The balance between GMD and OFUT1 regulates notch signaling pathway activity by modulating notch stability

The Notch signaling pathway plays an important role in development and physiology. In Drosophila, Notch is activated by its Delta or Serrate ligands, depending in part on the sugar modifications present in its extracellular domain. O-fucosyltransferase-1 (OFUT1) performs the first glycosylation step in this process, O-fucosylating various EGF repeats at the Notch extracellular domain. Besides its O-fucosyltransferase activity, OFUT1 also behaves as a chaperone during Notch synthesis and is able to down regulate Notch by enhancing its endocytosis and degradation. We have reevaluated the roles that O-fucosylation and the synthesis of GDP-fucose play in the regulation of Notch protein stability. Using mutants and the UAS/Gal4 system, we modified in developing tissues the amount of GDP-mannosedeshydratase (GMD), the first enzyme in the synthesis of GDP-fucose. Our results show that GMD activity, and likely the levels of GDPfucose and O-fucosylation, are essential to stabilize the Notch protein. Notch degradation observed under low GMD expression is absolutely dependent on OFUT1 and this is also observed in Notch Abruptex mutants, which have mutations in some potential O-fucosylated EGF domains. We propose that the GDP-fucose/OFUT1 balance determines the ability of OFUT1 to endocytose and degrade Notch in a manner that is independent of the residues affected by Abruptex mutations in Notch EGF domains.This work was funded by ICM P06-039F grant to A.G. and by a BFU2009-09403 grant of the M.E.C. to J.F.dC. An institutional grant from the Ramón Areces Foundation to the CBMSO is also acknowledged.Peer Reviewe

Temperature-dependent photoluminescence of anatase Li-doped TiO_(2) nanoparticles

TiO_(2) is currently one of the most employed material in photocatalysis and optoelectronic applications. By doping with different elements, tailored luminescent and optoelectronic properties can be obtained, which further enhances its applicability. The achievement of deeper knowledge and control on the recombination processes via light-metal doping engineering promises a wider use in optoelectronic applications. In this work, the luminescent properties of undoped and Li-doped anatase TiO_(2) nanoparticles obtained by hydrolysis process are studied, by means of photoluminescence (PL) measurements from 10 K to room-temperature. TiO_(2) presents a wide emission which covers the visible range, while Li-doping quenches the emission on the low visible region. By terms of time-resolved luminescence (TR-PL), lifetime of the recombination processes can be obtained, in which a decrease on lifetime values can be observed for the doped samples

Nutritional problems perceived by pediatricians in Spanish children younger than 3 years

Introducción: Los padres son los principales responsables de la educación nutricional de sus hijos y es labor del pediatra orientar y resolver problemas al respecto. En este estudio se pretende conocer la relevancia de las cuestiones nutricionales en la consulta del pediatra y los principales problemas nutricionales percibidos en los menores de 3 años. Métodos: Estudio descriptivo, transversal en dos fases. La primera consistió en entrevistas y grupos de discusión con 30 pediatras seleccionados aleatoriamente en Madrid y Barcelona. Los resultados se utilizaron para diseñar el cuestionario online (76 preguntas relacionadas con la nutrición en niños de 0-3 años) de la siguiente fase, en la que participaron pediatras seleccionados de forma aleatoria y representativa del territorio nacional. Resultados: De 258 pediatras seleccionados, completaron el cuestionario 151, que atendían a una media de 588 pacientes/mes. Los principales problemas nutricionales percibidos hasta los 12 meses fueron las deficiencias de hierro y vitaminas y la escasa ganancia de peso, y posteriormente la ingesta excesiva de carbohidratos y lípidos y el sobrepeso. Los padres fueron considerados los actores principales en la salud nutricional de sus hijos, pero su preocupación por esta cuestión se reduce significativamente (p < 0,0001) con la edad del niño. Los aspectos considerados más importantes para obtener unos buenos hábitos alimentarios fueron la alimentación adaptada a las necesidades del niño y respetar el tiempo de sueño. El porcentaje de pacientes que recibe recomendaciones de hábitos nutricionales varió del 88% (0-6 meses) al 61% (24-36 meses). Conclusiones: A pesar de considerar la salud nutricional importante, la intervención educativa del pediatra al respecto no es óptima. Los problemas nutricionales percibidos fueron distintos según la edadIntroduction: Parents are most responsible for nutritional education of children, and pediatritians must advise and help them with their doubts. The purpose of this study was to know the relevance of nutritional topics in daily practice and the main nutritional problems perceived by pediatritians in children under 3 years of age. Methods: Descriptive, cross-sectional study performed in 2 stages. First stage consisted on discussion meetings with 30 random-selected pediatritians from Madrid and Barcelona. Results were used to design the on-line questionnaire of the second stage (76 questions related to nutrition in children under 3 years). A random and representative sample of Spanish pediatritians was selected for this stage. Results: One hundred and fifty one pediatritians, among 258 sampled, completed the questionnaire. They referred to see a mean of 588 patients/month. The main perceived nutritional problems in the first year of life were iron and vitamin deficiencies and poor weight gain. In the next months, excess in carbohydrates and lipid intake and overweight were the main problems perceived. Parents were considered the main actors regarding their children’s nutritional health, but their concern in these questions significantly reduced with children’s age (p < 0,0001). Factors considered to have the greatest relevance in the acquisition of good nutritional habits were to provide a diet adjusted for children’s requirements and to observe the appropriate sleeping hours. The proportion of children who receive nutritional counseling varied from 88% (0-6 months) to 61% (24-36 months). Conclusions: Despite of the relevance given by pediatritians, educational intervention regarding nutritional health is not ideal. Nutritional problems perceived by pediatritians varied with children’s ageEste estudio ha sido financiado por Almiron/Danone Baby Nutrition

In situ local oxidation of SnO induced by laser irradiation: a stability study

In this work, semiconductor tin oxide (II) (SnO) nanoparticles and plates were synthesized at room conditions via a hydrolysis procedure. X-ray diffraction (XRD) and transmission electron microscopy (TEM) confirmed the high crystallinity of the as-synthesized romarchite SnO nanoparticles with dimensions ranging from 5 to 16 nm. The stability of the initial SnO and the controlled oxidation to SnO_2 was studied based on either thermal treatments or controlled laser irradiation using a UV and a red laser in a confocal microscope. Thermal treatments induced the oxidation from SnO to SnO2 without formation of intermediate SnO_x, as confirmed by thermodiffraction measurements, while by using UV or red laser irradiation the transition from SnO to SnO_2 was controlled, assisted by formation of intermediate Sn3O4, as confirmed by Raman spectroscopy. Photoluminescence and Raman spectroscopy as a function of the laser excitation source, the laser power density, and the irradiation duration were analyzed in order to gain insights in the formation of SnO_2 from SnO. Finally, a tailored spatial SnO/SnO_2 micropatterning was achieved by controlled laser irradiation with potential applicability in optoelectronics and sensing devices

Synergetic improvement of stability and conductivity of hybrid composites formed by PEDOT:PSS and SnO nanoparticles

In this work, layered hybrid composites formed by tin oxide (SnO) nanoparticles synthesized by hydrolysis and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) have been analyzed. Prior to the composite study, both SnO and PEDOT:PSS counterparts were characterized by diverse techniques, such as X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), photoluminescence (PL), atomic force microscopy (AFM), optical absorption and Hall effect measurements. Special attention was given to the study of the stability of the polymer under laser illumination, as well as the analysis of the SnO to SnO_2 oxidation assisted by laser irradiation, for which different laser sources and neutral filters were employed. Synergetic effects were observed in the hybrid composite, as the addition of SnO nanoparticles improves the stability and electrical conductivity of the polymer, while the polymeric matrix in which the nanoparticles are embedded hinders formation of SnO_2. Finally, the Si passivation behavior of the hybrid composites was studied

Genome-wide phenotypic RNAi screen in the Drosophila wing: Global parameters

We have screened a collection of UAS-RNAi lines targeting 10,920 Drosophila protein-coding genes for phenotypes in the adult wing. We identified 3653 genes (33%) whose knockdown causes either larval/pupal lethality or a mutant phenotype affecting the formation of a normal wing. The most frequent phenotypes consist of changes in wing size, vein differentiation, and patterning, defects in the wing margin and in the apposition of the dorsal and ventral wing surfaces. We also defined 16 functional categories encompassing the most relevant aspect of each protein function and assigned each Drosophila gene to one of these functional groups. This allowed us to identify which mutant phenotypes are enriched within each functional group. Finally, we used previously published gene expression datasets to determine which genes are or are not expressed in the wing disc. Integrating expression, phenotypic and molecular information offers considerable precision to identify the relevant genes affecting wing formation and the biological processes regulated by the

Influence of doping and controlled sn charge state on the properties and performance of SnO nanoparticles as anodes in li-ion batteries

Li-ion batteries (LiB) play nowadays a major role in several technological fields. In addition to enhanced high capacity and long cyclability, some other issues regarding safety, materials sustainability, and low cost remain unsolved. Tin oxide (SnO_2) presents several of those advantages as an anode material; however, some aspects still require to be investigated such as capacity fading over cycles. Herein, tin oxide nanoparticle-based anodes have been tested, showing high capacities and a significant cyclability over more than 150 cycles. A complementary strategy introducing doping elements such as Li and Ni during the synthesis by hydrolysis has been also evaluated versus the use of undoped materials, in order to assess the dependence on SnO_2 quality and properties of battery performance. Diverse aspects such as the Sn charge state in the synthesized nanoparticles, the variable incorporation of dopants, and the structure of defects have been considered in the understanding of the obtained capacity

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms)

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P <.05) and less refractoriness (4.5% vs 14.1%; P <.05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P <.05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P <.001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

Marco activo de recursos de innovación docente: Madrid

Una guía de espacios e instituciones para actividades educativas complementarias en enseñanza secundaria y Formación Profesional