315 research outputs found

    Host Galaxies of Gamma-Ray Bursts

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    Host galaxies are an excellent means of probing the natal environments that generate gamma-ray bursts (GRBs). Recent work on the host galaxies of short-duration GRBs has offered new insights into the parent stellar populations and ages of their enigmatic progenitors. Similarly, surveys of long-duration GRB (LGRB) host environments and their ISM properties have produced intriguing new results with important implications for long GRB progenitor models. These host studies are also critical in evaluating the utility of LGRBs as potential tracers of star formation and metallicity at high redshifts. I will summarize the latest research on LGRB host galaxies, and discuss the resulting impact on our understanding of these events' progenitors, energetics, and cosmological applications.Comment: 8 pages, 3 figures; to appear in Proceedings of IAU 279 "Death of Massive Stars: Supernovae and Gamma-ray Bursts

    Resolving the cofactor-binding site in the proline biosynthetic enzyme human pyrroline-5-carboxylate reductase 1

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    Pyrroline-5-carboxylate reductase (PYCR) is the final enzyme in proline biosynthesis, catalyzing the NAD(P)H-dependent reduction of [?]1-pyrroline-5-carboxylate (P5C) to proline. Mutations in the PYCR1 gene alter mitochondrial function and cause the connective tissue disorder cutis laxa. Furthermore, PYCR1 is overexpressed in multiple cancers, and the PYCR1 knock-out suppresses tumorigenic growth, suggesting that PYCR1 is a potential cancer target. However, inhibitor development has been stymied by limited mechanistic details for the enzyme, particularly in light of a previous crystallographic study that placed the cofactor-binding site in the C-terminal domain rather than the anticipated Rossmann fold of the N-terminal domain. To fill this gap, we report crystallographic, sedimentation- velocity, and kinetics data for human PYCR1. Structures of binary complexes of PYCR1 with NADPH or proline determined at 1.9 Ã… resolution provide insight into cofactor and substrate recognition.WeseeNADPHbound to the Rossmann fold, over 25 Ã… from the previously proposed site. The 1.85 Ã… resolution structure of a ternary complex containing NADPH and a P5C/proline analog provides a model of the Michaelis complex formed during hydride transfer. Sedimentation velocity shows that PYCR1 forms a concentration-dependent decamer in solution, consistent with the pentamer-of-dimers assembly seen crystallographically. Kinetic and mutational analysis confirmed several features seen in the crystal structure, including the importance of a hydrogen bond between Thr-238 and the substrate as well as limited cofactor discrimination

    Stellar migration and chemical enrichment in the milky way disc: a hybrid model

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    We develop a hybrid model of galactic chemical evolution that combines a multiring computation of chemical enrichment with a prescription for stellar migration and the vertical distribution of stellar populations informed by a cosmological hydrodynamic disc galaxy simulation. Our fiducial model adopts empirically motivated forms of the star formation law and star formation history, with a gradient in outflow mass loading tuned to reproduce the observed metallicity gradient. With this approach, the model reproduces many of the striking qualitative features of the Milky Way disc’s abundance structure: (i) the dependence of the [O/Fe]–[Fe/H] distribution on radius Rgal and mid-plane distance |z|; (ii) the changing shapes of the [O/H] and [Fe/H] distributions with Rgal and |z|; (iii) a broad distribution of [O/Fe] at sub-solar metallicity and changes in the [O/Fe] distribution with Rgal, |z|, and [Fe/H]; (iv) a tight correlation between [O/Fe] and stellar age for [O/Fe] > 0.1; (v) a population of young and intermediate-age α-enhanced stars caused by migration-induced variability in the Type Ia supernova rate; (vi) non-monotonic age–[O/H] and age–[Fe/H] relations, with large scatter and a median age of ∼4 Gyr near solar metallicity. Observationally motivated models with an enhanced star formation rate ∼2 Gyr ago improve agreement with the observed age–[Fe/H] and age–[O/H] relations, but worsen agreement with the observed age–[O/Fe] relation. None of our models predict an [O/Fe] distribution with the distinct bimodality seen in the observations, suggesting that more dramatic evolutionary pathways are required. All code and tables used for our models are publicly available through the Versatile Integrator for Chemical Evolution (VICE; https://pypi.org/project/vice)

    Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease

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    Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and coculture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS

    The Brief Solastalgia Scale: A Psychometric Evaluation and Revision

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    Witnessing degradation and loss to one’s home environment can cause the negative emotional experience of solastalgia. We review the psychometric properties of the 9-item Solastalgia subscale from the Environmental Distress Scale (Higginbotham et al. (EcoHealth 3:245–254, 2006)). Using data collected from three large, independent, adult samples (N = 4229), who were surveyed soon after the 2019/20 Australian bushfires, factor analyses confirmed the scale’s unidimensionality, while analyses derived from Item Response Theory highlighted the poor psychometric performance and redundant content of specific items. Consequently, we recommend a short-form scale consisting of five items. This Brief Solastalgia Scale (BSS) yielded excellent model fit and internal consistency in both the initial and cross-validation samples. The BSS and its parent version provide very similar patterns of associations with demographic, health, life satisfaction, climate emotion, and nature connectedness variables. Finally, multi-group confirmatory factor analysis demonstrated comparable construct architecture (i.e. configural, metric, and scalar invariance) across validation samples, gender categories, and age. As individuals and communities increasingly confront and cope with climate change and its consequences, understanding related emotional impacts is crucial. The BSS promises to aid researchers, decision makers, and practitioners to understand and support those affected by negative environmental change

    Txe, an endoribonuclease of the enterococcal Axe–Txe toxin–antitoxin system, cleaves mRNA and inhibits protein synthesis

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    The axe–txe operon encodes a toxin–antitoxin (TA) pair, Axe–Txe, that was initially identified on the multidrug-resistance plasmid pRUM in Enterococcus faecium. In Escherichia coli, expression of the Txe toxin is known to inhibit cell growth, and co-expression of the antitoxin, Axe, counteracts the toxic effect of Txe. Here, we report the nucleotide sequence of pS177, a 39 kb multidrug-resistant plasmid isolated from vancomycin-resistant Ent. faecium, which harbours the axe–txe operon and the vanA gene cluster. RT-PCR analysis revealed that the axe–txe transcript is produced by strain S177 as well as by other vancomycin-resistant enteroccoci. Moreover, we determine the mechanism by which the Txe protein exerts its toxic activity. Txe inhibits protein synthesis in E. coli without affecting DNA or RNA synthesis, and inhibits protein synthesis in a cell-free system. Using in vivo primer extension analysis, we demonstrate that Txe preferentially cleaves single-stranded mRNA at the first base after an AUG start codon. We conclude that Txe is an endoribonuclease which cleaves mRNA and inhibits protein synthesis
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