Toll-like receptor 2 promiscuity is responsible for the immunostimulatory activity of nucleic acid nanocarriers.

Lipopolyamines (LPAs) are cationic lipids; they interact spontaneously with nucleic acids to form lipoplexes used for gene delivery. The main hurdle to using lipoplexes in gene therapy lies in their immunostimulatory properties, so far attributed to the nucleic acid cargo, while cationic lipids were considered as inert to the immune system. Here we demonstrate for the first time that di-C18 LPAs trigger pro-inflammatory responses through Toll-like receptor 2 (TLR2) activation, and this whether they are bound to nucleic acids or not. Molecular docking experiments suggest potential TLR2 binding modes reminiscent of bacterial lipopeptide sensing. The di-C18 LPAs share the ability of burying their lipid chains in the hydrophobic cavity of TLR2 and, in some cases, TLR1, at the vicinity of the dimerization interface; the cationic headgroups form multiple hydrogen bonds, thus crosslinking TLRs into functional complexes. Unravelling the molecular basis of TLR1 and TLR6-driven heterodimerization upon LPA binding underlines the highly collaborative and promiscuous ligand binding mechanism. The prevalence of non-specific main chain-mediated interactions demonstrates that potentially any saturated LPA currently used or proposed as transfection agent is likely to activate TLR2 during transfection. Hence our study emphasizes the urgent need to test the inflammatory properties of transfection agents and proposes the use of docking analysis as a preliminary screening tool for the synthesis of new non-immunostimulatory nanocarriers.MP would like to thank the FRIA-FNRS (F3/5/5-MCF/XH/FC-17514) for its financial support. NG and MG would like to thank the Wellcome Trust (WT100321/z/12/Z) for financial support. CL is grateful to the foundation Wiener Anspach and the Marie Curie Actions (TLR4-CAT PIEF-GA-2012-326481) for financial support

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

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

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

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

Reduced engagement with social stimuli in 6-month-old infants with later Autism Spectrum Disorder: a longitudinal prospective study of infants at high familial risk

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of the population, and close to 20% of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months, and investigated the relationship to ASD outcome at 24 months. Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning