Russia and the Global Security Strategy of the European Union

The present article reviews the relations between the EU and Russia in the past decade and shows the deterioration of the bilateral relations. The Putin´s Russia has become a very active geostrategic player, with a worrying behaviour, breaking balances in the international scene established since the end of the Cold War. Russia is a priority in the Foreign and Security Policy of the European Global Security Strategy, but has become also a clear competitor. This last aspect is not sufficiently underlined in the Strategy and thus the strategic framework is not clear. In parallel, it is not clear in the Strategy which are the tools the EU has to defend its neighbourhood when their independence, sovereignty or territorial defence may be put in question. This question goes beyond the support to the resilience of those neighbours.

Novel Genetic Determinants of Diabetic Kidney Disease

Diabetic kidney disease (DKD) is a devastating diabetes complication, with known heritability not fully revealed by previous genetics studies. We performed the largest genome-wide association study of type 1 DKD to date, in a 13-cohort consortium of 15,590 individuals of European ancestry genotyped on the Illumina HumanCoreExome Beadchip, which allows exploration of coding variation in addition to genomic markers.

As prior work has shown that different characterizations of the DKD phenotype highlight distinct genetic associations, we investigated a spectrum of DKD definitions based on proteinuria and renal function criteria. Controls were DKD-free after a minimum of 15 years diabetes duration; cases had diabetes for at least 10 years prior to DKD diagnosis. We also performed a quantitative trait analysis of estimated glomerular filtration rate in all participants.

Our top finding was a missense mutation in COL4A3, rs55703767 (Asp326Tyr); the minor allele is common in Europeans (20%) and East Asians (13%) but not Africans (2%). This SNP had a genome-wide significant association with traditionally defined DKD (macroalbuminuria or end-stage renal disease [ESRD], (OR= 0.79, P=1.9×10-9), and a suggestive association with macroalbuminuria (OR= 0.79, P=1.6×10-6) and ESRD (OR= 0.79, P=4.5×10-5) individually. Though its PolyPhen score is 0.3 (benign), this SNP has been implicated as a splice site disruptor.

The COL4A3 gene encodes the alpha 3 subunit of Type IV collagen, the major structural component of basement membranes. Pathogenic mutations in COL4A3 have been identified in thin basement membrane nephropathy, familial focal segmental glomerulosclerosis, and Alport syndrome. A proxy (r2=0.6) for rs55703767 had no significant associations in the CKDGen consortium, suggesting its pathogenicity occurs solely in the setting of hyperglycemia.

By significantly increasing sample size we have discovered a novel locus underlying DKD risk, paving the way for better understanding of pathology, prevention, and treatment.

Towards Night

Sixty artists explore the nocturnal. Curated by Tom Hammick. The evening hour too gives us the irresponsibility which darkness and lamplight bestow. We are no longer quite ourselves. – Virginia Woolf, Street Haunting: A London Adventure, 1930 Towards Night is an exhibition exploring the nocturnal through paintings, prints and drawings by over sixty artists. Drawing on the nineteenth century European Romantic tradition, the show surveys contemporary and historical connections to wonderment and dystopia at dusk, twilight, night and dawn. Towards Night juxtaposes key paintings and prints by Constable, Friedrich, Munch, Nolde, Palmer and Turner, some of the best known visionaries of the Romantic tradition with contemporary artists who work with the transformative aspects of nightfall to convey emotional responses of awe, anxiety and solitude, love and loss, revelry, insomnia, and journey’s end. The exhibition opens with direct and positive responses to the natural world; Marc Chagall’s exotic dreamlike evening in The Poet Reclining (1915) sits close to eighteenth century Indian miniatures depicting brightly painted figures offset against darkening monsoon clouds, and William Crozier’s Balcony at Night, Antibes (2007), of a plant, blue and iridescent against the cool night sky. As the exhibition progresses, the dystopias become darker and more disturbing, and the connections between artists and works intensify: Emma Stibbon’s Rome Aqueduct (2011) takes on a heightened sense of pathos alongside Caspar David Friedrich’s Winter Landscape (1811); Peter Doig’s cinematic Echo Lake (1998) conjures up an increased sense of contemporary angst; and Prunella Clough’s False Flower (1993), a magical tree defying brutalism by growing out of concrete, becomes more miraculous near Night Shift (2015) Nick Carrick’s tomblike high rise. Tom Hammick’s Violetta Alone (2015) and Michael Craig Martin’s Ash Tray (2015), reinforce hedonistic aspects of night-time revelry alongside Four AM, Betsy Dadd’s young woman drinking in the early hours of the morning and L.S. Lowry’s drunken people in a pub in The Crowd (1922). In the final room, a cluster of works explores dreams and insomnia, from Louise Bourgeois’ Spirals (2010) to Munch’s lovers embracing in The Kiss (1902). Tom Hammick, curator of the show said “This exhibition has grown way beyond its original conception, to become a magnificent survey of painting and printmaking from over two hundred years based around the central tenet of night. The exhibition is a kind of painterly response to the way figurative artists use their artistic heroes as starting points for their own work, both compositionally and emotionally.” Artists featured in Towards Night: Christiane Baumgarter, Michael Craig-Martin, Julian Opie, Will Gill, Merlin James, Howard Hodgkin, WillIam Scott, Patrick Caulfield, George Shaw, Stephen Chambers, Basil Beattie, Betsy Dadd, Christopher Le Brun, L.S Lowry, Andrew Cranston, David Willetts, James Fisher, Emma Stibbon, Vija Celmins, William Blake, William Crozier, Tom Hammick, Georgia Keeling, Helen Turner, Humphrey Ocean, Julian Bell, Craigie Aitchison, Mark Wright, Ken Kiff, Matthew Burrows, Andrzej Jackowski, Sarah Raphael, Nick Bodimeade, Nick Carrick, Mary Newcomb, Hurvin Anderson, Peter Doig, Phoebe Unwin, Danny Markey, Sara Lee, Simon Burton, Susie Hamilton, Marc Chagall, Alfred Wallis, Emil Nolde, J.M.W. Turner, Prunella Clough, Samuel Palmer, Louise Bourgeois, Caspar David Friedrich, Alex Katz, Ewan Gibbs, Susie Hamilton, Andrzej Jackowski, Amanda Vesey, Edward Stott, Gertrude Hermes, Rose Wylie, Sidney Nolan, John Constable, J.M.W. Turner, Emil Nolde, Hiroshige, Edvard Munch, Samuel Palmer, Eileen Cooper, Charles Neame-Spencer, Samantha Cary.

Neiland's Choice

Catalogue for an exhibition with works selected exclusively by Brendan Neiland. Neiland, who attended the Birmingham College of Art and the Royal College of Art, London during the 1960s, has selected works from a range of artists including: Val Archer, Sarah Armstrong-Jones, Sir Peter Blake, Simon Burton, Grace Erskine Crum, Brad Faine, James Fisher, Martin Fuller, Christian Furr, Annabel Gault, Jason Gibilaro, Hugh Gilbert, Michael Harrison, David Hepher, Patrick Hughes, Andrzej Jackowski, David Mach, Danny Markey, Terry New, William Packer, Tom Phillips (RA), Donald Smith, Justine Smith, Steve Thomas, John Wilkins

This battle was not over: Parade’s End as a transitional text in the development of ‘disenchanted’ First World War literature.

This chapter argues that the novels of Ford's Parade's End tetralogy occupy a significant place in the development of "disenchanted" fiction about the First World War. The values of Ernest Raymond's patriotic Tell England are contrasted with those of C. E Montague's Disenchantment, providing a brief synopsis of the early 1920s response to the conflict. Parade's End is seen as introducing several key themes in to the post-First World War discursive field, including national identity, psychology, memory, and time. The presentation of these aligned with the formal aspects of the novel, allows it to push the boundaries of the readerly horizon of expectations. Frayn argues that Ford's readership, though moderately-sized, was influential from a literary point of view, and thus facilitated the reception of later, more vitriolic, criticisms of war.

Sistema de guiado para movimiento autónomo de vehículos en entornos estructurados

El objetivo de la invención es un sistema de guiado de vehículos autónomos mediante cámaras y/o fotodetectores para seguir una trayectoria, que se determina por un conjunto de emisores láser dispuestos en un entorno estructurado, por ejemplo, en los distintos pasillos de un invernadero, y que determina la trayectoria a seguir. Para el establecimiento de la trayectoria a seguir, se dispone de diversos emisores láser colocados en los pasillos del invernadero, que estarán activos en función de los pasillos que deba recorrer el vehículo para describir la trayectoria prevista.

The metabolic and epigenetic effects of the isocitrate dehydrogenase-1 mutation in glioma

Cancer cells have been noted to have an altered metabolic phenotype for over ninety years. In the presence of oxygen, differentiated cells predominately utilise the tricarboxylic acid (TCA) cycle and oxidative phosphorylation to efficiently produce energy and the metabolites necessary for protein and lipid synthesis. However, in hypoxia, this process is altered and cells switch to a higher rate of glycolysis and lactate production to maintain their energy and metabolic needs. In cancer cells, glycolysis is maintained at a high rate, even in the presence of oxygen; a term described as “aerobic glycolysis”. Tumour cells are rapidly dividing and have a much greater need for anabolism compared to normal differentiated cells. Rapid glucose metabolism enables faster ATP production as well as a greater redistribution of carbons to nucleotide, protein, and fatty acid synthesis, thus maximising cell growth. Recently, other metabolic changes, driven by mutations in genes related to the TCA cycle, indicate an alternative role for metabolism in cancer, the “oncometabolite”. This is where a particular metabolite builds up within the cell and contributes to the tumorigenic process. One of these genes is isocitrate dehydrogenase (IDH) IDH is an enzyme that forms part of the tricarboxylic acid (TCA) cycle and converts isocitrate to α-ketoglutarate (α-KG). It exists in three isoforms; IDH1, IDH2 and IDH3 with the former present in the cytoplasm and the latter two in the mitochondria. Point mutations have been identified in the IDH1 and IDH2 genes in glioma which result in a gain of function by converting α-KG to 2-hydroxyglutarate (2HG), an oncometabolite. 2HG acts as a competitive inhibitor of the α-KG dependent dioxygenases, a superfamily of enzymes that are involved in numerous cellular processes such as DNA and histone demethylation. It was hypothesised that the IDH1 mutation would result in other metabolic changes in the cell other than 2HG production, and could potentially identify pathways which could be targeted for therapeutic treatment. In addition, 2HG can act as a potential competitive inhibitor of α-KG dependent dioxygenases, so it was hypothesised that there would be an effect on histone methylation. This may alter gene expression and provide a mechanism for tumourogenesis and potentially identify further therapeutic targets. Metabolic analysis of clinical tumour samples identified changes associated with the IDH1 mutation, which included a reduction in α-KG and an increase in GABA, in addition to the increase in 2HG. This was replicated in several cell models, where 13C labelled metabolomics was also used to identify a possible increase in metabolic flux from glutamate to GABA, as well as from α-KG to 2HG. This may provide a mechanism whereby the cell can bypass the IDH1 mutation as GABA can be metabolised to succinate in the mitochondria by GABA transaminase via the GABA shunt. JMJ histone demethylases are a subset of the α-KG dependent dioxygenases, and are involved in removing methyl groups from histone tails. Changes in histone methylation are associated with changes in gene expression depending on the site and extent of chemical modification. To identify whether the increase in 2HG and fall in α-KG was associated with inhibition of histone demethylases a histone methylation screen was used. The IDH1 mutation was associated with an increase in methylation of H3K4, which is associated with gene activation. ChiP and RNA sequencing identified an increase in H3K4me3 at the transcription start site of the GABRB3 subunit, resulting in an increase in gene expression. The GABRB3 subunit forms part of the GABA-A receptor, a chloride channel, which on activation can reduce cell proliferation. The IDH1 mutation was associated with an increase in GABA and GABRB3 subunit of the GABA-A receptor. This raises the possibility of GABA transaminase as a potential therapeutic target. Inhibition of this enzyme could reduce GABA metabolism, potentially reducing any beneficial effect of the GABA shunt in IDH1 mutant tumours, and increasing activation of the GABA-A receptor by increasing the concentration of GABA in the brain. This in turn may reduce cell proliferation, and could be achieved by using Vigabatrin, a GABA transaminase inhibitor licensed for use in epilepsy.

Characterizing neural tissues with mass spectrometry imaging via enhanced computational approaches

Neuropeptides affect the activity of the myriad of neuronal circuits in the brain. They are under tight spatial and chemical control and the dynamics of their release and catabolism directly modify neuronal network activity. Understanding neuropeptide functioning requires approaches to determine their chemical and spatial heterogeneity within neural tissue, but most imaging techniques do not provide the complete information desired. To provide chemical information, most imaging techniques used to study the nervous system require preselection and labeling of the peptides of interest; however, mass spectrometry imaging (MSI) detects analytes across a broad mass range without the need to target a specific analyte. When used with matrix-assisted laser desorption/ionization (MALDI), MSI detects analytes in the mass range of neuropeptides. MALDI MSI simultaneously provides spatial and chemical information resulting in images that plot the spatial distributions of neuropeptides over the surface of a thin slice of neural tissue. Here a variety of approaches for neuropeptide characterization are developed. Specifically, several computational approaches are combined with MALDI MSI to create improved approaches that provide spatial distributions and neuropeptide characterizations. After successfully validating these MALDI MSI protocols, the methods are applied to characterize both known and unidentified neuropeptides from neural tissues. The methods are further adapted from tissue analysis to be able to perform tandem MS (MS/MS) imaging on neuronal cultures to enable the study of network formation. In addition, MALDI MSI has been carried out over the timecourse of nervous system regeneration in planarian flatworms resulting in the discovery of two novel neuropeptides that may be involved in planarian regeneration. In addition, several bioinformatic tools are developed to predict final neuropeptide structures and associated masses that can be compared to experimental MSI data in order to make assignments of neuropeptide identities. The integration of computational approaches into the experimental design of MALDI MSI has allowed improved instrument automation and enhanced data acquisition and analysis. These tools also make the methods versatile and adaptable to new sample types.

Jana Mazurkiewicza mitocentryczna koncepcja osobowości

The article deals with not well known theory of personality of Polish Neojacsonist psychiatrist Jan Mazurkiewicz. It describes its scientific background, biography and basic ideas and assumptions. The accent is put here on its, based on Lévi- Bruhl’s ideas but mostly original mythocentricity in psychological perspective and description of human symbolic thinking and acting.