Control of Salmonella Virulence in the Natural Host

The long term goal of this research is to understand the mechanisms that govern Salmonella virulence in the natural host. Much of the genetic and pathogenesis studies have focused on using the murine model of salmonellosis. Although the results from using the model have been useful, there have been several cases where mutants of Salmonella not showing virulence in mice have been virulent in the natural host and visa versa. Therefore, virulence may be mediated by the host to some degree. We have chosen Salmonella choleraesuis which is host-adapted to swine, to study particular genes that may be crucial in causing disease. Specifically, we have begun a project to evaluate several mutants of Salmonella choleraesuis and test them for virulence. We will use strains containing separately or in pairs the following mutations: sly, rpoS, and spvR

Vaccination with attenuated Salmonella enterica Dublin expressing E coli O157:H7 outer membrane protein Intimin induces transient reduction of fecal shedding of E coli O157:H7 in cattle

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>serogroup O157:H7 has emerged as an important zoonotic bacterial pathogen, causing a range of symptoms from self-limiting bloody diarrhea to severe hemorrhagic colitis and hemolytic-uremic syndrome in humans. Beef and dairy cattle are considered the most important animal reservoirs for this pathogen. One of the important virulence characteristics of <it>E. coli </it>O157:H7 is the <it>eaeA </it>gene encoding the 97 kDa surface protein intimin. Intimin is required for attachment and effacement during the interaction of enterohemorrhagic <it>E. coli </it>with human and bovine neonatal enterocytes. The present study was undertaken to test the hypothesis that an adaptive mucosal immune response directed against intimin will reduce or prevent enteric colonization and fecal shedding of <it>E. coli </it>O157:H7 in cattle.</p> <p>Results</p> <p>Cattle were orally inoculated with either milk (control), milk with live attenuated <it>Salmonella enterica </it>serovar Dublin (vector), or milk with live attenuated recombinant <it>S</it>. Dublin expressing intimin (vaccinated) on days 0, 14 and 28. On day 98, all calves were challenged orally with <it>E. coli </it>O157:H7 to evaluate whether vaccination with the recombinant <it>S</it>. Dublin expressing intimin would reduce the level of <it>E. coli </it>O157:H7 fecal shedding.</p> <p>During the first 28 days, vaccinated calves shed both the vector strain and the intimin-expressing <it>S</it>. Dublin strain at a similar level. The vector strain was shed for a significantly longer period as compared to the level of recombinant vaccine strain. Calves that received the intimin-expressed vaccine ceased shedding <it>S</it>. Dublin from day 28 to day 63. All calves were challenged with <it>E. coli </it>O157:H7 on day 98 to determine the effect on fecal shedding of <it>E. coli </it>O157:H7. The amount of <it>E. coli </it>O157:H7 in feces was measured for 30 days post-challenge. We observed a transient clearance of <it>E. coli </it>O157:H7 from the feces in the vaccinated calves. The magnitude of fecal <it>E. coli </it>O157:H7 shedding did not correlate with the presence of intimin-specific fecal IgA.</p> <p>Conclusion</p> <p>Oral vaccination with live attenuated recombinant <it>S</it>. Dublin expressing intimin reduced enteric colonization and fecal shedding of <it>E. coli </it>O157:H7. However, the transient clearance of <it>E. coli </it>O157:H7 was not associated with an enhanced IgA-mediated mucosal immune response.</p

Tracking forest phenology and seasonal physiology using digital repeat photography: a critical assessment

Digital repeat photography is becoming widely used for near-surface remote sensing of vegetation. Canopy greenness, which has been used extensively for phenological applications, can be readily quantified from camera images. Important questions remain, however, as to whether the observed changes in canopy greenness are directly related to changes in leaf-level traits, changes in canopy structure, or some combination thereof. We investigated relationships between canopy greenness and various metrics of canopy structure and function, using five years (2008–2012) of automated digital imagery, ground observations of phenological transitions, leaf area index (LAI) measurements, and eddy covariance estimates of gross ecosystem photosynthesis from the Harvard Forest, a temperate deciduous forest in the northeastern United States. Additionally, we sampled canopy sunlit leaves on a weekly basis throughout the growing season of 2011. We measured physiological and morphological traits including leaf size, mass (wet/dry), nitrogen content, chlorophyll fluorescence, and spectral reflectance and characterized individual leaf color with flatbed scanner imagery. Our results show that observed spring and autumn phenological transition dates are well captured by information extracted from digital repeat photography. However, spring development of both LAI and the measured physiological and morphological traits are shown to lag behind spring increases in canopy greenness, which rises very quickly to its maximum value before leaves are even half their final size. Based on the hypothesis that changes in canopy greenness represent the aggregate effect of changes in both leaf-level properties (specifically, leaf color) and changes in canopy structure (specifically, LAI), we developed a two end-member mixing model. With just a single free parameter, the model was able to reproduce the observed seasonal trajectory of canopy greenness. This analysis shows that canopy greenness is relatively insensitive to changes in LAI at high LAI levels, which we further demonstrate by assessing the impact of an ice storm on both LAI and canopy greenness. Our study provides new insights into the mechanisms driving seasonal changes in canopy greenness retrieved from digital camera imagery. The nonlinear relationship between canopy greenness and canopy LAI has important implications both for phenological research applications and for assessing responses of vegetation to disturbances.Organismic and Evolutionary Biolog

An ongoing case-control study to evaluate the NHS Bowel Cancer Screening Programme

© 2014 Massat et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences

Palladium-coated kapton for use on dust detectors in low earth orbit: Performance under hypervelocity impact and atomic oxygen exposure

Observation of dust and debris in the near Earth environment is a field of great commercial and scientific interest, vital to maximising the operational and commercial life-cycle of satellites and reducing risk to increasing numbers of astronauts in Low Earth Orbit (LEO). To this end, monitoring and assessment of the flux of particles is of paramount importance to the space industry and wider socio-economic interests that depend upon data products/services from orbital infrastructure. We have designed a passive space dust detector to investigate the dust environment in LEO—the Orbital Dust Impact Experiment (ODIE). ODIE is designed for deployment in LEO for ~1 year, whereupon it would be returned to Earth for analysis of impact features generated by dust particles. The design emphasises the ability to distinguish between the orbital debris (OD) relating to human space activity and the naturally occurring micrometeoroid (MM) population at millimetre to submillimetre scales. ODIE is comprised of multiple Kapton foils, which have shown great potential to effectively preserve details of the impacting particles’ size and chemistry, with residue chemistry being used to interpret an origin (OD vs. MM). LEO is a harsh environment—the highly erosive effects of atomic oxygen damage Kapton foil—requiring the use of a protective coating. Common coatings available for Kapton (e.g., Al, SiO2, etc.) are problematic for subsequent analysis and interpretation of OD vs. MM origin, being a common elemental component of MM or OD, or having X-ray emission peaks overlapping with those of elements used to distinguish MM from OD. We thus propose palladium coatings as an alternative for this application. Here we report on the performance of palladium as a protective coating for a Kapton-based passive dust detector when exposed to atomic oxygen and impact. When subjected to impact, we observe that thicker coatings suffer delamination such that a coating of <50 nm is recommended. Analysis of atomic oxygen exposed samples shows a thin 10 nm coating of palladium significantly reduces the mass loss of Kapton, while coatings of 25 nm and over perform as well as or better than other commonly used coating