Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Seed conformal blocks in 4D CFT

We compute in closed analytical form the minimal set of \u201cseed\u201d conformal blocks associated to the exchange of generic mixed symmetry spinor/tensor operators in an arbitrary representation (\u2113, \u2113) of the Lorentz group in four dimensional conformal field theories. These blocks arise from 4-point functions involving two scalars, one (0, |\u2113 12 \u2113|) and one (|\u2113 12 \u2113|, 0) spinors or tensors. We directly solve the set of Casimir equations, that can elegantly be written in a compact form for any (\u2113, \u2113), by using an educated ansatz and reducing the problem to an algebraic linear system. Various details on the form of the ansatz have been deduced by using the so called shadow formalism. The complexity of the conformal blocks depends on the value of p = |\u2113 12 \u2113| and grows with p, in analogy to what happens to scalar conformal blocks in d even space-time dimensions as d increases. These results open the way to bootstrap 4-point functions involving arbitrary spinor/tensor operators in four dimensional conformal field theories

Deconstructing Conformal Blocks in 4D CFT

We show how conformal partial waves (or conformal blocks) of spinor/tensor correlators can be related to each other by means of differential operators in four dimensional conformal field theories. We explicitly construct such differential operators for all possible conformal partial waves associated to four-point functions of arbitrary traceless symmetric operators. Our method allows any conformal partial wave to be extracted from a few \u201cseed\u201d correlators, simplifying dramatically the computation needed to bootstrap tensor correlators. \ua9 2015, The Author(s)

Consumption of Bt Maize Pollen Expressing Cry1Ab or Cry3Bb1 Does Not Harm Adult Green Lacewings, Chrysoperla carnea (Neuroptera: Chrysopidae)

Adults of the common green lacewing, Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae), are prevalent pollen-consumers in maize fields. They are therefore exposed to insecticidal proteins expressed in the pollen of insect-resistant, genetically engineered maize varieties expressing Cry proteins derived from Bacillus thuringiensis (Bt). Laboratory experiments were conducted to evaluate the impact of Cry3Bb1 or Cry1Ab-expressing transgenic maize (MON 88017, Event Bt176) pollen on fitness parameters of adult C. carnea. Adults were fed pollen from Bt maize varieties or their corresponding near isolines together with sucrose solution for 28 days. Survival, pre-oviposition period, fecundity, fertility and dry weight were not different between Bt or non-Bt maize pollen treatments. In order to ensure that adults of C. carnea are not sensitive to the tested toxins independent from the plant background and to add certainty to the hazard assessment, adult C. carnea were fed with artificial diet containing purified Cry3Bb1 or Cry1Ab at about a 10 times higher concentration than in maize pollen. Artificial diet containing Galanthus nivalis agglutinin (GNA) was included as a positive control. No differences were found in any life-table parameter between Cry protein containing diet treatments and control diet. However, the pre-oviposition period, daily and total fecundity and dry weight of C. carnea were significantly negatively affected by GNA-feeding. In both feeding assays, the stability and bioactivity of Cry proteins in the food sources as well as the uptake by C. carnea was confirmed. These results show that adults of C. carnea are not affected by Bt maize pollen and are not sensitive to Cry1Ab and Cry3Bb1 at concentrations exceeding the levels in pollen. Consequently, Bt maize pollen consumption will pose a negligible risk to adult C. carnea

Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design

Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221–228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant

Recommendations for the design of laboratory studies on non-target arthropods for risk assessment of genetically engineered plants

This paper provides recommendations on experimental design for early-tier laboratory studies used in risk assessments to evaluate potential adverse impacts of arthropod-resistant genetically engineered (GE) plants on non-target arthropods (NTAs). While we rely heavily on the currently used proteins from Bacillus thuringiensis (Bt) in this discussion, the concepts apply to other arthropod-active proteins. A risk may exist if the newly acquired trait of the GE plant has adverse effects on NTAs when they are exposed to the arthropod-active protein. Typically, the risk assessment follows a tiered approach that starts with laboratory studies under worst-case exposure conditions; such studies have a high ability to detect adverse effects on non-target species. Clear guidance on how such data are produced in laboratory studies assists the product developers and risk assessors. The studies should be reproducible and test clearly defined risk hypotheses. These properties contribute to the robustness of, and confidence in, environmental risk assessments for GE plants. Data from NTA studies, collected during the analysis phase of an environmental risk assessment, are critical to the outcome of the assessment and ultimately the decision taken by regulatory authorities on the release of a GE plant. Confidence in the results of early-tier laboratory studies is a precondition for the acceptance of data across regulatory jurisdictions and should encourage agencies to share useful information and thus avoid redundant testing

Toekomstige toepassing van genetisch gemodificeerde microbiële gewasbeschermingsmiddelen in de EU : Voldoen huidige EU wetgeving en risicobeoordeling?

alleen digitaal verschenenGenetisch gemodificeerde micro-organismen zijn in de toekomst mogelijk een alternatief voor chemische gewasbeschermingsmiddelen. Met behulp van genetische modificatie worden eigenschappen van micro-organismen toegevoegd of verbeterd, waardoor ze breder toepasbaar zijn dan 'gewone' microbiële middelen. Zo kan een bacterie Bacillus thuringiensis na een aanpassing een extra gifstof produceren van een verwante stam. Dan kan hij niet alleen schadelijke rupsen bestrijden maar ook een schadelijke vlieg. Ook kan het organisme zodanig aangepast worden dat het zijn werkzaamheid onder ongunstigere klimatologische omstandigheden behoudt. Tot nu toe worden maar een paar middelen buiten Europa gebruikt. Nederland wil erop voorbereid zijn als bedrijven een toelating voor dergelijke middelen tot de Europese markt aanvragen. Uit onderzoek van het RIVM blijkt dat de huidige Europese wettelijke instrumenten toereikend zijn om de veiligheid van dergelijke producten te garanderen. Europese wetgeving dekt de milieuveiligheid, de veiligheid voor omwonenden van landbouwgebieden en voor werknemers volledig af. Ook de belangrijkste aspecten voor voedsel- en veevoederveiligheid worden door Europese wetgeving afgedekt. Een uitzondering hierop is de hypothetische casus dat de samenstelling van een voedsel- of veevoederproduct wordt veranderd door een genetisch gemodificeerd microbieel gewasbeschermingsmiddel. Dit kan het geval zijn wanneer een genetisch gemodificeerd micro-organisme als gevolg van de modificatie invloed heeft op stofwisselingsprocessen in een plant waardoor allergene of giftige stoffen worden gevormd. Deze stoffen zouden dan in de voedsel- en veevoederproducten kunnen zitten, geconsumeerd kunnen worden en daardoor schadelijk zijn voor mens en dier. Hier zijn echter nog geen concrete voorbeelden van bekend. Voorgesteld wordt om, mochten er aanwijzingen zijn dat een plant gifstoffen of allergenen kan produceren als gevolg van de interactie met het genetisch gemodificeerd micro-organisme, dit van geval tot geval in de risicobeoordeling mee te wegen.In the future, genetically modified micro-organisms may offer an alternative to chemical plant protection products. Micro-organisms can be genetically altered to add or enhance certain properties, giving them a wider range of application than regular microbial products. The Bacillus thuringiensis bacterium, for instance, can be modified to produce an additional toxin that originates from a related strain. This allows the bacterium to be used as a pesticide against not only harmful caterpillars, but also a harmful species of fly. Organisms may also be modified to retain their effectiveness under unfavourable weather conditions. So far, only a few genetically modified micro-organisms are commercially available outside Europe as plant protection products. The Dutch government wants to be prepared to deal with companies that seek to obtain EU marketing authorization for such products. Research conducted by the Dutch National Institute for Public Health and the Environment (RIVM) shows that existing EU legislative instruments are sufficient to ensure the safety of such products. The applicable EU legislation provides all the necessary assurances for environmental protection, occupational health and safety, the safety of local residents in agricultural areas, and the main aspects of food and feed safety. However, there is one (currently hypothetical) situation that is not covered by existing legislation: a genetically modified microbial plant protection product may cause changes in the composition of a food or feed product. This can happen when allergenic or toxic substances are formed due to the effects of a genetically modified micro-organism on plant metabolic processes as a result of the genetic modification. These substances could then end up in food or feed products containing this plant, and could subsequently be harmful after consumption by humans or animals. No examples are currently available. If there are indications that a plant can produce allergenic or toxic substances due to the interaction with the genetically modified micro-organism, it is proposed to take this into account in the risk assessment on a case-by-case basis.Ministerie van I&MMinisterie van EZMinisterie van VW