to increases in intracellular calcium that exceed the threshold for cell survival

Anomalous peak in the superconducting condensate density of cuprate high T_{c} superconductors at a unique critical doping state

The doping dependence of the superconducting condensate density, n_{s}^{o}, has been studied by muon-spin-rotation for Y_{0.8}Ca_{0.2}Ba_{2}(Cu_{1-z}Zn_{z})_{3}O_{7-\delta} and Tl_{0.5-y}Pb_{0.5+y}Sr_{2}Ca_{1-x}Y_{x}Cu_{2}O_{7}. We find that n_{s}^{o} exhibits a pronounced peak at a unique doping state in the slightly overdoped regime. Its position coincides with the critical doping state where the normal state pseudogap first appears depleting the electronic density of states. A surprising correlation between n_{s}^{o} and the condensation energy U_{o} is observed which suggests unconventional behavior even in the overdoped region.Comment: 10 pages, 3 figure

Resonant Impurity States in the D-Density-Wave Phase

We study the electronic structure near impurities in the d-density-wave (DDW) state, a possible candidate phase for the pseudo-gap region of the high-temperature superconductors. We show that the local DOS near a non-magnetic impurity in the DDW state is {\it qualitatively} different from that in a superconductor with $d_{x^2-y^2}$-symmetry. Since this result is a robust feature of the DDW phase, it can help to identify the nature of the two different phases recently observed by scanning tunneling microscopy experiments in the superconducting state of underdoped Bi-2212 compounds

Antiferromagnetic Order of the Ru and Gd in Superconducting RuSr2GdCu2O8

Neutron diffraction has been used to study the magnetic order in RuSr{2}GdCu2O8. The Ru moments order antiferromagnetically at T{N}=136(2)K, coincident with the previously reported onset of ferromagnetism. Neighboring spins are antiparallel in all three directions, with a low T moment of 1.18(6) mu {B} along the c-axis. Our measurements put an upper limit of ~0.1 mu{B} to any net zero-field moment, with fields exceeding ~0.4T needed to induce a measurable magnetization. The Gd ions order independently at T{N}=2.50(2)K with the same spin configuration. PACS numbers: 74.72.Jt, 75.25.+z, 74.25.Ha, 75.30.KzComment: Four pages, Latex, 5 eps figure

Carbon Free Boston: Technical Summary

Part of a series of reports that includes: Carbon Free Boston: Summary Report; Carbon Free Boston: Social Equity Report; Carbon Free Boston: Buildings Technical Report; Carbon Free Boston: Transportation Technical Report; Carbon Free Boston: Waste Technical Report; Carbon Free Boston: Energy Technical Report; Carbon Free Boston: Offsets Technical Report; Available at http://sites.bu.edu/cfb/OVERVIEW: This technical summary is intended to argument the rest of the Carbon Free Boston technical reports that seek to achieve this goal of deep mitigation. This document provides below: a rationale for carbon neutrality, a high level description of Carbon Free Boston’s analytical approach; a summary of crosssector strategies; a high level analysis of air quality impacts; and, a brief analysis of off-road and street light emissions.Published versio

Magneto-transport study of intra- and intergrain transitions in the magnetic superconductors RuSr2GdCu2O8 and RuSr2(Gd1.5Ce0.5)Cu2O10

A characterization of the magnetic superconductors RuSr2GdCu2O8 [Ru-(1212)] and RuSr2(Gd1.5Ce0.5)Cu2O10 [Ru-(1222)] through resistance measurements as a function of temperature and magnetic field is presented. Two peaks in the derivative of the resistive curves are identified as intra- and intergrain superconducting transitions. Strong intragrain granularity effects are observed, and explained by considering the antiphase boundaries between structural domains of coherently rotated RuO6 octahedra as intragrain Josephson-junctions. A different field dependence of the intragrain transition temperature in these compounds was found. For Ru-(1212) it remains unchanged up to 0.1 T, decreasing for higher fields. In Ru-(1222) it smoothly diminishes with the increase in field even for a value as low as 100 Oe. These results are interpreted as a consequence of a spin-flop transition of the Ru moments. The large separation between the RuO2 layers in Ru-(1222) promotes a weak interlayer coupling, leading the magnetic transition to occur at lower fields. The suppression rate of the intragrain transition temperature is about five times higher for Ru-(1222), a result we relate to an enhancement of the 2D character of the vortex structure. A distinctive difference with conventional cuprates is the sharp increase in amplitude of the intergrain peak in both systems, as the field is raised, which is ascribed to percolation through a fraction of high quality intergrain junctions.Comment: Submitted for Physical Review

Synthesis effects on the magnetic and superconducting properties of RuSr2GdCu2O8

A systematic study on the synthesis of the Ru-1212 compound by preparing a series of samples that were annealed at increasing temperatures and then quenched has been performed. It results that the optimal temperature for the annealing lies around 1060-1065 C; a further temperature increase worsens the phase formation. Structural order is very important and the subsequent grinding and annealing improves it. Even if from the structural point of view the samples appear substantially similar, the physical characterization highlight great differences both in the electrical and magnetic properties related to intrinsic properties of the phase as well as to the connection between the grains as inferred from the resistive and the Curie Weiss behaviour at high temperature as well as in the visibility of ZFC anf FC magnetic signals.Comment: 17 pages, 12 figures. Proc. Int. Workshop " Ruthenate and rutheno-cuprate materials: theory and experiments", Vietri, October 2001. To be published on LNP Series, Springer Verlag, Berlin, C. Noce, A. Vecchione, M. Cuoco, A. Romano Eds, 200

An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence

A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior

Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes α7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons

Vertebrate alpha-bungarotoxin-like molecules of the Ly-6 superfamily have been implicated as balancers of activity and survival in the adult nervous system. To determine whether a member of this family could be involved in the development of the avian ciliary ganglion, we identified 6 Gallus genes by their homology in structure to mouse lynx1 and lynx2. One of these genes, an ortholog of prostate stem cell antigen (psca), is barely detectable at embryonic day (E) 8, before neuronal cell loss in the ciliary ganglion, but increases >100-fold as the number of neurons begins to decline between E9 and E14. PSCA is highly expressed in chicken and mouse telencephalon and peripheral ganglia and correlates with expression of alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs). Misexpressing PSCA before cell death in the ciliary ganglion blocks alpha7-nAChR activation by nicotine and rescues the choroid subpopulation from dying. Thus, PSCA, a molecule previously identified as a marker of prostate cancer, is a member of the Ly-6 neurotoxin-like family in the nervous system, and is likely to play a role as a modulator of alpha7 signaling-induced cell death during development