The challenge of using experimental infectivity data in risk assessment for Ebola virus: why ecology may be important

Analysis of published data shows that experimental passaging of Zaire ebolavirus (EBOV) in guinea pigs changes the risk of infection per plaque‐forming unit (PFU), increasing infectivity to some species while decreasing infectivity to others. Thus, a PFU of monkey‐adapted EBOV is 10⁷‐fold more lethal to mice than a PFU adapted to guinea pigs. The first conclusion is that the infectivity of EBOV to humans may depend on the identity of the donor species itself and, on the basis of limited epidemiological data, the question is raised as to whether bat‐adapted EBOV is less infectious to humans than nonhuman primate (NHP)‐adapted EBOV. Wildlife species such as bats, duikers and NHPs are naturally infected by EBOV through different species giving rise to EBOV with different wildlife species‐passage histories (heritages). Based on the ecology of these wildlife species, three broad ‘types’ of EBOV‐infected bushmeat are postulated reflecting differences in the number of passages within a given species, and hence the degree of adaptation of the EBOV present. The second conclusion is that the prior species‐transmission chain may affect the infectivity to humans per PFU for EBOV from individuals of the same species. This is supported by the finding that the related Marburg marburgvirus requires ten passages in mice to fully adapt. It is even possible that the evolutionary trajectory of EBOV could vary in individuals of the same species giving rise to variants which are more or less virulent to humans and that the probability of a given trajectory is related to the heritage. Overall the ecology of the donor species (e.g. dog or bushmeat species) at the level of the individual animal itself may determine the risk of infection per PFU to humans reflecting the heritage of the virus and may contribute to the sporadic nature of EBOV outbreaks.     

Using co‐occurrence network topology in assessing ecological stress in benthic macroinvertebrate communities

Ecological monitoring of streams has often focused on assessing the biotic integrity of individual benthic macroinvertebrate (BMI) communities through local measures of diversity, such as taxonomic or functional richness. However, as individual BMI communities are frequently linked by a variety of ecological processes at a regional scale, there is a need to assess biotic integrity of groups of communities at the scale of watersheds. Using 4,619 sampled communities of streambed BMIs, we investigate this question using co‐occurrence networks generated from groups of communities selected within California watersheds under different levels of stress due to upstream land use. Building on a number of arguments in theoretical ecology and network theory, we propose a framework for the assessment of the biotic integrity of watershed‐scale groupings of BMI communities using measures of their co‐occurrence network topology. We found significant correlations between stress, as described by a mean measure of upstream land use within a watershed, and topological measures of co‐occurrence networks such as network size (r = ?.81, p < 10^–4), connectance (r = .31, p < 10^–4), mean co‐occurrence strength (r = .25, p < 10^–4), degree heterogeneity (r = ?.10, p < 10^–4), and modularity (r = .11, p < 10^–4). Using these five topological measures, we constructed a linear model of biotic integrity, here a composite of taxonomic and functional diversity known as the California Stream Condition Index, of groups of BMI communities within a watershed. This model can account for 66% of among‐watershed variation in the mean biotic integrity of communities. These observations imply a role for co‐occurrence networks in assessing the current status of biotic integrity for BMI communities, as well as their potential use in assessing other ecological communities.     

Patterns in the top-down versus bottom-up regulation of heterotrophic nanoflagellates in temperate lakes

The importance of resources versus that of predators in determiningthe abundance of organisms is modulated by several factors whichvary over time and space. Here, we evaluate the abundance ofheterotrophic nanoflagellates (HNF), the main predators of planktonicbacteria, in the plankton of 16 Quebec lakes as a function ofthe abundance of resources and zooplankton (predators). We analyzethe data at two different scales: among lakes varying in resourcesupply and within lakes. Resource factors (total phosphorus,chlorophyll, bacterial concentration) best explained the abundancesof HNF among lakes differing in resource availability. Whenthe effect of resource availability was removed, the biomassof cladocerans became an important determinant of HNF abundance,with abundance declining and the ratio of bacteria per flagellateincreasing, as the cladocerans increased. Within lakes, HNFabundance was not a direct function of resource concentration.Multiple regression models based on data for many lakes showedthat both bottom-up (food) and top-down (predation) variablespredicted HNF abundance quite well. An examination of the seasonalpattern among individual lakes showed each group of variablesdiffering in importance: bottom-up variables were more importantin spring and top-down variables in midsummer. An examinationof the effects of different assemblages of zooplankton on HNFshowed cladocerans to exert the highest negative impact on HNFand to be responsible for keeping low HNF numbers during mostof the summer with that probably affecting the pathways of energyflux in those lakes dominated by cladocerans versus those dominatedby other zooplankton. The absolute, as well as the relative,importance of the different biotic and abiotic factors examinedin predicting the abundance of HNF is a function of the scaleof the investigation. Among lakes varying greatly in resourcesupply, resources are found to better correlate with HNF abundance.When the analysis is performed at another scale, within lakes,the relative importance of resources and predation in determiningHNF abundances changes depending on the variability superimposedby other factors (seasonality and lake food web structure).     

Divergence among arctic and alpine populations of the annual, Koenigia islandica: morphology, life-history, and phenology

Arctic and alpine habitats occur along complex environmental gradients, and over an extensive geographical range. Despite some selective forces common to these habitats, evolutionary divergence among populations of arctic and alpine plants along this gradient is expected. Of particular significance, both in the context of life-history theory and for implications of climate change, are the few annual species that have adapted to the constraints of an unpredictable, short growing season. In this study, morphological, life-history and phenological characters were found to differ significantly among six widely distributed populations of the arctic-alpine annual Koenigia islandica. On the basis of morphology and life-history traits, populations from high latitudes, with the exception of Svalbard, performed better in simulated arctic conditions, whereas the low latitude alpine plants from Colorado showed enhanced performance under simulated alpine conditions. On the basis of phenology, the six populations can be clearly grouped into arctic, high latitude alpine and alpine populations: arctic plants were found to develop and flower earliest; alpine plants latest. Because these results were obtained using seeds harvested from plants first grown through a complete generation in growth chambers, they indicate strong genetic differentiation. We discuss possible adaptive explanations for observed differences among the six geographically divergent populations.     

Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN sorting selectively enriched ergosterol and sphingolipid species in the immunoisolated secretory vesicles. This finding, for the first time, indicates that the TGN exhibits the capacity to sort membrane lipids. Furthermore, the observation that the immunoisolated vesicles exhibited a higher membrane order than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery.     

Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive state by RhoGDI1, which is found in a ternary complex with synectin and S4. Binding of S4 to synectin increases the latter''s binding to RhoGDI1, which in turn enhances RhoGDI1''s affinity for RhoG. S4 clustering activates PKCα, which phosphorylates RhoGDI1 at Ser⁹⁶. This phosphorylation triggers release of RhoG, leading to polarized activation of Rac1. Thus, FGF2-induced Rac1 activation depends on the suppression of RhoG by a previously uncharacterized ternary S4–synectin–RhoGDI1 protein complex and activation via PKCα.     

Avian Host-Selection by Culex pipiens in Experimental Trials

Evidence from field studies suggests that Culex pipiens, the primary mosquito vector of West Nile virus (WNV) in the northeastern and north central United States, feeds preferentially on American robins (Turdus migratorius). To determine the contribution of innate preferences to observed preference patterns in the field, we conducted host preference trials with a known number of adult female C. pipiens in outdoor cages comparing the relative attractiveness of American robins with two common sympatric bird species, European starling, Sternus vulgaris and house sparrow, Passer domesticus. Host seeking C. pipiens were three times more likely to enter robin-baited traps when with the alternate host was a European starling (n = 4 trials; OR = 3.06; CI [1.42–6.46]) and almost twice more likely when the alternative was a house sparrow (n = 8 trials; OR = 1.80; CI = [1.22–2.90]). There was no difference in the probability of trap entry when two robins were offered (n = 8 trials). Logistic regression analysis determined that the age, sex and weight of the birds, the date of the trial, starting-time, temperature, humidity, wind-speed and age of the mosquitoes had no effect on the probability of a choosing a robin over an alternate bird. Findings indicate that preferential feeding by C. pipiens mosquitoes on certain avian hosts is likely to be inherent, and we discuss the implications innate host preferences may have on enzootic WNV transmission.     

Subtle gene-environment interactions driving paranoia in daily life

It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol- O -methyltransferase (COMT) Val¹⁵⁸Met and brain-derived neurotrophic factor (BDNF) Val⁶⁶Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event-related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress-induced paranoia by COMT Val¹⁵⁸Met and BDNF Val⁶⁶Met genotypes. Catechol- O -methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain-derived neurotrophic factor Met carriers showed more social-stress-induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene–environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.