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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.

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.

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.

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.

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.

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.

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.

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

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. Este trabajo ha sido desarrollado en el marco del Proyecto de Innovación Docente del Vicerrectora de Ordenación Académica y Profesorado de la Universidad de Granada, con código PID-14-89, y parcialmente financiado por el proyecto P11-TIC-7460 de la Junta de Andalucía.

Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016., Limbs develop from limb buds composed of a core of limb progenitor cells covered by the surface ectoderm. A variety of experiments in chick and mouse embryos indicate that the fate of the distal limb progenitors is progressively restricted: early progenitors can form the whole proximo-distal elements of the limb while late progenitors can only form the digits. Here we have used RNA-seq to reveal the transcriptional features associated with this developmental transition. The analysis was performed in mouse forelimbs of 4 different stages (E9.5, E10.5, E11.5 and E12.5) and restricted to the distal 150μm with ectodermal and mesodermal components analyzed separately. Two biological replicates were used for each condition. Of 46,480 Ensembl-annotated genes, 3,416 were differentially expressed between ectoderm and mesoderm. In each tissue, the time serie analysis revealed that major changes occur between E9.5 and E10.5. The accuracy of the expression patterns was confirmed by in situ hybridization and by the truthful coincidence with published expression patterns. According to their temporal expression, six different dynamics of gene expression were identified. In general, the average expression of transcription factors decreased with age, whereas the average expression of extracellular molecules increased with age. The differentially expressed genes were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and showed diverse functional categories and signaling pathways. We are exploring their relevance in orchestrating age-specific developmental capacities of each tissue.

El proyecto objeto de la presente propuesta tiene por objetivo el estudio de las posibilidades que ofrece SDL para desarrollar interfaces hombre-máquina en plataformas abiertas. Para ello, el alumno deberá: a) Llevar a cabo una revisión sistemática del estado del arte con respecto a la librería SDL. b) Realizar la instalación, configuración y puesta en marcha del compilador C elegido (gcc) sobre el entorno integrado de desarrollo epecífico (Code::Blocks). c) Evaluar la funcionalidad de la librería SDL mediante la implementación y documentación de ejemplos de programación de aplicaciones básicas y avanzadas. d) Implementar una aplicación a modo de caso de estudio con soporte para comunicaciones UDP. e) Evaluar la funcionalidad de la librería sobre una plataforma de computación abierta tipo Raspberry Pi. SDL es una librería o biblioteca multiplataforma, es decir, todas las aplicaciones desarrolladas con esta librería pueden ser compiladas sin modificar el código en varios sistemas diferentes tal Windows, Mac OS X, Linux, iOS y Android. Fue diseñada para proporcionar acceso de bajo nivel a todos los dispositivos de PC, es decir, audio, teclado, ratón, joystick; Se trata de una librería ampliamente utilizada para distintos tipos de aplicaciones. Entre ellas se encuentra software para reproducir video MPG, emuladores y un gran número de juegos y adaptaciones de juegos entre plataformas. A partir del estudio realizado a dicha librería, se creará una aplicación en la que se envíe una señal y, una vez recibida, dicha señal aparezca mostrada en pantalla. Escuela Técnica Superior de Ingeniería Industrial Universidad Politécnica de Cartagena

Resumen del póster presentado al 11th Meeting Spanish Society for Developmental Biology, celebrado en Girona del 19 al 21 de octubre de 2016., Limbs develop from limb buds composed of a core of limb progenitor cells covered by the surface ectoderm. Cell trac- king experiments in chick showed that the limb progenitors located at the distal tip of the limb bud progressively res- trict their developmental potential in the proximo-distal axis. The mechanisms and models by which the limb progeni- tors acquire progressively more distal fates are subject to intense investigation and debate. To shed light into this issue we have generated expression profiles for each of the progressive differentiation step by RNA-seq. In parallel we have also generated the temporal transcriptome of the distal ectoderm including the Apical ectodermal ridge (the AER). We seek to unravel expression pattern specific of each of the progressive stages of the limb progenitors and of the AER trying to identify essential descriptors of their biological state (morphogenetic potential). Of 46,480 Ensembl-anno- tated genes, 3,416 were differentially expressed between ectoderm and mesoderm. Intriguingly, we observed that the number of genes changing between stages is similar between ectoderm and mesoderm, with the bulk of changes occurring from E9.5 to E10.5. Expression pattern validation was confirmed by in situ hybridization and trustful pre- viously published data. Gene Ontology analysis revealed, in general terms, a downregulation of transcription factors and an upregulation of extracellular molecules with age. We have identified a specific expression of HoxC genes in the limb ectoderm, which is currently on evaluation.

Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016., We have recently identified the crucial role played by Sp6 and Sp8, two transcription factors members of the Sp family, during limb development. In their absence or substantial reduction no limbs form and their progressive dose reduction associates a spectrum of limb malformations ranking from syndactyly through Split-hand/split-foot malformation, to olygodactyly. When digits form, they exhibit bidorsal tips. We have postulated that Sp6 and Sp8 are necessary, downstream of Wnt/B-catenin, to activate Fgf8 and downstream of Bmp signaling, possible cooperating with Smads, to activate En1, the marker of the ventral ectoderm. Currently we are exploring these suspected protein-protein interactions by co-immunoprecipitation (CoIP) and by bimolecular fluorescence complementation (BiFC). 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. We show by CoIP and BiFC that Sp8 homodimerizes. To determine the region involved in Sp8 interaction, we have generated different truncated versions of Sp8. Our results show that Sp8 homodimerizes at its C-terminal domain. Our study underscores the relevance of Sp6/8 in mediating B-catenin and Bmp signaling pathways in the limb ectoderm.

Las enfermedades tromboembólicas venosas están asociadas al cáncer entre un 20 y un 30%. Además de los factores de riesgos de la población general en los pacientes oncológicos se asocian los relacionados con el tipo de tumor, el estadio tumoral y los asociados al tratamiento que incrementan el riesgo en hasta 6 veces en comparación con los pacientes sin cáncer. El diagnóstico se realiza de igual forma que en los pacientes sin cáncer, aunque es más frecuente la presentación asintomática. Se han creado escalas específicas para estos pacientes con el objetivo de aumentar la certeza en el diagnóstico. La aparición de tromboembolismo pulmonar en los pacientes oncológicos se asocia con mayor mortalidad. Venous thromboembolic diseases are associated with cancer between 20 and 30%. In cancer patients besides the risk factors of general population exist those related with the tumour type, the stage of the disease and the cancer treatment that increase the risk in 6-fold as compared with patients without cancer. In cancer patients the diagnosis of venous thromboembolic disease is done similarly than in patients without cancer, although in cancer patients is more frequent the asymptomatic presentation. Specific scales have been designed for these patients in order to increase the accuracy in diagnosis. Pulmonary embolism in oncologic patients have been associated with higher morbidity and mortality. Medicina

PMCID: PMC4482672, [Background]: Precise temporal and spatial expression of the clustered Hox genes is essential for patterning the developing embryo. Temporal activation of Hox genes was shown to be cluster-autonomous. However, gene clustering appears dispensable for spatial colinear expression. Generally, a set of Hox genes expressed in a group of cells instructs these cells about their fate such that the differential expression of Hox genes results in morphological diversity. The spatial colinearity is considered to rely both on local and long-range cis regulation. [Results]: Here, we report on the global deregulation of HoxA and HoxD expression patterns upon inactivation of a subset of HOXA and HOXD proteins. [Conclusions]: Our data suggest the existence of a >self-regulation> mechanism, a process by which HOX proteins establish and/or maintain the spatial domains of the Hox gene family and we propose that the functionally dominant HOX proteins could contribute to generating the spatial parameters of Hox expression in a given tissue, i.e., HOX controlling the establishment of the ultimate HOX code., Grant sponsor: the Spanish Government; Grant number: BFU2011-24972; Grant sponsor: the Canadian Institutes for Health Research; Grant number: MOP-82880; Grant number: 126110. This work was supported by the Spanish Government to M.R. and by the Canadian Institutes for Health Research as well as the Canada Research Chair program to M.K. R.S was supported by a Formación Profesorado Universitario fellowship from the Spanish Ministry of Science and Innovation and currently supported by the Angelo Pizzagalli postdoctoral fellowship.

Introduction.

Resumen del trabajo presentado a los Congresos: 17th International Congress of Developmental Biology, 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting y XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo, celebrados en Cancún (México) del 16 al 20 de junio de 2013., The apical ectodermal ridge (AER) is a specialized epithelium located at the distal dorso-ventral (DV) rim of the developing limb that is crucial for limb bud development. The induction of the AER is a complex process that relies on intricate interactions among the FGF, WNT, and BMP signaling pathways operating within the ectoderm and between the ectoderm and mesoderm of the early limb bud. Furthermore, induction of the AER is linked to the establishment of DV patterning. Sp6 and Sp8 are two members of the Specificity Protein family of transcription factors that are expressed in the limb bud ectoderm and function downstream of WNT/ β Catenin signaling and upstream of Fgf8. Their individual genetic inactivations result in a mild syndactyly phenotype for Sp6 and limb truncation, due to the premature regression of the AER, for Sp8. To investigate a possible functional redundancy between Sp6 and Sp8, we generated double Sp6;Sp8 null mutants. We also generated Sp6-null; Sp8-conditional mutants using a Sp8 floxed allele with the Ap2-Cre and with the Msx2-Cre deleter lines. Our results show that double Sp6;Sp8 mutants are tetra-amelic. Initial budding occurs, but Fgf8 and Bmp4 are not activated in the limb ectoderm and the dorsal marker Wnt7a persists throughout the limb bud ectoderm. The phenotype of mutants bearing a single functional copy of Sp6 (Sp6 +/-;Sp8-/-) is indistinguishable from that of the double mutants, whereas the presence of a single functional allele of Sp8 (Sp6-/-;Sp8+/-) results in a Split Hand Foot Malformation phenotype. We conclude that Sp6 and Sp8 work in a redundant manner as indispensable mediators of WNT/ β Catenin signaling in the limb ectoderm and that their function links the Proximo-distal and DV axes.

Resumen del trabajo presentado a los Congresos: 17th International Congress of Developmental Biology, 72nd Annual Meeting of the Society for Developmental Biology, VII Latin American Society of Developmental Biology Meeting y XI Congreso de la Sociedad Mexicana de Biologia del Desarrollo, celebrados en Cancún (México) del 16 al 20 de junio de 2013.-- et al., One of the most intriguing questions in developmental biology is how organ growth and patterning are coordinated during embryogenesis. Limb development relies on an exquisite coordination between growth and patterning but the underlying mechanisms remain elusive. Previous studies showed that A-P and P-D limb bud growth and patterning relies on a positive feedback loop between Sonic Hedgehog (Shh), the BMP antagonist Gremlin1 (Grem1), both expressed in mesenchymal cells, and Fibroblast growth factors (Fgfs) produced in the Apical Ectodermal Ridge (AER). In addition, the collinear expression of HoxA and HoxD genes has a key role in A-P and P-D patterning by establishing positional identity along these axes. Here, we show that HoxA and HoxD genes are required at early stages for Grem1 activation and proper Fgf10 and Fgf8 expression and therefore are mandatory for the establishment of the Shh-Grem1-Fgf feedback loop. Our results provide evidence that, in addition to this early function, HoxA and HoxD genes remain indispensable for proper limb growth at later stages. Together, our results reveal a dual role of Hox genes in controlling limb growth and establishing the limb architecture and we propose that the intricate interactions between Hox function and growth pathways act as the molecular network coordinating limb bud growth and patterning.

Comunicación presentada a la 12th International Conference on Limb Development and Regeneration celebrada en Québec (Canadá) del 3 al 7 de Junio de 2012.

El trabajo fin de grado que voy a desarrollar va a tener como tema el tratamiento y rehabilitación de un lesionado medular con resultado de parálisis de miembro inferior. Este caso no va a ser real, va a ser fruto de mis estudios, experiencia y observación tanto en las practicas universitarias como en el trabajo posterior. La metodología que voy a utilizar y en la cual voy a centrar mi tratamiento será el Modelo de Ocupación Humana de Kielhofner. Este tratamiento va a trabajar con el paciente/usuario de una forma holística, tratando y mejorando todas las funciones del individuo y su desarrollo en las actividades básicas, instrumentales y de ocio. Para este tratamiento, como todos para que tenga éxito, se trabajará dentro de un equipo multidisciplinar, formado por médicos, enfermeras, fisioterapeuta, trabajador social, psicólogo y terapeuta ocupacional como mínimo; dado que este trabajo se desarrolla dentro del área de terapia ocupacional, se trabajará esencialmente en ese entorno. Los objetivos de este tratamiento van a ser: la recuperación de sus actividades anteriores con un desempeño adaptado y funcional, la adaptación de su hogar a su nueva condición, para conseguir una total autonomía en un ambiente adecuado. Como todo trabajo, al final habrá unas conclusiones y reflexiones, además de una bibliografía donde estarán los libros y documentos consultados para su realización.

Trabajo presentado al "Meeting on HOX and TALE Transcription Factors in Development and Disease" celebrado en Francia del 28 de septiembre al 1 de octubre de 2011.

Resumen tomado de la publicación La presencia de la música en los primeros años de la infancia del niño es de vital importancia tanto para la adquisición de destrezas específicamente musicales como para su evolución integral como individuo. Las estrategias cognitivas empleadas por los niños para la imitación, comprensión y realización improvisada de melodías y ritmos se adaptan a las diferentes etapas madurativas. A medida que el aprendizaje se torna más acumulativo, la influencia del entorno y de las experiencias anteriores resulta de gran transcendencia. Para que el proceso de asimilación se produzca en condiciones óptimas es imprescindible contar con profesorado preparado, capaz de organizar la acción pedagógica en función a las estructuras psicológicas que determina la teoría cognoscitiva, conforme a las metodologías activas, basándose en la estimulación mediante la creatividad y el juego. ESP

Resumen basado en el de la publicación El primer Conservatorio de Música creado en España es el de Madrid (1831), constituyendo durante muchos años el referente para el resto de Conservatorios que se fundan posteriormente en el territorio nacional y que carecen de una normativa específica que los regule. Por ello, se analizan las dos reglamentaciones, publicadas a finales del siglo XIX y principios del XX, que regulan el Conservatorio de la capital a partir de tres dimensiones que configuran su estructura : organización y funcionamiento del centro, currículo de las enseñanzas que en él se imparten y profesorado, dimensiones conformadas a su vez por varias subdimensiones que permiten un estudio más exhaustivo de la dinámica interna del Conservatorio madrileño, paradigma de las enseñanzas musicales nacionales. ESP