Coordination of tolerogenic immune responses by the commensal microbiota

All mammals are born ignorant to the existence of micro-organisms. Soon after birth, however, every mammal begins a lifelong association with a multitude of microbes that lay residence on the skin, mouth, vaginal mucosa and gastrointestinal (GI) tract. Approximately 500–1000 different species of microbes have highly evolved to occupy these bodily niches, with the highest density and diversity occurring within the intestine [1]. These organisms play a vital role in mammalian nutrient breakdown and provide resistance to colonization by pathogenic micro-organisms. More recently, however, studies have demonstrated that the microbiota can have a profound and long-lasting effect on the development of our immune system both inside and outside the intestine [2]. While our immune system has evolved to recognize and eradicate foreign entities, it tolerates the symbiotic micro-organisms of the intestine. How and why this tolerance occurs has remained unclear. Here we present evidence that the commensal microbes of the intestine actively induce tolerant responses from the host that coordinate healthy immune responses. Potentially, disruption of this dialogue between the host and microbe can lead to the development of autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), or Type I diabetes (TID). As a wealth of publications have focused on the impact of the microbiota on intestinal immune responses and IBD, this chapter will focus on the extra-intestinal impacts of the microbiota from development to disease and integrate the known mechanisms by which the microbiota is able to actively communicate with its host to promote health

Vegetative propagation of dieback-tolerant Fraxinus excelsior on

book chapterThis publication is based on the work of Action FP1103 FRAXBACK, supported by COST (European Cooperation in Science and Technology)Ash trees which are tolerant to Hymenoscyphus fraxineus may be selected in all age classes among heavily infected populations. They may be produced also by controlled crossings of disease tolerant trees, because the genetic component of inheritance for disease tolerance is high. For mature and juvenile plant material, the deployment of disease tolerant genotypes could be potentially achieved by vegetatively propagating selected genotypes. We describe a system to vegetatively propagate selected ash genotypes and we discuss the prospects and options for using vegetative propagation on all age classes of trees. Mature trees were rejuvenated through the process of micropropagation to establish mother plants in large trays which were cut back repeatedly (hedged) to produce at least two crops of cuttings per year. The rooting capacity of ten genotypes was tested by a commercial nursery over a period of three years, to assess the feasibility of using hedged mother plants for efficient propagation. Commercial practise was to treat cuttings with 0.25% IBA, insert them in plug pots and maintain them covered with fine plastic within low plastic tunnels in a non heated greenhouse and without supplementary heating at the cutting base. In the first year, the mean rooting rate was 53 % for the first crop of cuttings and 35 % for the second. In the second and third years the rooting rates improved to over 80% for each crop of cuttings as experience was gained in handling the material. Rooting rate varied among the genotypes. We assessed the growth and development of micropropagated ash trees in the field from an observation clonal trial, consisting of four mature genotypes which had been established in 2002 in five replicate plots. The micropropagated trees were generally similar in height and dbh to seed derived control trees and developed normally. These observations are discussed in the context of using vegetative propagation as a tool in breeding and for the large scale deployment of ash with tolerance to H. fraxineus.European Cooperation in Science and Technolog

A comparison of inferential analysis methods for multilevel studies: implications for drawing conclusions in animal welfare science

Investigations comparing the behaviour and welfare of animals in different environments have led to mixed and often conflicting results. These could arise from genuine differences in welfare, poor validity of indicators, low statistical power, publication bias, or inappropriate statistical analysis. Our aim was to investigate the effects of using four approaches for inferential analysis of datasets of varying size on model outcomes and potential conclusions. We considered aggression in 864 growing pigs over six weeks as measured by ear and body injury score and relationships with: less and more enriched environments, pig's relative weight, and sex. Pigs were housed in groups of 18 in one of four pens, replicating the experiment 12 times. We applied four inferential models that either used a summary statistic approach, or else fully or partially accounted for complexities in study design. We tested models using both the full dataset (n = 864) and also using small sample sizes (n = 72). The most appropriate inferential model was a mixed effects, repeated measures model to compare ear and body score. Statistical models that did not acco unt for the correlation between repeated measures and/or the random effects from replications and pens led to spurious associations between environmental factors and indicators of aggression, which were not supported by the initial exploratory analysis. For analyses on smaller datasets (n = 72), due to the effect size and number of independent factors, there was insufficient power to determine statistically significant associations. Based on the mixed effects, repeated measures models, higher body injury scores were associated with more enrichment (coef. est. = 0.09, p = 0.02); weight (coef. est. = 0.05, p < 0.001); pen location on the right side (coef. est. = 0.08, p = 0.03) and at the front of the experimental room (coef. est. = 0.11, p = 0.003). By comparison, lower ear injury scores were associated with more enrichment (coef. est. = -0.51, p = 0.005) and pen location at the front of the experimental room (coef. est. = -0.4, p = 0.02). These observed differences support the hypothesis that injuries to the body and ears arise from different risk factors. Although calculation of the minimum required sample size prior to conducting an experiment and selection of the inferential analysis method will contribute to the validity of the study results, conflict between the outcomes will require further investigation via different methods such as sensitivity and specificity analysis

How much of Me do I see in You: Neural correlates of self-other distinction in the affective domain

When inferring mental states of others, individuals’ judgments are influenced by their own state of mind, which has been referred to as egocentric bias. Especially in situations where one holds a different mental state than another person to be interpreted, self-other differentiation is key for an accurate interpretation on the other person’s mind. It has been suggested that the right supramarginal gyrus (rSMG) is involved in self-other differentiation and overcoming egocentric bias in the affective domain. In a double-blind, randomized study 47 healthy adults received active or sham anodal tDCS (1mA, 20min) or a sham stimulation to the rSMG prior to performing a newly developed emotional egocentricity paradigm (SOFE, Self-Other Facial Emotion Judgment Task). In SOFE, subjects are presented with emotionally ambiguous situations (happy or fearful) in which they have to continuously rate 1) their own emotion and 2) the emotion of another person whose facial expression is either congruent or incongruent to the subject’s emotion. Analyses confirmed the presence of an emotional egocentric bias in incongruent trials. We furthermore found that active tDCS applied to the rSMG increased subjects’ ability to overcome egocentric judgments. This effect was valence dependent with significant effects when inferring affective states of happy faces right after imagining oneself in a fear-evoking situation (p<0.05). Our findings extend previous research showing a causal role of the rSMG for emotional self-other distinction to the inferring of emotional states from pictorial stimuli. They additionally point towards valence-specific patterns of rSMG functionality. In a next step the SOFE task will be applied in autism spectrum disorder to characterize egocentric bias suppression and SMG network integrity in an effort to elucidate social cognitive dysfunction in affected individuals

Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model

B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora

Isotopic analysis of faunal material from South Uist, Western Isles, Scotland

This paper reports on the results from stable isotope analysis of faunal bone collagen from a number of Iron Age and later sites on the island of South Uist, in the Western Isles, Scotland. This preliminary investigation into the isotopic signatures of the fauna is part of a larger project to model the interaction between humans, animals, and the broader environment in the Western Isles. The results demonstrate that the island fauna data fall within the range of expected results for the UK, with the terrestrial herbivorous diets of cattle and sheep confi rmed. The isotopic composition for pigs suggests that some of these animals had an omnivorous diet, whilst a single red deer value might be suggestive of the consumption of marine foods, such as by grazing on seaweed. However, further analysis is needed in order to verify this anomalous isotopic ratio

Initial correlations effects on decoherence at zero temperature

We consider a free charged particle interacting with an electromagnetic bath at zero temperature. The dipole approximation is used to treat the bath wavelengths larger than the width of the particle wave packet. The effect of these wavelengths is described then by a linear Hamiltonian whose form is analogous to phenomenological Hamiltonians previously adopted to describe the free particle-bath interaction. We study how the time dependence of decoherence evolution is related with initial particle-bath correlations. We show that decoherence is related to the time dependent dressing of the particle. Moreover because decoherence induced by the T=0 bath is very rapid, we make some considerations on the conditions under which interference may be experimentally observed.Comment: 16 pages, 1 figur