Flaviviruses are a genus of (+)ssRNA (positive ssRNA) enveloped viruses that replicate in the cytoplasm of cells of diverse species from arthropods to mammals. Many are important human pathogens such ...as DENV-1-4 (dengue virus types 1-4), WNV (West Nile virus), YFV (yellow fever virus), JEV (Japanese encephalitis virus) and TBEV (tick-borne encephalitis). Given their RNA genomes it is not surprising that flaviviral life cycles revolve around critical RNA transactions. It is these we highlight in the present article. First, we summarize the mechanisms governing flaviviral replication and the central role of conserved RNA elements and viral protein-RNA interactions in RNA synthesis, translation and packaging. Secondly, we focus on how host RNA-binding proteins both benefit and inhibit flaviviral replication at different stages of their life cycle in mammalian hosts. Thirdly, we cover recent studies on viral non-coding RNAs produced in flavivirus-infected cells and how these RNAs affect various aspects of cellular RNA metabolism. Together, the article puts into perspective the central role of flaviviral RNAs in modulating both viral and cellular functions.
Eleven million tonnes of waste are produced yearly by the European pulp and paper industry, of which 70% originates from the production of deinked recycled paper. Wastes are very diverse in ...composition and consist of rejects, different types of sludges and ashes in mills having on-site incineration treatment. The production of pulp and paper from virgin pulp generates less waste but the waste has similar properties to waste from the production of deinked pulp, although with less inorganics. Due to legislation and increased taxes, landfills are quickly being eliminated as a final destination for wastes in Europe, and incineration with energy recovery is becoming the main waste recovery method. Other options such as pyrolysis, gasification, land spreading, composting and reuse as building material are being applied, although research is still needed for optimization of the processes. Due to the large volumes of waste generated, the high moisture content of the waste and the changing waste composition as a result of process conditions, recovery methods are usually expensive and their environmental impact is still uncertain. For this reason, it is necessary to continue research on different applications of wastes, while taking into account the environmental and economic factors of these waste treatments.
The horizontal-branch (HB) morphology of globular clusters (GCs) is mainly determined by metallicity. However, the fact that GCs with almost the same metallicity exhibit different HB morphologies ...demonstrates that at least one more parameter is needed to explain the HB morphology. It has been suggested that one of these should be a global parameter that varies from GC to GC and the other a nonglobal parameter that varies within the GC. In this study we provide empirical evidence corroborating this idea. We used the photometric catalogs obtained with the Advanced Camera for Surveys of the Hubble Space Telescope and analyze the color-magnitude diagrams of 74 GCs. The HB morphology of our sample of GCs has been investigated on the basis of the two new parameters L1 and L2 that measure the distance between the red giant branch and the coolest part of the HB and the color extension of the HB, respectively. We find that L1 correlates with both metallicity and age, whereas L2 most strongly correlates with the mass of the hosting GC. The range of helium abundance among the stars in a GC, characterized by Delta Y and associated with the presence of multiple stellar populations, has been estimated in a few GCs to date. In these GCs we find a close relationship among Delta Y, GC mass, and L2. We conclude that age and metallicity are the main global parameters, while the range of helium abundance within a GC is the main nonglobal parameter defining the HB morphology of Galactic GCs.
Although white-matter abnormalities have been reported in middle-aged patients with major depressive disorder (MDD), few data are available on treatment-resistant MDD and the influence of relevant ...variables related to clinical burden of illness is far from being well established.
The present study examined white-matter microstructure in a sample of 52 patients with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted-recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. Groups were comparable in age and gender distribution, and results were corrected for familywise error (FWE) rate.
Widespread significant reductions of fractional anisotropy (FA) - including the cingulum, corpus callosum, superior and inferior longitudinal fascicule - were evident in treatment-resistant/chronic MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected). Decreased FA was observed within the ventromedial prefrontal region in treatment-resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p < 0.05, FWE-corrected). Longer duration of illness (β = -0.49, p = 0.04) and higher depression severity (at a trend level: β = -0.26, p = 0.06) predicted lower FA in linear multiple regression analysis at the whole-brain level. The number of previous episodes and severity of symptoms were significant predictors when focused on the ventromedial prefrontal area (β = -0.28, p = 0.04; and β = -0.29, p = 0.03, respectively). Medication effects were controlled for in the analyses and results remained unaltered.
Our findings support the notion that disruptions of white-matter microstructure, particularly in fronto-limbic networks, are associated with resistance to treatment and higher current and past burden of depression.
Aims. The nature of the thick disc and its relation to the thin disc is presently an important subject of debate. In fact, the structural and chemo-dynamical transition between disc populations can ...be used as a test of the proposed models of Galactic disc formation and evolution. Methods. We used the atmospheric parameters, α/Fe abundances, and radial velocities, which were determined from the Gaia-ESO Survey GIRAFFE spectra of FGK-type stars (first nine months of observations) to provide a chemo-kinematical characterisation of the disc stellar populations. We focussed on a subsample of 1016 stars with high-quality parameters, covering the volume | Z | < 4.5 kpc and R in the range 2–13 kpc. Results. We have identified a thin to thick disc separation in the α/Fe vs. M/H plane, thanks to the presence of a low-density region in the number density distribution. The thick disc stars seem to lie in progressively thinner layers above the Galactic plane, as metallicity increases and α/Fe decreases. In contrast, the thin disc population presents a constant value of the mean distance to the Galactic plane at all metallicities. In addition, our data confirm the already known correlations between Vφ and M/H for the two discs. For the thick disc sequence, a study of the possible contamination by thin disc stars suggests a gradient up to 64 ± 9 km s-1 dex-1. The distributions of azimuthal velocity, vertical velocity, and orbital parameters are also analysed for the chemically separated samples. Concerning the gradients with galactocentric radius, we find, for the thin disc, a flat behaviour of the azimuthal velocity, a metallicity gradient equal to −0.058 ± 0.008 dex kpc-1 and a very small positive α/Fe gradient. For the thick disc, flat gradients in M/H and α/Fe are derived. Conclusions. Our chemo-kinematical analysis suggests a picture where the thick disc seems to have experienced a settling process, during which its rotation increased progressively and, possibly, the azimuthal velocity dispersion decreased. At M/H ≈ −0.25 dex and α/Fe≈ 0.1 dex, the mean characteristics of the thick disc in vertical distance to the Galactic plane, rotation, rotational dispersion, and stellar orbits’ eccentricity agree with that of the thin disc stars of the same metallicity, suggesting a possible connection between these two populations at a certain epoch of the disc evolution. Finally, the results presented here, based only on the first months of the Gaia ESO Survey observations, confirm how crucial large high-resolution spectroscopic surveys outside the solar neighbourhood are today for our understanding of the Milky Way history.
We present an automated procedure for the derivation of atmospheric parameters (T
eff, log g, M/H) and individual chemical abundances from stellar spectra. The MATrix Inversion for Spectral SynthEsis ...(MATISSE) algorithm determines a basis,
B
θ(λ), allowing the derivation of a particular stellar parameter θ by projection of an observed spectrum. The
B
θ(λ) function is determined from an optimal linear combination of theoretical spectra and it relates, in a quantitative way, the variations in the spectrum flux with variations in θ. An application of this method to the Gaia Radial Velocity Spectrograph spectral range is described, together with its performances for different types of stars of various metallicities. Blind tests with synthetic spectra of randomly selected parameters and observed input spectra are also presented. The method gives rapid, accurate and stable results and it can be efficiently applied to the study of stellar populations through the analysis of large spectral data sets, including moderate to low signal-to-noise ratio spectra.
Context. The chemical evolution of lithium in the Milky Way represents a major problem in modern astrophysics. Indeed, lithium is, on the one hand, easily destroyed in stellar interiors, and, on the ...other hand, produced at some specific stellar evolutionary stages that are still not well constrained. Aims. The goal of this paper is to investigate the lithium stellar content of Milky Way stars in order to put constraints on the lithium chemical enrichment in our Galaxy, in particular in both the thin and thick discs. Methods. Thanks to high-resolution spectra from the ESO archive and high quality atmospheric parameters, we were able to build a massive and homogeneous catalogue of lithium abundances for 7300 stars derived with an automatic method coupling, a synthetic spectra grid, and a Gauss-Newton algorithm. We validated these lithium abundances with literature values, including those of the Gaia benchmark stars. Results. In terms of lithium galactic evolution, we show that the interstellar lithium abundance increases with metallicity by 1 dex from M/H = −1 dex to + 0.0 dex. Moreover, we find that this lithium ISM abundance decreases by about 0.5 dex at super-solar metalllicity. Based on a chemical separation, we also observed that the stellar lithium content in the thick disc increases rather slightly with metallicity, while the thin disc shows a steeper increase. The lithium abundance distribution of α-rich, metal-rich stars has a peak at ALi ~ 3 dex. Conclusions. We conclude that the thick disc stars suffered of a low lithium chemical enrichment, showing lithium abundances rather close to the Spite plateau while the thin disc stars clearly show an increasing lithium chemical enrichment with the metallicity, probably thanks to the contribution of low-mass stars.
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood ...transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.
Currently there are no approved vaccines or specific therapies to prevent or treat Zika virus (ZIKV) infection. We interrogated a library of FDA-approved drugs for their ability to block infection of ...human HuH-7 cells by a newly isolated ZIKV strain (ZIKV MEX_I_7). More than 20 out of 774 tested compounds decreased ZIKV infection in our in vitro screening assay. Selected compounds were further validated for inhibition of ZIKV infection in human cervical, placental, and neural stem cell lines, as well as primary human amnion cells. Established anti-flaviviral drugs (e.g., bortezomib and mycophenolic acid) and others that had no previously known antiviral activity (e.g., daptomycin) were identified as inhibitors of ZIKV infection. Several drugs reduced ZIKV infection across multiple cell types. This study identifies drugs that could be tested in clinical studies of ZIKV infection and provides a resource of small molecules to study ZIKV pathogenesis.
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•774 FDA-approved drugs screened for anti-Zika virus activity in a human hepatoma cell line•Over 20 compounds showed anti-Zika virus activity•Selected compounds validated in human neural stem cells and primary amnion cells
Currently there is no approved therapy to treat Zika virus (ZIKV) infection. Barrows et al. present a screen of FDA-approved drugs for anti-ZIKV activity in a hepatoma cell line. Selected compounds from the more than 20 identified candidates were validated in human neural stem cells and primary amnion cells.
Abstract The habenula (Hb) can play an important role in major depressive disorder (MDD) as it is a key node between fronto-limbic areas and midbrain monoaminergic structures. In vivo neuroimaging ...studies have shown reductions in Hb volume in a post-mortem sample of patients with affective disorders but findings in unipolar MDD are not consistent. The current study aimed to investigate whether the Hb volume differed between patients with different stages of unipolar MDD and healthy subjects. We also explored differences in grey (GM) and white matter (WM) volumes and potential age and gender effects. High-resolution images were acquired using a 3T-scanner from 95 participants (21 with first-episode MDD; 20 with remitted-recurrent MDD; 20 with treatment-resistant/chronic MDD; and 34 healthy controls).Two researchers blinded to clinical data manually delineated habenular nuclei, with excellent inter-rater agreement. Multivariate analysis of covariance revealed a significant group-by-gender interaction ( F9,258 =2.22; p =0.02). Univariate effects emerged for Hb-WM volumes ( F3,86 =3.12; p =0.03) but not for total Hb volumes ( F3,86 =0.59; p =0.62) or Hb-GM volumes ( F3,86 =2.01; p =0.12). Women with a first-episode MDD had greater Hb-WM volumes than healthy controls and patients with treatment-resistant/chronic MDD ( p <0.01). These findings remained unaltered when controlled for total intracranial volume or medication load. Our results do not support decreased total Hb volumes in unipolar MDD, in patients with first-episode or in patients with long-lasting recurrent or chronic depression. However, the increased Hb-WM volume we observed in women with a first-episode suggests involvement of Hb and its projections in early stages of the recovery process and in the course of MDD.
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