Clonal analysis of meningococci during a 26 year period prior to the introduction of meningococcal serogroup C vaccines

Meningococcal disease remains a public health burden in the UK and elsewhere. Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were characterised retrospectively to examine the serogroup and clonal structure of the circulating population. 2607 isolates causing invasive disease were available for serogroup and MLST analysis whilst 2517 were available for multilocus sequence typing (MLST) analysis only. Serogroup distribution changed from year to year but serogroups B and C were dominant throughout. Serogroup B was dominant throughout the 1970s and early 1980s until serogroup C became dominant during the mid-1980s. The increase in serogroup C was not associated with one particular sequence type (ST) but was associated with a number of STs, including ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease seen in the 1990s that was due to expansion of the ST-11 clonal complex. While there was considerable diversity among the isolates (309 different STs among the 2607 isolates), a large proportion of isolates (59.9%) were associated with only 10 STs. These data highlight meningococcal diversity over time and the need for ongoing surveillance during the introduction of new meningococcal vaccines

Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods

While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1, and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labeling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean

Type II-P Supernovae from the SDSS-II Supernova Survey and the Standardized Candle Method

We apply the Standardized Candle Method (SCM) for Type II Plateau supernovae (SNe II-P), which relates the velocity of the ejecta of a SN to its luminosity during the plateau, to 15 SNe II-P discovered over the three season run of the Sloan Digital Sky Survey - II Supernova Survey. The redshifts of these SNe - 0.027 < z < 0.144 - cover a range hitherto sparsely sampled in the literature; in particular, our SNe II-P sample contains nearly as many SNe in the Hubble flow (z > 0.01) as all of the current literature on the SCM combined. We find that the SDSS SNe have a very small intrinsic I-band dispersion (0.22 mag), which can be attributed to selection effects. When the SCM is applied to the combined SDSS-plus-literature set of SNe II-P, the dispersion increases to 0.29 mag, larger than the scatter for either set of SNe separately. We show that the standardization cannot be further improved by eliminating SNe with positive plateau decline rates, as proposed in Poznanski et al. (2009). We thoroughly examine all potential systematic effects and conclude that for the SCM to be useful for cosmology, the methods currently used to determine the Fe II velocity at day 50 must be improved, and spectral templates able to encompass the intrinsic variations of Type II-P SNe will be needed.Comment: Accepted for publication by ApJ; data used in this paper can be downloaded from http://sdssdp47.fnal.gov/sdsssn/photometry/SNIIp.tgz; citation errors correcte

Type Ia Supernova Properties as a Function of the Distance to the Host Galaxy in the SDSS-II SN Survey

We use type-Ia supernovae (SNe Ia) discovered by the SDSS-II SN Survey to search for dependencies between SN Ia properties and the projected distance to the host galaxy center, using the distance as a proxy for local galaxy properties (local star-formation rate, local metallicity, etc.). The sample consists of almost 200 spectroscopically or photometrically confirmed SNe Ia at redshifts below 0.25. The sample is split into two groups depending on the morphology of the host galaxy. We fit light-curves using both MLCS2k2 and SALT2, and determine color (AV, c) and light-curve shape (delta, x1) parameters for each SN Ia, as well as its residual in the Hubble diagram. We then correlate these parameters with both the physical and the normalized distances to the center of the host galaxy and look for trends in the mean values and scatters of these parameters with increasing distance. The most significant (at the 4-sigma level) finding is that the average fitted AV from MLCS2k2 and c from SALT2 decrease with the projected distance for SNe Ia in spiral galaxies. We also find indications that SNe in elliptical galaxies tend to have narrower light-curves if they explode at larger distances, although this may be due to selection effects in our sample. We do not find strong correlations between the residuals of the distance moduli with respect to the Hubble flow and the galactocentric distances, which indicates a limited correlation between SN magnitudes after standardization and local host metallicity.Comment: Accepted for publication in The Astrophysical Journal (33 pages, 5 figures, 8 tables

Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods

While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1, and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labeling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean

The volumetric rate of normal type Ia supernovae in the local universe discovered by the Palomar Transient Factory

We present the volumetric rate of normal type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory (PTF). Using strict data-quality cuts, and considering only periods when the PTF maintained a regular cadence, PTF discovered 90 SNe Ia at $z\le0.09$ in a well-controlled sample over three years of operation (2010-2012). We use this to calculate the volumetric rate of SN Ia events by comparing this sample to simulations of hundreds of millions of SN Ia light curves produced in statistically representative realisations of the PTF survey. This quantifies the recovery efficiency of each PTF SN Ia event, and thus the relative weighting of each event. From this, the volumetric SN Ia rate was found to be $r_v=2.43\pm0.29\,\text{(stat)}_{-0.19}^{+0.33}\text{(sys)}\times10^{-5}\,\text{SNe yr}^{-1}\,\text{Mpc}^{-3}\, h_{70}^{3}$. This represents the most precise local measurement of the SN Ia rate. We fit a simple SN Ia delay-time distribution model, $\propto\mathrm{t}^{-\beta}$, to our PTF rate measurement combined with a literature sample of rate measurements from surveys at higher-redshifts. We find $\beta{\sim}1$, consistent with a progenitor channel governed by the gravitational in-spiral of binary white dwarfs.Comment: 14 pages, 8 figure

Decellularised skeletal muscles allow functional muscle regeneration by promoting host cell migration

Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis

Host galaxy identification for supernova surveys

Host galaxy identification is a crucial step for modern supernova (SN) surveys such as the Dark Energy Survey (DES) and the Large Synoptic Survey Telescope (LSST), which will discover SNe by the thousands. Spectroscopic resources are limited, so in the absence of real-time SN spectra these surveys must rely on host galaxy spectra to obtain accurate redshifts for the Hubble diagram and to improve photometric classification of SNe. In addition, SN luminosities are known to correlate with host-galaxy properties. Therefore, reliable identification of host galaxies is essential for cosmology and SN science. We simulate SN events and their locations within their host galaxies to develop and test methods for matching SNe to their hosts. We use both real and simulated galaxy catalog data from the Advanced Camera for Surveys General Catalog and MICECATv2.0, respectively. We also incorporate "hostless" SNe residing in undetected faint hosts into our analysis, with an assumed hostless rate of 5%. Our fully automated algorithm is run on catalog data and matches SNe to their hosts with 91% accuracy. We find that including a machine learning component, run after the initial matching algorithm, improves the accuracy (purity) of the matching to 97% with a 2% cost in efficiency (true positive rate). Although the exact results are dependent on the details of the survey and the galaxy catalogs used, the method of identifying host galaxies we outline here can be applied to any transient survey

Quantitative trait locus analysis identifies Gabra3 as a regulator of behavioral despair in mice

The Tail Suspension Test (TST), which measures behavioral despair, is widely used as an animal model of human depressive disorders and antidepressant efficacy. In order to identify novel genes involved in the regulation of TST performance, we crossed an inbred strain exhibiting low immobility in the TST (RIIIS/J) with two high-immobility strains (C57BL/6J and NZB/BlNJ) to create two distinct F2 hybrid populations. All F2 offspring (n = 655) were genotyped at high density with a panel of SNP markers. Whole-genome interval mapping of the F2 populations identified statistically significant quantitative trait loci (QTLs) on mouse chromosomes (MMU) 4, 6, and X. Microarray analysis of hippocampal gene expression in the three parental strains was used to identify potential candidate genes within the MMUX QTLs identified in the NZB/BlNJ × RIIIS/J cross. Expression of Gabra3, which encodes the GABAA receptor α3 subunit, was robust in the hippocampus of B6 and RIIIS mice but absent from NZB hippocampal tissue. To verify the role of Gabra3 in regulating TST behavior in vivo, mice were treated with SB-205384, a positive modulator of the α3 subunit. SB-205384 significantly reduced TST immobility in B6 mice without affecting general activity, but it had no effect on behavior in NZB mice. This work suggests that GABRA3 regulates a behavioral endophenotype of depression and establishes this gene as a viable new target for the study and treatment of human depression