Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses

Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand

Background - Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are required to assess control methods and develop effective population reduction strategies. Ae. aegypti develops primarily in artificial water holding containers. Release recapture studies indicate that most adult Ae. aegypti do not disperse over long distances. We expect, therefore, that containers in an area of high development site density are more likely to be oviposition sites and to be more frequently used as oviposition sites than containers that are relatively isolated from other development sites. After accounting for individual container characteristics, containers more frequently used as oviposition sites are likely to produce adult mosquitoes consistently and at a higher rate. To this point, most studies of Ae. aegypti populations ignore the spatial density of larval development sites. Methodology - Pupal surveys were carried out from 2004 to 2007 in rural Kamphaeng Phet, Thailand. In total, 84,840 samples of water holding containers were used to estimate model parameters. Regression modeling was used to assess the effect of larval development site density, access to piped water, and seasonal variation on container productivity. A varying-coefficients model was employed to account for the large differences in productivity between container types. A two-part modeling structure, called a hurdle model, accounts for the large number of zeroes and overdispersion present in pupal population counts. Findings - The number of suitable larval development sites and their density in the environment were the primary determinants of the distribution and abundance of Ae. aegypti pupae. The productivity of most container types increased significantly as habitat density increased. An ecological approach, accounting for development site density, is appropriate for predicting Ae. aegypti population levels and developing efficient vector control program

Interactive Effects of Large- and Small-Scale Sources of Feral Honey-Bees for Sunflower in the Argentine Pampas

Pollinators for animal pollinated crops can be provided by natural and semi-natural habitats, ranging from large vegetation remnants to small areas of non-crop land in an otherwise highly modified landscape. It is unknown, however, how different small- and large-scale habitat patches interact as pollinator sources. In the intensively managed Argentine Pampas, we studied the additive and interactive effects of large expanses (up to 2200 ha) of natural habitat, represented by untilled isolated “sierras”, and narrow (3–7 m wide) strips of semi-natural habitat, represented by field margins, as pollinator sources for sunflower (Helianthus annus). We estimated visitation rates by feral honey-bees, Apis mellifera, and native flower visitors (as a group) at 1, 5, 25, 50 and 100 m from a field margin in 17 sunflower fields 0–10 km distant from the nearest sierra. Honey-bees dominated the pollinator assemblage accounting for >90% of all visits to sunflower inflorescences. Honey-bee visitation was strongly affected by proximity to the sierras decreasing by about 70% in the most isolated fields. There was also a decline in honey-bee visitation with distance from the field margin, which was apparent with increasing field isolation, but undetected in fields nearby large expanses of natural habitat. The probability of observing a native visitor decreased with isolation from the sierras, but in other respects visitation by flower visitors other than honey-bees was mostly unaffected by the habitat factors assessed in this study. Overall, we found strong hierarchical and interactive effects between the study large and small-scale pollinator sources. These results emphasize the importance of preserving natural habitats and managing actively field verges in the absence of large remnants of natural habitat for improving pollinator services

An Emerging Infectious Disease Triggering Large-Scale Hyperpredation

Hyperpredation refers to an enhanced predation pressure on a secondary prey due to either an increase in the abundance of a predator population or a sudden drop in the abundance of the main prey. This scarcely documented mechanism has been previously studied in scenarios in which the introduction of a feral prey caused overexploitation of native prey. Here we provide evidence of a previously unreported link between Emergent Infectious Diseases (EIDs) and hyperpredation on a predator-prey community. We show how a viral outbreak caused the population collapse of a host prey at a large spatial scale, which subsequently promoted higher-than-normal predation intensity on a second prey from shared predators. Thus, the disease left a population dynamic fingerprint both in the primary host prey, through direct mortality from the disease, and indirectly in the secondary prey, through hyperpredation. This resulted in synchronized prey population dynamics at a large spatio-temporal scale. We therefore provide evidence for a novel mechanism by which EIDs can disrupt a predator-prey interaction from the individual behavior to the population dynamics. This mechanism can pose a further threat to biodiversity through the human-aided disruption of ecological interactions at large spatial and temporal scales.MM and JASZ were partially supported by a project of the Spanish Ministerio de Educación y Ciencia (reference CGL-2006-10689/BOS)

BUGS in the Analysis of Biodiversity Experiments: Species Richness and Composition Are of Similar Importance for Grassland Productivity

The idea that species diversity can influence ecosystem functioning has been controversial and its importance relative to compositional effects hotly debated. Unfortunately, assessing the relative importance of different explanatory variables in complex linear models is not simple. In this paper we assess the relative importance of species richness and species composition in a multilevel model analysis of net aboveground biomass production in grassland biodiversity experiments by estimating variance components for all explanatory variables. We compare the variance components using a recently introduced graphical Bayesian ANOVA. We show that while the use of test statistics and the R2 gives contradictory assessments, the variance components analysis reveals that species richness and composition are of roughly similar importance for primary productivity in grassland biodiversity experiments

Exploring behaviors of stochastic differential equation models of biological systems using change of measures

Stochastic Differential Equations (SDE) are often used to model the stochastic dynamics of biological systems. Unfortunately, rare but biologically interesting behaviors (e.g., oncogenesis) can be difficult to observe in stochastic models. Consequently, the analysis of behaviors of SDE models using numerical simulations can be challenging. We introduce a method for solving the following problem: given a SDE model and a high-level behavioral specification about the dynamics of the model, algorithmically decide whether the model satisfies the specification. While there are a number of techniques for addressing this problem for discrete-state stochastic models, the analysis of SDE and other continuous-state models has received less attention. Our proposed solution uses a combination of Bayesian sequential hypothesis testing, non-identically distributed samples, and Girsanov's theorem for change of measures to examine rare behaviors. We use our algorithm to analyze two SDE models of tumor dynamics. Our use of non-identically distributed samples sampling contributes to the state of the art in statistical verification and model checking of stochastic models by providing an effective means for exposing rare events in SDEs, while retaining the ability to compute bounds on the probability that those events occur

Awareness and acceptability of human papillomavirus vaccine: an application of the instrumental variables bivariate probit model

<p>Abstract</p> <p>Background</p> <p>Although lower uptake rates of the human papillomavirus (HPV) vaccine among socioeconomically disadvantaged populations have been documented, less is known about the relationships between awareness and acceptability, and other factors affecting HPV vaccine uptake.</p> <p>The current study aimed to estimate the potential effectiveness of increased HPV vaccine awareness on the acceptability of HPV vaccination in a nationally representative sample of women, using a methodology that controlled for potential non-random selection.</p> <p>Methods</p> <p>This study used a population-based sample from the 2007 Health Information National Trends Survey, a cross-sectional study of the US population aged 18 years or older, and focused on the subsample of 742 women who have any female children under the age of 18 years in the household. An instrumental variables bivariate probit model was used to jointly estimate HPV vaccine awareness and acceptability.</p> <p>Results</p> <p>The proportion of HPV vaccine acceptability among the previously aware and non-aware groups was 58% and 47%, respectively. Results from the instrumental variables bivariate probit model showed that the estimated marginal effect of awareness on acceptability was 46 percentage points, an effect that was even greater than observed.</p> <p>Conclusions</p> <p>Among populations who are not currently aware of the HPV vaccine, the potential impact of raising awareness on acceptability of HPV vaccination is substantial. This finding provides additional support to strengthening public health programs that increase awareness and policy efforts that address barriers to HPV vaccination.</p

HSV Usurps Eukaryotic Initiation Factor 3 Subunit M for Viral Protein Translation: Novel Prevention Target

Prevention of genital herpes is a global health priority. B5, a recently identified ubiquitous human protein, was proposed as a candidate HSV entry receptor. The current studies explored its role in HSV infection. Viral plaque formation was reduced by ∼90% in human cells transfected with small interfering RNA targeting B5 or nectin-1, an established entry receptor. However, the mechanisms were distinct. Silencing of nectin-1 prevented intracellular delivery of viral capsids, nuclear transport of a viral tegument protein, and release of calcium stores required for entry. In contrast, B5 silencing had no effect on these markers of entry, but inhibited viral protein translation. Specifically, viral immediate early genes, ICP0 and ICP4, were transcribed, polyadenylated and transported from the nucleus to the cytoplasm, but the viral transcripts did not associate with ribosomes or polysomes in B5-silenced cells. In contrast, immediate early gene viral transcripts were detected in polysome fractions isolated from control cells. These findings are consistent with sequencing studies demonstrating that B5 is eukaryotic initiation factor 3 subunit m (eIF3m). Although B5 silencing altered the polysome profile of cells, silencing had little effect on cellular RNA or protein expression and was not cytotoxic, suggesting that this subunit is not essential for host cellular protein synthesis. Together these results demonstrate that B5 plays a major role in the initiation of HSV protein translation and could provide a novel target for strategies to prevent primary and recurrent herpetic disease

Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

<p>Abstract</p> <p>Background</p> <p>Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients.</p> <p>Methods</p> <p>In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ_1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease.</p> <p>Results</p> <p>CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ_1-42in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections.</p> <p>Conclusions</p> <p>Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.</p