Balancing selection,genetic drift,and human‐mediated introgression interplay to shape MHC (functional) diversity in Mediterranean brown trout

The extraordinary polymorphism of major histocompatibility complex (MHC) genes is considered a paradigm of pathogen‐mediated balancing selection, although empirical evidence is still scarce. Furthermore, the relative contribution of balancing selection to shape MHC population structure and diversity, compared to that of neutral forces, as well as its interaction with other evolutionary processes such as hybridization, remains largely unclear. To investigate these issues, we analyzed adaptive (MHC‐DAB gene) and neutral (11 microsatellite loci) variation in 156 brown trout (Salmo trutta complex) from six wild populations in central Italy exposed to introgression from domestic hatchery lineages (assessed with the LDH gene). MHC diversity and structuring correlated with those at microsatellites, indicating the substantial role of neutral forces. However, individuals carrying locally rare MHC alleles/supertypes were in better body condition (a proxy of individual fitness/parasite load) regardless of the zygosity status and degree of sequence dissimilarity of MHC, hence supporting balancing selection under rare allele advantage, but not heterozygote advantage or divergent allele advantage. The association between specific MHC supertypes and body condition confirmed in part this finding. Across populations, MHC allelic richness increased with increasing admixture between native and domestic lineages, indicating introgression as a source of MHC variation. Furthermore, introgression across populations appeared more pronounced for MHC than microsatellites, possibly because initially rare MHC variants are expected to introgress more readily under rare allele advantage. Providing evidence for the complex interplay among neutral evolutionary forces, balancing selection, and human‐mediated introgression in shaping the pattern of MHC (functional) variation, our findings contribute to a deeper understanding of the evolution of MHC genes in wild populations exposed to anthropogenic disturbance.     

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose,short-term experimental model

Background

The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol.

Objectives

This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses.

Methods

Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE.

Results

Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses.

Conclusions

The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE.     

Rats go genomic

A report on the meeting 'Rat Genomics and Models', Cold Spring Harbor, USA, 8-11 December 2005.     

Habitat selection and activity patterns in Alpine mountain hare (Lepus timidus varronis)

We investigated activity patterns and habitat use of 34 radio-tracked mountain hares (Lepus timidus) in the Italian Alps. We first showed that hares were nocturnal and that activity patterns changed seasonally in parallel with circadian rhythms. We predicted that day home ranges will include suitable resting (shelter) habitats, and night home ranges will primarily include suitable foraging habitats. A hare's night-range was larger than its day-range. On average, night and day ranges overlapped by 36%, suggesting that selective pressures affecting space use were, at least partly, different at night than day. Dwarf mountain-pine was the most preferred habitat in all seasons and was selected both for active behaviour (night) and resting (day) and hares avoided the most open habitats. Exploring the effects of season, time of day (day vs. night) and site, we found that habitat use by mountain hares did not differ between seasons or between the active (night) and resting (day) period of circadian cycle. Also, we found no effects of differences in landscape structure (habitat patchiness and heterogeneity) on the patterns of habitat selection. Hares always preferred the dense, forested habitats, which seemed to provide food resources as well as shelter from predators throughout the year.     

Estimating and comparing food availability for tree‐seed predators in typical pulsed‐resource systems: Alpine conifer forests

Abstract

Alpine conifers produce pulsed resources for the community of tree‐seed consumers. Here, we describe field and statistical methods to estimate spatio‐temporal variation in seed‐crops in forests with different species composition. Annual and between‐site variation in seed production was high and characterised by occurrence of mast‐crops followed by seed‐crop failure the following year. Seed‐crops of different species did not fluctuate in parallel.

Abbreviations: DLSM, differences of least square means; CED, Cedrasco; OGA, Oga; VAL, Valfurva; BOR, Bormio; RHE, Rhemes; COG, Cogne     

Snapshots of enzymatic Baeyer-Villiger catalysis: oxygen activation and intermediate stabilization

Baeyer-Villiger monooxygenases catalyze the oxidation of carbonylic substrates to ester or lactone products using NADPH as electron donor and molecular oxygen as oxidative reactant. Using protein engineering, kinetics, microspectrophotometry, crystallography, and intermediate analogs, we have captured several snapshots along the catalytic cycle which highlight key features in enzyme catalysis. After acting as electron donor, the enzyme-bound NADP(H) forms an H-bond with the flavin cofactor. This interaction is critical for stabilizing the oxygen-activating flavin-peroxide intermediate that results from the reaction of the reduced cofactor with oxygen. An essential active-site arginine acts as anchoring element for proper binding of the ketone substrate. Its positively charged guanidinium group can enhance the propensity of the substrate to undergo a nucleophilic attack by the flavin-peroxide intermediate. Furthermore, the arginine side chain, together with the NADP(+) ribose group, forms the niche that hosts the negatively charged Criegee intermediate that is generated upon reaction of the substrate with the flavin-peroxide. The fascinating ability of Baeyer-Villiger monooxygenases to catalyze a complex multistep catalytic reaction originates from concerted action of this Arg-NADP(H) pair and the flavin subsequently to promote flavin reduction, oxygen activation, tetrahedral intermediate formation, and product synthesis and release. The emerging picture is that these enzymes are mainly oxygen-activating and "Criegee-stabilizing" catalysts that act on any chemically suitable substrate that can diffuse into the active site, emphasizing their potential value as toolboxes for biocatalytic applications.     

Automatic synthesis of rulesets for programmable stochastic self-assembly of rotationally symmetric robotic modules

Programmable stochastic self-assembly of modular robots provides promising means to formation of structures at different scales. One way to address the design of dedicated control rulesets for self-assembling robotic modules is to leverage formalisms based on graph grammar. While these tools are powerful and allow for formal analysis of the resulting controllers, expressing the embodiment of the robotic modules and therefore the physical structure of assemblies of such modules is not readily possible with such formalisms. This typically results in inefficient representation of ruleset controllers and poses limitations on automatizing ruleset synthesis methods, requiring manual design or tuning of the rules before deployment on the robotic modules. In this work, we consider robotic modules endowed with identical latching connectors arranged in a rotationally symmetric configuration. We extend a grammar formalism based on graphs and propose a new encoding of the modules’ internal states. This allows for formulating formal methods capable of automatically deriving the rules based on the morphology of the robotic modules, in particular their number of connectors. The derived rules are directly applicable to robotic modules with no further tuning. In addition, we show that our method allows for a reduced complexity in the rulesets, a particularly welcome feature in the case of limited on-board storage, computation, and communication resources. In order to illustrate the application of our method, we extend two synthesis algorithms from the literature, namely Singleton and Linchpin, to automatically synthesize rules applicable to our resource-constrained robotic modules. In order to increase the prototyping speed and the thoroughness of the validation for the synthesis algorithms, we leverage two complementary simulation frameworks capturing the system at different levels of abstraction. Finally, employing the generated rulesets, we conduct experiments with our robotic platform to demonstrate several assemblies.     

Distributed scalable multi-robot learning using particle swarm optimization

Designing effective behavioral controllers for mobile robots can be difficult and tedious; this process can be circumvented by using online learning techniques which allow robots to generate their own controllers online in an automated fashion. In multi-robot systems, robots operating in parallel can potentially learn at a much faster rate by sharing information amongst themselves. In this work, we use an adapted version of the Particle Swarm Optimization algorithm in order to accomplish distributed online robotic learning in groups of robots with access to only local information. The effectiveness of the learning technique on a benchmark task (generating high-performance obstacle avoidance behavior) is evaluated for robot groups of various sizes, with the maximum group size allowing each robot to individually contain and manage a single PSO particle. To increase the realism of the technique, different PSO neighborhoods based on limitations of real robotic communication are tested and compared in this scenario. We explore the effect of varying communication power for one of these communication-based PSO neighborhoods. To validate the effectiveness of these learning techniques, fully distributed online learning experiments are run using a group of 10 real robots, generating results which support the findings from our simulations.