Ecological and genetic models of host-pathogen coevolution

A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution

One million dog vaccinations recorded on mHealth innovation used to direct teams in numerous rabies control campaigns

<div><p>Background</p><p>Canine transmitted rabies kills an estimated 59,000 people annually, despite proven methods for elimination through mass dog vaccination. Challenges in directing and monitoring numerous remote vaccination teams across large geographic areas remain a significant barrier to the up-scaling of focal vaccination programmes to sub-national and national level. Smartphone technology (mHealth) is increasingly being used to enhance the coordination and efficiency of public health initiatives in developing countries, however examples of successful scaling beyond pilot implementation are rare. This study describes a smartphone app and website platform, “Mission Rabies App”, used to co-ordinate rabies control activities at project sites in four continents to vaccinate over one million dogs.</p><p>Methods</p><p>Mission Rabies App made it possible to not only gather relevant campaign data from the field, but also to direct vaccination teams systematically in near real-time. The display of user-allocated boundaries on Google maps within data collection forms enabled a project manager to define each team’s region of work, assess their output and assign subsequent areas to progressively vaccinate across a geographic area. This ability to monitor work and react to a rapidly changing situation has the potential to improve efficiency and coverage achieved, compared to regular project management structures, as well as enhancing capacity for data review and analysis from remote areas. The ability to plot the location of every vaccine administered facilitated engagement with stakeholders through transparent reporting, and has the potential to motivate politicians to support such activities.</p><p>Results</p><p>Since the system launched in September 2014, over 1.5 million data entries have been made to record dog vaccinations, rabies education classes and field surveys in 16 countries. Use of the system has increased year-on-year with adoption for mass dog vaccination campaigns at the India state level in Goa and national level in Haiti.</p><p>Conclusions</p><p>Innovative approaches to rapidly scale mass dog vaccination programmes in a sustained and systematic fashion are urgently needed to achieve the WHO, OIE and FAO goal to eliminate canine-transmitted human deaths by 2030. The Mission Rabies App is an mHealth innovation which greatly reduces the logistical and managerial barriers to implementing large scale rabies control activities. Free access to the platform aims to support pilot campaigns to better structure and report on proof-of-concept initiatives, clearly presenting outcomes and opportunities for expansion. The functionalities of the Mission Rabies App may also be beneficial to other infectious disease interventions.</p></div

Effectiveness of a hand-held fan for breathlessness: a randomised phase II trial

<p>Abstract</p> <p>Background</p> <p>Breathlessness is common and distressing in advanced disease. This phase II study aimed to determine the use and acceptance of a hand-held fan (HHF) to relieve breathlessness, to test the effectiveness of the HHF and to evaluate the recruitment into the study.</p> <p>Methods</p> <p>RCT embedded within a longitudinal study testing a HHF over time compared to a wristband. Patients were included in the longitudinal study when suffering from breathlessness due to advanced cancer or COPD III/IV and could opt in the RCT. Primary outcome was use of the HHF and the wristband after two months. Secondary outcomes were recruitment into the trial and change of breathlessness severity after two months, measured on the modified Borg scale. Baseline data were collected in a personal interview and follow-up data by monthly postal questionnaires.</p> <p>Results</p> <p>109 patients were recruited in the longitudinal study of which 70 patients (64%) participated in the RCT. Non-participants had statistically significant less breathlessness (Borg mean 2.6 (SD 1.48) versus 3.7 (SD 1.83); p = 0.003) and a better functional status (Karnofsky status mean 61.9 (SD 11.2) versus 66.7 (SD 11.0); p = 0.03). Attrition due to drop out or death was high in both groups. After two months, about half of the patients used the HHF but only 20% the wristband without a statistical difference (Fisher's exact test p = 0.2). 9/16 patients judged the HHF as helpful after two months and 4/5 patients the wristband. There was no difference in mean breathlessness change scores between the HHF (Borg change score: mean 0.6 (SD 2.10)) and the wristband (mean 0.8 (SD 2.67)) after two months (p = 0.90).</p> <p>Conclusions</p> <p>Symptom burden and low functional status did not restrain patients from participation in the study. Finding a control for a visible intervention is challenging and needs careful consideration to what is acceptable to patients. The preliminary evidence of effectiveness of the HHF could not be proved. Patients often stopped using the HHF but a small group seemed to benefit which was not necessarily related to a relief in breathlessness. Therefore, more work is necessary on selecting and identifying those who might benefit from the HHF.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT01123902</p

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Varying Herbivore Population Structure Correlates with Lack of Local Adaptation in a Geographic Variable Plant-Herbivore Interaction

Local adaptation of parasites to their hosts due to coevolution is a central prediction of many theories in evolutionary biology. However, empirical studies looking for parasite local adaptation show great variation in outcomes, and the reasons for such variation are largely unknown. In a previous study, we showed adaptive differentiation in the arctiid moth Utetheisa ornatrix to its host plant, the pyrrolizidine alkaloid-bearing legume Crotalaria pallida, at the continental scale, but found no differentiation at the regional scale. In the present study, we sampled the same sites to investigate factors that may contribute to the lack of differentiation at the regional scale. We performed field observations that show that specialist and non-specialist polyphagous herbivore incidence varies among populations at both scales. With a series of common-garden experiments we show that some plant traits that may affect herbivory (pyrrolizidine alkaloids and extrafloral nectaries) vary at the regional scale, while other traits (trichomes and nitrogen content) just vary at the continental scale. These results, combined with our previous evidence for plant population differentiation based on larval performance on fresh fruits, suggest that U. ornatrix is subjected to divergent selection even at the regional scale. Finally, with a microsatellite study we investigated population structure of U. ornatrix. We found that population structure is not stable over time: we found population differentiation at the regional scale in the first year of sampling, but not in the second year. Unstable population structure of the herbivore is the most likely cause of the lack of regional adaptation

Effect of hosts on competition among clones and evidence of differential selection between pathogenic and saprophytic phases in experimental populations of the wheat pathogen Phaeosphaeria nodorum

<p>Abstract</p> <p>Background</p> <p>Monoculture, multi-cropping and wider use of highly resistant cultivars have been proposed as mechanisms to explain the elevated rate of evolution of plant pathogens in agricultural ecosystems. We used a mark-release-recapture experiment with the wheat pathogen <it>Phaeosphaeria nodorum </it>to evaluate the impact of two of these mechanisms on the evolution of a pathogen population. Nine <it>P. nodorum </it>isolates marked with ten microsatellite markers and one minisatellite were released onto five replicated host populations to initiate epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out over two consecutive host growing seasons and two pathogen collections were made during each season.</p> <p>Results</p> <p>A total of 637 pathogen isolates matching the marked inoculants were recovered from inoculated plots over two years. Genetic diversity in the host populations affected the evolution of the corresponding <it>P. nodorum </it>populations. In the cultivar mixture the relative frequencies of inoculants did not change over the course of the experiment and the pathogen exhibited a low variation in selection coefficients.</p> <p>Conclusions</p> <p>Our results support the hypothesis that increasing genetic heterogeneity in host populations may retard the rate of evolution in associated pathogen populations. Our experiment also provides indirect evidence of fitness costs associated with host specialization in <it>P. nodorum </it>as indicated by differential selection during the pathogenic and saprophytic phases.</p

Paleogene Radiation of a Plant Pathogenic Mushroom

Background: The global movement and speciation of fungal plant pathogens is important, especially because of the economic losses they cause and the ease with which they are able to spread across large areas. Understanding the biogeography and origin of these plant pathogens can provide insights regarding their dispersal and current day distribution. We tested the hypothesis of a Gondwanan origin of the plant pathogenic mushroom genus Armillaria and the currently accepted premise that vicariance accounts for the extant distribution of the species. Methods: The phylogeny of a selection of Armillaria species was reconstructed based on Maximum Parsimony (MP), Maximum Likelihood (ML) and Bayesian Inference (BI). A timeline was then placed on the divergence of lineages using a Bayesian relaxed molecular clock approach. Results: Phylogenetic analyses of sequenced data for three combined nuclear regions provided strong support for three major geographically defined clades: Holarctic, South American-Australasian and African. Molecular dating placed the initial radiation of the genus at 54 million years ago within the Early Paleogene, postdating the tectonic break-up of Gondwana. Conclusions: The distribution of extant Armillaria species is the result of ancient long-distance dispersal rather than vicariance due to continental drift. As these finding are contrary to most prior vicariance hypotheses for fungi, our result

Impaired CK1 Delta Activity Attenuates SV40-Induced Cellular Transformation In Vitro and Mouse Mammary Carcinogenesis In Vivo

Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP) gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T) mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA repair. Our data show that inactivating mutations in CK1δ impair SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo

Phylogenetic structure and host abundance drive disease pressure in communities

Pathogens play an important part in shaping the structure and dynamics of natural communities, because species are not affected by them equally. A shared goal of ecology and epidemiology is to predict when a species is most vulnerable to disease. A leading hypothesis asserts that the impact of disease should increase with host abundance, producing a ‘rare-species advantage. However, the impact of a pathogen may be decoupled from host abundance, because most pathogens infect more than one species, leading to pathogen spillover onto closely related species. Here we show that the phylogenetic and ecological structure of the surrounding community can be important predictors of disease pressure. We found that the amount of tissue lost to disease increased with the relative abundance of a species across a grassland plant community, and that this rare-species advantage had an additional phylogenetic component: disease pressure was stronger on species with many close relatives. We used a global model of pathogen sharing as a function of relatedness between hosts, which provided a robust predictor of relative disease pressure at the local scale. In our grassland, the total amount of disease was most accurately explained not by the abundance of the focal host alone, but by the abundance of all species in the community weighted by their phylogenetic distance to the host. Furthermore, the model strongly predicted observed disease pressure for 44 novel host species we introduced experimentally to our study site, providing evidence for a mechanism to explain why phylogenetically rare species are more likely to become invasive when introduced. Our results demonstrate how the phylogenetic and ecological structure of communities can have a key role in disease dynamics, with implications for the maintenance of biodiversity, biotic resistance against introduced weeds, and the success of managed plants in agriculture and forestry