Bioaccessibility of heavy metals and risk assessment in urban gardens of Madrid

Human health problems and solutions. Urban gardening has spread worldwide in recent years as it enhances food security and selfsupply and promotes community integration. However urban soils are significantly enriched in trace elements relative to background levels. Exposure to the soil in urban gardens may therefore result in adverse health effects depending on the degree of contact during gardening, infant recreational activities and ingestion of vegetables grown in them. In order to evaluate this potential risk, 36 composite samples were collected from the top 20 cm of the soil of 6 urban gardens in Madrid. The aqua regia (pseudototal) and glycine-extractable (bioaccessible) concentrations of Co, Cr, Cu, Ni, Pb and Zn were determined by atomic absorption spectrophotometry. Additionally, pH, texture, Fe, Ca, and Mn concentrations, and organic matter and calcium carbonate contents were determined in all urban gardens and their influence on trace element bioaccessibility was analyzed.

Tools for mixed-criticality partitioned systems: partitioning algorithm and extensibility support

The development of mixed-criticality virtualized multicore systems poses new challenges that are being subject of active research work. There is an additional complexity: it is now required to identify a set of partitions, and allocate applications to partitions. In this job, a number of issues have to be considered, such as the criticality level of the application, security and dependability requirements, operating system used by the application, time requirements granularity, specific hardware needs, etc. MultiPARTES [6] toolset relies on Model Driven Engineering (MDE) [12], which is a suitable approach in this setting. In this paper, it is described the support provided for automatic system partitioning generation and toolset extensibility.

A maternal diet high in n − 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring

We hypothesized that feeding pregnant rats with a high-fat diet would increase both circulating 17β-estradiol (E2) levels in the dams and the risk of developing carcinogen-induced mammary tumors among their female offspring. Pregnant rats were fed isocaloric diets containing 12% or 16% (low fat) or 43% or 46% (high fat) of calories from corn oil, which primarily contains the n − 6 polyunsaturated fatty acid (PUFA) linoleic acid, throughout pregnancy. The plasma concentrations of E2 were significantly higher in pregnant females fed a high n − 6 PUFA diet. The female offspring of these rats were fed with a laboratory chow from birth onward, and when exposed to 7,12-dimethylbenz(a)anthracene had a significantly higher mammary tumor incidence (60% vs. 30%) and shorter latency for tumor appearance (11.4 ± 0.5 weeks vs. 14.2 ± 0.6 weeks) than the offspring of the low-fat mothers. The high-fat offspring also had puberty onset at a younger age, and their mammary glands contained significantly higher numbers of the epithelial structures that are the targets for malignant transformation. Comparable changes in puberty onset, mammary gland morphology, and tumor incidence were observed in the offspring of rats treated daily with 20 ng of E2 during pregnancy. These data, if extrapolated to humans, may explain the link among diet, early puberty onset, mammary parenchymal patterns, and breast cancer risk, and indicate that an in utero exposure to a diet high in n − 6 PUFA and/or estrogenic stimuli may be critical for affecting breast cancer risk.

In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen

T cells recognizing poorly displayed self determinants escape tolerance mechanisms and persist in the adult repertoire. The process by which these T cells are primed is not clear, but once activated, they can cause autoimmunity. Here, we show that dendritic cells treated with interleukin 6 (IL-6) process and present determinants from a model native antigen in a qualitatively altered hierarchy, activating T cells in vitro and in vivo against determinants that were previously cryptic because of poor display. IL-6 does not induce conventional maturation of dendritic cells but alters the pH of peripheral, early endosomal compartments and renders the cells more susceptible to killing by chloroquine. Acidification of endosomes by ouabain mimics the effect of IL-6 and allows processing of the same cryptic determinant. These results suggest that cytokines such as IL-6 could initiate and help to propagate an autoimmune disease process by differentiating dendritic cells into a state distinct from that induced by normal maturation.

Evolution of paired domains: Isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6

Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide.

Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model

Atherosclerosis is a complex disease resulting from the interaction of multiple genes. We have used the Ldlr knockout mouse model in an interspecific genetic cross to map atherosclerosis susceptibility loci. A total of 174 (MOLF/Ei × B6.129S7-Ldlrtm1Her) × C57BL/6J-Ldlrtm1Her backcross mice, homozygous for the Ldlr null allele, were fed a Western-type diet for 3 months and then killed for quantification of aortic lesions. A genome scan was carried out by using DNA pools and microsatellite markers spaced at ≈18-centimorgan intervals. Quantitative trait locus analysis of individual backcross mice confirmed linkages to chromosomes 4 (Athsq1, logarithm of odds = 6.2) and 6 (Athsq2, logarithm of odds = 6.7). Athsq1 affected lesions in females only whereas Athsq2 affected both sexes. Among females, the loci accounted for ≈50% of the total variance of lesion area. The susceptible allele at Athsq1 was derived from the MOLF/Ei genome whereas the susceptible allele at Athsq2 was derived from C57BL/6J. Inheritance of susceptible alleles at both loci conferred a 2-fold difference in lesion area, suggesting an additive effect of Athsq1 and Athsq2. No associations were observed between the quantitative trait loci and levels of plasma total cholesterol, high density lipoprotein cholesterol, non-high density lipoprotein cholesterol, insulin, or body weight. We provide strong evidence for complex inheritance of atherosclerosis in mice with elevated plasma low density lipoprotein cholesterol and show a major influence of nonlipoprotein-related factors on disease susceptibility. Athsq1 and Athsq2 represent candidate susceptibility loci for human atherosclerosis, most likely residing on chromosomes 1p36–32 and 12p13–12, respectively.

Crystallographic evidence for the action of potassium, thallium, and lithium ions on fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze alpha-D-fructose 1,6-bisphosphate. Although not required for catalysis, monovalent cations modify the enzyme activity; K+ and Tl+ ions are activators, whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown. We report here crystallographic structures of pig kidney Fru-1,6-Pase complexed with K+, Tl+, or both Tl+ and Li+. In the T form Fru-1,6-Pase complexed with the substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) and Tl+ or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by Glu-97, Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P2; site 2 is defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally, site 3 is defined by Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P2. The Tl+ or K+ ions at sites 1 and 2 are very close to the positions previously identified for the divalent metal ions. Site 3 is specific to K+ or Tl+. In the divalent metal ion complexes, site 3 is occupied by the guanidinium group of Arg-276. These observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the active site and polarize the 1-phosphate group, thus facilitating nucleophilic attack on the phosphorus center. In the T form complexed with both Tl+ and Li+ ions, Li+ replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs as it binds to this site, thus retarding turnover or phosphate release. The present study provides a structural basis for a similar mechanism of inhibition for inositol monophosphatase, one of the potential targets of lithium ions in the treatment of manic depression.

EEAS 2.0. A legal commentary on Council Decision 2010/427/EU establishing the organisation and functioning of the European External Action Service. EIPA Working Paper, 2013

From the Preface. Pursuant to Article 13(3) of Council Decision 2010/427/EU of 26 July 2010 establishing the organisation and functioning of the European External Action Service, the High Representative is held to provide a review of the organisation and functioning of the EEAS by mid-­‐2013. This review will cover, inter alia, the implementation of Article 6(6), (8) and (11), so as to ensure an adequate geographical and gender balance and a meaningful presence of nationals from all member states in the EEAS. If necessary, the review will be accompanied by appropriate proposals for the revision of the 2010 Council Decision (e.g., suggestions for additional specific measures to correct possible imbalances of staffing). In that case, the Council will, in accordance with Article 27(3) TEU, revise the Decision in light of the review by the beginning of 2014. This short and user-­‐friendly legal commentary on the 2010 Council Decision is the first of its kind and is intended to inform those involved in the review process and to serve as a reference document for practitioners and analysts dealing with the EEAS. This commentary is not an elaborate doctrinal piece, but rather a textual and contextual analysis of each article, that takes account of i) other relevant legal provisions (primary, secondary, international), ii) the process leading to the adoption of the 2010 Council Decision (i.e. travauxpréparatoires), iii) the preamble of the Council Decision, and iv) insofar as it is possible at this stage, early implementation. Wherever relevant, cross-­‐references to other provisions of the EEAS Council Decision have been made so as to tie in the different commentaries and ensure overall consistency.

The Impact of Visa Liberalisation in Eastern Partnership Countries, Russia and Turkey on Trans-Border Mobility. CEPS Liberty and Security in Europe No. 63, March 2014

Schengen Visa liberalisation in the Eastern Partnership countries, Russia and Turkey has proven to have a huge transformative potential across the justice, liberty and security policies of the countries where it has been deployed. Far-reaching technical reforms in the fields of document security, irregular migration and border management, public order security and fundamental rights have to be implemented so that visa-free travel can be allowed. Evidence provided by visa applications data reveals that visa liberalisation is a logical step, provided that the technical reforms are adopted and implemented. This study analyses the current state of play of the implementation of the EU visa policy instruments and assesses the positive impact of visa-free travel on trans-border mobility according to current visa application statistics.

Ukraine and Security Disorder in Europe – A Defining Moment for the OSCE? CEPS Commentary, 24 April 2014

The Organization for Security and Cooperation in Europe (OSCE) is the first and currently the only international body to have a monitoring mission deployed in Ukraine. This is as it should be, argues Erwan Fouéré. Today, with EU members making up half the membership of the OSCE, the EU needs to show greater responsibility and far-sightedness in its dealings with the OSCE. In the run-up to the 40th anniversary of the Helsinki Final Act, and faced with its most serious security crisis since the fall of the Berlin Wall, the EU should take the lead once again in fostering collective responsibility on the part of all Participating States to ensure a meaningful and effective role for the OSCE.

Ukraine and Security Disorder in Europe - A Defining Moment for the OSCE? CEPS Commentary, 24 April 2014

The Organization for Security and Cooperation in Europe (OSCE) is the first and currently the only international body to have a monitoring mission deployed in Ukraine. This is as it should be, argues Erwan Fouéré. Today, with EU members making up half the membership of the OSCE, the EU needs to show greater responsibility and far-sightedness in its dealings with the OSCE. In the run-up to the 40th anniversary of the Helsinki Final Act, and faced with its most serious security crisis since the fall of the Berlin Wall, the EU should take the lead once again in fostering collective responsibility on the part of all Participating States to ensure a meaningful and effective role for the OSCE.

Financing European Defence: Time to Call the European Investment Bank? IES Policy Brief Issue 2014/05/July 2014

Summary. Financing research and development programmes have never been more expensive in Europe. Defence budgets are on the wane, international competition is fierce and high-end technologies are increasingly expensive. Europe’s defence-industrial base is under significant strain, and options are needed to fund elements of a sector that is still crucial to Europe’s security and industry. This Policy Brief argues that the European Investment Bank could play a much greater role in Europe’s defence sector. As a public-private institution the Bank could serve as a life-line to defence R&D, dual-use projects and support for SMEs, especially where regional clusters are involved.

The European Union as a System of Differentiated Integration: Interdependence, Politicization and Differentiation. IHS Political Science Series No. 137, 10 July 2014

This paper conceptualizes the European Union (EU) as a system of differentiated integration characterized by both variation in levels of centralization (vertical differentiation) and variation in territorial extension (horizontal differentiation) across policy areas. Differentiation has been a concomitant of deepening and widening and has increased and consolidated as the EU’s powers, policy scope, and membership have grown. Turning to explanation, the paper attributes the pattern of differentiated integration in the EU to the interaction of interdependence and politicization. Differentiation among the member states (internal differentiation) results from supranational integration under conditions of high interdependence and politicization. By contrast, external differentiation (the selective policy integration of non-member states) occurs in highly interdependent but weakly politicized policy areas. These constellations are illustrated in case studies of differentiation in the internal market, monetary union, and defence.

spotlight europe #2015/02—July 2015: A Gulf CSC Could Bring Peace and Greater Security to the Middle East

Wars continue to ravage in Syria, Iraq and Yemen. Refugees are wandering around aimlessly in the Middle East with many fleeing to Europe. Saudi Arabia and Iran are adding fuel to the flames. They are vying for supremacy while remaining highly suspicious of each other. A Conference for Security and Cooperation could help to ease existing tensions. Many years ago the CSCE was a resounding success. It could thus serve as a blueprint with the nuclear agreement with Iran as a starting point of such a venture.

The Ukraine crisis and the demise of the European Security order. EPC Policy Brief, 1 December 2015

The annexation of Crimea by Russia and the subsequent war in the Donbas have delivered a severe blow to the European security order, and have increased tensions between the West and Russia to a level unprecedented since the end of the Cold War. In this context, it would be difficult to start negotiating a new commitment to the principles of the European security order. In this Policy Brief, Paul Ivan analyses the Ukraine crisis and its effect on European security and calls for the EU and NATO to stand firm on their own principles, but also to engage carefully with Russia to develop mechanisms to contain risks and avoid escalation and military confrontation, whether in Syria, the Baltic, the Mediterranean or the Black seas. The recent shooting down of a Russian jet by Turkish forces makes clear the need to prevent such incidents with potential rapid escalatory dynamics.