We report the detection of a CO emission line from the submillimeter galaxy (SMG) GN10 in the GOODS-N field. GN10 lacks any counterpart in extremely deep optical and near-IR imaging obtained with the ...Hubble Space Telescope and ground-based facilities. This is a prototypical case of a source that is extremely obscured by dust, for which it is practically impossible to derive a spectroscopic redshift in the optical/near-IR. Under the hypothesis that GN10 is part of a proto-cluster structure previously identified at z ~ 4.05 in the same field, we searched for CO4-3 at 91.4 GHz with the IRAM Plateau de Bure Interferometer, and successfully detected a line. We find that the most likely redshift identification is z = 4.0424 ± 0.0013, based on: (1) the very low chance that the CO line is actually serendipitous from a different redshift; (2) a radio-IR photometric redshift analysis; (3) the identical radio-IR spectral energy distribution, within a scaling factor of 2 other SMGs at the same redshift. The faintness at optical/near-IR wavelengths requires an attenuation of A V ~ 5-7.5 mag. This result supports the case that a substantial population of very high-z SMGs exists that had been missed by previous spectroscopic surveys. This is the first time that a CO emission line has been detected for an SMG that is invisible in the optical and near-IR. Our work demonstrates the power of existing and planned facilities for completing the census of star formation and stellar mass in the distant universe by measuring redshifts of the most obscured galaxies through millimeter spectroscopy.
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute fever and acute and chronic musculoskeletal pain in humans. Since 2004, CHIKV has caused millions of cases of disease ...in the Indian Ocean region and has emerged in new areas, including Europe, the Middle East, and the Pacific region. The mosquito vectors for this virus are globally distributed in tropical and temperate zones, providing the opportunity for CHIKV to continue to expand into new geographic regions. In October 2013, locally acquired cases of CHIKV infection were identified on the Caribbean island of Saint Martin, signaling the arrival of the virus in the Western Hemisphere. In just 9 months, CHIKV has spread to 22 countries in the Caribbean and Central and South America, resulting in hundreds of thousands of cases. CHIKV disease can be highly debilitating, and large epidemics have severe economic consequences. Thus, there is an urgent need for continued research into the epidemiology, pathogenesis, prevention, and treatment of these infections.
Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions ...has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long‐term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some ...of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.
A practical consideration for many intellectually able adults with autism spectrum disorder (ASD) is whether to disclose their diagnostic status or try to mask their autistic characteristics to avoid ...judgment and discrimination. Here, we assessed first impressions of adults with ASD and typically developing controls (N = 40) made by typically developing observers (N = 215) when their diagnostic status was either withheld, accurately provided, or inaccurately provided. First impressions were less favorable for ASD participants compared to typically developing controls across a range of judgments, but were significantly more positive when accurately labeled as ASD compared to when no label was provided, when mislabeled as typically developing, or when mislabeled as having schizophrenia. For typically developing participants, ratings did not change when accurately labeled but improved when mislabeled as ASD. Greater autistic traits for the ASD and typically developing participants were associated with less favorable first impressions, and females were rated more favorably than males. Autism knowledge of the raters, but not age, IQ, or autistic traits, was positively associated with more favorable impressions of ASD participants. Collectively, these findings suggest that first impressions for intellectually able adults with ASD improve with diagnostic disclosure and increased autism understanding on the part of peers.
Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in ...2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3
), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected
mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of
mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of
mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.
The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.
Many viruses utilize the lymphohematogenous route for dissemination; however, they may not freely use this highway unchecked. The reticuloendothelial system (RES) is an innate defense system that ...surveys circulating blood, recognizing and capturing viral particles. Examination of the literature shows that the bulk of viral clearance is mediated by the liver; however, the precise mechanism(s) mediating viral vascular clearance vary between viruses and, in many cases, remains poorly defined. Herein, we summarize what is known regarding the recognition and capture of virions from the circulation prior to the generation of a specific antibody response. We also discuss the consequences of viral capture on viral pathogenesis and the fate of the captor cell. Finally, this understudied topic has implications beyond viral pathogenesis, including effects on arbovirus ecology and the application of virus-vectored gene therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
We describe an algorithm for application of the classic “drizzle” technique to produce 3D spectral cubes using data obtained from the slicer-type integral field unit (IFU) spectrometers on ...board the James Webb Space Telescope. This algorithm relies upon the computation of overlapping volume elements (composed of two spatial dimensions and one spectral dimension) between the 2D detector pixels and the 3D data cube voxels, and is greatly simplified by treating the spatial and spectral overlaps separately at the cost of just 0.03% in spectrophotometric fidelity. We provide a matrix-based formalism for the computation of spectral radiance, variance, and covariance from arbitrarily dithered data and comment on the performance of this algorithm for the Mid-Infrared Instrument’s Medium Resolution IFU Spectrometer. We derive a series of simplified scaling relations to account for covariance between cube spaxels in spectra extracted from such cubes, finding multiplicative factors ranging from 1.5–3 depending on the wavelength range and kind of data cubes produced. Finally, we discuss how undersampling produces periodic amplitude modulations in the extracted spectra in addition to those naturally produced by fringing within the instrument; reducing such undersampling artifacts below 1% requires a four-point dithering strategy and spectral extraction radii of 1.5 times the point-spread function FWHM or greater.
Chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-transmitted alphaviruses that cause debilitating acute and chronic musculoskeletal disease. Monocytes are implicated in the ...pathogenesis of these infections; however, their specific roles are not well defined. To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus pathogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by administration of diptheria toxin (DT). DT-treated CCR2-DTR mice displayed more severe disease following CHIKV and RRV infection and had fewer Ly6Chi monocytes and NK cells in circulation and muscle tissue compared with DT-treated WT mice. Furthermore, depletion of CCR2+ or Gr1+ cells, but not NK cells or neutrophils alone, restored virulence and increased viral loads in mice infected with an RRV strain encoding attenuating mutations in nsP1 to levels detected in monocyte-depleted mice infected with fully virulent RRV. Disease severity and viral loads also were increased in DT-treated CCR2-DTR+;Rag1-/- mice infected with the nsP1 mutant virus, confirming that these effects are independent of adaptive immunity. Monocytes and macrophages sorted from muscle tissue of RRV-infected mice were viral RNA positive and had elevated expression of Irf7, and co-culture of Ly6Chi monocytes with RRV-infected cells resulted in induction of type I IFN gene expression in monocytes that was Irf3;Irf7 and Mavs-dependent. Consistent with these data, viral loads of the attenuated nsP1 mutant virus were equivalent to those of WT RRV in Mavs-/- mice. Finally, reconstitution of Irf3-/-;Irf7-/- mice with CCR2-DTR bone marrow rescued mice from severe infection, and this effect was reversed by depletion of CCR2+ cells, indicating that CCR2+ hematopoietic cells are capable of inducing an antiviral response. Collectively, these data suggest that MAVS-dependent production of type I IFN by monocytes is critical for control of acute alphavirus infection and that determinants in nsP1, the viral RNA capping protein, counteract this response.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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