Restricting microbial exposure in early life negates the immune benefits associated with gut colonization in environments of high microbial diversity

Background: Acquisition of the intestinal microbiota in early life corresponds with the development of the mucosal immune system. Recent work on caesarean-delivered infants revealed that early microbial composition is influenced by birthing method and environment. Furthermore, we have confirmed that early-life environment strongly influences both the adult gut microbiota and development of the gut immune system. Here, we address the impact of limiting microbial exposure after initial colonization on the development of adult gut immunity. Methodology/Principal Findings: Piglets were born in indoor or outdoor rearing units, allowing natural colonization in the immediate period after birth, prior to transfer to high-health status isolators. Strikingly, gut closure and morphological development were strongly affected by isolator-rearing, independent of indoor or outdoor origins of piglets. Isolator-reared animals showed extensive vacuolation and disorganization of the gut epithelium, inferring that normal gut closure requires maturation factors present in maternal milk. Although morphological maturation and gut closure were delayed in isolatorreared animals, these hard-wired events occurred later in development. Type I IFN, IL-22, IL-23 and Th17 pathways were increased in indoor-isolator compared to outdoor-isolator animals during early life, indicating greater immune activation in pigs originating from indoor environments reflecting differences in the early microbiota. This difference was less apparent later in development due to enhanced immune activation and convergence of the microbiota in all isolator-reared animals. This correlated with elevation of Type I IFN pathways in both groups, although T cell pathways were still more affected in indoor-reared animals. Conclusions/Significance: Environmental factors, in particular microbial exposure, influence expression of a large number of immune-related genes. However, the homeostatic effects of microbial colonization in outdoor environments require sustained microbial exposure throughout development. Gut development in high-hygiene environments negatively impacts on normal succession of the gut microbiota and promotes innate immune activation which may impair immune homeostasis.

Theory and generalization of Monte Carlo models of the BOLD signal source

The dependency of the blood oxygenation level dependent (BOLD) signal on underlying hemodynamics is not well understood. Building a forward biophysical model of this relationship is important for the quantitative estimation of the hemodynamic changes and neural activity underlying functional magnetic resonance imaging (fMRI) signals. We have developed a general model of the BOLD signal which can model both intra- and extravascular signals for an arbitrary tissue model across a wide range of imaging parameters. The model of the BOLD signal was instantiated as a look-up-table (LuT), and was verified against concurrent fMRI and optical imaging measurements of activation induced hemodynamics. Magn Reson Med, 2008. © 2008 Wiley-Liss, Inc.

Modulation of stretch-induced myocyte remodeling and gene expression by nitric oxide: a novel role for lipoma preferred partner in myofibrillogenesis

Prolonged hemodynamic load as a result of hypertension eventually leads to maladaptive cardiac adaptation and heart failure. The signalling pathways that underlie these changes are still poorly understood. The adaptive response to mechanical load is mediated by mechanosensors which convert the mechanical stimuli into a biological response. We examined the effect of cyclic mechanical stretch on myocyte adaptation using neonatal rat ventricular myocytes with 10% (adaptive) or 20% (maladaptive) maximum strain, 1Hz for 48 hours to mimic in vivo mechanical stress. Cells were also treated with and without L-NAME, a general nitric oxide synthase (NOS) inhibitor to suppress NO production. Maladaptive 20% mechanical stretch led to a significant loss of intact sarcomeres which was rescued by LNAME (P<0.05, n≥5 cultures). We hypothesized that the mechanism was through NOinduced alteration of myocyte gene expression. L-NAME up-regulated the mechanosensing proteins Muscle LIM protein (MLP (by 100%, p<0.05, n=4 cultures)) and lipoma preferred partner, a novel cardiac protein (LPP (by 80%, p<0.05, n=4 cultures)). L-NAME also significantly altered the subcellular localisation of LPP and MLP in a manner that favoured growth and adaptation. These findings suggest that NO participates in stretch-mediated adaptation. The use of isoform selective NOS inhibitors indicated a complex interaction between iNOS and nNOS isoforms regulate gene expression. LPP knockdown by siRNA led to formation of α-actinin aggregates and Z-bodies showing that myofibrillogenesis was impaired. There was an up-regulation of E3 ubiquitin ligase (MUL1) by 75% (P<0.05, n=5 cultures). This indicates that NO contributes to stretch-mediated adaptation via the upregulation of proteins associated mechansensing and myofibrillogenesis, thereby presenting potential therapeutic targets during the progression of heart failure. Keywords: Mechanotransduction, heart failure, stretch, heart, hypertrophy

The Liberal Way of War? French representations of the Allies, 1944-2008

This chapter looks at the ways in which Anglo-American participants in the Liberation of France have been represented in French narratives in the decades since the Second World War, through the developing French historiography of Allied participation in the War, and through the various roles assigned to the Allies in key postwar memorialisation ceremonies in France.

Connecting the complex ‘lived’ world(s) of Fairtrade

Although certified Fairtrade continues to use discourses of defetishization, its move into mainstream markets has acted to refetishize the consumer–producer relationship through the use of a standardized label, which acts as a substitute for engaged knowledges. Through Fairhills, a South African Fairtrade wine project, this paper explores the contextual complexity on the producer side of the commodity network. By incorporating the national discourse of Black Economic Empowerment into its operations, both in Fairhills and in South Africa in general, Fairtrade has adapted to this context, ensuring its relevance and credibility to stakeholders. However, in the UK, little more information than that commonly associated with Fairtrade is offered to Fairhills consumers. The particular market challenges facing Fairtrade wine in the UK make this negotiation between regulation and representation extremely pertinent. A productive way forward may be to conceptualize commodity fetishism as a continuum rather than a binary particularly when considering the difficult balance required when adding complexity to the targeted message of the existing label. This strategy for the sustainability of Fairtrade may be enhanced by utilizing the micro-level dynamism and adaptability that this paper shows is inherent, and indeed essential, to the durability and transferability of the discourse of Fairtrade.

Dust sources and deposition during the last glacial maximum and current climate: a comparison of model results with paleodata from ice cores and marine sediments

Mineral dust aerosols in the atmosphere have the potential to affect the global climate by influencing the radiative balance of the atmosphere and the supply of micronutrients to the ocean. Ice and marine sediment cores indicate that dust deposition from the atmosphere was at some locations 2–20 times greater during glacial periods, raising the possibility that mineral aerosols might have contributed to climate change on glacial-interglacial time scales. To address this question, we have used linked terrestrial biosphere, dust source, and atmospheric transport models to simulate the dust cycle in the atmosphere for current and last glacial maximum (LGM) climates. We obtain a 2.5-fold higher dust loading in the entire atmosphere and a twenty-fold higher loading in high latitudes, in LGM relative to present. Comparisons to a compilation of atmospheric dust deposition flux estimates for LGM and present in marine sediment and ice cores show that the simulated flux ratios are broadly in agreement with observations; differences suggest where further improvements in the simple dust model could be made. The simulated increase in high-latitude dustiness depends on the expansion of unvegetated areas, especially in the high latitudes and in central Asia, caused by a combination of increased aridity and low atmospheric [CO2]. The existence of these dust source areas at the LGM is supported by pollen data and loess distribution in the northern continents. These results point to a role for vegetation feedbacks, including climate effects and physiological effects of low [CO2], in modulating the atmospheric distribution of dust.

Competing effects of toxin-producing phytoplankton on overall plankton populations in the Bay of Bengal

The coexistence of a large number of phytoplankton species on a seemingly limited variety of resources is a classical problem in ecology, known as ‘the paradox of the plankton’. Strong fluctuations in species abundance due to the external factors or competitive interactions leading to oscillations, chaos and short-term equilibria have been cited so far to explain multi-species coexistence and biodiversity of phytoplankton. However, none of the explanations has been universally accepted. The qualitative view and statistical analysis of our field data establish two distinct roles of toxin-producing phytoplankton (TPP): toxin allelopathy weakens the interspecific competition among phytoplankton groups and the inhibition due to ingestion of toxic substances reduces the abundance of the grazer zooplankton. Structuring the overall plankton population as a combination of nontoxic phytoplankton (NTP), toxic phytoplankton, and zooplankton, here we offer a novel solution to the plankton paradox governed by the activity of TPP. We demonstrate our findings through qualitative analysis of our sample data followed by analysis of a mathematical model.

The extent to which potential benefits to EU farmers of adopting transgenic crops are reduced by cost of compliance with coexistence regulations

This article forecasts the extent to which the potential benefits of adopting transgenic crops may be reduced by costs of compliance with coexistence regulations applicable in various member states of the EU. A dynamic economic model is described and used to calculate the potential yield and gross margin of a set of crops grown in a selection of typical rotation scenarios. The model simulates varying levels of pest, weed, and drought pressures, with associated management strategies regarding pesticide and herbicide application, and irrigation. We report on the initial use of the model to calculate the net reduction in gross margin attributable to coexistence costs for insect-resistant (IR) and herbicide-tolerant (HT) maize grown continuously or in a rotation, HT soya grown in a rotation, HT oilseed rape grown in a rotation, and HT sugarbeet grown in a rotation. Conclusions are drawn about conditions favoring inclusion of a transgenic crop in a crop rotation, having regard to farmers’ attitude toward risk.

Novel single trial movement classification based on temporal dynamics of EEG

Various complex oscillatory processes are involved in the generation of the motor command. The temporal dynamics of these processes were studied for movement detection from single trial electroencephalogram (EEG). Autocorrelation analysis was performed on the EEG signals to find robust markers of movement detection. The evolution of the autocorrelation function was characterised via the relaxation time of the autocorrelation by exponential curve fitting. It was observed that the decay constant of the exponential curve increased during movement, indicating that the autocorrelation function decays slowly during motor execution. Significant differences were observed between movement and no moment tasks. Additionally, a linear discriminant analysis (LDA) classifier was used to identify movement trials with a peak accuracy of 74%.

Farmers' interest in growing GM crops in the UK, in the context of a range of on-farm coexistence issues

Although no GM crops currently are licensed for commercial production in the UK, as opposition to GM crops by consumers softens, this could change quickly. Although past studies have examined attitudes of UK farmers toward GM technologies in general, there has been little work on the impact of possible coexistence measures on their attitudes toward GM crop production. This could be because the UK Government has not engaged in any public dialogue on the coexistence measures that might be applied on farms. Based on a farm survey, this article examines farmers’ attitudes toward GM technologies and planting intentions for three crops (maize, oilseed rape, and sugar beet) based on a GM availability scenario. The article then nuances this analysis with a review of farmer perceptions of the level of constraint associated with a suite of notional farm-level coexistence measures and issues, based on current European Commission guidelines and practice in other EU Member States.

Brain-computer music interfacing for continuous control of musical tempo

A Brain-computer music interface (BCMI) is developed to allow for continuous modification of the tempo of dynamically generated music. Six out of seven participants are able to control the BCMI at significant accuracies and their performance is observed to increase over time.

An assessment of the impact of trees upon archaeology within a relict wetland

An evaluation of a surviving stretch of the Abbot's Way, in the Somerset Levels and Moors, was undertaken to assess the consequences of the previous management regime and inform future management of the site. The scheduled site appeared to have been dewatered and desiccated as a consequence of tree planting and the effects of a deep, adjacent drainage ditch during the previous decade. The evaluation considered the condition of the Neolithic timbers and associated palaeoenvironmental record from three trenches and, where possible, compared the results with those obtained form the 1974 excavation (Girling, 1976). The results of this analysis suggest that the hydrological consequences of tree planting and colonization had a detrimental effect on both the condition of the timbers and insect remains. However, pollen and plant macro-fossils survived well although there was modern contamination. A trench opened outside the scheduled area. where the ground was waterlogged and supported a wet acid grassland flora, revealed similar problems of survival and condition. This almost certainly reflects a period of peat extraction and an associated seasonally fluctuating water table in the 1950s and 1960s; in fact pollen survived better in the scheduled dewatered area. These results are compared with those recovered from the Sweet Track which was evaluated in 1996. Both sites have been subject to recent tree growth but the Sweet Track has been positively managed in terms of hydrology. The most notable difference between the two sites is that insects and wood survived better at the Sweet Track sites than at the Abbot's Way. Insects seem to be a more sensitive indicator of site desiccation than plant remains. It is recommended that any programme of management of wetland for archaeology should avoid deliberate tree planting and natural scrub and woodland generation. It should also take into account past as well as present land use.