Visualizing and quantifying structural diversity around mobile resistance genes.

Understanding the evolution of mobile genes is important for understanding the spread of antimicrobial resistance (AMR). Many clinically important AMR genes have been mobilized by mobile genetic elements (MGEs) on the kilobase scale, such as integrons and transposons, which can integrate into both chromosomes and plasmids and lead to rapid spread of the gene through bacterial populations. Looking at the flanking regions of these mobile genes in diverse genomes can highlight common structures and reveal patterns of MGE spread. However, historically this has been a largely descriptive process, relying on gene annotation and expert knowledge. Here we describe a general method to visualize and quantify the structural diversity around genes using pangraph to find blocks of homologous sequence. We apply this method to a set of 12 clinically important beta-lactamase genes and provide interactive visualizations of their flanking regions at https://liampshaw.github.io/flanking-regions. We show that nucleotide-level variation in the mobile gene itself generally correlates with increased structural diversity in its flanking regions, demonstrating a relationship between rates of mutational evolution and rates of structural evolution, and find a bias for greater structural diversity upstream. Our framework is a starting point to investigate general rules that apply to the horizontal spread of new genes through bacterial populations

PanGraph: scalable bacterial pan-genome graph construction

The genomic diversity of microbes is commonly parameterized as SNPs relative to a reference genome of a well-characterized, but arbitrary, isolate. However, any reference genome contains only a fraction of the microbial pangenome, the total set of genes observed in a given species. Reference-based approaches are thus blind to the dynamics of the accessory genome, as well as variation within gene order and copy number. With the widespread usage of long-read sequencing, the number of high-quality, complete genome assemblies has increased dramatically. In addition to pangenomic approaches that focus on the variation in the sets of genes present in different genomes, complete assemblies allow investigations of the evolution of genome structure and gene order. This latter problem, however, is computationally demanding with few tools available that shed light on these dynamics. Here, we present PanGraph, a Julia-based library and command line interface for aligning whole genomes into a graph. Each genome is represented as a path along vertices, which in turn encapsulate homologous multiple sequence alignments. The resultant data structure succinctly summarizes population-level nucleotide and structural polymorphisms and can be exported into several common formats for either downstream analysis or immediate visualization

Space Telescope Imaging Spectrograph slitless observations of Small Magellanic Cloud Planetary Nebulae: a study on morphology, emission line intensity, and evolution

A sample of 27 Planetary Nebulae (PNs) in the Small Magellanic Clouds (SMC) have been observed with the Hubble Space Telescope Imaging Spectrograph (HST/STIS) to determine their morphology, size, and the spatial variation of the ratios of bright emission lines. The morphologies of SMC PNs are similar to those of LMC and Galactic PNs. However, only a third of the resolved SMC PNs are asymmetric, compared to half in the LMC. The low metallicity environment of the SMC seems to discourage the onset of bipolarity in PNs. We measured the line intensity, average surface brightness (SB), and photometric radius of each nebula in halpha, hbeta, [O III] lambda4959 and 5007, [NII] 6548 and 6584, [S II] lambda6716 and 5731, He I 6678, and [OI] 6300 and 6363. We show that the surface brightness to radius relationship is the same as in LMC PNs, indicating its possible use as a distance scale indicator for Galactic PNs. We determine the electron densities and the ionized masses of the nebulae where the [S II] lines were measured accurately, and we find that the SMC PNs are denser than the LMC PNs by a factor of 1.5. The average ionized mass of the SMC PNs is 0.3 Msun. We also found that the median [O III]/hbeta intensity ratio in the SMC is about half than the corresponding LMC median. We use Cloudy to model the dependence of the [O III]/hbeta ratio on the oxygen abundance. Our models encompass very well the average observed physical quantities. We suggest that the SMC PNs are principally cooled by the carbon lines, making it hard to study their excitation based on the optical lines at our disposal.Comment: Accepted for publication in the Astrophysical Journal, 30 pages, 13 figures, 6 tables. For high resolution version of Figs 1 to 6, see http://archive.stsci.edu/hst/mcpn/home.htm

The relationship between antihypertensive medications and mood disorders: analysis of linked healthcare data for 1.8 million patients

Background: Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD). Method: Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression. Results: For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD. Conclusions: There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD

The curious case of Swift J1753.5-0127: A black hole low-mass X-ray binary analogue to Z cam type dwarf novae

Swift J1753.5-0127 (J1753) is a candidate black hole low-mass X-ray binary (BH-LMXB) that was discovered in outburst in 2005 May. It remained in outburst for ~12 yr, exhibiting a wide range of variability on various time-scales, before entering quiescence after two shortlived, low-luminosity 'mini-outbursts' in 2017 April. The unusually long outburst duration in such a short-period (Porb ˜ 3.24 hr) source, and complex variability observed during this outburst period, challenges the predictions of the widely accepted disc-instability model, which has been shown to broadly reproduce the behaviour of LMXB systems well. The long-term behaviour observed in J1753 is reminiscent of the Z Cam class of dwarf novae, whereby variablemass transfer from the companion star drives unusual outbursts, characterized by stalled decays and abrupt changes in luminosity. Using sophisticated modelling of the multiwavelength light curves and spectra of J1753, during the ~12 yr the source was active, we investigate the hypothesis that periods of enhanced mass transfer from the companion star may have driven this unusually long outburst. Our modelling suggests that J1753 is in fact a BH-LMXB analogue to Z Cam systems, where the variable mass transfer from the companion star is driven by the changing irradiation properties of the system, affecting both the disc and companion star

Large Magellanic Cloud Planetary Nebula Morphology: Probing Stellar Populations and Evolution

Planetary Nebulae (PNe) in the Large Magellanic Cloud (LMC) offer the unique opportunity to study both the Population and evolution of low- and intermediate-mass stars, by means of the morphological type of the nebula. Using observations from our LMC PN morphological survey, and including images available in the HST Data Archive, and published chemical abundances, we find that asymmetry in PNe is strongly correlated with a younger stellar Population, as indicated by the abundance of elements that are unaltered by stellar evolution (Ne, Ar, S). While similar results have been obtained for Galactic PNe, this is the first demonstration of the relationship for extra-galactic PNe. We also examine the relation between morphology and abundance of the products of stellar evolution. We found that asymmetric PNe have higher nitrogen and lower carbon abundances than symmetric PNe. Our two main results are broadly consistent with the predictions of stellar evolution if the progenitors of asymmetric PNe have on average larger masses than the progenitors of symmetric PNe. The results bear on the question of formation mechanisms for asymmetric PNe, specifically, that the genesis of PNe structure should relate strongly to the Population type, and by inference the mass, of the progenitor star, and less strongly on whether the central star is a member of a close binary system.Comment: The Astrophysical Journal Letters, in press 4 figure

Brune Park Sports Hall

This report (ETSU S 1160/18) is one of a series of Energy Performance Assessment full technical reports describing the research results from detailed investigations and long-term (> one year) monitoring of a series of innovative passive buildings in the UK. Brune Park Sports Hall, Gosport, Southampton is a community sports hall designed to exploit daylight to displace electric lighting to reduce electricity use