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

High-spin structure in K-40

High-spin states of K-40 have been populated in the fusion-evaporation reaction C-12(Si-30,np)K-40 and studied by means of gamma-ray spectroscopy techniques using one triple-cluster detector of the Advanced Gamma Tracking Array at the Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Legnaro. Several states with excitation energy up to 8 MeV and spin up to 10(-) have been discovered. These states are discussed in terms of J = 3 and T = 0 neutron-proton hole pairs. Shell-model calculations in a large model space have shown good agreement with the experimental data for most of the energy levels. The evolution of the structure of this nucleus is here studied as a function of excitation energy and angular momentum. ©2012 American Physical SocietyWe would like to thank the Swedish National Infrastructure for Computing (SNIC) and the Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) for the computer resources used in parts of the analysis.This work was financed by EURONS AGATA (Contract no. 506065-R113), the Swedish Research Council under contracts 621-2008-4163, 621-2011-4522, 822-2005-3332 and 821-2010-6024, the Japan Society for the Promotion of Science (JSPS) Kakenhi Grant No. 23·01752, Ankara University (BAP Project number 05B4240002), the Polish Ministry of Science and Higher Education under grants number DPN/N190/AGATA/2009 and N N202 073935, the German BMBF under Grants 06K-167, 06KY205I and 06KY9136I, the Knut and Alice Wallenberg Foundation contract number 2005.0184 and STFC (UK). A. Gadea and E. Farnea acknowledge the support of MICINN, Spain, and INFN, Italy through the AIC-D-2011-0746 bilateral action. A. Gadea’s activity has been partially supported by the Generalitat Valenciana, Spain, under grant PROMETEO/2010/101. A. Gadea, A. Jungclaus, A. Poves and B. Quintana acknowledge support from the MICINN, Spain, under grant FPA2011-29854. A. Pove is partially supported by the Comunidad de Madrid (Spain) (HEPHACOS S2009-ESP-1473). G. Jaworski acknowledges the support of the Center for Advanced Studies of Warsaw University of Technology. B. Cederwall acknowledge the support of the Göran Gustafsson FoundationPeer Reviewe

CB1 Cannabinoid Receptor Activation Dose-Dependently Modulates Neuronal Activity within Caudal but not Rostral Song Control Regions of Adult Zebra Finch Telencephalon

CB1 cannabinoid receptors are distinctly expressed at high density within several regions of zebra finch telencephalon including those known to be involved in song learning (lMAN and Area X) and production (HVC and RA). Because: (1) exposure to cannabinoid agonists during developmental periods of auditory and sensory-motor song learning alters song patterns produced later in adulthood and; (2) densities of song region expression of CB1 waxes-and-wanes during song learning, it is becoming clear that CB1 receptor-mediated signaling is important to normal processes of vocal development. To better understand mechanisms involved in cannabinoid modulation of vocal behavior we have investigated the dose-response relationship between systemic cannabinoid exposure and changes in neuronal activity (as indicated by expression of the transcription factor, c- Fos) within telencephalic brain regions with established involvement in song learning and/or control. In adults we have found that low doses (0.1 mg/kg) of the cannabinoid agonist WIN-55212-2 decrease neuronal activity (as indicated by densities of c-fos-expressing nuclei) within vocal motor regions of caudal telencephalon (HVC and RA) while higher doses (3 mg/kg) stimulate activity. Both effects were reversed by pretreatment with the CB1-selective antagonist rimonabant. Interestingly, no effects of cannabinoid treatment were observed within the rostral song regions lMAN and Area X, despite distinct and dense CB1 receptor expression within these areas. Overall, our results demonstrate that, depending on dosage, CB1 agonism can both inhibit and stimulate neuronal activity within brain regions controlling adult vocal motor output, implicating involvement of multiple CB1-sensitive neuronal circuits. Originally published Psychopharmacology, Vol. 199, No. 2, Aug 200

Crystal structure of 1-butyl-2,3-di-methylimidazolium dicarba-7,8-nido-undecaborate

AL thanks Professor Maitland Jones for the generous donation of the starting orthocarborane stock and Dr John Holbrey for the supply of imidazolium halide reagents. The research support by ACS PRF and Cottrell College awards (44692.01-GB and CC6755) is gratefully acknowledged.Peer reviewedPublisher PD

Searches for New Quarks and Leptons Produced in Z-Boson Decay

We have searched for events with new-particle topologies in 390 hadronic Z decays with the Mark II detector at the SLAC Linear Collider. We place 95%-confidence-level lower limits of 40.7 GeV/c^2 for the top-quark mass, 42.0 GeV/c^2 for the mass of a fourth-generation charge - 1/3 quark, and 41.3 GeV/c^2 for the mass of an unstable Dirac neutral lepton

Measurement of Z Decays into Lepton Pairs

We present measurements by the Mark II experiment of the ratios of the leptonic partial widths of the Z boson to the hadronic partial width. The results are Γ_(ee)/Γ_(had)=0.037_(-0.012^()+0.016),Γ_(µµ)/Γ_(had)=0.053-_(0.015)^(+0.020), and Γ_(ττ)/Γ_(had)=0.066_(-0.017)^(+0.021), in good agreement with the standard-model prediction of 0.048. From the average leptonic width result, Γ_(ll)/Γ_(had)=0.053_(-0.009)^(+0.010), we derive Γ_(had)=1.56_(-0.24)^(+0.28) GeV. We find for the vector coupling constants of the tau and muon v_τ^2=0.31±0.31_(-0.30)^(+0.43) and v_μ^2=0.05±0.30_(-0.23)^(+0.34)

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

Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers

The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin), three decongestants (naphazoline, oxymetazoline, xylometazoline) and the antiviral drug oseltamivir’s active metabolite, oseltamivir carboxylate (OC), were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010) and the inter-pandemic periods (May 2011). A large and small wastewater treatment plant (WWTP) were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP’s influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively). Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max = 6,870 and 2,930 ng/L, respectively). Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L) and effluent (696 and 307 ng/L), respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009’s weekly river samples (max = 193 ng/L), but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17–74 ng/L, with clarithromycin (max = 292 ng/L) and erythromycin (max = 448 ng/L) yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater epidemiology approach owing to its nature as a prodrug, recalcitrance and temporally- and spatially-resolved prescription statistics

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