Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling

The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutieres syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases

A full quantal theory of one-neutron halo breakup reactions

We present a theory of one-neutron halo breakup reactions within the framework of post-form distorted wave Born approximation wherein pure Coulomb, pure nuclear and their interference terms are treated consistently in a single setup. This formalism is used to study the breakup of one-neutron halo nucleus 11Be on several targets of different masses. We investigate the role played by the pure Coulomb, pure nuclear and the Coulomb-nuclear interference terms by calculating several reaction observables. The Coulomb-nuclear interference terms are found to be important for more exclusive observables.Comment: 22 pages latex, 9 figures, submitted to Phy. Rev.

Coulomb Breakup Mechanism of Neutron-Halo Nuclei in a Time-Dependent Method

The mechanism of the Coulomb breakup reactions of the nuclei with neutron-halo structure is investigated in detail. A time-dependent Schr\"odinger equation for the halo neutron is numerically solved by treating the Coulomb field of a target as an external field. The momentum distribution and the post-acceleration effect of the final fragments are discussed in a fully quantum mechanical way to clarify the limitation of the intuitive picture based on the classical mechanics. The theory is applied to the Coulomb breakup reaction of $^{11}$Be + $^{208}$Pb. The breakup mechanism is found to be different between the channels of $j^{\pi}=\frac{1}{2}^{-}$ and $\frac{3}{2}^{-}$, reflecting the underlying structure of $^{11}$Be. The calculated result reproduces the energy spectrum of the breakup fragments reasonably well, but explains only about a half of the observed longitudinal momentum difference.Comment: 15 pages,revtex, 9 figures (available upon request

In vivo detection of cortical optical changes associated with seizure activity with optical coherence tomography.

The most common technology for seizure detection is with electroencephalography (EEG), which has low spatial resolution and minimal depth discrimination. Optical techniques using near-infrared (NIR) light have been used to improve upon EEG technology and previous research has suggested that optical changes, specifically changes in near-infrared optical scattering, may precede EEG seizure onset in in vivo models. Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth resolved cross-sectional images. In this study, OCT was used to detect changes in optical properties of cortical tissue in vivo in mice before and during the induction of generalized seizure activity. We demonstrated that a significant decrease (P < 0.001) in backscattered intensity during seizure progression can be detected before the onset of observable manifestations of generalized (stage-5) seizures. These results indicate the feasibility of minimally-invasive optical detection of seizures with OCT

More Differences Between Writing with the Dominant and Nondominant Hand by Normal Geriatric Subjects: Eight Perceptual And Eight Computerized Measures on a Sentence Dictation Task

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Dynamical description of the breakup of one-neutron halo nuclei 11Be and 19C

We investigate the breakup of the one-neutron halo nuclei 11Be and 19C within a dynamical model of the continuum excitation of the projectile. The time evolution of the projectile in coordinate space is described by solving the three-dimensional time dependent Schroedinger equation, treating the projectile-target (both Coulomb and nuclear) interaction as a time dependent external perturbation. The pure Coulomb breakup dominates the relative energy spectra of the fragments in the peak region, while the nuclear breakup is important at higher relative energies. The coherent sum of the two contributions provides a good overall description of the experimental spectra. Cross sections of the first order perturbation theory are derived as a limit of our dynamical model. The dynamical effects are found to be of the order of 10-15% for the beam energies in the range of 60 - 80 MeV/nucleon. A comparison of our results with those of a post form distorted wave Born approximation shows that the magnitudes of the higher order effects are dependent on the theoretical model.Comment: 15 pages, ReVTeX, 5 figures, typos corrected, accepted for publication in Physical Review