Evaluation of the anti-angiogenic potential of hydroxytyrosol derivatives

Angiogenesis, a process which allows the formation of new vessels from pre-existing ones, is an essential phenomenon for tumor survival since it allows cancer cells to obtain nutrients and oxygen. This explains the increasing interest showed by many groups of research and pharmaceutical companies to find compounds with potential to disrupt at least one of the steps within the angiogenic process. Hydroxytyrosol (3,4-dihydroxyphenyl ethanol) has been identified as the most important health-related phenolic compound of virgin olive oil because of its pleiotropic effects on multiple targets. In 2012, our group identified hydroxytyrosol as an anti-angiogenic compound able to inhibit several key steps in the angiogenic process. In the present study, the potential effects of six hydroxytyrosol derivatives are tested and compared with those exhibited by hydroxytyrosol by making use of several in vitro and in vivo assays. Results indicate that these are candidate new anti-angiogenic compounds with potential utility in anti-tumor and anti-angiogenic therapies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communication has the support of a travel grant

An improved model for fast and reliable harbour wave agitation assessment

ABSTRACT: This study presents the new advances achieved in the field of harbour agitation climate assessment. Based on the improvement of an elliptic mild-slope model (MSP), which realistically reconstructs waves inside any-sized basin, represented by high-detailed unstructured meshes, and forced by real-shaped outer spectral data. A new solver is proposed for high performance runs, which allow fast agitation hindcast for statistical downtime analysis within an iterative and multi-scenario approach. Also, a realistic assimilation of partial reflection processes in quays/docks/wharfs/breakwaters is proposed. The model has been successfully validated in several harbours of special relevance in Spain with in situ measurements, through the assimilation of the hybrid downscaling (Camus et al., 2011) technique combined with monochromatic-based wave spectral reconstruction.This work has been also partially funded under the RETOS program of the Spanish Ministry of Science, Innovation and Universities (BIA2017-87213-R). We would like to thank Puertos del Estado of Spain for providing spectral outer wave spectral forcing and wave agitation measurements, for gather/organize each Port Authority base data required

The Role of ABA in Plant Immunity is Mediated through the PYR1 Receptor

[EN] ABA is involved in plant responses to a broad range of pathogens and exhibits complex antagonistic and synergistic relationships with salicylic acid (SA) and ethylene (ET) signaling pathways, respectively. However, the specific receptor of ABA that triggers the positive and negative responses of ABA during immune responses remains unknown. Through a reverse genetic analysis, we identified that PYR1, a member of the family of PYR/PYL/RCAR ABA receptors, is transcriptionally upregulated and specifically perceives ABA during biotic stress, initiating downstream signaling mediated by ABA-activated SnRK2 protein kinases. This exerts a damping effect on SA-mediated signaling, required for resistance to biotrophic pathogens, and simultaneously a positive control over the resistance to necrotrophic pathogens controlled by ET. We demonstrated that PYR1-mediated signaling exerted control on a priori established hormonal cross-talk between SA and ET, thereby redirecting defense outputs. Defects in ABA/PYR1 signaling activated SA biosynthesis and sensitized plants for immune priming by poising SA-responsive genes for enhanced expression. As a trade-off effect,pyr1-mediated activation of the SA pathway blunted ET perception, which is pivotal for the activation of resistance towards fungal necrotrophs. The specific perception of ABA by PYR1 represented a regulatory node, modulating different outcomes in disease resistance.This research was founded by the Spanish AEI agency by grant BIO2017-82503-R to P.L.R. and by grant RTI2018-098501-B-I00 to P.V.García-Andrade, J.; González, B.; Gonzalez-Guzman, M.; Rodríguez Egea, PL.; Vera Vera, P. (2020). The Role of ABA in Plant Immunity is Mediated through the PYR1 Receptor. International Journal of Molecular Sciences. 21(16):1-21. https://doi.org/10.3390/ijms21165852S1212116Malamy, J., Carr, J. P., Klessig, D. F., & Raskin, I. (1990). Salicylic Acid: A Likely Endogenous Signal in the Resistance Response of Tobacco to Viral Infection. Science, 250(4983), 1002-1004. doi:10.1126/science.250.4983.1002Métraux, J. P., Signer, H., Ryals, J., Ward, E., Wyss-Benz, M., Gaudin, J., … Inverardi, B. (1990). Increase in Salicylic Acid at the Onset of Systemic Acquired Resistance in Cucumber. Science, 250(4983), 1004-1006. doi:10.1126/science.250.4983.1004Glazebrook, J. (2005). Contrasting Mechanisms of Defense Against Biotrophic and Necrotrophic Pathogens. Annual Review of Phytopathology, 43(1), 205-227. doi:10.1146/annurev.phyto.43.040204.135923Verhage, A., van Wees, S. C. M., & Pieterse, C. M. J. (2010). Plant Immunity: It’s the Hormones Talking, But What Do They Say?: Figure 1. Plant Physiology, 154(2), 536-540. doi:10.1104/pp.110.161570Broekaert, W. F., Delauré, S. L., De Bolle, M. F. C., & Cammue, B. P. A. (2006). The Role of Ethylene in Host-Pathogen Interactions. Annual Review of Phytopathology, 44(1), 393-416. doi:10.1146/annurev.phyto.44.070505.143440Grant, M. R., & Jones, J. D. G. (2009). Hormone (Dis)harmony Moulds Plant Health and Disease. Science, 324(5928), 750-752. doi:10.1126/science.1173771Pieterse, C. M. J., Van der Does, D., Zamioudis, C., Leon-Reyes, A., & Van Wees, S. C. M. (2012). Hormonal Modulation of Plant Immunity. Annual Review of Cell and Developmental Biology, 28(1), 489-521. doi:10.1146/annurev-cellbio-092910-154055Thaler, J. S., & Bostock, R. M. (2004). INTERACTIONS BETWEEN ABSCISIC-ACID-MEDIATED RESPONSES AND PLANT RESISTANCE TO PATHOGENS AND INSECTS. Ecology, 85(1), 48-58. doi:10.1890/02-0710Spoel, S. H., Koornneef, A., Claessens, S. M. C., Korzelius, J. P., Van Pelt, J. A., Mueller, M. J., … Pieterse, C. M. J. (2003). NPR1 Modulates Cross-Talk between Salicylate- and Jasmonate-Dependent Defense Pathways through a Novel Function in the Cytosol. The Plant Cell, 15(3), 760-770. doi:10.1105/tpc.009159Thomma, B. P. H. J., Eggermont, K., Tierens, K. F. M.-J., & Broekaert, W. F. (1999). Requirement of Functional Ethylene-Insensitive 2Gene for Efficient Resistance of Arabidopsis to Infection by Botrytis cinerea  . Plant Physiology, 121(4), 1093-1101. doi:10.1104/pp.121.4.1093Gu, Y.-Q., Yang, C., Thara, V. K., Zhou, J., & Martin, G. B. (2000). Pti4 Is Induced by Ethylene and Salicylic Acid, and Its Product Is Phosphorylated by the Pto Kinase. The Plant Cell, 12(5), 771-785. doi:10.1105/tpc.12.5.771Berrocal-Lobo, M., Molina, A., & Solano, R. (2002). Constitutive expression ofETHYLENE-RESPONSE-FACTOR1inArabidopsisconfers resistance to several necrotrophic fungi. The Plant Journal, 29(1), 23-32. doi:10.1046/j.1365-313x.2002.01191.xDı́az, J., ten Have, A., & van Kan, J. A. L. (2002). The Role of Ethylene and Wound Signaling in Resistance of Tomato to Botrytis cinerea  . Plant Physiology, 129(3), 1341-1351. doi:10.1104/pp.001453Leslie, C. A., & Romani, R. J. (1988). Inhibition of Ethylene Biosynthesis by Salicylic Acid. Plant Physiology, 88(3), 833-837. doi:10.1104/pp.88.3.833Chen, H., Xue, L., Chintamanani, S., Germain, H., Lin, H., Cui, H., … Zhou, J.-M. (2009). ETHYLENE INSENSITIVE3 and ETHYLENE INSENSITIVE3-LIKE1 Repress SALICYLIC ACID INDUCTION DEFICIENT2 Expression to Negatively Regulate Plant Innate Immunity in Arabidopsis    . The Plant Cell, 21(8), 2527-2540. doi:10.1105/tpc.108.065193Huang, P., Dong, Z., Guo, P., Zhang, X., Qiu, Y., Li, B., … Guo, H. (2019). Salicylic Acid Suppresses Apical Hook Formation via NPR1-Mediated Repression of EIN3 and EIL1 in Arabidopsis. The Plant Cell, 32(3), 612-629. doi:10.1105/tpc.19.00658Spoel, S. H., Johnson, J. S., & Dong, X. (2007). Regulation of tradeoffs between plant defenses against pathogens with different lifestyles. Proceedings of the National Academy of Sciences, 104(47), 18842-18847. doi:10.1073/pnas.0708139104Cutler, S. R., Rodriguez, P. L., Finkelstein, R. R., & Abrams, S. R. (2010). Abscisic Acid: Emergence of a Core Signaling Network. Annual Review of Plant Biology, 61(1), 651-679. doi:10.1146/annurev-arplant-042809-112122Mauch-Mani, B., & Mauch, F. (2005). The role of abscisic acid in plant–pathogen interactions. Current Opinion in Plant Biology, 8(4), 409-414. doi:10.1016/j.pbi.2005.05.015Asselbergh, B., De Vleesschauwer, D., & Höfte, M. (2008). Global Switches and Fine-Tuning—ABA Modulates Plant Pathogen Defense. Molecular Plant-Microbe Interactions®, 21(6), 709-719. doi:10.1094/mpmi-21-6-0709Fan, J., Hill, L., Crooks, C., Doerner, P., & Lamb, C. (2009). Abscisic Acid Has a Key Role in Modulating Diverse Plant-Pathogen Interactions      . Plant Physiology, 150(4), 1750-1761. doi:10.1104/pp.109.137943Sánchez-Vallet, A., López, G., Ramos, B., Delgado-Cerezo, M., Riviere, M.-P., Llorente, F., … Molina, A. (2012). Disruption of Abscisic Acid Signaling Constitutively Activates Arabidopsis Resistance to the Necrotrophic Fungus Plectosphaerella cucumerina    . Plant Physiology, 160(4), 2109-2124. doi:10.1104/pp.112.200154Adie, B. A. T., Pérez-Pérez, J., Pérez-Pérez, M. M., Godoy, M., Sánchez-Serrano, J.-J., Schmelz, E. A., & Solano, R. (2007). ABA Is an Essential Signal for Plant Resistance to Pathogens Affecting JA Biosynthesis and the Activation of Defenses in Arabidopsis. The Plant Cell, 19(5), 1665-1681. doi:10.1105/tpc.106.048041García-Andrade, J., Ramírez, V., Flors, V., & Vera, P. (2011). Arabidopsis ocp3 mutant reveals a mechanism linking ABA and JA to pathogen-induced callose deposition. The Plant Journal, 67(5), 783-794. doi:10.1111/j.1365-313x.2011.04633.xJensen, M. K., Hagedorn, P. H., de Torres-Zabala, M., Grant, M. R., Rung, J. H., Collinge, D. B., & Lyngkjaer, M. F. (2008). Transcriptional regulation by an NAC (NAM-ATAF1,2-CUC2) transcription factor attenuates ABA signalling for efficient basal defence towardsBlumeria graminisf. sp.hordeiin Arabidopsis. The Plant Journal, 56(6), 867-880. doi:10.1111/j.1365-313x.2008.03646.xDe Torres-Zabala, M., Truman, W., Bennett, M. H., Lafforgue, G., Mansfield, J. W., Rodriguez Egea, P., … Grant, M. (2007). Pseudomonas syringae pv. tomato hijacks the Arabidopsis abscisic acid signalling pathway to cause disease. The EMBO Journal, 26(5), 1434-1443. doi:10.1038/sj.emboj.7601575Mine, A., Berens, M. L., Nobori, T., Anver, S., Fukumoto, K., Winkelmüller, T. M., … Tsuda, K. (2017). Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity. Proceedings of the National Academy of Sciences, 114(28), 7456-7461. doi:10.1073/pnas.1702613114Peng, Z., Hu, Y., Zhang, J., Huguet-Tapia, J. C., Block, A. K., Park, S., … White, F. F. (2019). Xanthomonas translucens commandeers the host rate-limiting step in ABA biosynthesis for disease susceptibility. Proceedings of the National Academy of Sciences, 116(42), 20938-20946. doi:10.1073/pnas.1911660116Chen, W., Provart, N. J., Glazebrook, J., Katagiri, F., Chang, H.-S., Eulgem, T., … Zhu, T. (2002). Expression Profile Matrix of Arabidopsis Transcription Factor Genes Suggests Their Putative Functions in Response to Environmental Stresses[W]. The Plant Cell, 14(3), 559-574. doi:10.1105/tpc.010410Anderson, J. P., Badruzsaufari, E., Schenk, P. M., Manners, J. M., Desmond, O. J., Ehlert, C., … Kazan, K. (2004). Antagonistic Interaction between Abscisic Acid and Jasmonate-Ethylene Signaling Pathways Modulates Defense Gene Expression and Disease Resistance in Arabidopsis. The Plant Cell, 16(12), 3460-3479. doi:10.1105/tpc.104.025833Yang, Z., Tian, L., Latoszek-Green, M., Brown, D., & Wu, K. (2005). Arabidopsis ERF4 is a transcriptional repressor capable of modulating ethylene and abscisic acid responses. Plant Molecular Biology, 58(4), 585-596. doi:10.1007/s11103-005-7294-5Dittrich, M., Mueller, H. M., Bauer, H., Peirats-Llobet, M., Rodriguez, P. L., Geilfus, C.-M., … Hedrich, R. (2019). The role of Arabidopsis ABA receptors from the PYR/PYL/RCAR family in stomatal acclimation and closure signal integration. Nature Plants, 5(9), 1002-1011. doi:10.1038/s41477-019-0490-0Hubbard, K. E., Nishimura, N., Hitomi, K., Getzoff, E. D., & Schroeder, J. I. (2010). Early abscisic acid signal transduction mechanisms: newly discovered components and newly emerging questions. Genes & Development, 24(16), 1695-1708. doi:10.1101/gad.1953910Klingler, J. P., Batelli, G., & Zhu, J.-K. (2010). ABA receptors: the START of a new paradigm in phytohormone signalling. Journal of Experimental Botany, 61(12), 3199-3210. doi:10.1093/jxb/erq151Raghavendra, A. S., Gonugunta, V. K., Christmann, A., & Grill, E. (2010). ABA perception and signalling. Trends in Plant Science, 15(7), 395-401. doi:10.1016/j.tplants.2010.04.006Umezawa, T., Sugiyama, N., Mizoguchi, M., Hayashi, S., Myouga, F., Yamaguchi-Shinozaki, K., … Shinozaki, K. (2009). Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis. Proceedings of the National Academy of Sciences, 106(41), 17588-17593. doi:10.1073/pnas.0907095106Vlad, F., Rubio, S., Rodrigues, A., Sirichandra, C., Belin, C., Robert, N., … Merlot, S. (2009). Protein Phosphatases 2C Regulate the Activation of the Snf1-Related Kinase OST1 by Abscisic Acid inArabidopsis . The Plant Cell, 21(10), 3170-3184. doi:10.1105/tpc.109.069179Fujii, H., Chinnusamy, V., Rodrigues, A., Rubio, S., Antoni, R., Park, S.-Y., … Zhu, J.-K. (2009). In vitro reconstitution of an abscisic acid signalling pathway. Nature, 462(7273), 660-664. doi:10.1038/nature08599Ma, Y., Szostkiewicz, I., Korte, A., Moes, D., Yang, Y., Christmann, A., & Grill, E. (2009). Regulators of PP2C Phosphatase Activity Function as Abscisic Acid Sensors. Science, 324(5930), 1064-1068. doi:10.1126/science.1172408Park, S.-Y., Fung, P., Nishimura, N., Jensen, D. R., Fujii, H., Zhao, Y., … Cutler, S. R. (2009). Abscisic Acid Inhibits Type 2C Protein Phosphatases via the PYR/PYL Family of START Proteins. Science, 324(5930), 1068-1071. doi:10.1126/science.1173041Umezawa, T., Sugiyama, N., Takahashi, F., Anderson, J. C., Ishihama, Y., Peck, S. C., & Shinozaki, K. (2013). Genetics and Phosphoproteomics Reveal a Protein Phosphorylation Network in the Abscisic Acid Signaling Pathway in Arabidopsis thaliana. Science Signaling, 6(270). doi:10.1126/scisignal.2003509Gonzalez-Guzman, M., Pizzio, G. A., Antoni, R., Vera-Sirera, F., Merilo, E., Bassel, G. W., … Rodriguez, P. L. (2012). Arabidopsis PYR/PYL/RCAR Receptors Play a Major Role in Quantitative Regulation of Stomatal Aperture and Transcriptional Response to Abscisic Acid. The Plant Cell, 24(6), 2483-2496. doi:10.1105/tpc.112.098574González-Guzmán, M., Rodríguez, L., Lorenzo-Orts, L., Pons, C., Sarrión-Perdigones, A., Fernández, M. A., … Rodríguez, P. L. (2014). Tomato PYR/PYL/RCAR abscisic acid receptors show high expression in root, differential sensitivity to the abscisic acid agonist quinabactin, and the capability to enhance plant drought resistance. Journal of Experimental Botany, 65(15), 4451-4464. doi:10.1093/jxb/eru219Helander, J. D. M., Vaidya, A. S., & Cutler, S. R. (2016). Chemical manipulation of plant water use. Bioorganic & Medicinal Chemistry, 24(3), 493-500. doi:10.1016/j.bmc.2015.11.010Antoni, R., Gonzalez-Guzman, M., Rodriguez, L., Rodrigues, A., Pizzio, G. A., & Rodriguez, P. L. (2011). Selective Inhibition of Clade A Phosphatases Type 2C by PYR/PYL/RCAR Abscisic Acid Receptors    . Plant Physiology, 158(2), 970-980. doi:10.1104/pp.111.188623Tischer, S. V., Wunschel, C., Papacek, M., Kleigrewe, K., Hofmann, T., Christmann, A., & Grill, E. (2017). Combinatorial interaction network of abscisic acid receptors and coreceptors fromArabidopsis thaliana. Proceedings of the National Academy of Sciences, 114(38), 10280-10285. doi:10.1073/pnas.1706593114Antoni, R., Gonzalez-Guzman, M., Rodriguez, L., Peirats-Llobet, M., Pizzio, G. A., Fernandez, M. A., … Rodriguez, P. L. (2012). PYRABACTIN RESISTANCE1-LIKE8 Plays an Important Role for the Regulation of Abscisic Acid Signaling in Root      . Plant Physiology, 161(2), 931-941. doi:10.1104/pp.112.208678Fujii, H., Verslues, P. E., & Zhu, J.-K. (2007). Identification of Two Protein Kinases Required for Abscisic Acid Regulation of Seed Germination, Root Growth, and Gene Expression in Arabidopsis. The Plant Cell, 19(2), 485-494. doi:10.1105/tpc.106.048538García-Andrade, J., Ramírez, V., López, A., & Vera, P. (2013). Mediated Plastid RNA Editing in Plant Immunity. PLoS Pathogens, 9(10), e1003713. doi:10.1371/journal.ppat.1003713Rubio, S., Rodrigues, A., Saez, A., Dizon, M. B., Galle, A., Kim, T.-H., … Rodriguez, P. L. (2009). Triple Loss of Function of Protein Phosphatases Type 2C Leads to Partial Constitutive Response to Endogenous Abscisic Acid      . Plant Physiology, 150(3), 1345-1355. doi:10.1104/pp.109.137174Schweighofer, A., Hirt, H., & Meskiene, I. (2004). Plant PP2C phosphatases: emerging functions in stress signaling. Trends in Plant Science, 9(5), 236-243. doi:10.1016/j.tplants.2004.03.007Carrasco, J. L. (2003). A novel transcription factor involved in plant defense endowed with protein phosphatase activity. The EMBO Journal, 22(13), 3376-3384. doi:10.1093/emboj/cdg323Carrasco, J. L., Castelló, M. J., Naumann, K., Lassowskat, I., Navarrete-Gómez, M., Scheel, D., & Vera, P. (2014). Arabidopsis Protein Phosphatase DBP1 Nucleates a Protein Network with a Role in Regulating Plant Defense. PLoS ONE, 9(3), e90734. doi:10.1371/journal.pone.0090734Clarke, J. D., Volko, S. M., Ledford, H., Ausubel, F. M., & Dong, X. (2000). Roles of Salicylic Acid, Jasmonic Acid, and Ethylene in cpr-Induced Resistance in Arabidopsis. The Plant Cell, 12(11), 2175-2190. doi:10.1105/tpc.12.11.2175Wildermuth, M. C., Dewdney, J., Wu, G., & Ausubel, F. M. (2001). Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature, 414(6863), 562-565. doi:10.1038/35107108Garcion, C., Lohmann, A., Lamodière, E., Catinot, J., Buchala, A., Doermann, P., & Métraux, J.-P. (2008). Characterization and Biological Function of the ISOCHORISMATE SYNTHASE2 Gene of Arabidopsis. Plant Physiology, 147(3), 1279-1287. doi:10.1104/pp.108.119420Mauch-Mani, B., Baccelli, I., Luna, E., & Flors, V. (2017). Defense Priming: An Adaptive Part of Induced Resistance. Annual Review of Plant Biology, 68(1), 485-512. doi:10.1146/annurev-arplant-042916-041132Gaffney, T., Friedrich, L., Vernooij, B., Negrotto, D., Nye, G., Uknes, S., … Ryals, J. (1993). Requirement of Salicylic Acid for the Induction of Systemic Acquired Resistance. Science, 261(5122), 754-756. doi:10.1126/science.261.5122.754Cheng, W.-H., Endo, A., Zhou, L., Penney, J., Chen, H.-C., Arroyo, A., … Sheen, J. (2002). A Unique Short-Chain Dehydrogenase/Reductase in Arabidopsis Glucose Signaling and Abscisic Acid Biosynthesis and Functions. The Plant Cell, 14(11), 2723-2743. doi:10.1105/tpc.006494Koiwai, H., Nakaminami, K., Seo, M., Mitsuhashi, W., Toyomasu, T., & Koshiba, T. (2004). Tissue-Specific Localization of an Abscisic Acid Biosynthetic Enzyme, AAO3, in Arabidopsis. Plant Physiology, 134(4), 1697-1707. doi:10.1104/pp.103.036970Endo, A., Koshiba, T., Kamiya, Y., & Nambara, E. (2008). Vascular system is a node of systemic stress responses. Plant Signaling & Behavior, 3(12), 1138-1140. doi:10.4161/psb.3.12.7145Endo, A., Sawada, Y., Takahashi, H., Okamoto, M., Ikegami, K., Koiwai, H., … Nambara, E. (2008). Drought Induction of Arabidopsis 9-cis-Epoxycarotenoid Dioxygenase Occurs in Vascular Parenchyma Cells    . Plant Physiology, 147(4), 1984-1993. doi:10.1104/pp.108.116632Alvarez, M. E., Pennell, R. I., Meijer, P.-J., Ishikawa, A., Dixon, R. A., & Lamb, C. (1998). Reactive Oxygen Intermediates Mediate a Systemic Signal Network in the Establishment of Plant Immunity. Cell, 92(6), 773-784. doi:10.1016/s0092-8674(00)81405-1Yu, A., Lepere, G., Jay, F., Wang, J., Bapaume, L., Wang, Y., … Navarro, L. (2013). Dynamics and biological relevance of DNA demethylation in Arabidopsis antibacterial defense. Proceedings of the National Academy of Sciences, 110(6), 2389-2394. doi:10.1073/pnas.1211757110Flors, V., Ton, J., Van Doorn, R., Jakab, G., García-Agustín, P., & Mauch-Mani, B. (2007). Interplay between JA, SA and ABA signalling during basal and induced resistance against Pseudomonas syringae and Alternaria brassicicola. The Plant Journal, 54(1), 81-92. doi:10.1111/j.1365-313x.2007.03397.xPétriacq, P., Stassen, J. H. M., & Ton, J. (2016). Spore Density Determines Infection Strategy by the Plant Pathogenic Fungus Plectosphaerella cucumerina. Plant Physiology, 170(4), 2325-2339. doi:10.1104/pp.15.00551Koornneef, A., & Pieterse, C. M. J. (2008). Cross Talk in Defense Signaling. Plant Physiology, 146(3), 839-844. doi:10.1104/pp.107.112029Ton, J., Flors, V., & Mauch-Mani, B. (2009). The multifaceted role of ABA in disease resistance. Trends in Plant Science, 14(6), 310-317. doi:10.1016/j.tplants.2009.03.006De Vleesschauwer, D., Yang, Y., Vera Cruz, C., & Höfte, M. (2010). Abscisic Acid-Induced Resistance against the Brown Spot Pathogen Cochliobolus miyabeanus in Rice Involves MAP Kinase-Mediated Repression of Ethylene Signaling      . Plant Physiology, 152(4), 2036-2052. doi:10.1104/pp.109.152702De Torres Zabala, M., Bennett, M. H., Truman, W. H., & Grant, M. R. (2009). Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses. The Plant Journal, 59(3), 375-386. doi:10.1111/j.1365-313x.2009.03875.xBelin, C., de Franco, P.-O., Bourbousse, C., Chaignepain, S., Schmitter, J.-M., Vavasseur, A., … Thomine, S. (2006). Identification of Features Regulating OST1 Kinase Activity and OST1 Function in Guard Cells  . Plant Physiology, 141(4), 1316-1327. doi:10.1104/pp.106.079327Planes, M. D., Niñoles, R., Rubio, L., Bissoli, G., Bueso, E., García-Sánchez, M. J., … Serrano, R. (2014). 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. Journal of Experimental Botany, 66(3), 813-825. doi:10.1093/jxb/eru44

A simplified courtship conditioning protocol to test learning and memory in Drosophila

In Drosophila, a male that has previously been sexually rejected reduces its courtship behavior when confronted again with an unreceptive female. This reduced courting time reflects a memory formation process. Here, we describe a simplified protocol to perform the courtship conditioning assay for assessing the reduced courting time, using regular lab equipment and handmade tools. Every step of the procedure, from raising flies and training to testing and quantification of this memory-related behavior, can be implemented in any practice laboratory.We would like to thank Javier Gil Castillo for its invaluable help and advices in 3D printing. We also thank the flies from Bloomington Stock Center. We would like to thank BioRender (www.biorender.com) for the open-access platform used to create the graphical abstract. This work was supported by the Spanish Research Agency (Ministerio de Innovacion y Ciencia [MICINN]) under the grant PGC2018-094630-B-100 to F.A.M., cofinanced by the European Regional Development Fund (ERDF) to F.A.M. F.A.M. is a recipient of a RyC-2014-14961 contract. B.G.-M. is a recipient of a FPI-UAM predoctoral fellowship, grant number SFPI/2020/00878. C.G.B. is a recipient of a FPU predoctoral fellowship, grant number FPU19/04449 (MEFP). S.P.-F. is a recipient of a JAE intro fellowship, grant number JAEINT_21_02520 (CSIC)

The relationship between diabetes, diabetes-related complications and productive activities among older Europeans

To assess the impact of diabetes and diabetes-related complications on two measures of productivity for people in the labour force and out of it, namely "being afraid health limits ability to work before retirement" and "volunteering". Logistic regressions were run to test the impact of diabetes and its complications on the probability of being afraid health limits work and being a formal volunteer. The longitudinal sample for the former outcome includes 53,631 observations, clustered in 34,393 individuals, aged 50-65 years old whereas the latter consists of 45,384 observations, grouped in 29,104 individuals aged 65 and above across twelve European countries taken from the Survey of Health, Ageing and Retirement in Europe, from 2006 to 2013. Diabetes increased the probability of being afraid health limited work by nearly 11% points, adjusted by clinical complications, and reduced the likelihood of being a formal volunteer by 2.7% points, additionally adjusted by mobility problems. We also found that both the probability of being afraid health limits work and the probability of being a formal volunteer increased during and after the crisis. Moreover, having diabetes had a larger effect on being afraid health limits work during the year 2010, possibly related to the financial crisis. Our findings show that diabetes significantly affects the perception of people regarding the effects of their condition on work, increasing the fear that health limits their ability to work, especially during the crisis year 2010, as well as the participation in volunteering work among retired people

Different approaches to analyze the impact of future climate change on the exploitation of wave energy

The increment of the share of renewable energies in the global mix implies that all renewable energies must be exploited. In this sense, it is necessary to make significant research and investment effort in the particular case of wave energy to reach the degree of maturity of other marine energies in the near future. Apart from the inherent factors that hinder the development of wave energy, such as the non-existence of a market-leading type of capturing device, uncertainties about the available future resource also hamper its growth. In this article, a review of the procedures followed in the literature to deal with the future wave energy resources and their subsequent exploitation is described. These procedures include the evaluation of the best future atmospheric models to drive wave models, the different downscaling techniques to evaluate the resource in large regions with high spatial resolution, and the analysis of the variability of the future energy resource and its future exploitability in a certain region taking into account different types of devices. Additionally, the current state of the art of previous studies dealing with future wave energy resources for different locations worldwide is described. Despite the difficulties involved in studying future wave energy resources, the high technological readiness level of the offshore wind industry, the creation of power generation farms with combined technologies, and the growth of marine aquaculture in the coming years could generate synergies that provide the definitive impulse to achieve the necessary technological development.Agencia Estatal de Investigación | Ref. PID2020‐113245RB‐I00Agencia Estatal de Investigación | Ref. TED2021-129479A-I00Xunta de Galicia | Ref. ED431C 2021/44Agencia Estatal de Investigación | Ref. IJC2020-043745-IAgencia Estatal de Investigación | Ref. PRE2021-097580European Cooperation in Science and TechnologyUniversidade de Vigo/CISU

Expresión de p53, proteína bcl-2 y ki-67 en carcinomas basocelulares

Objetivo: Determinar la expresión de las proteínas p53, bcl-2 y Ki-67 en distintas variantes histológicas del carcinoma basocelular. Diseño del estudio: Estudio piloto de variables inmunohistoquímicas (p53, Bcl-2 y ki67) en 20 carcinomas basocelulares diagnosticados y tratados a lo largo de un periodo de 9 meses. Resultados: La inmunotinción fue positiva en el 35% de los casos para la proteína p53 y en el 70% para la proteína Bcl-2. La expresión proteica de Ki-67 osciló entre un mínimo de 0% y un máximo de 60%. Conclusiones: Podríamos concluir que el índice de proliferación celular medido con el anticuerpo Ki-67 es negativa en las formas nodulares y positiva en las no nodulares, la expresión de la proteína Bcl-2 es débilmente positiva en las variantes no nodulares y por último la expresión de p53 mutado si bien se ve en ambos grupos, tiene mayor expresión en las formas no nodulares. Se necesitarían estudios con mayor volumen de pacientes y grupo control para que estos resultados sean estadísticamente significativos

What does the freshwater clam, Corbicula largillierti, have to tell us about chlorothalonil effects?

Chlorothalonil (CLT) is a broad spectrum, and non-systemic fungicide applied in foliar structures to prevent and treat pathogens. This compound reaches to aquatic environments and affects the biota. In this context, the main goal of this study was to assess the effects of CLT at biochemical, tissular, and individual levels of biological organization using the invasive bivalve Corbicula largillierti as a bioindicator species. Clams were exposed to different sublethal concentrations (0, 10, 20 and 50 µg. L−1 CLT) for 96 h. At biochemical level, the enzymatic activity (Glutathione-s-Transferase, Catalase, Acetyl-, Butiryl- and Carboxyl-esterases) and lipid peroxidation were measured in gills and the visceral mass. Also, the digestive gland morphometry through quantitative histological indexes was registered at the tissular level. Finally, filtering activity and burial behavior at the individual level were measured. At the highest CLT concentration, the most significant changes were observed in enzymatic activity (except for butyrylcholinesterase), lipid peroxidation and in digestive gland morphometry. It was also registered increases of the filtering activity and the latency time to burial. Most of the biomarkers assessed showed significant responses under CLT exposure. Therefore, taking into account that C. largillierti was affected by CLT, it can be expected that other species could be in a potential risk if this fungicide is present in freshwater systems.Fil: Reyna, Paola Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Albá, M. L.. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Rodriguez, Florencia Anahi. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; ArgentinaFil: Gonzalez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pegoraro, César Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaFil: Hued, Andrea Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Tatian, Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; ArgentinaFil: Ballesteros, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentin

Estudio clínico y epidemiológico de las enfermedades ampollosas autoinmunes en la Cátedra de Dermatología de la Facultad de Ciencias Médicas de la Universidad Nacional de Asunción. Años 2002 – 2007

Introducción: Las enfermedades ampollosas autoinmunes constituyen un grupo de entidades relativamente infrecuentes caracterizadas por la presencia de ampollas y originadas por un mecanismo autoinmune. Se clasifican en intraepidérmicas y subepidérmicas. Objetivo: Describir la frecuencia y las características clínicas de los pacientes con enfermedades ampollares autoinmunes en la Cátedra de Dermatología del Hospital de Clínicas. FCM - UNA. Clasificar y subclasificar los tipos de enfermedades ampollares autoinmunes. Material y Método: El presente trabajo es un estudio descriptivo de corte trasversal, retrospectivo de 3000 consultas de la Cátedra de Dermatología del Hospital de Clínicas en el periodo 2002-2007. Resultado: Se encontraron 71 pacientes con enfermedades ampollares autoinmunes que hacen un 2,73% de frecuencia. Siendo el Pénfigo Foliáceo más frecuentes con 36 pacientes que hacen un 56,7%. Conclusión: Las enfermedades ampollares constituyeron una patología de consulta importante en la Cátedra de Dermatología del Hospital de Clínicas

AI: Can It Make a Difference to the Predictive Value of Ultrasound Breast Biopsy?

(1) Background: This study aims to compare the ground truth (pathology results) against the BI-RADS classification of images acquired while performing breast ultrasound diagnostic examinations that led to a biopsy and against the result of processing the same images through the AI algorithm KOIOS DS TM (KOIOS). (2) Methods: All results of biopsies performed with ultrasound guidance during 2019 were recovered from the pathology department. Readers selected the image which better represented the BI-RADS classification, confirmed correlation to the biopsied image, and submitted it to the KOIOS AI software. The results of the BI-RADS classification of the diagnostic study performed at our institution were set against the KOIOS classification and both were compared to the pathology reports. (3) Results: 403 cases were included in this study. Pathology rendered 197 malignant and 206 benign reports. Four biopsies on BI-RADS 0 and two images are included. Of fifty BI-RADS 3 cases biopsied, only seven rendered cancers. All but one had a positive or suspicious cytology; all were classified as suspicious by KOIOS. Using KOIOS, 17 B3 biopsies could have been avoided. Of 347 BI-RADS 4, 5, and 6 cases, 190 were malignant (54.7%). Because only KOIOS suspicious and probably malignant categories should be biopsied, 312 biopsies would have resulted in 187 malignant lesions (60%), but 10 cancers would have been missed. (4) Conclusions: KOIOS had a higher ratio of positive biopsies in this selected case study vis-à-vis the BI-RADS 4, 5 and 6 categories. A large number of biopsies in the BI-RADS 3 category could have been avoided