University of Naples Federico II

About: University of Naples Federico II is a education organization based out in Naples, Campania, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29291 authors who have published 68803 publications receiving 1920149 citations. The organization is also known as: Università degli Studi di Napoli Federico II & Naples University.

Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism

Abstract: Peripheral cannabinoid receptors exert a powerful inhibitory control over pain initiation, but the endocannabinoid signal that normally engages this intrinsic analgesic mechanism is unknown. To address this question, we developed a peripherally restricted inhibitor (URB937) of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of the endocannabinoid anandamide. URB937 suppressed FAAH activity and increased anandamide levels outside the rodent CNS. Despite its inability to access brain and spinal cord, URB937 attenuated behavioral responses indicative of persistent pain in rodent models of peripheral nerve injury and inflammation and prevented noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CB₁ cannabinoid receptor blockade prevented these effects. These results suggest that anandamide-mediated signaling at peripheral CB₁ receptors controls the access of pain-related inputs to the CNS. Brain-impenetrant FAAH inhibitors, which strengthen this gating mechanism, might offer a new approach to pain therapy.

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6E20 protons on target

Abstract: We report on measurements of neutrino oscillation using data from the T2K long-baseline neutrino experiment collected between 2010 and 2013. In an analysis of muon neutrino disappearance alone, we find the following estimates and 68% confidence intervals for the two possible mass hierarchies: Normal Hierarchy: $\sin^2\theta_{23}=0.514^{+0.055}_{-0.056}$ and $\Delta m^2_{32}=(2.51\pm0.10)\times 10^{-3}$ eV$^2$/c$^4$ Inverted Hierarchy: $\sin^2\theta_{23}=0.511\pm0.055$ and $\Delta m^2_{13}=(2.48\pm0.10)\times 10^{-3}$ eV$^2$/c$^4$ The analysis accounts for multi-nucleon mechanisms in neutrino interactions which were found to introduce negligible bias. We describe our first analyses that combine measurements of muon neutrino disappearance and electron neutrino appearance to estimate four oscillation parameters and the mass hierarchy. Frequentist and Bayesian intervals are presented for combinations of these parameters, with and without including recent reactor measurements. At 90% confidence level and including reactor measurements, we exclude the region: $\delta_{CP}=[0.15,0.83]\pi$ for normal hierarchy and $\delta_{CP}=[-0.08,1.09]\pi$ for inverted hierarchy. The T2K and reactor data weakly favor the normal hierarchy with a Bayes Factor of 2.2. The most probable values and 68% 1D credible intervals for the other oscillation parameters, when reactor data are included, are: $\sin^2\theta_{23}=0.528^{+0.055}_{-0.038}$ and $|\Delta m^2_{32}|=(2.51\pm0.11)\times 10^{-3}$ eV$^2$/c$^4$.

A new pattern for helix-turn-helix recognition revealed by the PU.1 ETS-domain-DNA complex.

Abstract: THE Ets family of transcription factors, of which there are now about 35 members1,2, regulate gene expression during growth and development. They share a conserved domain of around 85 amino acids3 which binds as a monomer to the DNA sequence 5'-C/ AGGAA/T-3'. We have determined theocrystal structure of an ETS domain complexed with DNA, at 2.3-A resolution. The domain is similar to α+β (winged) 'helix–turn–helix' proteins and interacts with a ten-base-pair region of duplex DNA which takes up a uniform curve of 8°. The domain contacts the DNA by a novel loop–helix–loop architecture. Four of the amino acids that directly interact with the DNA are highly conserved: two arginines from the recognition helix lying in the major groove, one lysine from the 'wing' that binds upstream of the core GGAA sequence, and another lysine, from the 'turn' of the 'helix–turn–helix' motif, which binds downstream and on the opposite strand.