Pass-through of unfair trading practices in EU food supply chains

This report presents the results of the research project “Pass-Through of Unfair Trading Practices in EU Food Supply Chains: Methodology and Empirical Application”. The purpose of the project is to design and test a monitoring system of unfair trading practices (UTP) along the agri-food supply chain. The investigation has special focus on assessment of the “pass-through effect”, defined as the consequences for the entire supply chain of UTPs adopted in a specific transaction. The report includes: (i) a review of the economic literature for a better understanding of the economic principles of UTPs; (ii) a review of available data sources and past experiences in UTP monitoring; (iii) the illustration of two alternative approaches for UTP monitoring: B-SEA (broad-scope empirical analysis) and IDEA (in-depth analysis); (iv) a test application of the two approaches to the EU fresh fruit sector; (v) a comparative analysis of the IDEA and B-SEA results and (vi) a discussion of the implications of our research.JRC.D.4-Economics of Agricultur

Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor Prognosis

The identification of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding of cancer. Hypoxia is an important factor in cancer biology, and associated splice variants may present new markers to help with planning treatment. A method was developed to analyse alternative splicing in exon array data, using probeset multiplicity to identify genes with changes in expression across their loci, and a combination of the splicing index and a new metric based on the variation of reliability weighted fold changes to detect changes in the splicing patterns. The approach was validated on a cancer/normal sample dataset in which alternative splicing events had been confirmed using RT-PCR. We then analysed ten head and neck squamous cell carcinomas using exon arrays and identified differentially expressed splice variants in five samples with high versus five with low levels of hypoxia-associated genes. The analysis identified a splice variant of LAMA3 (Laminin α 3), LAMA3-A, known to be involved in tumour cell invasion and progression. The full-length transcript of the gene (LAMA3-B) did not appear to be hypoxia-associated. The results were confirmed using qualitative RT-PCR. In a series of 59 prospectively collected head and neck tumours, expression of LAMA3-A had prognostic significance whereas LAMA3-B did not. This work illustrates the potential for alternatively spliced transcripts to act as biomarkers of disease prognosis with improved specificity for particular tissues or conditions over assays which do not discriminate between splice variants

Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype

CA IX is a hypoxia-induced, cancer-associated carbonic anhydrase isoform with functional involvement in pH control and cell adhesion. Here we describe an alternative splicing variant of the CA9 mRNA, which does not contain exons 8–9 and is expressed in tumour cells independently of hypoxia. It is also detectable in normal tissues in the absence of the full-length transcript and can therefore produce false-positive data in prognostic studies based on the detection of the hypoxia- and cancer-related CA9 expression. The splicing variant encodes a truncated CA IX protein lacking the C-terminal part of the catalytic domain. It shows diminished catalytic activity and is intracellular or secreted. When overexpressed, it reduces the capacity of the full-length CA IX protein to acidify extracellular pH of hypoxic cells and to bind carbonic anhydrase inhibitor. HeLa cells transfected with the splicing variant cDNA generate spheroids that do not form compact cores, suggesting that they fail to adapt to hypoxic stress. Our data indicate that the splicing variant can functionally interfere with the full-length CA IX. This might be relevant particularly under conditions of mild hypoxia, when the cells do not suffer from severe acidosis and do not need excessive pH control

Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2

Endosialin is a transmembrane glycoprotein selectively expressed in blood vessels and stromal fibroblasts of various human tumours. It has been functionally implicated in angiogenesis, but the factors that control its expression have remained unclear. As insufficient delivery of oxygen is a driving force of angiogenesis in growing tumours, we investigated whether hypoxia regulates endosialin expression. Here, we demonstrate that endosialin gene transcription is induced by hypoxia predominantly through a mechanism involving hypoxia-inducible factor-2 (HIF-2) cooperating with the Ets-1 transcription factor. We show that HIF-2 activates the endosialin promoter both directly, through binding to a hypoxia-response element adjacent to an Ets-binding site in the distal part of the upstream regulatory region, and indirectly, through Ets-1 and its two cognate elements in the proximal promoter. Our data also suggest that the SP1 transcription factor mediates responsiveness of the endosialin promoter to high cell density. These findings elucidate important aspects of endosialin gene regulation and provide a rational frame for future investigations towards better understanding of its biological significance

La representación de los personajes femeninos en la ‘ola exuberante’ del cine de la Nueva Ola Checoslovaca

Tutor: Manuel Garín Boronat Treball de fi de Màster en Estudis de Cinema y Audiovisual ContemporanisEn el marco de la Nueva Ola Checoslovaca (1962-1970) surgió un cine estética y narrativamente exuberante que contó con la aparición de obras vanguardistas únicas como Sedmikrásky (Las margaritas, 1966) de Věra Chytilová o Vtać̌kovia, siroty a blaźni (Pájaros, huérfanos y locos, 1969) de Juraj Jakubisko, entre otras. En las atmósferas oníricas, absurdas y repletas de detalles de estas películas surgen personajes femeninos singulares, subversivos y con características emancipadoras. Esta investigación pretende aproximarse a esta representación femenina a partir de tres ópticas: la naturaleza, el hambre y el humor. Se trata de tres vías que abrirán camino a la exploración, el debate y la construcción de mapas visuales alrededor de la representación de los personajes femeninos de lo que hemos denominado “la ola exuberante”

COMPETITIVENESS OF THE UNITED KINGDOM AGRI-FOOD TRADE IN RELATION TO THE EU MARKET

The United Kingdom as a member of the EU can enjoy full access to the Single European Market. In terms of agri-food trade, EU is UK's most important partner. However, in June 2016, the UK opted to leave EU. This decision will significantly influence the whole economy of the UK including agri-food trade. The objective of this paper is to examine development and comparative advantages of The UK's agri-food trade with respect to the EU-27 markets. The analysis is based on Balassa index and its stability over the period. The agri-food trade data were acquired from Eurostat Comext database and cover the period 2000-2016. The analysis showed that over the period, the UK was able to retain comparative advantages only in three categories – HS 03 Fish, HS 21 Miscellaneous edible preparations, HS 22 Beverages, spirits and vinegar. In the rest of agri-food commodities the declining trend can be observed and in 2016 the UK had comparative disadvantages in 21 agri-food commodities. Based on the results of regression focused on the stability of distribution of Balassa indices over time, we can conclude that the degree of specialization in the agri-food trade between the United Kingdom and the rest of the EU has been decreasing as the number of commodity groups with a comparative advantage has been declining. With respect to Brexit, the agrarian trade of the UK deserves special attention, because the potential increases in trade costs are expected to affect the UK proportionally more than the EU-27

Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy.

One of the recently emerging anticancer strategies is the use of natural dietary compounds, such as sulforaphane, a cancer-chemopreventive isothiocyanate found in broccoli. Based on the growing evidence, sulforaphane acts through molecular mechanisms that interfere with multiple oncogenic pathways in diverse tumor cell types. Herein, we investigated the anticancer effects of bioavailable concentrations of sulforaphane in ovarian carcinoma cell line A2780 and its two derivatives, adriamycin-resistant A2780/ADR and cisplatin-resistant A2780/CP cell lines. Since tumor microenvironment is characterized by reduced oxygenation that induces aggressive tumor phenotype (such as increased invasiveness and resistance to chemotherapy), we evaluated the effects of sulforaphane in ovarian cancer cells exposed to hypoxia (2% O2). Using the cell-based reporter assay, we identified several oncogenic pathways modulated by sulforaphane in hypoxia by activating anticancer responses (p53, ARE, IRF-1, Pax-6 and XRE) and suppressing responses supporting tumor progression (AP-1 and HIF-1). We further showed that sulforaphane decreases the level of HIF-1alpha protein without affecting its transcription and stability. It can also diminish transcription and protein level of the HIF-1 target, CA IX, which protects tumor cells from hypoxia-induced pH imbalance and facilitates their migration/invasion. Accordingly, sulforaphane treatment leads to diminished pH regulation and reduced migration of ovarian carcinoma cells. These effects occur in all three ovarian cell lines suggesting that sulforaphane can overcome the chemoresistance of cancer cells. This offers a path potentially exploitable in sensitizing resistant cancer cells to therapy, and opens a window for the combined treatments of sulforaphane either with conventional chemotherapy, natural compounds, or with other small molecules

Impairment of Hypoxia-Induced CA IX by Beta-Blocker Propranolol—Impact on Progression and Metastatic Potential of Colorectal Cancer Cells

The coexistence of cancer and other concomitant diseases is very frequent and has substantial implications for treatment decisions and outcomes. Beta-blockers, agents that block the beta-adrenergic receptors, have been related also to cancers. In the model of multicellular spheroids formed by colorectal cancer cells we described a crosstalk between beta-blockade by propranolol and tumour microenvironment. Non-selective beta-blocker propranolol decreased ability of tumour cells to adapt to hypoxia by reducing levels of HIF1α and carbonic anhydrase IX in 3D spheroids. We indicated a double action of propranolol in the tumour microenvironment by inhibiting the stability of HIF1α, thus mediating decrease of CA IX expression and, at the same time, by its possible effect on CA IX activity by decreasing the activity of protein kinase A (PKA). Moreover, the inhibition of β-adrenoreceptors by propranolol enhanced apoptosis, decreased number of mitochondria and lowered the amount of proteins involved in oxidative phosphorylation (V-ATP5A, IV-COX2, III-UQCRC2, II-SDHB, I-NDUFB8). Propranolol reduced metastatic potential, viability and proliferation of colorectal cancer cells cultivated in multicellular spheroids. To choose the right treatment strategy, it is extremely important to know how the treatment of concomitant diseases affects the superior microenvironment that is directly related to the efficiency of anti-cancer therap