Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

Background Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABAA) and metabotropic (GABAB) receptors. GABAB receptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABAB receptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABAB receptors is unclear. Results In order to elucidate the functional relevance of GABAB receptors expressed in peripheral nociceptive neurons in pain modulation we generated and analyzed conditional mouse mutants lacking functional GABAB(1) subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-GABAB(1)-/- mice). Lack of the GABAB(1) subunit precludes the assembly of functional GABAB receptor. We analyzed SNS-GABAB(1)-/- mice and their control littermates in several models of acute and neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-GABAB(1)-/- mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar formalin injection was prolonged in the SNS-GABAB(1)-/- animals as compared to their control littermates. Pharmacological experiments revealed that systemic baclofen-induced inhibition of formalin-induced nociceptive behaviors was not dependent upon GABAB(1) expression in nociceptors. Conclusion This study addressed contribution of GABAB receptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABAB agonist was significantly changed upon a specific deletion of GABAB receptors from peripheral nociceptive neurons in vivo. This lets us conclude that GABAB receptors in the peripheral nervous system play a less important role than those in the central nervous system in the regulation of pain

The Semileptonic BB to K1(1270,1400)K_1(1270,1400) Decays in QCD Sum Rules

We analyze the semileptonic rare decays of $B$ meson to $K_{1} (1270)$ and $K_{1} (1400)$ axial vector mesons. The $B\to K_{1} (1270,1400) \ell^+ \ell^-$ decays are significant flavor changing neutral current decays of the $B$ meson. These decays are sensitive to the new physics beyond SM, since these processes are forbidden at tree level at SM. These decays occurring at the quark level via $b\to s \ell^+ \ell^-$ transition, also provide new opportunities for calculating the CKM matrix elements $V_{bt}$ and $V_{ts}$. In this study, the transition form factors of the $B\to K_{1} (1270,1400) \ell^+ \ell^-$ decays are calculated using three-point QCD sum rules approach. The resulting form factors are used to estimate the branching fractions of these decays.Comment: 18 pages, 7 figures, version to appear in JP

Lack of functional GABA receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression in the medial basal hypothalamus at postnatal day 4

Background/Aims: Adult mice lacking functional GABAB receptors (GABAB1KO) show altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus (POA-AH) and females display disruption of cyclicity and fertility. Here we addressed whether sexual differentiation of the brain and the proper wiring of the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4) GABAB1KO mice. Methods: PND4 wild-type (WT) and GABAB1KO mice of both sexes were sacrificed; tissues were collected to determine mRNA expression (qPCR), amino acids (HPLC), and hormones (RIA and/or IHC). Results: GnRH neuron number (IHC) did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH) was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO males. Hypothalamic GnRH (RIA) was sexually different in WTs (males < females), but this sex difference was lost in GABAB1KOs; the same pattern was observed when analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females. Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males. Serum LH and gonadal estradiol content were also increased in GABAB1KOs. Conclusion: We demonstrate that GABABRs participate in the sexual differentiation of the ARC/MBH, because sex differences in several reproductive genes, such as Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4, probably altering the organization and development of neural circuits governing the reproductive axis. (c) 2013 S. Karger AG, Basel

Search for lepton-flavour-violating decays of Higgs-like bosons.

A search is presented for a Higgs-like boson with mass in the range 45 to 195 GeV/c2 decaying into a muon and a tau lepton. The dataset consists of proton-proton interactions at a centre-of-mass energy of 8 TeV , collected by the LHCb experiment, corresponding to an integrated luminosity of 2 fb-1 . The tau leptons are reconstructed in both leptonic and hadronic decay channels. An upper limit on the production cross-section multiplied by the branching fraction at 95% confidence level is set and ranges from 22 pb for a boson mass of 45 GeV/c2 to 4 pb for a mass of 195 GeV/c2

Disorder and diffuse scattering in single-chirality (TaSe4_4)2_2I crystals

The quasi-one-dimensional chiral compound (TaSe$_4$)$_2$I has been extensively studied as a prime example of a topological Weyl semimetal. Upon crossing its phase transition temperature $T_\textrm{CDW}$ $\approx$ 263 K, (TaSe$_4$)$_2$I exhibits incommensurate charge density wave (CDW) modulations described by the well-defined propagation vector $\sim$(0.05, 0.05, 0.11), oblique to the TaSe$_4$ chains. Although optical and transport properties greatly depend on chirality, there is no systematic report about chiral domain size for (TaSe$_4$)$_2$I. In this study, our single-crystal scattering refinements reveal a bulk iodine deficiency, and Flack parameter measurements on multiple crystals demonstrate that separate (TaSe$_4$)$_2$I crystals have uniform handedness, supported by direct imaging and helicity dependent THz emission spectroscopy. Our single-crystal X-ray scattering and calculated diffraction patterns identify multiple diffuse features and create a real-space picture of the temperature-dependent (TaSe$_4$)$_2$I crystal structure. The short-range diffuse features are present at room temperature and decrease in intensity as the CDW modulation develops. These transverse displacements, along with electron pinning from the iodine deficiency, help explain why (TaSe$_4$)$_2$I behaves as an electronic semiconductor at temperatures above and below $T_\textrm{CDW}$, despite a metallic band structure calculated from density functional theory of the ideal structure.Comment: 24 pages, 20 figures, 3 table

KCTD12 Auxiliary Proteins Modulate Kinetics of GABAB Receptor-Mediated Inhibition in Cholecystokinin-Containing Interneurons

Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABAB receptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins

Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−

The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions

Measurement of the relative rate of prompt χc0, χc1 and χc2 production at √s=7TeV

Prompt production of charmonium χc0, χc1 and χc2 mesons is studied using proton-proton collisions at the LHC at a centre-of-mass energy of √s=7TeV. The χc mesons are identified through their decay to J/ψγ, with J/ψ→μ+mu− using photons that converted in the detector. A data sample, corresponding to an integrated luminosity of 1.0fb−1 collected by the LHCb detector, is used to measure the relative prompt production rate of χc1 and χc2 in the rapidity range 2.0<y<4.5 as a function of the J/ψ transverse momentum from 3 to 20 GeV/c. First evidence for χc0 meson production at a hadron collider is also presented