17 research outputs found

    A novel source of arterial valve cell linked to bicuspid aortic valve without rephe in mice

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    Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe.British Heart Foundation RG/12/15/29935 Lorriane Eley Rachel V Richardson Lindsay Murphy Bill Chaudhry Deborah J Henderson; British Heart Foundation PG/15/46/31589 Lorriane Eley Bill Chaudhry Deborah J Henderson; Ministerio de Ciencia, Innovacion y Universidades of Spain CB16/11/00399 (Ciber Cardiovascular) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain SAF2016-78370-R Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain RD16/0011/0021 (Red de Terapia Celular, TERCEL) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.S

    Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

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    In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries.This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, project “Estudios sobre vigilancia epidemiológica molecular del VIH-1 en España,” PI16CIII/00033; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I+D+I, project RD16ISCIII/0002/0004; scientific agreements with Consellería de Sanidade, Government of Galicia (MVI 1004/16) and Osakidetza-Servicio Vasco de Salud, Government of Basque Country (MVI 1001/16); European Research Infrastructures for Poverty Related Diseases (EURIPRED). Seventh Framework Program: FP7-Capacities-infrastructures-2012-1, grant agreement 312661; and Dirección General de Farmacia, Ministerio de Sanidad, Servicios Sociales e Igualdad, Government of Spain (grant EC11-272).S

    Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain

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    In Western Europe, the HIV-1 epidemic among men who have sex with men (MSM) is dominated by subtype B. However, recently, other genetic forms have been reported to circulate in this population, as evidenced by their grouping in clusters predominantly comprising European individuals. Here we describe four large HIV-1 non-subtype B clusters spreading among MSM in Spain. Samples were collected in 9 regions. A pol fragment was amplified from plasma RNA or blood-extracted DNA. Phylogenetic analyses were performed via maximum likelihood, including database sequences of the same genetic forms as the identified clusters. Times and locations of the most recent common ancestors (MRCA) of clusters were estimated with a Bayesian method. Five large non-subtype B clusters associated with MSM were identified. The largest one, of F1 subtype, was reported previously. The other four were of CRF02_AG (CRF02_1; n = 115) and subtypes A1 (A1_1; n = 66), F1 (F1_3; n = 36), and C (C_7; n = 17). Most individuals belonging to them had been diagnosed of HIV-1 infection in the last 10 years. Each cluster comprised viruses from 3 to 8 Spanish regions and also comprised or was related to viruses from other countries: CRF02_1 comprised a Japanese subcluster and viruses from 8 other countries from Western Europe, Asia, and South America; A1_1 comprised viruses from Portugal, United Kingom, and United States, and was related to the A1 strain circulating in Greece, Albania and Cyprus; F1_3 was related to viruses from Romania; and C_7 comprised viruses from Portugal and was related to a virus from Mozambique. A subcluster within CRF02_1 was associated with heterosexual transmission. Near full-length genomes of each cluster were of uniform genetic form. Times of MRCAs of CRF02_1, A1_1, F1_3, and C_7 were estimated around 1986, 1989, 2013, and 1983, respectively. MRCA locations for CRF02_1 and A1_1 were uncertain (however initial expansions in Spain in Madrid and Vigo, respectively, were estimated) and were most probable in Bilbao, Spain, for F1_3 and Portugal for C_7. These results show that the HIV-1 epidemic among MSM in Spain is becoming increasingly diverse through the expansion of diverse non-subtype B clusters, comprising or related to viruses circulating in other countries

    Macrocicles pseudopeptídics metàl·lics. Estudi de processos de reconeixement molecular d'aminoàcids

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    Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2014, Tutors: Dra. Laura Rodríguez Raurell i Dr. Ignacio Alfonso RodríguezThe aim of this work is the synthesis of the chiral pseudopeptidic macrocycle 5b and its use, together with analogue macrocycle 5a (Scheme 1) as ligands for Cu2+, in molecular recognition processes of amino acids. The two dinuclear complexes will be used as receptors in molecular recognition processes. The synthesis of the [2+2] pseudopeptidic macrocycle through a reductive amination is carried out by using an anionic template which places the four subunits in the right orientation for their union. The obtained product is characterized by ESI-MS and NMR. Copper complexes are prepared starting with the meta macrocycle and its para analogue. The resulting products are characterized by ESI MS. A comparative study of many amino acids and analogues behavior with the two macrocyclic complexes is carried out by UV-Vis spectrophotometry. After that, recognition tests are made with the two possible Malate isomers and association constants values are calculated for both isomers with macrocyclic copper complex

    Ciència a Secundària: Com abordar l’assignatura de Física i Química al primer cicle

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    [cat] En aquest treball s’analitza l’estat de l’ensenyament de la ciència a Espanya, en base als resultats estatals obtinguts de proves PISA i ALTIS. Aquests resultats, juntament amb l’experiència pròpia, motiven el replantejament que es fa sobre com ha de ser una persona competent en ciència i com s’ha d’abordar al primer cicle aquesta formació. Les característiques del coneixement científic i el model dimensional de la competència científica són els pilars amb es què es basa la proposta feta en aquest treball. Per tal de construïr un coneixement funcional, es recorre a un procés d’ensenyament que introdueix els continguts com a conceptes explicatius de fenòmens naturals. La part competencial es treballa a través d’una varietat d’activitats que incideixen sobre diferents dominis de la competència. Aquest procés s’avalua de forma continua fent us de pràctiques formatives i formadores

    Analysis and optimization of a high dynamic range video method

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    Treball de fi de grau en Sistemes AudiovisualsTutors: Marcelo Bertalmío i Raquel GilThis work presents an optimization of a computationally expensive technique to generate high resolution high dynamic range videos from images alternating pairs of rows taken under different ISO values. This technique generates two single full-frame images, one for each ISO value and combines them to obtain a single high dynamic range image without the presence of ghosting artifacts. Different optimization techniques and parallel programming are used to reduce the initial execution time while preserving the same quality result. This work also presents an analysis of the different image-dependent parameters used in the algorithm as well as the effect of choosing different values in order to achieve the best compromise between image quality and execution time. Finally, two versions of this approach are introduced to obtain similar visual quality results that require less computation time and both approaches are discussed and compared with the original technique.Aquest treball presenta l’optimitzacio d’una tècnica computacionalment costosa per generar videos d’alta resolucio d’alt rang din ´ amic a partir d’imatges que alternen parelles de files preses amb diferents valors de ISO. Aquesta èecnica genera dues imatges d’alta resolucio, una per cada valor de ISO i les combina per obtenir una sola imatge d’alt rang dinamic lliure de la presència d’artefactes fantasma. Diverses tecniques d’optimització i programació paral·lela s’han fet servir per reduir el temps d’execucio inicial preservant la mateixa qualitat en els resultats. Aquest treball tambe presenta un anàlisis dels diferents paràmetres dependents de la imatge utilitzats per l’algoritme així com l’afecte de l’eleccio de diferents valors per tal d’aconseguir el millor comprom´ıs entre qualitat d’imatgei temps d’execucio. Finalment, s’introdueixen dues variants d’aquest mètode per obtenir resultats de qualitat visual similar que requereixen menys temps de calcul, i tots dos enfocaments es discuteixen i es comparen amb la tècnica original

    Semantic image inpainting through improved Wasserstein generative adversarial networks

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    Comunicació presentada a: VISAPP 2019, celebrada a Praga, República Txeca, del 25 al 27 de febrer de 2019Image inpainting is the task of filling-in missing regions of a damaged or incomplete image. In this work we tackle this problem not only by using the available visual data but also by incorporating image semantics through the use of generative models. Our contribution is twofold: First, we learn a data latent space by training an improved version of the Wasserstein generative adversarial network, for which we incorporate a new generator and discriminator architecture. Second, the learned semantic information is combined with a new optimization loss for inpainting whose minimization infers the missing content conditioned by the available data. It takes into account powerful contextual and perceptual content inherent in the image itself. The benefits include the ability to recover large regions by accumulating semantic information even it is not fully present in the damaged image. Experiments show that the presented method obtains qualitative and quantitative top-tier results in different experimental situations and also achieves accurate photo-realism comparable to state-of-the-art works.The authors acknowledge partial support by MINECO/FEDER UE project, reference TIN2015-70410-C2-1 and by H2020-MSCA-RISE-2017 project, reference 777826 NoMADS

    Semantic image inpainting through improved Wasserstein generative adversarial networks

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    Comunicació presentada a: VISAPP 2019, celebrada a Praga, República Txeca, del 25 al 27 de febrer de 2019Image inpainting is the task of filling-in missing regions of a damaged or incomplete image. In this work we tackle this problem not only by using the available visual data but also by incorporating image semantics through the use of generative models. Our contribution is twofold: First, we learn a data latent space by training an improved version of the Wasserstein generative adversarial network, for which we incorporate a new generator and discriminator architecture. Second, the learned semantic information is combined with a new optimization loss for inpainting whose minimization infers the missing content conditioned by the available data. It takes into account powerful contextual and perceptual content inherent in the image itself. The benefits include the ability to recover large regions by accumulating semantic information even it is not fully present in the damaged image. Experiments show that the presented method obtains qualitative and quantitative top-tier results in different experimental situations and also achieves accurate photo-realism comparable to state-of-the-art works.The authors acknowledge partial support by MINECO/ FEDER UE project, reference TIN2015-70410-C2-1 and by H2020-MSCA-RISE-2017 project, reference 777826 NoMAD

    Characterization and Local Emission Sources for Ammonia in an Urban Environment

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    Ammonia levels were evaluated in the urban environment of Madrid City, Spain. A total of 110 samplers were distributed throughout the city. Vehicle traffic density, garbage containers and sewers were identified as local emission sources of ammonia. The average ammonia concentrations were 4.66 ± 2.14 µg/m3 (0.39-11.23 µg/m3 range) in the winter and 5.30 ± 1.81 µg/m3 (2.33-11.08 µg/m3 range) in the summer. Spatial and seasonal variations of ammonia levels were evaluated. Hotspots were located in the south and center of Madrid City in both winter and summer seasons, with lower ammonia concentrations located in the north (winter) and in the west and east (summer). The number of representative points that were needed to establish a reliable air quality monitoring network for ammonia was determined using a combined clustering and kriging approach. The results indicated that 40 samplers were sufficient to provide a reliable estimate for Madrid City.The authors gratefully acknowledge the members of the Department of Atmospheric Pollution from the National Center for Environmental Health for their assistance in sample collection. This work was supported by the Municipality of Madrid

    Mosmo Is Required for Zebrafish Craniofacial Formation

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    Hedgehog (Hh) signaling is a highly regulated molecular pathway implicated in many developmental and homeostatic events. Mutations in genes encoding primary components or regulators of the pathway cause an array of congenital malformations or postnatal pathologies, the extent of which is not yet fully defined. Mosmo (Modulator of Smoothened) is a modulator of the Hh pathway, which encodes a membrane tetraspan protein. Studies in cell lines have shown that Mosmo promotes the internalization and degradation of the Hh signaling transducer Smoothened (Smo), thereby downmodulating pathway activation. Whether this modulation is essential for vertebrate embryonic development remains poorly explored. Here, we have addressed this question and show that in zebrafish embryos, the two mosmo paralogs, mosmoa and mosmob, are expressed in the head mesenchyme and along the entire ventral neural tube. At the cellular level, Mosmoa localizes at the plasma membrane, cytoplasmic vesicles and primary cilium in both zebrafish and chick embryos. CRISPR/Cas9 mediated inactivation of both mosmoa and mosmob in zebrafish causes frontonasal hypoplasia and craniofacial skeleton defects, which become evident in the adult fish. We thus suggest that MOSMO is a candidate to explain uncharacterized forms of human congenital craniofacial malformations, such as those present in the 16p12.1 chromosomal deletion syndrome encompassing the MOSMO locusSpanish MINECO (BFU2016-75412-R with FEDER funds); AEI (PID2019-104186RB-I00 and RED2018-102553-T) and a grant from the Fundación Ramon Areces to PB. CC-M and MC are supported by predoctoral contract from the CIBERER and a Juan de la Cierva postdoctoral contract from the AEI (IJCI-2016-27683), respectively. IG is supported by a contract (CAM20_CBM_AI_06) from the 2020 program “Garantía Juvenil” of the Comunidad Autónoma de Madri
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