Microbial modification of host long-distance dispersal capacity

Background  

Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider,Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'.     

Countergradient variation in body shape between two populations of Atlantic cod (Gadus morhua)

Variation in morphological traits is generally thought to be cogradient, with environmental effects on phenotypic expression reinforcing genetic differences between populations. We compared body shape between two populations of Atlantic cod (Gadus morhua). Striking shape differences occurred between juveniles from the two populations when reared in a common laboratory environment. However, no difference in body shape occurred between wild-reared juveniles from the two populations, suggesting that the genetic differences between populations were obscured by opposing effects of the environmental differences experienced in the wild. We suggest that much of the genetic diversity in body shape of fishes may be cryptic, with stabilizing selection for the same optimal phenotype resulting in genetic divergence between populations subject to contrasting environmental influences.     

Therapeutic antibodies directed at G protein-coupled receptors

G protein-coupled receptors (GPCRs) are one of the most important classes of targets for small molecule drug discovery, but many current GPCRs of interest are proving intractable to small molecule discovery and may be better approached with bio-therapeutics. GPCRs are implicated in a wide variety of diseases where antibody therapeutics are currently used. These include inflammatory diseases such as rheumatoid arthritis and Crohn disease, as well as metabolic disease and cancer. Raising antibodies to GPCRs has been difficult due to problems in obtaining suitable antigen because GPCRs are often expressed at low levels in cells and are very unstable when purified. A number of new developments in overexpressing receptors, as well as formulating stable pure protein, are contributing to the growing interest in targeting GPCRs with antibodies. This review discusses the opportunities for targeting GPCRs with antibodies using these approaches and describes the therapeutic antibodies that are currently in clinical development.Key words: G protein-coupled receptor, transmembrane spanning domain, chemokine receptor, extracellular domain, extracellular loop     

Implications of host genetic variation on the risk and prevalence of infectious diseases transmitted through the environment

Previous studies have shown that host genetic heterogeneity in the response to infectious challenge can affect the emergence risk and the severity of diseases transmitted through direct contact between individuals. However, there is substantial uncertainty about the degree and direction of influence owing to different definitions of genetic variation, most of which are not in line with the current understanding of the genetic architecture of disease traits. Also, the relevance of previous results for diseases transmitted through environmental sources is unclear. In this article a compartmental genetic-epidemiological model was developed to quantify the impact of host genetic diversity on epidemiological characteristics of diseases transmitted through a contaminated environment. The model was parameterized for footrot in sheep. Genetic variation was defined through continuous distributions with varying shape and degree of dispersion for different disease traits. The model predicts a strong impact of genetic heterogeneity on the disease risk and its progression and severity, as well as on observable host phenotypes, when dispersion in key epidemiological parameters is high. The impact of host variation depends on the disease trait for which variation occurs and on environmental conditions affecting pathogen survival. In particular, compared to homogeneous populations with the same average susceptibility, disease risk and severity are substantially higher in populations containing a large proportion of highly susceptible individuals, and the differences are strongest when environmental contamination is low. The implications of our results for the recording and analysis of disease data and for predicting response to selection are discussed.     

Draft genome sequence of Streptomyces strain S4, a symbiont of the leaf-cutting ant Acromyrmex octospinosus

Streptomyces spp. are common symbionts of the leaf-cutting ant species Acromyrmex octospinosus, which feeds on basidiomycete fungus leaf matter and harvests the lipid- and carbohydrate-rich gongylidia as a food source. A. octospinosus and other ant genera use antifungal compounds produced by Streptomyces spp. and other actinomycetes in order to help defend their fungal gardens from parasitic fungi. Herein, we report the draft genome sequence of Streptomyces strain S4, an antifungal-producing symbiont of A. octospinosus.     

Population size,habitat fragmentation,and the nature of adaptive variation in a stream fish

Whether and how habitat fragmentation and population size jointly affect adaptive genetic variation and adaptive population differentiation are largely unexplored. Owing to pronounced genetic drift, small, fragmented populations are thought to exhibit reduced adaptive genetic variation relative to large populations. Yet fragmentation is known to increase variability within and among habitats as population size decreases. Such variability might instead favour the maintenance of adaptive polymorphisms and/or generate more variability in adaptive differentiation at smaller population size. We investigated these alternative hypotheses by analysing coding-gene, single-nucleotide polymorphisms associated with different biological functions in fragmented brook trout populations of variable sizes. Putative adaptive differentiation was greater between small and large populations or among small populations than among large populations. These trends were stronger for genetic population size measures than demographic ones and were present despite pronounced drift in small populations. Our results suggest that fragmentation affects natural selection and that the changes elicited in the adaptive genetic composition and differentiation of fragmented populations vary with population size. By generating more variable evolutionary responses, the alteration of selective pressures during habitat fragmentation may affect future population persistence independently of, and perhaps long before, the effects of demographic and genetic stochasticity are manifest.     

Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

Background

Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.

Results

In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5⁺ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5⁺ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.

Conclusions

Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.