Smart lanthanide antennas for sensing water

Two new families of lanthanide antennas are described. 8-Methoxy- 4,5-dihydrocyclopenta[de]quinolin-2(1H)-one phosphonates or carboxylates behave as selective antennas exhibiting Eu3+ luminescence in organic solvents, while quinolin-2(1H)-one analogues selectively sensitize the Tb3+ emission. These emissions are quenched by H2O addition. Based on this behaviour, the new lanthanide antennas can be used as highly sensitive water sensors.Spanish Ministerio de Economia y Competividad SAF2012-32209 FU2015-67284-RMinisterio de Ciencia e Innovacion/Agencia Estatal de Investigacion/European Regional Development Fund CTQ2017-85658-R CTQ2015-63997-C2Consejo Superior de Investigaciones Cientificas (CSIC) 201580E07

Mesenchymal stromal cells (MSC) from JAK2+ myeloproliferative neoplasms differ from normal MSC and contribute to the maintenance of neoplastic hematopoiesis

[EN]There is evidence of continuous bidirectional cross-talk between malignant cells and bone marrow-derived mesenchymal stromal cells (BM-MSC), which favors the emergence and progression of myeloproliferative neoplastic (MPN) diseases. In the current work we have compared the function and gene expression profile of BM-MSC from healthy donors (HDMSC) and patients with MPN (JAK2V617F), showing no differences in the morphology, proliferation and differentiation capacity between both groups. However, BM-MSC from MPN expressed higher mean fluorescence intensity (MIF) of CD73, CD44 and CD90, whereas CD105 was lower when compared to controls. Gene expression profile of BM-MSC showed a total of 169 genes that were differentially expressed in BM-MSC from MPN patients compared to HD-MSC. In addition, we studied the ability of BM-MSC to support the growth and survival of hematopoietic stem/progenitor cells (HSPC), showing a significant increase in the number of CFU-GM colonies when MPN-HSPC were co-cultured with MPN-MSC. Furthermore, MPN-MSC showed alteration in the expression of genes associated to the maintenance of hematopoiesis, with an overexpression of SPP1 and NF-kB, and a downregulation of ANGPT1 and THPO. Our results suggest that BM-MSC from JAK2+ patients differ from their normal counterparts and favor the maintenance of malignant clonal hematopoietic cell

Persistent Pulmonary Hypertension in Corrected Valvular Heart Disease: Hemodynamic Insights and Long-Term Survival.

Background The determinants and consequences of pulmonary hypertension after successfully corrected valvular heart disease remain poorly understood. We aim to clarify the hemodynamic bases and risk factors for mortality in patients with this condition. Methods and Results We analyzed long-term follow-up data of 222 patients with pulmonary hypertension and valvular heart disease successfully corrected at least 1 year before enrollment who had undergone comprehensive hemodynamic and imaging characterization as per the SIOVAC (Sildenafil for Improving Outcomes After Valvular Correction) clinical trial. Median (interquartile range) mean pulmonary pressure was 37 mm Hg (32-44 mm Hg) and pulmonary artery wedge pressure was 23 mm Hg (18-26 mm Hg). Most patients were classified either as having combined precapillary and postcapillary or isolated postcapillary pulmonary hypertension. After a median follow-up of 4.5 years, 91 deaths accounted for 4.21 higher-than-expected mortality in the age-matched population. Risk factors for mortality were male sex, older age, diabetes mellitus, World Health Organization functional class III and higher pulmonary vascular resistance-either measured by catheterization or approximated from ultrasound data. Higher pulmonary vascular resistance was related to diabetes mellitus and smaller residual aortic and mitral valve areas. In turn, the latter correlated with prosthetic nominal size. Six-month changes in the composite clinical score and in the 6-minute walk test distance were related to survival. Conclusions Persistent valvular heart disease-pulmonary hypertension is an ominous disease that is almost universally associated with elevated pulmonary artery wedge pressure. Pulmonary vascular resistance is a major determinant of mortality in this condition and is related to diabetes mellitus and the residual effective area of the corrected valve. These findings have important implications for individualizing valve correction procedures. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00862043.This study was funded by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Spain, the European Union–European Regional Development Fund (EC07/90772 and PI19/00649), and the Consorcio de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV).S

Structural Analysis and Active strain-field for Induced Seismicity in gas storage facilities: Hontomin study-case (SPAIN)

La determinación de las fallas capaces de disparar terremotos en zonas adyacentes con formaciones geológicas aptas para el almacenamiento profundo de gas, es una tarea que mitiga la ocurrencia de sismicidad inducida por operaciones subterráneas y movimiento de fluidos. Para ello, la determinación del campo de esfuerzos/deformación tectónicos activo ayuda a entender los patrones tridimensionales de fracturación cartografiados no solo en la zona, sino también en la propia roca almacén. Por este motivo, se presenta un protocolo de trabajo para la obtención del campo de deformación (σHmax, σhmin) que ayude a entender el papel de cada conjunto de fallas cartografiado. Para ello, aplicamos el Análisis Poblacional de fallas en dos zonas de influencia: 1) Campo cercano: 10 km de diámetro del almacenamiento y 2) Campo Lejano: 20 km de diámetro. Sobre estas zonas calculamos las trayectorias de deformación y llevamos a cabo una cartografía sistemática de fallas. Se presentan los resultados preliminares de Hontomín.The cartography of seismogenic active faults in adjacent areas of underground gas storage helps in the management for Induced Seismicity related to deep fluid movement and injection/extraction manoeuvres. In this sense, the determination of the Active Stress field into the area allows the understanding of the 3D fracture patterns and their role in earthquake occurrence. We introduce a protocol for study active tectonic stress by using the classical Structural Analysis based on brittle techniques. Accordingly, we have defined two different areas for studying: (1) Near field, 10 km of diameter from the Storage Site and (2) Far Field, 20 km diameter. Preliminary results for Hontomin site are presented.Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasTRUEUnión Europea. Horizonte 2020pu

The Spanish Infrared Camera onboard the EUSO-BALLOON (CNES) flight on August 24, 2014

The EUSO-Balloon (CNES) campaign was held during Summer 2014 with a launch on August 24. In the gondola, next to the Photo Detector Module (PDM), a completely isolated Infrared camera was allocated. Also, a helicopter which shooted flashers flew below the balloon. We have retrieved the Cloud Top Height (CTH) with the IR camera, and also the optical depth of the nonclear atmosphere have been inferred with two approaches: The first one is with the comparison of the brightness temperature of the cloud and the real temperature obtained after the pertinent corrections. The second one is by measuring the detected signal from the helicopter flashers by the IR Camera, considering the energy of the flashers and the location of the helicopter

Evidencias de terremotos cuaternarios en una sima hipogénica: La Sima de Benís (Murcia, SE España)

La interacción entre una cueva hipogénica y la actividad de una falla cuaternaria es la principal responsable de la génesis de la cueva más profunda de la Región de Murcia y una de las mayores cavidades hipogénicas del sur de la península. La Sima de Benís presenta una amplia y única variedad de espeleotemas y de estructuras de disolución que se encuentran afectadas por deformaciones sísmicas producidas tanto por paleoterremotos durante el Pleistoceno Superior, como por terremotos instrumentales (Mw 4,8; VI EMS-98, 1999; Mula). Además, dentro de las zonas más profundas de la cueva aparecen restos fósiles “in situ” de macromamíferos (Lynx pardinus spelaeus), los cuales hemos relacionado con la actividad sísmica en el interior de la caverna. En cuanto a su topografía, esta cavidad presenta dos sectores bien diferenciados: (1) un primer sector de 150-160 m de desarrollo vertical con pozos de origen hipogénico con desarrollo de golpes de gubia y conductos de disolución ascendentes (con “outlets” y “megascallops”) y (2) un segundo sector entre los 150 - 160 m y los 320 m de profundidad, el cual se desarrolla sobre un plano de falla normal de dirección N-S (Falla de Benís). Este segundo sector de la sima es el que presenta evidencias paleosísmicas cuaternarias, dividiéndose a su vez en dos zonas en relación a la dinámica kárstica dominante: (2.a) una zona vadosa dominada por estructuras hipogénicas (donde aparecen folias y corales), junto con marcas cinemáticas de movimiento de la falla (estrías con recristalizaciones y concreciones carbonatadas) y (2.b) una zona freática profunda controlada por la precipitación de nubes de calcita bajo lámina de agua y de tamaño métrico que se desarrolla hasta los - 320 m de profundidad. En cuanto a la parte hipogénica superior de la sima, se desarrolla a favor de una fractura con relleno de calcita y de orientación E-W sobre carbonatos del Cretácico superior y el Paleoceno, con un espesor centimétrico y evidencias de relleno posterior y circulación de fluidos. La potencial actividad paleosísmica ha podido ser datada en 65 ± 17,6 ka (OIS 4) mediante el análisis de racemización de aminoácidos de los colmillos de un lince de las cavernas, el cual pudo ser afectado por un terremoto. Por último, se ha estimado el tamaño del último sismo relacionado con la actividad de la falla a partir de relaciones empíricas, con un valor de Mw oscilando entre 5,5 y 6. Para ello se ha estimado la longitud en superficie de la traza de falla que controla la cueva en profundidad y se ha comparado con el último salto cosísmico observable en el interior de la sima. Estimaciones del salto de falla acumulado y la datación del último paleoterremoto, sugieren que parte de la evolución hipogénica con paleoterremotos de esta cavidad de forma conjunta se produjo al menos, desde hace 250 ka (OIS 7)

Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor

Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions.Trabajo financiado por: Ministerio de Economía y Competitividad. Proyectos BFU2011-22678, SAF2014-51813-R (I+D+i) para Pedro María Fernández Salguero Ministerio de Economía y Competitividad, Instituto Carlos III, Red Temática de Investigación Cooperativa en Cáncer Junta de Extremadura. Ayudas GR10008, GR15008 CICE-FEDER-P09-CTS-4980, CICE-FEDERP12-CTS-2256, Plan Nacional de I+D+I 2008–2011 y 2013–2016 (FIS-FEDER-PI11/01489, FIS-FEDERPI14/02152), PCIN-2014-115-ERA-NET NEURON II, para José Luis García Pérez European Research Council ERC-Consolidator ERC-STG-2012-233764 International Early Career Scientist Beca de la Howard Hughes Medical Institute IECS-55007420 Programa Unión Europea de Fondos FEDERpeerReviewe

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.</p> <p>Methods</p> <p>CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in <it>ADH1C</it>, <it>APC</it>, <it>CCDN1</it>, <it>IL6</it>, <it>IL8</it>, <it>IRS1</it>, <it>MTHFR</it>, <it>PPARG</it>, <it>VDR </it>and <it>ARL11</it>, and 18 selected variants in the mucin gene family.</p> <p>Results</p> <p>None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a <it>P</it>-value < 0.05 in EPICOLON stage 1 [rs698 in <it>ADH1C </it>(OR = 1.63, 95% CI = 1.06-2.50, <it>P</it>-value = 0.02, recessive), rs1800795 in <it>IL6 </it>(OR = 1.62, 95% CI = 1.10-2.37, <it>P</it>-value = 0.01, recessive), rs3803185 in <it>ARL11 </it>(OR = 1.58, 95% CI = 1.17-2.15, <it>P</it>-value = 0.007, codominant), and rs2102302 in <it>GALNTL2 </it>(OR = 1.20, 95% CI = 1.00-1.44, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, <it>P</it>-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, <it>P</it>-value = 0.09, log-additive 0, 1, 2 alleles).</p> <p>Conclusions</p> <p><it>ARL11</it>, <it>ADH1C</it>, <it>GALNTL2 </it>and <it>IL6 </it>genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.</p