The Role of SHI/STY/SRS Genes in Organ Growth and Carpel Development Is Conserved in the Distant Eudicot Species Arabidopsis thaliana and Nicotiana benthamiana

[EN] Carpels are a distinctive feature of angiosperms, the ovule-bearing female reproductive organs that endow them with multiple selective advantages likely linked to the evolutionary success of flowering plants. Gene regulatory networks directing the development of carpel specialized tissues and patterning have been proposed based on genetic and molecular studies carried out in Arabidopsis thaliana. However, studies on the conservation/diversification of the elements and the topology of this network are still scarce. In this work, we have studied the functional conservation of transcription factors belonging to the SHI/STY/SRS family in two distant species within the eudicots, Eschscholzia californica and Nicotiana benthamiana. We have found that the expression patterns of EcSRS-L and NbSRS-L genes during flower development are similar to each other and to those reported for Arabidopsis SHI/STY/SRS genes. We have also characterized the phenotypic effects of NbSRS-L gene inactivation and overexpression in Nicotiana. Our results support the widely conserved role of SHI/STY/SRS genes at the top of the regulatory network directing style and stigma development, specialized tissues specific to the angiosperm carpels, at least within core eudicots, providing new insights on the possible evolutionary origin of the carpels.This work was supported by the Spanish MINECO/FEDER grants no BIO2012-32902 and BIO2015-64531-R to CFe. AG-F was supported by a predoctoral contract of the Generalitat Valenciana (ACIF/2013/044). We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Gomariz, A.; Sánchez-Gerschon, V.; Fourquin, C.; Ferrandiz Maestre, C. (2017). The Role of SHI/STY/SRS Genes in Organ Growth and Carpel Development Is Conserved in the Distant Eudicot Species Arabidopsis thaliana and Nicotiana benthamiana. Frontiers in Plant Science. 8:1-17. https://doi.org/10.3389/fpls.2017.00814S1178Alvarez, J. P., Goldshmidt, A., Efroni, I., Bowman, J. L., & Eshed, Y. (2009). The NGATHA Distal Organ Development Genes Are Essential for Style Specification in Arabidopsis. The Plant Cell, 21(5), 1373-1393. doi:10.1105/tpc.109.065482ALVAREZBUYLLA, E., BENITEZ, M., DAVILA, E., CHAOS, A., ESPINOSASOTO, C., & PADILLALONGORIA, P. (2007). Gene regulatory network models for plant development. Current Opinion in Plant Biology, 10(1), 83-91. doi:10.1016/j.pbi.2006.11.008Ballester, P., & Ferrándiz, C. (2017). Shattering fruits: variations on a dehiscent theme. Current Opinion in Plant Biology, 35, 68-75. doi:10.1016/j.pbi.2016.11.008Bombarely, A., Rosli, H. G., Vrebalov, J., Moffett, P., Mueller, L. A., & Martin, G. B. (2012). A Draft Genome Sequence of Nicotiana benthamiana to Enhance Molecular Plant-Microbe Biology Research. Molecular Plant-Microbe Interactions®, 25(12), 1523-1530. doi:10.1094/mpmi-06-12-0148-taBowman, J. L., Smyth, D. R., & Meyerowitz, E. M. (1989). Genes directing flower development in Arabidopsis. The Plant Cell, 1(1), 37-52. doi:10.1105/tpc.1.1.37Bradley, D., Carpenter, R., Sommer, H., Hartley, N., & Coen, E. (1993). Complementary floral homeotic phenotypes result from opposite orientations of a transposon at the plena locus of antirrhinum. Cell, 72(1), 85-95. doi:10.1016/0092-8674(93)90052-rChávez Montes, R. A., Herrera-Ubaldo, H., Serwatowska, J., & de Folter, S. (2015). Towards a comprehensive and dynamic gynoecium gene regulatory network. Current Plant Biology, 3-4, 3-12. doi:10.1016/j.cpb.2015.08.002Clemente, T. (s. f.). Nicotiana (Nicotiana tobaccum, Nicotiana benthamiana). Agrobacterium Protocols, 143-154. doi:10.1385/1-59745-130-4:143Clough, 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.xColombo, M., Brambilla, V., Marcheselli, R., Caporali, E., Kater, M. M., & Colombo, L. (2010). A new role for the SHATTERPROOF genes during Arabidopsis gynoecium development. Developmental Biology, 337(2), 294-302. doi:10.1016/j.ydbio.2009.10.043Crawford, B. C. W., Ditta, G., & Yanofsky, M. F. (2007). The NTT Gene Is Required for Transmitting-Tract Development in Carpels of Arabidopsis thaliana. Current Biology, 17(13), 1101-1108. doi:10.1016/j.cub.2007.05.079Crawford, B. C. W., & Yanofsky, M. F. (2011). HALF FILLED promotes reproductive tract development and fertilization efficiency in Arabidopsis thaliana. Development, 138(14), 2999-3009. doi:10.1242/dev.067793Curtis, 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.103.027979Davidson, E. H., & Levine, M. S. (2008). Properties of developmental gene regulatory networks. Proceedings of the National Academy of Sciences, 105(51), 20063-20066. doi:10.1073/pnas.0806007105Davies, B., Motte, P., Keck, E., Saedler, H., Sommer, H., & Schwarz-Sommer, Z. (1999). PLENA and FARINELLI: redundancy and regulatory interactions between two Antirrhinum MADS-box factors controlling flower development. The EMBO Journal, 18(14), 4023-4034. doi:10.1093/emboj/18.14.4023Davila-Velderrain, J., Martinez-Garcia, J. C., & Alvarez-Buylla, E. R. (2016). Dynamic network modelling to understand flowering transition and floral patterning. Journal of Experimental Botany, 67(9), 2565-2572. doi:10.1093/jxb/erw123De Lucas, M., & Brady, S. M. (2013). Gene regulatory networks in the Arabidopsis root. Current Opinion in Plant Biology, 16(1), 50-55. doi:10.1016/j.pbi.2012.10.007Dreni, L., Pilatone, A., Yun, D., Erreni, S., Pajoro, A., Caporali, E., … Kater, M. M. (2011). Functional Analysis of All AGAMOUS Subfamily Members in Rice Reveals Their Roles in Reproductive Organ Identity Determination and Meristem Determinacy. The Plant Cell, 23(8), 2850-2863. doi:10.1105/tpc.111.087007Eklund, D. M., Cierlik, I., Ståldal, V., Claes, A. R., Vestman, D., Chandler, J., & Sundberg, E. (2011). Expression of Arabidopsis SHORT INTERNODES/STYLISH Family Genes in Auxin Biosynthesis Zones of Aerial Organs Is Dependent on a GCC Box-Like Regulatory Element. Plant Physiology, 157(4), 2069-2080. doi:10.1104/pp.111.182253Eklund, D. M., Ståldal, V., Valsecchi, I., Cierlik, I., Eriksson, C., Hiratsu, K., … Sundberg, E. (2010). The Arabidopsis thaliana STYLISH1 Protein Acts as a Transcriptional Activator Regulating Auxin Biosynthesis. The Plant Cell, 22(2), 349-363. doi:10.1105/tpc.108.064816Eklund, D. M., Thelander, M., Landberg, K., Staldal, V., Nilsson, A., Johansson, M., … Sundberg, E. (2010). Homologues of the Arabidopsis thaliana SHI/STY/LRP1 genes control auxin biosynthesis and affect growth and development in the moss Physcomitrella patens. Development, 137(8), 1275-1284. doi:10.1242/dev.039594Ferrándiz, C., & Fourquin, C. (2013). Role of the FUL–SHP network in the evolution of fruit morphology and function. Journal of Experimental Botany, 65(16), 4505-4513. doi:10.1093/jxb/ert479Fourquin, C., & Ferrándiz, C. (2012). Functional analyses of AGAMOUS family members in Nicotiana benthamiana clarify the evolution of early and late roles of C-function genes in eudicots. The Plant Journal, 71(6), 990-1001. doi:10.1111/j.1365-313x.2012.05046.xFourquin, C., & Ferrándiz, C. (2014). The essential role of NGATHA genes in style and stigma specification is widely conserved across eudicots. New Phytologist, 202(3), 1001-1013. doi:10.1111/nph.12703Fourquin, C., Primo, A., Martínez-Fernández, I., Huet-Trujillo, E., & Ferrándiz, C. (2014). The CRC orthologue from Pisum sativum shows conserved functions in carpel morphogenesis and vascular development. Annals of Botany, 114(7), 1535-1544. doi:10.1093/aob/mcu129Fourquin, C., Vinauger-Douard, M., Chambrier, P., Berne-Dedieu, A., & Scutt, C. P. (2007). Functional Conservation between CRABS CLAW Orthologues from Widely Diverged Angiosperms. Annals of Botany, 100(3), 651-657. doi:10.1093/aob/mcm136Fourquin, C., Vinauger-Douard, M., Fogliani, B., Dumas, C., & Scutt, C. P. (2005). Evidence that CRABS CLAW and TOUSLED have conserved their roles in carpel development since the ancestor of the extant angiosperms. Proceedings of the National Academy of Sciences, 102(12), 4649-4654. doi:10.1073/pnas.0409577102Fridborg, I., Kuusk, S., Robertson, M., & Sundberg, E. (2001). The Arabidopsis Protein SHI Represses Gibberellin Responses in Arabidopsis and Barley. Plant Physiology, 127(3), 937-948. doi:10.1104/pp.010388Gremski, K., Ditta, G., & Yanofsky, M. F. (2007). The HECATE genes regulate female reproductive tract development in Arabidopsis thaliana. Development, 134(20), 3593-3601. doi:10.1242/dev.011510Heijmans, K., Ament, K., Rijpkema, A. S., Zethof, J., Wolters-Arts, M., Gerats, T., & Vandenbussche, M. (2012). Redefining C and D in the Petunia ABC. The Plant Cell, 24(6), 2305-2317. doi:10.1105/tpc.112.097030Ishikawa, M., Ohmori, Y., Tanaka, W., Hirabayashi, C., Murai, K., Ogihara, Y., … Hirano, H.-Y. (2009). The spatial expression patterns of DROOPING LEAF orthologs suggest a conserved function in grasses. Genes & Genetic Systems, 84(2), 137-146. doi:10.1266/ggs.84.137Islam, M. A., Lütken, H., Haugslien, S., Blystad, D.-R., Torre, S., Rolcik, J., … Clarke, J. L. (2013). Overexpression of the AtSHI Gene in Poinsettia, Euphorbia pulcherrima, Results in Compact Plants. PLoS ONE, 8(1), e53377. doi:10.1371/journal.pone.0053377Kim, S.-G., Lee, S., Kim, Y.-S., Yun, D.-J., Woo, J.-C., & Park, C.-M. (2010). Activation tagging of an Arabidopsis SHI-RELATED SEQUENCE gene produces abnormal anther dehiscence and floral development. Plant Molecular Biology, 74(4-5), 337-351. doi:10.1007/s11103-010-9677-5Kumar, S., Stecher, G., & Tamura, K. (2016). MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Molecular Biology and Evolution, 33(7), 1870-1874. doi:10.1093/molbev/msw054Kuusk, S., Sohlberg, J. J., Magnus Eklund, D., & Sundberg, E. (2006). Functionally redundantSHIfamily genes regulate Arabidopsis gynoecium development in a dose-dependent manner. The Plant Journal, 47(1), 99-111. doi:10.1111/j.1365-313x.2006.02774.xLarsson, E., Franks, R. G., & Sundberg, E. (2013). Auxin and the Arabidopsis thaliana gynoecium. Journal of Experimental Botany, 64(9), 2619-2627. doi:10.1093/jxb/ert099Larsson, E., Roberts, C. J., Claes, A. R., Franks, R. G., & Sundberg, E. (2014). Polar Auxin Transport Is Essential for Medial versus Lateral Tissue Specification and Vascular-Mediated Valve Outgrowth in Arabidopsis Gynoecia. Plant Physiology, 166(4), 1998-2012. doi:10.1104/pp.114.245951Lee, J.-Y. (2005). Recruitment of CRABS CLAW to promote nectary development within the eudicot clade. Development, 132(22), 5021-5032. doi:10.1242/dev.02067Marsch-Martínez, N., & de Folter, S. (2016). Hormonal control of the development of the gynoecium. Current Opinion in Plant Biology, 29, 104-114. doi:10.1016/j.pbi.2015.12.006Martínez-Fernández, I., Sanchís, S., Marini, N., Balanzá, V., Ballester, P., Navarrete-Gómez, M., … Ferrándiz, C. (2014). The effect of NGATHA altered activity on auxin signaling pathways within the Arabidopsis gynoecium. Frontiers in Plant Science, 5. doi:10.3389/fpls.2014.00210Morris, A. L., MacArthur, M. W., Hutchinson, E. G., & Thornton, J. M. (1992). Stereochemical quality of protein structure coordinates. Proteins: Structure, Function, and Genetics, 12(4), 345-364. doi:10.1002/prot.340120407Moubayidin, L., & Østergaard, L. (2014). Dynamic Control of Auxin Distribution Imposes a Bilateral-to-Radial Symmetry Switch during Gynoecium Development. Current Biology, 24(22), 2743-2748. doi:10.1016/j.cub.2014.09.080Ó’Maoiléidigh, D. S., Graciet, E., & Wellmer, F. (2013). Gene networks controllingArabidopsis thalianaflower development. New Phytologist, 201(1), 16-30. doi:10.1111/nph.12444Orashakova, S., Lange, M., Lange, S., Wege, S., & Becker, A. (2009). TheCRABS CLAWortholog from California poppy (Eschscholzia californica,Papaveraceae), EcCRC, is involved in floral meristem termination, gynoecium differentiation and ovule initiation. The Plant Journal, 58(4), 682-693. doi:10.1111/j.1365-313x.2009.03807.xPabón-Mora, N., Ambrose, B. A., & Litt, A. (2012). Poppy APETALA1/FRUITFULL Orthologs Control Flowering Time, Branching, Perianth Identity, and Fruit Development. Plant Physiology, 158(4), 1685-1704. doi:10.1104/pp.111.192104Pabón-Mora, N., Wong, G. K.-S., & Ambrose, B. A. (2014). Evolution of fruit development genes in flowering plants. Frontiers in Plant Science, 5. doi:10.3389/fpls.2014.00300Pan, I. L., McQuinn, R., Giovannoni, J. J., & Irish, V. F. (2010). Functional diversification of AGAMOUS lineage genes in regulating tomato flower and fruit development. Journal of Experimental Botany, 61(6), 1795-1806. doi:10.1093/jxb/erq046Pfannebecker, K. C., Lange, M., Rupp, O., & Becker, A. (2016). An Evolutionary Framework for Carpel Developmental Control Genes. Molecular Biology and Evolution, msw229. doi:10.1093/molbev/msw229Pfannebecker, K. C., Lange, M., Rupp, O., & Becker, A. (2017). Seed plant specific gene lineages involved in carpel development. Molecular Biology and Evolution, msw297. doi:10.1093/molbev/msw297Ratcliff, F., Martin-Hernandez, A. M., & Baulcombe, D. C. (2008). Technical Advance: Tobacco rattle virus as a vector for analysis of gene function by silencing. The Plant Journal, 25(2), 237-245. doi:10.1046/j.0960-7412.2000.00942.xReyes-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.2013.08.002Sohlberg, J. J., Myrenås, M., Kuusk, S., Lagercrantz, U., Kowalczyk, M., Sandberg, G., & Sundberg, E. (2006). STY1regulates auxin homeostasis and affects apical-basal patterning of the Arabidopsis gynoecium. The Plant Journal, 47(1), 112-123. doi:10.1111/j.1365-313x.2006.02775.xStåldal, V., Cierlik, I., Chen, S., Landberg, K., Baylis, T., Myrenås, M., … Sundberg, E. (2012). The Arabidopsis thaliana transcriptional activator STYLISH1 regulates genes affecting stamen development, cell expansion and timing of flowering. Plant Molecular Biology, 78(6), 545-559. doi:10.1007/s11103-012-9888-zStåldal, V., Sohlberg, J. J., Eklund, D. M., Ljung, K., & Sundberg, E. (2008). Auxin can act independently ofCRC,LUG,SEU,SPTandSTY1in style development but not apical-basal patterning of theArabidopsisgynoecium. New Phytologist, 180(4), 798-808. doi:10.1111/j.1469-8137.2008.02625.xSundberg, E., & Ostergaard, L. (2009). Distinct and Dynamic Auxin Activities During Reproductive Development. Cold Spring Harbor Perspectives in Biology, 1(6), a001628-a001628. doi:10.1101/cshperspect.a001628Tian, C., & Jiao, Y. (2015). A systems approach to understand shoot branching. Current Plant Biology, 3-4, 13-19. doi:10.1016/j.cpb.2015.08.001Trigueros, M., Navarrete-Gómez, M., Sato, S., Christensen, S. K., Pelaz, S., Weigel, D., … Ferrándiz, C. (2009). The NGATHA Genes Direct Style Development in the Arabidopsis Gynoecium. The Plant Cell, 21(5), 1394-1409. doi:10.1105/tpc.109.065508Vialette-Guiraud, A. C. M., Andres-Robin, A., Chambrier, P., Tavares, R., & Scutt, C. P. (2016). The analysis of Gene Regulatory Networks in plant evo-devo. Journal of Experimental Botany, 67(9), 2549-2563. doi:10.1093/jxb/erw119Wege, S., Scholz, A., Gleissberg, S., & Becker, A. (2007). Highly Efficient Virus-induced Gene Silencing (VIGS) in California Poppy (Eschscholzia californica): An Evaluation of VIGS as a Strategy to Obtain Functional Data from Non-model Plants. Annals of Botany, 100(3), 641-649. doi:10.1093/aob/mcm118Yamada, T., Yokota, S., Hirayama, Y., Imaichi, R., Kato, M., & Gasser, C. S. (2011). Ancestral expression patterns and evolutionary diversification of YABBY genes in angiosperms. The Plant Journal, 67(1), 26-36. doi:10.1111/j.1365-313x.2011.04570.xYamaguchi, T., Nagasawa, N., Kawasaki, S., Matsuoka, M., Nagato, Y., & Hirano, H.-Y. (2004). The YABBY Gene DROOPING LEAF Regulates Carpel Specification and Midrib Development in Oryza sativa. The Plant Cell, 16(2), 500-509. doi:10.1105/tpc.018044Yellina, A. L., Orashakova, S., Lange, S., Erdmann, R., Leebens-Mack, J., & Becker, A. (2010). Floral homeotic C function genes repress specific B function genes in the carpel whorl of the basal eudicot California poppy (Eschscholzia californica). EvoDevo, 1(1), 13. doi:10.1186/2041-9139-1-13Youssef, H. M., Eggert, K., Koppolu, R., Alqudah, A. M., Poursarebani, N., Fazeli, A., … Schnurbusch, T. (2016). VRS2 regulates hormone-mediated inflorescence patterning in barley. Nature Genetics, 49(1), 157-161. doi:10.1038/ng.3717Yuo, T., Yamashita, Y., Kanamori, H., Matsumoto, T., Lundqvist, U., Sato, K., … Taketa, S. (2012). A SHORT INTERNODES (SHI) family transcription factor gene regulates awn elongation and pistil morphology in barley. Journal of Experimental Botany, 63(14), 5223-5232. doi:10.1093/jxb/ers182Zawaski, C., Kadmiel, M., Ma, C., Gai, Y., Jiang, X., Strauss, S. H., & Busov, V. B. (2011). SHORT INTERNODES-like genes regulate shoot growth and xylem proliferation in Populus. New Phytologist, 191(3), 678-691. doi:10.1111/j.1469-8137.2011.03742.

Incidence, seasonality and serotypes of rotavirus in Gipuzkoa (Basque Country), Spain. A 14-year study

Over a 14-year period (1984–97) the presence of rotavirus in stool samples from children under 15 years with acute gastroenteritis was studied by enzymoimmunoanalysis. Serotyping (G1–G4) was performed using monoclonal antibodies. A total of 17348 children under 15 were investigated. Rotavirus was detected in 3637 (21·0%) specimens, 74·6% of which were from children younger than 2 years old. G1 and G4 were the most frequent serotypes. In 1991–7, the minimum incidence of rotavirus gastroenteritis in children under 4 years of age was 21·7 cases/1000 children/year. By the age of 5 years, at least 1 out of 11·3 children and probably 1 out of every 5–6 children in this area had experienced an episode of rotavirus gastroenteritis that required medical care. In the 1984–90 period a clear seasonality was not observed but in the second period of the study (1991–7), seasonality was marked, with peak activity in winter

Vasoactive intestinal peptide axis is dysfunctional in patients with Graves’ disease

Vasoactive intestinal peptide (VIP) is a neuropeptide with potent immunoregulatory properties. Reduced serum VIP levels and alterations in VIP receptors/signaling on immune cells have been associated with different inflammatory/autoimmune diseases. However, its role in autoimmune thyroid diseases (AITD) remains unknown. This study examined the interrelationship between VIP system, autoimmune background and thyroid hormones in peripheral immune cells in patients with AITD. Only Graves’ disease (GD) patients showed significantly lower serum VIP levels when compared to healthy subjects and to Hashimoto’s thyroiditis patients. Serum VIP levels were lower at the onset of GD, showing a significant negative correlation with thyroid hormone levels. The expression of VIP receptors, VPAC1 and VPAC2, was significantly upregulated in peripheral blood mononuclear cells (PBMC) from GD patients. There was an impairment of VIP signalling in these patients, probably attributable to a dysfunction of VPAC1 with preservation of VPAC2. The correlation between VPAC1 and thyroid hormone receptor expression in PBMC from healthy subjects was lost in GD patients. In summary, the VIP system is altered in peripheral immune cells of GD patients and this finding is associated with different thyroid hormone receptor patterns, showing a dynamic inter-regulation and a prominent role of VIP in this setting.This work has been supported by Instituto de Salud Carlos III, Spain, cofinanced by FEDER, European Union: RETICS program, Red de Investigación en Inflamación y Enfermedades Reumáticas (RD16/0012/0008, PI17/00027, PI16-02091, PIE13-0004) and from Consejería de Educación, Juventud y Deporte, Comunidad de Madrid: B2017/BMD372

The relict population of Pinna nobilis in the Mar Menor is facing an uncertain future

Pinna nobilis is undergoing one of the most dramatic events suffered by an endangered species. An emerging disease has relegated its populations to coastal lagoons or estuaries with salinities beyond the 36.5–39.7 psu range. The Mar Menor is one of two such locations on the Spanish coastline. Poor environmental conditions and eutrophication and anoxia events, that became critical in 2016, 2019 and 2021, have reduced its population in >99 %. In this work, the spatial distribution of the species within the lagoon and the factors determining its survival along the successive crises of eutrophication are studied using a two-stage (presence/absence estimation and density modelling) Species Distribution Model. A potential area of 200.97 ha and an average density of 1.05 ind.100 m2 is estimated for 2020. The viability of the Mar Menor population depends on management actions designed both for the species and to improve the lagoon environmental state.This research was supported by the EU LIFE Programme Project “Protection and restoration of Pinna nobilis populations as a response to the catastrophic pandemic started in 2016” (LIFE PINNARCA) [grant number LIFE20 NAT/ES/001265] and the Biodiversity Foundation of the Ministry for Ecological Transition and the Demographic Challenge Project RECUPERA PINNA [grant number IRTA1-21T]. This research was supported by the Dirección General del Mar Menor, Consejería de Agua, Agricultura, Ganadería, Pesca y Medio Ambiente (CARM), Project “Proyecto para la cría ex situ de Pinna nobilis y creación del Banco de Especies protegidas y singulares del Mar Menor”

Identification of a Human SOCS1 Polymorphism That Predicts Rheumatoid Arthritis Severity

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an autoimmune response in the joints and an exacerbation of cytokine responses. A minority of patients with RA experience spontaneous remission, but most will show moderate/high disease activity, with aggressive joint damage and multiple systemic manifestations. There is thus is a great need to identify prognostic biomarkers for disease risk to improve diagnosis and prognosis, and to inform on the most appropriate therapy. Here we focused on suppressor of cytokine signaling 1 (SOCS1), a physiological negative regulator of cytokines that modulates cell activation. Using four independent cohorts of patients with arthritis, we characterized the correlation between SOCS1 mRNA levels and clinical outcome. We found a significant inverse correlation between SOCS1 mRNA expression and disease activity throughout the follow-up of patients with RA. Lower baseline SOCS1 levels were associated with poorer disease control in response to methotrexate and other conventional synthetic disease-modifying anti-rheumatic drugs in early arthritis, and to rituximab in established (active) RA. Moreover, we identified several single nucleotide polymorphisms in the SOCS1 gene that correlated with SOCS1 mRNA expression, and that might identify those patients with early arthritis that fulfill RA classification criteria. One of them, rs4780355, is in linkage disequilibrium with a microsatellite (TTTTC)3−5, mapped 0.9 kb downstream of the SNP, and correlated with reduced SOCS1 expression in vitro. Overall, our data support the association between SOCS1 expression and disease progression, disease severity and response to treatment in RA. These observations underlie the relevance of SOCS1 mRNA levels for stratifying patients prognostically and guiding therapeutic decisions

Assessment of the resilience of Barcelona urban services in case of flooding. The RESCCUE project

[ES] En el marco del Proyecto europeo RESCCUE, las proyecciones climáticas para la ciudad de Barcelona muestran aumentos significativos de las intensidades máximas de precipitación para el horizonte del 2071-2100. En este trabajo se presenta la evaluación de la resiliencia de los servicios urbanos de la ciudad frente a episodios de inundación para condiciones de lluvia actuales y futuras. El uso de modelos sectoriales e integrados ha permitido valorar la respuesta del sistema de drenaje de la ciudad tanto a nivel de sistema de alcantarillado subterráneo como a nivel superficial analizando el comportamiento hidráulico del conjunto de las superficies urbanas (calles, plazas, parques, etc.). Por otro lado, los parámetros asociados a las inundaciones superficiales (extensión de las zonas inundables, calado y velocidad) han sido empleados para estimar potenciales afectaciones futuras en otros servicios urbanos estratégicos como el tráfico superficial, el sistema eléctrico y el sistema de recogida de residuos.[EN] Within the framework of the European RESCCUE Project, climate projections for the city of Barcelona show significant increases in maximum rainfall intensities for the 2071-2100 horizon. This paper presents the evaluation of the resilience of urban services in the city against flood episodes for current and future rainfall conditions. The use of sectorial and integrated models allows to assess the response of the city’s drainage system both at the underground sewer system level and at the surface level by analyzing the hydraulic behavior of all urban surfaces (streets, squares, parks, etc.). On the other hand, the parameters associated with surface flooding (extension of flood areas, flow depth and velocity) can be used to estimate potential impacts on other strategic urban services such as surface traffic, the electrical system and the waste collection service.Proyecto RESCCUE (RESilience to cope with Climate Change in Urban arEas - a multisectorial approach focusing on water), financiado por el programa H2020 de la Unión Europea (Acuerdo No. 700174)Russo, B.; Velasco, M.; Monjo, R.; Martínez-Gomariz, E.; Sánchez, D.; Domínguez, JL.; Gabàs, A.... (2020). Evaluación de la resiliencia de los servicios urbanos frente a episodios de inundación en Barcelona. El Proyecto RESCCUE. Ingeniería del agua. 24(2):101-118. https://doi.org/10.4995/ia.2020.12179OJS101118242Ecologia Urbana. 2018. Pla Clima 2018-2030. Ajuntament de Barcelona.Evans, B. 2017. Deliverable 3.1. Selection of methods for quantification of impacts of identified hazards. Deliverable 3.1. RESCCUE Project. Grant Agreement No. 700174. Disponible en http://www.resccue.euEvans, B. 2019. Deliverable 3.4. Impact assessments of multiple hazards in case study areas. Deliverable 3.4. RESCCUE Project. Grant Agreement No. 700174. Disponible en http://www.resccue.euFederal Emergency Management Agency (FEMA). 2009. Multi-Hazard Loss Estimation Methodology, Flood Model: Hazus-MH MR4 Technical Manual. 2009th ed. Disponible en https://www.fema.gov/media-library-data/20130726-1820-25045-8292/hzmh2_1_fl_tm.pdf.Martínez-Gomariz, E., Gómez, M., Russo, B. 2016. Estabilidad de personas en flujos de agua. Ingeniería del agua, 20,(1), 43-58. https://doi.org/10.4995/ia.2016.4231Martínez-Gomariz, E., Gómez, M., Russo, B. 2017. A new experiments-based methodology to obtain the stability threshold for any real vehicle exposed to flooding. Urban Water Journal, 14(9), 930-939. https://doi.org/10.1080/1573062X.2017.1301501Martínez-Gomariz, E., Gómez, M., Russo, B. 2018a. Stability criteria for flooded vehicles: A state of the art review. Journal of Flood Risk Management, 11, S817-S826. https://doi.org/10.1111/jfr3.12262Martínez‐Gomariz, E., Gómez, M., Russo, B., Sánchez, P., Montes, J. A. 2018b. Methodology for the damage assessment of vehicles exposed to flooding in urban areas. Journal of Flood Risk Management, 12(3), e12475 (Early View). https://doi.org/10.1111/jfr3.12475Monjo R., Gaitán E., Pórtoles J., Ribalaygua J., Torres L. 2016. Changes in extreme precipitation over Spain using statistical downscaling of CMIP5 projections. International Journal of Climatology, 36, 757-769. https://doi.org/10.1002/joc.4380Monjo R., Paradinas C., Gaitán E., Redolat D., Paradinas C., Prado C., Portolés J., Torres L., Ribalaygua J. Russo B., Velasco M., Pouget L., Vela S., David M. L., Morais M., Ribalaygua J. 2018. Report on extreme events predictions. Deliverable 1.3 RESCCUE Project. Grant Agreement No. 700174. Disponible en http://www.resccue.euPenning-Rowsell, E., Johnson, C., Tunstall, S., Tapsell, S., Morris, J., Chatterton, J., Green, C. 2005. The benefits of flood and coastal risk management: A handbook of assessment techniques. North London Business Park, Oakleigh Road South, London, England: Flood Hazard Research Centre, Middlesex University Press.Pyatkova K., Chen A. S., Djordjevic S., Butler D., Vojinovic Z., Abebe Y. A., Hammond M. 2015. Flood Impacts on Road transportation Using Microscopic Traffic Modelling Technique [Conference]. SUMO User Conference.Reiter, P. 2000. International methods of Risk Analysis, Damage evaluation and social impact studies concerning Dam-Break accidents. EU-Project RESCDAM. Seinäjoki, Finlandia.Russo, B., Gómez, M., Macchione, F. 2013. Pedestrian hazard criteria for flooded urban areas. Nat Hazards, 69, 251-265. https://doi.org/10.1007/s11069-013-0702-2Russo B., Pouget L., Malgrat P., García J. 2011. Evaluación del impacto del cambio climático en un caso de estudio de Barcelona a través de una modelización 2D-1D del drenaje dual. JIA2011. Barcelona, España. ISBN: 13-978-84-615-4023-5.Russo B., Sunyer D., Velasco M., Djordjević S. 2015. Analysis of extreme flooding events through a calibrated 1D/2D coupled model: the case of Barcelona (Spain). Journal of Hydroinformatics, 17(3), 473-491. https://doi.org/10.2166/hydro.2014.063Russo B. 2018. Multi-hazards assessment related to water cycle extreme events for current scenario. Deliverable 2.4 RESCCUE Project. Grant Agreement No. 700174. Disponible en http://www.resccue.euRusso B. 2019. Multi-hazards assessment related to water cycle extreme events for future scenarios (Business As Usual). Deliverable 2.3 RESCCUE Project. Grant Agreement No. 700174. Disponible en http://www.resccue.euShand, T.D., Cox, R., Blacka, M.J., Smith G.P. 2011. Australian Rainfall and Runoff (AR&R). Revision Project 10: Appropriate Safety Criteria for Vehicles (Report Number: P10/S2/020).U.S. Army Corps of Engineers (USACE). 2009. Economic Guidance Memorandum, 09-04, Generic Depth-Damage Relationships for Vehicles. Washington, D.C, USAVelasco, M., Russo, B., Martínez, M., Malgrat, P., Monjo, R., Djordjevic, S., Fontanals, I., Vela, S., Cardoso, M.A., Buskute, A. 2018. Resilience to cope with climate change in urban areas-A multisectorial approach focusing on water-The RESCCUE project. Water, 10, 1356-1366. https://doi.org/10.3390/w1010135

Nanometer Scale Dielectric Fluctuations at the Glass Transition

Using non-contact scanning probe microscopy (SPM) techniques, dielectric properties were studied on 50 nanometer length scales in poly-vinyl-acetate (PVAc) films in the vicinity of the glass transition. Low frequency (1/f) noise observed in the measurements, was shown to arise from thermal fluctuations of the electric polarization. Anomalous variations observed in the noise spectrum provide direct evidence for cooperative nano-regions with heterogeneous kinetics. The cooperative length scale was determined. Heterogeneity was long-lived only well below the glass transition for faster than average processes.Comment: 4 pages, 4 embedded PS figures, RevTeX - To appear in Phys. Rev. Let

Estudio de la musculatura axial en lubina salvaje y lubina atlántica cultivada, Dicentrarchus labrax L., de talla comercial. I: Estudio en fresco.

En este trabajo se realiza un estudio comparativo de la musculatura de la lubina, Dicentrarchus labrax L., procedente del medio natural (salvajes) y lubina de origen Atlántico cultivada bajo condiciones naturales de temperatura y fotoperiodo y alimentada con dietas artificiales. Se estudiaron un total de 25 ejemplares de tamaño comercial: 14 salvajes y 11 cultivados. Se midieron sus longitudes y pesos y se realizó una sección transversal en la zonal caudal (a nivel de la apertura anal) y en la zona craneal (a nivel del 4º radio de la aleta dorsal) con el fin de estudiar los siguientes parámetros: área transversal del total del miotomo y del músculo blanco, área y número de fibras blancas. Los ejemplares salvajes mostraron un mayor tamaño del área total del miotomo que los mantenidos a temperatura ambiente, aunque estas diferencias no fueron estadísticamente significativas. Asímismo, la constitución interna del miotomo fue diferente entre ambas poblaciones, de tal forma que los ejemplares de lubina salvaje presentaron un mayor número de fibras que los ejemplares cultivados de lubina atlántica (p<0.05). Por el contrario, el área de las fibras fue mayor en lubina atlántica (p<0.05). Este estudio pone de manifiesto que las condiciones medioambientales y el origen genético influyen sobre los mecanismos de crecimiento y la constitución fibrilar, lo que puede incidir en la calidad final del producto.MCYT. Proyecto AGL2000-1738-C03-0

First signs and symptoms of spondyloarthritis—data from an inception cohort with a disease course of two years or less (REGISPONSER-Early)

Objective. To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA

Comparison of performance of the Assessment of Spondyloarthritis International Society, the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis

Early diagnosis of spondyloarthritis (SpA) is essential as anti-tumor necrosis factor therapy can achieve significant symptomatic relief and control of disease activity. This study aims to compare the clinical characteristics, disease activity, and functional status of a Chinese cohort of SpA patients who were re-classified into ankylosing spondylitis (AS) patients fulfilling the modified New York (MNY) criteria, those with undifferentiated SpA (USpA) fulfilling the European Spondyloarthropathy Study Group (ESSG) classification criteria only (USpA/ESSG) and those who fulfill Assessment of SpondyloArthritis International Society (ASAS) only (USpA/ASAS). Disease activity was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), severity of morning stiffness, patient global assessment, and C-reactive protein. Functional status was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI), modified Schober index, and dimension of chest expansion. One hundred and twenty-eight patients with disease duration of 16.3 ± 10.4 years were recruited. Patients in USpA/ESSG and USpA/ASAS were significantly younger (p = 0.01), had shorter disease duration (p < 0.01), and lower BASFI (p = 0.03) than established AS patients. All three groups have active disease with comparable BASDAI >3. BASFI correlated inversely with dimension of chest expansion and negatively modified Schober index in AS patients (p < 0.01) and modestly with BASDAI (r = 0.25, p < 0.01). BASFI correlated moderately with BASDAI in USpA/ESSG (r = 0.61, p < 0.01) but not with chest expansion or modified Schober index. Compared with established AS patients recognized by MNY criteria, patients fulfilling USpA defined by ESSG or ASAS criteria had earlier disease, as active disease and less irreversible functional deficit