Comparison of human hepatoma HepaRG cells with human and rat hepatocytes in uptake transport assays in order to predict drug induced hepatotoxicity

Human hepatocytes are the gold standard for toxicological studies but they have several drawbacks, like scarce availability, high inter-individual variability, a short lifetime, which limits their applicability. The aim of our investigations was to determine, whether HepaRG cells could replace human hepatocytes in uptake experiments for toxicity studies. HepaRG is a hepatoma cell line with most hepatic functions, including a considerable expression of uptake transporters in contrast to other hepatic immortalized cell lines. We compared the effect of cholestatic drugs (bosentan, cyclosporinA, troglitazone,) and bromosulfophthalein on the uptake of taurocholate and estrone-3-sulfate in human and rat hepatocytes and HepaRG cells. The substrate uptake was significantly slower in HepaRG cells than in human hepatocytes, still, in the presence of drugs we observed a concentration dependent decrease in uptake. In all cell types, the culture time had a significant impact not only on the uptake process but on the inhibitory effect of drugs too. The most significant drug effect was measured at 4 h after seeding. Our report is among the first concerning interactions of the uptake transporters in the HepaRG, at the functional level. Results of the present study clearly show that concerning the inhibition of taurocholate uptake by cholestatic drugs, HepaRG cells are closer to human hepatocytes than rat hepatocytes. In conclusion, we demonstrated that HepaRG cells provide a suitable tool for hepatic uptake studies

Short Combo Strategy Using Barrier Options and its Application in Hedging

AbstractThis paper deals with a Short Combo option strategy and its application in hedging against an underlying price increase assuming the given underlying asset will be bought in the future. The key difference between the previous studies is that in this paper we are concentrated on single barrier options. Barrier options were formed to provide risk managers with cheaper means to hedge their exposures without paying for the price changes they believed unlikely to occur. The methodology is based on the profit functions in analytical form. We propose various hedging possibilities and show its practical application. In our analysis we used vanilla and barrier European options on SPDR Gold Shares. The results show that the Short Combo strategy formation using barrier options gives the end-users greater flexibility to express a precise view in the specific future price situations

Sustainable Energy Portfolios for Small Island States

The study presents a cost effective electricity generation portfolio for six island states for a 20-year period (2015-2035). The underlying concept investigates whether adding sizeable power capacities of renewable energy sources (RES) options could decrease the overall costs and contribute to a more sustainable, indigenous electricity generation at the same time. Often, island states rely on fossil fuels which apart from dependence on foreign resources also includes an additional, significant transport cost. This is an extra motive to study the extent in which island states represent primary locations for RES technologies. For the aims of the present study an optimization model has been developed and following numerous runs the obtained results show that installing PV and battery capacities can delay-reduce the huge investments in fossil options in early periods. Thus, investment on RES can have a positive, long-term effect on the overall energy mix. This prompt development can happen without adding new subsidies but there is a need to address the existing socio-economic barriers with intelligent design of financing and economic instruments and capacity building as discussed in the conclusions.JRC.F.7-Renewables and Energy Efficienc

Prevalence of Atopic Dermatitis Among Children Under 19 in an East-Hungarian Agricultural County

The prevalence of atopic dermatitis has significantly increased in developed countries during the past several decades. Surveys performed in Hungary also show a growing number of atopic dermatitis (AD) cases, although, a carefully designed case-controlled studies have not been performed. Therefore, we investigated the prevalence of AD in individuals under 19 years of age within the agricultural area of East-Hungary. Combined data obtained with Schultz-Larsen questionnaire on 1158 children were analyzed, and 25% of the index persons were examined by dermatologist. The mean prevalence of AD determined by questionnaires appeared to be 17.5% in the entire study population. Result of dermatological examination verified the validity and sensitivity of the questionnaire. A negative correlation was found between the severity of the disease and the length of breast feeding period. (Spearman's correlation coefficient = − 0.2247, p = 0.034). The prevalence of AD in an East-Hungarian agricultural area is nearly as high as that reported for populations residing in industrially developed countries, with a higher prevalence during childhood. Data suggest that premature abruption of breast feeding maybe one of the major factors among other environmental factors that is contributing to the development of AD

The Contribution of Amino Acid Region ASP695-TYR698 of Factor V to Procofactor Activation and Factor VA Function

There is strong evidence that a functionally important cluster of amino acids is located on the COOH-terminal portion of the heavy chain of factor Va, between amino acid residues 680 and 709. To ascertain the importance of this region for cofactor activity, we have synthesized five overlapping peptides representing this amino acid stretch (10 amino acids each, HC1-HC5) and tested them for inhibition of prothrombinase assembly and function. Two peptides, HC3 (spanning amino acid region 690-699) and HC4 (containing amino acid residues 695-704), were found to be potent inhibitors of prothrombinase activity with IC(50) values of approximately 12 and approximately 10 microm, respectively. The two peptides were unable to interfere with the binding of factor Va to active site fluorescently labeled Glu-Gly-Arg human factor Xa, and kinetic analyses showed that HC3 and HC4 are competitive inhibitors of prothrombinase with respect to prothrombin with K(i) values of approximately 6.3 and approximately 5.3 microm, respectively. These data suggest that the peptides inhibit prothrombinase because they interfere with the incorporation of prothrombin into prothrombinase. The shared amino acid motif between HC3 and HC4 is composed of Asp(695)-Tyr-Asp-Tyr-Gln(699) (DYDYQ). A pentapeptide with this sequence inhibited both prothrombinase function with an IC(50) of 1.6 microm (with a K(D) for prothrombin of 850 nm), and activation of factor V by thrombin. Peptides HC3, HC4, and DYDYQ were also found to interact with immobilized thrombin. A recombinant factor V molecule with the mutations Asp(695) --\u3e Lys, Tyr(696) --\u3e Phe, Asp(697) --\u3e Lys, and Tyr(698) --\u3e Phe (factor V(2K2F)) was partially resistant to activation by thrombin but could be readily activated by RVV-V activator (factor Va(RVV)(2K2F)) and factor Xa (factor Va(Xa)(2K2F)). Factor Va(RVV)(2K2F) and factor Va(Xa)(2K2F) had impaired cofactor activity within prothrombinase in a system using purified reagents. Our data demonstrate for the first time that amino acid sequence 695-698 of factor Va heavy chain is important for procofactor activation and is required for optimum prothrombinase function. These data provide functional evidence for an essential and productive contribution of factor Va to the activity of prothrombinase

Water-Energy-Food nexus interactions assessment: Renewable energy sources to support water access and quality in West Africa

The present Technical Report examines the potential synergies between energy, water and agricultural production in Africa. It aims to highlight strategies that address important challenges in an integrated manner. In this regard, the deployment of clean energy sources through the utilization of indigenous African renewable sources aims to provide the required energy to extract, process and convey water resources that will eventually support agricultural activities and food production.JRC.C.2-Energy Efficiency and Renewable

ABCG2 Is a Selectable Marker for Enhanced Multilineage Differentiation Potential in Periodontal Ligament Stem Cells.

Periodontal ligament stem cells (PDLSCs) provide an important source for tissue regeneration and may become especially useful in the formation of osteogenic seeds. PDLSCs can be cultured, expanded, and differentiated in vitro; thus, they may be applied in the long-term treatment of the defects in the dental regions. Here we studied numerous potential markers allowing the selection of human PDLSCs with a maximum differentiation potential. We followed the expression of the ATP-binding cassette subfamily G member 2 (ABCG2) membrane transporter protein and isolated ABCG2-expressing cells by using a monoclonal antibody, recognizing the transporter at the cell surface in intact cells. The expression of the ABCG2 protein, corresponding to the so-called side-population phenotype in various tissue-derived stem cells, was found to be a useful marker for the selection of PDLSCs with enhanced osteogenic, chondrogenic, and adipogenic differentiation. These findings may have important applications in achieving efficient dental tissue regeneration by using stem cells from extracted teeth

Mapping the least-cost option for rural electrification in Burkina Faso: Scaling-up renewable energies

This report describes the current status and limitations of the power sector in Burkina Faso and develops a new methodology that through spatial analysis processes aims to provide a possible pathway for universal electricity access through a sustainable energy mix. Two percent of the rural population in Burkina Faso has access to electricity and supply is lacking at many social structures such as schools and hospitals. Energy access achievements in Burkina Faso are still very modest. The rural electrification strategy for Burkina Faso is scattered in several electricity sector development policies: there is a need of defining a concrete action plan. Planning and coordination between grid extension and off-grid electrification programmes is essential to reach a long-term sustainable energy model and to avoid high unnecessary infrastructure investments. This report describes the development and the results obtained with a dynamic planning tool to support national government and development partners in defining an alternative electrification plan. Currently, the common national policy for electrification is dominated almost exclusively by grid extension with the government subsidising fossil fuel electricity production. However, the results of our analysis suggest that an electrification plan mainly based on further grid extension becomes inefficient and unsustainable in order to reach the national energy access targets. Our results also suggest that Burkina Faso’s rural electrification strategy should be driven by distributed minigrids powered by local renewable resources. We find that this approach would connect more people to power more quickly, and would reduce imported fossil fuel dependence/consumption that would otherwise be necessary for grid extension options.JRC.C.2-Energy Efficiency and Renewable

The Current Status of Germplum Database: a Tool for Characterization of Plum Genetic Resources in Romania

In Romania, Prunus genetic resources are kept in collections of varieties, populations and biotypes, mainly located in research and development institutes or fruit growing stations and, in the last years, by some private enterprises. Creating the experimental model for the Germplum database based on phenotypic descriptors and SSR molecular markers analysis is an important and topical objective for the efficient characterization of genetic resources and also for establishing a public-private partnership for the effective management of plum germplasm resources in Romania. The technical development of the Germplum database was completed and data will be added continuously after characterizing each new accession