Fundacion Ramon Areces Research Articles

Refined electron-spin transport model for single-element ferromagnetic systems: Application to nickel nanocontacts

This work was supported by the Generalitat Valenciana through Grant No. PROMETEO2017/139. C.S. gratefully acknowledges financial support from the Dean Fellowship of the Weizmann Institute of Science and Generalitat Valenciana (Grant No. CDEIGENT2018/028). O.T. appreciates the support of the Harold Perlman family, and acknowledges funding by a research grant from Dana and Yossie Hollander, the Israel Science Foundation (Grant No. 1089/15), the Minerva Foundation (Grant No. 120865), and The Ministry of Science and Technology of Israel (Grant No. 3-16244). J.J.P. acknowledges financial support from Spanish MINECO through Grants No. FIS2016-80434-P and No. PID2019-109539GB-C43, the Fundacion Ramon Areces, the Maria de Maeztu Program for Units of Excellence in R&D (Grant No. CEX2018-000805-M), the Comunidad Autonoma de Madrid through the Nanomag COST-CM Program (Grant No. S2018/NMT-4321), the European Union Seventh Framework Programme under Grant Agreement No. 604391 Graphene Flagship, the Centro de Computacion Cientifica of the Universidad Autonoma de Madrid and the computer resources at MareNostrum and the technical support provided by the Barcelona Supercomputing Center (Grant No. FI-2019-2-0007). The SLD and DFT calculations in this paper were performed on the high-performance computing facilities of the University of Alicante and the University of South Africa.

Molecular Mechanisms of Hypoxia‐Induced Extracellular Vesicle Release

BackgroundExtracellular vesicles (EVs) are released by many cells and provide a mechanism for intercellular communication in autocrine and paracrine fashion. EVs of various sizes, namely microvesicles (ranging from 100–1000 nm) or exosomes (with sizes between 30–150 nm) are released by most eukaryotic cells. EVs are known to contain bioactive molecules including proteins lipids and nucleic acids including miRNAs and LNC RNAs that regulate gene expression and cell functions in recipient cells. For example, tumour released exosomes remodel the microenvironment allowing cancer cells to survive and thrive. Low oxygen (hypoxia) is known to increase the release of exosomes in cancer cells. Hypoxia leads to the activation of hypoxia inducible factor (HIF) transcription factors, considered master regulators of the hypoxic response. The objective of this study was to investigate whether hypoxia induced EV (exosome) release is dependent on hypoxia inducible factor (HIF) proteins.MethodsWe isolated exosomes and microvesicles by differential centrifugation of conditioned media of cells exposed to normoxia or hypoxia (1% Oxygen) for different lengths of time ranging from 1–24hrs. We determined, size distribution and concentration of vesicles by nanoparticle tracking analysis (NTA). Expression of HIF1 and HIF2 was monitored by western blot of cellular lysates. We expressed oxygen‐stable mutated HIF1 and HIF2 isoforms either alone or in combination and determined EV release by NTA. We used chemical inhibitors of dioxygenase (PHD) and von Hippel–Lindau (VHL) proteins, the two proteins involved in HIF degradation under oxygen conditions, to stabilize HIF expression in normoxic cells and analysed EV release and HIF expression. We also analysed EV release in a cell line lacking VHL and after a VHL knock‐in. Western blotting of cellular lysates was used to monitor HIFs, VHL, and VEGF proteins. NTA was used to determine EV concentration and size. ANOVA statistical analysis was performed to analyse the data.ResultsHypoxia increased the amount extracellular vesicles in the conditioned media of all cells tested. The release of small vesicles (exosomes) was most increased following the exposure to hypoxia. HIF protein expression increased steadily during the time course of hypoxia, reaching a plateau after 2hrs following exposure. Expression of mutated (oxygen stable) HIF1 and HIF2 proteins in normoxic cells, either alone or in combination, did not increase exosome release. Chemical inhibition of PHD or VHL did not affect EV release. Exosome release was not different in VHL KD or KI cells.Conclusionthese data suggest that hypoxia driven exosome release is HIF independent.Support or Funding InformationSponsored by Fundacion Ramon Areces

Herpesvirus Infections in Patients Treated with the Mood Stabilizer Valproic Acid: A Nested Case-Control Study in the Spanish Primary Care Database, BIFAP

Purpose: The objective of this study is to evaluate the risk of infections for herpesviruses in patients exposed to Valproic acid and derivatives (VPA) in the Spanish research database BIFAP. Methods: We performed a case-control study nested in a primary cohort selected from the Spanish primary care population-based research database BIFAP over the period 2001 to 2015. The events of interest were those diseases caused by any of the herpesviruses known to infect humans, specifically. For each case, up to 10 controls per case matched by age, gender and calendar date were randomly selected using risk set sampling. A conditional logistic regression was used to compute adjusted odds ratios (OR) and their 95% confidence intervals (95%CI) for infection for herpesviruses associated to the use of VPA after adjusting for potential confounders. Results: Current use of VPA was associated with a trend towards a reduced risk of infection by herpesviruses as compared to non-users (OR 0.84; CI95% 0.7-1.0), being these differences marginally significant (p=0.053). Among current users, a trend to a decreased risk with treatment durations longer than 90 days was also observed. Conclusions: The results of this study show a trend to a reduced risk of infection for herpesviruses in patients exposed to VPA, especially in those with treatment durations longer than 90 days. These results are consistent with in vitro studies showing that, in cultured cells, VPA inhibits the production of infectious progeny of different enveloped viruses causing relevant human and veterinary diseases, including herpesviruses. Funding Statement: Work at Centro de Biologia Molecular Severo Ochoa was supported by grants from the Spanish Ministerio de Economia y Competitividad (AGL2014-52395-C2-1-R and AGL2017-84097-C2-1- R), and by an institutional grant from the Fundacion Ramon Areces and Banco Santander Central Hispano. Work at INIA (MAM-A) was supported by grant AGL2014-56518-JIN. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The scientific committee of BIFAP granted a positive opinion to the study protocol (#08/2015). The investigators had access to only fully anonymized data, and under this condition, no specific ethics review was required according to Spanish law.

Locomotor performance in a running toad: roles of morphology, sex and agrosystem versus natural habitat

The author was partly supported by a Fundacion Ramon Areces postdoctoral fellowship, and by a Juan de la Cierva-Formacion postdoctoral fellowship from the Spanish Ministerio de Economia, Industria y Competitividad.

B31 Striatal Deregulation Of Cdk5 Alters Mitochondrial Dynamics In Huntington's Disease

Huntington’s disease (HD) is characterised by motor disturbances associated to dysfunction and degeneration of the medium spiny neurons within the striatum. 1,2 The molecular mechanisms underlying striatal vulnerability are still unknown, but growing evidences suggest that mitochondrial dysfunction occurs during the pathogenesis of the disease. 3 We previously described that deregulation of cyclin-dependent kinase 5 (Cdk5) activity induced by mutant huntingtin increases the susceptibility of striatal neurons to dopamine via D1 receptor activation. 4 Interestingly, Cdk5 has been shown to act as a mitochondrial regulator during neuronal apoptosis. 5 Here, we investigated whether this aberrant Cdk5 signalling contributes to the striatal neurodegeneration by altering mitochondrial dynamics processes. We first observed that striatal cells expressing mutant huntingtin (mHtt) present increased mitochondrial fragmentation that worsens after dopaminergic stimuli. These mitochondrial defects can be widely rescued by Cdk5 inhibition with roscovitine or Cdk5 knockdown with siRNA transfection. Furthermore we found that mHtt deregulates the levels and the subcellular distribution of fission/fusion proteins while activation of D1 receptors promotes an increase in the levels of the fission protein Drp1 and its translocation to the mitochondria. We demonstrated that mHtt-induced Cdk5 activation is involved in the deregulation of the Drp1 GTPase activity since its inhibition prevents the aberrant activation of this fission protein. Altogether, our findings support the hypothesis that Cdk5 plays a crucial role in mitochondrial defects involved in the striatal neurodegeneration in HD. This study was supported by Ministerio de Innovacion y Ciencia SAF2012–39142, CHDI Ministerio deSanidad y Consumo (CIBERNED CB06/05/0054), Fundacion Ramon Areces. References 1Ferrante RJ, Kowall NW, Beal MF, Martin JB, Bird ED, Richardson EPJr. Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington’s disease. J Neuropathol Exp Neurol. 1987; 46 :12–27 2Myers RH, Vonsattle JP, Stevens TJ, Cupples LA, Richardson EP, Martin JB, Bird ED. Clinical and neuropathologic assesment of severity in Huntington’s disease. Neurology 1988; 38 :341–347 3Damiano M, Galvan L, Deglon N, Brouillet E. Mitochondria in Huntington’s disease. Biochim Biophys Acta 2010;1802:52–61 4Paoletti P, Vila I, Rife M, Lizcano JM, Alberch J, Gines S. Dopaminergic and glutamatergic signaling crosstalk in Huntington’s disease neurodegeneration: the role of p25/cyclin dependent kinase 5. J Neurosci 2008; 28 (40):10090–10101 5Meuer K, Suppanz IE, Lingor P, Planchamp V, Goricke B, Fichtner L, Braus GH, Dietz GP, Jakobs S, Bahr M, Weishaupt JH. Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. Cell Death Differ 2007; 14 (4):651–61

Two novel missense mutations in iron transport protein transferrin causing hypochromic microcytic anaemia and haemosiderosis: molecular characterization and structural implications

This study was supported in part by a grant BT/PR-13968/MED/12/465/2010 from the Department of Biotechnology, Government of India to ES and by the grant SAF2012-40106 from the Spanish Secretary of Research, Development and Innovation (MINECO) and the grant CIVP16A1857 “Ayudas a proyectos de Investigacion en Ciencias de la Vida- Fundacion Ramon Areces” to M.S. M.S. held a research contract under the Ramon y Cajal program from the Spanish Ministry of Science and Innovation (RYC-2008-02352).

Role of arachidonic acid metabolites in Trypanosoma cruzi infection

Event Abstract Back to Event Role of arachidonic acid metabolites in Trypanosoma cruzi infection Néstor A. Guerrero1, Manuel Fresno1 and Núria Gironès1* 1 Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Spain Cardiac inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Lipid mediators derived from arachidonic acid (AA), like prostaglandins and leukotrienes, are considered regulators of homeostasis and inflammation. These molecules are produced by a biosynthetic pathway controlled by enzymes as cyclooxygenases and lipoxygenases. The role of cyclooxygenase-2 (COX-2) in immunosuppression during the acute phase of T. cruzi infection has been described using non-steroidal anti-inflammatory drugs, which are inhibitors of this enzyme. In this study, we first investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Susceptible and non-susceptible mouse models of infection were used to further analyze the role of lipid mediators in T. cruzi infection. Our results confirm the expression of several of these enzymes in T. cruzi-infected heart, in particular COX-2. CD68+ heart-infiltrating macrophages were the major cell type expressing COX-2. CD11b+ heart-infiltrating myeloid cells were purified and they were able to produce prostaglandins PGE2 and PGF2α. Studies using gene-deficient mouse models indicated that regulation of COX-2 and PGE2, through PGE2 receptor 2 signaling, was in part responsible of cardiac inflammation in T. cruzi infection. The key role of lipid mediators in Chagas disease inflammation and the availability of drugs that inhibit their synthesis and their receptors could be useful for the treatment of this neglected disease. Acknowledgements This work was supported by grants: SAF2007-61716, SAF2005-02220, PS09/00538, RECAVA RD06/0014/1013, RICET RD06/0021/0016, HEALTH-FE-2008-22303,ChagasEpiNet, CC08-UAM/SAL-4440/08, AECID A/025417/09 and ‘‘Fundacion Ramon Areces". M. Fresno and N. Girones are professors at the UAM. N.A.G. was a recipient of a fellowship from ISCIII and RICET. We thank Beatriz Barrocal, Maria A. Chorro, M.C. Maza and Carlos Chillon for their technical assistance. Keywords: Trypanosoma cruzi, Cyclooxigenase-2, Prostaglandin E2 receptor 2, Cardiac inflammation, in vivo infection Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Guerrero NA, Fresno M and Gironès N (2013). Role of arachidonic acid metabolites in Trypanosoma cruzi infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01131 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jul 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Núria Gironès, Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid, 28049, Spain, ngirones@cbm.csic.es Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Néstor A Guerrero Manuel Fresno Núria Gironès Google Néstor A Guerrero Manuel Fresno Núria Gironès Google Scholar Néstor A Guerrero Manuel Fresno Núria Gironès PubMed Néstor A Guerrero Manuel Fresno Núria Gironès Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

What do the Papers Sell? a Model of Advertising and Media Bias

We gratefully acknowledge financial support from the Spanish Ministry of Science and Technology (Grants SEJ2006-09993, SEJ2007-64340/ECON and Ram¶on y Cajal fellowships) as well as from CREA and the Fundacion Ramon Areces.

Preface: Cannabinoids as New Tools for the Treatment of Neurological Disorders

This special issue that the editorial board of Molecular Neurobiology has kindly accepted to host has been prepared from the lectures presented in an International Symposium on “Cannabinoids: new tools for the treatment of neurological disorders” held in Madrid, Spain, in March 2006, organized by the “Fundacion Ramon Areces”. Since 1998, this was the third time that this Spanish foundation includes an international event on different aspects of the physiology and pathophysiology of the cannabinoid system in its yearly scientific program. We want to thank all members responsible for this foundation, in particular, Professor Julio Rodriguez Villanueva, for his continuous support to the progress in the research of these clinically promising molecules. These thanks must also be extended to Professor Nicolas Bazan, the senior editor of Molecular Neurobiology, for accepting that the symposium lectures become in review articles available for all readership of this important review journal, and of course, to all researchers that contributed with excellent lectures in the symposium which have been continued by excellent review articles for this special issue. In this International Symposium, we addressed the reasons for the great increase experienced by cannabinoid research during the last 10 years. There is consensus that this is directly related to the discovery of the so-called “endogenous cannabinoid system”, a new intercellular messenger system that is active at both central and peripheral levels. This goal has provided the basis to explain why cannabinoids present inCannabis sativa, the so-called plant-derived cannabinoids, had already shown for a long time to have therapeutic properties, but also, it has allowed to further explore the modifications that this system undergoes in certain pathologies, and then, to determine the best pharmacological treatment in each case. The different elements that constitute this intercellular messenger system are already known. The endogenous ligands are mostly derived from arachidonic acid, and they are synthesized on demand by different enzymes widely acting in lipid metabolism. These ligands activate various membrane receptors, mainly the so-called cannabinoid CB1 and CB2 receptors, although the existence of other cannabinoid receptor types and the involvement of other related receptors, such as the vanilloid TRPV1 receptors, cannot be ruled out. Cannabinoid receptors contain seven transmembrane domains typical of GTP-binding protein-coupled receptors, and their activation triggers various intracellular cascades and/or modifies the conductance for several ions. The mechanism involved in the finalization of the biological action of cannabinoids is also known and involves two processes, an uptake mechanism through the cell membrane and the action of various enzymes involved in the hydrolysis of endogenous cannabinoids. All this general information, divided in two parts, one dealing with specific biochemical aspects and another addressed to review the pharmacological compounds targeting the different proteins Mol Neurobiol (2007) 36:1–2 DOI 10.1007/s12035-007-8005-9

On the transfructosylation activity and selectivity of microbial beta-fructofuranosidases for the production of prebiotics

This work was supported by a grant from the Spanish Ministry of Education and Science (BIO2004-03773-C04), by Genoma Espana (the National Foundation for Promoting Genomics and Proteomics), and by an institutional grant from the Fundacion Ramon Areces to the Centro de Biologia Molecular Severo Ochoa

Fiscal Policy and Minimum Wage for Redistribution: An Equivalence Result

Abstract: In this paper, we derive conditions under which a minimum-wage law combined with anonymous taxes and transfers and an agent-specific tax-transfer scheme are equivalent policies. JEL classification: E62, H21 Key words: redistribution policy, minimum wage, tax-transfer scheme, equivalence result Financial support from Fundacion Ramon Areces and 9/UPV 00035.321-13511/2001 is acknowledged. The views expressed here are the authors' and not necessarily those of the Federal Reserve Bank of Atlanta or the Federal Reserve System. Any remaining errors are the authors' responsibility. Please address questions regarding content to Arantza Gorostiaga, Universidad del Pais Vasco, Avenida Lehendakari Aguirre, 83, 48015 Bilbao (Spain), +34 94 601 38 14, arantza.gorostiaga@ehu.es, or Juan Franciso Rubio-Ramirez, Federal Reserve Bank of Atlanta, 1000 Peachtree Street, NE, Atlanta, GA 30309, 404-498-8057, juan.rubio@atl.frb.org. Federal Reserve Bank of Atlanta working papers, including revised versions, are available on the Atlanta Fed's Web site at www.frbatlanta.org. Click Publications and then Working Papers. Use the WebScriber Service (at www.frbatlanta.org) to receive e-mail notifications about new papers. 1. Introduction Many papers in the literature have considered the use of a minimum wage legislation jointly with a tax-transfer scheme to redistribute income among differently productive agents. Moreover, articles such as Allen (1987), Guesnerie and Roberts (1987) and Gorostiaga and Rubio-Ramirez (2004) have shown that minimum wages might be optimal when combined with linear taxes and transfers in a static general equilibrium model. In this paper we prove that any equilibrium allocation attained under a minimum wage law and anonymous taxes and transfers could be implemented through an agent-specific tax-transfer scheme. We also show that the reverse implication is not always true. The equivalence depends on imposing some conditions on the initial agent-specific policy. 2. The basic setup We consider a static general equilibrium model. The economy is populated by two types of agent: low and high productivity households. A proportion [gamma] of households are high-skilled (H), and a proportion 1 - [gamma] are low-skilled (L). This a production economy where a single consumption good is produced. The resource constraint is: [gamma][c.sub.H] + (1 - [gamma])[c.sub.L] = y, (1) where y is the aggregate production, and [c.sub.H] and [c.sub.L] are high-skilled and low-skilled consumption respectively. Firms The available constant returns to scale technology can be represented through the following CES production function: y = F [[gamma](1 - [l.sub.H]), (1 - [gamma])(1 - [l.sub.H])] = [[[phi][[[gamma](1 - [l.sub.H])].sup.[[delta]] + [[(1 - [gamma])(1 - [l.sub.H])].sup.[delta]]].sup.1/[delta]], (2) where [delta] [member of] (0; 1), [phi] > 1, and (1 - [l.sub.H]) and (1 - [l.sub.H]) are high-skilled and low-skilled labor respectively. Firms are price takers and inverse labor demands are: [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] (3) [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] (4) Households Households in this economy derive utility from consumption and leisure. The utility function U([c.sub.i], [l.sub.i]) is assumed to be strictly increasing and concave in both arguments. Households are endowed with one unit of time which can be devoted to work or leisure, and face the following budget constraint: [c.sub.i] = (1 - [[tau].sub.i])[[omega].sub.i](1 - [l.sub.i]) + [T.sub.i], (5) where [[omega].sub.i] is the wage, [[tau].sub.i] is the income tax rate and [T.sub.i] is a lump-sum transfer. Government We consider two alternative policy schemes: Policy scheme A The redistribution policy is implemented through a minimum wage law that sets a lower bound on low-skilled wages, [[omega]. …

Symposium: "Herman Phaff: Learning from Yeast" Santiago de Compostela, Spain, 23-24 September 2003.

Thomas Gonzalez Villa , Professor of Microbiology at the University of Santiago de Compostela and former postdoctoral fellow in the laboratory of Herman J. Phaff , in conjunction with the Fundacion Ramon Areces, organized a symposium in memory of the former Professor at the University of California, Davis. The symposium, held during the 29th annual meeting of the Spanish Society for Microbiology (SEM), offered a panoramic view of Phaff's enormous contributions to the knowledge of yeast biology, taxonomy and ecology. Seminars were presented by former Phaff students and postdocs covering various aspects of yeast research originated and associated with the stay in Davis, while some Spanish yeast scientists discussed investigations indirectly inspired by Phaff. Introductory remarks were made by Thomas Villa , Carlos Hardisson , President of the Spanish Society of Microbiology, and Julio Villanueva for the Fundacion Ramon Areces. Then Arnold Demain (R.I.S.E.-Drew University, Madison, NJ) began with a moving review of Phaff's career: “ Herman Jan Phaff: professor , mentor , friend and colleague ”. Phaff left the family wine-trade in Winschoten, The Netherlands, to pursue a degree in Chemical Engineering at the Technical University of Delft under Albert Jan Kluyver. This was followed by a move to the United States and a brilliant career, first at University of California, Berkeley, and then at UC Davis. This seminar, together with that of Sally Ann Meyer (Georgia State University): “ Beer , bread and beyond ”, offered a very human picture of a great yeast scientist. Phaff was remembered as an inexhaustible worker, a stickler for details, a global scientist and a …

Revolutionary stirrings in Spain

Workshop: The Revolution in Systematics, Fundacion Ramon Areces, Madrid, Spain, 23–24 February 1998.

Control of the Photonic Crystal Properties of fcc-Packed Submicrometer SiO2 Spheres by Sintering

We acknowledge M. Planes for his help during SEM characterization. This work was partially financed by the Spanish CICyT project No. MAT97-0698-C04 and the Fundacion Ramon Areces

The human CD53 gene, coding for a four transmembrane domain protein, maps to chromosomal region 1p13

This work has been supported by grants from Fundacion Ramon Areces and CICYT (SAL90-0209 and SAL91-0043) to P.A.L. and FIS(92-0889) to S.R.C

NOTES

The research was supported by CSIC-DGICYT (project PB87-0405)and Fundacion Ramon Areces