Did GW170817 harbor a pulsar?

If the progenitor of GW170817 harbored a pulsar, then a Poynting flux dominated bow-shock cavity would have been expected to form around the traveling binary. The characteristic size of this evacuated region depends strongly on the spin-down evolution of the pulsar companion, which in turn depends on the merging timescale of the system. If this evacuated region is able to grow to a sufficiently large scale, then the deceleration of the jet, and thus the onset of the afterglow, would be noticeably delayed. The first detection of afterglow emission, which was uncovered 9.2 days after the $\gamma$-ray burst trigger, can thus be used to constrain the size of a pre-existing pulsar-wind cavity. We use this information, together with a model of the jet to place limits on the presence of a pulsar in GW170817 and discuss the derived constraints in the context of the observed double neutron star binary population. We find that the majority of Galactic systems that are close enough to merge within a Hubble time would have carved a discernibly large pulsar-wind cavity, inconsistent with the onset timescale of the X-ray afterglow of GW170817. Conversely, the recently detected system J1913+1102, which host a low-luminosity pulsar, provides a congruous Milky Way analog of GW170817's progenitor model. This study highlights the potential of the proposed observational test for gaining insight into the origin of double neutron star binaries, in particular if the properties of Galactic systems are representative of the overall merging population.Comment: Accepted for publication in ApJL, 6 pages, 5 figure

The Biology and Biochemistry of PhoH2 proteins

PhoH2 proteins are found in a diverse range of organisms. To date little is known about these proteins and the role they play in the organisms in which they reside. PhoH2 is a PIN PhoH domain fusion, and these proteins are currently annotated as having unknown function and are described as PhoH like. PhoH domains are thought to be ATPases and all characterised PIN domain proteins are RNases. Most efforts have focussed on determining the role of PIN domain proteins that comprise the toxic component (VapC) of VapBC toxin antitoxin systems, in which the PIN domain is coexpressed as part of an operon with an inhibitor (VapB). In the remaining cases where PIN domain proteins can be found such as PIN PhoH domain fusions, these cases remain unexamined. This thesis describes the biological and biochemical characterisation of the PIN PhoH protein, PhoH2 from Mycobacterium tuberculosis and Mycobacterium smegmatis, along with a preliminary structural characterisation of a thermophilic PhoH2 protein homologue. The phoH2 gene from both mycobacterial organisms was found to be expressed as part of a long mRNA transcript. Examination of these transcripts revealed possible alternative 5’ start sites out of frame with the phoH2 gene. For protein overexpression, and ‘normal’ growth and colony formation with conditional overexpression, phoH2 from M. tuberculosis required 152 bp of the 5’ sequence directly upstream of the annotated phoH2 gene (annotated here as phoH2alt). PhoH2 proteins: PhoH2alt MTB, PhoH2alt MSMEG and PhoH2MSMEG show ATP/Mg²⁺ dependent, sequence specific RNA unwinding and cleavage. The sequence (A C) (A/U) (A/U) (G/C) U was deduced as a substrate for PhoH2, and PhoH2alt MTB also demonstrated unwinding and cleavage activity on its upstream ~152 base RNA transcript, suggesting a potential autoregulatory mechanism. Structural analysis of a thermophilic PhoH2 protein homologue has provided preliminary crystallographic data which along with electron microscopy suggest a ring like hexameric PhoH2 oligomer

A marker of biological ageing predicts adult risk preference in European starlings, Sturnus vulgaris

Why are some individuals more prone to gamble than others? Animals often show preferences between 2 foraging options with the same mean reward but different degrees of variability in the reward, and such risk preferences vary between individuals. Previous attempts to explain variation in risk preference have focused on energy budgets, but with limited empirical support. Here, we consider whether biological ageing, which affects mortality and residual reproductive value, predicts risk preference. We studied a cohort of European starlings (Sturnus vulgaris) in which we had previously measured developmental erythrocyte telomere attrition, an established integrative biomarker of biological ageing. We measured the adult birds’ preferences when choosing between a fixed amount of food and a variable amount with an equal mean. After controlling for change in body weight during the experiment (a proxy for energy budget), we found that birds that had undergone greater developmental telomere attrition were more risk averse as adults than were those whose telomeres had shortened less as nestlings. Developmental telomere attrition was a better predictor of adult risk preference than either juvenile telomere length or early-life food supply and begging effort. Our longitudinal study thus demonstrates that biological ageing, as measured via developmental telomere attrition, is an important source of lasting differences in adult risk preferences

Mass spectrometry of the white adipose metabolome in a hibernating mammal reveals seasonal changes in alternate fuels and carnitine derivatives

Mammalian hibernators undergo substantial changes in metabolic function throughout the seasonal hibernation cycle. We report here the polar metabolomic profile of white adipose tissue isolated from active and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Polar compounds in white adipose tissue were extracted from five groups representing different timepoints throughout the seasonal activity-torpor cycle and analyzed using hydrophilic interaction liquid chromatography-mass spectrometry in both the positive and negative ion modes. A total of 224 compounds out of 660 features detected after curation were annotated. Unsupervised clustering using principal component analysis revealed discrete clusters representing the different seasonal timepoints throughout hibernation. One-way analysis of variance and feature intensity heatmaps revealed metabolites that varied in abundance between active and torpid timepoints. Pathway analysis compared against the KEGG database demonstrated enrichment of amino acid metabolism, purine metabolism, glycerophospholipid metabolism, and coenzyme A biosynthetic pathways among our identified compounds. Numerous carnitine derivatives and a ketone that serves as an alternate fuel source, betahydroxybutyrate (BHB), were among molecules found to be elevated during torpor. Elevated levels of the BHB-carnitine conjugate during torpor suggests the synthesis of beta-hydroxybutyrate in white adipose mitochondria, which may contribute directly to elevated levels of circulating BHB during hibernation

Mass spectrometry of the white adipose metabolome in a hibernating mammal reveals seasonal changes in alternate fuels and carnitine derivatives

Mammalian hibernators undergo substantial changes in metabolic function throughout the seasonal hibernation cycle. We report here the polar metabolomic profile of white adipose tissue isolated from active and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Polar compounds in white adipose tissue were extracted from five groups representing different timepoints throughout the seasonal activity-torpor cycle and analyzed using hydrophilic interaction liquid chromatography-mass spectrometry in both the positive and negative ion modes. A total of 224 compounds out of 660 features detected after curation were annotated. Unsupervised clustering using principal component analysis revealed discrete clusters representing the different seasonal timepoints throughout hibernation. One-way analysis of variance and feature intensity heatmaps revealed metabolites that varied in abundance between active and torpid timepoints. Pathway analysis compared against the KEGG database demonstrated enrichment of amino acid metabolism, purine metabolism, glycerophospholipid metabolism, and coenzyme A biosynthetic pathways among our identified compounds. Numerous carnitine derivatives and a ketone that serves as an alternate fuel source, betahydroxybutyrate (BHB), were among molecules found to be elevated during torpor. Elevated levels of the BHB-carnitine conjugate during torpor suggests the synthesis of beta-hydroxybutyrate in white adipose mitochondria, which may contribute directly to elevated levels of circulating BHB during hibernation

Early-life adversity accelerates cellular ageing and affects adult inflammation: experimental evidence from the European starling

Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points

The three lipocalins of egg-white: only Ex-FABP inhibits siderophore-dependent iron sequestration by Salmonella Enteritidis

Salmonella Enteritidis is the most prevalent food-borne pathogen associated with egg-related outbreaks in the European Union. During egg colonization, S. Enteritidis must resist the powerful anti-bacterial activities of egg white (EW) and overcome ovotransferrin-imposed iron-restriction (the most important anti-bacterial mechanism of EW). Many pathogens respond to iron restriction by secreting iron-chelating chemicals called siderophores but EW contains a siderophore-sequestering “lipocalin” protein (Ex-FABP) that is predicted to limit the usefulness of siderophores in EW. S. Enteritidis produces two siderophores: enterobactin, which is strongly bound by Ex-FABP; and the di-glucosylated enterobactin-derivative, salmochelin (a so-called “stealth” siderophore), which is not recognized by Ex-FABP. Thus, production of salmochelin may allow S. Enteritidis to escape Ex-FABP-mediated growth inhibition under iron restriction although it is unclear whether its EW concentration is sufficient to inhibit pathogens. Further, two other lipocalins (Cal-γ and α-1-ovoglycoprotein) are found in EW but their siderophore sequestration potential remains unexplored. In addition, the effect of EW lipocalins on the major EW pathogen, S. Enteritidis, has yet to be reported. We overexpressed and purified the three lipocalins of EW and investigated their ability to interact with the siderophores of S. Enteritidis, as well as their EW concentrations. The results show that Ex-FABP is present in EW at concentrations (5.1 μM) sufficient to inhibit growth of a salmochelin-deficient S. Enteritidis mutant under iron restriction but has little impact on the salmochelin-producing wildtype. Neither Cal-γ nor α-1-ovoglycoprotein bind salmochelin or enterobactin, nor do they inhibit iron-restricted growth of S. Enteritidis. However, both are present in EW at significant concentrations (5.6 and 233 μM, respectively) indicating that α-1-ovoglycoprotein is the 4th most abundant protein in EW, with Cal-γ and Ex-FABP at 11th and 12th most abundant. Further, we confirm the preference (16-fold) of Ex-FABP for the ferrated form (Kd of 5.3 nM) of enterobactin over the iron-free form (Kd of 86.2 nM), and its lack of affinity for salmochelin. In conclusion, our findings show that salmochelin production by S. Enteritidis enables this key egg-associated pathogen to overcome the enterobactin-sequestration activity of Ex-FABP when this lipocalin is provided at levels found in EW

The hydrodynamic evolution of binary black holes embedded within the vertically stratified disks of active galactic nuclei

Stellar-mass black holes can become embedded within the gaseous disks of active galactic nuclei (AGNs). Afterwards, their interactions are mediated by their gaseous surroundings. In this work, we study the evolution of stellar-mass binary black holes (BBHs) embedded within AGN disks using a combination of three-dimensional hydrodynamic simulations and analytic methods, focusing on environments in which the AGN disk scale height $H$ is $\gtrsim$ the BBH sphere of influence. We model the local surroundings of the embedded BBHs using a wind tunnel formalism and characterize different accretion regimes based on the local properties of the disk, which range from wind-dominated to quasi-spherical. We use our simulations to develop prescriptions for mass accretion and drag for embedded BBHs. We use these prescriptions, along with AGN disk models that can represent the Toomre-unstable outer regions of AGN disks, to study the long-term evolution of the BBHs as they migrate through the disk. We find that BBHs typically merge within $\lesssim 5-30\,{\rm Myr}$, increasing their mass significantly in the process, allowing BBHs to enter (or cross) the pair-instability supernova mass gap. The rate at which gas is supplied to these BBHs often exceeds the Eddington limit, sometimes by several orders of magnitude. We conclude that most embedded BBHs will merge before migrating significantly in the disk. Depending on the conditions of the ambient gas and the distance to the system, LISA can detect the transition between the gas-dominated and gravitational wave dominated regime for inspiraling BBHs that are formed sufficiently close to the AGN ($\lesssim$ 0.1 pc). We also discuss possible electromagnetic signatures during and following the inspiral, finding that it is generally unlikely but not inconceivable for the bolometric luminosity of the BBH to exceed that of the host AGN.Comment: 19 pages, 8 figures, submitted to Ap

Understanding the educational experiences and opinions, attainment, achievement and aspirations of looked after children in Wales

This report presents the findings of research that explored the educational experiences attainment and aspirations of looked after children and young people (LACYP) in Wales. The findings of the report are drawn from interviews with LACYP and an analysis of available statistics and literature on the looked after children population