A novel population of cholinergic neurons in the macaque spinal dorsal horn of potential clinical relevance for pain therapy.

Endogenous acetylcholine (ACh) is a well-known modulator of nociceptive transmission in the spinal cord of rodents. It arises mainly from a sparse population of cholinergic interneurons located in the dorsal horn of the spinal cord. This population was thought to be absent from the spinal cord of monkey, what might suggest that spinal ACh would not be a relevant clinical target for pain therapy. In humans, however, pain responses can be modulated by spinal ACh, as evidenced by the increasingly used analgesic procedure (for postoperative and labor patients) consisting of the epidural injection of the acetylcholinesterase inhibitor neostigmine. The source and target of this ACh remain yet to be elucidated. In this study, we used an immunolabeling for choline acetyltransferase to demonstrate, for the first time, the presence of a plexus of cholinergic fibers in laminae II-III of the dorsal horn of the macaque monkey. Moreover, we show the presence of numerous cholinergic cell bodies within the same laminae and compared their density and morphological properties with those previously described in rodents. An electron microscopy analysis demonstrates that cholinergic boutons are presynaptic to dorsal horn neurons as well as to the terminals of sensory primary afferents, suggesting that they are likely to modulate incoming somatosensory information. Our data suggest that this newly identified dorsal horn cholinergic system in monkeys is the source of the ACh involved in the analgesic effects of epidural neostigmine and could be more specifically targeted for novel therapeutic strategies for pain management in humans.journal articleresearch support, non-u.s. gov't2013 Feb 27importe

Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination.

Epsilon toxin (ET) is produced by Clostridium perfringens types B and D and causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes and astrocytes, we found that ET (10(-9) M and 10(-7) M) binds to oligodendrocytes, but not to astrocytes. ET induces an increase in extracellular glutamate, and produces oscillations of intracellular Ca(2+) concentration in oligodendrocytes. These effects occurred without any change in the transmembrane resistance of oligodendrocytes, underlining that ET acts through a pore-independent mechanism. Pharmacological investigations revealed that the Ca(2+) oscillations are caused by the ET-induced rise in extracellular glutamate concentration. Indeed, the blockade of metabotropic glutamate receptors type 1 (mGluR1) prevented ET-induced Ca(2+) signals. Activation of the N-methyl-D-aspartate receptor (NMDA-R) is also involved, but to a lesser extent. Oligodendrocytes are responsible for myelinating neuronal axons. Using organotypic cultures of cerebellar slices, we found that ET induced the demyelination of Purkinje cell axons within 24 h. As this effect was suppressed by antagonizing mGluR1 and NMDA-R, demyelination is therefore caused by the initial ET-induced rise in extracellular glutamate concentration. This study reveals the novel possibility that ET can act on oligodendrocytes, thereby causing demyelination. Moreover, it suggests that for certain cell types such as oligodendrocytes, ET can act without forming pores, namely through the activation of an undefined receptor-mediated pathway.journal articleresearch support, non-u.s. gov't2015 Mar2014 10 31importe

A search for the decay B+→K+ννˉB^+ \to K^+ \nu \bar{\nu}

We search for the rare flavor-changing neutral-current decay $B^+ \to K^+ \nu \bar{\nu}$ in a data sample of 82 fb$^{-1}$ collected with the {\sl BABAR} detector at the PEP-II B-factory. Signal events are selected by examining the properties of the system recoiling against either a reconstructed hadronic or semileptonic charged-B decay. Using these two independent samples we obtain a combined limit of ${\mathcal B}(B^+ \to K^+ \nu \bar{\nu})<5.2 \times 10^{-5}$ at the 90% confidence level. In addition, by selecting for pions rather than kaons, we obtain a limit of ${\mathcal B}(B^+ \to \pi^+ \nu \bar{\nu})<1.0 \times 10^{-4}$ using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let

High-reflectivity broadband distributed Bragg reflector lattice matched to ZnTe

We report on the realization of a high quality distributed Bragg reflector with both high and low refractive index layers lattice matched to ZnTe. Our structure is grown by molecular beam epitaxy and is based on binary compounds only. The high refractive index layer is made of ZnTe, while the low index material is made of a short period triple superlattice containing MgSe, MgTe, and ZnTe. The high refractive index step of Delta_n=0.5 in the structure results in a broad stopband and the reflectivity coefficient exceeding 99% for only 15 Bragg pairs.Comment: 4 pages, 3 figure

Improved measurement of CP asymmetries in B-0 ->(c(c)over-bar)K0((*)) decays

We present results on time-dependent CP asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 227x10(6) Upsilon(4S)-> B (B) over bar decays collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. The amplitude of the CPasymmetry, sin2 beta in the standard model, is derived from decay-time distributions from events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B-0 or (0) from its decay products. We measure sin2 beta=0.722 +/- 0.040(stat)+/- 0.023(syst) in agreement with the standard model expectation

CNGS Progress Report 2004

The CNGS project is progressing according to schedule, with the aim to be ready for beam in spring 2006. In this paper, the project status and recent changes to the design of systems and components are summarized. The actions taken in response to the recommendations of the 2003 CNGS Review are described. This report has been drafted in view of the third CNGS Review, held in June 2004

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at root s=10.6 GeV

New measurements of D-s(+) and D-s(*+) meson production rates from B decays and from q(q) over bar continuum events near the Y(4S) resonance are presented. Using 20.8 fb(-1) of data on the Y(4S) resonance and 2.6 fb(-1) off-resonance, we find the inclusive branching fractions B(B-->Ds+X) = (10.93+/-0.19+/-0.58+/-2.73)% and B(B-->Ds*+X) = (7.9+/-0.8+/-0.7+/-2.0)%, where the first error is statistical, the second is systematic, and the third is due to the D-s(+)-->phipi(+) branching fraction uncertainty. The production cross sections sigma(e(+)e(-)-->Ds+X)xB(D-s(+)-->phipi(+)) = 7.55+/-0.20+/-0.34 pb and sigma(e(+)e(-)-->Ds*+/-X)xB(D-s(+)-->phipi(+)) = 5.8+/-0.7+/-0.5 pb are measured at center-of-mass energies about 40 MeV below the Y(4S) mass. The branching fractions SigmaB(B-->D-s((*)+)(D) over bar ((*))) = (5.07+/-0.14+/-0.30+/-1.27)% and SigmaB(B-->D-s(*+)(D) over bar ((*))) = (4.1+/-0.2+/-0.4+/-1.0)% are determined from the D-s((*)+) momentum spectra. The mass difference m(D-s(+)) -m(D+) = 98.4+/-0.1+/-0.3 MeV/c(2) is also measured

Measurement of Ds+ and Ds*+ production in B meson decays and from continuum e+e- annihilation at √s=10.6 GeV

New measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured