Human macrophages differentiated in the presence of vitamin D3 restrict dengue virus infection and innate responses by downregulating mannose receptor expression

ABSTARCT: Severe dengue disease is associated with high viral loads and overproduction of pro-inflammatory cytokines, suggesting impairment in the control of dengue virus (DENV) and the mechanisms that regulate cytokine production. Vitamin D3 has been described as an important modulator of immune responses to several pathogens. Interestingly, increasing evidence has associated vitamin D with decreased DENV infection and early disease recovery, yet the molecular mechanisms whereby vitamin D reduces DENV infection are not well understood. METHODS AND PRINCIPAL FINDINGS: Macrophages represent important cell targets for DENV replication and consequently, they are key drivers of dengue disease. In this study we evaluated the effect of vitamin D3 on the differentiation of monocyte-derived macrophages (MDM) and their susceptibility and cytokine response to DENV. Our data demonstrate that MDM differentiated in the presence of vitamin D3 (D3-MDM) restrict DENV infection and moderate the classical inflammatory cytokine response. Mechanistically, vitamin D3-driven differentiation led to reduced surface expression of C-type lectins including the mannose receptor (MR, CD206) that is known to act as primary receptor for DENV attachment on macrophages and to trigger of immune signaling. Consequently, DENV bound less efficiently to vitamin D3-differentiated macrophages, leading to lower infection. Interestingly, IL-4 enhanced infection was reduced in D3-MDM by restriction of MR expression. Moreover, we detected moderate secretion of TNF-α, IL-1β, and IL-10 in D3-MDM, likely due to less MR engagement during DENV infection. CONCLUSIONS/SIGNIFICANCE: Our findings reveal a molecular mechanism by which vitamin D counteracts DENV infection and progression of severe disease, and indicates its potential relevance as a preventive or therapeutic candidate

Evidence For A Mixed Mass Composition At The ‘ankle’ In The Cosmic-ray Spectrum

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Genetic variability for carotenoid content of grains in a composite maize population

Local maize (Zea mays L.) varieties are cultivated by small-scale farmers in western Santa Catarina (SC) State, in southern Brazil. These small areas frequently present many problems related to biotic and non-biotic stresses, which have limited the economic output and income of the farmers. Production from local varieties for human consumption would be an alternative way of improving income and stimulating on farm conservation. The genetic variability of the total carotenoid content (TCC) of kernels in a local maize population was evaluated for their economic exploitation potential as biofortified food. Two independent samples of 96 half-sib families (HSF) plus four checks were evaluated in two groups of experiments in western SC and each one was carried out in two environments. They were set out in a 10 × 10 partially balanced lattice with three replications per location; plots consisted of one row, 5.0 m long with 1.0 m between rows. TCC ranged from 11 to 23 µg g-1, averaging ≈16 µg g-1 in the pooled analysis over the two sets. The local composite population exhibited genetic variability in order to increase the TCC of grains in the second cycle of selection by the convergent-divergent scheme

Astrophysical Interpretation Of Pierre Auger Observatory Measurements Of The Uhecr Energy Spectrum And Mass Composition

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The Pierre Auger Observatory Status And Latest Results

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Search for high-energy neutrinos from gravitational wave event GW151226 and candidate LVT151012 with ANTARES and IceCube

The Advanced LIGO observatories detected gravitational waves from two binary black hole mergers during their first observation run (O1). We present a high-energy neutrino follow-up search for the second gravitational wave event, GW151226, as well as for gravitational wave candidate LVT151012. We find two and four neutrino candidates detected by IceCube, and one and zero detected by Antares, within ±500 s around the respective gravitational wave signals, consistent with the expected background rate. None of these neutrino candidates are found to be directionally coincident with GW151226 or LVT151012. We use nondetection to constrain isotropic-equivalent high-energy neutrino emission from GW151226, adopting the GW event's 3D localization, to less than 2×1051-2×1054 erg. © 2017 American Physical Society

Depth Of Maximum Of Air-shower Profiles At The Pierre Auger Observatory. I. Measurements At Energies Above 1017.8ev

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KELT-25 b and KELT-26 b: A Hot Jupiter and a Substellar Companion Transiting Young A Stars Observed by TESS

We present the discoveries of KELT-25 b (TIC 65412605, TOI-626.01) and KELT-26 b (TIC 160708862, TOI-1337.01), two transiting companions orbiting relatively bright, early A stars. The transit signals were initially detected by the KELT survey and subsequently confirmed by Transiting Exoplanet Survey Satellite (TESS) photometry. KELT-25 b is on a 4.40 day orbit around the V = 9.66 star CD-24 5016 (Teff=8280-180+440 K, M ∗ = 2.18-0.11+0.12 M o˙), while KELT-26 b is on a 3.34 day orbit around the V = 9.95 star HD 134004 (Teff = 8640-240+500 K, M ∗ = 1.93-0.16+0.14 M o˙), which is likely an Am star. We have confirmed the substellar nature of both companions through detailed characterization of each system using ground-based and TESS photometry, radial velocity measurements, Doppler tomography, and high-resolution imaging. For KELT-25, we determine a companion radius of R P = 1.64-0.043+0.039 R J and a 3σ upper limit on the companion's mass of ∼64 M J. For KELT-26 b, we infer a planetary mass and radius of M P = 1.41-0.51+0.43MJ and R P = 1.94-0.058+0.060 R J. From Doppler tomographic observations, we find KELT-26 b to reside in a highly misaligned orbit. This conclusion is weakly corroborated by a subtle asymmetry in the transit light curve from the TESS data. KELT-25 b appears to be in a well-aligned, prograde orbit, and the system is likely a member of the cluster Theia 449

Pulsar Wind Nebulae with Bow Shocks: Non-thermal Radiation and Cosmic Ray Leptons

Pulsars with high spin-down power produce relativistic winds radiating a non-negligible fraction of this power over the whole electromagnetic range from radio to gamma-rays in the pulsar wind nebulae (PWNe). The rest of the power is dissipated in the interactions of the PWNe with the ambient interstellar medium (ISM). Some of the PWNe are moving relative to the ambient ISM with supersonic speeds producing bow shocks. In this case, the ultrarelativistic particles accelerated at the termination surface of the pulsar wind may undergo reacceleration in the converging flow system formed by the plasma outflowing from the wind termination shock and the plasma inflowing from the bow shock. The presence of magnetic perturbations in the flow, produced by instabilities induced by the accelerated particles themselves, is essential for the process to work. A generic outcome of this type of reacceleration is the creation of particle distributions with very hard spectra, such as are indeed required to explain the observed spectra of synchrotron radiation with photon indices Γ≲ 1.5. The presence of this hard spectral component is specific to PWNe with bow shocks (BSPWNe). The accelerated particles, mainly electrons and positrons, may end up containing a substantial fraction of the shock ram pressure. In addition, for typical ISM and pulsar parameters, the e+ released by these systems in the Galaxy are numerous enough to contribute a substantial fraction of the positrons detected as cosmic ray (CR) particles above few tens of GeV and up to several hundred GeV. The escape of ultrarelativistic particles from a BSPWN—and hence, its appearance in the far-UV and X-ray bands—is determined by the relative directions of the interstellar magnetic field, the velocity of the astrosphere and the pulsar rotation axis. In this respect we review the observed appearance and multiwavelength spectra of three different types of BSPWNe: PSR J0437-4715, the Guitar and Lighthouse nebulae, and Vela-like objects. We argue that high resolution imaging of such objects provides unique information both on pulsar winds and on the ISM. We discuss the interpretation of imaging observations in the context of the model outlined above and estimate the BSPWN contribution to the positron flux observed at the Earth