12,980 research outputs found

    Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

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    BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection

    Parsec-scale jet properties of the gamma-ray quasar 3C 286

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    The quasar 3C~286 is one of two compact steep spectrum sources detected by the {\it Fermi}/LAT. Here, we investigate the radio properties of the parsec(pc)-scale jet and its (possible) association with the γ\gamma-ray emission in 3C~286. The Very Long Baseline Interferometry (VLBI) images at various frequencies reveal a one-sided core--jet structure extending to the southwest at a projected distance of \sim1 kpc. The component at the jet base showing an inverted spectrum is identified as the core, with a mean brightness temperature of 2.8×1092.8\times 10^{9}~K. The jet bends at about 600 pc (in projection) away from the core, from a position angle of 135-135^\circ to 115-115^\circ. Based on the available VLBI data, we inferred the proper motion speed of the inner jet as 0.013±0.0110.013 \pm 0.011 mas yr1^{-1} (βapp=0.6±0.5\beta_{\rm app} = 0.6 \pm 0.5), corresponding to a jet speed of about 0.5c0.5\,c at an inclination angle of 4848^\circ between the jet and the line of sight of the observer. The brightness temperature, jet speed and Lorentz factor are much lower than those of γ\gamma-ray-emitting blazars, implying that the pc-scale jet in 3C~286 is mildly relativistic. Unlike blazars in which γ\gamma-ray emission is in general thought to originate from the beamed innermost jet, the location and mechanism of γ\gamma-ray emission in 3C~286 may be different as indicated by the current radio data. Multi-band spectrum fitting may offer a complementary diagnostic clue of the γ\gamma-ray production mechanism in this source.Comment: 9 pages, 4 figures, accept for publication in MNRA

    Excited-state intramolecular proton transfer to carbon atoms: nonadiabatic surface-hopping dynamics simulations

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    Excited-state intramolecular proton transfer (ESIPT) between two highly electronegative atoms, for example, oxygen and nitrogen, has been intensely studied experimentally and computationally, whereas there has been much less theoretical work on ESIPT to other atoms such as carbon. We have employed CASSCF, MS-CASPT2, RI-ADC(2), OM2/MRCI, DFT, and TDDFT methods to study the mechanistic photochemistry of 2-phenylphenol, for which such an ESIPT has been observed experimentally. According to static electronic structure calculations, irradiation of 2-phenylphenol populates the bright S1 state, which has a rather flat potential in the Franck–Condon region (with a shallow enol minimum at the CASSCF level) and may undergo an essentially barrierless ESIPT to the more stable S1 keto species. There are two S1/S0 conical intersections that mediate relaxation to the ground state, one in the enol region and one in the keto region, with the latter one substantially lower in energy. After S1 → S0 internal conversion, the transient keto species can return back to the S0 enol structure via reverse ground-state hydrogen transfer in a facile tautomerization. This mechanistic scenario is verified by OM2/MRCI-based fewest-switches surface-hopping simulations that provide detailed dynamic information. In these trajectories, ESIPT is complete within 118 fs; the corresponding S1 excited-state lifetime is computed to be 373 fs in vacuum. Most of the trajectories decay to the ground state via the S1/S0 conical intersection in the keto region (67%), and the remaining ones via the enol region (33%). The combination of static electronic structure computations and nonadiabatic dynamics simulations is expected to be generally useful for understanding the mechanistic photophysics and photochemistry of molecules with intramolecular hydrogen bonds

    AN UNSTRUCTURED DISCONTINUOUS FINITE ELEMENT METHOD FOR THREE-DIMENSIONAL RADIATIVE TRANSFER IN PARTICIPATING MEDIA

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    ABSTRACT This paper presents a discontinuous finite element (or discontinuous Galerkin) computational methodology for the numerical solution of internal thermal radiation problems in three-dimensional geometries using unstructured meshes. Mathematical formulation and numerical details using the discontinuous Galerkin method for internal radiation heat transfer calculations are given. Computational procedures are presented. Numerical examples are given for radiative transfer in 3-D geometries filled with a non-scattering or scattering medium. The computed results are given and are compared well with analytical solutions whenever available or the data reported in references

    Multipotent stem cells with neural crest stem cells characteristics exist in bovine adipose tissue

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    Neural crest stem cells (NCSCs) often referred to as the fourth germ layer, comprise a migratory, stem and progenitor cell population and are synonymous with vertebrate evolution and development. The cells follow specific paths to migrate to different locations of the body where they generate a diverse array of cell types and tissues. There are NCSCs which are maintained in an undifferentiated state throughout the life in the animal tissues. Based on some cells migratory property, we successfully developed a separation strategy to isolate and identify a population of adipose-derived stem cells with neural crest stem cell features in adult bovine adipose tissues within minimally-invasive surgical procedures. The cells have a high degree of multi-potency and self-renewal capabilities, can be cultured and maintained in feeder-free adhesion conditions as monolayer cells, and also be able to grow in the suspension condition in the form of neurosphere. For the purpose of simple description, we name this type cell as bovine adipose-derived neural crest stem cell (baNCSC). Taken together our study describes a readily accessible source of multipotent baNCSC for autologous tissue engineer and cell-based therapeutic researches

    AHL-mediated quorum sensing regulates the variations of microbial community and sludge properties of aerobic granular sludge under low organic loading

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    © 2019 The Authors Aerobic granular sludge (AGS) is promising in wastewater treatment. However, the formation and existence of AGS under low organic loading rate (OLR) is still not fully understood due to a knowledge gap in the variations and correlations of N-acyl-homoserine lactones (AHLs), the microbial community, extracellular polymeric substances (EPS) and other physiochemical granule properties. This study comprehensively investigated the AHL-mediated quorum sensing (QS) and microbial community characters in the AGS fed with ammonium-rich wastewater under a low OLR of 0.15 kg COD (m3 d)−1. The results showed that the AGS appeared within 90 days, and the size of mature granules was over 700 μm with strong settleability and ammonium removal performance. More tightly-bound extracellular polysaccharide and tightly-bound extracelluar protein were produced in the larger AGS. C10-HSL and C12-HSL gradually became dominant in sludge, and short-chain AHLs dominated in water. EPS producers and autotrophic nitrifiers were successfully retained in the AGS under low OLR. AHL-mediated QS utilized C10-HSL, C12-HSL and 3OC6-HSL as the critical AHLs to regulate the TB-EPS in aerobic granulation, and autotrophic nitrifiers may perform interspecific communication with C10-HSL. The correlations of bacterial genera with AGS properties and AHLs were complex due to the dynamic fluctuations of microbial composition and other variable factors in the mixed-culture system. These findings confirmed the participation of AHL-mediated QS in the regulation of microbial community characters and AGS properties under low OLR, which may provide guidance for the operation of AGS systems under low OLR from a microbiological viewpoint

    Atomistic simulations of self-trapped exciton formation in silicon nanostructures: The transition from quantum dots to nanowires

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    Using an approximate time-dependent density functional theory method, we calculate the absorption and luminescence spectra for hydrogen passivated silicon nanoscale structures with large aspect ratio. The effect of electron confinement in axial and radial directions is systematically investigated. Excited state relaxation leads to significant Stokes shifts for short nanorods with lengths less than 2 nm, but has little effect on the luminescence intensity. The formation of self-trapped excitons is likewise observed for short nanostructures only; longer wires exhibit fully delocalized excitons with neglible geometrical distortion at the excited state minimum.Comment: 10 pages, 4 figure
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