Improved Development of Somatic Cell Cloned Mouse Embryos by Vitamin C and Latrunculin A

Impaired development of embryos produced by somatic cell nuclear transfer (SCNT) is mostly associated with faulty reprogramming of the somatic nucleus to a totipotent state and can be improved by treatment with epigenetic modifiers. Here we report that addition of 100 μM vitamin C (VitC) to embryo culture medium for at least 16 h post-activation significantly increases mouse blastocyst formation and, when combined with the use of latrunculin A (LatA) during micromanipulation and activation procedures, also development to term. In spite of this, no significant effects on pluripotency (OCT4 and NANOG) or nuclear reprogramming markers (H3K14 acetylation, H3K9 methylation and DNA methylation and hydroxymethylation) could be detected. The use of LatA alone significantly improved in vitro development, but not full-term development. On the other hand, the simultaneous treatment of cloned embryos with VitC and the histone deacetylase inhibitor psammaplin A (PsA), in combination with the use of LatA, resulted in cloning efficiencies equivalent to those of VitC or PsA treatments alone, and the effects on pluripotency and nuclear reprogramming markers were less evident than when only the PsA treatment was applied. These results suggest that although both epigenetic modifiers improve cloning efficiencies, possibly through different mechanisms, they do not show an additive effect when combined. Improvement of SCNT efficiency is essential for its applications in reproductive and therapeutic cloning, and identification of molecules which increase this efficiency should facilitate studies on the mechanism of nuclear reprogramming and acquisition of totipotency

La Real Fábrica del Conde de Aranda (Alcora-Castellón) : caracteres constructivos y criterios de intervención

El presente trabajo se centra en la investigación del conjunto de la Real Fábrica de Loza y Porcelana de l’Alcora, fundada por el Conde de Aranda en 1726. Los objetivos perseguidos son desvelar el grado de conservación del edificio original y establecer líneas estratégicas generales para afrontar un futuro estudio de rehabilitación. La metodología se ha basado en el estudio in situ de uno de los edificios del conjunto, con el apoyo de los datos obtenidos en documentación histórica y bibliografía relacionada: se ha realizado el levantamiento gráfico y catas en paramentos, para buscar posibles revestimientos históricos. El material obtenido pone de manifiesto la pervivencia de uno de los edificios más relevantes del municipio de l’Alcora, la industria que definió su actual identidad.This project focuses on the investigation of the Royal Factory of Faience and Porcelain in l’Alcora (Castellón), founded by the Count of Aranda in 1726. The main goals have been to discover the level of conservation of the foundational building and to establish the general strategies for facing the future rehabilitation study. The methodology has been based on the on-site study of one building of the factory, with the support of data obtained from historical documentation and related publications: the graphic survey and tests on walls in order to looking for historical coverings. The results show the survival of one of the most important buildings of l’Alcora, the factory which defined its current identity.El present treball es centra en la investigació del conjunt de la Reial Fàbrica de Pisa i Porcellana de l’Alcora, fundada per el Comte d’Aranda en 1726. Els objectius han sigut desvetllar el grau de conservació de l’edifici original i establir unes línies estratègiques generals per afrontar un futur estudi de rehabilitació. La metodologia s’ha basat en l’estudi in situ d’un dels edificis del conjunt, amb el suport de les dades obtingudes a la documentació històrica i bibliografia relacionada: s’ha realitzat l’alçament gràfic i inspeccions als paraments per a buscar possibles revestiments històrics. Els resultats obtinguts posa de manifest la pervivència d’un dels edificis més rellevants de l’Alcora, la indústria que va definir la seua identitat actual.Mallol Olivares, A. (2017). La Real Fábrica del Conde de Aranda (Alcora-Castellón) : caracteres constructivos y criterios de intervención. http://hdl.handle.net/10251/9142

Dynamics of alternative splicing during somatic cell reprogramming reveals functions for RNA-binding proteins CPSF3, hnRNP UL1, and TIA1

C.V. was recipient of an FPI-Severo Ochoa Fellowship from the Spanish Ministry of Economy and Competitiveness. Work in J.V. laboratory is supported by the European Research Council (ERC AdvG 670146), AGAUR, Spanish Ministry of Economy and Competitiveness (BFU 2017 89308-P) and the Centre of Excellence Severo Ochoa. Work in T.G.'s laboratory was supported by the European Research Council FP7/2007-2013 (ERC Synergy Grant 4D-Genome) the Ministerio de Educación y Ciencia (SAF.2012-37167) and AGAUR. We acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership and the CERCA Programme / Generalitat de Catalunya.UDTRIASBackground: Somatic cell reprogramming is the process that allows differentiated cells to revert to a pluripotent state. In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, the dynamics of post-transcriptional changes and their associated regulatory mechanisms remain poorly understood. Here we study the dynamics of alternative splicing changes occurring during efficient reprogramming of mouse B cells into induced pluripotent stem (iPS) cells and compare them to those occurring during reprogramming of mouse embryonic fibroblasts. Results: We observe a significant overlap between alternative splicing changes detected in the two reprogramming systems, which are generally uncoupled from changes in transcriptional levels. Correlation between gene expression of potential regulators and specific clusters of alternative splicing changes enables the identification and subsequent validation of CPSF3 and hnRNP UL1 as facilitators, and TIA1 as repressor of mouse embryonic fibroblasts reprogramming. We further find that these RNA-binding proteins control partially overlapping programs of splicing regulation, involving genes relevant for developmental and morphogenetic processes. Conclusions: Our results reveal common programs of splicing regulation during reprogramming of different cell types and identify three novel regulators of this process and their targets

El paper del CRAI-Biblioteca en l’adquisició de competències informacionals: col·laboració i contagi

Amb la desaparició dels crèdits de lliure elecció, es constata la dificultat d’atreure als alumnes cap activitats formatives que es facin fora del seu horari lectiu. Paral·lelament, als taulells d’informació, es detecta un increment de preguntes sobre els recursos d’informació i serveis que ofereix el CRAI Biblioteca del Campus de Mundet. A partir del curs acadèmic 2012-13, es fixa l’objectiu de promoure actuacions encaminades a fomentar l’ús autònom per part dels estudiants dels recursos i serveis esmentats

Desenvolupament transversal de la competència informacional al segon semestre del Grau de Psicologia.

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18).Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18)

Metabolomics reveals impaired maturation of HDL particles in adolescents with hyperinsulinaemic androgen excess.

Hyperinsulinaemic androgen excess (HIAE) in prepubertal and pubertal girls usually precedes a broader pathological phenotype in adulthood that is associated with anovulatory infertility, metabolic syndrome and type 2 diabetes. The metabolic derangements that determine these long-term health risks remain to be clarified. Here we use NMR and MS-based metabolomics to show that serum levels of methionine sulfoxide in HIAE girls are an indicator of the degree of oxidation of methionine-148 residue in apolipoprotein-A1. Oxidation of apo-A1 in methionine-148, in turn, leads to an impaired maturation of high-density lipoproteins (HDL) that is reflected in a decline of large HDL particles. Notably, such metabolic alterations occur in the absence of impaired glucose tolerance, hyperglycemia and hypertriglyceridemia, and were partially restored after 18 months of treatment with a low-dose combination of pioglitazone, metformin and flutamide

A baseline metabolomic signature is associated with immunological CD4+ T-Cell recovery after 36 months of art in HIV-infected patients

Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after ART in order to envisage the underlying mechanistic pathways that influence the treatment response.Peer reviewe

Vascular Endothelial Growth Factor-Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass

Type 2 diabetes (T2D) results from insulin resistance and inadequate insulin secretion. Insulin resistance initially causes compensatory islet hyperplasia that progresses to islet disorganization and altered vascularization, inflammation, and, finally, decreased functional β-cell mass and hyperglycemia. The precise mechanism(s) underlying β-cell failure remain to be elucidated. In this study, we show that in insulin-resistant high-fat diet-fed mice, the enhanced islet vascularization and inflammation was parallel to an increased expression of vascular endothelial growth factor A (VEGF). To elucidate the role of VEGF in these processes, we have genetically engineered β-cells to overexpress VEGF (in transgenic mice or after adeno-associated viral vector-mediated gene transfer). We found that sustained increases in β-cell VEGF levels led to disorganized, hypervascularized, and fibrotic islets, progressive macrophage infiltration, and proinflammatory cytokine production, including tumor necrosis factor-α and interleukin-1β. This resulted in impaired insulin secretion, decreased β-cell mass, and hyperglycemia with age. These results indicate that sustained VEGF upregulation may participate in the initiation of a process leading to β-cell failure and further suggest that compensatory islet hyperplasia and hypervascularization may contribute to progressive inflammation and β-cell mass loss during T2D

A baseline metabolomic signature is associated with immunological CD4 + T-cell recovery after 36 months of antiretroviral therapy in HIV-infected patients

Poor immunological recovery in treated HIV-infected patients is associated with greater morbidity and mortality. To date, predictive biomarkers of this incomplete immune reconstitution have not been established. We aimed to identify a baseline metabolomic signature associated with a poor immunological recovery after antiretroviral therapy (ART) to envisage the underlying mechanistic pathways that influence the treatment response. This was a multicentre, prospective cohort study in ART-naive and a pre-ART low nadir (<200 cells/μl) HIV-infected patients (n = 64). We obtained clinical data and metabolomic profiles for each individual, in which low molecular weight metabolites, lipids and lipoproteins (including particle concentrations and sizes) were measured by NMR spectroscopy. Immunological recovery was defined as reaching CD4 + T-cell count at least 250 cells/μl after 36 months of virologically successful ART. We used univariate comparisons, Random Forest test and receiver-operating characteristic curves to identify and evaluate the predictive factors of immunological recovery after treatment. HIV-infected patients with a baseline metabolic pattern characterized by high levels of large high density lipoprotein (HDL) particles, HDL cholesterol and larger sizes of low density lipoprotein particles had a better immunological recovery after treatment. Conversely, patients with high ratios of non-HDL lipoprotein particles did not experience this full recovery. Medium very-low-density lipoprotein particles and glucose increased the classification power of the multivariate model despite not showing any significant differences between the two groups. In HIV-infected patients, a baseline healthier metabolomic profile is related to a better response to ART where the lipoprotein profile, mainly large HDL particles, may play a key role