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Learning objectives Background Findings and procedure details Conclusion Personal information and conflict of interest References, Learning objectives: To use MRI findings as a retrospective learning resource to improve the performance of CT diagnosing. To emphasize the importance of correlating the findings obtained by MRI and CT. To explain possible sources of error and useful practices to...

Learning objectives Background Findings and procedure details Conclusion Personal information and conflict of interest References, Learning objectives: To explain the systemic thrombotic complications that can be associate with the evolution of the COVID-19 disease. To show the most frequent imaging manifestations of systemic thrombotic events in order to help radiologists identify them when...

Learning objectives Background Findings and procedure details Conclusion Personal information and conflict of interest References, Learning objectives: To define the Syndrome of Combined Pulmonary Fibrosis and Emphysema, by reviewing the terminology, definitions, characteristics and imaging features that characterize it. To summarize and simplify diagnostic criteria for CPFE. To illustrate the...

Trabajo presentado en la conferencia "Ocupabilidad y Formación Universitaria en el ámbito de las Biociencias", celebrado en Barcelona (España) el 15 de diciembre de 2022.

Trabajo presentado en el 19th International Congress of Developmental Biology, celebrado en Guia (Portugal) del 16 al 20 de octubre de 2022., Regeneration in mammals is limited to the digit tips. The amputation of the distal tip of the terminal phalanx triggers the formation of an undifferentiated pool of progenitor cells called a blastema that will regenerate the multiple tissues required to restore the missing part. Digit tip regeneration is linked to the presence of the dorsal nail organ, as only amputations that conserve the nail matrix regenerate. However, the regenerative potential of digits without nails has not yet been tested. To evaluate nailless digits, we used dLARM1/2 mutants that develop digits with no nails due to the limb-specific loss of the dorsal limb determinant Lmx1b. We report that dLARM1/2 mutant digits are unable to regenerate, although they form a blastema. To test whether the lack of regeneration was due to the absence of dorso-ventral (DV) polarity, a concept suggested in amphibia, we evaluated Del(27) mutants that also lack DV polarity with nails on both dorsal and ventral aspects of distal phalanges due to ventral overexpression of Lmx1b. Unlike dLARM1/2 mutants, Del(27) mutant digits regenerated indicating that DV polarity is dispensable for regeneration. Interestingly, Lmx1b expression (which continues in the nail dermis postnatally) is detected uniformly in the blastema of WT, but not dLARM1/2 mutant mice. In addition, comparison of dLARM1/2 vs WT blastemal transcriptomes revealed that the mutants had defective pro regenerative processes such as vasculogenesis and extracellular matrix remodeling, while inflammatory pathways were exacerbated. Gene expressions typical of the nail dermis were also lost in dLARM1/2 digit tips, suggesting regulation by Lmx1b. Collectively, our data suggest a direct role for Lmx1b in digit tip regeneration maintaining the nail dermis and promoting a competent blastema.

Trabajo presentado en el 19th International Congress of Developmental Biology, celebrado en Guia (Portugal) del 16 al 20 de octubre de 2022., The dorso-ventral (DV) limb asymmetry is crucial for its function; however, little is known about how it is accomplished during morphogenesis. Lmx1b is the key regulator of DV patterning during limb development as it is both necessary and sufficient to specify dorsal fates, but its regulation remains poorly known. We recently demonstrated a complex autoregulatory mode of transcriptional Lmx1b regulation mediated by two limb-specific enhancers, LARM1 and LARM2. The deletion of both enhancers (dLARM1/2) reproduces the Lmx1b-null phenotype in the limb, while the removal of each enhancer produced a double ventral phenotype restricted to the posterior (dLARM1) or anterior (dLARM2) half of the limb. To investigate the regulatory logic of the Lmx1b locus in detail, we dissected the LARM1 element into its enhancer and silencer sequences and explored the functional contribution of the two Lmx1b-associated lncRNAs. The results confirm the presence of a functional repressor contained in LARM1 and underscore the positional specificity of the LARM sequences. The data suggests that Lmx1b transcription uses different regulatory elements in different positions probably reflecting the integration of the local transcriptional environment. Indeed, published ChIP-seq data showed the Gli3 and Hox13 are significantly enriched in the LARM sequences exposing their interaction with major limb regulators. Finally, considering that the double-ventral limbs of dLARM1/2 mutants fail to support locomotion, even to lift the body weight, we hypothesized that the elaboration of the DV asymmetry by modification of Lmx1b regulation, or its functional targets, had to accompany the fin to limb transition. We have identified orthologs of the LARMs in fishes and all of them show activity in the pectoral fin in zebrafish reporter essays, revealing the deep roots of Lmx1b regulation., Spanish Ministry of Science and Innovation Grant PID2020-114525GB-I00 to Marian Ros. Sofía Zdral is supported by a PhD fellowship of the University of Cantabria and Alejandro Castilla Ibeas by a PhD fellowship of the Ministry of Science and Innovation (FSE/AEI/PRE2018-083421).

Trabajo presentado en la 16th International Conference on Limb Development, regeneration, and evolution, celebrada en Cambridge (Estados Unidos) del 08 al 11 de agosto de 2022., The dorso-ventral (DV) organization of limb morphology is crucial for its function but little is known about how it is implemented during morphogenesis. Lmx1b is the key regulator of DV patterning as it is both necessary and sufficient to specify dorsal fates, but its regulation remains poorly known. Recently, we reported that Lmx1b is subject to a complex and autoregulatory mode of transcriptional regulation mediated by two limb-specific enhancers termed LARM1 and LARM2. Interestingly, these enhancers display anterior-posterior (AP) spatial modularity with LARM1 controlling Lmx1b expression in the anterior and LARM2 in the posterior half of the limb. To investigate the regulatory logic of the Lmx1b locus in higher detail, we have dissected the LARM1 enhancer and explored the functional contribution of two Lmx1b associated lncRNAs. The results confirm the presence of a functional repressor and underscore the AP positional specificity of the LARM sequences. Conjointly, the data suggests that Lmx1b transcription uses different regulatory elements in different positions probably reflecting the integration of the local transcriptional environment. Finally, since the double-ventral limbs of dLARM1/2 mutants fail to support locomotion, we hypothesized that the elaboration of the DV axis, possible driven by changes in the regulatory genome, had to accompany the fin transition towards appendages capable of lifting the body weight. In this direction, we have identified orthologs of the LARM sequences from chondrichthyans. All these sequences show activity in the pectoral fin in zebrafish reporter assays, revealing the deep roots of Lmx1b regulation.

Trabajo presentado en el 16th International Conference on Limb Development, Regeneration, and Evolution, celebrado en Cambridge (Estados Unidos) del 08 al 11 de agosto de 2022., Mammalian limb regeneration is restricted to the distal third of terminal phalanges. Amputation of distal digit tips results in blastema formation and restoration of the missing part. This regenerative response has been linked to the presence of the nail, but digits without nails have not been evaluated. Here we interrogate the regenerative ability of the double-ventral digits of dLARM1/2 mutants, which lack dorsal nails due to the limb-specific absence of Lmx1b. We report that these nail-less digits fail to regenerate, supporting the nail requirement. Because the absence of dorso-ventral (DV) polarity could also impair regeneration, as reported in amphibians, we tested the double-dorsal double-nail digits of Del(27) mutants, which lack DV polarity due to the limb-restricted loss of En1. Since Del(27) digits did regenerate, we concluded that DV polarity is not required for digit tip regeneration. We documented continued dorsal expression of Lmx1b postnatally in the wild-type (WT) nail dermis. Moreover, there is uniform Lmx1b expression in WT regeneration-competent blastemas. Transcriptomic comparison between WT and dLARM1/2 mutant blastemas revealed differential up-regulation of gene signatures functionally associated with vascularization and connective tissue remodeling in WT mice. In contrast, the dLARM1/2 non-regenerative blastemas that lack Lmx1b expression show differential up-regulation of genes associated with inflammation and inflammatory processes. Conjointly, our data implicate a direct role for Lmx1b in digit tip regeneration by maintaining the nail dermis and promoting a competent blastema.

Trabajo presentado en The Company of Biologists Workshop Molecular mechanisms of developmental and regenerative biology (EMBO), celebrado en modalidad virtual del 26 al 29 de abril de 2022., The regeneration of the digit tip is an exceptional model of multi-tissue regeneration in mammals, with remarkable potential to advance regenerative medicine. Digit tip regeneration positively correlates with the presence of the nail organ, most likely because of the environment of the nail stem cells, but the underlying mechanisms are still unclear. The fact that the nail is a dorsal structure links regeneration with dorso-ventral (DV) polarity. Here, to evaluate the nail function more directly, and to disentangle it from DV positional information, we tested the regenerative ability of double-ventral digits and double-dorsal digits resulting from the limb-specific loss of Lmx1b and of En1 expression, respectively. Our results indicate that DV polarity is not required for digit tip regeneration but that an excessive inflammatory response prevents regeneration in the absence of Lmx1b. The possible causes of the exacerbated inflammation in the absence of Lmx1b are discussed.

El trabajo que presentamos analiza la evolución del tratamiento jurídico de la insolvencia a lo largo de las civilizaciones antiguas más sobresalientes: mesopotámica, griega y romana. Llegado a la civilización romana es obligado profundizar en el estudio de las instituciones directamente relacionadas con el tratamiento de la insolvencia: cessio bonorum, bonorum venditio y bonorum distractio. A partir de ese punto, seguimos en la España medieval para rastrear la impronta de dichas instituciones en la legislación del reino de Toledo; así como en las compilaciones visigóticas y su adaptación en los reinos cristianos, hasta la promulgación de Las Siete Partidas. En el recorrido legislativo analizamos los códigos legales siguientes: Liber Iudiciorum; Fuero Viejo de Castilla; Fuero Real; así como, los posteriores Ordenamiento de Alcalá y Leyes de Toro.La última parte del trabajo se adentra en la Edad Contemporánea, para conocer el procedimiento de quiebra y suspensión de pagos, regulado en las Ordenanzas de Bilbao de 1737 y en los Códigos de Comercio de 1829 y 1885, respectivamente. Finalizamos con el análisis de la Ley, 26 de julio de 1922, de “suspensión de pagos” y la regulación actual que se encuentra en el Real Decreto legislativo 1/2020, de 5 de mayo, por el que se aprueba el texto refundido de la Ley concursal.

[ES] Este TFG se lleva a cabo durante 5 meses de prácticas en la empresa Carpigiani Horeca. Es una empresa que se dedica a la fabricación y comercialización de maquinaria para la hostelería, en concreto, de heladería y granizados. Puesto que la empresa está en pleno crecimiento, se están realizando diversas mejoras que permitan incrementar la productividad y la calidad de los productos. Éste es el objetivo principal del presente trabajo, que se centra en una de las ocho líneas de producción de la planta, donde es especialmente necesario estandarizar los métodos de trabajo en las estaciones, así como equilibrar la línea para una mayor eficiencia productiva. Para conseguir dichos objetivos, primeramente, se expone como es y por qué se ha seleccionado la línea en la que se centra el proyecto. Y a continuación, se lleva a cabo un análisis de la situación inicial, con el fin de definir y categorizar las incidencias que se dan con mayor frecuencia. Estas servirán de punto de partida para la propuesta y aplicación del método de las 5S en dicha línea de producción, que además se estudia aplicar en dos fases sucesivas, una de iteración inicial, y otra más centrada en la estandarización. Dado que la línea está formada por 4 estaciones de trabajo con tiempos de ciclo muy largos, es necesario estimar los tiempos con distintas técnicas complementarias de medición del trabajo, que son debidamente detalladas. Una vez estandarizados los métodos de trabajo y definidos los tiempos de cada tarea, se realizan varias propuestas de re equilibrado de la línea, evaluando pros y contras de cada una y proponiendo plan de implantación para la configuración finalmente elegida, en base a varios criterios que son debidamente definidos. Finalmente, se elabora el correspondiente presupuesto de las acciones realizadas y propuestas., [CA] Aquest TFG es duu a terme durant 5 mesos de pràctiques a l'empresa Carpigiani Horeca. És una empresa que es dedica a la fabricació i comercialització de maquinària per a l'hostaleria, en concret, de gelateria i granissats. Com que l'empresa està en ple creixement, s'estan fent diverses millores que permetin incrementar la productivitat i la qualitat dels productes. Aquest és l'objectiu principal del present treball, que se centra en una de les vuit línies de producció de la planta, on és especialment necessari estandarditzar els mètodes de treball a les estacions, així com equilibrar la línia per a una major eficiència productiva. Per aconseguir aquests objectius, primerament, s'exposa com és i perquè s'ha seleccionat la línia en què se centra el projecte. I a continuació, es fa una anàlisi de la situació inicial, per tal de definir i categoritzar les incidències que es donen amb més freqüència. Aquestes servirán de punt de partida per a la proposta i l'aplicació del mètode de les 5S en aquesta línia de producció, que a més s'estudia aplicar en dues fases successives, una d'iteració inicial, i una altra de més centrada en l'estandardització. Atès que la línia està formada per 4 estacions de treball amb temps de cicle molt llargs, cal estimar els temps amb diferents tècniques complementàries de mesurament del treball, que són degudament detallades. Un cop estandarditzats els mètodes de treball i definits els temps de cada tasca, es realitzen diverses propostes de reequilibrament de la línia, avaluant pros i contres de cadascuna i proposant pla d'implantació per a la configuració escollida, en base a diversos criteris que són degudament definits. Finalment, s'elabora el pressupost corresponent de les accions realitzades i proposades., [EN] This TFG is carried out during 5 months of work experience in the company Carpigiani Horeca. It is a company that manufactures and sells machinery for the hotel and catering industry, specifically ice cream and slush drinks. As the company is growing, several improvements are being made to increase productivity and product quality. This is the main objective of the present work, which focuses on one of the plant's eight production lines, where it is especially necessary to standardize the working methods at the stations, as well as to balance the line for greater production efficiency. In order to achieve these objectives, first of all, it is explained how and why the line on which the project is focused has been selected. Next, an analysis of the initial situation is carried out in order to define and categories the most frequent incidents. These will serve as a starting point for the proposal and application of the 5S method on this production line, which will also be applied in two successive phases, one of initial iteration, and the other more focused on standardization. Given that the line is made up of 4 workstations with very long cycle times, it is necessary to estimate the times with different complementary work measurement techniques, which are duly detailed. Once the working methods have been standardized and the times of each task have been defined, several proposals are made for rebalancing the line, evaluating the pros and cons of each one and proposing an implementation plan for the configuration finally chosen, based on various criteria that are duly defined. Finally, the corresponding budget is drawn up for the actions carried out and proposed.

A través del relato de la participación en diferentes rituales, y de un ejercicio de reflexividad, exploro las categorías “experiencia religiosa”, el rol del cuerpo en ellas, y el ejercicio de “soltar el cuerpo”, para discutir situacionalmente algunas de las vetas por las que los antropólogos estudiamos la religión. De esta manera, busco también responder al cuestionamiento sobre cómo el estudio de lo religioso y el contacto con diferentes rituales afecta mi propio trabajo como antropóloga.

Para este proyecto, la pregunta con la que hemos trabajado desde 2020 fue: ¿de qué manera nos ha afectado la religión -las experiencias religiosas propias o de otros- en nuestro quehacer antropológico? Esta pregunta alude directamente a nuestros trabajos de campo y al tipo de antropología que elaboramos posteriormente. O, dicho de otra manera, ¿qué significan estas experiencias que luego dejamos de lado en nuestros escritos, y de qué manera nos re-significaron nuestro entendimiento del ejercicio antropológico? Todavía un poco más allá: ¿cómo modificaron nuestra subjetividad y qué impacto tuvo en nuestras formas de posicionarnos en el mundo? No obstante, más allá de un ejercicio de autoetnografía en el que nos situáramos con nuestras identidades en campo, una antropología de la experiencia de lo religioso como finalmente la llamamos, nos coloca en un quehacer más complejo.

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2020/2021 Introducción: La inmunoterapia es la única terapia capaz de cambiar el curso natural de las enfermedades alérgicas. Sin embargo, también pueden producirse efectos adversos durante su uso, aunque actualmente faltan evidencia y estudios sobre los algoritmos de gesYón de estas terapias, así como sobre la seguridad y la prevención de las reacciones adversas, o el tratamiento de las mismas si se producen. ObjeAvos: elaboración de un protocolo asistencial sobre seguridad en la ITA y un algoritmo de manejo de las posibles reacciones adversas, aplicables en el Hospital General Universitario de Castellón. Proceso de elaboración: se realizó una búsqueda bibliográfica entre octubre (2020) y febrero (2021), reuniendo información de diversas fuentes, principalmente de PubMed. Se evaluaron los niveles de evidencia de la bibliogra_a incluida en el protocolo mediante las escalas CEBM y se resumieron en tablas. Se obtuvieron una serie de recomendaciones en las que se basó el presente protocolo. Conclusiones: durante el tratamiento con ITA debe evaluarse su seguridad realizando visitas cada 3-4 meses para asegurarnos de que no se dan reacciones adversas. Cuando se den, usaremos la escala “WAO 2010” , modificada, para clasificarlas y saber cómo tratarlas. IntroducAon: Immunotherapy is the only therapy capable of changing the natural course of allergic diseases. However, adverse effects may also occur during their use, but there is currently a lack of evidence and work on management algorithms for these therapies, as well as on the safety and prevenYon of adverse effects, or the treatment of adverse effects if they do occur. ObjecAves: development of a healthcare protocol on safety in AIT and an algorithm for the management of possible adverse reacYons, applicable to the Hospital General Universitario of Castellón. ElaboraAon process: a literature search was conducted between october (2020) and february (2021), gathering informaYon from various sources, mainly PubMed. The levels of evidence of the literature included in the protocol were evaluated using the CEBM scales and summarized in tables. A series of recommendaYons were obtained on which the present protocol was based. Conclusions: during treatment with AIT, safety should be assessed with visits every 3-4 months to ensure that adverse reacYons do not occur. When they do occur, we will use the modified "WAO 2010" scale to classify them and know how to treat them.

Trabajo presentado en el EMBO Workshop: Enhanceropathies: understanding enhancer function to understand human disease, celebrado en Santander (España) del 06 al 09 de octubre de 2021., Lmx1b is the key regulator of dorso-ventral (DV) pattern in the limb, as it is both necessary and sufficient to specify dorsal fates. Accordingly, targeted disruption of Lmx1b results in double ventral limbs. In humans, mutations in the LMX1B gene are responsible for the autosomal dominant Nail-Patella Syndrome (OMIM #161200), characterized by incomplete limb dorsalization. Here, we report on two enhancers located upstream of the gene, LARM1 and LARM2, that regulate Lmx1b specifically in the limb. These sequences contain several canonical Lmx1b binding sites that mediate a positive loop of Lmx1b autoregulation. Deletion of these enhancers together results in mice with double ventral limbs, like these of Lmx1b-nul mice. Remarkably, deletion of each individual enhancer produced a double ventral phenotype clearly restricted to the posterior half of the limb in LARM1 mutants and to the anterior in LARM2 mutants, indicating differential activity of these enhancers along the anterior-posterior axis. These results reflect an unexpected complex, modular and autoregulatory mode of Lmx1b transcriptional regulation during limb development. We also report on several NPS patient families with normal LMX1B coding sequence but variations in the LARM region that exhibit limb restricted phenotypes, stressing the role of regulatory modules in disease pathogenesis.

Resumen del trabajo presentado en el 17th Spanish Society for Developmental Biology Meeting Virtual Meeting, celebrado en modalidad virtual del 18 al 20 de noviembre de 2020., Vertebrate Hox genes are critical developmental regulators in the establishment of the basic body plan of bilaterian animals and, subsequently, in the organization of secondary axial structures such asthe appendages. At postnatal stages and in adulthood, Hox genes also play important roles in homeostasis and disease. Here we concentrate in the study of the function of the HoxC cluster in the ectoderm, using the mouse limb bud as a model. We report that Hoxc genes are activated in a colinear manner in the embryonic limb ectoderm and are subsequently transcribed in developing nails and hairs. Accordingly, mice lacking the complete HoxC cluster display anonychia (absence of the nail organ), a condition stronger than the misshaped nails previously reported in the loss of function of Hoxc13, which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identify two mammalian-specific enhancers located upstream of the HoxC cluster that show ectodermal restricted activity in mouse transient transgenic reporter assays. The individual and combined deletions of these two enhancers indicate that they act together to control the transcription level of Hoxc gene necessary for correct hair and nail development.

Resumen del trabajo presentado en el 17th Spanish Society for Developmental Biology Meeting Virtual Meeting, celebrado en modalidad virtual del 18 al 20 de noviembre de 2020., Lmx1b is a LIM homeodomain transcription factor that plays essential roles in a wide range of developmental processes including the development of the kidney, the eye, the dopaminergic and serotonergic neurons and the limb. In the limb, Lmx1b expression is restricted to the dorsal mesenchyme and is responsible for limb dorsalization. Mice lacking functional Lmx1b die at birth because of multisystemic malformations. Homozygous Lmx1b mutants develop a double-ventral limb phenotype with loss of dorsal structures such as the patella, whereas the ventral ones such as the sesamoid bones are duplicated and dorsal tendons and muscles are transformed into mirror images of ventral ones. At superficial level, hair and nails are absent while typical ventral features such as pads are also duplicated. Herein, we report on two conserved Lmx1bassociated cis-regulatory modules (LARM1 and LARM2) located upstream of Lmx1b that are bound by Lmx1b and mediate an autoregulatory loop required to provide adequate levels of Lmx1b expression necessary for limb dorsalization. Combined removal of both enhancer lead to a limb restricted phenotype identical to that of the Lmx1b Knockout mice with no other Lmx1b-related systemic defects, indicating that they are limb specific enhancers. Unexpectedly, the CRISPR/Cas9 deletion of each individual enhancer produced a double ventral phenotype clearly restricted to the posterior or anterior half of the autopod in LARM1 and LARM2 respectively, unveiling spatial modularity in the transcriptional control of Lmx1b in the limb. In humans, LMX1B haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Of most interest, we report on two NPS patient families with normal LMX1B coding sequence and limb-restricted phenotype, but with loss-of-function variations in the LARM1/2 region, stressing the role of regulatory modules in disease pathogenesis.

Resumen del trabajo presentado en el 17th Spanish Society for Developmental Biology Meeting Virtual Meeting (2020), celebrado en modalidad virtual del 18 al 20 de noviembre de 2020., In recent years, the development of CRISPR technologies has provided an excellent tool for genomic editing. We have taken advantage of this technology to set up a CRISPR service at our Institute that based on the electroporation of mouse zygotes (day 0.5) generates desired mouse genomic modifications in a highly efficient, rapid and unexpensive manner. We have applied this methodology to the generation of several mouse models of human congenital hand malformations, especially focussing on the Split Hand Foot Malformation (SHFM), a rare and highly variable malformation characterized by the loss or deformity of the central digit rays. We have previously shown the involvement of Sp6 and Sp8 transcription factors in the generation of SHFM phenotypes in mouse and the interaction of these two factors with Dlx family members. Dlx genes are the genes involved in human SHFM types 1 (Dlx5/Dlx6) and 5 (Dlx1/Dlx2). With the aim of fully investigating the implication of the Dlx-Sp interactions in the pathogenesis of SHFM, we have generated a couple of mouse models: the Dlx5/Dlx6 double deletion and the Sp6- V5 tagged knock-in. Additionally, and based on studies in Drosophila indicating that Sp factors control appendage development through the Notch pathway, we have also generated a Jag2 KO mutant. We are currently using the generated animal models to advance our understanding of the mechanisms subjacent to the SHFM.

[ES] El proyecto trata el desarrollo de un nuevo modelo habitacional entendido como un organismo con vida propia que apuesta por la autosuficiencia y proporciona al habitante el poder de la acción individual. Se trata de una comunidad transitoria localizada en el periurbano este del barrio de Benimaclet, en Valencia, cuyo eje motor es la recuperación de la huerta, ahondando en sus valores productivo, paisajístico y natural. Las viviendas, reciclables y sostenibles, acogerán a personas en riesgo de exclusión social por lo que la comunidad será un punto de confluencia de diferentes culturas e ideologías. Además, se dará cabida a usos auxiliares vinculados a la acción social, educación y relaciones interpersonales., [EN] The project deals with the development of a new housing model understood as a living organism base on the self-sufficiency and the power of individual action. It is a transitory community located in the eastern peri-urban neighborhood of Benimaclet, in Valencia, whose driving force is the recovery of the vegetable garden, delving into its productive, landscape and natural values. The homes, recyclable and sustainable, will welcome people at risk of social exclusion so the community will be a point of confluence of different cultures and ideologies. In addition, the community will develop auxiliary uses about social action, education and interpersonal relationships.

Resumen del trabajo presentado en 17th Spanish Society for Developmental Biology Meeting Virtual Meeting, celebrado en modalidad virtual del 18 al 20 de noviembre de 2020., Epimorphic regeneration is a type of multi-tissue regeneration defined by the formation of a blastema. In contrast to amphibians, which can regenerate their entire limbs, mammals can only regenerate the distal tip of their digits, hence investigating the mechanisms involved is of maximum interest for regenerative medicine. Interestingly, in mice and humans this regeneration associates with the nail organ, particularly with the Wnt/ß-catenin active nail matrix. Nails are ectodermal appendages of the dorsal tip of the digits. Their development reflects the dorso-ventral polarity of the limb, established in the early limb bud ectoderm by the interaction of three central molecules. En1, expressed in the ventral ectoderm, restricts Wnt7a to the dorsal ectoderm. Wnt7a induces Lmx1b, the dorsal determinant, in the subjacent mesoderm. Lmx1b-null mice display bi-ventral distal limbs and die perinatally due to multisystemic defects. Recent studies have identified two Lmx1b limb-specific enhancers named LARM1 and LARM2. CRISPR/Cas9-mediated deletion of these two enhancers (LARM1/2-/-) yielded mice with a limb-restricted Lmx1b-null phenotype, but no other systemic defects. LARM1/2 null mutants show absence of nails in their digit tips, providing an opportunity to directly test the involvement of the nail in digit tip regeneration. As expected, LARM1/2 mutants fail to regenerate their digit tips, as histological and ¿CT analyses demonstrate. Importantly, disregarding the lack of regeneration, a blastema does form at the tip of the LARM1/2 stump. Our preliminary results point to a reduction of proliferation in the LARM1/2 blastema compared to wild-type, and to an absence of Wnt/ß-catenin active epidermis in mutants, as an explanation of the regenerative failure. Our results confirm that bi-ventral digits do not regenerate their digit tips and set the LARM1/2 mutant as a useful model to investigate the mechanisms of regenerative blastema, with the aim of enhancing regeneration.

Trabajo presentado en el Limb Development and Regeneration: New Tools for a Classic Model System EMBO Workshop, celebrado en Barcelona (España) del 2 al 5 de julio de 2019., In amniotes, Hox genes are found in 4 clusters, two of them, the HoxA and HoxD clusters, play remarkable roles in limb development. In contrast, the HoxB or HoxC clusters seem to be practically dispensable for proper limb growth and skeletal patterning. Recently, we turned our attention to Hoxc genes as the temporal transcriptome of the isolated limb components (mesoderm and ectoderm) exposed a collinear activation of the HoxC cluster specifically in the limb ectoderm. In situ hybridization supported this temporal colinear activation and showed a progressive restriction of the expression of more 5' HoxC members to the dorsal side of thedigit tip coincident with the claw/nail region. The histological an immunohistochemical reevaluation of mice lacking the complete HoxC cluster showed the absence of the nail organ. To identify the cis-regulatory mechanism controlling Hoxc gene transcription in the limb ectoderm, we used the ATACseq technique. These experiments revealed two open chromatin region located 5' to the HoxC cluster, termed EC1 and EC2, that were highly conserved in mammals and in placentaria, respectively. These two regulatory regions were able to elicit reporter gene activity in the limb ectoderm in mouse transgenic assays, although the CRISPR-mediated individual deletion of either EC1 or EC2 had no phenotypic consequence. To further clarify the role of EC1 and EC2, we are currently generating the CRISPR-mediated combined deletion of both putative enhancer regions. Our study sheds light on the HoxC dependent control on nail/claw/hoof formation at the tip of the digits. The form and size of this epidermal derivative always correlates with that of the distal phalanx showing together a wide range of adaptive strategies across tetrapod species.

Treball Final de Grau en Mestre o Mestra d'Educació Infantil. Codi: MI1040. Curs acadèmic: 2018/2019 Las emociones están presentes siempre en todo lo que hacemos. Las personas nos sentimos de una forma u otra. La Inteligencia emocional empieza a tener una gran importancia desde 1995 cuando Daniel Goleman nos enseñó a todos el gran poder que tienen las emociones sobre nosotros. Así como nos señala la necesidad de educar a los niños y niñas en este enfoque. Ya que de la educación en esta es necesaria para el desarrollo integral de la persona. Asimismo, se ha demostrado una conexión entre la música y las emociones, esto encuentra en el cerebro una asociación neurobiológica, por lo que todas las personas pueden acceder al contenido emocional de una obra musical, como dice Pirfano. Por otra parte, la creatividad, si la entendemos como cualquier actividad que lleve la producción de algo nuevo, ya sea referente a la tecnología, la ciencia o el arte (De Haan y Hanvighurts,2005, citado a través de Chacón,2005) está constantemente presente, ya que continuamente se crean cosas nuevas. Por tanto, el objetivo de este proyecto es trabajar cinco emociones básicas que aparecen en el cuento El monstruo de colores y que asocien cinco leitmotiv a cada una de estas. Así mismo, que sepan reconocerlos, diferenciarlos y decir con qué emoción/personaje se identifica cada uno de ellos. Optando por un enfoque distinto y ampliando las generalidades relacionadas con: “las tonalidades mayores evocan la alegría, y las tonalidades menores a la tristeza”.

Trabajo presentado en el 52nd Annual Meeting of the Japanese Society of Developmental Biologists, celebrado en Osaka (Japón) del 14 al 17 de mayo de 2019.

Modern dietary patterns, collectively termed Western diet, are characterized by an inadequate composition that leads to an excessive intake of sugar, unsaturated fatty acids, salt, etc. and a lack of essential nutrients. Undoubtedly, this type of nutrition has important consequences on health and affects an individual’s risk for developing diseases such as hypertension, heart disease, stroke, cancer, and many immune-mediated diseases. A great gathering of evidence has demonstrated that following an incorrect diet may result in altered microbiota (dysbiosis), which is currently considered to be the central element that links diet and physiological homeostasis. This essential interaction is mediated through many different pathways that frequently involve the immune system. However, the exact mechanisms are yet to be established. This review tries to profoundly explain the most recent investigations that shed light on these mechanisms and their consequences, focusing on the role of the microbiota. Consequently, it will allow understanding of the pathophysiology behind the development of many diseases conditioned by diet. Finally, possible dietary interventions that could be very useful in the treatment and prevention of many increasingly prevalent medical conditions are discussed. RESUMEN: Los patrones dietéticos modernos, denominados colectivamente Dieta occidental, se caracterizan por una composición inadecuada que conduce a una ingesta excesiva de azúcar, ácidos grasos insaturados, sal, etc. y a la falta de nutrientes esenciales. Sin lugar a dudas, este tipo de nutrición tiene consecuencias importantes para la salud y aumenta el riesgo individual de desarrollar enfermedades como hipertensión, cardiopatías, ictus, cáncer y muchas enfermedades inmumediadas. Una gran recopilación de evidencia ha demostrado que seguir una dieta incorrecta puede producir una alteración de la microbiota (disbiosis), considerada actualmente el elemento central que vincula la dieta y la homeostasis fisiológica. Esta interacción esencial está mediada a través de muchas vías diferentes que frecuentemente involucran al sistema inmunológico. Sin embargo, los mecanismos exactos aún no se han establecido. Esta revisión trata de explicar en profundidad las investigaciones más recientes que arrojan luz sobre estos mecanismos y sus consecuencias, centrándose en el papel de la microbiota. En consecuencia, permitirá comprender la fisiopatología detrás del desarrollo de muchas enfermedades condicionadas por la dieta. Finalmente, se discuten posibles intervenciones dietéticas que podrían ser muy útiles en el tratamiento y la prevención de muchas afecciones médicas cada vez más prevalentes. Grado en Medicina

Trabajo presentado en el European Developmental Biology Congress, celebrado en Alicante (España) del 23 al 26 de octubre de 2019.

Trabajo presentado en el Limb Development and Regeneration: New Tools for a Classic Model System EMBO Workshop, celebrado en Barcelona (España) del 2 al 5 de julio de 2019.

Resumen del trabajo presentado en el 4th Meeting of the portuguese society for developmental biology, celebrado en Oporto (Portugal) del 07 al 10 de noviembre de 2018., SP6 and SP8 are two members of the SP family of transcription factors that are conjointly required in the limb bud ectoderm for correct proximo-distal and dorso-ventral patterning (Talamillo et al., 2010; Haro et al., 2014). To identify the SP8 regulatory network in the limb ectoderm, we performed ChIPmentation and RNA-seq experiments in the E10.5 limb bud ectoderm. The genome-wide binding pattern of SP8 yielded 1,451 conserved and significantly enriched regions while the comparison between the transcriptional signature of WT and Sp8 null mutant embryos found 892 differentially expressed genes (DEG). The combination of the ChIPmentation and DEG datasets identified 183 direct SP8 target genes, 30% repressed and 70% activated by SP8. Further analyses revealed that SP8 acted on these direct targets mainly from distally located binding sites. We also found that AT-rich motifs, described as the preferential motif of SP7 to indirectly bind the DNA through DLX5, were predominant when SP8 functions as an activator. Accordingly, Co¿Immunoprecipitation (CoIP) experiments showed binding between SP8 and DLX5. Interestingly, SP1 like CG-rich motifs were more frequent when SP8 acts as a repressor. Finally, CoIP and Bimolecular Fluorescence Complementation assays also showed that SP8 and SP6 form homo and heterodimers providing some insights into their functional redundancy.

Resumen del trabajo presentado en el 41 Congreso de la Sociedad Española de Bioquímica y Biología Molecular SEBBM, celebrado en Santander (España) del 10 al 13 de septiembre de 2018.

Trabajo presentado en el 41 Congreso de la Sociedad Española de Bioquímica y Biología Molecular SEBBM, celebrado en Santander (España) del 10 al 13 de septiembre de 2018.

Trabajo presentado en el 41 Congreso de la Sociedad Española de Bioquímica y Biología Molecular SEBBM, celebrado en Santander (España) del 10 al 13 de septiembre de 2018.

Tesis-Universidad de Murcia., Consulte la tesis en: BCA. GENERAL. DEPOSITO. T.M-2104.

La parcela desde el principio se planteó subdividida en dos partes con vistas a resolver la relación barrio-paseo: la antigua Calle del Castell de Pop que ahora se convertía en calle peatonal, quedaría cubierta y albergaría el mercado temporal, en el resto de días de la semana funcionaría como paseo cubierto que conectaría con el parque oeste. La antigua parcela del cine de verano albergaría el mercado. Se dividió el sistema en dos grandes grupos: puestos de carnes y pescados, a los que se dotará de una circulación de dirección única, formando un pasillo donde la introducción de luz natural será controlada y desde el cual se tendrá acceso perpendicularmente a las otras partes del mercado; y puestos de frutas y verduras, que no requieren de un control tan exhaustivo del ambiente permitiendo un contacto más directo con el exterior y conformando un sistema de circulaciones más diverso y menos controlado.

Resumen del trabajo presentado en Experimental Biology 2018, celebrado en San Diego (Estados Unidos) del 21 al 25 de abril de 2018., The developing vertebrate limb has long proved as an excellent system for studying the mechanisms involved in pattern formation and morphogenesis and more recently in transcriptional regulation and morphological evolution. To elucidate the stage-specific expression profiles of the components of the developing limb, we have generated the temporal transcriptome of the limb progenitors and of the overlying ectoderm separately. Our study has uncovered a collinear activation of Hoxc genes in the limb ectoderm that we have validated by in situ hybridization. However, while members of the HoxA and HoxD clusters show complex and dynamic patterns of expression during limb development that correlate with the morphology of the different limb segments, no specific function for the HoxC or HoxB clusters has been identified (1-3). To investigate the function of Hoxc genes in the limb ectoderm, we have reexamined the HoxC cluster null mice. Remarkably, and despite exhibiting normal terminal phalanges, these mice didn¿t form claws (anonychia). Morphological and immunohistochemical analysis identified a failure in the differentiation of the main components of the nail/claw organ. To unravel the transcriptional regulation of Hoxc genes in the limb ectoderm, we used the ATACseq technique. Using this approach, we identified two putative regulatory regions which activity was tested in mouse transgenic enhancer assays. It is currently considered that Hox genes have played a key role in the evolution of morphological traits, probably associated with changes in their regulatory landscapes (4). Given that the form and size of the distal limb integumentary organ (nail, claw or hoof) correlates with that of the distal phalanx and that the development of hooves was a major innovation in the evolution of a cursorial lifestyle, we are also exploring the possible implication of Hoxc genes in the nail/claw/hoof transition.

Trabajo presentado en el IV Congreso de Estudiantes de Medicina de la Universidad de Oviedo, celebrado en Oviedo (España) del 01 al 03 de marzo de 2018., La Biología del Desarrollo es una faceta fundamental de la Medicina y de la Biología que intenta entender cómo una única célula, el zigoto, da lugar a un organismo completo con mas de 200 tipos celulares distintos. Durante el desarrollo, las células embrionarias no solo se diferencian sino que además se organizan formando los complejos patrones morfológicos característicos de los diferentes tejidos y órganos (morfogénesis). En la actualidad, los procesos de morfogénesis se abordan desde un punto de vista molecular y genético. En el curso de la charla se expondrán las principales contribuciones de la Biología del desarrollo a la salud humana incluyendo facetas tan diversas como el manejo de los problemas de fertilidad y de las malformaciones congénitas así como la generación de modelos animales de enfermedad. Con particular atención se tratarán los temas de la clonación y la biología de las células madre con su aplicación a la Medicina regenerativa y a la Ingeniería tisular.

Trabajo presentado en Gordon Research Conference Musculoskeletal Biology and Bioengineering, celebrada en Andover (Inglaterra) del 05 al 10 de agosto de 2018.

Feeding the world’s population sustainably is a major challenge of our society and has been stated as one of the key priorities for development cooperation by the EU policy framework on food security. However, the current pattern of natural resources exploitation to meet humanity’s demand for food threatens long-term food security. Food systems represent around 30 % of final energy use, generating up to 30 % of greenhouse gas (GHG) emissions. Given the expected increase of global population (9 billion people by 2050) and the amount of food losses and waste generated (a third of global food production), improving the efficiency of food systems along the supply chain is essential to ensure food security. This work combines life cycle assessment (LCA) and data envelopment analysis (DEA) to assess the efficiency of Spanish agri-food system and propose improvement actions in order to reduce energy usage and GHG emissions. Results suggest that sweets and vegetable fats categories provide the largest nutritional energy to consumer per unit of embedded energy in its production. Around a 70 % average reduction target is estimated for the Spanish agri-food system to be efficient, with a similar reduction in related greenhouse gas emissions. The authors are grateful for the funding of the Spanish Ministry of Economy and Competitiveness through the Ceres-Procom: Food production and consumption strategies for climate change mitigation (CTM2016-76176- C2-1-R) (AEI/FEDER, UE).

The presence of residues of antibiotics in milk from animals that have been treated with veterinary medicinal products either therapeutic or prophylactic without respecting the good practices of use, can have serious consequences for public health and the dairy sector. In the case of the manufacture of cheese, depending on the nature of the antibiotic it can be held mostly in curd or be disposed with the whey. Must be borne in mind that whey can be used in animal feed or employee for the manufacture of other products (curd, concentrated of protein, whey powder, etc.) by which the presence of residues of antibiotics in whey may represent a risk to food safety and animal health, as well as for the environment making it necessary to have a control system. Screening methods for detection of antibiotics are currently available from a commercial standpoint in milk which may be microbiological type that are non-specific or binding to protein receptors that are specific for the detection of one, two or several families of antibiotics. All of these methods have been validated for use in milk of different species but not for use in whey from the cheese making. Therefore, the objective of this work has been the validation criteria of Decision 2002/657/EC of microbiological method Eclipse Farm 3 G® coupled to the team e - Reader® and 3 screening methods of binding to receptors (TwinSensor®, 3AminoSensor® and QuinoSensor®) for the detection of antibiotics used in dairy goats. The whey samples from experimental elaborations of cheese from goat's milk were used without antibiotics and also fortified with different concentrations of antibiotics (amoxicillin, penicillin, cephalexin, oxytetracycline, gentamicin, tylosin, sullfatiazol and enrofloxacin) and then were analysed using the screening methods. The results for the Eclipse Farm method 3G® coupled to e - Reader® indicates that it is necessary to samples predifusion for one hour at room temperature when whey is analyzed. The method presented with this array of very high specificity (97.7%) indicating a low rate of false-positive results. In addition the method is suitable for the detection of ß-lactam antibiotics (except for amoxicillin), aminoglycosides and tetracyclines presenting cscarce sensitivity for the detection of quinolones. In the case of methods of receptors binding is necessary to elongated the time of incubation in the analysis of whey, presenting the TwinSensor® high detection capability for ß-lactam (except for Cephalexin) and tetracyclines, as it was also adequate found with QuinoSensor® for enrofloxacin, while 3 AminoSensor® showed a less sensitivity in the detection of gentamicin. In all cases the methods of receptor binding show a high specificity (100%). In conclusion, the commercial screening methods using specific analysis protocol could be an appropriate tool in the establishment of a control system for the presence of antibiotics in the whey., La presencia de residuos de antibióticos en la leche procedente de animales que han sido tratados con medicamentos veterinarios de forma terapéutica o profiláctica sin respetar las buenas prácticas de uso, puede tener graves consecuencias para la salud pública y el sector lácteo. En el caso de la fabricación de queso, dependiendo de la naturaleza del antibiótico este puede quedar retenido mayoritariamente en la cuajada o ser eliminado junto al lactosuero. Hay que tener en cuenta que el lactosuero puede ser utilizado en alimentación animal o empleado para la elaboración de otros productos derivados (requesón, concentrados de proteínas, suero en polvo, etc) por lo que la presencia de residuos de antibióticos en el lactosuero puede representar un riesgo para la Seguridad alimentaria y la salud animal, así como para el medio ambiente, lo que hace necesario disponer de un sistema de control. Actualmente se encuentran disponibles desde un punto de vista comercial métodos de cribado para la detección de antibióticos en la leche que pueden ser de tipo microbiológico que son inespecíficos o de unión a receptores proteicos que son específicos para la detección de una, dos o varias familias de antibióticos. Todos estos métodos han sido validados para su uso en leche de diferentes especies pero no para su empleo en lactosuero procedente de la elaboración del queso. Por ello, el objetivo de este trabajo ha sido la validación de acuerdo a los criterios de la Decisión 2002/657/CE del método microbiológico Eclipse Farm 3G® acoplado al equipo e-Reader® y 3 métodos de cribado de unión a receptores (TwinSensor®, 3AminoSensor® y QuinoSensor®) para la detección de los antibióticos más empleados en ganado caprino lechero. Para su realización se han empleado muestras de lactosuero procedente de elaboraciones experimentales de queso a partir de leche de cabra adicionada con distintas concentraciones de antibióticos (amoxicilina, bencilpenicilina, cefalexina, oxitetraciclina, gentamicina, tilosina, sullfatiazol y enrofloxacina) que se analizaron mediante los métodos de cribado. Los resultados obtenidos para el método Eclipse Farm 3G® acoplado a e-Reader® indican que resulta necesario la difusión durante una hora a temperatura ambiente cuando se analiza lactosuero. El método presentó una especificidad con esta matriz muy elevada (97.7%) indicando un porcentaje bajo de resultados falsos positivos. Además el método resulta adecuado para la detección de antibióticos β-lactámicos (excepto para la amoxicilina), aminoglucosidos y tetraciclinas presentando poca sensibilidad para la detección de quinolonas. En el caso de los métodos de unión a receptores se alargaron los tiempos de incubación en el análisis de lactosuero, presentando el TwinSensor® una elevada capacidad de detección para β-lactámicos (excepto para la cefalexina) y tetraciclinas, así como también fue adecuada la encontrada con el QuinoSensor® para la enrofloxacina, mientras que el 3 AminoSensor® mostró una sensibilidad baja en la detección de gentamicina. En todos los casos la especificidad de los métodos de unión a receptores fue del 100%. En conclusión, los métodos comerciales de cribado con el protocolo específico de análisis podrían ser una herramienta apropiada para el establecimiento de un sistema de control de la presencia de antibióticos en el lactosuero., [CA] La presència de residus d’antibiòtics en la llet procedent d’animals que han sigut tractats amb medicaments veterinaris de forma terapéutica o profilàctica sense respectar les bones practiques d’ús, pot tindre greus conseqüències per a la salut pública i al sector làctic. En el cas de la fabricació de formatge, depenent de la naturalesa del antibiòtic aquest pot quedar retingut mejoritàriament en la quellada o ser eliminat junt al lactosèrum. Cal tindre en compte que el lactosèrum pot ser utilitzat en la alimentació animal o empleat per a l'elaboració d'altres productes derivats (mató, concentrats de proteïnes, sèrum en pols, etc.) pel que la presència de residus d’antibiòtics pot representar un risc per a la seguretat alimentària i la sanitat animal, així com per al medi ambient, sent necessari disposar d’un sistema de control. Actualment es troben disponibles des d’un punt de vista comercial mètodes de cribatge per a la detecció d’antibiòtics a la llet, que poden ser de tipus microbiològic que són inespecífics o de unió a receptors proteics que són específics per a la detecció de una, dos o diverses famílies d’antibiòtics. Tots aquests mètodes han sigut validats per al seu ús a la llet de diferents espècies però no per al seu empleu al lactosèrum procedent de l’ elaboració del formatge. Per això, l’objetiu d’aquest treball ha sigut la validació d’acord a la Decisió 2002/657/CE del mètode microbiològic Eclipse Farm 3G® acoplat al equip e-Reader® i 3 mètodes de cribatge d’unió a receptors (TwinSensor®, 3AminoSensor® i QuinoSensor®) per a la detecció dels antibiòtics més empleats al bestiar caprí lleter. Per a la seua realització se han empleat mostres de lactosèrum procedent d’elaboracions experimentals de formatge a partir de la llet de cabra addicionada amb distintes concentracions d’antibiòtics (amoxicilina, bencilpenicilina, oxitetraciclina, gentamicina, tilosina, sullfatiazol i enrofloxacina) que van ser analitzades amb els mètodes de cribatge. Els resultats obtinguts amb el mètode Eclipse Farm 3G® acoplat amb e-Reader® indiquen que resulta necessari la difusió durant una hora a temperatura ambient quan s’analitzat lactosèrum. El mètode va presentar una especificitat amb aquesta matriu molt elevada (97.7%) indicant un percentatge baix de resultat falsos positius. A més, el mètode resulta adequat per a la detecció d’antibiòtics β-lactàmics (excepte per a la amoxicilina), aminoglucòsids i tetraciclines presentant poca sensibilitat per a la detecció de quinolones. En el cas dels mètodes d’unió a receptors es van allargar els temps d’incubació al anàlisis del lactosèrum, presentant el TwinSensor® una elevada capacitat de detecció per a β-lactàmics (excepte per a la cefalexina) i tetraciclines, així com també va ser adequada la trobada amb el QuinoSensor® per a la enrofloxacina mentre que 3AminoSensor® va mostrar una sensibilitat baixa en la detecció de gentamicina. En tots els casos la especificitat dels mètodes d’unió a receptors va ser del 100%. En conclusió, els mètodes comercials de cribatge seguint el protocol específic d’anàlisis poden ser una eina apropiada en el estableciment d’un sistema de control de la presència d’antibiótics al lactosèrum.

Resumen del trabajo presentado a la 14th International Limb Development and Regeneration Conference, celebrada en Edimburgo (UK) del 23 al 26 de julio de 2017., To clarify the genetic networks controlling limb elongation, we have performed the temporal expression profiling of the distal mouse limb ectoderm. Comparison between successive stages showed that major changes occurred between E9.5 and E10.5 (295 differentially expressed genes) while only a few genes changed between E10.5 and 11.5 and between E11.5 and E12.5. Interestingly, several members of the HoxC cluster were among the identified regulated genes and the RNA-seq tracks revealed a pattern of Hoxc gene collinear activation in the distal limb ectoderm which was confirmed by in situ hybridization. Since it is known that Hoxc13 is involved in hair and nail development and that HOXC13 is causative for the Pure Hair and Nail Ectodermal Dysplasia, we decided to further study the function of Hoxc genes in the limb ectoderm (Godwin & Capecchi, 1998; Lin et al., 2012). We observed that, in the complete absence of the HoxC cluster, development of the nails was absent or severely impaired and we are currently characterizing the cellular and molecular features of the mutant digit tips. We also sought to investigate the accessible chromatin in the HoxC landscape using ATAC-seq and identified two putative regulatory regions located 5' of the cluster. Because the hoof, just a modified nail, is a major and necessary innovation in the evolution of a cursorial lifestyle, we also seek to unravel the possible role Hoxc genes may have played in the nail/claw/hoof transition as a way to generate a variety of evolutionary changes in distal limb appendages.

Resumen del trabajo presentado a la 14th International Limb Development and Regeneration Conference, celebrada en Edimburgo (UK) del 23 al 26 de julio de 2017., Sp6 and Sp8, two members of the specificity protein (Sp) family of zinc-finger transcription factors, are specifically expressed in the limb ectoderm where they are required, in a dose dependent manner, for the induction of Fgf8 and En1 (Haro et al., 2014). Accordingly, the progressive reduction in Sp6/Sp8 gene dosage led to progressively more severe morphologies that transit from syndactyly, to split-hand/foot malformation phenotype, oligodactyly, truncation and finally amelia. In addition, when digits form, they exhibit a double dorsal tip. Therefore, we have suggested that the function of these two factors link the induction of the AER and the dorsalventral patterning during limb development. Here, to further the understanding of Sp6/8 function, we have investigated Sp6/8 suspected protein-protein interactions by coimmunoprecipitation (CoIP) and by bimolecular fluorescence complementation (BiFC). To this end, Sp6, Sp8 and Smads were tagged with Myc or FLAG epitopes to their Nterminal end and with YFP full length or YFP moieties to their Cterminal end. Heterologous expression in HEK293 cells show that Sp6/8 form homo and heterodimers and that they form complexes with BMP RSmads and with Smad4. All these interactions require the Zinc finger domain of Sps. We are currently determining Sp6/8 DNA binding activity by luciferase reporter. Furthermore, to analyze the genome-wide Sp8-DNA associations in the limb ectoderm, we have generated a knock-in mouse containing the endogenous Sp8 tagged with 3xFLAG at the C-terminal domain as strategy for ChIP-seq study., Supported by Grant BFU2015‐70193‐REDT and the Celmoves Network red de excelencia of the MEIC.

Resumen del trabajo presentado a la 14th International Limb Development and Regeneration Conference, celebrada en Edimburgo (UK) del 23 al 26 de julio de 2017., A fundamental question in biology is how an organ or tissue is built, how a cluster of progenitor cells ends up producing a perfect and fully functional limb. While the fundamental question remains unchanged, the way to tackle it has moved in the past few decades from the traditional embryonic experimental manipulation to more molecular and genetic approaches and lately to functional genomics. The limb begins its development when the limb progenitors detach from the epithelial somatopleure and accumulate under the surface ectoderm where they induce the apical ectodermal ridge (AER), a crucial signaling center for limb outgrowth. Two aspects of limb development will be predominantly discussed: the induction of the AER and the mechanisms by which the limb progenitors acquire progressively more distal fates. The former involves the function of Sp6 and Sp8, two members of the Sp family of transcription factors expressed in the limb ectoderm, and that are at the crossroad between proximo-distal and dorso-ventral patterning. The later involves the analysis of the temporal transcriptome of the distal limb progenitors, to identify the gene expression sets characteristic of their distinct proximo-distal specification states, and of the AER, to get information on the genetic control of its development, maturation and regression. The goal is to increase our understanding of the mechanisms regulating the orderly and progressive differentiation of the limb.

Resumen del trabajo presentado al XL Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Barcelona del 23 al 26 de octubre de 2017., Hox genes are a family of important developmental regulators critical for the establishment of the basic body plan of bilaterian animals. In vertebrates, Hox genes are organized in four clusters (A, B, C and D) two of which, HoxA and HoxD cluster, are critical for the outgrowth and patterning of the tetrapod limb (Kmita et al. 2005; Woltering et al. 2014). In contrast, no specific function for the HoxC or HoxB clusters has been identified during limb development, as no obvious limb defect is observed in the complete absence of either of these clusters (Suemori & Noguchi, 2000). Recently, with the generation of the temporal expression profiles of the limb progenitors and of the ectoderm, separately, we have exposed a temporal collinear activation of the HoxC cluster in the limb ectoderm. Furthermore, by in situ hybridization we found a progressive restriction of 5¿Hoxc genes to the nail primary fi eld, correlating with the nail defect exhibited by Hoxc13 mutants (Godwin & Cappechi, 1998). A re-examination of the phenotype of mice lacking the entire HoxC cluster (Suemori & Noguchi, 2000) revealed remarkable nail development defects suggesting the involvement of Hoxc genes in nail/claw morphogenesis. As a first step to identify the cis-regulatory mechanisms underlying Hoxc gene transcription, we performed ATAC-seq of the limb ectoderm and identified two conserved regions 5' of the HoxC cluster that we are currently evaluating for activity in mouse transgenesis. Moreover, given the role of Hox genes in the evolution of form, we are expanding our analysis to other species with a particular development of nail organ (hoof) in order to investigate the role of Hoxc genes in the nail-claw-hoof transition and its putative contribution to the diversity of distal limb structures.

In this commentary we focus on the function of FGFs during limb development and morphogenesis. Our goal is to understand, interpret and, when possible, reconcile the interesting findings and conflicting results that remain unexplained. For example, the cell death pattern observed after surgical removal of the AER versus genetic removal of the AER-Fgfs is strikingly different and the field is at an impasse with regard to an explanation. We also discuss the idea that AER function may involve signaling components in addition to the AER-FGFs and that signaling from the non-AER ectoderm may also have a significant contribution. We hope that a re-evaluation of current studies and a discussion of outstanding questions will motivate new experiments, especially considering the availability of new technologies, that will fuel further progress toward understanding the intricate ectoderm-to-mesoderm crosstalk during limb development., Grant sponsor: Spanish Ministry of Science; Grant number: BFU2014-57216-P; Grant sponsor: University of Southern California.

Aprender a programar es una tarea compleja que requiere del desarrollo de diversas habilidades. Los estudiantes que se inician en la programación se encuentran con serias dificultadas en el aprendizaje de esta materia. Actualmente en los nuevos Grados se han introducido asignaturas relacionadas con las tecnologías de la información, en donde se realiza un primer contacto con la programación. En esta comunicación presentamos el trabajo realizado para el desarrollo de una metodología docente para la enseñanza de programación, basada en el uso de metodologías activas y el empleo de gamificación para incentivar la participación del alumnado y aumentar su motivación. Comentamos la implantación de esta metodología en un curso de iniciación a la programación del Grado en Ingeniería Informática y exponemos los resultados obtenidos. Learning programming is a complex task that requires the development of various skills. Students who are new to programming encounter serious difficulties in learning the subject. Nowadays degrees in the new study system have introduced subjects related to information technology, where students make their first contact with programming. In this paper we present the work done to develop a methodology for teaching programming based on the use of active methodologies and gamification, to encourage student participation and increase motivation. We discuss the implementation of this methodology in an introductory course to programming in the Degree in Computer Science and present some results.

Antecedentes: se espera que la prevalencia de las enfermedades cardiovasculares (ECV) de los ancianos institucionalizados sea alta, ya que tienen una alta comorbilidad, presentan polifarmacia y la edad es el mayor riesgo para que estas se desarrollen, pero no está claramente descrito. Objetivo: describir la prevalencia de las enfermedades cardiovasculares en los pacientes institucionalizados de la Comunidad Valenciana. Diseño: observacional, analítico, transversal, multicéntrico y retrospectivo. Contexto: seis residencias geriátricas en la Comunidad Valenciana entre febrero y junio del 2015. Pacientes: fueron recogidos y tratados los datos de 435 residentes con edad mayor de 64 años con los que se determinó una alta prevalencia de las ECV estudiadas. Mediciones: prevalencia de las enfermedades cardiovasculares estudiadas (hipertensión arterial, fibrilación auricular, otras arritmias distintas a la fibrilación auricular, insuficiencia cardíaca y accidente cerebrovascular).Resultados: la prevalencia fue mayor en los mayores de 74 años. Por sexos, fue mayor la prevalencia de hipertensión arterial (HTA), fibrilación auricular (FA) y el resto de arritmias en mujeres, mientras que la de insuficiencia cardíaca (IC) y accidente cerebrovascular (ACV) fueron superiores en hombres. El 86 % de los residentes presentaba polifarmacia y esta aumentaba con la edad. El 13,1 % de los residentes recibía tratamiento profiláctico de ACV, y en los residentes con FA que además padecían otra ECV, la más prevalente fue la HTA. Conclusión: las ECV presentan una elevada prevalencia en el anciano institucionalizado de la Comunidad Valenciana. Background: it is expected that the prevalence of Cardiovascular diseases of institutionalized elderly was high, as they have a high comorbidity, polypharmacy and the age is the greatest risk for developing these diseases, but it’s unclear. Aim: to describe the prevalence of cardiovascular diseases in institutionalized elderly from Comunidad Valenciana. Design: it was followed a multi-center, observational, analytical, cross-sectional and retrospective design. Context: six nursing homes in Comunidad Valenciana between February-June 2015. Patients: it was collected and processed data of 435 residents older than 64 years. Measuring: the prevalence of cardiovascular diseases studied (Arterial Hypertension, Atrial Fibrillation, other arrhythmias than Atrial Fibrillation, Heart Failure and stroke). Results: the prevalence was higher in those over 74 years old. By gender, the prevalence of hypertension, atrial fibrillation and other arrhythmias was higher in women, while the heart failure and stroke was higher in men. The 86 % of residents had polypharmacy, what increases with the age. The 13,1 % of residents received prophylactic stroke treatment. In the atrial fibrillation residents that suffered from other cardiovascular diseases as well, it was the hypertension the most prevalent one. Conclusion: cardiovascular diseases are highly prevalent in the institutionalized elderly from Comunidad Valenciana. Medicina

El reciente desarrollo de agentes antivirales de acción directa (AAD) para el tratamiento de la infección por VHC ha demostrado que son fármacos bien tolerados y altamente eficaces en comparación con las terapias anteriores,basadas en interferón. Un problema especial es la población coinfectada con el VIH, donde los datos disponibles son más limitados. El objetivo de este estudio es describir la eficacia y seguridad de las terapias libres de interferón en el tratamiento del VHC en la práctica clínica, fuera del contexto de los ensayos clínicos,en pacientes coinfectados con VIH.

La borreliosis de Lyme es una enfermedad infecciosa causada por las bacteria del grupo Borrelia burgdorferi. El único vector de esta enfermedad en Europa es la garrapata de la especie Ixodes ricinus y sus reservorios son pequeños mamíferos (principalmente roedores) y aves. Ixodes ricinus es muy sensible a los cambios de temperatura y humedad, pues necesita un hábitat con unas condiciones climáticas muy concretas para su supervivencia. Está considerada como la enfermedad transmitida por vectores con mayor prevalencia en Europa. Pese a ello, no es una enfermedad de declaración obligatoria para casi ningún país europeo. Debido a su interés para la salud pública, es necesario reforzar las medidas preventivas, la información al público, la vigilancia y elaborar una definición común de la enfermedad para todo el territorio europeo. Este estudio tiene como objetivo explicar la prevalencia de las unidades administrativas del estado de Baviera (donde la enfermedad es de declaración obligatoria) con variables climáticas que expliquen un nicho ecológico de la enfermedad. Hemos usado series de datos climáticos interpolados, que incluyen temperatura y precipitación (WorldClim) que se han integrado en un sistema de información geográfica (qGIS). El grupo completo de datos, incluyendo prevalencia y clima, se ha usado para construir un modelo de regresión logística múltiple que explique las zonas con diferentes tasas de prevalencia en Baviera. También se han usado datos de temperatura y estrés vegetal proporcionados por la serie de satélites MODIS, que han producido un peor ajuste. Aunque el modelo produce algunas clasificaciones erróneas, podemos concluir que la enfermedad tiene un nicho ambiental, en el que la temperatura tiene una importancia pequeña (probablemente debido a que todo el territorio estudiado es adecuado para la supervivencia del vector) mientras que la precipitación en diversos periodos juega un papel importante delineando las áreas con diversa prevalencia.

Resumen del póster presentado al 11th Meeting Spanish Society for Developmental Biology, celebrado en Girona del 19 al 21 de octubre de 2016., We have recently shown that the transcription factors Sp6 and Sp8 are conjointly necessary for limb development as no limbs form in their absence or substantial reduction. The study of the allelic series of double Sp6;Sp8 mutant also revealed that mice with only a functional copy of Sp8 exhibit the Split-hand/split-foot malformation. Based on the mo- lecular study of mutant limbs, we have postulated that Sp6 and Sp8 are necessary in the limb ectoderm, downstream of Wnt/ß-catenin, to activate Fgf8 and downstream of Bmp signaling, possibly cooperating with Smads for dorso-ven- tral patterning. Here we have used co-immunoprecipitation (CoIP) and bimolecular fluorescence complementation (BiFC) to explore these suspected protein-protein interactions. To this end, Sp6, Sp8 and Smads were tagged with Myc or Flag epitopes to their N-terminal end and with YFP full length or YFP moieties to their C-terminal end. By CoIP and BiFC we show that Sp6 and Sp8 can homo and heterodimerize and that they can also interact with Smads. Finally, by generating different truncated versions of Sp8 we resolve the protein regions responsible of these interaction. Our study underscores the mechanisms by which Sp6/8 meditare Wnt/ß -catenin and Bmp signaling in the limb ectoderm.

Total phenolics (TP), vitamin C, antioxidant activity and colour of preserved peppers were evaluated at 4, 25 and 50 C storage during 30-day intervals. Except for 4 C, TP decreased during storage at 25 C and 50 C, being softer for fortified samples with b-CDs. The protective effect was evident, since 50 C samples containing b-CDs exhibited lower TP loss (19%) than control samples (38%) for 5 months storage. A decrease in the vitamin C content was observed for both samples as time and temperature progressed. In samples stored at 50 C the protective effect of b-CD only was evident at the first month, since fortified samples showed lower vitamin C loss (10%) than control samples. The fortified samples with b-CDs exhibited lowest antioxidant activity loss (40%) during 90-day storage at 50 C, than control samples (64%). The colour changes were in line with those observed for total phenolics and at the end of study, the presence of 1% b-CDs delayed the darkening of samples at both (25 and 50 C) storage conditions. Ciencias de la Alimentación

[EN] Topographic changes have been significant in the city of Cartagena and its surroundings along history. The city that Polybius described in II century B.C. has spread northward, occupying the old Almarjal, now desiccated by the diversion of the wadis that flooded it. The palaeotopography of the city has been documented and analyzed from the lithology of 377 geotechnical drillings and other 20 new continuous drilling within the framework of the Project "Surveying and planning of a privileged Mediterranean city, Arqueotopos I and II". Digital terrain models (DTM) of the layers of interest, consisting of anthropic fills and sediments, have been generated. Thickness of each layer has been studied by drawing longitudinal profiles. Finally, a three-dimensional virtual reconstruction has been made to show graphically the documented changes in each layer, to serve both research and divulgation of knowledge., [ES] Los cambios topográficos experimentados por la ciudad de Cartagena y su entorno a lo largo de la historia han sido considerables. La ciudad que describió Polibio en el s. II a.C. se ha extendido hacia el norte, ocupando el antiguo Almarjal, ahora desecado por el desvio de las ramblas que recurrentemente lo inundaban. La paleotopografía de la ciudad se ha documentado y analizado a partir de la litología de 377 sondeos geotécnicos y de otros 20 sondeos nuevos realizados en el marco de los Proyectos “Topografía y urbanismo de una urbe mediterránea privilegiada, Arqueotopos I y II”. Se han elaborado los modelos digitales del terreno (MDT) de las capas de interés, constituidos por rellenos y sedimentos. Se ha estudiado la potencia de cada capa trazando los correspondientes perfiles longitudinales. Finalmente, se ha realizado una reconstrucción virtual tridimensional que permite apreciar gráficamente los cambios documentados producidos en cada capa, con fines tanto investigadores como de divulgación