Incomplete pneumolysin oligomers form membrane pores

Pneumolysin is a member of the cholesterol-dependent cytolysin (CDC) family of pore-forming proteins that are produced as water-soluble monomers or dimers, bind to target membranes and oligomerize into large ring-shaped assemblies comprising approximately 40 subunits and approximately 30 nm across. This pre-pore assembly then refolds to punch a large hole in the lipid bilayer. However, in addition to forming large pores, pneumolysin and other CDCs form smaller lesions characterized by low electrical conductance. Owing to the observation of arc-like (rather than full-ring) oligomers by electron microscopy, it has been hypothesized that smaller oligomers explain smaller functional pores. To investigate whether this is the case, we performed cryo-electron tomography of pneumolysin oligomers on model lipid membranes. We then used sub-tomogram classification and averaging to determine representative membrane-bound low-resolution structures and identified pre-pores versus pores by the presence of membrane within the oligomeric curve. We found pre-pore and pore forms of both complete (ring) and incomplete (arc) oligomers and conclude that arc-shaped oligomeric assemblies of pneumolysin can form pores. As the CDCs are evolutionarily related to the membrane attack complex/perforin family of proteins, which also form variably sized pores, our findings are of relevance to that class of proteins as well.     

Social Network Analysis Predicts Health Behaviours and Self-Reported Health in African Villages

The provision of healthcare in rural African communities is a highly complex and largely unsolved problem. Two main difficulties are the identification of individuals that are most likely affected by disease and the prediction of responses to health interventions. Social networks have been shown to capture health outcomes in a variety of contexts. Yet, it is an open question as to what extent social network analysis can identify and distinguish among households that are most likely to report poor health and those most likely to respond to positive behavioural influences. We use data from seven highly remote, post-conflict villages in Liberia and compare two prominent network measures: in-degree and betweenness. We define in-degree as the frequency in which members from one household are named by another household as a friends. Betweenness is defined as the proportion of shortest friendship paths between any two households in a network that traverses a particular household. We find that in-degree explains the number of ill family members, whereas betweenness explains engagement in preventative health. In-degree and betweenness independently explained self-reported health and behaviour, respectively. Further, we find that betweenness predicts susceptibility to, instead of influence over, good health behaviours. The results suggest that targeting households based on network measures rather than health status may be effective for promoting the uptake of health interventions in rural poor villages.     

Optimizing the Prediction Process: From Statistical Concepts to the Case Study of Soccer

We present a systematic approach for prediction purposes based on panel data, involving information about different interacting subjects and different times (here: two). The corresponding bivariate regression problem can be solved analytically for the final statistical estimation error. Furthermore, this expression is simplified for the special case that the subjects do not change their properties between the last measurement and the prediction period. This statistical framework is applied to the prediction of soccer matches, based on information from the previous and the present season. It is determined how well the outcome of soccer matches can be predicted theoretically. This optimum limit is compared with the actual quality of the prediction, taking the German premier league as an example. As a key step for the actual prediction process one has to identify appropriate observables which reflect the strength of the individual teams as close as possible. A criterion to distinguish different observables is presented. Surprisingly, chances for goals turn out to be much better suited than the goals themselves to characterize the strength of a team. Routes towards further improvement of the prediction are indicated. Finally, two specific applications are discussed.     

Diel fragrance pattern correlates with olfactory preferences of diurnal and nocturnal flower visitors in Salix caprea (Salicaceae)

Floral scent, often a complex mixture of several volatile organic compounds (VOCs), has generally been interpreted as an adaptation to attract pollinators. However, not many studies have analysed which VOCs are functionally relevant for the reproductive success of a plant. Here, we show that, in Salix caprea (Salicaceae), temporal changes in floral scent emission during the day and night attract two different types of flower visitor: bees during the day and moths during the evening and night. We analysed the contribution of the two flower visitor groups to the reproductive success of the plant. The differences in scent emitted during the peak activity times of flower visitors (day versus night) were quantified and the response of 13 diurnal/nocturnal pollinator taxa to the floral scents was tested using gas chromatographic and electroantennographic techniques. Many of the c. 40 identified scent compounds were physiologically active, and bees and moths responded to nearly identical sets of compounds, although the response strengths differed. In bioassays, bees preferred the most abundant 1,4‐dimethoxybenzene over lilac aldehyde, a compound with increased emission at night, whereas moths preferred lilac aldehyde over 1,4‐dimethoxybenzene. Pollination by wind plus nocturnal pollinators (mainly moths) or by wind alone contributed less to seed set than pollination by wind plus diurnal pollinators (mainly bees). This suggests that the emission of scent during the night and attracting moths have no significant effect on reproductive success. It is possible that the emission of lilac aldehydes and other compounds at night is s result of phylogenetic constraints. Future studies should investigate whether moths may produce a marginal fitness gain in some years and/or some populations. © 2014 The Linnean Society of London, Botanical Journal of the Linnean Society, 2014, 175 , 624–640.     

Numerical chromosome variation and mitotic segregation defects in the adult brain of teleost fish

Teleost fish are distinguished by their enormous potential for the generation of new cells in both the intact and the injured adult brain. Here, we present evidence that these cells are a genetic mosaic caused by somatic genomic alteration. Metaphase chromosome spreads from whole brains of the teleost Apteronotus leptorhynchus revealed an euploid complement of 22 chromosomes in only 22% of the cells examined. The rate of aneuploidy is substantially higher in brain cells than in liver cells, as shown by both metaphase chromosome spreads and flow cytometric analysis. Among the aneuploid cells in the brain, approximately 84% had fewer, and the remaining 16% more, than 22 chromosomes. Typically, multiple chromosomes were lost or gained. The aneuploidy is putatively caused by segregation defects during mitotic division. Labeling of condensed chromosomes of M-phase cells by phosphorylated histone-H3 revealed laggards, anaphase bridges, and micronuclei, all three of which indicate displaced mitotic chromosomes. Quantitative analysis has shown that in the entire brain on average 14% of all phosphorylated histone-H3-labeled cells exhibit such signs of segregation defects. Together with the recent discovery of aneuploidy in the adult mammalian brain, the results of the present investigation suggest that the loss or gain of chromosomes might provide a mechanism to regulate gene expression during development of new cells in the adult vertebrate brain.     

Heterogeneous adaptive trajectories of small populations on complex fitness landscapes

Background

Small populations are thought to be adaptively handicapped, not only because they suffer more from deleterious mutations but also because they have limited access to new beneficial mutations, particularly those conferring large benefits.

Methodology/Principal Findings

Here, we test this widely held conjecture using both simulations and experiments with small and large bacterial populations evolving in either a simple or a complex nutrient environment. Consistent with expectations, we find that small populations are adaptively constrained in the simple environment; however, in the complex environment small populations not only follow more heterogeneous adaptive trajectories, but can also attain higher fitness than the large populations. Large populations are constrained to near deterministic fixation of rare large-benefit mutations. While such determinism speeds adaptation on the smooth adaptive landscape represented by the simple environment, it can limit the ability of large populations from effectively exploring the underlying topography of rugged adaptive landscapes characterized by complex environments.

Conclusions

Our results show that adaptive constraints often faced by small populations can be circumvented during evolution on rugged adaptive landscapes.