Evolutionary divergence in the bioactive jasmonate in land plants

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 21-09-2017Esta tesis tiene embargado el acceso al texto completo hasta el 21-03-2019Los jasmonatos son fitohormonas implicadas en activación de defensas y en procesos de desarrollo. En eudicotiledóneas la hormona activa, JA-Ile, induce la interacción entre los dos componentes del co-receptor: la F-box COI1 y uno de los represores JAZ. La ruta de señalización del jasmonato se ha estudiado fundamentalmente en la planta modelo Arabidopsis thaliana, pero apenas se ha caracterizado en otros grupos de plantas. El análisis de genomas disponibles de diversos linajes vegetales sugiere que todos los componentes de la ruta de señalización de jasmonatos ya estaban presentes en el ancestro común de las plantas terrestres. Los briófitos actuales son el grupo más primitivo de este tipo de plantas, y dentro de ellos, las hepáticas se consideran el linaje hermano al resto de plantas terrestres. En este trabajo hemos utilizado como planta modelo la hepática Marchantia polymorpha para estudiar la evolución y la conservación funcional de la ruta del jasmonato. Además de su posición evolutiva privilegiada, M. polymorpha tiene una redundancia génica extraordinariamente baja, lo que facilita el análisis funcional de familias multigénicas en plantas superiores. Nuestros resultados demuestran que la percepción de jasmonatos y su maquinaria de señalización están conservados en plantas terrestres, pero la hormona es diferente en briófitos y plantas vasculares. Hemos identificado el dinor-OPDA como la hormona activa en briófitos y hemos demostrado que un solo aminoácido en el receptor COI1 determina la especificidad de ligando. En conjunto, nuestros resultados explican los acontecimientos evolutivos que condujeron a la aparición del JA-Ile y COI1 en plantas vasculares a partir de sus ortólogos ancestrales. Además, la caracterización del co-receptor COI1/JAZ en plantas terrestres nos ha permitido desarrollar un antagonista específico de la percepción de JA-Ile con potencial biotecnológicoJasmonates are phytohormones involved in defence and developmental processes such as fertility. In eudicots, the active hormone JA-Ile induces the interaction between the two members of the coreceptor: the F-box COI1 and one of the JAZ repressors. The jasmonate signalling pathway has been mainly studied in the model plant Arabidopsis thaliana, but little is known about this pathway in other plant lineages. Sequence analyses of available algae and land plants genomes showed that all the signalling components of the JA-Ile pathway might have been already present in the common ancestor of all land plants. Extant bryophytes are the most basal group of land plants, and among them, liverworts are considered the sister lineage to all other land plants. In this work, we have used the model liverwort Marchantia polymorpha to study the evolution and functional conservation of the jasmonate pathway. Besides its key evolutionary position, M. polymorpha shows an extraordinary low gene redundancy that facilitates the study of large gene families. Our results demonstrate that the jasmonate perception and signalling machinery are conserved in land plants but the hormone is different in bryophytes and vascular plants. We have identified dinor-OPDA as the active hormone in bryophytes as well as the residue that determines the ligand specificity in COI1. Taken together our results explain the evolutionary events that lead to the appearance of JA-Ile and COI1 in vascular plants from their ancestral counterparts. In addition, the characterization of the COI1/JAZ co-receptor in land plants has allowed us to develop a specific antagonist of JA-Ile perception with biotechnological potential

Characterization of beet necrotic yellow vein furovirus from Spanish sugar beets

Rhizomania is a viral disease, caused by beet necrotic yellow vein furovirus (BNYVV), which was detected in Spanish sugar beets in 1988, it being focused on the Castilla y León region. BNYVV has five RNA fragments with specific functions, and the different composition and proportion of RNA in the virions allow their separation and the characterization of their activities during the development of the disease. Thirty–six samples of sugar beet rootlets and frozen pulps from three different sugar beet zones of Castilla y León were analyzed by DAS-ELISA and Immunocapture-Reverse Transcription-Polymerase Chain Reaction (IC-RT-PCR) using specific primers. The identity of the cDNA products was confirmed by nested- PCR and restriction fragment length polymorphism (RFLP). The uniformity of the patterns obtained by RFLP analyses with nine endonucleases showed the existence of a unique strain of BNYVV in 80,000 Ha of crop surface which could be explained by a recent arrival of the rhizomania disease to this region. The isolates studied were more similar to type A, which has been previously described in BNYVV, but a nonexpected cleavage site for this molecular group was observed with endonuclease Hinc II on the RNA-2 IC-RT-PCR product (nt 2133–3293) in the thirty–six Spanish samples and also in a North American strain taken as reference. The use of frozen pulps obtained as a previous step to the industrial extraction of sugar avoids problems due to erratic distribution of the virus in the roots, provides repetitive results for a particular sample, and facilitates epidemiological and distributional studies on rhizomania disease

FGF2, but not EGF, Induces multiciliated ependymal cells to dedifferentiate and adopt radial glial features in vitro

Multiciliated ependymal cells form an epithelium lining most of the ventricular cavities of vertebrates brain. Although considered postmitotic and completely differentiated, ependymal cells maintain some phenotypic characteristics of neural stem cells. Thereby, under specific conditions they behave as neural stem cells, developing radial glia characteristics, and undergoing asymmetric division. Our group is searching for factors that promote dedifferentiation of ependymal cells in vitro. We developed a simple method to obtain pure cultures of non-adherent multiciliated ependymal cells from adult rats. These cultures were used to investigate the effect of FGF2 on the differentiation state and the aggregation of ependymal cells. Thus, FGF2 treated ependymal cells lose cilia and hence mobility, and after 7 days they aggregate to form irregular spheres (diameter ≥ 20-30 μm). Such changes were not observed when EFG was used instead of FGF2. To assess the specificity of FGF2 action on cell aggregation, the FGF receptor inhibitor PD166866 and an anti-FGF2 neutralizing antibody were used. In both conditions the aggregative effect of FGF2 was abolished. No cell proliferation was observed during sphere formation, at least in such experimental conditions. Spheres were analyzed by immunocytochemistry using radial glia markers. They were positive for GFAP, vimentin, BLBP and GLAST. These data suggest that FGF2 promotes the identity loss in multiciliated ependymal cells in vitro, which are transformed into cells with radial glia features.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)

Modelling and operation of industrial vibrocooling units.

[EN]Product quality is paramount for companies to maintain the trust from their customers. Powder products and in particular fertilizers can suffer damage during storage if the temperature and moisture are not appropriate. Most of the work has focused on drying, but the last stage of cooling is responsible for avoiding product out of specification. A first principles model has been developed for industrial fluidized vibrating cooling units following a multiscale approach, from the particle to the entire unit, to evaluate their operation. The unit consists of two sections using atmospheric and cool air, respectively. A refrigeration cycle is also modelled to compute the needs to cool the air. The unit’s model only includes two adjustable parameters, the heat transfer efficiency from the particle to the air as well as for the losses from the unit to atmosphere. The model has been validated using industrial data, resulting in heat flow efficiency from the particle equal to 0.30 and the flow of losses of 1.17 kW/K. The model can reproduce the industrial data within reasonable error and allows predicting the cooling cycle needs and estimating the cost of its operation as a function of the weather. The location of the facility results in the fact that during June-August the atmospheric air cannot cool the product below the critical temperature and the refrigeration cycle needs to operate.LANZADERA_TCUE21–23_008 project from TCUE as well, the PSEM3 GIR and the support from MIRAT Fertilizantes S.L-

Compounds and their use as antagonists of jasmonate perception

The invention provides compounds, methods and uses suitable for modifying the characteristics of a plant, seed, or plant grown from the seed, by inhibiting jasmonate-mediated processes in the plant. In particular the invention provides jasmonate analogs, or other structurally related analogs, which function as antagonists. These can be used, for example, for improving disease resistance against one or more biotrophic or hemi-biotrophic pathogens, or for improving resistance against abiotic stress.Peer reviewedConsejo Superior de Investigaciones Científicas, Lipidox COA1 Solicitud de adición a la patent

Un análisis comparativo del comportamiento diferencial de los glaciares en los Andes Tropicales usando teledetección

En este trabajo de investigación, se analizó el comportamiento de los glaciares de los Andes Tropicales en un clima cambiante; para esto se emplearon imágenes satelitales multiespectrales de diversas fuentes en conjunto con datos meteorológicos. El estudio se enfocó en glaciares representativos de cuatro zonas climáticas diferentes, a saber: trópicos interiores, trópicos exteriores húmedos del norte, trópicos exteriores húmedos del sur y trópicos exteriores secos. Se calcularon los cambios en la línea de nieve máxima anual para el período de 1985―2015, y también los cambios decenales en el área entre 1975 y 2015. Además, se analizó la tasa de retroceso de los glaciares durante la ocurrencia de El Niño―Oscilación del Sur y la Oscilación Decenal del Pacífico. Se observó que los glaciares tanto de los trópicos interiores como de los trópicos exteriores se sometieron a retroceso durante todo el período de estudio, con énfasis entre 1975 y 1997, lapso coincidente con el período de calentamiento del Pacífico. Se observaron variaciones excepcionales en la altitud de la línea de nieve cuando se produce un evento de El Niño durante la fase cálida de la Oscilación Decenal del Pacífico. Se observó que no hay señales significativas del hiato reciente en el calentamiento global, excepto en los trópicos exteriores secos, localizados cerca de la región subtropical

Un análisis comparativo del comportamiento diferencial de los glaciares en los Andes Tropicales usando teledetección

In this research paper, we analysed the behaviour of Tropical Andean glaciers in a changing climate. We used multi-source satellite images as well as meteorological datasets to achieve this objective. Representative glaciers in four different climatic zones, namely the inner tropics, northern wet outer tropics, southern wet outer tropics and dry outer tropics, were considered in this study. Changes in annual maximum snowline during 1985 - 2015 and also the decadal changes in the area between 1975 and 2015 of these glaciers were calculated. Furthermore, we analysed the rate of glacier retreat during the occurrence of El Niño–Southern Oscillation and Pacific Decadal Oscillation. It is observed that the glaciers in both the inner and outer tropics underwent retreat during the study period and most of this retreat occurred during 1975 - 1997 which is parallel with the so-called Pacific shift. Exceptional variations in snowline altitude were observed when an El Niño event occurs during the warm phase of the Pacific Decadal Oscillation. No significant signals of the recent hiatus in global warming were observed, except in the dry outer tropics which are situated near the subtropical region.En este trabajo de investigación, se analizó el comportamiento de los glaciares de los Andes Tropicales en un clima cambiante; para esto se emplearon imágenes satelitales multiespectrales de diversas fuentes en conjunto con datos meteorológicos. El estudio se enfocó en glaciares representativos de cuatro zonas climáticas diferentes, a saber: trópicos interiores, trópicos exteriores húmedos del norte, trópicos exteriores húmedos del sur y trópicos exteriores secos. Se calcularon los cambios en la línea de nieve máxima anual para el período de 1985―2015, y también los cambios decenales en el área entre 1975 y 2015. Además, se analizó la tasa de retroceso de los glaciares durante la ocurrencia de El Niño―Oscilación del Sur y la Oscilación Decenal del Pacífico. Se observó que los glaciares tanto de los trópicos interiores como de los trópicos exteriores se sometieron a retroceso durante todo el período de estudio, con énfasis entre 1975 y 1997, lapso coincidente con el período de calentamiento del Pacífico. Se observaron variaciones excepcionales en la altitud de la línea de nieve cuando se produce un evento de El Niño durante la fase cálida de la Oscilación Decenal del Pacífico. Se observó que no hay señales significativas del hiato reciente en el calentamiento global, excepto en los trópicos exteriores secos, localizados cerca de la región subtropical

Schuurs-Hoeijmakers syndrome (PACS1 neurodevelopmental disorder): seven novel patients and a review

Schuurs-Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the PACS1 gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins. It is upregulated during human embryonic brain development and has low expression after birth. So far, only 54 patients with SHMS have been reported. In this work, we report on seven new identified SHMS individuals with the classical c.607C > T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75% of patients), frequent (50-74%), infrequent (26-49%) and rare (less than ≤25%)