Searching for Earth analogues around the nearest stars: the disk age-metallicity relation and the age distribution in the Solar Neighbourhood

The chemical composition of Earth's atmosphere has undergone substantial evolution over the course of its history. It is possible, even likely, that terrestrial planets in other planetary systems have undergone similar changes; consequently, the age distribution of nearby stars is an important consideration in designing surveys for Earth-analogues. Valenti & Fischer (2005) provide age and metallicity estimates for 1039 FGK dwarfs in the Solar Neighbourhood. Using the Hipparcos catalogue as a reference to calibrate potential biases, we have extracted volume-limited samples of nearby stars from the Valenti-Fischer dataset. Unlike other recent investigations, our analysis shows clear evidence for an age-metallicity relation in the local disk, albeit with substantial dispersion at any epoch. The mean metallicity increases from -0.3 dex at a lookback time of ~10 Gyrs to +0.15 dex at the present day. Supplementing the Valenti-Fischer measurements with literature data to give a complete volume-limited sample, the age distribution of nearby FGK dwarfs is broadly consistent with a uniform star-formation rate over the history of the Galactic disk. In striking contrast, most stars known to have planetary companions are younger than 5 Gyrs; however, stars with planetary companions within 0.4 AU have a significantly flatter age distribution, indicating that those systems are stable on timescales of many Gyrs. Several of the older, lower metallicity host stars have enhanced [alpha/Fe] ratios, implying membership of the thick disk. If the frequency of terrestrial planets is also correlated with stellar metallicity, then the median age of such planetary system is likely to be ~3 Gyrs. We discuss the implications of this hypothesis in designing searches for Earth analogues among the nearby stars.Comment: Accepted for publication in Ap

A Serpin shapes the extracellular environment to prevent influenza A virus maturation

Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response

Dengue Virus Hijacks a Noncanonical Oxidoreductase Function of a Cellular Oligosaccharyltransferase Complex

Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation. However, the OST subunit MAGT1, which associates with STT3B, is also required for DENV propagation. MAGT1 expression requires STT3B, and a catalytically inactive STT3B also rescues MAGT1 expression, supporting the hypothesis that STT3B serves to stabilize MAGT1 in the context of DENV infection. We found that the oxidoreductase CXXC active site motif of MAGT1 was necessary for DENV propagation, as cells expressing an AXXA MAGT1 mutant were unable to support DENV infection. Interestingly, cells expressing single-cysteine CXXA or AXXC mutants of MAGT1 were able to support DENV propagation. Utilizing the engineered peroxidase APEX2, we demonstrate the close proximity between MAGT1 and NS1 or NS4B during DENV infection. These results reveal that the oxidoreductase activity of the STT3B-containing OST is necessary for DENV infection, which may guide the development of antiviral agents targeting DENV. IMPORTANCE The host oligosaccharyltransferase (OST) complexes have been identified as essential host factors for dengue virus (DENV) replication; however, their functions during DENV infection are unclear. A previous study showed that the canonical OST activity was dispensable for DENV replication, suggesting that the OST complexes serve as scaffolds for DENV replication. However, our work demonstrates that one function of the OST complex during DENV infection is to provide oxidoreductase activity via the OST subunit MAGT1. We also show that MAGT1 associates with DENV NS1 and NS4B during viral infection, suggesting that these nonstructural proteins may be targets of MAGT1 oxidoreductase activity. These results provide insight into the cell biology of DENV infection, which may guide the development of antivirals against DENV

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs

The effects of maximising the UK's Tobacco Control Score on inequalities in smoking prevalence and premature coronary heart disease mortality: a modelling

Background Smoking is more than twice as common among the most disadvantaged socioeconomic groups in England compared to the most affluent and is a major contributor to health-related inequalities. The United Kingdom (UK) has comprehensive smoking policies in place: regular tax increases; public information campaigns; on-pack pictorial health warnings; advertising bans; cessation; and smoke-free areas. This is confirmed from its high Tobacco Control Scale (TCS) score, an expert-developed instrument for assessing the strength of tobacco control policies. However, room remains for improvement in tobacco control policies. Our aim was to evaluate the cumulative effect on smoking prevalence of improving all TCS components in England, stratified by socioeconomic circumstance. Methods Effect sizes and socioeconomic gradients for all six types of smoking policy in the UK setting were adapted from systematic reviews, or if not available, from primary studies. We used the IMPACT Policy Model to link predicted changes in smoking prevalence to changes in premature coronary heart disease (CHD) mortality for ages 35–74. Health outcomes with a time horizon of 2025 were stratified by quintiles of socioeconomic circumstance. Results The model estimated that improving all smoking policies to achieve a maximum score on the TCS might reduce smoking prevalence in England by 3 % (95 % Confidence Interval (CI): 1–4 %), from 20 to 17 % in absolute terms, or by 15 % in relative terms (95 % CI: 7–21 %). The most deprived quintile would benefit more, with absolute reductions from 31 to 25 %, or a 6 % reduction (95 % CI: 2–7 %). There would be some 3300 (95 % CI: 2200–4700) fewer premature CHD deaths between 2015–2025, a 2 % (95 % CI: 1.4–2.9 %) reduction. The most disadvantaged quintile would benefit more, reducing absolute inequality of CHD mortality by about 4 % (95 % CI: 3–9 %). Conclusions Further, feasible improvements in tobacco control policy could substantially improve population health, and reduce health-related inequalities in England

Prenatal cocaine effects on brain structure in early infancy

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life

The Century Survey Galactic Halo Project III: A Complete 4300 deg^2 Survey of Blue Horizontal Branch Stars in the Metal-Weak Thick Disk and Inner Halo

We present a complete spectroscopic survey of 2414 2MASS-selected blue horizontal branch (BHB) candidates selected over 4300 deg^2 of the sky. We identify 655 BHB stars in this non-kinematically selected sample. We calculate the luminosity function of field BHB stars and find evidence for very few hot BHB stars in the field. The BHB stars located at a distance from the Galactic plane |Z|<4 kpc trace what is clearly a metal-weak thick disk population, with a mean metallicity of [Fe/H]= -1.7, a rotation velocity gradient of dv_{rot}/d|Z|= -28+-3.4 km/s in the region |Z|<6 kpc, and a density scale height of h_Z= 1.26+-0.1 kpc. The BHB stars located at 5<|Z|<9 kpc are a predominantly inner-halo population, with a mean metallicity of [Fe/H]= -2.0 and a mean Galactic rotation of -4+-31 km/s. We infer the density of halo and thick disk BHB stars is 104+-37 kpc^-3 near the Sun, and the relative normalization of halo to thick-disk BHB stars is 4+-1% near the Sun.Comment: 12 pages in emulateapj format, accepted for publication in February A