The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates

Objective: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. Methods: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Results: Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins.Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate.By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation.ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Conclusions: Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active cytokine induced caspase 3/7 apoptotic pathway and is responsive to ER stress initiation factors. The cells' ability to proliferate can be further increased by already known compounds as well as by novel peptides and proteins. Based on its robust performance during the functionality assessment assays, the EndoC-βH1 cell line was successfully used as a screening platform for identification of novel anti-diabetic drug candidates. Keywords: EndoC-βH1, Pseudoislets, Glucose stimulated insulin secretion, Somatostatin signaling, Proliferatio

The role of war in deep transitions: exploring mechanisms, imprints and rules in sociotechnical systems

This paper explores in what ways the two world wars influenced the development of sociotechnical systems underpinning the culmination of the first deep transition. The role of war is an underexplored aspect in both the Techno-Economic Paradigms (TEP) approach and the Multi-level perspective (MLP) which form the two key conceptual building blocks of the Deep Transitions (DT) framework. Thus, we develop a conceptual approach tailored to this particular topic which integrates accounts of total war and mechanisms of war from historical studies and imprinting from organisational studies with the DT framework’s attention towards rules and meta-rules. We explore in what ways the three sociotechnical systems of energy, food, and transport were affected by the emergence of new demand pressures and logistical challenges during conditions of total war; how war impacted the directionality of sociotechnical systems; the extent to which new national and international policy capacities emerged during wartime in the energy, food, and transport systems; and the extent to which these systems were influenced by cooperation and shared sacrifice under wartime conditions. We then explore what lasting changes were influenced by the two wars in the energy, food, and transport systems across the transatlantic zone. This paper seeks to open up a hitherto neglected area in analysis on sociotechnical transitions and we discuss the importance of further research that is attentive towards entanglements of warfare and the military particularly in the field of sustainability transitions

Evaluation of the shucking of certain species of scallops contaminated with lipophilic toxins with a view to the production of edible parts meeting the safety requirements foreseen in the Union legislation

EFSA was asked by the European Commission to provide information on levels of lipophilic shellfish toxins in whole scallops that would ensure levels in edible parts below the regulatory limits after shucking, i.e. removal of non-edible parts. This should include the okadaic acid (OA), the azaspiracid (AZA) and the yessotoxin (YTX) groups, and five species of scallops. In addition, EFSA was asked to recommend the number of scallops in an analytical sample. To address these questions, EFSA received suitable data on the three toxin groups in two scallop species, Aequipecten opercularis and Pecten maximus, i.e. data on individual and pooled samples of edible and non-edible parts from contamination incidents. The majority of the concentration levels were below limit of quantification (LOQ)/limit of detection (LOD), especially in adductor muscle but also in gonads. Shucking in most cases resulted in a strong decrease in the toxin levels. For Pecten maximus, statistical analysis showed that levels in whole scallops should not exceed 256 \u3bcg OA eq/kg or 217 \u3bcg AZA1 eq/kg to ensure that levels in gonads are below the regulatory limits of 160 \u3bcg OA or AZA1 eq/kg with 99% certainty. Such an analysis was not possible for yessotoxins or any toxin in Aequipecten opercularis and an assessment could only be based on upper bound levels. To ensure a 95% correct prediction on whether the level in scallops in an area or lot is correctly predicted to be compliant/non-compliant, it was shown that 10 scallops per sample would be sufficient to predict with 95% certainty if levels of OA-group toxins in the area/lot were 25% below or above the regulatory limit. However, to predict with a 95% certainty for levels between 140 and 180 \u3bcg OA eq/kg, a pooled sample of more than 30 scallops would have to be tested