Publisher Correction: Science diplomacy for plant health.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Conducting fit-for-purpose food safety risk assessments.

The interplay between science, risk assessment and risk management has always been complex, and even more so in a world increasingly characterised by rapid technical innovation, new modes of communication, suspicion about authorities and experts, and demands for people to have a say in decisions that are made on their behalf. In this challenging era where scientific advice on food safety has never been in greater demand, risk managers should effectively navigate the interplay between facts and values and be able to rely on robust and fit-for-purpose risk assessments to aid them. The fact that societal resistance is often encountered when scientific advice on food safety operates at a distance from social values and fails to actively engage with citizens, has led to increasing emphasis on the need to advance forms of risk assessment that are more contextual, and socially sound and accountable. EFSA's third Scientific Conference explored how risk assessments could be constructed to most usefully meet society's needs and thus connect science with society, while remaining scientifically robust. Contributors to the conference highlighted the need to: (1) frame risk assessments by clear policy goals and decision-making criteria; (2) begin risk assessments with an explicit problem formulation to identify relevant information; (3) make use of reliable risk assessment studies; (4) be explicit about value judgements; (5) address and communicate scientific uncertainty; (6) follow trustworthy processes; (7) publish the evidence and data, and report the way in which they are used in a transparent manner; (8) ensure effective communication throughout the risk analysis process; (9) involve society, as appropriate; and (10) weigh risks and benefits on request. Implementation of these recommendations would contribute to increased credibility and trustworthiness of food safety risk assessments.

Proposed criteria for identifying GE crop plants that pose a low or negligible risk to the environment under conditions of low-level presence in seed.

The low-level presence (LLP) of genetically engineered (GE) seeds that have been approved in the country of origin but not the country of import presents challenges for regulators in both seed importing and exporting countries, as well as for the international seed trade and the farmers who rely on it. In addition to legal, financial and regulatory challenges, such LLP situations in seed may also require an environmental risk assessment by the country of import. Such assessments have typically been informed by the national framework established to support decisions related to wide scale cultivation, and frequently do not take into account the low environmental exposure and prior regulatory history of the GE plant. In addition, such assessment processes may not be well suited to the decision-making timeframe that is necessary when dealing with an LLP situation in imported seed. In order to facilitate regulatory decision making, this paper proposes a set of scientific criteria for identifying GE crop plants that are expected to pose a low or negligible risk to the environment under LLP conditions in seed. Regulatory decision makers in some importing countries may decide to use these criteria to assist in risk analysis associated with LLP situations they are experiencing or could experience in the future, and might choose to proactively apply the criteria to identify existing GE plants with regulatory approvals in other countries that would be expected to pose low risk under conditions of LLP in seed.

A comparative analysis of insertional effects in genetically engineered plants: considerations for pre-market assessments.

During genetic engineering, DNA is inserted into a plant's genome, and such insertions are often accompanied by the insertion of additional DNA, deletions and/or rearrangements. These genetic changes are collectively known as insertional effects, and they have the potential to give rise to unintended traits in plants. In addition, there are many other genetic changes that occur in plants both spontaneously and as a result of conventional breeding practices. Genetic changes similar to insertional effects occur in plants, namely as a result of the movement of transposable elements, the repair of double-strand breaks by non-homologous end-joining, and the intracellular transfer of organelle DNA. Based on this similarity, insertional effects should present a similar level of risk as these other genetic changes in plants, and it is within the context of these genetic changes that insertional effects must be considered. Increased familiarity with genetic engineering techniques and advances in molecular analysis techniques have provided us with a greater understanding of the nature and impact of genetic changes in plants, and this can be used to refine pre-market assessments of genetically engineered plants and food and feeds derived from genetically engineered plants.

Ignition of eyelash extensions during routine minor eyelid surgery.

Preoperative patient questionnaires enquiring about the presence of prosthetics are routine. Eyelash extensions are not part of standard preoperative questionnaires. This case illustrates how this impacts patient safety during minor eyelid surgery.

Genetically engineered trees for plantation forests: key considerations for environmental risk assessment.

Forests are vital to the world's ecological, social, cultural and economic well-being yet sustainable provision of goods and services from forests is increasingly challenged by pressures such as growing demand for wood and other forest products, land conversion and degradation, and climate change. Intensively managed, highly productive forestry incorporating the most advanced methods for tree breeding, including the application of genetic engineering (GE), has tremendous potential for producing more wood on less land. However, the deployment of GE trees in plantation forests is a controversial topic and concerns have been particularly expressed about potential harms to the environment. This paper, prepared by an international group of experts in silviculture, forest tree breeding, forest biotechnology and environmental risk assessment (ERA) that met in April 2012, examines how the ERA paradigm used for GE crop plants may be applied to GE trees for use in plantation forests. It emphasizes the importance of differentiating between ERA for confined field trials of GE trees, and ERA for unconfined or commercial-scale releases. In the case of the latter, particular attention is paid to characteristics of forest trees that distinguish them from shorter-lived plant species, the temporal and spatial scale of forests, and the biodiversity of the plantation forest as a receiving environment.

Laminin chain assembly is regulated by specific coiled-coil interactions.

Laminins are large heterotrimeric, multidomain proteins that play a central role in organising and establishing all basement membranes. Despite a total of 45 potential heterotrimeric chain combinations formed through the coiled-coil domain of the 11 identified laminin chains (alpha1-5, beta1-3, gamma1-3), to date only 15 different laminin isoforms have been reported. This observation raises the question whether laminin assembly is regulated by differential gene expression or specific chain recognition. To address this issue, we here perform a complete analysis of laminin chain assembly and specificity. Using biochemical and biophysical techniques, all possible heterotrimeric combinations from recombinant C-terminal coiled-coil fragments of all chains were analysed. Apart from laminin 323 (alpha3, beta2, gamma3), for which no biochemical evidence of its existence in vivo is available, these experiments confirmed all other known laminin isoforms and identified two novel potential chain combinations, laminins 312 (alpha3, beta1, gamma2) and 422 (alpha4, beta2, gamma4). Our findings contribute to the understanding of basement membrane structure, function and diversity.

Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope.

Angiogenesis is essential for tissue repair and regeneration during wound healing but also plays important roles in many pathological processes including tumor growth and metastasis. The receptor protein tyrosine kinase Tie2 and its ligands, the angiopoietins, have important functions in the regulation of angiogenesis. Here, we report a detailed structural and functional characterization of the extracellular region of Tie2. Sequence analysis of the extracellular domain revealed an additional immunoglobulin-like domain resulting in a tandem repeat of immunoglobulin-like domains at the N terminus of the protein. The same domain organization was also found for the Tie1 receptor that shares a high degree of homology with Tie2. Based on structural similarities to other receptor tyrosine kinases and cell adhesion molecules, we demonstrate that the N-terminal two immunoglobulin-like domains of Tie2 harbor the angiopoietin-binding site. Using transmission electron microscopy we furthermore show that the extracellular domain of Tie receptors consists of a globular head domain and a short rod-like stalk that probably forms a spacer between the cell surface and the angiopoietin-binding site. Mutational analysis demonstrated that the head domain consists of the three immunoglobulin-like domains and the three epidermal growth factor-like modules and that the stalk is formed by the three fibronectin type III repeats. These findings might be of particular interest for drug development because Tie receptors are potential targets for treatment of angiogenesis-associated diseases.

Evidence that monoclonal antibodies directed against the integrin beta subunit plexin/semaphorin/integrin domain stimulate function by inducing receptor extension.

The overall structure of integrins is that of a ligand-binding head connected to two long legs. The legs can exhibit a pronounced bend at the "knees," and it has been proposed that the legs undergo a dramatic straightening when integrins transit from a low affinity to a high affinity state. The knee region contains domains from both alpha and beta subunits, including the N-terminal plexin/semaphorin/integrin (PSI) domain of the beta subunit. The role played by the knee domains in the regulation of integrin-ligand binding is uncertain. Here we show that: (i) monoclonal antibodies (mAbs) N29 and 8E3 have epitopes in the beta(1) subunit PSI domain and stimulate ligand binding to alpha(5)beta(1); (ii) N29 and 8E3 cause long range conformational changes that alter the ligand binding activity of the head region; (iii) the stimulatory action of these mAbs is dependent on the calf-1 domain, which forms part of the alpha subunit knee; and (iv) the epitopes of 8E3 and N29 map close to the extreme N terminus of the PSI and are likely to lie on the side of this domain that faces the alpha subunit. Taken together, our data suggest that the binding of these mAbs results in a levering apart of the PSI and calf-1 domains, and thereby causes the alpha and beta subunit knees to separate. Several major inferences can be drawn from our findings. First, the PSI domain appears to form part of an interface with the alpha subunit that normally restrains the integrin in a bent state. Second, the PSI domain is important for the transduction of conformational changes from the knee to head. Third, unbending is likely to provide a general mechanism for control of integrin-ligand recognition.