156 research outputs found
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 Ξ±2Ξ΄3 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 PIP5KΞ± and PI3KΞ³ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3KΞ³ kinase-dead knock-in mice to PI3KΞ³ lipid kinase activity. Using single primary sensory neuron recording, PI3KΞ³ 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. Β© 2012 Neely et al
Bioinformatics in China: A Personal Perspective
Biochemical Research MethodsMathematical & Computational BiologySCI(E)PubMed3EDITORIAL MATERIAL4e1000020
Measurement of the matrix element for the decay Ξ·β²βΞ·Ο +Ο -
The Dalitz plot of Ξ·ββ²βΞ·Οβ+Οβ- decay is studied using (225.2Β±2.8)Γ106 J/Ο events collected with the BESIII detector at the BEPCII eβ+eβ- collider. With the largest sample of Ξ·ββ² decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ΟβΞ³Ξ·ββ² is determined to be (4.84Β±0.03Β±0.24)Γ10β-3, where the first error is statistical and the second systematic. Β© 2011 American Physical Society.published_or_final_versio
First observation of the decays ΟcJβΟ0Ο0Ο0Ο0
We present a study of the P-wave spin-triplet charmonium Ο cJ decays (J=0, 1, 2) into Ο0Ο0Ο0Ο0. The analysis is based on 106Γ106 Οββ² decays recorded with the BESIII detector at the BEPCII electron positron collider. The decay into the Ο0Ο0Ο0Ο0 hadronic final state is observed for the first time. We measure the branching fractions B(Ο c0βΟ0Ο0Ο0Ο0)=(3.34Β±0. 06Β±0.44)Γ10β-3, B(Ο c1βΟ0Ο0Ο0Ο0) =(0.57Β±0.03Β±0.08)Γ10β-3, and B(Ο c2βΟ0Ο0Ο0Ο0)=(1.21Β±0.05Β±0.16) Γ10β-3, where the uncertainties are statistical and systematical, respectively. Β© 2011 American Physical Society.published_or_final_versio
Study of a00(980)-f0(980) mixing
Using samples of 2.25Γ108 J/Ο events and 1.06Γ108 Ο β² events collected with the BES III detector, we study the f 0(980)βa00(980) and a00(980)βf 0(980) transitions in the processes J/ΟβΟf 0(980) βΟa00(980) and Ο c1βΟ0a00(980)βΟ0f 0(980), respectively. Evidence for f 0(980)βa00(980) is found with a significance of 3.4Ο, while in the case of a00(980)βf 0(980) transition, the significance is 1.9Ο. Measurements and upper limits of both branching ratios and mixing intensities are determined. Β© 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 states to
final states are presented. Intermediate and resonance states are observed, and
branching fractions for ,
, and are reported. We also
measure branching fractions for direct
decays. These are first observations of decays to unstable baryon
resonances and provide useful information about the states. The
experiment uses samples of mesons produced via radiative
transitions from 106 million mesons collected in the BESIII
detector at the BEPCII collider.Comment: 16 pages, 5 figure
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