Análisis de la distribución espacial en el complejo poliploide de Centaurea aspera (2n) - C.x subdecurrens (3n) - C. seridis (4n) en sus zonas de contacto

[ES] El género Centaurea L. pertenece a la familia Asteraceae (Compositae). Esta familia es una de las más diversas, ya que incluye unos 1.620 géneros y más de 23.600 especies. Esta gran diversificación de Centaurea se produce en gran medida mediante mecanismos de poliploidización e hibridación. De hecho, la capacidad de hibridación en el género Centaurea es una de las más altas conocidas, afectando sobre todo a especies cercanas o de la misma sección (Mateo y Crespo, 2009). A lo largo de la costa levantina tenemos la suerte de contar con uno de los complejos poliploides más interesantes de este género, producido por la hibridación de C. aspera subsp. stenophylla (2n), C. seridis subsp. maritima (4n) y su híbrido estéril C. x subdecurrens (3n). La genética y taxonomía de estos complejos híbridos han sido estudiados recientemente por el equipo de investigación que dirige este proyecto (Ferriol 2015 y anteriores) aunque las relaciones ecológicas y la distribución espacial a micro y meso escala todavía no están suficientemente estudiadas. Ruíz (2014; Ruiz et al. 2014) ya realizó una primera aproximación a la distribución espacial a macro y microescala y estudió las condiciones del microhábitat de cada uno de los taxones de este complejo poliploide en el Saler, utilizando parcelas estrechas y alargadas para intentar dilucidad los gradientes asociados con la distancia al mar. En sus resultados se observa que este gradiente no es tan claro como se esperaba y que es necesario realizar parcelas mucho más grandes para poder determinar a qué escala se están produciendo los procesos de atracción (similitud de nicho) y repulsión (competencia) entre los tres taxones. Además, es necesario realizar análisis de la distribución de los taxones en todas las zonas donde coexisten, para comprobar si existen o no diferencias en los patrones de distribución y en las frecuencias de los distintos citotipos en función de la latitud (desde Chilches, en Castellón, hasta Calblanque, en Murcia). Por ello, los objetivos del presente estudio son: 1. Comparar los patrones de distribución espacial en diferentes complejos híbridos de diferentes localidades, desde Chilches a Calblanque, pasando por la Marjal dels Moros, El Saler, Guardamar del Segura, Torrevieja (La Mata) y Santa Pola. 2. En cada una de estas localidades, realizar parcelas lo más grandes posible, de forma sistemática, para por un lado comparar las proporciones existentes de los tres taxones a lo largo de un gradiente latitudinal, y por otro lado poder observar los patrones de distribución de éstos a diferentes escalas. Para ello se tomarán datos de posicionamiento en el campo para cada individuo y se realizarán los análisis estadísticos a través de la herramienta informática R, que permitirá relacionar la posición de los tres taxones entre ellos y en relación a parámetros ecológicos como distancia al mar o proximidad de caminos e infrastructuras. Bibliografía citada en el Resumen: Ferriol, María, Alfonso Garmendia, Ana Gonzalez, y Hugo Merle. (2015) «Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids». PLoS ONE 10:1-13. doi:10.1371/journal.pone.0140465. Ruiz, P. (2014)Distribución y microhábitat de Centaurea aspera (2n), C. seridis (4n) y C. x subdecurrens (3n) en la provincia de Valencia. TFC. UPV, Valencia, Marzo de 2014. Ruiz, P., Garmendia, A., Ferriol, M., Merle, H. (2014) Distribución de Centaurea aspera (2n), C. seridis (4n) y su híbrido C. x subdecurrens (3n) a diferentes escalas. Eds: cámara R., Rodriguez B., Muriel JL., ¿Biogeografía de sistemas litorales. Dinámica y conservación¿. Pp: 409-412. Universidad de Sevilla.[EN] The genus Centaurea L. belongs to the Asteraceae (Compositae) family. This family is one of the most varied, since it includes more than 1,620 kinds and more than 23,600 species. This great diversification of Centaurea occurs largely through mechanisms of hybridization and polyploidization. In fact, the ability of hybridization in the genus Centaurea is one of the highest known, affecting mostly closely related species or the same section (Matthew and Crespo, 2009). Along the east coast we are lucky to have one of the most interesting polyploid complexes of this type produced by hybridization of C. aspera subsp. stenophylla (2n), C. seridis subsp. maritima (4n) and sterile hybrid C. x subdecurrens (3n). The genetics and taxonomy of these hybrid complexes have been recently studied by the equipment of investigation that directs this project (Ferriol 2015 and earlier) but the ecological relationships and spatial distribution at the micro and meso scale are still not sufficiently studied. Ruíz (2014; Ruiz et to. 2014) already realized the first approximation to the spatial distribution to macro and it microscale and he studied the conditions of the microhabitat of each one of the taxones of this polyploid complex in the Saler, using plots narrow and elongated to try explain the gradients associated with the distance with the sea. In his results is observed that this gradient is not so clear as expected and that it is necessary to realize much bigger plots to be able to determine to what scale there are taking place the processes of attraction (similarity of niche) and repulsion (competition) between the three taxones. In addition, it is necessary to realize analysis of the distribution of taxa in all areas where coexist, to check whether there are or not differences in patterns of distribution and frequencies of the different citotypes depending on the latitude (from Chilches, in Castellón, up to Calblanque, in Murcia). For it, the aims of the present study are: 1. Compare the patterns of spatial distribution in different complex hybrids of different localities, from Chilches to Calblanque, passing by the Marjal dels Moros, El Saler Guardamar del Segura, Torrevieja (La Mata) and Santa Pola. 2. In each of these localities, to realice plots the largest possible, of systematic form to compare the existing proportions of the three taxa along a gradient latitudinal, and on the other hand be able to observe the patterns of distribution of these at different scales. For it there will take information of positioning in the field for every individual and the statistical analyses will be realized across the it computer tool R, that will allow to relate the position of the three taxa between them and in relation to ecological parameters such as distance to the sea or proximity of roads and infrastructure. Bibliography cited in the summary Ferriol, María, Alfonso Garmendia, Ana Gonzalez, y Hugo Merle. (2015) «Allogamy-Autogamy Switch Enhance Assortative Mating in the Allotetraploid Centaurea seridis L. Coexisting with the Diploid Centaurea aspera L. and Triggers the Asymmetrical Formation of Triploid Hybrids». PLoS ONE 10:1-13. doi:10.1371/journal.pone.0140465. Ruiz, P. (2014) Distribución y microhábitat de Centaurea aspera (2n), C. seridis (4n) y C. x subdecurrens (3n) en la provincia de Valencia. TFC. UPV, Valencia, Marzo de 2014. Ruiz, P., Garmendia, A., Ferriol, M., Merle, H. (2014) Distribución de Centaurea aspera (2n), C. seridis (4n) y su híbrido C. x subdecurrens (3n) a diferentes escalas. Eds: cámara R., Rodriguez B., Muriel JL., ¿Biogeografía de sistemas litorales. Dinámica y conservación¿. Pp: 409-412. Universidad de Sevilla.Gómez Laporta, M. (2016). Análisis de la distribución espacial en el complejo poliploide de Centaurea aspera (2n) - C.x subdecurrens (3n) - C. seridis (4n) en sus zonas de contacto. http://hdl.handle.net/10251/69070.TFG

Role of VEGF polymorphisms in the susceptibility and severity of interstitial lung disease

The search for biomarkers that can help to establish an early diagnosis and prognosis of interstitial lung disease (ILD) is of potential interest. VEGF polymorphisms have been implicated in the development of several lung disorders. Consequently, we assessed, for the first time, the role of VEGF polymorphisms in the susceptibility and severity of ILD. A total of 436 Caucasian ILD patients (244 with idiopathic interstitial pneumonias (IIPs) and 192 with non-IIP) and 536 ethnically-matched healthy controls were genotyped for VEGF rs833061, rs1570360, rs2010963, rs3025020, and rs3025039 polymorphisms by TaqMan assays. Pulmonary function tests were collected from all the patients. VEGF serum levels were determined by ELISA in a subgroup of patients. No VEGF genotype, allele, carrier, or haplotype differences were found between ILD patients and controls as well as between IIP and non-IIP patients. However, an association of rs1570360 with IIP in women and also with lung function in IIP patients was found. None of the VEGF polymorphisms were associated with VEGF levels. In conclusion, our results suggest that VEGF does not seem to play a relevant role in ILD, although rs1570360 may influence the severity of ILD in women and a worse outcome in IIP patients.Funding: This research was partially supported by a grant from Spanish Society of Pulmonology and Thoracic Surgery (SEPAR 474-2017). S.R.-M. was supported by funds of the RETICS Program (RD16/0012/0009) from the “Instituto de Salud Carlos III” (ISCIII), co-funded by the European Regional Development Fund. V.P.-C. was supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). B.A.-M. was recipient of a “López Albo” post-residency program funded by Servicio Cántabro de Salud. L.L.-G. was supported by funds from IDIVAL (INNVAL 20/06). O.G. was beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10. R.L.-M. was a recipient of a Miguel Servet type I program fellowship from the ISCIII, co-funded by the ESF, “Investing in your future” (grant CP16/00033)

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease

IntroductionWe conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF.MethodsWe studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy.ResultsWe found a prevalence of 10% (CI 4.6%–15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement.Conclusion10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients

Influence of MUC5B gene on antisynthetase syndrome

ABSTRACT: MUC5B rs35705950 (G/T) is strongly associated with idiopathic pulmonary fibrosis (IPF) and also contributes to the risk of interstitial lung disease (ILD) in rheumatoid arthritis (RA-ILD) and chronic hypersensitivity pneumonitis (CHP). Due to this, we evaluated the implication of MUC5B rs35705950 in antisynthetase syndrome (ASSD), a pathology characterised by a high ILD incidence. 160 patients with ASSD (142 with ILD associated with ASSD [ASSD-ILD+]), 232 with ILD unrelated to ASSD (comprising 161 IPF, 27 RA-ILD and 44 CHP) and 534 healthy controls were genotyped. MUC5B rs35705950 frequency did not significantly differ between ASSD-ILD+ patients and healthy controls nor when ASSD patients were stratified according to the presence/absence of anti Jo-1 antibodies or ILD. No significant differences in MUC5B rs35705950 were also observed in ASSD-ILD+ patients with a usual interstitial pneumonia (UIP) pattern when compared to those with a non-UIP pattern. However, a statistically significant decrease of MUC5B rs35705950 GT, TT and T frequencies in ASSD-ILD+ patients compared to patients with ILD unrelated to ASSD was observed. In summary, our study does not support a role of MUC5B rs35705950 in ASSD. It also indicates that there are genetic differences between ILD associated with and that unrelated to ASSD.We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was partially supported by grants from the Foundation for Research in Rheumatology (FOREUM). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ‘Instituto de Salud Carlos III’ (ISCIII), co-funded by the European Social Fund (ESF, ‘Investing in your future’) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009), co-funded by the European Regional Development Fund (ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ESF). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF). OG is Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). OG,is member of RETICS Programme, RD16/0012/0014 (RIER: Red de Investigación en Inflamación y Enfermedades Reumáticas) via Instituto de Salud Carlos III (ISCIII) and FEDER. The work of OG (PI17/00409), was funded by Instituto de Salud Carlos III and FEDER. OG is a beneficiary of a project funded by Research Executive Agency of the European Union in the framework of MSCA-RISE Action of the H2020 Programme (Project number 734899). OG is beneficiary of a grant funded by Xunta de Galicia, Consellería de Educación, Universidade e Formación Profesional and Consellería de Economía, Emprego e Industria (GAIN), GPC IN607B2019/10

Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM

Role of MUC1 rs4072037 polymorphism and serum KL-6 levels in patients with antisynthetase syndrome

Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients

Demographic and clinical profile of idiopathic pulmonary fibrosis patients in Spain: the SEPAR National Registry

BackgroundLittle is known on the characteristics of patients diagnosed with idiopathic pulmonary fibrosis (IPF) in Spain. We aimed to characterize the demographic and clinical profile of IPF patients included in the IPF National Registry of the Spanish Respiratory Society (SEPAR).MethodsThis is a prospective, observational, multicentre and nationwide study that involved 608 IPF patients included in the SEPAR IPF Registry up to June 27th, 2017, and who received any treatment for their disease. IPF patients were predominantly males, ex-smokers, and aged in their 70s, similar to other registries.ResultsUpon inclusion, meanSD predicted forced vital capacity was 77.6%+/- 19.4, diffusing capacity for carbon monoxide was 48.5%+/- 17.7, and the 6-min walk distance was 423.5m +/- 110.4. The diagnosis was mainly established on results from the high-resolution computed tomography in the proper clinical context (55.0% of patients), while 21.2% of patients required invasive procedures (surgical lung biopsy) for definitive diagnosis. Anti-fibrotic treatment was prescribed in 69.4% of cases, 51.5% pirfenidone and 17.9% nintedanib, overall with a good safety profile.Conclusions The SEPAR IPF Registry should help to further characterize current characteristics and future trends of IPF patients in Spain and compare/pool them with other registries and cohorts

Identification of potential invasive alien species in Spain through horizon scanning

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.This work is one of the main results of the InvaNET network (RED2018-102571-T, RED2022-134338-T, https://invasiber.org/InvaNET/), financially supported by MCIN/AEI/10.13039/501100011033. We thank Guido Jones, funded by the Cabildo de Tenerife under the TFinnova Programme supported by MEDI and FDCAN, for revising the English.Peer reviewe

Informe final del escaneo de horizonte sobre futuras especies exóticas invasoras en España

73 p.La introducción de especies exóticas invasoras (EEI) es una de las principales causas de la pérdida de biodiversidad a nivel global, que provoca grandes costes socioeconómicos. Sin embargo, el número de nuevas introducciones continúa creciendo año tras año. Por lo tanto, urge identificar posibles futuras EEI con el objetivo de diseñar e implementar medidas que prevengan y mitiguen los efectos negativos de su introducción. Así, el objetivo de este estudio es prospectar qué especies exóticas no establecidas en España podrían llegar fácilmente en los próximos 10 años, establecerse y causar importantes impactos ecológicos. Para ello, se ha realizado un escaneo de horizonte, siguiendo la metodología establecida en trabajos previos, siendo el primero para el conjunto de las especies exóticas invasoras en España. Se añadieron en el análisis especies que no son autóctonas de España, incluyendo los archipiélagos de Canarias y Baleares, y que no están establecidas en España. Un total de 39 científicos, expertos en distintos grupos taxonómicos y ecosistemas, ha evaluado 933 especies. Con el objetivo de analizar el acuerdo entre las evaluaciones individuales de los expertos y su consistencia, se llevaron a cabo dos análisis de fiabilidad complementarios, cuyos resultados se discuten en este informe. Como resultado del escaneo, se obtuvo una lista priorizada de 105 especies (46 con riesgo muy alto y 59 con riesgo alto). La mayoría de estas especies (84,8%), sin embargo, no están incluidas actualmente en el Catálogo Español de Especies Exóticas Invasoras. Por lo tanto, se recomienda la realización de un análisis de riesgo más detallado de estas especies y, si se confirma el riesgo alto, la solicitud de su incorporación en dicho catálogo o en el Listado de especies alóctonas susceptibles de competir con las especies silvestres autóctonas, alterar su pureza genética o los equilibrios ecológicos. Del mismo modo, se propone la realización de escaneos de horizonte específicos para los archipiélagos de Canarias y Baleares, ya que muchas de las especies autóctonas de la Península no lo son de las islas y podrían tener un gran impacto si allí se introdujeran. Este informe también analiza la afinidad taxonómica (i.e. filo) y funcional (i.e. productor primario, depredador, omnívoro, herbívoro o filtrador) de las especies de la lista priorizada, su origen geográfico y las principales vías de introducción. Por último, discute los mecanismos de impacto de dichas especies.Ministerio de Ciencia e Innovació