Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface.

DiC14-amidine is a cationic lipid that was originally designed as a lipid nanocarrier for nucleic acid transport, and turned out to be a Toll-like receptor 4 (TLR4) agonist as well. We found that while E. coli lipopolysaccharide (LPS) is a TLR4 agonist in all species, diC14-amidine nanoliposomes are full agonists for human, mouse and cat receptors but weak horse agonists. Taking advantage of this unusual species specificity, we used chimeric constructs based on the human and horse sequences and identified two regions in the human TLR4 that modulate the agonist activity of diC14-amidine. Interestingly, these regions lie outside the known LPS-binding domain. Competition experiments also support our hypothesis that diC14-amidine interacts primarily with TLR4 hydrophobic crevices located at the edges of the TLR4/TLR4* dimerization interface. We have characterized potential binding modes using molecular docking analysis and suggest that diC14-amidine nanoliposomes activate TLR4 by facilitating its dimerization in a process that is myeloid differentiation 2 (MD-2)-dependent and cluster of differentiation 14 (CD14)-independent. Our data suggest that TLR4 may be activated through binding at different anchoring points, expanding the repertoire of TLR4 ligands to non-MD-2-binding lipids.C.L. is a IEF Marie Curie Action Research Fellow (TLR4-CAT PIEF-GA-2012-326481) and would like to thank the Wiener-Anspach Foundation for financial support. K.L.I. was supported by a HBLB Veterinary Research Training scholarship. This work was supported by program grant support from the Wellcome Trust and the MRC to N.J.G and C.E.B.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00018-015-1915-

Use of organic inputs by arable farmers in six agro-ecological zones across Europe: Drivers and barriers

Soil organic matter (SOM) in agricultural soils builds up via – among others - the use of organic inputs such as straw, compost, farmyard manure or the cultivation of green manures or cover crops. SOM has benefits for long-term soil fertility and can provide ecosystem services. Farmer behaviour is however known to be motivated by a larger number of factors. Using the theory of planned behaviour, we aimed to disentangle these factors. We addressed the following research question: What are currently the main drivers and barriers for arable farmers in Europe to use organic inputs? Our study focuses on six agro-ecological zones in four European countries (Austria, Flanders [Belgium], Italy and the Netherlands) and four practices (straw incorporation, green manure or cover crops, compost and farmyard manure). In a first step, relevant factors were identified for each practice with farmers using 5 to ten semi-structured interviews per agro-ecological zone. In a second step, the relevance of these factors was quantified and they were classified as either drivers or barriers in a large scale farm survey with 1263 farmers. In the semi-structured interviews, 110 factors that influenced farmer decisions to use an organic input were identified. In the larger farm survey, 60% of the factors included were evaluated as drivers, while 40% were evaluated as barriers for the use of organic inputs. Major drivers to use organic inputs were related to the perceived effects on soil quality (such as improved soil structure or reduced erosion) and the positive influence from social referents (such as fellow farmers or agricultural advisors). Major barriers to use organic inputs were financial (increased costs or foregone income) and perceived effects on crop protection (such as increased weeds, pests and diseases, or increased pesticide use). Our study shows that motivating farmers to use organic inputs requires specific guidance on how to adapt cultivation practices to reduce weeds, pests and diseases for specific soil types, weather conditions, and crops. In addition, more research is needed on the long-term financial consequences of using organic inputs

Farmers review of Best Management Practices: drivers and barriers as seen by adopters and non-adopters

Assessing farmers’ intention to adopt best management practices across eight European countrie

Assessing farmers’ intention to adopt soil conservation practices across Europe

During the past decennia, soil conservation practices (SCPs) have been developed in order to maintain or restore soil health which is essential to the resilience of the farm. However, the adoption rate in practice is rather low. Amongst other reasons, these practices might lack onfarm compatibility, or farmers may lack confidence in the proposed measures. To increase the adoption rate of SCPs, capturing farmers’ opinions, given their specific farming context, can aid future strategies to get the SCPs implemented. Therefore, the aim of this study is to identify and compare different barriers and drivers towards the adoption of SCPs across 25 major farm type agri-environmental zone combinations in 8 European countries. To unravel farmer’s motivation and ability to implement a certain SCP, we applied a sequential mixed method approach based on the theory of planned behavior, a socio-psychological framework to predict human behavior. Qualitative semi-structured interviews with farmers reveal a first indication of possible barriers and drivers. These serve as the basis for a broad quantitative survey in each of the 25 major farm type zones, all characterized by their own soil, climate, regulatory and socio-economic context. Due to this context, the selected SCPs in the questionnaire differ among the major farm type zones, although with cover crops and reduced and/or non-inversion tillage, two wide-spread practices, were included across nearly all farm type zones. An EU-wide comparison between different regions allows us to better relate differences in barriers, motivators and farmers’ intention to differences in bio-physical, economic, institutional, social and regulatory conditions. To obtain a correct interpretation and clarification of the most striking results, we organize regional focus groups with experts and farmers. The results will offer valuable insights to advice EU policy, extension and scientific research. They will be able to take into account the specific context o

Examining ecological validity in social interaction: problems of visual fidelity, gaze, and social potential

Social interaction is an essential part of the human experience, and much work has been done to study it. However, several common approaches to examining social interactions in psychological research may inadvertently either unnaturally constrain the observed behaviour by causing it to deviate from naturalistic performance, or introduce unwanted sources of variance. In particular, these sources are the differences between naturalistic and experimental behaviour that occur from changes in visual fidelity (quality of the observed stimuli), gaze (whether it is controlled for in the stimuli), and social potential (potential for the stimuli to provide actual interaction). We expand on these possible sources of extraneous variance and why they may be important. We review the ways in which experimenters have developed novel designs to remove these sources of extraneous variance. New experimental designs using a ‘two-person’ approach are argued to be one of the most effective ways to develop more ecologically valid measures of social interaction, and we suggest that future work on social interaction should use these designs wherever possible

Purification of Nanoparticles by Size and Shape

Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions