Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival

Additive Antinociceptive Effects of a Combination of Vitamin C and Vitamin E after Peripheral Nerve Injury

Accumulating evidence indicates that increased generation of reactive oxygen species (ROS) contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states

Construction of a Global Pain Systems Network Highlights Phospholipid Signaling as a Regulator of Heat Nociception

The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. © 2012 Neely et al

Bioinformatics in China: A Personal Perspective

Biochemical Research MethodsMathematical & Computational BiologySCI(E)PubMed3EDITORIAL MATERIAL4e1000020

Study of a00(980)-f0(980) mixing

Using samples of 2.25×108 J/ψ events and 1.06×108 ψ ′ events collected with the BES III detector, we study the f 0(980)→a00(980) and a00(980)→f 0(980) transitions in the processes J/ψ→φf 0(980) →φa00(980) and χ c1→π0a00(980)→π0f 0(980), respectively. Evidence for f 0(980)→a00(980) is found with a significance of 3.4σ, while in the case of a00(980)→f 0(980) transition, the significance is 1.9σ. Measurements and upper limits of both branching ratios and mixing intensities are determined. © 2011 American Physical Society.published_or_final_versio

Observation of \chi_{cJ} decaying into the p\bar{p}K^{+}K^{-} final state

First measurements of the decays of the three $\chi_{cJ}$ states to $p\bar{p}K^{+}K^{-}$ final states are presented. Intermediate $\phi\to K^{+}K^{-}$ and $\Lambda(1520)\to pK^{-}$ resonance states are observed, and branching fractions for $\chi_{cJ}\to \bar{p}K^{+}\Lambda(1520)$, $\Lambda(1520) \bar{\Lambda}(1520)$, and $\phi p\bar{p}$ are reported. We also measure branching fractions for direct $\chi_{cJ}\to p\bar{p} K^{+}K^{-}$ decays. These are first observations of $\chi_{cJ}$ decays to unstable baryon resonances and provide useful information about the $\chi_{cJ}$ states. The experiment uses samples of $\chi_{cJ}$ mesons produced via radiative transitions from 106 million $\psi^{\prime}$ mesons collected in the BESIII detector at the BEPCII $e^+e^-$ collider.Comment: 16 pages, 5 figure

Evidence for psi' decays into gamma pi^0 and gamma eta

The decays psi'->gamma pi^0, gamma eta and gamma eta' are studied using data collected with the BESIII detector at the BEPCII e^+e^- collider. Processes psi'->gamma pi^0 and psi'->gamma eta are observed for the first time with signal significances of 4.6 sigma and 4.3 sigma, respectively. The branching fractions are determined to be: B(psi'->gamma pi^0)=(1.58+-0.40+-0.13)x10^{-6}, B(psi'->gamma eta)=(1.38+-0.48+-0.09)x10^{-6}, and B(psi'->gamma eta')=(126+-3+-8) x 10^{-6}, where the first errors are statistical and the second ones systematic.Comment: 6 pages, 4 figure