Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

BACKGROUND: Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. RESULTS: Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio) that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density) or with increased transmission. CONCLUSIONS: We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality) and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical research and adds support to the prediction that partially effective vaccines may select for increasingly virulent malaria parasite strains. By contrast, there was no consistent correlation between transmission and sub-lethal anaemia, a more common outcome of malaria infection. However, overall, the data are not inconsistent with the recent proposal that sub-lethal effects may impose an upper limit on virulence. Moreover, clone specific differences in transmission phenotypes linked to anaemia do suggest that there is considerable adaptive potential relating anaemia and transmission that may lead to uncertain consequences following intervention strategies

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Cryofracture electron microscopy of the ookinete pellicle of Plasmodium gallinaceum reveals the existence of novel pores in the alveolar membranes.

The malaria parasite invades the midgut tissue of its mosquito host as a motile form called the ookinete. We have examined the pellicle of the ookinete of Plasmodium gallinaceum by freeze-fracture and quick-freeze, deep-etch electron microscopy. The general organization is analogous to that of invasive stages of other members of Apicomplexa. The pellicle is composed of three membranes: the plasma membrane, and the two linked intermediate and inner membranes, which in the ookinete form one flattened vacuole that is located beneath the plasma membrane. The edges of this vacuole form a longitudinal suture. Beneath the vacuole is found an array of microtubules that are connected to the inner membrane by intramembranous particles. During freeze-fracture, the membranes can split along their hydrophobic planes, thus yielding six fracture faces, each of which displays a characteristic pattern of intramembranous particles. Additionally, we find that the ookinete pellicle differs from all other apicomplexan motile stages by the presence of large pores. These pores are of unknown function, but clearly might constitute a novel pathway for the transport of molecules to and from the cortex, which is independent of the well-described route through the apical micronemal/rhoptry complex. The pores may be the route by which motor proteins or other non micronemal surface proteins are trafficked, such as P25/P28 and SOAP, some of which are implicated in transmission blocking immunity

Application Of Stable Isotope Analysis To Study Temporal Changes In Foraging Ecology In A Highly Endangered Amphibian

Background -- Understanding dietary trends for endangered species may be essential to assessing the effects of ecological disturbances such as habitat modification, species introductions or global climate change. Documenting temporal variation in prey selection may also be crucial for understanding population dynamics. However, the rarity, secretive behaviours and obscure microhabitats of some endangered species can make direct foraging observations difficult or impossible. Furthermore, the lethality or invasiveness of some traditional methods of dietary analysis (e.g. gut contents analysis, gastric lavage) makes them inappropriate for such species. Stable isotope analysis facilitates non-lethal, indirect analysis of animal diet that has unrealized potential in the conservation of endangered organisms, particularly amphibians. Methodology/findings -- I determined proportional contributions of aquatic macroinvertebrate prey to the diet of an endangered aquatic salamander Eurycea sosorum over a two-year period using stable isotope analysis of 13/12C and 15/14N and the Bayesian stable isotope mixing model SIAR. I calculated Strauss’ dietary electivity indices by comparing these proportions with changing relative abundance of potential prey species through time. Stable isotope analyses revealed that a previously unknown prey item (soft-bodied planarian flatworms in the genus Dugesia) made up the majority of E. sosorum diet. Results also demonstrate that E. sosorum is an opportunistic forager capable of diet switching to include a greater proportion of alternative prey when Dugesia populations decline. There is also evidence of intra-population dietary variation. Conclusions/significance -- Effective application of stable isotope analysis can help circumvent two key limitations commonly experienced by researchers of endangered species: the inability to directly observe these species in nature and the invasiveness or lethality of traditional methods of dietary analysis. This study illustrates the feasibility of stable isotope analysis in identifying preferred prey species that can be used to guide conservation management of both wild and captive food sources for endangered species.This work was generously funded by a Sigma Xi Grant-In-Aid of Research (http://www.sigmaxi.org/programs/giar/ind​ex.shtml), a Howard McCarley Student Research Award from the Southwestern Association of Naturalists (http://biosurvey.ou.edu/swan/stuaeng.htm​#_HOWARD_MCCARLEY), a grant from the Barton Springs Salamander Conservation Fund (administered by the City of Austin and Austin Community Foundation; http://www.austincommunityfoundation.org​/?nd=news#Salamander) and grants from the Zoology Scholarship Endowment for Excellence, Dorothea Bennett Memorial Graduate Fellowship and Terrell H. Hamilton Endowed Graduate Fellowship at the University of Texas at Austin (http://www.biosci.utexas.edu/graduate/ee​b/current.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Trends of the dengue serotype-4 circulation with epidemiological, phylogenetic, and entomological insights in Lao PDR between 2015 and 2019

Dengue outbreaks have regularly been recorded in Lao People's Democratic Republic (PDR) since the first detection of the disease in 1979. In 2012, an integrated arbovirus surveillance network was set up in Lao PDR and an entomological surveillance has been implemented since 2016 in Vientiane Capital. Here, we report a study combining epidemiological, phylogenetic, and entomological analyzes during the largest DENV-4 epidemic ever recorded in Lao PDR (2015-2019). Strikingly, from 2015 to 2019, we reported the DENV-4 emergence and spread at the country level after two large epidemics predominated by DENV-3 and DENV-1, respectively, in 2012-2013 and 2015. Our data revealed a significant difference in the median age of the patient infected by DENV-4 compared to the other serotypes. Phylogenetic analysis demonstrated the circulation of DENV-4 Genotype I at the country level since at least 2013. The entomological surveillance showed a predominance of <i>Aedes</i><i>aegypti</i> compared to <i>Aedes</i><i>albopictus</i> and high abundance of these vectors in dry and rainy seasons between 2016 and 2019, in Vientiane Capital. Overall, these results emphasized the importance of an integrated approach to evaluate factors, which could impact the circulation and the epidemiological profile of dengue viruses, especially in endemic countries like Lao PDR

Low seroprevalence of COVID-19 in Lao PDR, late 2020

Background In 2020 Lao PDR had low reported COVID-19 cases but it was unclear whether this masked silent transmission. A seroprevalence study was done August - September 2020 to determine SARS-CoV-2 exposure. Methods Participants were from the general community (n=2433) or healthcare workers (n=666) in five provinces and bat/wildlife contacts (n=74) were from Vientiane province. ELISAs detected anti- SARS-CoV-2 Nucleoprotein (N; n=3173 tested) and Spike (S; n=1417 tested) antibodies. Double-positive samples were checked by IgM/IgG rapid tests. Controls were confirmed COVID-19 cases (n=15) and pre-COVID-19 samples (n=265). Seroprevalence for the general community was weighted to account for complex survey sample design, age and sex. Findings In pre-COVID-19 samples, 5·3%, [95% CI=3·1-8·7%] were anti-N antibody single-positive and 1·1% [0·3-3·5%] were anti-S antibody single positive. None were double positive. Anti-N and anti-S antibodies were detected in 5·2% [4·2-6·5%] and 2·1% [1·1-3·9%] of the general community, 2·0% [1·1-3·3%] and 1·4% [0·5-3·7%] of healthcare workers and 20·3% [12·6-31·0%] and 6·8% [2·8-15·3%] of bat/wildlife contacts. 0·1% [0·02-0·3%] were double positive for anti-N and anti-S antibodies (rapid test negative). Interpretation We find no evidence for significant SARS-CoV-2 circulation in Lao PDR before September 2020. This likely results from early decisive measures taken by the government, social behavior, and low population density. High anti-N /low anti-S seroprevalence in bat/wildlife contacts may indicate exposure to cross-reactive animal coronaviruses with threat of emerging novel viruses. Funding Agence Française de Développement. Additional; Institut Pasteur du Laos, Institute Pasteur, Paris and Luxembourg Ministry of Foreign and European Affairs (“PaReCIDS II”)

An analysis on human personality and hotel web design : a Kohonen network approach

Having an eye catching and attractive website could help hotels to compete in the vigorous online market. This study attempts to examine the relationship between human personality and the web design preferences. Kohonen Networks were adopted to cluster people with similar personality characteristics and identify their differences on web design preferences. Empirical results indicated people with similar personality traits have similar design preferences. For example, to attract those who got high scores in agreeableness, conscientiousness and openness but low score in neuroticism, a web page should start with a language selection page with introductory movie, one large image on the web page showing hotel interior design with hotel guest in the photo, and with background music