Molecular characterisation of virulence graded field isolates of myxoma virus

<p>Abstract</p> <p>Background</p> <p><it>Myxoma virus </it>(MV) has been endemic in Europe since shortly after its deliberate release in France in 1952. While the emergence of more resistant hosts and more transmissible and attenuated virus is well documented, there have been relatively few studies focused on the sequence changes incurred by the virus as it has adapted to its new host. In order to identify regions of variability within the MV genome to be used for phylogenetic studies and to try to investigate causes of MV strain attenuation we have molecularly characterised nine strains of MV isolated in Spain between the years 1992 and 1995 from wide ranging geographic locations and which had been previously graded for virulence by experimental infection of rabbits.</p> <p>Results</p> <p>The findings reported here show the analysis of 16 genomic regions accounting for approximately 10% of the viral genomes. Of the 20 genes analysed 5 (M034L, M069L, M071L, M130R and M135R) were identical in all strains and 1 (M122R) contained only a single point mutation in an individual strain. Four genes (M002L/R, M009L, M036L and M017L) showed insertions or deletions that led to disruption of the ORFs.</p> <p>Conclusions</p> <p>The findings presented here provide valuable tools for strain differentiation and phylogenetic studies of MV isolates and some clues as to the reasons for virus attenuation in the field.</p

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early

Early Vegetation Development on an Exposed Reservoir: Implications for Dam Removal

The 4-year drawdown of Horsetooth Reservoir, Colorado, for dam maintenance, provides a case study analog of vegetation response on sediment that might be exposed from removal of a tall dam. Early vegetation recovery on the exposed reservoir bottom was a combination of (1) vegetation colonization on bare, moist substrates typical of riparian zones and reservoir sediment of shallow dams and (2) a shift in moisture status from mesic to the xeric conditions associated with the pre-impoundment upland position of most of the drawdown zone. Plant communities changed rapidly during the first four years of exposure, but were still substantially different from the background upland plant community. Predictions from the recruitment box model about the locations of Populus deltoides subsp. monilifera (plains cottonwood) seedlings relative to the water surface were qualitatively confirmed with respect to optimum locations. However, the extreme vertical range of water surface elevations produced cottonwood seed regeneration well outside the predicted limits of drawdown rate and height above late summer stage. The establishment and survival of cottonwood at high elevations and the differences between the upland plant community and the community that had developed after four years of exposure suggest that vegetation recovery following tall dam removal will follow a trajectory very different from a simple reversal of the response to dam construction, involving not only long time scales of establishment and growth of upland vegetation, but also possibly decades of persistence of legacy vegetation established during the reservoir to upland transition

Cellular Immunity Confers Transient Protection in Experimental Buruli Ulcer following BCG or Mycolactone-Negative Mycobacterium ulcerans Vaccination

BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-gamma T cell response in the draining lymph node (DLN). BCG vaccination also resulted in cell-mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-gamma and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

The effects of size of opening in vegetation and litter cover on seedling establishment of goldenrods ( Solidago spp.)

We investigated the effects of size of opening in the vegetation and litter cover on seedling establishment of two species of goldenrods ( Solidago spp.) in an abandoned field in southwestern Michigan, U.S.A. Seeds of S. canadensis and S. juncea were sown into clipped plots, ranging from 0 cm (control, unclipped) to 100 cm in diameter, with and without litter. Seedling emergence, survival and growth were followed for one year. Soil moisture was not significantly different among the opening sizes, but, within a size, tended to be lower when litter was removed. Light intensity at the soil surface was positively related to opening size early in the growing season, but later in the growing season reached a maximum in intermediate-sized openings and then leveled off.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47747/1/442_2004_Article_BF00379516.pd

Species trait shifts in vegetation and soil seed bank during fen degradation

Fens in Central Europe are characterised by waterlogged organic substrate and low productivity. Human-induced changes due to drainage and mowing lead to changes in plant species composition from natural fen communities to fen meadows and later to over-drained, degraded meadows. Moderate drainage leads to increased vegetation productivity, and severe drainage results in frequent soil disturbances and less plant growth. In the present article, we analyse changes in plant trait combinations in the vegetation and the soil seed bank as well as changes in the seed bank types along gradient of drainage intensity. We hypothesize that an increase in productivity enhances traits related to persistence and that frequent disturbance selects for regeneration traits. We use multivariate statistics to analyse data from three disturbance levels: undisturbed fen, slightly drained fen meadow and severely drained degraded meadow. We found that the abundance of plants regenerating from seeds and accumulating persistent seed banks was increasing with degradation level, while plants reproducing vegetatively were gradually eliminated along the same trajectory. Plants with strong resprouting abilities increased during degradation. We also found that shifts in trait combinations were similar in the aboveground vegetation and in soil seed banks. We found that the density of short-term persistent seeds in the soil is highest in fen meadows and the density of long-term persistent seeds is highest in degraded meadows. The increase in abundance of species with strong regeneration traits at the cost of species with persistence-related traits has negative consequences for the restoration prospects of severely degraded sites

The architecture and effect of participation: a systematic review of community participation for communicable disease control and elimination. Implications for malaria elimination

Community engagement and participation has played a critical role in successful disease control and elimination campaigns in many countries. Despite this, its benefits for malaria control and elimination are yet to be fully realized. This may be due to a limited understanding of the influences on participation in developing countries as well as inadequate investment in infrastructure and resources to support sustainable community participation. This paper reports the findings of an atypical systematic review of 60 years of literature in order to arrive at a more comprehensive awareness of the constructs of participation for communicable disease control and elimination and provide guidance for the current malaria elimination campaign.Evidence derived from quantitative research was considered both independently and collectively with qualitative research papers and case reports. All papers included in the review were systematically coded using a pre-determined qualitative coding matrix that identified influences on community participation at the individual, household, community and government/civil society levels. Colour coding was also carried out to reflect the key primary health care period in which community participation programmes originated. These processes allowed exhaustive content analysis and synthesis of data in an attempt to realize conceptual development beyond that able to be achieved by individual empirical studies or case reports.Of the 60 papers meeting the selection criteria, only four studies attempted to determine the effect of community participation on disease transmission. Due to inherent differences in their design, interventions and outcome measures, results could not be compared. However, these studies showed statistically significant reductions in disease incidence or prevalence using various forms of community participation. The use of locally selected volunteers provided with adequate training, supervision and resources are common and important elements of the success of the interventions in these studies. In addition, qualitative synthesis of all 60 papers elucidates the complex architecture of community participation for communicable disease control and elimination which is presented herein.The current global malaria elimination campaign calls for a health systems strengthening approach to provide an enabling environment for programmes in developing countries. In order to realize the benefits of this approach it is vital to provide adequate investment in the 'people' component of health systems and understand the multi-level factors that influence their participation. The challenges of strengthening this component of health systems are discussed, as is the importance of ensuring that current global malaria elimination efforts do not derail renewed momentum towards the comprehensive primary health care approach. It is recommended that the application of the results of this systematic review be considered for other diseases of poverty in order to harmonize efforts at building 'competent communities' for communicable disease control and optimising health system effectiveness

Varying constants, Gravitation and Cosmology

Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit