Modelling the Influence of Foot-and-Mouth Disease Vaccine Antigen Stability and Dose on the Bovine Immune Response

Foot and mouth disease virus causes a livestock disease of significant global socio-economic importance. Advances in its control and eradication depend critically on improvements in vaccine efficacy, which can be best achieved by better understanding the complex within-host immunodynamic response to inoculation. We present a detailed and empirically parametrised dynamical mathematical model of the hypothesised immune response in cattle, and explore its behaviour with reference to a variety of experimental observations relating to foot and mouth immunology. The model system is able to qualitatively account for the observed responses during in-vivo experiments, and we use it to gain insight into the incompletely understood effect of single and repeat inoculations of differing dosage using vaccine formulations of different structural stability

Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen

Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals

Herbal supplements in the print media: communicating benefits and risks

Background The rise in use of food supplements based on botanical ingredients (herbal supplements) is depicted as part of a trend empowering consumers to manage their day-to-day health needs, which presupposes access to clear and accurate information to make effective choices. Evidence regarding herbal supplement efficacy is extremely variable so recent regulations eliminating unsubstantiated claims about potential effects leave producers able to provide very little information about their products. Medical practitioners are rarely educated about herbal supplements and most users learn about them via word-of-mouth, allowing dangerous misconceptions to thrive, chief among them the assumption that natural products are inherently safe. Print media is prolific among the information channels still able to freely discuss herbal supplements. Method This study thematically analyses how 76 newspaper/magazine articles from the UK, Romania and Italy portray the potential risks and benefits of herbal supplements. Results Most articles referenced both risks and benefits and were factually accurate but often lacked context and impartiality. More telling was how the risks and benefits were framed in service of a chosen narrative, the paucity of authoritative information allowing journalists leeway to recontextualise herbal supplements in ways that serviced the goals and values of their specific publications and readerships. Conclusion Providing sufficient information to empower consumers should not be the responsibility of print media, instead an accessible source of objective information is required.</p

Function of SSA Subfamily of Hsp70 Within and Across Species Varies Widely in Complementing Saccharomyces cerevisiae Cell Growth and Prion Propagation

BACKGROUND:The cytosol of most eukaryotic cells contains multiple highly conserved Hsp70 orthologs that differ mainly by their spatio-temporal expression patterns. Hsp70s play essential roles in protein folding, transport or degradation, and are major players of cellular quality control processes. However, while several reports suggest that specialized functions of Hsp70 orthologs were selected through evolution, few studies addressed systematically this issue. METHODOLOGY/PRINCIPAL FINDINGS:We compared the ability of Ssa1p-Ssa4p from Saccharomyces cerevisiae and Ssa5p-Ssa8p from the evolutionary distant yeast Yarrowia lipolytica to perform Hsp70-dependent tasks when expressed as the sole Hsp70 for S. cerevisiae in vivo. We show that Hsp70 isoforms (i) supported yeast viability yet with markedly different growth rates, (ii) influenced the propagation and stability of the [PSI(+)] and [URE3] prions, but iii) did not significantly affect the proteasomal degradation rate of CFTR. Additionally, we show that individual Hsp70 orthologs did not induce the formation of different prion strains, but rather influenced the aggregation properties of Sup35 in vivo. Finally, we show that [URE3] curing by the overexpression of Ydj1p is Hsp70-isoform dependent. CONCLUSION/SIGNIFICANCE:Despite very high homology and overlapping functions, the different Hsp70 orthologs have evolved to possess distinct activities that are required to cope with different types of substrates or stress situations. Yeast prions provide a very sensitive model to uncover this functional specialization and to explore the intricate network of chaperone/co-chaperone/substrates interactions

Probing Galaxy Evolution in Massive Clusters Using ACT and DES: Splashback as a Cosmic Clock

We measure the projected number density profiles of galaxies and the splashback feature in clusters selected by the Sunyaev–Zel'dovich effect from the Advanced Atacama Cosmology Telescope (AdvACT) survey using galaxies observed by the Dark Energy Survey (DES). The splashback radius is consistent with CDM-only simulations and is located at ${2.4}_{-0.4}^{+0.3}\,\mathrm{Mpc}\,{h}^{-1}$. We split the galaxies on color and find significant differences in their profile shapes. Red and green-valley galaxies show a splashback-like minimum in their slope profile consistent with theory, while the bluest galaxies show a weak feature at a smaller radius. We develop a mapping of galaxies to subhalos in simulations and assign colors based on infall time onto their hosts. We find that the shift in location of the steepest slope and different profile shapes can be mapped to the average time of infall of galaxies of different colors. The steepest slope traces a discontinuity in the phase space of dark matter halos. By relating spatial profiles to infall time, we can use splashback as a clock to understand galaxy quenching. We find that red galaxies have on average been in clusters over 3.2 Gyr, green galaxies about 2.2 Gyr, while blue galaxies have been accreted most recently and have not reached apocenter. Using the full radial profiles, we fit a simple quenching model and find that the onset of galaxy quenching occurs after a delay of about a gigayear and that galaxies quench rapidly thereafter with an exponential timescale of 0.6 Gyr

Foot-and-mouth disease:overview of motives of disease spread and efficacy of available vaccines

Control and prevention of foot and mouth disease (FMD) by vaccination remains unsatisfactory in endemic countries. Indeed, consistent and new FMD epidemics in previously disease-free countries have precipitated the need for a worldwide control strategy. Outbreaks in vaccinated animals require that a new and safe vaccine be developed against foot and mouth virus (FMDV). FMDV can be eradicated worldwide based on previous scientific information about its spread using existing and modern control strategies

First Measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary-Black-hole Merger GW170814

We present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in ${H}_{0}={75}_{-32}^{+40}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find {H}_{0 {78}_{-24}^{+96}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1} (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

Examination by triangulation : a model for practice teaching

Problems in measuring students' practice abilities are briefly described. A model of examining the competence of students on placements is described. A brief example of how the model might work in practice is offered