Commensal-derived OMVs elicit a mild proinflammatory response in intestinal epithelial cells

Under normal physiological conditions, the intestinal immunity remains largely hyporesponsive to the commensal microbiota, yet also retains the inherent ability to rapidly respond to pathogenic antigens. However, immunomodulatory activities of extracellular products from commensal bacteria have been little studied, with previous investigations generally utilising the live bacterium to study microbiota-epithelial interactions. In this study, we demonstrate that extracellular products of a commensal bacterium, Escherichia coli C25, elicit a moderate release of proinflammatory IL-8 and stimulate transcriptional up-regulation of Toll-like receptors (TLRs) in intestinal epithelial cell lines, HT29-19A and Caco-2. Additionally, we show that removal of outer membrane vesicles (OMVs) diminishes the proinflammatory effect of secreted products from E. coli C25. Furthermore, we show that isolated OMVs have a dose-dependent proinflammatory effect on IECs. Interestingly, a relatively high concentration (10x culture concentration) of OMVs had no significant regulatory effects on TLR mRNA expression in both cell lines. Finally, we also demonstrate a that pre-incubation with E. coli C25-derived OMVs subsequently inhibited the internalisation of the bacterium itself in both cell lines. Taken together, our results suggest that commensal-derived extracellular products, in particular OMVs, could significantly contribute to intestinal homeostasis. We also demonstrate a unique interaction between commensal-derived OMVs and host cells

Kinetic and structure–activity studies of the triazolium ion-catalysed benzoin condensation

Steady-state kinetic and structure–activity studies of a series of six triazolium-ion pre-catalysts 2a–2f were investigated for the benzoin condensation. These data provide quantitative insight into the role of triazolium N-aryl substitution under synthetically relevant catalytic conditions in a polar solvent environment. Kinetic behaviour was significantly different to that previously reported for a related thiazolium-ion pre-catalyst 1, with the observed levelling of initial rate constants to νmax at high aldehyde concentrations for all triazolium catalysts. Values for νmax for 2a–2f increase with electron withdrawing N-aryl substituents, in agreement with reported optimal synthetic outcomes under catalytic conditions, and vary by 75-fold across the series. The levelling of rate constants supports a change in rate-limiting step and evidence supports the assignment of the Breslow-intermediate forming step to the plateau region. Correlation of νmax reaction data yielded a positive Hammett ρ-value (ρ = +1.66) supporting the build up of electron density adjacent to the triazolium N-Ar in the rate-limiting step favoured by electron withdrawing N-aryl substituents. At lower concentrations of aldehyde, both Breslow-intermediate and benzoin formation are partially rate-limiting

NE Baidrag block, Mongolia, records anticlockwise metamorphic paths at c. 890−790 Ma indicating peri-Rodinian back-arc compression followed with c. 560-520 Ma burial

The Barrovian type metamorphism affecting the peri-Siberian tract of the Central Asian Orogenic Belt is mostly dated indirectly on zircon from (syn-tectonic) magmatic rocks as Late Proterozoic - Early Cambrian. However, in-situ monazite geochronology in micaschists and migmatite gneisses at the northern part of the Precambrian Baidrag block, central Mongolia, revealed that the Baikalian Late Proterozoic - Early Cambrian cycle overprints an earlier Tonian phase of metamorphism. The apparent Barrovian-type zoning ranging from garnet, staurolite, kyanite to kyanite/sillimanite migmatitic gneisses is thus false and points to hidden metamorphic discontinuities and mixed metamorphic histories from different times. Therefore, to decipher and interpret the record of different tectono-metamorphic events it is necessary to unreveal complete P-T-t paths from individual samples. Two localities with Tonian-age monazite show anticlockwise P-T paths: 1) Grt−Sil−Ky gneiss records burial to the sillimanite stability (~720°C, 6.0 kbar) followed by burial to the kyanite stability (~750°C, 9 kbar) and, 2) The Grt−St schist records burial to the staurolite stability field (~620°C, 6 kbar), further followed by almost isothermal burial (~590°C, 8.5 kbar). Based on monazite textural positon, internal zoning, and REE patterns, the time of prograde burial under a thermal gradient of 27-32°C/km is estimated at c. 890−853 Ma and further burial under a geothermal gradient of 18-22°C/km is dated at c. 835−815 Ma. On the other hand three localities with Late Proterozoic to Cambrian monazite ages show clockwise metamorphic paths at variable P-T gradients: 3) P-T conditions of the Grt schist reaches ~5 kbar and 500 °C and 4) the Grt−St−Ky schist reaches conditions of 9 kbar and 670 °C, indicating burial under a geothermal gradient of 20-26 °C/km. 5) Grt-Sil gneiss shows peak of 6-7 kbar and 700-750 °C, indicating melting conditions at 30-32 °C/km gradient. Monazite included in porphyroblasts and in the matrix indicate that these P-T conditions reached under variable geothermal gradient were semi-contemporaneous and occurred between 570 and 520 Ma. By correlation with published zircon ages of 600-530 Ma from granitoid magmatic rocks we suggest that the areas with higher geothermal gradient may be explained by closer vicinity of magmatic intrusions. These P−T and geochronology data from a continuous Barrovian metamorphic section suggest that anticlockwise P−T evolution from c. 930 to 750 Ma can be interpreted as a result of thickening of peri-Rodinian supra-subduction extensional and hot edifice. This metamorphic event was followed by a clockwise P−T evolution from c. 570 to 520 Ma possibly related to the collision of the Baidrag continental active margin with peri-Siberian continental mass further north

Understanding the importance of illness narratives in people with multiple sclerosis who participated in an exercise rehabilitation trial; a qualitative study

Objectives: To understand how illness narrative master plots may be expressed and associated together and to determine how stories are used to demonstrate the psychological benefits of exercise rehabilitation. Design: A subtle realist paradigmatic position was assumed which utilised a hermeneutic henomenological methodology. Setting: Two community centres within the UK. Participants: A purposive sample of 10 individuals with MS (7 female, 3 male) were included. Individuals were eligible if: (a) they had undertaken at least 8 weeks of an exercise rehabilitation trial, (b) if they were older than 19 years, and (c) could understand English. Intervention: Participants had undertaken at least 8 weeks from a 12-week cycle ergometer randomised control rehabilitation trial. The trial varied the exercise intensity experienced by participants. Main Outcome Measure: A single semi-structured interview with six sub-sections that included elements related to emotional regulation. A categorical content narrative analysis was undertaken. The analysis was supplemented by integrating findings from past research studies. Results: Two themes were identified: (1) Identification of a model of narrative expression. This model establishes how narrative master plots may be associated with each other and broadly represent coping or succumbing responses to the experiences of MS. The transition in expression of master plots is detailed and associated with psychological adaptation to illness (2) The role of physical activity in contributing to psychological benefits of exercise rehabilitation identified through narrative expression. This research highlighted a dominant process of narrative master plot expression from detective, to didactic and then heroic master plot. Conclusion: The research has developed a new model for understanding the cycles related to dominant master narrative plots. Further work is needed to establish these results and future studies are needed to establish if there is feasible way to use illness narrative within clinical environments

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection

Vision for navigation: what can we learn from ants?

The visual systems of all animals are used to provide information that can guide behaviour. In some cases insects demonstrate particularly impressive visually-guided behaviour and then we might reasonably ask how the low-resolution vision and limited neural resources of insects are tuned to particular behavioural strategies. Such questions are of interest to both biologists and to engineers seeking to emulate insectlevel performance with lightweight hardware. One behaviour that insects share with many animals is the use of learnt visual information for navigation. Desert ants, in particular, are expert visual navigators. Across their foraging life, ants can learn long idiosyncratic foraging routes. What's more, these routes are learnt quickly and the visual cues that define them can be implemented for guidance independently of other social or personal information. Here we review the style of visual navigation in solitary foraging ants and consider the physiological mechanisms that underpin it. Our perspective is to consider that robust navigation comes from the optimal interaction between behavioural strategy, visual mechanisms and neural hardware.We consider each of these in turn, highlighting the value of ant-like mechanisms in biomimetic endeavours

A Simple Iterative Model Accurately Captures Complex Trapline Formation by Bumblebees Across Spatial Scales and Flower Arrangements

PMCID: PMC3591286This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

How do field of view and resolution affect the information content of panoramic scenes for visual navigation? A computational investigation

The visual systems of animals have to provide information to guide behaviour and the informational requirements of an animal’s behavioural repertoire are often reflected in its sensory system. For insects, this is often evident in the optical array of the compound eye. One behaviour that insects share with many animals is the use of learnt visual information for navigation. As ants are expert visual navigators it may be that their vision is optimised for navigation. Here we take a computational approach in asking how the details of the optical array influence the informational content of scenes used in simple view matching strategies for orientation. We find that robust orientation is best achieved with low-resolution visual information and a large field of view, similar to the optical properties seen for many ant species. A lower resolution allows for a trade-off between specificity and generalisation for stored views. Additionally, our simulations show that orientation performance increases if different portions of the visual field are considered as discrete visual sensors, each giving an independent directional estimate. This suggests that ants might benefit by processing information from their two eyes independently

A mechanistically and operationally simple route to metal-N-heterocyclic carbene (NHC) Complexes

We gratefully acknowledge VLAIO (SBO project CO2PERATE), King Saud University (Distinguished Scientist Fellowship Program) and King Abdullah University of Science and Technology for support. The Special Research Fund (BOF) of Ghent University is also acknowledged (Doctoral Scholarship to N.V.T.). COST action (CA15106-CHAOS) is thanked for mobility support to N.V.T. Umicore AG is acknowledged for generous gifts of materials.We have been puzzled by the involvement of weak organic and inorganic bases in the synthesis of metal‐N‐heterocyclic carbene (NHC) complexes. Such bases are insufficiently strong to permit the presumed required deprotonation of the azolium salt (the carbene precursor) prior to metal binding. Experimental and computational studies provide support for a base‐assisted concerted process that does not require free NHC formation. The synthetic protocol was found applicable to a number of Transition Metal‐ and Main Group‐centered NHC compounds and could become the synthetic route of choice to form M‐NHC bonds.PostprintPeer reviewe