Co-Evolution of quasispecies: B-cell mutation rates maximize viral error catastrophes

Co-evolution of two coupled quasispecies is studied, motivated by the competition between viral evolution and adapting immune response. In this co-adaptive model, besides the classical error catastrophe for high virus mutation rates, a second ``adaptation-'' catastrophe occurs, when virus mutation rates are too small to escape immune attack. Maximizing both regimes of viral error catastrophes is a possible strategy for an optimal immune response, reducing the range of allowed viral mutation rates to a minimum. From this requirement one obtains constraints on B-cell mutation rates and receptor lengths, yielding an estimate of somatic hypermutation rates in the germinal center in accordance with observation.Comment: 4 pages RevTeX including 2 figure

Immunological changes in nestlings growing under predation risk

Predation is one of the most relevant selective forces in nature. However, the physiological mechanisms behind anti-predator strategies have been overlooked, despite their importance to understand predator-prey interactions. In this context, the immune system could be especially revealing due to its relationship with other critical functions and its ability to enhance prey's probabilities of survival to a predator's attack. Developing organisms (e.g. nestlings) are excellent models to study this topic because they suffer a high predation pressure while undergoing the majority of their development, which maximizes potential trade-offs between immunity and other biological functions. Using common blackbirds Turdus merula as model species, we experimentally investigated whether an elevated nest predation risk during the nestling period affects nestlings' immunity and its possible interactions with developmental conditions (i.e. body condition and growth). Experimental nestlings modified some components of their immunity, but only when considering body condition and growth rate, indicating a multifaceted immunological response to predation risk and an important mediator role of nestlings' developmental conditions. Predation risk induced a suppression of IgY but an increase in lymphocytes in nestlings with poor body condition. In addition, experimental but not control nestlings showed a negative correlation between growth and heterophils, demonstrating that nest predation risk can affect the interaction between growth and immunity. This study highlights the importance of immunity in anti-predator response in nestlings and shows the relevance of including physiological components to the study of predation risk.</p

Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin-10 and glial inhibitors

<p>Abstract</p> <p>Background</p> <p>In addition to caudal subnucleus caudalis (Vc) of the spinal trigeminal complex, recent studies indicate that the subnuclei interpolaris/caudalis (Vi/Vc) transition zone plays a unique role in processing deep orofacial nociceptive input. Studies also suggest that glia and inflammatory cytokines contribute to the development of persistent pain. By systematically comparing the effects of microinjection of the antiinflammatory cytokine interleukin (IL)-10 and two glial inhibitors, fluorocitrate and minocycline, we tested the hypothesis that there was a differential involvement of Vi/Vc and caudal Vc structures in deep and cutaneous orofacial pain.</p> <p>Results</p> <p>Deep or cutaneous inflammatory hyperalgesia, assessed with von Frey filaments, was induced in rats by injecting complete Freund's adjuvant (CFA) into the masseter muscle or skin overlying the masseter, respectively. A unilateral injection of CFA into the masseter or skin induced ipsilateral hyperalgesia that started at 30 min, peaked at 1 d and lasted for 1-2 weeks. Secondary hyperalgesia on the contralateral site also developed in masseter-, but not skin-inflamed rats. Focal microinjection of IL-10 (0.006-1 ng), fluorocitrate (1 μg), and minocycline (0.1-1 μg) into the ventral Vi/Vc significantly attenuated masseter hyperalgesia bilaterally but without an effect on hyperalgesia after cutaneous inflammation. Injection of the same doses of these agents into the caudal Vc attenuated ipsilateral hyperalgesia after masseter and skin inflammation, but had no effect on contralateral hyperalgesia after masseter inflammation. Injection of CFA into the masseter produced significant increases in N-methyl-D-aspartate (NMDA) receptor NR1 serine 896 phosphorylation and glial fibrillary acidic protein (GFAP) levels, a marker of reactive astrocytes, in Vi/Vc and caudal Vc. In contrast, cutaneous inflammation only produced similar increases in the Vc.</p> <p>Conclusion</p> <p>These results support the hypothesis that the Vi/Vc transition zone is involved in deep orofacial injury and suggest that glial inhibition and interruption of the cytokine cascade after inflammation may provide pain relief.</p

Indução da atividade fagocitária e produção de óxido nítrico numa população natural de Trypanosoma cruzi I e II do Estado do Paraná, Brasil

Twelve strains of Trypanosoma cruzi isolated from wild reservoirs, triatomines, and chronic chagasic patients in the state of Paraná, southern Brazil, and classified as T. cruzi I and II, were used to test the correlation between genetic and biological diversity. The Phagocytic Index (PI) and nitric-oxide (NO) production in vitro were used as biological parameters. The PI of the T. cruzi I and II strains did not differ significantly, nor did the PI of the T. cruzi strains isolated from humans, triatomines, or wild reservoirs. There was a statistical difference in the inhibition of NO production between T. cruzi I and II and between parasites isolated from humans and the strains isolated from triatomines and wild reservoirs, but there was no correlation between genetics and biology when the strains were analyzed independently of the lineages or hosts from which the strains were isolated. There were significant correlations for Randomly Amplified Polymorphic Deoxyribonucleic acid (RAPD) and biological parameters for T. cruzi I and II, and for humans or wild reservoirs when the lineages or hosts were considered individually.Doze cepas de Trypanosoma cruzi isoladas de reservatórios silvestres, triatomíneos e de pacientes chagásicos crônicos do Estado do Paraná, Brasil, classificadas como Tc I e II foram usadas para avaliar a correlação entre genética e diversidade biológica. Índice fagocítico (IF) e produção de óxido nítrico (ON) in vitro foram os parâmetros biológicos utilizados. O IF de cepas T. cruzi I e II não diferiram significativamente assim como o IF de cepas isoladas de humanos, triatomíneos ou de reservatórios silvestres. Há diferença estatística na inibição da produção de ON entre T. cruzi I e II e entre parasitos isolados de humanos e de cepas isoladas de triatomíneos e reservatórios silvestres, mas não foi observada correlação entre genética e biologia quando as cepas foram analisadas independentemente da linhagem ou hospedeiros das quais elas foram isoladas. Observou-se correlação significativa para amplificação aleatória do DNA polimórfico e parâmetros biológicos de Tc I ou II e para os seres humanos ou reservatório silvestre quando linhagens ou hospedeiros são consideradas separadamente

Evolution of defence portfolios in exploiter-victim systems

Some organisms maintain a battery of defensive strategies against their exploiters (predators, parasites or parasitoids), while others fail to employ a defence that seems obvious. In this paper, we shall investigate the circumstances under which defence strategies might be expected to evolve. Brood parasites and their hosts provide our main motivation, and we shall discuss why the reed warbler Acrocephalus scirpaceus has evolved an egg-rejection but not a chick-rejection strategy as a defence against the common (Eurasian) cuckoo Cuculus canorus, while the superb fairy-wren Malurus cyaneus has evolved a chick-rejection but not an egg-rejection strategy as a defence against Horsfield's bronze-cuckoo Chrysococcyx basalis. We suggest that the answers lie in strategy-blocking, where one strategy (the blocking strategy) prevents the appearance of another (the blocked strategy) that would be adaptive in its absence. This may be common in exploiter-victim systems. © 2006 Springer Science+Business Media, Inc

Mixed-strain housing for female C57BL/6, DBA/2, and BALB/c mice: validating a split-plot design that promotes refinement and reduction

Abstract Background Inefficient experimental designs are common in animal-based biomedical research, wasting resources and potentially leading to unreplicable results. Here we illustrate the intrinsic statistical power of split-plot designs, wherein three or more sub-units (e.g. individual subjects) differing in a variable of interest (e.g. genotype) share an experimental unit (e.g. a cage or litter) to which a treatment is applied (e.g. a drug, diet, or cage manipulation). We also empirically validate one example of such a design, mixing different mouse strains -- C57BL/6, DBA/2, and BALB/c -- within cages varying in degree of enrichment. As well as boosting statistical power, no other manipulations are needed for individual identification if co-housed strains are differentially pigmented, so also sparing mice from stressful marking procedures. Methods The validation involved housing 240 females from weaning to 5 months of age in single- or mixed- strain trios, in cages allocated to enriched or standard treatments. Mice were screened for a range of 26 commonly-measured behavioural, physiological and haematological variables. Results Living in mixed-strain trios did not compromise mouse welfare (assessed via corticosterone metabolite output, stereotypic behaviour, signs of aggression, and other variables). It also did not alter the direction or magnitude of any strain- or enrichment-typical difference across the 26 measured variables, or increase variance in the data: indeed variance was significantly decreased by mixed- strain housing. Furthermore, using Monte Carlo simulations to quantify the statistical power benefits of this approach over a conventional design demonstrated that for our effect sizes, the split- plot design would require significantly fewer mice (under half in most cases) to achieve a power of 80 %. Conclusions Mixed-strain housing allows several strains to be tested at once, and potentially refines traditional marking practices for research mice. Furthermore, it dramatically illustrates the enhanced statistical power of split-plot designs, allowing many fewer animals to be used. More powerful designs can also increase the chances of replicable findings, and increase the ability of small-scale studies to yield significant results. Using mixed-strain housing for female C57BL/6, DBA/2 and BALB/c mice is therefore an effective, efficient way to promote both refinement and the reduction of animal-use in research