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Digital.CSIC (158.952 recursos)

Repositorio institucional del Consejo Superior de Investigaciones Científicas. Digital.CSIC es un depósito de documentos digitales, cuyo objetivo es organizar, archivar, preservar y difundir en modo de acceso abierto la producción intelectual resultante de la actividad investigadora del CSIC.

(IBMCP) Artículos post-print

Mostrando recursos 1 - 20 de 93

  1. Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: A new target for a privileged structure

    Balsera, Beatriz; Mulet Soler, José; Fernández-Carvajal, Asia; Torre-Martínez, Roberto de la; Ferrer-Montiel, Antonio; Hernández-Jiménez, José G.; Estévez-Herrera, Judith; Borges, Ricardo; Freitas, Andiara E.; López, Manuela G.; García-López, M. Teresa; González-Muñiz, Rosario; Pérez de Vega, M. Jesús; Valor, Luis M.; Svobodová, Lucie; Sala, Salvador; Sala, Francisco; Criado, Manuel
    The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α77...

  2. The causes of epistasis

    De Visser, J.; Cooper, Tim F.; Elena, Santiago F.; Arjan, G. M.
    Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions—called epistasis—have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype–phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the...

  3. A Plant Virus Movement Protein Regulates the Gcn2p Kinase in Budding Yeast

    Aparicio Herrero, Frederic; Aparicio-Sanchís, Rafael; Gadea Vacas, José; Sánchez-Navarro, J. A.; Pallás Benet, Vicente; Murguía Ibáñez, José Ramón
    Virus life cycle heavily depends on their ability to command the host machinery in order to translate their genomes. Animal viruses have been shown to interfere with host translation machinery by expressing viral proteins that either maintain or inhibit eIF2a function by phosphorylation. However, this interference mechanism has not been described for any plant virus yet. Prunnus necrotic ringspot virus (PNRSV) is a serious pathogen of cultivated stone fruit trees. The movement protein (MP) of PNRSV is necessary for the cell-to-cell movement of the virus. By using a yeast-based approach we have found that overexpression of the PNRSV MP caused a severe growth defect in...

  4. A Plant Virus Movement Protein Regulates the Gcn2p Kinase in Budding Yeast

    Aparicio Herrero, Frederic; Aparicio-Sanchís, Rafael; Gadea Vacas, José; Sánchez-Navarro, J. A.; Pallás Benet, Vicente; Murguía, José Ramón
    Virus life cycle heavily depends on their ability to command the host machinery in order to translate their genomes. Animal viruses have been shown to interfere with host translation machinery by expressing viral proteins that either maintain or inhibit eIF2a function by phosphorylation. However, this interference mechanism has not been described for any plant virus yet. Prunnus necrotic ringspot virus (PNRSV) is a serious pathogen of cultivated stone fruit trees. The movement protein (MP) of PNRSV is necessary for the cell-to-cell movement of the virus. By using a yeast-based approach we have found that overexpression of the PNRSV MP caused a severe growth defect in...

  5. Peptidyl-prolyl cis-trans isomerase ROF2 modulates intracellular pH homeostasis in Arabidopsis

    Bissoli, Gaetano; Niñoles, Regina; Fresquet, Sandra; Palombieri, Samuela; Bueso, Eduardo; Rubio, Lourdes; García-Sánchez, María J.; Fernández, José A.; Mulet-Salort, José Miguel; Serrano, Ramón
    Intracellular pH must be kept close to neutrality to be compatible with cellular functions, but the mechanisms of pH homeostasis and the responses to intracellular acidification are mostly unknown. In the plant Arabidopsis thaliana, we found that intracellular acid stress generated by weak organic acids at normal external pH induces expression of several chaperone genes, including ROF2, which encodes a peptidyl-prolyl cis-trans isomerase of the FK506-binding protein class. Loss of function of ROF2, and especially double mutation of ROF2 and the closely related gene ROF1, results in acid sensitivity. Over-expression of ROF2 confers tolerance to intracellular acidification by increasing proton...

  6. A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress

    Hueso Lorente, Guillem; Aparicio-Sanchís, Rafael; Montesinos, Consuelo; Lorenz, Silvia; Murguía, José Ramón; Serrano, Ramón
    Intracellular pH conditions many cellular systems, but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification, and either leucine oversupplementation or overexpression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2α (eukaryotic initiation factor 2α) (Sui2)...

  7. A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane H+-ATPase and decreased cytosolic pH, K+ and anions

    Planes, María Dolores; Niñoles, Regina; Rubio, Lourdes; Bissoli, Gaetano; Bueso, Eduardo; García-Sánchez, María J.; Alejandro, Santiago; González-Guzmán, Miguel; Hedrich, Rainer; Pedro L., Rodriguez; Fernández, José A.; Serrano, Ramón
    The stress hormone abscisic acid (ABA) induces expression of defense genes in many organs, modulates ion homeostasis and metabolism in guard cells and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for H+ efflux (wat1-1D, over-expression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than wild type. This suggested that ABA could inhibit H+ efflux (H+-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA...

  8. Experimental Virus Evolution Reveals a Role of Plant Microtubule Dynamics and TORTIFOLIA1/SPIRAL2 in RNA Trafficking

    Pena, Eduardo Jose; Ferriol, Inmaculada; Sambade, Adrián; Buschmann, Henrik; Niehl, Annette; Elena, Santiago F.; Rubio, Luis; Heinlein, Manfred
    1 tabla y 2 figuras

  9. Viroids: Survivors from the RNA World?

    Flores, Ricardo; Gago, Selma; Serra, Pedro; Sanjuán, Rafael
    Because RNA can be a carrier of genetic information and a biocatalyst, there is a consensus that it emerged before DNA and proteins, which eventually assumed these roles and relegated RNA to intermediate functions. If such a scenario--the so-called RNA world--existed, we might hope to find its relics in our present world. The properties of viroids that make them candidates for being survivors of the RNA world include those expected for primitive RNA replicons: (a) small size imposed by error-prone replication, (b) high G + C content to increase replication fidelity, (c) circular structure for assuring complete replication without genomic...

  10. Orchestration of floral initiation by APETALA1

    Kaufmann, Kerstin; Ferrier, Thilia; Serrano Mislata, Antonio; Madueño Albi, Francisco; Riechmann, José Luis
    Kaufmann, Kerstin et al.

  11. De novo designed library of linear helical peptides: An exploratory tool in the discovery of protein-protein interaction modulators

    Bonache de Marcos, María Ángeles; Balsera, Beatriz; López-Méndez, Blanca; Millet, Óscar; Brancaccio, Diego; Gómez-Monterrey, Isabel; Carotenuto, Alfonso; Pavone, Luigi M.; Reille-Seroussi, Marie; Gagey-Eilstein, Nathalie; Vidal, Michel; Torre-Martínez, Roberto de la; Fernández-Carvajal, Asia; Ferrer-Montiel, Antonio; García-López, M. Teresa; Martín-Martínez, Mercedes; Pérez de Vega, M. Jesús; González-Muñiz, Rosario
    Protein-protein interactions (PPIs) have emerged as important targets for pharmaceutical intervention because of their essential role in numerous physiological and pathological processes, but screening efforts using small-molecules have led to very low hit rates. Linear peptides could represent a quick and effective approach to discover initial PPI hits, particularly if they have inherent ability to adopt specific peptide secondary structures. Here, we address this hypothesis through a linear helical peptide library, composed of four sublibraries, which was designed by theoretical predictions of helicity (Agadir software). The 13-mer peptides of this collection fixes either a combination of three aromatic or two...

  12. Effects of the number of genome segments on primary and systemic infection for a multipartite plant RNA virus

    Elena, Santiago F.; Sánchez-Navarro, J. A.; Zwart, Mark P.
    Multipartite plant viruses were discovered because of discrepancies between the observed dose response and predictions of the independent-action hypothesis (IAH) model. Theory suggests that the number of genome segments predicts the shape of the dose-response curve, but a rigorous test of this hypothesis has not been reported. Here, Alfalfa mosaic virus (AMV), a tripartite Alfamovirus, and transgenic Nicotiana tabacum plants expressing no (wild type), one (P2), or two (P12) viral genome segments were used to test whether the number of genome segments necessary for infection predicts the dose response. The dose-response curve of wild-type plants was steep and congruent with...

  13. Experimental evolution of pseudogenization and gene loss in a plant RNA virus

    Elena, Santiago F.; Daròs, José-Antonio; Zwart, Mark P.
    Viruses have evolved highly streamlined genomes and a variety of mechanisms to compress them, suggesting that genome size is under strong selection. Horizontal gene transfer has, on the other hand, played an important role in virus evolution. However, evolution cannot integrate initially nonfunctional sequences into the viral genome if they are rapidly purged by selection. Here we report on the experimental evolution of pseudogenization in virus genomes using a plant RNA virus expressing a heterologous gene. When long 9-week passages were performed, the added gene was lost in all lineages, whereas viruses with large genomic deletions were fixed in only...

  14. Hal4 and Hal5 protein kinases are required for general control of carbon and nitrogen uptake and metabolism

    Pérez-Valle, Jorge; Rothe, Jessica; Primo, Cecilia; Martínez Pastor, Mar; Ariño, Joaquín; Pascual-Ahuir, Amparo; Mulet-Salort, José Miguel; Serrano, Ramón; Yenush, Lynne
    The yeast protein kinases Sat4/Hal4 and Hal5 are required for the plasma membrane stability of the K+ transporter Trk1 and some amino acid and glucose permeases. The transcriptomic analysis presented here indicates alterations in the general control of the metabolism of both nitrogen and carbon. Accordingly, we observed reduced uptake of methionine and leucine in the hal4 hal5 mutant. This decrease correlates with activation of the Gcn2-Gcn4 pathway, as measured by expression of the lacZ gene under the control of the GCN4 promoter. However, with the exception of methionine biosynthetic genes, few amino acid biosynthetic genes are induced in the...

  15. Fine-tuning tomato agronomic properties by computational genome redesign

    Carrera, Javier; Fernández-del-Carmen, Asun; Fernández-Muñoz, Rafael; Rambla, José Luis; Pons, Clara; Jaramillo, Alfonso; Elena, Santiago F.; Granell, Antonio
    This is an open-access article distributed under the terms of the Creative Commons Attribution License.

  16. A fertilization-independent developmental program triggers partial fruit development and senescence processes in pistils of Arabidopsis

    Carbonell-Bejerano, Pablo; Úrbez, Cristina; Carbonell-Gisbert, Juan; Granell, Antonio; Pérez-Amador, Miguel A.
    Free via Open: Open Access articles can be viewed online without a subscription.

  17. Abscisic acid: Emergence of a core signaling network

    Cutler, Sean R.; Rodríguez, Pedro L.; Finkelstein, R.; Abrams, Suzanne R.
    Abscisic acid (ABA) regulates numerous developmental processes and adaptive stress responses in plants. Many ABA signaling components have been identified, but their interconnections and a consensus on the structure of the ABA signaling network have eluded researchers. Recently, several advances have led to the identification of ABA receptors and their three-dimensional structures, and an understanding of how key regulatory phosphatase and kinase activities are controlled by ABA. A new model for ABA action has been proposed and validated, in which the soluble PYR/PYL/RCAR receptors function at the apex of a negative regulatory pathway to directly regulate PP2C phosphatases, which in...

  18. Coevolution analyses illuminate the dependencies between amino acid sites in the chaperonin system GroES-L

    Ruiz-González, Mario X; Fares, Mario A.
    Abstract Background GroESL is a heat-shock protein ubiquitous in bacteria and eukaryotic organelles. This evolutionarily conserved protein is involved in the folding of a wide variety of other proteins in the cytosol, being essential to the cell. The folding activity proceeds through strong conformational changes mediated by the co-chaperonin GroES and ATP. Functions alternative to folding have been previously described for GroEL in different bacterial groups, supporting enormous functional and structural plasticity for this molecule and the existence of a hidden combinatorial code in the protein sequence enabling such functions. Describing this plasticity can shed light on the functional diversity...

  19. Coevolution analyses illuminate the dependencies between amino acid sites in the chaperonin system GroES-L

    Ruiz-González, Mario X.; Fares, Mario A.
    Abstract Background GroESL is a heat-shock protein ubiquitous in bacteria and eukaryotic organelles. This evolutionarily conserved protein is involved in the folding of a wide variety of other proteins in the cytosol, being essential to the cell. The folding activity proceeds through strong conformational changes mediated by the co-chaperonin GroES and ATP. Functions alternative to folding have been previously described for GroEL in different bacterial groups, supporting enormous functional and structural plasticity for this molecule and the existence of a hidden combinatorial code in the protein sequence enabling such functions. Describing this plasticity can shed light on the functional diversity...

  20. Emergence and Phylodynamics of Citrus tristeza virus in Sicily, Italy

    Davino, Salvatore; Willemsen, Anouk; Panno, Stefano; Davino, Mario; Catara, Antonino; Elena, Santiago F.; Rubio, Luis
    Citrus tristeza virus (CTV) outbreaks were detected in Sicily island, Italy for the first time in 2002. To gain insight into the evolutionary forces driving the emergence and phylogeography of these CTV populations, we determined and analyzed the nucleotide sequences of the p20 gene from 108 CTV isolates collected from 2002 to 2009. Bayesian phylogenetic analysis revealed that mild and severe CTV isolates belonging to five different clades (lineages) were introduced in Sicily in 2002. Phylogeographic analysis showed that four lineages co-circulated in the main citrus growing area located in Eastern Sicily. However, only one lineage (composed of mild isolates) spread to distant areas of...

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