Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation

Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations

Treatment of patients with COPD and recurrent exacerbations : the role of infection and inflammation

Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations

Gibberellins negatively modulate ovule number in plants

[EN] Ovule formation is a complex developmental process in plants, with a strong impact on the production of seeds. Ovule primordia initiation is controlled by a gene network, including components of the signaling pathways of auxin, brassinosteroids and cytokinins. By contrast, gibberellins (GAs) and DELLA proteins, the negative regulators of GA signaling, have never been shown to be involved in ovule initiation. Here, we provide molecular and genetic evidence that points to DELLA proteins as novel players in the determination of ovule number in Arabidopsis and in species of agronomic interest, such as tomato and rapeseed, adding a new layer of complexity to this important developmental process. DELLA activity correlates positively with ovule number, acting as a positive factor for ovule initiation. In addition, ectopic expression of a dominant DELLA in the placenta is sufficient to increase ovule number. The role of DELLA proteins in ovule number does not appear to be related to auxin transport or signaling in the ovule primordia. Possible crosstalk between DELLA proteins and the molecular and hormonal network controlling ovule initiation is also discussed.This work was supported by grants from the Ministerio de Economia y Competitividad and the European Regional Development Fund (BIO2014-55946) and Generalitat Valenciana (ACOMP/2014/106) to M.A.P.-A, from the National Science Foundation (MCB-0923727) to J.M.A., and from the National Institutes of Health (R01GM112976-01A1) and the Saltman Endowed Chair in Science and Education to M.F.Y. Deposited in PMC for release after 12 months.Gómez Jiménez, MD.; Barro-Trastoy, D.; Escoms, E.; Saura-Sanchez, M.; Sanchez, I.; Briones-Moreno, A.; Vera Sirera, FJ.... (2018). Gibberellins negatively modulate ovule number in plants. Development. 145(13). https://doi.org/10.1242/dev.163865S14513Anders, S., & Huber, W. (2010). Differential expression analysis for sequence count data. Genome Biology, 11(10). doi:10.1186/gb-2010-11-10-r106Bai, M.-Y., Shang, J.-X., Oh, E., Fan, M., Bai, Y., Zentella, R., … Wang, Z.-Y. (2012). Brassinosteroid, gibberellin and phytochrome impinge on a common transcription module in Arabidopsis. Nature Cell Biology, 14(8), 810-817. doi:10.1038/ncb2546Balanzà, V., Martínez-Fernández, I., Sato, S., Yanofsky, M. F., Kaufmann, K., Angenent, G. C., … Ferrándiz, C. (2018). Genetic control of meristem arrest and life span in Arabidopsis by a FRUITFULL-APETALA2 pathway. Nature Communications, 9(1). doi:10.1038/s41467-018-03067-5Bartrina, I., Otto, E., Strnad, M., Werner, T., & Schmülling, T. (2011). Cytokinin Regulates the Activity of Reproductive Meristems, Flower Organ Size, Ovule Formation, and Thus Seed Yield in Arabidopsis thaliana. The Plant Cell, 23(1), 69-80. doi:10.1105/tpc.110.079079Bencivenga, S., Simonini, S., Benková, E., & Colombo, L. (2012). The Transcription Factors BEL1 and SPL Are Required for Cytokinin and Auxin Signaling During Ovule Development in Arabidopsis. The Plant Cell, 24(7), 2886-2897. doi:10.1105/tpc.112.100164Benková, E., Michniewicz, M., Sauer, M., Teichmann, T., Seifertová, D., Jürgens, G., & Friml, J. (2003). Local, Efflux-Dependent Auxin Gradients as a Common Module for Plant Organ Formation. Cell, 115(5), 591-602. doi:10.1016/s0092-8674(03)00924-3Carbonell-Bejerano, P., Urbez, C., Carbonell, J., Granell, A., & Perez-Amador, M. A. (2010). A Fertilization-Independent Developmental Program Triggers Partial Fruit Development and Senescence Processes in Pistils of Arabidopsis. Plant Physiology, 154(1), 163-172. doi:10.1104/pp.110.160044Carrera, E., Ruiz-Rivero, O., Peres, L. E. P., Atares, A., & Garcia-Martinez, J. L. (2012). Characterization of the procera Tomato Mutant Shows Novel Functions of the SlDELLA Protein in the Control of Flower Morphology, Cell Division and Expansion, and the Auxin-Signaling Pathway during Fruit-Set and Development. Plant Physiology, 160(3), 1581-1596. doi:10.1104/pp.112.204552Ceccato, L., Masiero, S., Sinha Roy, D., Bencivenga, S., Roig-Villanova, I., Ditengou, F. A., … Colombo, L. (2013). Maternal Control of PIN1 Is Required for Female Gametophyte Development in Arabidopsis. PLoS ONE, 8(6), e66148. doi:10.1371/journal.pone.0066148Christensen, C. A., King, E. J., Jordan, J. R., & Drews, G. N. (1997). Megagametogenesis in Arabidopsis wild type and the Gf mutant. Sexual Plant Reproduction, 10(1), 49-64. doi:10.1007/s004970050067Clough, S. J., & Bent, A. F. (1998). Floral dip: a simplified method forAgrobacterium-mediated transformation ofArabidopsis thaliana. The Plant Journal, 16(6), 735-743. doi:10.1046/j.1365-313x.1998.00343.xCucinotta, M., Colombo, L., & Roig-Villanova, I. (2014). Ovule development, a new model for lateral organ formation. Frontiers in Plant Science, 5. doi:10.3389/fpls.2014.00117Cucinotta, M., Manrique, S., Guazzotti, A., Quadrelli, N. E., Mendes, M. A., Benkova, E., & Colombo, L. (2016). Cytokinin response factors integrate auxin and cytokinin pathways for female reproductive organ development. Development, 143(23), 4419-4424. doi:10.1242/dev.143545Curtis, M. D., & Grossniklaus, U. (2003). A Gateway Cloning Vector Set for High-Throughput Functional Analysis of Genes in Planta. Plant Physiology, 133(2), 462-469. doi:10.1104/pp.103.027979Cutcliffe, J. W., Hellmann, E., Heyl, A., & Rashotte, A. M. (2011). CRFs form protein–protein interactions with each other and with members of the cytokinin signalling pathway in Arabidopsis via the CRF domain. Journal of Experimental Botany, 62(14), 4995-5002. doi:10.1093/jxb/err199Czechowski, T., Stitt, M., Altmann, T., Udvardi, M. K., & Scheible, W.-R. (2005). Genome-Wide Identification and Testing of Superior Reference Genes for Transcript Normalization in Arabidopsis. Plant Physiology, 139(1), 5-17. doi:10.1104/pp.105.063743Davière, J.-M., & Achard, P. (2016). A Pivotal Role of DELLAs in Regulating Multiple Hormone Signals. Molecular Plant, 9(1), 10-20. doi:10.1016/j.molp.2015.09.011De Vleesschauwer, D., Van Buyten, E., Satoh, K., Balidion, J., Mauleon, R., Choi, I.-R., … Höfte, M. (2012). Brassinosteroids Antagonize Gibberellin- and Salicylate-Mediated Root Immunity in Rice. Plant Physiology, 158(4), 1833-1846. doi:10.1104/pp.112.193672Deveaux, Y., Toffano-Nioche, C., Claisse, G., Thareau, V., Morin, H., Laufs, P., … Lecharny, A. (2008). Genes of the most conserved WOX clade in plants affect root and flower development in Arabidopsis. BMC Evolutionary Biology, 8(1), 291. doi:10.1186/1471-2148-8-291Dill, A., Jung, H.-S., & Sun, T. -p. (2001). The DELLA motif is essential for gibberellin-induced degradation of RGA. Proceedings of the National Academy of Sciences, 98(24), 14162-14167. doi:10.1073/pnas.251534098Dorcey, E., Urbez, C., Blázquez, M. A., Carbonell, J., & Perez-Amador, M. A. (2009). Fertilization-dependent auxin response in ovules triggers fruit development through the modulation of gibberellin metabolism in Arabidopsis. The Plant Journal, 58(2), 318-332. doi:10.1111/j.1365-313x.2008.03781.xElliott, R. C., Betzner, A. S., Huttner, E., Oakes, M. P., Tucker, W. Q., Gerentes, D., … Smyth, D. R. (1996). AINTEGUMENTA, an APETALA2-like gene of Arabidopsis with pleiotropic roles in ovule development and floral organ growth. The Plant Cell, 8(2), 155-168. doi:10.1105/tpc.8.2.155Endress, P. K. (2011). Angiosperm ovules: diversity, development, evolution. Annals of Botany, 107(9), 1465-1489. doi:10.1093/aob/mcr120Ezura, K., Ji-Seong, K., Mori, K., Suzuki, Y., Kuhara, S., Ariizumi, T., & Ezura, H. (2017). Genome-wide identification of pistil-specific genes expressed during fruit set initiation in tomato (Solanum lycopersicum). PLOS ONE, 12(7), e0180003. doi:10.1371/journal.pone.0180003Ferreira, L. G., de Alencar Dusi, D. M., Irsigler, A. S. T., Gomes, A. C. M. M., Mendes, M. A., Colombo, L., & de Campos Carneiro, V. T. (2017). GID1 expression is associated with ovule development of sexual and apomictic plants. Plant Cell Reports, 37(2), 293-306. doi:10.1007/s00299-017-2230-0Fuentes, S., Ljung, K., Sorefan, K., Alvey, E., Harberd, N. P., & Østergaard, L. (2012). Fruit Growth in Arabidopsis Occurs via DELLA-Dependent and DELLA-Independent Gibberellin Responses. The Plant Cell, 24(10), 3982-3996. doi:10.1105/tpc.112.103192Galbiati, F., Sinha Roy, D., Simonini, S., Cucinotta, M., Ceccato, L., Cuesta, C., … Colombo, L. (2013). An integrative model of the control of ovule primordia formation. The Plant Journal, 76(3), 446-455. doi:10.1111/tpj.12309Gallego-Bartolome, J., Minguet, E. G., Grau-Enguix, F., Abbas, M., Locascio, A., Thomas, S. G., … Blazquez, M. A. (2012). Molecular mechanism for the interaction between gibberellin and brassinosteroid signaling pathways in Arabidopsis. Proceedings of the National Academy of Sciences, 109(33), 13446-13451. doi:10.1073/pnas.1119992109Gallego-Giraldo, C., Hu, J., Urbez, C., Gomez, M. D., Sun, T., & Perez-Amador, M. A. (2014). Role of the gibberellin receptors GID1 during fruit-set in Arabidopsis. The Plant Journal, 79(6), 1020-1032. doi:10.1111/tpj.12603García-Hurtado, N., Carrera, E., Ruiz-Rivero, O., López-Gresa, M. P., Hedden, P., Gong, F., & García-Martínez, J. L. (2012). The characterization of transgenic tomato overexpressing gibberellin 20-oxidase reveals induction of parthenocarpic fruit growth, higher yield, and alteration of the gibberellin biosynthetic pathway. Journal of Experimental Botany, 63(16), 5803-5813. doi:10.1093/jxb/ers229Gasser, C. S., Broadhvest, J., & Hauser, B. A. (1998). GENETIC ANALYSIS OF OVULE DEVELOPMENT. Annual Review of Plant Physiology and Plant Molecular Biology, 49(1), 1-24. doi:10.1146/annurev.arplant.49.1.1Gomez, M. D., Ventimilla, D., Sacristan, R., & Perez-Amador, M. A. (2016). Gibberellins Regulate Ovule Integument Development by Interfering with the Transcription Factor ATS. Plant Physiology, 172(4), 2403-2415. doi:10.1104/pp.16.01231Gomez-Mena, C. (2005). Transcriptional program controlled by the floral homeotic gene AGAMOUS during early organogenesis. Development, 132(3), 429-438. doi:10.1242/dev.01600Gupta, R., & Chakrabarty, S. K. (2013). Gibberellic acid in plant. Plant Signaling & Behavior, 8(9), e25504. doi:10.4161/psb.25504Hassidim, M., Harir, Y., Yakir, E., Kron, I., & Green, R. M. (2009). Over-expression of CONSTANS-LIKE 5 can induce flowering in short-day grown Arabidopsis. Planta, 230(3), 481-491. doi:10.1007/s00425-009-0958-7Heisler, M. G., Ohno, C., Das, P., Sieber, P., Reddy, G. V., Long, J. A., & Meyerowitz, E. M. (2005). Patterns of Auxin Transport and Gene Expression during Primordium Development Revealed by Live Imaging of the Arabidopsis Inflorescence Meristem. Current Biology, 15(21), 1899-1911. doi:10.1016/j.cub.2005.09.052Huang, H.-Y., Jiang, W.-B., Hu, Y.-W., Wu, P., Zhu, J.-Y., Liang, W.-Q., … Lin, W.-H. (2013). BR Signal Influences Arabidopsis Ovule and Seed Number through Regulating Related Genes Expression by BZR1. Molecular Plant, 6(2), 456-469. doi:10.1093/mp/sss070Khanna, R., Kronmiller, B., Maszle, D. R., Coupland, G., Holm, M., Mizuno, T., & Wu, S.-H. (2009). The Arabidopsis B-Box Zinc Finger Family. The Plant Cell, 21(11), 3416-3420. doi:10.1105/tpc.109.069088Li, Q.-F., Wang, C., Jiang, L., Li, S., Sun, S. S. M., & He, J.-X. (2012). An Interaction Between BZR1 and DELLAs Mediates Direct Signaling Crosstalk Between Brassinosteroids and Gibberellins in Arabidopsis. Science Signaling, 5(244), ra72-ra72. doi:10.1126/scisignal.2002908Mantegazza, O., Gregis, V., Mendes, M. A., Morandini, P., Alves-Ferreira, M., Patreze, C. M., … Colombo, L. (2014). Analysis of the arabidopsis REM gene family predicts functions during flower development. Annals of Botany, 114(7), 1507-1515. doi:10.1093/aob/mcu124La Rosa, N. M. -d., Sotillo, B., Miskolczi, P., Gibbs, D. J., Vicente, J., Carbonero, P., … Blazquez, M. A. (2014). Large-Scale Identification of Gibberellin-Related Transcription Factors Defines Group VII ETHYLENE RESPONSE FACTORS as Functional DELLA Partners. PLANT PHYSIOLOGY, 166(2), 1022-1032. doi:10.1104/pp.114.244723Marín-de la Rosa, N., Pfeiffer, A., Hill, K., Locascio, A., Bhalerao, R. P., Miskolczi, P., … Alabadí, D. (2015). Genome Wide Binding Site Analysis Reveals Transcriptional Coactivation of Cytokinin-Responsive Genes by DELLA Proteins. PLOS Genetics, 11(7), e1005337. doi:10.1371/journal.pgen.1005337Matias-Hernandez, L., Battaglia, R., Galbiati, F., Rubes, M., Eichenberger, C., Grossniklaus, U., … Colombo, L. (2010). VERDANDI Is a Direct Target of the MADS Domain Ovule Identity Complex and Affects Embryo Sac Differentiation in Arabidopsis. The Plant Cell, 22(6), 1702-1715. doi:10.1105/tpc.109.068627McAbee, J. M., Hill, T. A., Skinner, D. J., Izhaki, A., Hauser, B. A., Meister, R. J., … Gasser, C. S. (2006). ABERRANT TESTA SHAPE encodes a KANADI family member, linking polarity determination to separation and growth of Arabidopsis ovule integuments. The Plant Journal, 46(3), 522-531. doi:10.1111/j.1365-313x.2006.02717.xMoore, I., Samalova, M., & Kurup, S. (2006). Transactivated and chemically inducible gene expression in plants. The Plant Journal, 45(4), 651-683. doi:10.1111/j.1365-313x.2006.02660.xMoubayidin, L., Perilli, S., Dello Ioio, R., Di Mambro, R., Costantino, P., & Sabatini, S. (2010). The Rate of Cell Differentiation Controls the Arabidopsis Root Meristem Growth Phase. Current Biology, 20(12), 1138-1143. doi:10.1016/j.cub.2010.05.035Murashige, T., & Skoog, F. (1962). A Revised Medium for Rapid Growth and Bio Assays with Tobacco Tissue Cultures. Physiologia Plantarum, 15(3), 473-497. doi:10.1111/j.1399-3054.1962.tb08052.xNole-Wilson, S., Azhakanandam, S., & Franks, R. G. (2010). Polar auxin transport together with AINTEGUMENTA and REVOLUTA coordinate early Arabidopsis gynoecium development. Developmental Biology, 346(2), 181-195. doi:10.1016/j.ydbio.2010.07.016Pagnussat, G. C. (2005). Genetic and molecular identification of genes required for female gametophyte development and function in Arabidopsis. Development, 132(3), 603-614. doi:10.1242/dev.01595Peng, J., Carol, P., Richards, D. E., King, K. E., Cowling, R. J., Murphy, G. P., & Harberd, N. P. (1997). The Arabidopsis GAI gene defines a signaling pathway that negatively regulates gibberellin responses . Genes & Development, 11(23), 3194-3205. doi:10.1101/gad.11.23.3194Plackett, A. R. G., Ferguson, A. C., Powers, S. J., Wanchoo‐Kohli, A., Phillips, A. L., Wilson, Z. A., … Thomas, S. G. (2013). DELLA activity is required for successful pollen development in the Columbia ecotype of Arabidopsis. New Phytologist, 201(3), 825-836. doi:10.1111/nph.12571Porri, A., Torti, S., Romera-Branchat, M., & Coupland, G. (2012). Spatially distinct regulatory roles for gibberellins in the promotion of flowering of Arabidopsis under long photoperiods. Development, 139(12), 2198-2209. doi:10.1242/dev.077164Reyes-Olalde, J. I., Zuñiga-Mayo, V. M., Chávez Montes, R. A., Marsch-Martínez, N., & de Folter, S. (2013). Inside the gynoecium: at the carpel margin. Trends in Plant Science, 18(11), 644-655. doi:10.1016/j.tplants.2013.08.002José Ripoll, J., Bailey, L. J., Mai, Q.-A., Wu, S. L., Hon, C. T., Chapman, E. J., … Yanofsky, M. F. (2015). microRNA regulation of fruit growth. Nature Plants, 1(4). doi:10.1038/nplants.2015.36Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2009). edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26(1), 139-140. doi:10.1093/bioinformatics/btp616Romera-Branchat, M., Ripoll, J. J., Yanofsky, M. F., & Pelaz, S. (2012). TheWOX13homeobox gene promotes replum formation in theArabidopsis thalianafruit. The Plant Journal, 73(1), 37-49. doi:10.1111/tpj.12010Ross, J. J., & Quittenden, L. J. (2016). Interactions between Brassinosteroids and Gibberellins: Synthesis or Signaling? The Plant Cell, 28(4), 829-832. doi:10.1105/tpc.15.00917Schneitz, K., Hulskamp, M., & Pruitt, R. E. (1995). Wild-type ovule development in Arabidopsis thaliana: a light microscope study of cleared whole-mount tissue. The Plant Journal, 7(5), 731-749. doi:10.1046/j.1365-313x.1995.07050731.xSkinner, D. J., & Gasser, C. S. (2009). Expression-based discovery of candidate ovule development regulators through transcriptional profiling of ovule mutants. BMC Plant Biology, 9(1), 29. doi:10.1186/1471-2229-9-29Skinner, D. J. (2004). Regulation of Ovule Development. THE PLANT CELL ONLINE, 16(suppl_1), S32-S45. doi:10.1105/tpc.015933Smyth, D. R., Bowman, J. L., & Meyerowitz, E. M. (1990). Early flower development in Arabidopsis. The Plant Cell, 2(8), 755-767. doi:10.1105/tpc.2.8.755Sun, T. (2010). Gibberellin-GID1-DELLA: A Pivotal Regulatory Module for Plant Growth and Development. Plant Physiology, 154(2), 567-570. doi:10.1104/pp.110.161554Feraru, E., Feraru, M. I., Kleine-Vehn, J., Martinière, A., Mouille, G., Vanneste, S., … Friml, J. (2011). PIN Polarity Maintenance by the Cell Wall in Arabidopsis. Current Biology, 21(4), 338-343. doi:10.1016/j.cub.2011.01.036Sun, Y., Fan, X.-Y., Cao, D.-M., Tang, W., He, K., Zhu, J.-Y., … Wang, Z.-Y. (2010). Integration of Brassinosteroid Signal Transduction with the Transcription Network for Plant Growth Regulation in Arabidopsis. Developmental Cell, 19(5), 765-777. doi:10.1016/j.devcel.2010.10.010Suzuki, H., Park, S.-H., Okubo, K., Kitamura, J., Ueguchi-Tanaka, M., Iuchi, S., … Nakajima, M. (2009). Differential expression and affinities of Arabidopsis gibberellin receptors can explain variation in phenotypes of multiple knock-out mutants. The Plant Journal, 60(1), 48-55. doi:10.1111/j.1365-313x.2009.03936.xSwain, S. M., & Singh, D. P. (2005). Tall tales from sly dwarves: novel functions of gibberellins in plant development. Trends in Plant Science, 10(3), 123-129. doi:10.1016/j.tplants.2005.01.007Tanaka, K., Nakamura, Y., Asami, T., Yoshida, S., Matsuo, T., & Okamoto, S. (2003). Physiological Roles of Brassinosteroids in Early Growth of Arabidopsis: Brassinosteroids Have a Synergistic Relationship with Gibberellin as well as Auxin in Light-Grown Hypocotyl Elongation. Journal of Plant Growth Regulation, 22(3), 259-271. doi:10.1007/s00344-003-0119-3Tong, H., Xiao, Y., Liu, D., Gao, S., Liu, L., Yin, Y., … Chu, C. (2014). Brassinosteroid Regulates Cell Elongation by Modulating Gibberellin Metabolism in Rice. The Plant Cell, 26(11), 4376-4393. doi:10.1105/tpc.114.132092Truernit, E., Bauby, H., Dubreucq, B., Grandjean, O., Runions, J., Barthélémy, J., & Palauqui, J.-C. (2008). High-Resolution Whole-Mount Imaging of Three-Dimensional Tissue Organization and Gene Expression Enables the Study of Phloem Development and Structure in Arabidopsis. The Plant Cell, 20(6), 1494-1503. doi:10.1105/tpc.107.056069Unterholzner, S. J., Rozhon, W., Papacek, M., Ciomas, J., Lange, T., Kugler, K. G., … Poppenberger, B. (2015). Brassinosteroids Are Master Regulators of Gibberellin Biosynthesis in Arabidopsis. The Plant Cell, 27(8), 2261-2272. doi:10.1105/tpc.15.00433Vera-Sirera, F. , Gomez, M. D. and Perez-Amador, M. A. (2015). DELLA proteins, a group of GRAS transcription regulators, mediate gibberellin signaling. In Plant Transcription Factors: Evolutionary, Structural and Functional Aspects (ed. D. H. Gonzalez ), pp. 313-328. San Diego: Elsevier/Academic Press.Villarino, G. H., Hu, Q., Manrique, S., Flores-Vergara, M., Sehra, B., Robles, L., … Franks, R. G. (2016). Transcriptomic Signature of the SHATTERPROOF2 Expression Domain Reveals the Meristematic Nature of Arabidopsis Gynoecial Medial Domain. Plant Physiology, 171(1), 42-61. doi:10.1104/pp.15.01845Weigel, D. and Glazebrook, J. (2002). Arabidopsis: A laboratory Manual . Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.Yadegari, R. (2004). Female Gametophyte Development. THE PLANT CELL ONLINE, 16(suppl_1), S133-S141. doi:10.1105/tpc.018192Zhang, Z.-L., Ogawa, M., Fleet, C. M., Zentella, R., Hu, J., Heo, J.-O., … Sun, T. (2011). SCARECROW-LIKE 3 promotes gibberellin signaling by antagonizing master growth repressor DELLA in Arabidopsis. Proceedings of the National Academy of Sciences, 108(5), 2160-2165. doi:10.1073/pnas.101223210

Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer

Evolutionary Analysis of DELLA-Associated Transcriptional Networks

[EN] DELLA proteins are transcriptional regulators present in all land plants which have been shown to modulate the activity of over 100 transcription factors in Arabidopsis, involved in multiple physiological and developmental processes. It has been proposed that DELLAs transduce environmental information to pre-wired transcriptional circuits because their stability is regulated by gibberellins (GAs), whose homeostasis largely depends on environmental signals. The ability of GAs to promote DELLA degradation coincides with the origin of vascular plants, but the presence of DELLAs in other land plants poses at least two questions: what regulatory properties have DELLAs provided to the behavior of transcriptional networks in land plants, and how has the recruitment of DELLAs by GA signaling affected this regulation. To address these issues, we have constructed gene co-expression networks of four different organisms within the green lineage with different properties regarding DELLAs: Arabidopsis thaliana and Solanum lycopersicum (both with GA- regulated DELLA proteins), Physcomitrella patens (with GA- independent DELLA proteins) and Chlamydomonas reinhardtii (a green alga without DELLA), and we have examined the relative evolution of the subnetworks containing the potential DELLA-dependent transcriptomes. Network analysis indicates a relative increase in parameters associated with the degree of interconnectivity in the DELLA-associated subnetworks of land plants, with a stronger effect in species with GA- regulated DELLA proteins. These results suggest that DELLAs may have played a role in the coordination of multiple transcriptional programs along evolution, and the function of DELLAs as regulatory 'hubs' became further consolidated after their recruitment by GA signaling in higher plants.Work in the laboratories was funded by grants BFU2016-80621-P and BIO2014-52425-P of the Spanish Ministry of Economy, Industry and Competitiveness, and H2020-MSCA-RISE-2014-644435 of the European Union. AB-M and JH-G hold Fellowships of the Spanish Ministry of Education, Culture and Sport FPU14/01941 and FPU15/01756, respectively.Briones-Moreno, A.; Hernández-García, J.; Vargas-Chávez, C.; Romero-Campero FJ; Romero, J.; Valverde, F.; Blazquez Rodriguez, MA. (2017). Evolutionary Analysis of DELLA-Associated Transcriptional Networks. Frontiers in Plant Science. 8(626):1-11. https://doi.org/10.3389/fpls.2017.00626S111862

Regulation of xylem fiber differentiation by gibberellins through DELLA-KNAT1 interaction

[EN] The thickening of plant organs is supported by secondary growth, a process by which new vascular tissues (xylem and phloem) are produced. Xylem is composed of several cell types, including xylary fibers, parenchyma and vessel elements. In Arabidopsis, it has been shown that fibers are promoted by the class-I KNOX gene KNAT1 and the plant hormones gibberellins, and are repressed by a small set of receptor-like kinases; however, we lack a mechanistic framework to integrate their relative contributions. Here, we show that DELLAs, negative elements of the gibberellin signaling pathway, physically interact with KNAT1 and impair its binding to KNAT1-binding sites. Our analysis also indicates that at least 37% of the transcriptome mobilized by KNAT1 is potentially dependent on this interaction, and includes genes involved in secondary cell wall modifications and phenylpropanoid biosynthesis. Moreover, the promotion by constitutive overexpression of KNAT1 of fiber formation and the expression of genes required for fiber differentiation were still reverted by DELLA accumulation, in agreement with post-translational regulation of KNAT1 by DELLA proteins. These results suggest that gibberellins enhance fiber development by promoting KNAT1 activity.This work was funded by the Ministerio de Ciencia y Tecnologia (BFU2016-80621-P, BIO2016-71933-P and BIO2016-79147-R to M.A.B., D.A. and J.A., respectively). A.F-B. and N.B-T. were recipients of a Ministerio de Economia y Competitividad FPI Fellowships (BES-2011-045689 and BES-2014-068868, respectively), and A.S.-M. and M.A.B. acknowledge funding from the European Union (H2020-MSCA-IF-2016-746396). J.A. is supported by a Ramon y Cajal contract from the Ministerio de Economia y Competitividad (RYC-2014-15752).Felipo-Benavent, A.; Urbez Lagunas, C.; Blanco-Touriñán, N.; Serrano Mislata, A.; Baumberger, N.; Achard, P.; Agustí, J.... (2018). Regulation of xylem fiber differentiation by gibberellins through DELLA-KNAT1 interaction. Development. 145(23). https://doi.org/10.1242/dev.164962S1452

In Vivo Near-Infrared Imaging Using Ternary Selenide Semiconductor Nanoparticles with an Uncommon Crystal Structure

The implementation of in vivo fluorescence imaging as a reliable diagnostic imaging modality at the clinical level is still far from reality. Plenty of work remains ahead to provide medical practitioners with solid proof of the potential advantages of this imaging technique. To do so, one of the key objectives is to better the optical performance of dedicated contrast agents, thus improving the resolution and penetration depth achievable. This direction is followed here and the use of a novel AgInSe2 nanoparticle-based contrast agent (nanocapsule) is reported for fluorescence imaging. The use of an Ag2Se seeds-mediated synthesis method allows stabilizing an uncommon orthorhombic crystal structure, which endows the material with emission in the second biological window (1000–1400 nm), where deeper penetration in tissues is achieved. The nanocapsules, obtained via phospholipid-assisted encapsulation of the AgInSe2 nanoparticles, comply with the mandatory requisites for an imaging contrast agent—colloidal stability and negligible toxicity—and show superior brightness compared with widely used Ag2S nanoparticles. Imaging experiments point to the great potential of the novel AgInSe2-based nanocapsules for high-resolution, whole-body in vivo imaging. Their extended permanence time within blood vessels make them especially suitable for prolonged imaging of the cardiovascular system

XIPE: the X-ray Imaging Polarimetry Explorer

X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017 but not selected. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus and two additional GPDs filled with pressurized Ar-DME facing the sun. The Minimum Detectable Polarization is 14 % at 1 mCrab in 10E5 s (2-10 keV) and 0.6 % for an X10 class flare. The Half Energy Width, measured at PANTER X-ray test facility (MPE, Germany) with JET-X optics is 24 arcsec. XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil).Comment: 49 pages, 14 figures, 6 tables. Paper published in Experimental Astronomy http://link.springer.com/journal/1068

Diversidade do campesinato Expressões e categorias

Coleção História Social do Campesinato no Brasil.Volumen 1: Construções identitárias e sociabilidadesVolumen 2: Estratégias de reprodução socialVolumen 1: apresenta a diversidade sociocultural das configurações camponesas no Brasil e suas estratégias de reprodução social. Os artigos aqui reunidos aliam discussão teórica à apresentação de um contexto empírico concreto e dados etnográficos. Em Culturas e sociabilidades, parte-se do pressuposto de que não só a reprodução dos fundamentos econômicos é indispensável à existência e reprodução das sociedades. A relação encontrada entre trabalho e festa e o significado da partilha do alimento como expressão das regras de reciprocidade são alguns dos temas dessa primeira parte, assim como a descrição do trabalho camponês em determinados lugares do Brasil, o universo religioso, retratado com a festa de Nossa Senhora do Rosário, e a “cosmologia cabocla” dos camponeses e pescadores da Amazônia Oriental, do Pará e da ilha de Marajó. A segunda temática, Identidades e territorialidades, trata de situações que trouxeram renovação ao campo de estudos sobre populaçõe rurais e da criação de novos sujeitos políticos. Esses artigos apresentam as preocupações antropológicas em relação às políticas de construção da identidade e aos processos que não ficam restritos ao aspecto local, mas estão relacionados com movimentos maiores dentro do Estado nacional dados pelos novos ordenamentos jurídicos, onde se encaixa a luta pelos chamados “direitos étnicos”.Vol. 2: buscam restituir um debate que responda às demandas de vários setores sociais por uma sistematização do conhecimento acerca destas populações. O resultado é um mosaico que revela a diversidade de realidades historicamente construídas a partir de múltiplas formas de apropriação e usos da terra e demais recursos naturais. Na primeira parte, os capítulos mostram como o controle da terra é feito mediante “normas específicas instituídas para além do código legal vigente”, discutem o processo de ocupação camponesa e sua reprodução no sertão matogrossense e destacam as relações sociais estabelecidas entre os que buscam os meios de existência baseados no criatório. A segunda parte aborda as práticas ecológicas, revelando uma percepção moral da relação com a terra e entre os homens, além de apresentar estratégias de reprodução social que se desenvolvem por meio de práticas diferenciadas. Temos ainda questões sobre territorialidade, diversidade, organização social e cultural e algumas especificidades do campesinato da Amazônia.Na terceira parte, somos convidados a pensar acerca das transformações do rural, da diversidade das formas de existência e sobre o conhecimento aí produzido. Os capítulos destacam, entre outros pontos, as tentativas de “reconversão” por meio da migração, o uso de termos lingüísticos para estudar a mobilidade de atores sociais nos contextos rurais e a intervenção de instituições e organizações políticas que criam e recriam diversas categorias de classificação desses agentes sociai

The Pierre Auger Observatory III: Other Astrophysical Observations

Astrophysical observations of ultra-high-energy cosmic rays with the Pierre Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference, Beijing, China, August 201