Phylogenetic and non-phylogenetic structure in trophic links between gall-forming herbivores and their parasitoid natural enemies.

Revealing processes that structure species interactions is central to understanding community assembly and dynamics. Species interact via their phenotypes, but identifying and quantifying the traits that structure species-specific interactions (links) can be challenging. Where these traits show phylogenetic signal, however, link properties are predictable using models that incorporate phylogenies in place of trait data. We analysed variation in link richness, frequency, and identity in a multi-site dataset of interactions between host oak cynipid galls and parasitoid natural enemies, using a Bayesian mixed modelling framework allowing concurrent fitting of terms for phylogenies of both trophic levels. In both link incidence (presence/absence) and link frequency datasets, we identified strong signatures of cophylogeny (related parasitoids attack related host galls) and patterns independent of either phylogeny. Our results are robust to simulations of substantially reduced sample completeness, and are consistent with the structuring of trophic interactions by a combination of phylogenetically conserved and convergently evolving traits at both trophic levels. We discuss our results in light of phenotypic traits thought to structure gall-parasitoid interactions and wider applications of this approach, including inference of underlying community assembly processes and prediction of economically important trophic interactions

Phylogenetic and non-phylogenetic structure in trophic links between gall-forming herbivores and their parasitoid natural enemies.

Revealing processes that structure species interactions is central to understanding community assembly and dynamics. Species interact via their phenotypes, but identifying and quantifying the traits that structure species-specific interactions (links) can be challenging. Where these traits show phylogenetic signal, however, link properties are predictable using models that incorporate phylogenies in place of trait data. We analysed variation in link richness, frequency, and identity in a multi-site dataset of interactions between host oak cynipid galls and parasitoid natural enemies, using a Bayesian mixed modelling framework allowing concurrent fitting of terms for phylogenies of both trophic levels. In both link incidence (presence/absence) and link frequency datasets, we identified strong signatures of cophylogeny (related parasitoids attack related host galls) and patterns independent of either phylogeny. Our results are robust to simulations of substantially reduced sample completeness, and are consistent with the structuring of trophic interactions by a combination of phylogenetically conserved and convergently evolving traits at both trophic levels. We discuss our results in light of phenotypic traits thought to structure gall-parasitoid interactions and wider applications of this approach, including inference of underlying community assembly processes and prediction of economically important trophic interactions

Structure and composition of tritrophic communities associated with Fagaceae-feeding cynipid gallwasps in Sichuan, China

We provide the first description and analysis of species-rich communities of Fagaceae host plants, cynipid gall inducers and Hymenopteran parasitoids from two sites in western Sichuan, China. We use quantified interaction data to test the hypothesis that metabolically intimate cynipid-Fagaceae interactions are more specialised, resulting in more modular networks and stronger signatures of turnover than nestedness for beta diversity, than associations between parasitoids and Fagaceae. Rearing of nearly 27,000 cynipid gall specimens from 22 host plant species in Castanea, Castanopsis, Lithocarpus and Quercus (sections Cerris, Cyclobalanopsis, Ilex and Quercus) yielded 168 morphologically distinct cynipid gall morphotypes, and 3800 parasitoids in 67 morphospecies. The Sichuan parasitoid assemblage is similar in composition to cynipid-centred communities in the Western Palearctic and Nearctic. All of our predictions were confirmed. We discuss our findings in light of the processes thought to structure tritrophic interactions centred on gall inducing insect herbivores

Evolution of host-plant associations and biogeographic patterns on a global scale within the oak gall wasps

Co-evolutionary interactions between insect herbivores and their host plants underlie much contemporary biodiversity and are vital to assembly of natural ecosystems. Assemblages of galls on oaks induced by Cynipini wasps (Hymenoptera: Cynipidae) occur across much of the Northern Hemisphere, their diversity peaking in the Nearctic and on white oaks (Quercus section Quercus). However, the evolutionary history of the clade has been debated with respect to geographic origins, direction and timings of dispersal events, and shifts in host plant associations. We examined these questions using a global-scale, 6-gene phylogeny of 430 Cynipini species and a dataset of their associated host plants encompassing all eight sections within Quercus plus five Fagaceae genera. Likelihood-based ancestral state reconstructions demonstrate a Nearctic origin of the Cynipini followed by repeated colonisations of the Palearctic via both westwards and eastwards dispersal. These inferences are robust to bias in taxon sampling across continents and the inclusion of Protobalandricus as the sister lineage to Cynipini sensu stricto. Likewise, the association with white oaks is probably ancestral and has been retained by many Cynipini lineages. However, host shifts to other sections within Quercus and related Fagaceae genera are widely distributed across the cynipid phylogeny. They are associated with both global-scale range shifts and within-bioregion exploitation of alternative hosts, and their frequency typically correlates with host-plant relatedness. These findings highlight the evolutionary success of cynipids on white oak hosts and the connectedness of continental assemblages of gall wasps over evolutionary time

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. © 2014 Keyel et al

Rescue of heterochromatin organization in Hutchinson-Gilford progeria by drug treatment

Hutchinson-Gilford progeria (HGPS) is a premature aging syndrome associated with LMNA mutations. Progeria cells bearing the G608G LMNA mutation are characterized by accumulation of a mutated lamin A precursor (progerin), nuclear dysmorphism and chromatin disorganization. In cultured HGPS fibroblasts, we found worsening of the cellular phenotype with patient age, mainly consisting of increased nuclear-shape abnormalities, progerin accumulation and heterochromatin loss. Moreover, transcript distribution was altered in HGPS nuclei, as determined by different techniques. In the attempt to improve the cellular phenotype, we applied treatment with drugs either affecting protein farnesylation or chromatin arrangement. Our results show that the combined treatment with mevinolin and the histone deacetylase inhibitor trichostatin A dramatically lowers progerin levels, leading to rescue of heterochromatin organization and reorganization of transcripts in HGPS fibroblasts. These results suggest that morpho-functional defects of HGPS nuclei are directly related to progerin accumulation and can be rectified by drug treatment

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis

Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma

This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2′-2′-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity andexpression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m−2 min−1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m−2 and the doses were increased by 500 mg m−2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m−2 died because of toxicity; therefore; the MTD was established at 6500 mg m−2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m−2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P<0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation