Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces

Background: Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results: Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in earlylife environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoorhoused pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results.

Balance model for equatorial long waves

Geophysical fluid models often support both fast and slow motions. As the dynamics are often dominated by the slow motions, it is desirable to filter out the fast motions by constructing balance models. An example is the quasi geostrophic (QG) model, which is used widely in meteorology and oceanography for theoretical studies, in addition to practical applications such as model initialization and data assimilation. Although the QG model works quite well in the mid-latitudes, its usefulness diminishes as one approaches the equator. Thus far, attempts to derive similar balance models for the tropics have not been entirely successful as the models generally filter out Kelvin waves, which contribute significantly to tropical low-frequency variability. There is much theoretical interest in the dynamics of planetary-scale Kelvin waves, especially for atmospheric and oceanic data assimilation where observations are generally only of the mass field and thus do not constrain the wind field without some kind of diagnostic balance relation. As a result, estimates of Kelvin wave amplitudes can be poor. Our goal is to find a balance model that includes Kelvin waves for planetary-scale motions. Using asymptotic methods, we derive a balance model for the weakly nonlinear equatorial shallow-water equations. Specifically we adopt the ‘slaving’ method proposed by Warn et al. (Q. J. R. Meteorol. Soc., vol. 121, 1995, pp. 723–739), which avoids secular terms in the expansion and thus can in principle be carried out to any order. Different from previous approaches, our expansion is based on a long-wave scaling and the slow dynamics is described using the height field instead of potential vorticity. The leading-order model is equivalent to the truncated long-wave model considered previously (e.g. Heckley & Gill, Q. J. R. Meteorol. Soc., vol. 110, 1984, pp. 203–217), which retains Kelvin waves in addition to equatorial Rossby waves. Our method allows for the derivation of higher-order models which significantly improve the representation of Rossby waves in the isotropic limit. In addition, the ‘slaving’ method is applicable even when the weakly nonlinear assumption is relaxed, and the resulting nonlinear model encompasses the weakly nonlinear model. We also demonstrate that the method can be applied to more realistic stratified models, such as the Boussinesq model.

Staphylococcus aureus lipoteichoic acid inhibits platelet activation and thrombus formation via the Paf receptor

Impaired healing is common in wounds infected with the major human pathogen Staphylococcus aureus, although the underlying mechanisms are poorly understood. Here, we show that S.aureus lipoteichoic acid (LTA) inhibits platelet aggregation caused by physiological agonists and S. aureus and reduced platelet thrombus formation in vitro. The presence of D-alanine on LTA is necessary for the full inhibitory effect. Inhibition of aggregation was blocked using a monoclonal anti-platelet activating factor receptor (PafR) antibody and Ginkgolide B, a well-defined PafR antagonist, demonstrating that the LTA inhibitory signal occurs via PafR. Using a cyclic AMP (cAMP) assay and a western blot for phosphorylated VASP, we determined that cAMP levels increase upon platelet incubation with LTA, an effect which inhibits platelet activation. This was blocked when platelets were preincubated with Ginkgolide B. Furthermore, LTA reduced haemostasis in a mouse tail-bleed assay.

The Marlborough mound, Wiltshire. A further Neolithic monumental mound by the River Kennet.

Recent radiocarbon dates obtained from two soil cores taken through the Marlborough Castle mound, Wiltshire, show the main body of it to be a contemporaneous monument to Silbury Hill, dating to the second half of the 3rd millennium cal bc. In light of these dates, this paper considers the sequence identified within the cores, which includes two possible flood events early in the construction of the mound. It also describes four cores taken through the surrounding ditch, as well as small-scale work to the north-east of the mound. The topographic location of the mound in a low-lying area and close to rivers and springs is discussed, and the potential for Late Neolithic sites nearby is set out, with the land to the south of the mound identified as an area for future research. The paper ends with the prospect that other apparent mottes in Wiltshire and beyond may well also have prehistoric origins

Preferential dust sources: a geomorphological classification designed and for use in global aerosol models

We present a simple theoretical land-surface classification that can be used to determine the location and temporal behavior of preferential sources of terrestrial dust emissions. The classification also provides information about the likely nature of the sediments, their erodibility and the likelihood that they will generate emissions under given conditions. The scheme is based on the dual notions of geomorphic type and connectivity between geomorphic units. We demonstrate that the scheme can be used to map potential modern-day dust sources in the Chihuahuan Desert, the Lake Eyre Basin and the Taklamakan. Through comparison with observed dust emissions, we show that the scheme provides a reasonable prediction of areas of emission in the Chihuahuan Desert and in the Lake Eyre Basin. The classification is also applied to point source data from the Western Sahara to enable comparison of the relative importance of different land surfaces for dust emissions. We indicate how the scheme could be used to provide an improved characterization of preferential dust sources in global dust-cycle models.

Evaluation of reach and grasp robot-assisted therapy suggests similar functional recovery patterns on proximal and distal arm segments in sub-acute hemiplegia

This paper provides some additional evidence in support of the hypothesis that robot therapies are clinically beneficial in neurorehabilitation. Although only 4 subjects were included in the study, the design of the intervention and the measures were done so as to minimise bias. The results are presented as single case studies, and can only be interpreted as such due to the study size. The intensity of intervention was 16 hours and the therapy philosophy (based on Carr and Shepherd) was that coordinated movements are preferable to joint based therapies, and that coordinating distal movements (in this case grasps) helps not only to recover function in these areas, but has greater value since the results are immediately transferable to daily skills such as reach and grasp movements.

The effect of increased convective entrainment on Asian monsoon biases in the MetUM General Circulation Model

We demonstrate that summer precipitation biases in the South Asian monsoon domain are sensitive to increasing the convective parametrisation’s entrainment and detrainment rates in the Met Office Unified Model. We explore this sensitivity to improve our understanding of the biases and inform efforts to improve convective parametrisation. We perform novel targeted experiments in which we increase the entrainment and detrainment rates in regions of especially large precipitation bias. We use these experiments to determine whether the sensitivity at a given location is a consequence of the local change to convection or is a remote response to the change elsewhere. We find that a local change leads to different mean-state responses in comparable regions. When the entrainment and detrainment rates are increased globally, feedbacks between regions usually strengthen the local responses. We choose two regions of tropical ascent that show different mean-state responses, the western equatorial Indian Ocean and western north Pacific, and analyse them as case studies to determine the mechanisms leading to the different responses. Our results indicate that several aspects of a region’s mean-state, including moisture content, sea surface temperature and circulation, play a role in local feedbacks that determine the response to increased entrainment and detrainment.

In vitro and in vivo models of colorectal cancer: antigenotoxic activity of berries.

The etiology of colorectal cancer (CRC), a common cause of cancer-related mortality globally, has strong associations with diet. There is considerable epidemiological evidence that fruits and vegetables are associated with reduced risk of CRC. This paper reviews the extensive evidence, both from in vitro studies and animal models, that components of berry fruits can modulate biomarkers of DNA damage and that these effects may be potentially chemoprotective, given the likely role that oxidative damage plays in mutation rate and cancer risk. Human intervention trials with berries are generally consistent in indicating a capacity to significantly decrease oxidative damage to DNA, but represent limited evidence for anticarcinogenicity, relying as they do on surrogate risk markers. To understand the effects of berry consumption on colorectal cancer risk, future studies will need to be well controlled, with defined berry extracts, using suitable and clinically relevant end points and considering the importance of the gut microbiota.

Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo

The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.