Trade-off between constitutive and inducible resistance against herbivores is only partially explained by gene expression and glucosinolate production.

The hypothesis that constitutive and inducible plant resistance against herbivores should trade-off because they use the same resources and impose costs to plant fitness has been postulated for a long time. Negative correlations between modes of deployment of resistance and defences have been observed across and within species in common garden experiments. It was therefore tested whether that pattern of resistance across genotypes follows a similar variation in patterns of gene expression and chemical defence production. Using the genetically tractable model Arabidopsis thaliana and different modes of induction, including the generalist herbivore Spodoptera littoralis, the specialist herbivore Pieris brassicae, and jasmonate application, constitutive and inducibility of resistance was measured across seven A. thaliana accessions that were previously selected based on constitutive levels of defence gene expression. According to theory, it was found that modes of resistance traded-off among accessions, particularly against S. littoralis, in which accessions investing in high constitutive resistance did not increase it substantially after attack and vice-versa. Accordingly, the average expression of eight genes involved in glucosinolate production negatively predicted larval growth across the seven accessions. Glucosinolate production and genes related to defence induction on healthy and herbivore-damaged plants were measured next. Surprisingly, only a partial correlation between glucosinolate production, gene expression, and the herbivore resistance results was found. These results suggest that the defence outcome of plants against herbivores goes beyond individual molecules or genes but stands on a complex network of interactions.

Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the peptide-MHC (pMHC) on cells is a key parameter for cell-mediated immunity. Yet a fundamental feature of most tumor antigen-specific CD8(+) T cells is that this avidity is low. In this study, we addressed the need to identify and select tumor-specific CD8(+) T cells of highest avidity, which are of the greatest interest for adoptive cell therapy in patients with cancer. To identify these rare cells, we developed a peptide-MHC multimer technology, which uses reversible Ni(2+)-nitrilotriacetic acid histidine tags (NTAmers). NTAmers are highly stable but upon imidazole addition, they decay rapidly to pMHC monomers, allowing flow-cytometric-based measurements of monomeric TCR-pMHC dissociation rates of living CD8(+) T cells on a wide avidity spectrum. We documented strong correlations between NTAmer kinetic results and those obtained by surface plasmon resonance. Using NTAmers that were deficient for CD8 binding to pMHC, we found that CD8 itself stabilized the TCR-pMHC complex, prolonging the dissociation half-life several fold. Notably, our NTAmer technology accurately predicted the function of large panels of tumor-specific T cells that were isolated prospectively from patients with cancer. Overall, our results demonstrated that NTAmers are effective tools to isolate rare high-avidity cytotoxic T cells from patients for use in adoptive therapies for cancer treatment.

Discovery-dominance trade-off among widespread invasive ant species

Ants are among the most problematic invasive species. They displace numerous native species, alter ecosystem processes, and can have negative impacts on agriculture and human health. In part, their success might stem from a departure from the discovery-dominance trade-off that can promote co-existence in native ant communities, that is, invasive ants are thought to be at the same time behaviorally dominant and faster discoverers of resources, compared to native species. However, it has not yet been tested whether similar asymmetries in behavioral dominance, exploration, and recruitment abilities also exist among invasive species. Here, we establish a dominance hierarchy among four of the most problematic invasive ants (Linepithema humile, Lasius neglectus, Wasmannia auropunctata, Pheidole megacephala) that may be able to arrive and establish in the same areas in the future. To assess behavioral dominance, we used confrontation experiments, testing the aggressiveness in individual and group interactions between all species pairs. In addition, to compare discovery efficiency, we tested the species' capacity to locate a food resource in a maze, and the capacity to recruit nestmates to exploit a food resource. The four species differed greatly in their capacity to discover resources and to recruit nestmates and to dominate the other species. Our results are consistent with a discovery-dominance trade-off. The species that showed the highest level of interspecific aggressiveness and dominance during dyadic interactions.

Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens.

The animal gut plays a central role in tackling two common ecological challenges, nutrient shortage and food-borne parasites, the former by efficient digestion and nutrient absorption, the latter by acting as an immune organ and a barrier. It remains unknown whether these functions can be independently optimised by evolution, or whether they interfere with each other. We report that Drosophila melanogaster populations adapted during 160 generations of experimental evolution to chronic larval malnutrition became more susceptible to intestinal infection with the opportunistic bacterial pathogen Pseudomonas entomophila. However, they do not show suppressed immune response or higher bacterial loads. Rather, their increased susceptibility to P. entomophila is largely mediated by an elevated predisposition to loss of intestinal barrier integrity upon infection. These results may reflect a trade-off between the efficiency of nutrient extraction from poor food and the protective function of the gut, in particular its tolerance to pathogen-induced damage.

International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

Temporal Patterns of Alcohol Consumption and Alcohol-Related Road Accidents in Young Swiss Men: Seasonal, Weekday and Public Holiday Effects.

AIMS: To assess seasonal, weekday, and public holiday effects on alcohol-related road accidents and drinking diaries among young Swiss men. METHODS: Federal road accident data (35,485 accidents) from Switzerland and drinking diary data from a large cohort of young Swiss men (11,930 subjects) were analysed for temporal effects by calendar week, weekday and public holiday (Christmas, New Years, National Day). Alcohol-related accidents were analysed using rate ratios for observed versus expected numbers of accidents and proportions of alcohol-related accidents relative to the total number. Drinking diaries were analysed for the proportion of drinkers, median number of drinks consumed, and the 90th percentile's number of drinks consumed. RESULTS: Several parallel peaks were identified in alcohol-related accidents and drinking diaries. These included increases on Fridays and Saturdays, with Saturday drinking extending until early Sunday morning, an increase during the summer on workdays but not weekends, an increase at the end of the year, and increases on public holidays and the evening before. CONCLUSIONS: Our results suggest specific time-windows that are associated with increases in drinking and alcohol-related harm. Established prevention measures should be enforced during these time-windows to reduce associated peaks.

Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift-off test of varying duration.

Intravoxel incoherent motion (IVIM) MRI is a method to extract microvascular blood flow information out of diffusion-weighted images acquired at multiple b-values. We hypothesized that IVIM can identify the muscles selectively involved in a specific task, by measuring changes in activity-induced local muscular perfusion after exercise. We tested this hypothesis using a widely used clinical maneuver, the lift-off test, which is known to assess specifically the subscapularis muscle functional integrity. Twelve shoulders from six healthy male volunteers were imaged at 3 T, at rest, as well as after a lift-off test hold against resistance for 30 s, 1 and 2 min respectively, in three independent sessions. IVIM parameters, consisting of perfusion fraction (f), diffusion coefficient (D), pseudo-diffusion coefficient D* and blood flow-related fD*, were estimated within outlined muscles of the rotator cuff and the deltoid bundles. The mean values at rest and after the lift-off tests were compared in each muscle using a one-way ANOVA. A statistically significant increase in fD* was measured in the subscapularis, after a lift-off test of any duration, as well as in D. A fD* increase was the most marked (30 s, +103%; 1 min, +130%; 2 min, +156%) and was gradual with the duration of the test (in 10(-3) mm(2) /s: rest, 1.41 ± 0.50; 30 s, 2.86 ± 1.17; 1 min, 3.23 ± 1.22; 2 min, 3.60 ± 1.21). A significant increase in fD* and D was also visible in the posterior bundle of the deltoid. No significant change was consistently visible in the other investigated muscles of the rotator cuff and the other bundles of the deltoid. In conclusion, IVIM fD* allows the demonstration of a task-related microvascular perfusion increase after a specific task and suggests a direct relationship between microvascular perfusion and the duration of the effort. It is a promising method to investigate non-invasively skeletal muscle physiology and clinical perfusion-related muscular disorders.

Single Heartstring aortotomy for multiple off-pump venous bypass grafts.

Off-pump coronary bypass grafting may decrease the rate of stroke, due to minimal aortic manipulation. For venous grafts, clampless hemostasis when performing the proximal anastomosis can be achieved using the Heartstring device. We describe a technique using a single device to suture two veins to one aortotomy. This technique requires less space and could be advantageous in very short, small, and calcified aortas. In to our experience, this technique is rapid, simple, easy to reproduce, and cost-saving.

Are Public Private Partnerships that Rigid ? And Why ? : Evidence from Toll Road Concession Contracts

Transport concession contracts are commonly said to be standardized and too rigid. They would not allow public authorities to adapt them to evolving context and circumstances. This paper aims at challenging this view and, more particularly, the view that contractual rigidity for transport concessions is exogenous. Using a transaction cost framework, we disentangle between three main determinants of contractual rigidity: traffic uncertainty; connivance between contracting parties; quality of the institutional environment. Using an original database of toll road concession contracts, we observe a great variety of provisions for toll adjustment. We find that these exogenous determinants significantly influence contractual choices.