The evolution and comparative neurobiology of endocannabinoid signalling

CB(1)- and CB(2)-type cannabinoid receptors mediate effects of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide in mammals. In canonical endocannabinoid-mediated synaptic plasticity, 2-AG is generated postsynaptically by diacylglycerol lipase alpha and acts via presynaptic CB(1)-type cannabinoid receptors to inhibit neurotransmitter release. Electrophysiological studies on lampreys indicate that this retrograde signalling mechanism occurs throughout the vertebrates, whereas system-level studies point to conserved roles for endocannabinoid signalling in neural mechanisms of learning and control of locomotor activity and feeding. CB(1)/CB(2)-type receptors originated in a common ancestor of extant chordates, and in the sea squirt Ciona intestinalis a CB(1)/CB(2)-type receptor is targeted to axons, indicative of an ancient role for cannabinoid receptors as axonal regulators of neuronal signalling. Although CB(1)/CB(2)-type receptors are unique to chordates, enzymes involved in biosynthesis/inactivation of endocannabinoids occur throughout the animal kingdom. Accordingly, non-CB(1)/CB(2)-mediated mechanisms of endocannabinoid signalling have been postulated. For example, there is evidence that 2-AG mediates retrograde signalling at synapses in the nervous system of the leech Hirudo medicinalis by activating presynaptic transient receptor potential vanilloid-type ion channels. Thus, postsynaptic synthesis of 2-AG or anandamide may be a phylogenetically widespread phenomenon, and a variety of proteins may have evolved as presynaptic (or postsynaptic) receptors for endocannabinoids

Structure of 55Sc and development of the N=34 subshell closure

The low-lying structure of $^{55}$Sc has been investigated using in-beam $\gamma$-ray spectroscopy with the $^{9}$Be($^{56}$Ti,$^{55}$Sc+$\gamma$)$X$ one-proton removal and $^{9}$Be($^{55}$Sc,$^{55}$Sc+$\gamma$)$X$ inelastic-scattering reactions at the RIKEN Radioactive Isotope Beam Factory. Transitions with energies of 572(4), 695(5), 1539(10), 1730(20), 1854(27), 2091(19), 2452(26), and 3241(39) keV are reported, and a level scheme has been constructed using $\gamma\gamma$ coincidence relationships and $\gamma$-ray relative intensities. The results are compared to large-scale shell-model calculations in the $sd$-$pf$ model space, which account for positive-parity states from proton-hole cross-shell excitations, and to it ab initio shell-model calculations from the in-medium similarity renormalization group that includes three-nucleon forces explicitly. The results of proton-removal reaction theory with the eikonal model approach were adopted to aid identification of positive-parity states in the level scheme; experimental counterparts of theoretical $1/2^{+}_{1}$ and $3/2^{+}_{1}$ states are suggested from measured decay patterns. The energy of the first $3/2^{-}$ state, which is sensitive to the neutron shell gap at the Fermi surface, was determined. The result indicates a rapid weakening of the $N=34$ subshell closure in $pf$-shell nuclei at $Z>20$, even when only a single proton occupies the $\pi f_{7/2}$ orbital

Cannabinoid exposure during zebra finch sensorimotor vocal learning persistently alters expression of endocannabinoid signaling elements and acute agonist responsiveness

<p>Abstract</p> <p>Background</p> <p>Previously we have found that cannabinoid treatment of zebra finches during sensorimotor stages of vocal development alters song patterns produced in adulthood. Such persistently altered behavior must be attributable to changes in physiological substrates responsible for song. We are currently working to identify the nature of such physiological changes, and to understand how they contribute to altered vocal learning. One possibility is that developmental agonist exposure results in altered expression of elements of endocannabinoid signaling systems. To test this hypothesis we have studied effects of the potent cannabinoid receptor agonist WIN55212-2 (WIN) on endocannabinoid levels and densities of CB₁immunostaining in zebra finch brain.</p> <p>Results</p> <p>We found that late postnatal WIN treatment caused a long-term global disregulation of both levels of the endocannabinoid, 2-arachidonyl glycerol (2-AG) and densities of CB₁immunostaining across brain regions, while repeated cannabinoid treatment in adults produced few long-term changes in the endogenous cannabinoid system.</p> <p>Conclusions</p> <p>Our findings indicate that the zebra finch endocannabinoid system is particularly sensitive to exogenous agonist exposure during the critical period of song learning and provide insight into susceptible brain areas.</p

Central Pb+Pb Collisions at 158 A GeV/c Studied by Pion-Pion Interferometry

Two-particle correlations have been measured for identified negative pions from central 158 AGeV Pb+Pb collisions and fitted radii of about 7 fm in all dimensions have been obtained. A multi-dimensional study of the radii as a function of kT is presented, including a full correction for the resolution effects of the apparatus. The cross term Rout-long of the standard fit in the Longitudinally CoMoving System (LCMS) and the vl parameter of the generalised Yano-Koonin fit are compatible with 0, suggesting that the source undergoes a boost invariant expansion. The shapes of the correlation functions in Qinv and Qspace have been analyzed in detail. They are not Gaussian but better represented by exponentials. As a consequence, fitting Gaussians to these correlation functions may produce different radii depending on the acceptance of the experimental setup used for the measurement.Comment: 13 pages including 10 figure

Bayesian and Markov chain Monte Carlo methods for identifying nonlinear systems in the presence of uncertainty

In this paper, the authors outline the general principles behind an approach to Bayesian system identification and highlight the benefits of adopting a Bayesian framework when attempting to identify models of nonlinear dynamical systems in the presence of uncertainty. It is then described how, through a summary of some key algorithms, many of the potential difficulties associated with a Bayesian approach can be overcome through the use of Markov chain Monte Carlo (MCMC) methods. The paper concludes with a case study, where an MCMC algorithm is used to facilitate the Bayesian system identification of a nonlinear dynamical system from experimentally observed acceleration time histories

Search for Heavy Neutral and Charged Leptons in e+ e- Annihilation at LEP

A search for exotic unstable neutral and charged heavy leptons as well as for stable charged heavy leptons is performed with the L3 detector at LEP. Sequential, vector and mirror natures of heavy leptons are considered. No evidence for their existence is found and lower limits on their masses are set