Immunogenicity and Protective Efficacy of a Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen in Pigs

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain (rPICV-H3). T04 was vaccinated with the recombinant HA protein antigen of the same H3N2 strain. Pigs were vaccinated twice at day 0 and day 21 and challenged at day 43 by intra-tracheal inoculation with the homologous H3N2 IAV-S strain. After vaccination, all pigs in T03 and T04 groups were seroconverted and exhibited high titers of plasma neutralizing antibodies. After challenge, high levels of IAV-S RNA were detected in the nasal swabs and bronchioalveolar lavage fluid of pigs in T01 and T02 but not in the T03 and T04 groups. Similarly, lung lesions were observed in T01 and T02, but not in the T03 and T04 groups. No significant difference in terms of protection was observed between the T03 and T04 group. Collectively, our results demonstrate that the rPICV-H3 vectored vaccine elicited protective immunity against IAV-S challenge. This study shows that rPICV is a promising viral vector for the development of vaccines against IAV-S

HETDEX pilot survey for emission-line galaxies - I. Survey design, performance, and catalog

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 sq.arcmin with a 3500-5800 Ang. bandpass under 5 Ang. full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4-20 E-17 erg/s/sq.cm depending on the wavelength, and Ly-alpha luminosities between 3-6 E42 erg/s are detectable. This survey method complements narrowband and color-selection techniques in the search for high redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 104 galaxies via their high redshift Ly-alpha emission at 1.9<z<3.8, and the majority of the remainder objects are low redshift [OII]3727 emitters at z<0.56. The classification between low and high redshift objects depends on rest frame equivalent width, as well as other indicators, where available. Based on matches to X-ray catalogs, the active galactic nuclei (AGN) fraction amongst the Ly-alpha emitters (LAEs) is 6%. We also analyze the survey's completeness and contamination properties through simulations. We find five high-z, highly-significant, resolved objects with full-width-half-maximum sizes >44 sq.arcsec which appear to be extended Ly-alpha nebulae. We also find three high-z objects with rest frame Ly-alpha equivalent widths above the level believed to be achievable with normal star formation, EW(rest)>240 Ang.Comment: 45 pages, 36 figures, 5 tables, submitted to ApJ

SMPDB: The Small Molecule Pathway Database

The Small Molecule Pathway Database (SMPDB) is an interactive, visual database containing more than 350 small-molecule pathways found in humans. More than 2/3 of these pathways (>280) are not found in any other pathway database. SMPDB is designed specifically to support pathway elucidation and pathway discovery in clinical metabolomics, transcriptomics, proteomics and systems biology. SMPDB provides exquisitely detailed, hyperlinked diagrams of human metabolic pathways, metabolic disease pathways, metabolite signaling pathways and drug-action pathways. All SMPDB pathways include information on the relevant organs, organelles, subcellular compartments, protein cofactors, protein locations, metabolite locations, chemical structures and protein quaternary structures. Each small molecule is hyperlinked to detailed descriptions contained in the Human Metabolome Database (HMDB) or DrugBank and each protein or enzyme complex is hyperlinked to UniProt. All SMPDB pathways are accompanied with detailed descriptions, providing an overview of the pathway, condition or processes depicted in each diagram. The database is easily browsed and supports full text searching. Users may query SMPDB with lists of metabolite names, drug names, genes/protein names, SwissProt IDs, GenBank IDs, Affymetrix IDs or Agilent microarray IDs. These queries will produce lists of matching pathways and highlight the matching molecules on each of the pathway diagrams. Gene, metabolite and protein concentration data can also be visualized through SMPDB’s mapping interface. All of SMPDB’s images, image maps, descriptions and tables are downloadable. SMPDB is available at: http://www.smpdb.ca

The cytotoxic T cell proteome and its shaping by the kinase mTOR

High-resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes and mTORC1 selectively repressed and promoted expression of subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3)) production in CTL. mTORC1 was shown to repress PtdIns(3,4,5)P(3) production and to determine the mTORC2 requirement for activation of the kinase Akt. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function

Career guidance and the changing world of work: Contesting responsibilising notions of the future.

Career guidance is an educational activity which helps individuals to manage their participation in learning and work and plan for their futures. Unsurprisingly career guidance practitioners are interested in how the world of work is changing and concerned about threats of technological unemployment. This chapter argues that the career guidance field is strongly influenced by a “changing world of work” narrative which is drawn from a wide body of grey literature produced by think tanks, supra-national bodies and other policy influencers. This body of literature is political in nature and describes the future of work narrowly and within the frame of neoliberalism. The ‘changing world of work’ narrative is explored through a thematic analysis of grey literature and promotional materials for career guidance conferences. The chapter concludes by arguing that career guidance needs to adopt a more critical stance on the ‘changing world of work’ and to offer more emancipatory alternatives.N/