Effectiveness of method improvements to reduce variability of brood termination rate in honey bee brood studies under semi-field conditions

Quantitative assessments of adverse effects of plant protection products on honey bee brood (Apis mellifera L.) may be carried out according to the methods given by the OECD Guidance Document No. 75 (2007). In recent years a number of studies displayed a strong variability in brood termination rates, a key endpoint. Due to these variances no definite conclusions regarding potential brood effects were possible, and the studies needed to be repeated. Due to this, attempts to improve the methodology were initiated by the Working Group ‘Honey bee brood' of the German AG Bienenschutz. In 2011, honey bee brood studies adapted to these identified possible improvements resulted in better results compared to historical data. Based on the analysed results, the working group recommends to improve the method by using bigger colonies with more brood, using 4 instead of 3 replicates for better interpretation of data, starting the study early in the season, avoiding major modifications of the colonies shortly before application and using larger tunnels with effective crop areas preferably > 80 m². To carry out quicker brood cell assessments to reduce stress for the colonies, it is recommended to use digital brood assessment, which allows marking a higher number of cells (e.g. 200 to 400 cells)

Compilation of results of the ICPPR non-Apis working group with a special focus on the bumblebee acute oral and contact toxicity ring test 2014 ICPPR Non-Apis Working Group

Although honeybee risk assessment for chemicals has been rigorously revised recently, methods and techniques available for non-apis pollinators are scarce. An ICPPR working group “non-apis” was established in 2013 to address these knowledge gaps. Acute contact tests were designed and performed with solitary bees Osmia sp. but still require further optimization. Ring tests on acute oral and contact toxicity for the bumblebee Bombus sp. were developed and performed in 2014. Thirteen European laboratories participated in the trials and in most cases control mortality was < 10% after 96h, indicating that the developed methodologies were feasible in a variety of laboratories. The oral exposure and the group contact exposure tests were each found to generate more variable LD50 estimates, whereas the endpoints obtained in the single contact tests were more consistent among laboratories. The difference in the two different contact test designs indicates the presence of a ‘housing’ effect, which makes the group housing less favorable. In addition, the use of Tween80 as a wetting agent was found to be unsuccessful

Targeting microRNAs for immunomodulation

microRNAs (miRNA) are small regulatory RNAs exerting pleiotropic functions in virtually any immune cell-type. Dozens of miRNAs with a known function in the immune system constitute interesting drug targets for immunomodulation. Chemical modifications of nucleic acid-based miRNA mimics and inhibitors largely solved instability issues but delivery to immune cells remains a major challenge. However, recent success targeting the acidic tumor microenvironment is very promising for inflammatory diseases. Moreover, small molecules are being explored as an interesting alternative. Although RNA is often considered 'undruggable' by small molecules recent progress modulating miRNA function through small molecules is encouraging. Computational approaches even allow predictions about specific small molecule/RNA interactions. Finally, recent clinical success demonstrates that drugs targeting RNAs work in humans

microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis

microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17-92 expression resulted in exacerbated experimental autoimmune encephalitis and failure to establish clinical remission. Using peptide-MHC tetramers, we demonstrate that the miR-17-92 cluster was specifically required for the accumulation of activated Ag-specific Treg and for differentiation into IL-10-producing effector Treg

microRNA-17–92 Regulates IL-10 Production by Regulatory T Cells and Control of Experimental Autoimmune Encephalomyelitis

microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17–92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17–92–deficient Tregs, expression of the miR-17–92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17–92 expression resulted in exacerbated experimental autoimmune encephalitis and failure to establish clinical remission. Using peptide-MHC tetramers, we demonstrate that the miR-17–92 cluster was specifically required for the accumulation of activated Ag-specific Treg and for differentiation into IL-10–producing effector Treg

DISCERNIBLE CELL SURFACE PROTEIN VARIANTS FOR USE IN CELL THERAPY

The present invention relates to the use of cells having discernible surface protein with engineered or naturally occurring mutation(s) but functional surface protein for use in therapy. The present invention also relates to the use of cells having discernible CD123 surface protein variants but functional surface protein for use in therapy, in particular adoptive cell therapy