Caracterización de mecanismos implicados en la regulación de la respuesta a estrés por frío en plantas

[ES] En un contexto de calentamiento global, el estrés abiótico se ha convertido en una de las mayores amenazas para la productividad agrícola. El estrés por frío es uno de estos factores limitantes. Por lo tanto, estudiar a nivel molecular la respuesta de la planta a este tipo de estrés e identificar los genes o los microRNAs cuya función es determinante en la resistencia a este tipo de estrés puede aportar información fundamental para desarrollar plantas tolerantes a frío y así poder aumentar la producción de alimentos en condiciones ambientales adversas. En esta tesis pretendemos dar un enfoque transversal para poder identificar genes implicados en la respuesta a estrés. Por un lado utilizamos un enfoque de biología molecular clásica, y por otro una visión basada en la biología de sistemas y en la secuenciación a gran escala. Mediante esta estrategia hemos sido capaces de identificar y caracterizar el gen BvCOLD1 de Beta vulgaris que codifica una aquaporina localizada en el retículo endoplásmico y que al ser sobrexpresado en plantas de Arabidopsis thaliana confiere tolerancia a frío y a condiciones limitantes de Boro (B). Por lo que demostramos que es un gen fundamental para el transporte de este oligoelemento esencial. En paralelo desarrollamos un abordaje de biología de sistemas a partir de plantas de melón (Cucumis melo) sometidas a estrés por frío. Lo que nos permitió identificar 20 familias de miRNA implicadas en la respuesta en condiciones de frío. En el tercer capítulo profundizamos en la regulación de uno de estos miRNA (miR319) y descubrimos que el frío induce el procesamiento de una forma alternativa de esta molécula.[CA] En un context d'escalfament global, l'estrès abiòtic s'ha convertit en una de les majors amenaces per a la productivitat agrícola global. L'estrès per fred és un d'aquests factors limitants. Per tant, Estudiar a nivell molecular la resposta de la planta a fred i identificar els gens o els microRNA la funció dels quals és determinant en aquestes condicions pot aportar informació fonamental per desenvolupar plantes tolerants a aquest estrès i així poder augmentar la producció d'aliments en condicions adverses. En aquesta tesi hem utilitzat un enfocament transversal per poder identificar gens implicats en la resposta a estrès. D'una banda hem fet servir mètodes de biologia molecular clàssica, que ens ha permès identificar i caracteritzar el gen BvCOLD1 de Beta vulgaris que codifica una aquaporina localitzada en el reticle endoplasmàtic i que en ser sobrexpresada en plantes d'Arabidopsis thaliana conferia tolerància a fred i a condicions limitants de bor. Pel que hem demostrat que és un gen fonamental per al transport d'aquest oligoelement essencial. En paral·lel hem desenvolupat un abordatge de biologia de sistemes a partir de plantes de meló (Cucumis melo) sotmeses a estrès per fred. El que ens va permetre identificar 20 famílies de miRNA implicades en la resposta en condicions de fred. Hem aprofundit en la regulació d'un d'aquests miRNA (el mi319) i hem descobert que el fred indueix la formació d'una forma alternativa d'aquesta molècula.[EN] In a context of global warming, abiotic stress has become one of the greatest threats to global agricultural productivity. Cold stress is one of these limiting factors. Therefore, Studying the plant response at the molecular level and identifying the genes or microRNAs whose function is determinant in these conditions can provide fundamental information to develop plants tolerant to this stress and thus be able to increase the production of food under adverse conditions. In this Ph.D. Thesis we have used a transversal approach to identify genes involved in stress response. We have used two different approaches. First we used classical molecular biology methods, which has allowed us to identify and characterize the BvCOLD1 gene of Beta vulgaris that encodes an aquaporin located in the endoplasmic reticulum and which upon overexpression in Arabidopsis thaliana conferred tolerance to cold and limiting conditions of Boron. So we showed that it is a fundamental gene for the transport of this essential trace element. In parallel, we undertook a systems biology approach based on melon plants (Cucumis melo) subjected to cold stress. This allowed us to identify 20 families of miRNA involved in the response to cold conditions. We have further studied the regulation of one of these miRNAs (miR319) and discovered that cold induces the alternative processing of its precursor.Bustamante González, AJ. (2019). Caracterización de mecanismos implicados en la regulación de la respuesta a estrés por frío en plantas [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/118800TESI

BvCOLD1: A novel aquaporin from sugar beet (Beta vulgaris L.) involved in boron homeostasis and abiotic stress

[EN] In this report we have identified BvCOLD1, a novel aquaporin from sugar beet (Beta vulgaris) which is only conserved in the Chenopodioideae family. BvCOLD1 is expressed in all plant organs investigated and located in the endoplasmic reticulum. Transport experiments in yeast indicated that BvCOLD1 is able to transport glycerol and boron, the most limiting oligoelement for sugar beet cultivation. Overexpression of BvCOLD1 in Arabidopsis thaliana plants conferred tolerance to cold, to different abiotic stresses and the ability to grow under boron limiting conditions, therefore this novel aquaporin may be an important target to design new crops with enhanced boron homeostasis and abiotic stress tolerance.Ministerio de Economia y Competitividad, Grant/Award Number: BIO2016-77776-P; Secretaria de Estado de Investigacion, Desarrollo e Innovacion, Grant/Award Number: AGL2013-47886-R; Direccion General Investigacion Cientifica; MINECO, Grant/Award Numbers: BIO2014-61826 and BIO2016-77776-P; Universitat Politecnica de Valencia, Grant/Award Number: PAID-06-10-1496Porcel, R.; Bustamante-González, AJ.; Ros, R.; Serrano Salom, R.; Mulet, JM. (2018). BvCOLD1: A novel aquaporin from sugar beet (Beta vulgaris L.) involved in boron homeostasis and abiotic stress. Plant Cell & Environment. 41(12):2844-2857. https://doi.org/10.1111/pce.13416284428574112Aroca, R., Amodeo, G., Fernández-Illescas, S., Herman, E. M., Chaumont, F., & Chrispeels, M. J. (2004). The Role of Aquaporins and Membrane Damage in Chilling and Hydrogen Peroxide Induced Changes in the Hydraulic Conductance of Maize Roots. Plant Physiology, 137(1), 341-353. doi:10.1104/pp.104.051045Biancardi, E. (2005). Genetics and Breeding of Sugar Beet. doi:10.1201/9781482280296Bienert, G. P., Møller, A. L. B., Kristiansen, K. A., Schulz, A., Møller, I. M., Schjoerring, J. K., & Jahn, T. P. (2006). Specific Aquaporins Facilitate the Diffusion of Hydrogen Peroxide across Membranes. Journal of Biological Chemistry, 282(2), 1183-1192. doi:10.1074/jbc.m603761200Bissoli, G., Niñoles, R., Fresquet, S., Palombieri, S., Bueso, E., Rubio, L., … Serrano, R. (2012). Peptidyl-prolyl cis-trans isomerase ROF2 modulates intracellular pH homeostasis in Arabidopsis. 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Early transcriptional changes in Beta vulgaris in response to low temperature. Planta, 242(1), 187-201. doi:10.1007/s00425-015-2299-zMulet, J. M., Alemany, B., Ros, R., Calvete, J. J., & Serrano, R. (2004). Expression of a plant serine O-acetyltransferase inSaccharomyces cerevisiae confers osmotic tolerance and creates an alternative pathway for cysteine biosynthesis. Yeast, 21(4), 303-312. doi:10.1002/yea.1076Muries, B., Faize, M., Carvajal, M., & Martínez-Ballesta, M. del C. (2011). Identification and differential induction of the expression of aquaporins by salinity in broccoli plants. Molecular BioSystems, 7(4), 1322. doi:10.1039/c0mb00285bNoguchi, K., Yasumori, M., Imai, T., Naito, S., Matsunaga, T., Oda, H., … Fujiwara, T. (1997). bor1-1, an Arabidopsis thaliana Mutant That Requires a High Level of Boron. Plant Physiology, 115(3), 901-906. doi:10.1104/pp.115.3.901Nozawa, A., Takano, J., Kobayashi, M., von Wirén, N., & Fujiwara, T. (2006). Roles of BOR1, DUR3, and FPS1 in boron transport and tolerance inSaccharomyces cerevisiae. FEMS Microbiology Letters, 262(2), 216-222. doi:10.1111/j.1574-6968.2006.00395.xO’Neill, M. A., Warrenfeltz, D., Kates, K., Pellerin, P., Doco, T., Darvill, A. G., & Albersheim, P. (1996). Rhamnogalacturonan-II, a Pectic Polysaccharide in the Walls of Growing Plant Cell, Forms a Dimer That Is Covalently Cross-linked by a Borate Ester. Journal of Biological Chemistry, 271(37), 22923-22930. doi:10.1074/jbc.271.37.22923Pang, Y., Li, L., Ren, F., Lu, P., Wei, P., Cai, J., … Wang, X. (2010). Overexpression of the tonoplast aquaporin AtTIP5;1 conferred tolerance to boron toxicity in Arabidopsis. Journal of Genetics and Genomics, 37(6), 389-397. doi:10.1016/s1673-8527(09)60057-6Patankar, H. V., Al-Harrasi, I., Al-Yahyai, R., & Yaish, M. W. (2018). Identification of Candidate Genes Involved in the Salt Tolerance of Date Palm (Phoenix dactylifera L.) Based on a Yeast Functional Bioassay. DNA and Cell Biology, 37(6), 524-534. doi:10.1089/dna.2018.4159Peiro, A., Izquierdo‐Garcia, A. C., Sanchez‐Navarro, J. A., Pallas, V., Mulet, J. M., & Aparicio, F. (2014). Patellins 3 and 6, two members of the P lant P atellin family, interact with the movement protein of A lfalfa mosaic virus and interfere with viral movement. Molecular Plant Pathology, 15(9), 881-891. doi:10.1111/mpp.12146Porcel, R., Aroca, R., Azcón, R., & Ruiz-Lozano, J. M. (2006). PIP Aquaporin Gene Expression in Arbuscular Mycorrhizal Glycine max and Lactuca  sativa Plants in Relation to Drought Stress Tolerance. Plant Molecular Biology, 60(3), 389-404. doi:10.1007/s11103-005-4210-yROZEMA, J., BRUIN, J., & BROEKMAN, R. A. (1992). Effect of boron on the growth and mineral economy of some halophytes and non-halophytes. New Phytologist, 121(2), 249-256. doi:10.1111/j.1469-8137.1992.tb01111.xSayle, R. (1995). RASMOL: biomolecular graphics for all. Trends in Biochemical Sciences, 20(9), 374-376. doi:10.1016/s0968-0004(00)89080-5Serrano, R., Montesinos, C., Gaxiola, R., Ríos, G., Forment, J., Leube, M., … Ros, R. (2003). FUNCTIONAL GENOMICS OF SALT TOLERANCE: THE YEAST OVEREXPRESSION APPROACH. Acta Horticulturae, (609), 31-38. doi:10.17660/actahortic.2003.609.2Shorrocks, V. M. (1997). Plant and Soil, 193(2), 121-148. doi:10.1023/a:1004216126069Soto, G., Alleva, K., Mazzella, M. A., Amodeo, G., & Muschietti, J. P. (2008). AtTIP1;3andAtTIP5;1, the only highly expressed Arabidopsis pollen-specific aquaporins, transport water and urea. FEBS Letters, 582(29), 4077-4082. doi:10.1016/j.febslet.2008.11.002Sreedharan, S., Shekhawat, U. K. S., & Ganapathi, T. R. (2015). Constitutive and stress-inducible overexpression of a native aquaporin gene (MusaPIP2;6) in transgenic banana plants signals its pivotal role in salt tolerance. Plant Molecular Biology, 88(1-2), 41-52. doi:10.1007/s11103-015-0305-2Su, Y., Liang, W., Liu, Z., Wang, Y., Zhao, Y., Ijaz, B., & Hua, J. (2017). Overexpression of GhDof1 improved salt and cold tolerance and seed oil content in Gossypium hirsutum. Journal of Plant Physiology, 218, 222-234. doi:10.1016/j.jplph.2017.07.017Takano, J., Noguchi, K., Yasumori, M., Kobayashi, M., Gajdos, Z., Miwa, K., … Fujiwara, T. (2002). Arabidopsis boron transporter for xylem loading. Nature, 420(6913), 337-340. doi:10.1038/nature01139Tanaka, M., & Fujiwara, T. (2007). Physiological roles and transport mechanisms of boron: perspectives from plants. Pflügers Archiv - European Journal of Physiology, 456(4), 671-677. doi:10.1007/s00424-007-0370-8Tanaka, M., Wallace, I. S., Takano, J., Roberts, D. M., & Fujiwara, T. (2008). NIP6;1 Is a Boric Acid Channel for Preferential Transport of Boron to Growing Shoot Tissues in Arabidopsis. 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Clinico-pathological characteristics and outcomes of patients with early-onset colorectal cancer

[Background]: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC). [Methods]: We included all of the patients with pathologically confirmed diagnosis of CRC at Hospital Universitario La Paz from October 2016 to September 2020. EOCRC age cut-off was 50 years. All statistical analyses were carried out using SPSS v.25. [Results]: A total of 1152 patients were diagnosed with CRC, fifty-nine (5,1%) of them were After a median follow-up of 24 months, 279 patients have died. Median overall survival (OS) was not reached in either group (p = 0,06). Three-year OS was 80% (95%CI: 73-87) and 67 (95%CI: 65-69) in the younger and older group, respectively. In patients with localized disease that underwent surgery or other antineoplastic treatment ( n = 856), 159 events for disease-free survival (DFS) were observed. Median DFS was [Conclusions]: Patients with EOCRC are diagnosed at a more advanced stage and display distinct biological features (more prevalence of dMMR and WT tumors among others). Studies focusing on screening in this population and deeper molecular profiling are needed

Clinico-pathological characteristics and outcomes of patients with early-onset colorectal cancer

[Background]: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC).[Methods]: We included all of the patients with pathologically confirmed diagnosis of CRC at Hospital Universitario La Paz from October 2016 to September 2020. EOCRC age cut-off was 50 years. All statistical analyses were carried out using SPSS v.25. [Results]: A total of 1152 patients were diagnosed with CRC, fifty-nine (5,1%) of them were After a median follow-up of 24 months, 279 patients have died. Median overall survival (OS) was not reached in either group (p ¼ 0,06). Three-year OS was 80% (95% CI: 73-87) and 67 (95%CI: 65-69) in the younger and older group, respectively. In patients with localized disease that underwent surgery or other antineoplastic treatment ( n ¼ 856), 159 events for disease-free survival (DFS) were observed. Median DFS was not reached in either group (p ¼0,144). Three-year DFS was 86% (95%CI: 79-93) and 73% (95%CI: 71-75, respectively). In patients with metastatic disease (n ¼ 332; synchronous or metachronic), median OS was not reach in the EOCRC group vs 18,1 (95%CI: 13,8-22,4), p ¼ 0,05). In those patients with metastatic EOCRC with mutational status assessed (n ¼23), no difference in OS according to RAS was observed (p ¼ 0,55).[Conclusions]: Patients with EOCRC are diagnosed at a more advanced stage and display distinct biological features (more prevalence of dMMR and WT tumors among others). Studies focusing on screening in this population and deeper molecular profiling are needed.Peer reviewe

Groundwater abstraction has caused extensive ecological damage to the Doñana World Heritage Site, Spain

Se incluye información suplementaria.Acreman et al. (2022) reviewed evidence for ecological damage to the Doñana wetlands (UNESCO World Heritage Site [WHS] and Ramsar site), Spain, associated with intensification of groundwater use, particularly for agriculture. Acreman et al. presented a multistep methodology for evidence-based risk assessment that involves identification of conservation issues, and a systematic review of scientific evidence for ecological damage and its causes. However, they involved few local scientists, used a questionable methodology in stakeholder selection and involvement, used a flawed conceptual framework, and an incomplete literature review. We propose improvements to their methodology. They overlooked or misinterpreted key evidence, and underestimated the impacts that abstraction for irrigation for red fruits (mainly strawberries), rice and other crops has had on Doñana and its biodiversity. They reported groundwater level depletion of up to 10 m in the deep aquifer, but wrongly concluded that there is no evidence for impacts on the natural marsh ecosystem, the dune ponds or the ecotone. Groundwater drawdowns are actually up to 20 m, and have inverted the formerly ascending vertical hydraulic gradient in discharge areas. Phreatic levels have been lowered from 0.5 to 2 m in some areas. Groundwater abstraction has caused multiple ecological impacts to temporary ponds and marshes in the WHS, as well as to terrestrial vegetation, and should be urgently reduced. Furthermore, Acreman et al. focused on groundwater quantity while overlooking the importance of severe impacts on quality of both surface and groundwater, intimately connected to the use of agrochemicals for irrigated crops.Part of this work (marsh hydroperiod and water depth) has been funded by eLTER Plus project (INFRAIA, Horizon 2020, Agreement No 871128) and FEDER actions [SUMHAL, LIFEWATCH-2019-09-CSIC-13, POPE 2014-2020] by the Ministry of Science, Innovation and Universities, Subtask LWE2103022: Integration into VRE in the framework of the CSIC Interdisciplinary Thematic Platforms (PTI) PTI EcoBioDiv and Teledetect. PMRG was funded by the Portuguese Foundation for Science and Technology (FCT), through the Individual Stimulus to Scientific Employment Programme with the 2020.03356.CEECIND grant, and Forest Research Centre by the FCT (UIDB/00239/2020) grant.N

Seminario de Economía Mexicana

Serie de ponencias referentes al Seminario de Economía Mexicana. Memorias del Seminario de Economía Mexicana de 199

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research